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PurposeThe British Columbia COVID-19 Cohort (BCC19C) was developed from an innovative, dynamic surveillance platform and is accessed/analyzed through a cloud-based environment. The platform integrates recently developed provincial COVID-19 datasets (refreshed daily) with existing administrative holdings and provincial registries (refreshed weekly/monthly). The platform/cohort were established to inform the COVID-19 response in near “real-time” and to answer more in-depth epidemiologic questions.ParticipantsThe surveillance platform facilitates the creation of large, up-to-date analytic cohorts of people accessing COVID-19 related services and their linked medical histories. The program of work focused on creating/analyzing these cohorts is referred to as the BCC19C. The administrative/registry datasets integrated within the platform are not specific to COVID-19 and allow for selection of “control” individuals who have not accessed COVID-19 services.Findings to dateThe platform has vastly broadened the range of COVID-19 analyses possible, and outputs from BCC19C analyses have been used to create dashboards, support routine reporting and contribute to the peer-reviewed literature. Published manuscripts (total of 15 as of July, 2023) have appeared in high-profile publications, generated significant media attention and informed policy and programming. In this paper, we conducted an analysis to identify sociodemographic and health characteristics associated with receiving SARS-CoV-2 laboratory testing, testing positive, and being fully vaccinated. Other published analyses have compared the relative clinical severity of different variants of concern; quantified the high “real-world” effectiveness of vaccines in addition to the higher risk of myocarditis among younger males following a 2nd dose of an mRNA vaccine; developed and validated an algorithm for identifying long-COVID patients in administrative data; identified a higher rate of diabetes and healthcare utilization among people with long-COVID; and measured the impact of the pandemic on mental health, among other analyses.Future plansWhile the global COVID-19 health emergency has ended, our program of work remains robust. We plan to integrate additional datasets into the surveillance platform to further improve and expand covariate measurement and scope of analyses. Our analyses continue to focus on retrospective studies of various aspects of the COVID-19 pandemic, as well as prospective assessment of post-acute COVID-19 conditions and other impacts of the pandemic.

Here we report whole genome sequencing of four individuals (H3, H4, H5, and H6) from a family of Pakistani descent. Whole genome sequencing yielded 1084.92, 894.73, 1068.62, and 1005.77 million mapped reads corresponding to 162.73, 134.21, 160.29, and 150.86 Gb sequence data and 52.49x, 43.29x, 51.70x, and 48.66x average coverage for H3, H4, H5, and H6, respectively. We identified 3,529,659, 3,478,495, 3,407,895, and 3,426,862 variants in the genomes of H3, H4, H5, and H6, respectively, including 1,668,024 variants common in the four genomes. Further, we identified 42,422, 39,824, 28,599, and 35,206 novel variants in the genomes of H3, H4, H5, and H6, respectively. A major fraction of the variants identified in the four genomes reside within the intergenic regions of the genome. Single nucleotide polymorphism (SNP) genotype based comparative analysis with ethnic populations of 1000 Genomes database linked the ancestry of all four genomes with the South Asian populations, which was further supported by mitochondria based haplogroup analysis. In conclusion, we report whole genome sequencing of four individuals of Pakistani descent.

We previously investigated the transcriptome and proteome profiles of the murine ocular lens at six developmental time points including two embryonic (E15 and E18) and four postnatal time points (P0, P3, P6, and P9). Here, we extend our analyses to identify novel transcripts and peptides in developing  mouse lens. We identified a total of 9,707 novel transcripts and 325 novel fusion genes in developing mouse lens. Additionally, we identified 13,281 novel alternative splicing (AS) events in mouse lens including 6,990 exon skipping (ES), 2,447 alternative 3' splice site (A3SS), 1,900 alternative 5' splice site (A5SS), 1,771 mutually exclusive exons (MXE), and 173 intron retention (IR). Finally, we integrated our OMIC (Transcriptome and Proteome) datasets identifying 20 novel peptides in mouse lens. All 20 peptides were validated through matching MS/MS spectra of synthetic peptides. To the best of our knowledge, this is the first report integrating OMIC datasets to identify novel peptides in developing murine lens.

