Patellofemoral contact forces and knee gait mechanics 3 months after ACL reconstruction are associated with cartilage degradation 24 months after surgery.

OBJECTIVE: Evaluate patellofemoral cartilage health, as assessed by quantitative magnetic resonance imaging (qMRI) T2 relaxation times, 24-months after ACL reconstruction (ACLR) and determine if they were associated with patellofemoral contact forces and knee mechanics during gait 3 months after surgery. DESIGN: Thirty individuals completed motion analysis during overground walking at a self-selected speed 3 months after ACLR. An EMG-driven neuromusculoskeletal model was used to determine muscle forces, which were then used in a previously described model to estimate patellofemoral contact forces. Biomechanical variables of interest included peak patellofemoral contact force, peak knee flexion angle and moment, and walking speed. These same participants underwent a sagittal bilateral T2 mapping qMRI scan 24-months after surgery. T2 relaxation times were estimated for both patellar and trochlear cartilage. Paired t-tests were used to compare T2 relaxation times between limbs while Pearson correlations and linear regressions were utilized to assess the association between the biomechanical variables of interest and T2 relaxation times. RESULTS: Prolonged involved limb trochlear T2 relaxation times (vs uninvolved) were present 24-months after surgery, indicating worse cartilage health. No differences were detected in patellar cartilage. Significant negative associations were present within the involved limb for all the biomechanical variables of interest 3 months after ACLR and trochlear T2 relaxation times at 24-months. No associations were found in patellar cartilage or within the uninvolved limb. CONCLUSIONS: Altered involved limb trochlear cartilage health is present 24-months after ACLR and may be related to patellofemoral loading and other walking gait mechanics 3 months after surgery.

Avian metapneumovirus subtype C in Wild Waterfowl in Ontario, Canada.

Avian metapneumovirus (aMPV) is an emerging poultry pathogen that has a significant economic impact on poultry production worldwide. The geographic range of the virus continues to expand, and wild birds have been implicated as reservoirs of aMPV that have the potential to spread the virus over long distances. Our objective was to determine the apparent prevalence of aMPV subtype C in wild waterfowl in Ontario, Canada. Wild waterfowl were captured in August and September, 2016 as part of routine migratory waterfowl population monitoring by the Ontario Ministry of Natural Resources and Forestry. Oropharyngeal and cloacal swabs were collected from each bird and placed together for aMPV testing using real-time RT-PCR. A total of 374 live wild birds from 23 lakes were sampled and tested for aMPV. Among all ducks tested, 84 (22%) were positive for aMPV. The proportion of samples that tested positive ranged from 0% in ring-necked ducks (Aythya collaris) and green-winged teal (Anas carolinensis) to 44% (8 of 18) in American black ducks (A. rubripes). Waterfowl positive for aMPV were found at 14 of 23 lakes in the study area and the percent positive at these 14 lakes ranged between 5% and 84%. Although subtype C aMPV has been detected in a variety of wild birds in North America, this is the first report of aMPV in wild ducks in Ontario, Canada. The high apparent prevalence, particularly in mallards and American black ducks (37 and 44%, respectively), suggests that these species may be important reservoirs of aMPV. Given the potential impact of aMPV on domestic poultry and the potential role of wild birds as reservoirs of the virus, further investigation of the geographic distribution, risk factors associated with aMPV carriage in wild waterfowl and potential role of other birds in the epidemiology of aMPV in Canada is warranted.

Raccoon rabies outbreak in Hamilton, Ontario: A progress report.

BACKGROUND: Raccoon rabies is caused by a variant of the rabies virus found in raccoons but transmissible to other mammalian species, including humans. The disease of rabies caused by raccoon variant rabies virus is indistinguishable from rabies caused by other rabies virus variants. OBJECTIVE: This paper describes the raccoon rabies outbreak in Ontario (identified in December 2015) and the control measures undertaken to curb the spread of the epizootic using the One Health approach. INVESTIGATION AND RESULTS: Representatives from local, provincial and federal agencies collectively activated a raccoon rabies response that involved policy updates, enhanced surveillance, a public education campaign and mass vaccination of wildlife and domestic animals. Between December 2015 and June 2017, 338 animals tested positive for raccoon rabies in Ontario. While the majority of the cases were raccoons, there was significant spillover into striped skunks, as well as other species including two cats, a fox and a llama. Viral genome sequencing determined that this epizootic was likely caused by long-distance translocation from the United States. CONCLUSION: This outbreak of raccoon rabies is by far the largest to have occurred in Canada and the first raccoon rabies outbreak documented in a densely populated urban area. This is also the first time this rabies virus variant has been identified in a domestic animal in Canada. A collaborative approach involving numerous stakeholders in the public and private sectors has been instrumental in addressing this epizootic. Though case incidence appears to be declining, several years will likely be required to reach elimination. Continued collaboration between these agencies is necessary to achieve this goal.

Maternal obesity, gestational diabetes, breastfeeding and childhood overweight at age 2 years.

BACKGROUND: Maternal obesity, excessive gestational weight gain (EGWG), gestational diabetes mellitus (GDM) and breastfeeding are four important factors associated with childhood obesity. OBJECTIVES: The objective of the study was to assess the interplay among these four factors and their independent contributions to childhood overweight in a cohort with standard clinical care. METHODS: The cohort included 15 710 mother-offspring pairs delivered in 2011. Logistic regression was used to assess associations between maternal exposures and childhood overweight (body mass index >85th percentile) at age 2 years. RESULTS: Mothers with pre-pregnancy obesity or overweight were more likely to have EGWG, GDM and less likely to breastfeed ≥6 months. Mothers with GDM had 40-49% lower EGWG rates and similar breastfeeding rates compared with mothers without GDM. Analysis adjusted for exposures and covariates revealed an adjusted odds ratio (95% confidence interval) associated with childhood overweight at age 2 years of 2.34 (2.09-2.62), 1.50 (1.34-1.68), 1.23 (1.12-1.35), 0.95 (0.83-1.10) and 0.76 (0.69-0.83) for maternal obesity, overweight, EGWG, GDM and breastfeeding ≥6 months vs. <6 months, respectively. CONCLUSIONS: In this large clinical cohort, GDM was not associated with, but maternal pre-pregnancy obesity or overweight and EGWG were independently associated with an increased risk, and breastfeeding ≥6 months was associated with a decreased risk of childhood overweight at age 2 years.

Chikungunya in Jamaica: Public health effects and clinical features in children / Chikungunya en Jamaica ­ Efectos en la Salud Pública y Características Clínicas en Niños

Chikungunya virus (CHIKV) entered the Caribbean for the first time in 2013 and Jamaica experienced its maiden epidemic with Chikungunya Fever in 2014. We aimed to describe the public health effects and describe the clinical features in children and adolescents in Jamaica. METHODS: This study reviewed the public health effects of the illness in Jamaica by reviewing available data sources and the clinical features in 210 children and adolescents meeting the case definition at two hospitals, Bustamante Hospital for Children and University Hospital of the West Indies between August 23 and October 31, 2014 by chart review. Descriptive analyses and comparisons between groups using the Mann-Whitney U test were performed with SPSS version 22. RESULTS: The majority of households were affected by the illness which caused widespread absenteeism from school and work, loss of productivity and economic losses estimated at 60 billion dollars. The health sector was impacted by increased numbers seen in clinics and emergency departments, increased need for bed space and pharmaceuticals. Ninety-nine per cent of the children were febrile with a median maximal temperature of 102.4 F. Ninety-three per cent had household contacts of 0­20 persons. In addition to fever, maculopapular rash and joint pains, infants six months and younger presented with irritability and groaning (p = 0.00) and those between six months and six years presented with febrile seizures (p = 0.00). Neurologic involvement was noted in 24%. Apart from anaemia, few had other laboratory derangements. Few had severe organ dysfunction and there were no deaths. CONCLUSION: The Chikungunya Fever epidemic had significant public health and economic impact in Jamaica. In children, there were characteristic presentations in neonates and young infants and in children six months to six years. Neurologic involvement was common but other organ dysfunction was rare. These findings underscore the need to prevent further epidemics and the quest for a vaccine.(AU)