BackgroundThe overdose crisis in North America has prompted system-level efforts to restrict opioid prescribing for chronic pain. However, little is known about how discontinuing or tapering prescribed opioids for chronic pain shapes overdose risk, including possible differential effects among people with and without concurrent opioid use disorder (OUD). We examined associations between discontinuation and tapering of prescribed opioids and risk of overdose among people on long-term opioid therapy for pain, stratified by diagnosed OUD and prescribed opioid agonist therapy (OAT) status.Methods and findingsFor this retrospective cohort study, we used a 20% random sample of residents in the provincial health insurance client roster in British Columbia (BC), Canada, contained in the BC Provincial Overdose Cohort. The study sample included persons aged 14 to 74 years on long-term opioid therapy for pain (≥90 days with ≥90% of days on therapy) between October 2014 and June 2018 (n = 14,037). At baseline, 7,256 (51.7%) persons were female, the median age was 55 years (quartile 1-3: 47-63), 227 (1.6%) persons had been diagnosed with OUD (in the past 3 years) and recently (i.e., in the past 90 days) been prescribed OAT, and 483 (3.4%) had been diagnosed with OUD but not recently prescribed OAT. The median follow-up duration per person was 3.7 years (quartile 1-3: 2.6-4.0). Marginal structural Cox regression with inverse probability of treatment weighting (IPTW) was used to estimate the effect of prescribed opioid treatment for pain status (discontinuation versus tapered therapy versus continued therapy [reference]) on risk of overdose (fatal or nonfatal), stratified by the following groups: people without diagnosed OUD, people with diagnosed OUD receiving OAT, and people with diagnosed OUD not receiving OAT. In marginal structural models with IPTW adjusted for a range of demographic, prescription, comorbidity, and social-structural exposures, discontinuing opioids (i.e., ≥7-day gap[s] in therapy) was associated with increased overdose risk among people without OUD (adjusted hazard ratio [AHR] = 1.44; 95% confidence interval [CI] 1.12, 1.83; p = 0.004), people with OUD not receiving OAT (AHR = 3.18; 95% CI 1.87, 5.40; p < 0.001), and people with OUD receiving OAT (AHR = 2.52; 95% CI 1.68, 3.78; p < 0.001). Opioid tapering (i.e., ≥2 sequential decreases of ≥5% in average daily morphine milligram equivalents) was associated with decreased overdose risk among people with OUD not receiving OAT (AHR = 0.31; 95% CI 0.14, 0.67; p = 0.003). The main study limitations are that the outcome measure did not capture overdose events that did not result in a healthcare encounter or death, medication dispensation may not reflect medication adherence, residual confounding may have influenced findings, and findings may not be generalizable to persons on opioid therapy in other settings.ConclusionsDiscontinuing prescribed opioids was associated with increased overdose risk, particularly among people with OUD. Prescribed opioid tapering was associated with reduced overdose risk among people with OUD not receiving OAT. These findings highlight the need to avoid abrupt discontinuation of opioids for pain. Enhanced guidance is needed to support prescribers in implementing opioid therapy tapering strategies with consideration of OUD and OAT status.

Few studies have examined the sex differences in left ventricle (LV) structure and physiology from early life stages. We aimed to assess the role of sex and overweight/obesity on left ventricular mass (LVM) and LV volume in Chinese children without preexisting cardiovascular risk factors. We selected 934 healthy children aged 6–8 years from an existing cohort in Beijing, China. Linear regression models were used to regress body mass index (BMI), fat mass, systolic blood pressure, diastolic blood pressure, waist circumference, and visceral fat area (VFA) with LVM, left ventricle end-diastolic volume (LVEDV) and end-systolic volume (LVESV). Higher BMI, fat mass, waist circumference, VFA, and stroke volume (SV) predicted higher LVM, LVEDV, and LVESV in both sexes. Multivariable analysis showed that boys with an elevated BMI had greater LV hypertrophy. LVEDV and LVESV were higher among boys than among girls and increased with higher BMI in both boys and girls. LVEDV and LVESV were associated with VFA in boys. We observed sex differences in LVM, LVESV, and LVEDV among prepubertal children, independent of obesity, with higher values observed in boys. Sex differences in cardiac structure in children may help explain the higher incidence of cardiovascular disease in male adults. Whether interventions to reduce childhood obesity can improve the trajectory of cardiac dynamics is worth investigating.