Antecedentes: El virus de Chikungunya (CHIKV) entró en el Caribe por primera vez en 2013, y Jamaica experimentó su primera epidemia de fiebre de Chikungunya en 2014. Nos propusimos como objetivo describir sus efectos en la salud pública y describir sus características clínicas en niños y adolescentes en Jamaica. Métodos: Este estudio examinó los efectos de la enfermedad en la salud pública en Jamaica. El examen se realizó mediante la revisión de fuentes de datos disponibles y las características clínicas en 210 niños y adolescentes que cumplían con la definición del caso en dos hospitales ­ Hospital Pediátrico Bustamante y el Hospital Universitario de West Indies ­ entre el 23 de agosto y 31 de octubre de 201, según las historias clínicas. Se realizaron análisis descriptivos y comparaciones entre los grupos usando la prueba U de Mann-Whitney y la versión 22 de SPSS Resultados: La mayoría de los hogares fueron afectados por la enfermedad, que causó un ausentismo generalizado en escuelas y trabajos, pérdida de productividad, y pérdidas económicas estimadas en 60 billones de dólares. El sector de la salud fue afectado por un aumento del número de personas atendidas en clínicas y departamentos de urgencias, y una mayor necesidad de camas en los hospitales y productos farmacéuticos. Noventa y nueve por ciento de los niños presentaron un estado febril con una temperatura mediana máxima de 102.4 F. Un noventa y tres por ciento tuvo contactos domésticos de personas de 0­20. Además de fiebre, erupciones maculopapulares y dolores en las articulaciones, los niños de seis meses o menos edad, presentaron irritabilidad y quejidos (p = 0.00), y aquellos entre seis meses y seis años de edad presentaron convulsiones febriles (p = 0.00). Se observó compromiso neurológico en el 24%. Aparte de anemia, algunos tenían otros trastornos de laboratorio. Otros presentaban una disfunción orgánica severa y no hubo muertes. Conclusión: La epidemia de fiebre de Chikungunya tuvo un impacto significativo tanto en la salud pública como en la economía de Jamaica. Los niños presentaron manifestaciones características, observadas tanto en recién nacidos y bebés pequeños como en niños de seis meses a seis años. El compromiso neurológico fue común, pero cualquiera otra disfunción orgánica fue rara. Estos hallazgos subrayan la necesidad de hacer más por evitar las epidemias y buscar la solución de una vacuna.(AU)

A more informed evaluation of medial compartment loading: the combined use of the knee adduction and flexor moments.

OBJECTIVE: To evaluate if the peak knee flexor moment (pKFM) provides unique and meaningful information about peak medial compartment loading above and beyond what is obtained from the peak knee adduction moment. METHODS: Standard video-based motion capture and EMG recordings were collected for 10 anterior cruciate ligament (ACL) reconstructed subjects walking at a self-selected speed. Knee joint moments were obtained using inverse dynamics and medial contact force was computed using an EMG-driven musculoskeletal model. Linear regression with the peak adductor moment entered first was implemented to isolate the unique contribution of the peak flexor moment to peak medial loading. RESULTS: Peak moments and medial contact force occurred during weight acceptance at approximately 23% of stance. The peak knee adduction moment (pKAM) was a significant predictor of peak medial loading (P = 0.004) accounting for approximately 63% of the variance. The pKFM was also a significant predictor (P = 0.009) accounting for an additional 22% of the variance. When entered together pKAM and pKFM accounted for more than 85% of the variance in peak medial compartment loading. CONCLUSION: The combined use of the peak knee flexor and adductor moments provides a significantly more accurate estimate of peak medial joint loading than the peak adduction moment alone. More accurate inferences of joint contact force will assist clinicians and researchers investigating relationships between joint loading and the onset and progression of knee osteoarthritis (OA).

Living near a freeway is associated with lower bone mineral density among Mexican Americans.

UNLABELLED: We hypothesized that chronic exposures to traffic combustion products may lower bone mineral density (BMD). We found that proximity to freeways was associated with reduced BMD. Our findings suggest that traffic-related pollution may contribute to the occurrence of osteopenia and osteoporosis. INTRODUCTION: Adults residing in rural areas have been linked with higher BMD. We aimed to determine if this difference is due in part to air pollution by examining the relationships between traffic metrics and ambient air pollution with total body and pelvic BMD. METHODS: Mexican American adults (n = 1,175; mean 34 years; 72 % female) who had participated in the BetaGene study of air pollution, obesity, and insulin resistance were included in this analysis. Total body and pelvic BMD were estimated using dual-energy X-ray absorptiometry. Traffic and ambient air pollutant exposures were estimated at residences using location and ambient monitoring data. Variance component models were used to analyze the associations between residential distance to the nearest freeway and ambient air pollutants with BMD. RESULTS: Residential proximity to a freeway was associated with lower total body BMD (p-trend = 0.01) and pelvic BMD (p-trend = 0.03) after adjustment for age, sex, weight, and height. The adjusted mean total body and pelvic BMD in participants living within 500 m of a freeway were 0.02 and 0.03 g/cm(2) lower than participants living greater than 1,500 m from a freeway. These associations did not differ significantly by age, sex, or obesity status. Results were similar after further adjustment for body fat and weekly physical activity minutes. Ambient air pollutants (NO2, O3, and PM2.5) were not significantly associated with BMD. CONCLUSIONS: Traffic-related exposures in overweight and obese Mexican Americans may adversely affect BMD. Our findings indicate that long-term exposures to traffic may contribute to the occurrence of osteoporosis and its consequences.

Biodistribution and Radiation Dosimetry for the Novel SV2A Radiotracer [(18)F]UCB-H: First-in-Human Study.

PURPOSE: [(18)F]UCB-H is a novel radiotracer with a high affinity for synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in synaptic vesicles. SV2A is the binding site of levetiracetam, a "first-in-class" antiepileptic drug with a distinct but still poorly understood mechanism of action. The objective of this study was to determine the biodistribution and radiation dosimetry of [(18)F]UCB-H in a human clinical trial and to establish injection limits according to biomedical research guidelines. Additionally, the clinical radiation dosimetry results were compared to estimations in previously published preclinical data. PROCEDURES: Dynamic whole body positron emission tomography/X-ray computed tomography (PET/CT) imaging was performed over approximately 110 min on five healthy male volunteers after injection of 144.5 ± 7.1 MBq (range, 139.1-156.5 MBq) of [(18)F]UCB-H. Major organs were delineated on CT images, and time-activity curves were obtained from co-registered dynamic PET emission scans. The bladder could only be delineated on PET images. Time-integrated activity coefficients were calculated as area under the curve using trapezoidal numerical integration. Urinary excretion data based on PET activities including voiding was also simulated using the dynamic bladder module of OLINDA/EXM. The radiation dosimetry was calculated using OLINDA/EXM. RESULTS: The effective dose to the OLINDA/EXM 70-kg standard male was 1.54 × 10(-2) ± 6.84 × 10(-4) millisieverts (mSv)/MBq, with urinary bladder wall, gallbladder wall, and the liver receiving the highest absorbed dose. The brain, the tracer's main organ of interest, received an absorbed dose of 1.89 × 10(-2) ± 2.32 × 10(-3) mGy/MBq. CONCLUSIONS: This first human dosimetry study of [(18)F]UCB-H indicated that the tracer shows similar radiation burdens to widely used common clinical tracers. Single injections of at maximum 672 MBq for US practice and 649 MBq for European practice keep radiation exposure below recommended limits. Recently published preclinical dosimetry data extrapolated from mice provided satisfactory prediction of total body and effective dose but showed significant differences in organ absorbed doses compared to human data.

HOMA and Matsuda indices of insulin sensitivity: poor correlation with minimal model-based estimates of insulin sensitivity in longitudinal settings.