Objectives The COVID-19 pandemic has necessitated access to large health system datasets to inform the public health response. To meet this need, the Provincial Health Services Authority and the British Columbia (BC) Ministry of Health collaborated to create a population-based platform that integrates COVID-19 datasets with sociodemographic and administrative health data. Approach A BC COVID Data Library proof-of-concept was created as a cloud-based, dynamic platform composed of de-identified datasets. The BC COVID-19 Cohort (BCC19C) represents a subset composed of people accessing COVID-19 health services (e.g., testing, vaccination) and linked health histories. Provincial COVID-19 datasets are updated daily and include COVID-19 lab tests, case surveillance, vaccinations and hospitalizations/deaths. These can be linked to administrative data holdings for the BC population, which are updated weekly/monthly and include vital statistics, medications, hospital admissions, medical visits, among others. A patient matching algorithm creates unique patient keys that allows the same individual to be linked across datasets. Results The BCC19C has been used provincially to 1) support ongoing surveillance, reporting, and modelling of COVID-19; 2) describe and characterize the epidemiology of COVID-19; and 3) inform acute care planning, public health interventions and health care services in BC. Ongoing and completed BCC19C analyses include assessment of vaccine safety, vaccine effectiveness, and characteristics associated with infection and severe outcomes; use of medical visit data for syndromic surveillance and monitoring of unintended outcomes of the pandemic (e.g., mental health visits); and characterization of long-COVID. Availability of linked administrative data holdings has been crucial for identifying non-COVID control groups, measuring sociodemographics and co-morbidities, and complementing COVID-19 datasets for more complete capture of health outcomes (e.g., deaths, hospitalizations). Conclusions The large scope/breadth and timeliness of the linkable datasets integrated within the COVID Data Library and the BCC19C has supported the public health response in BC. Additional linkage to other data sources will further strengthen this data platform.

During the operation of the ITER machine, hundreds of MW/Var of active and reactive power will be exchanged with the grid. The E‐STATCOM scheme composed of the Modular Multilevel Converter (MMC) and split supercapacitor energy storage has been proposed to improve the power compensation performance of the existing reactive power compensation system in the previous study. However, one of the main technical challenges which is lack of research is to precharge all submodule capacitors and supercapacitors from zero to their nominal voltage values efficiently during a startup process. As the capacitance and operating voltage of supercapacitors are much different from capacitors in each submodule, the startup of E‐STATCOM is a more complicated process. To coordinate the energy exchange between submodule capacitors and supercapacitors, submodule capacitors and the grid, this paper presents an optimized four‐stage AC side startup strategy for the E‐STATCOM. The proposed method minimizes the use of current‐limiting resistors while suppressing the surge current in the zero‐voltage startup process of supercapacitors, in addition to optimizing the energy consumption. The pulse current charging, constant current charging and constant power charging strategies of supercapacitors are adopted in different charging stages, and the detailed coordinated control scheme between submodule capacitors and supercapacitors are described and analyzed. The effectiveness and performance of the proposed method are verified by simulation results and hardware‐in‐the‐loop (HIL) experiments. [ABSTRACT FROM AUTHOR]

This document is a detailed description of a study on the oxidative chlorination of alkanes using visible light and HCl as the chlorine reagent. The researchers found that simple alkanes cannot be chlorinated effectively under the same reaction conditions, but functionalized alkanes with electron-withdrawing groups can undergo chlorination. The study includes experimental procedures, results, and characterization of the compounds using NMR analysis. The document also acknowledges the funding source and provides additional supporting information. [Extracted from the article]

FOXE3 is a lens-specific transcription factor that has been associated with anterior segment ocular dysgenesis. To determine the transcriptional target(s) of FOXE3 that are indispensable for the anterior segment development, we examined the transcriptome and the proteome of cells expressing truncated FOXE3 responsible for Peters anomaly identified through linkage-coupled next-generation whole-exome sequencing. We found that DNAJB1, an autophagy-associated protein, was the only candidate exhibiting differential expression in both screens. We confirmed the candidacy of DNAJB1 through chromatin immunoprecipitation and luciferase assays while knockdown of DNAJB1 in human lens epithelial cells resulted in a mitotic arrest. Subsequently, we targeted dnajb1a in zebrafish through injection of a splice-blocking morpholino. The dnajb1a morphants exhibited underdeveloped cataractous lenses with persistent apoptotic nuclei. In conclusion, here we report DNAJB1 is a transcriptional target of FOXE3 in a novel pathway that is crucial for the development of the anterior segment of the eye.

UnlabelledThe intracellular protozoan Toxoplasma gondii dramatically reprograms the transcriptome of host cells it infects, including substantially up-regulating the host oncogene c-myc. By applying a flow cytometry-based selection to infected mouse cells expressing green fluorescent protein fused to c-Myc (c-Myc-GFP), we isolated mutant tachyzoites defective in this host c-Myc up-regulation. Whole-genome sequencing of three such mutants led to the identification of MYR1 (Myc regulation 1; TGGT1_254470) as essential for c-Myc induction. MYR1 is a secreted protein that requires TgASP5 to be cleaved into two stable portions, both of which are ultimately found within the parasitophorous vacuole and at the parasitophorous vacuole membrane. Deletion of MYR1 revealed that in addition to its requirement for c-Myc up-regulation, the MYR1 protein is needed for the ability of Toxoplasma tachyzoites to modulate several other important host pathways, including those mediated by the dense granule effectors GRA16 and GRA24. This result, combined with its location at the parasitophorous vacuole membrane, suggested that MYR1 might be a component of the machinery that translocates Toxoplasma effectors from the parasitophorous vacuole into the host cytosol. Support for this possibility was obtained by showing that transit of GRA24 to the host nucleus is indeed MYR1-dependent. As predicted by this pleiotropic phenotype, parasites deficient in MYR1 were found to be severely attenuated in a mouse model of infection. We conclude, therefore, that MYR1 is a novel protein that plays a critical role in how Toxoplasma delivers effector proteins to the infected host cell and that this is crucial to virulence.ImportanceToxoplasma gondii is an important human pathogen and a model for the study of intracellular parasitism. Infection of the host cell with Toxoplasma tachyzoites involves the introduction of protein effectors, including many that are initially secreted into the parasitophorous vacuole but must ultimately translocate to the host cell cytosol to function. The work reported here identified a novel protein that is required for this translocation. These results give new insight into a very unusual cell biology process as well as providing a potential handle on a pathway that is necessary for virulence and, therefore, a new potential target for chemotherapy.

PurposeTranscriptome is the entire repertoire of transcripts present in a cell at any particular time. We undertook a next-generation whole transcriptome sequencing approach to gain insight into the transcriptional landscape of the developing mouse lens.MethodsWe ascertained mouse lenses at six developmental time points including two embryonic (E15 and E18) and four postnatal stages (P0, P3, P6, and P9). The ocular tissue at each time point was maintained as two distinct pools serving as biological replicates for each developmental stage. The mRNA and small RNA libraries were paired-end sequenced on Illumina HiSeq 2000 and subsequently analyzed using bioinformatics tools.ResultsMapping of mRNA and small RNA libraries generated 187.56 and 154.22 million paired-end reads, respectively. We detected a total of 14,465 genes in the mouse ocular lens at the above-mentioned six developmental stages. Of these, 46 genes exhibited a 40-fold differential (higher or lower) expression at one the five developmental stages (E18, P0, P3, P6, and P9) compared with their expression level at E15. Likewise, small RNA profiling identified 379 microRNAs (miRNAs) expressed in mouse lens at six developmental time points. Of these, 49 miRNAs manifested an 8-fold differential (higher or lower) expression at one the five developmental stages, as mentioned above compared with their expression level at E15.ConclusionsWe report a comprehensive profile of developing murine lens transcriptome including both mRNA and miRNA through next-generation RNA sequencing. A complete repository of the lens transcriptome of six developmental time points will be monumental in elucidating processes essential for the development of the ocular lens and maintenance of its transparency.

Purpose Prescription opioids (POs) are widely prescribed for chronic non-cancer pain but are associated with several risks and limited long-term benefit. Large, linked data sources are needed to monitor their harmful effects. We developed and characterised a retrospective cohort of people dispensed POs.Participants We used a large linked administrative database to create the Opioid Prescribing Evaluation and Research Activities cohort of individuals dispensed POs for non-cancer pain in British Columbia (BC), Canada (1996–2015). We created definitions to categorise episodes of PO use based on a review of the literature (acute, episodic, chronic), developed an algorithm for inferring clinical indication and assessed patterns of PO use across a range of characteristics.Findings to date The current cohort includes 1.1 million individuals and 3.4 million PO episodes (estimated to capture 40%–50% of PO use in BC). The majority of episodes were acute (81%), with most prescribed for dental or surgical pain. Chronic use made up 3% of episodes but 88% of morphine equivalents (MEQ). Across the acute to episodic to chronic episode gradient, there was an increasing prevalence of higher potency POs (hydromorphone, oxycodone, fentanyl, morphine), long-acting formulations and chronic pain related indications (eg, back, neck, joint pain). Average daily dose (MEQ) was similar for acute/episodic but higher for chronic episodes. Approximately 7% of the cohort had a chronic episode and chronic pain was the characteristic most strongly associated with chronic PO use. Individuals initiating a chronic episode were also more likely to have higher social/material deprivation and previous experience with a mental health condition or a problem related to alcohol or opioid use. Overall, these findings suggest our episode definitions have face validity and also provide insight into characteristics of people initiating chronic PO therapy.Future plans The cohort will be refreshed every 2 years. Future analyses will explore the association between POs and adverse outcomes.

This study identified factors associated with hospital admission among people with laboratory-diagnosed COVID-19 cases in British Columbia. The study used data from the BC COVID-19 Cohort, which integrates data on all COVID-19 cases with data on hospitalizations, medical visits, emergency room visits, prescription drugs, chronic conditions and deaths. The analysis included all laboratory-diagnosed COVID-19 cases in British Columbia to 15 January 2021. We evaluated factors associated with hospital admission using multivariable Poisson regression analysis with robust error variance. Of the 56,874 COVID-19 cases included in the analysis, 2298 were hospitalized. Factors associated with increased hospitalization risk were as follows: male sex (adjusted risk ratio (aRR) = 1.27; 95% CI = 1.17–1.37), older age (p-trend < 0.0001 across age groups increasing hospitalization risk with increasing age [aRR 30–39 years = 3.06; 95% CI = 2.32–4.03, to aRR 80+ years = 43.68; 95% CI = 33.41–57.10 compared to 20–29 years-old]), asthma (aRR = 1.15; 95% CI = 1.04–1.26), cancer (aRR = 1.19; 95% CI = 1.09–1.29), chronic kidney disease (aRR = 1.32; 95% CI = 1.19–1.47), diabetes (treated without insulin aRR = 1.13; 95% CI = 1.03–1.25, requiring insulin aRR = 5.05; 95% CI = 4.43–5.76), hypertension (aRR = 1.19; 95% CI = 1.08–1.31), injection drug use (aRR = 2.51; 95% CI = 2.14–2.95), intellectual and developmental disabilities (aRR = 1.67; 95% CI = 1.05–2.66), problematic alcohol use (aRR = 1.63; 95% CI = 1.43–1.85), immunosuppression (aRR = 1.29; 95% CI = 1.09–1.53), and schizophrenia and psychotic disorders (aRR = 1.49; 95% CI = 1.23–1.82). In an analysis restricted to women of reproductive age, pregnancy (aRR = 2.69; 95% CI = 1.42–5.07) was associated with increased risk of hospital admission. Older age, male sex, substance use, intellectual and developmental disability, chronic comorbidities, and pregnancy increase the risk of COVID-19-related hospitalization.

IntroductionBritish Columbia (BC), Canada declared a public health emergency in April 2016 for opioid overdose. Comprehensive data was needed to identify risk factors, inform interventions, and evaluate response actions. We describe the development of an overdose cohort, including linkage strategy, case definitions, and data governance model, and present the resulting characteristics, including data linkage yields and case overlap among data sources.MethodsOverdose events from hospital admissions, physician visits, poison centre and ambulance calls, emergency department visits, and coroner's data were grouped into episodes if records were present in multiple sources. A minimum of five years of universal health care records (all prescription dispensations, fee-for-service physician billings, emergency department visits and hospitalizations) were appended for each individual. A 20% random sample of BC residents and a 1:5 matched case-control set were generated. Consultation and prioritization ensured analysts worked to address questions to directly inform public health actions.Results10,456 individuals suffered 14,292 overdoses from January 1, 2015 to Nov 30, 2016. Only 28% of overdose events were found in more than one dataset with the unique contribution of cases highest from ambulance records (32%). Compared with fatal overdoses, non-fatal events more often involved females, younger individuals (20 to 29 years) and those 60 or older. In 78% of illegal drug deaths, there was no associated ambulance response. In the year prior to first recorded overdose, 60% of individuals had at least one ED visit, 31% at least one hospital admission, 80% at least one physician visit, and 87% had filled at least one prescription in a community pharmacy.ConclusionWhile resource-intensive to establish, a linked cohort is useful for characterizing the full extent of the epidemic, defining sub-populations at risk, and patterns of contact with the health system. Overdose studies in other jurisdictions should consider the inclusion of multiple data sources.

Abstract Background Recent studies have shown an increasing incidence of herpes zoster (HZ) infection, which may be related to the introduction of varicella vaccination programs in children. We examined the epidemiology and treatment costs of HZ and post-herpetic neuralgia (PHN) over time in British Columbia, Canada. Methods The cohort consisted of all cases with HZ infection from January 1, 1997 and December 31, 2012. Incident zoster was defined as a case (ICD-9 053 or ICD-10 B02) without a previous episode of HZ or PHN in the previous 12 months. We determined the incidence for HZ and PHN and the age-sex standardized rate for the overall population. We determined the association between the varicella vaccination program and increased HZ rates by evaluating the rate ratios in the publicly-funded varicella vaccine period compared to the non-publicly funded period in a regression model. We evaluated the hospitalization rates, treatment by GPs and their associated yearly costs for HZ and PHN. Results HZ incidence increased for the entire study period from 3.2 per 1000 population in 1997 to 4.5 in 2012. HZ rates were higher for females than males and all age groups had an increased incidence rate, except the 0–9 year olds, where the rate decreased. Crude and age-sex standardized incidence rates of PHN demonstrated very similar patterns to HZ incidence. Based on the regression model, rates of HZ were higher in the older individuals. No significant increase with HZ incidence was seen during the publically funded varicella vaccination program compared to the non-publicly funded period. From 1997 to 2012, the annual HZ-related costs associated with hospitalizations and GP visits were over $CDN4.9 million and $CDN537,286, respectively; treatment costs for hospitalizations have increased significantly over time. Majority of PHN-related cases are managed by GPs, with a steady increase over time in number of cases and associated annual costs. Conclusions The incidence of zoster and PHN is increasing with time, particularly in the elderly population and the risk is greater in the over 65 year olds. Treatment costs for both HZ and PHN represent a significant burden on the Canadian healthcare system.

Peter's Anomaly is a developmental disorder of the eye and has been linked to mutations in a range of genes, including the transcription factor FOXE3. Here the authors use next-generation RNA sequencing and mass spectrometry to identify an autophagy-associated protein, DNAJB1 as the transcriptional target of FOXE3.

BackgroundThrombocytopenia-associated multi-organ failure (TAMOF) in children is a well-described factor for increased hospital mortality. Low cardiac output syndrome (LCOS) and the effects of cardiopulmonary bypass may manifest with several adverse physiologic and immunologic effects, with varying degrees of thrombocytopenia and multi-organ dysfunction, sometimes very similar to TAMOF. LCOS is a common occurrence in children with critical heart disease, presenting in as much as 23.8% of infants postoperative of congenital heart surgery. Therapeutic plasma exchange (TPE) has been offered as a promising therapy for TAMOF; however, the therapeutic implications of this modality in children with critical heart disease and a clinical diagnosis of TAMOF are unknown.ObjectivesWe describe our institutional experience with TPE as an adjuvant rescue therapy for children with critical heart disease and a clinical diagnosis of TAMOF, while supported by extracorporeal membrane oxygenation (ECMO).MethodsSingle-center retrospective analysis of children with critical heart disease admitted to the CICU and supported by ECMO, undergoing TPE for a clinical diagnosis of TAMOF between January 2006 and June 2015.ResultsForty-one patients were included for analysis. Median age and weight of patients was 0.6 years (range 0.0–17.2) and 8.5 kg (range 1.5–80.0). TPE was initiated at a median of 1 day (0–13) after initiation of ECMO. Modified organ failure index (MOFI) and platelet count improved after TPE start (p

Objective: The recommendations of the American Institute of Medicine (IOM) were revised recently in order to enhance maternal and neonatal health. The aim of our study was to investigate the risk of low birth weight (LBW) among women who follow the IOM recommendations. Materials and methods: Gestational weight gain (GWG) and rate of weight gain (RWG) across the different periods of pregnancy among women who delivered LBW fetuses were analyzed retrospectively. The logistic regression was used to analyze the risk of LBW and to identify recommendations. Results: From January 2008 to December 2009, 117 out of 4924 (2.4%) women delivered term LBW fetuses. After exclusions, 88 LBW and 91 control subjects were enrolled into the study. There was increased risk of cesarean delivery [odds ratio (OR) with 95% confidence interval (CI): 2.53 (1.33–4.83)] and neonatal asphyxia within 7 days of birth [OR 95% CI: 5.71 (1.21–26.83)] for the LBW group compared with the control group. Normal weight women [body mass index (BMI): 18.5–24.9 kg/m2] who followed the GWG and RWG recommendations of the IOM had no increased risk of LBW. However, there was a two-to three-fold increased LBW risk among normal weight women who followed the IOM guidelines when, during the 2nd trimester, their GWG was ≤7 kg [OR 95% CI: 2.21 (1.28–6.49)] or their RWG was ≤0.45 kg/week [OR 95% CI: 3.14 (1.32–7.47)]. Among underweight women (BMI

BACKGROUND: Drug resistance indexes (DRIs) quantify the cumulative impact of antimicrobial resistance on the likelihood that a given pathogen will be susceptible to antimicrobial therapy.

OBJECTIVES:To determine whether utilization of moxifloxacin, a broad-spectrum fluoroquinolone antibiotic, has changed since its addition to the British Columbia provincial formulary in 2009 and to determine whether utilization was guideline concordant.

Objective: This study aimed to investigate the risk of birth weights over 4000 g (macrosomia) in association with following the 2009 American Institute of Medicine (AIOM) recommendations. Materials and Methods: Seventy-six nondiabetic women who delivered a singleton, term macrosomic fetus and 82 women who delivered a singleton, term fetus weighing 1000 mL at delivery (35.5% vs. 6.1%, p 11.5 kg, the risk of macrosomia increased nine-fold (OR = 9.63; 95% CI 1.76–52.74). Conclusion: Macrosomia resulted in more cesarean deliveries and greater maternal blood loss at birth. In Taiwan, to prevent macrosomia, we suggest that the total gestational weight gain should be

ABSTRACT The intracellular protozoan Toxoplasma gondii dramatically reprograms the transcriptome of host cells it infects, including substantially up-regulating the host oncogene c-myc. By applying a flow cytometry-based selection to infected mouse cells expressing green fluorescent protein fused to c-Myc (c-Myc–GFP), we isolated mutant tachyzoites defective in this host c-Myc up-regulation. Whole-genome sequencing of three such mutants led to the identification of MYR1 (Myc regulation 1; TGGT1_254470) as essential for c-Myc induction. MYR1 is a secreted protein that requires TgASP5 to be cleaved into two stable portions, both of which are ultimately found within the parasitophorous vacuole and at the parasitophorous vacuole membrane. Deletion of MYR1 revealed that in addition to its requirement for c-Myc up-regulation, the MYR1 protein is needed for the ability of Toxoplasma tachyzoites to modulate several other important host pathways, including those mediated by the dense granule effectors GRA16 and GRA24. This result, combined with its location at the parasitophorous vacuole membrane, suggested that MYR1 might be a component of the machinery that translocates Toxoplasma effectors from the parasitophorous vacuole into the host cytosol. Support for this possibility was obtained by showing that transit of GRA24 to the host nucleus is indeed MYR1-dependent. As predicted by this pleiotropic phenotype, parasites deficient in MYR1 were found to be severely attenuated in a mouse model of infection. We conclude, therefore, that MYR1 is a novel protein that plays a critical role in how Toxoplasma delivers effector proteins to the infected host cell and that this is crucial to virulence. IMPORTANCE Toxoplasma gondii is an important human pathogen and a model for the study of intracellular parasitism. Infection of the host cell with Toxoplasma tachyzoites involves the introduction of protein effectors, including many that are initially secreted into the parasitophorous vacuole but must ultimately translocate to the host cell cytosol to function. The work reported here identified a novel protein that is required for this translocation. These results give new insight into a very unusual cell biology process as well as providing a potential handle on a pathway that is necessary for virulence and, therefore, a new potential target for chemotherapy.

BACKGROUND:The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. METHODS:The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. RESULTS:Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90-100%). CONCLUSION:Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.

Paper dust is a kind of cellulosic waste that is generated by converting operations in paper mills. It was derived to a low-grade cellulose acetate in this study. Papers made from recycled fiber were then impregnated with the resultant cellulose acetate. Effects of impregnation conditions on the paper properties were statistically investigated by employing central composite design (CCD) based response surface methodology (RSM). Four response variables, namely density, burst index, smoothness, and rate of surface wettability were analyzed. Polynomial estimation model of each response was developed as functions of three independent variables, which are pressing temperature (T), dipping time (D), and concentration of cellulose acetate (C). The paper which was impregnated based on the calculated optimum condition (T: 163 oC, D: 2.8 minutes, and C: 2.7 percent), possessed a density of 0.5450 g/cm3, rate of surface wettability of 0.012o/s, burst index of 2.84 kPa m2/g, and paper smoothness of 475 mL/min. There was no significant difference between the experimental values and the predicted values calculated from estimation models. The cellulose acetate impregnated Braille papers made from recycled fibre was found to have better properties than those of commercial Braille paper in terms of rate of surface wettability and burst index.

Species identification and characterization in tropical environments is an emerging field in tropical remote sensing. Significant efforts are currently aimed at the detection of tree species, of levels of forest successional stages, and the extent of liana occurrence at the top of canopies. In this paper we describe our use of high resolution imagery from the Quickbird Satellite to estimate the flowering population of Tabebuia guayacan trees at Barro Colorado Island (BCI), in Panama. The imagery was acquired on 29 April 2002 and 21 March 2004. Spectral Angle Mapping via a One-Class Support Vector machine was used to detect the presence of 422 and 557 flowering tress in the April 2002 and March 2004 imagery. Of these, 273 flowering trees are common to both dates. This study presents a new perspective on the effectiveness of high resolution remote sensing for monitoring a phenological response and its use as a tool for potential conservation and management of natural resources in tropical environments.

OBJECTIVE: Antibiotic resistance is accelerated by the overuse of antibiotics. Do Bugs Need Drugs? is an educational program adapted in British Columbia to target both the public and health care professionals, with the aim of reducing unnecessary prescribing. The current article presents a descriptive evaluation of the impact of the program over the first four years.