AIMS/HYPOTHESIS: Little is known about the performance of surrogates in assessing changes in insulin sensitivity over time. This report compared updated HOMA of insulin sensitivity (HOMA2-%S) and the Matsuda index from OGTTs with minimal model-based estimates of insulin sensitivity (SI) from frequently sampled IVGTTs (FSIGTs) in longitudinal settings and cross-sectional settings. METHODS: Two longitudinal studies were used: one a natural observational study in which 338 individuals were followed for a median of 4 years; one a clinical treatment study in which 97 individuals received pioglitazone treatment and were followed for 1 year. Pairs of OGTTs and FSIGTs were performed at baseline and follow-up. Correlations were computed. Impact of measurement uncertainty was investigated through simulation studies. RESULTS: Correlations between HOMA2-%S and SI from baseline or follow-up data were in the range reported previously (0.61-0.69). By contrast, correlations for changes over time were only 0.35-0.39. The corresponding correlations between the Matsuda index and SI were 0.66-0.72 for cross-sectional data and 0.40-0.48 for longitudinal change. Correlations for changes were significantly lower than the cross-sectional correlations in both studies (p < 0.03). Simulation results demonstrated that the reduced correlations for change were not explained by error propagation, supporting a real limitation of surrogates to fully capture longitudinal changes in insulin sensitivity. CONCLUSIONS/INTERPRETATION: HOMA and Matsuda indices derived from cross-sectional data should be used cautiously in assessing longitudinal changes in insulin sensitivity.

The hotel study: multimorbidity in a community sample living in marginal housing.

OBJECTIVE: The health of people living in marginal housing is not well characterized, particularly from the perspective of multimorbid illness. The authors investigated this population in a community sample. METHOD: A prospective community sample (N=293) of adults living in single-room occupancy hotels was followed for a median of 23.7 months. Assessment included psychiatric and neurological evaluation, multimodal MRI, and viral testing. RESULTS: Previous homelessness was described in 66.6% of participants. Fifteen deaths occurred during 552 person-years of follow-up. The standardized mortality ratio was 4.83 (95% CI=2.91-8.01). Substance dependence was ubiquitous (95.2%), with 61.7% injection drug use. Psychosis was the most common mental illness (47.4%). A neurological disorder was present in 45.8% of participants, with definite MRI findings in 28.0%. HIV serology was positive in 18.4% of participants, and hepatitis C virus serology in 70.3%. The median number of multimorbid illnesses (from a list of 12) was three. Burden of multimorbidity was significantly correlated with lower role functioning score. Comorbid addiction or physical illness significantly decreased the likelihood of treatment for psychosis but not the likelihood of treatment for opioid dependence or HIV disease. Participants who died during follow-up appeared to have profiles of multimorbidity similar to those of the overall sample. CONCLUSIONS: This marginally housed cohort had greater than expected mortality and high levels of multimorbidity with adverse associations with role function and likelihood of treatment for psychosis. These findings may guide the development of effective health care delivery in the setting of marginal housing.

Effect of pioglitazone on body composition and bone density in subjects with prediabetes in the ACT NOW trial.

AIMS: This study examined the effects of pioglitazone on body weight and bone mineral density (BMD) prospectively in patients with impaired glucose tolerance as pioglitazone (TZD) increases body weight and body fat in diabetic patients and increases the risk of bone fractures. METHODS: A total of 71 men and 163 women aged 49.3 (10.7) years [mean (s.d.)]; body mass index (BMI), 34.5 (5.9) kg/m(2) were recruited at five sites for measurements of body composition by dual energy X-ray absorptiometry at baseline and at conversion to diabetes or study end, if they had not converted. RESULTS: Mean follow-up was 33.6 months in the pioglitazone group and 32.1 months in the placebo group. Body weight increased 4.63 ± 0.60 (m ± s.e.) kg in the pioglitazone group compared to 0.98 ± 0.62 kg in the PIO group (p < 0.0001). Body fat rose 4.89 ± 0.42 kg in the pioglitazone group compared to 1.41 ± 0.44 kg, (p < 0.0001) in placebo-treated subjects. The increase in fat was greater in legs and trunk than in the arms. BMD was higher in all regions in men and significantly so in most. PIO decreased BMD significantly in the pelvis in men and women, decreased BMD in the thoracic spine and ribs of women and the lumbar spine and legs of men. Bone mineral content also decreased significantly in arms, legs, trunk and in the total body. CONCLUSIONS: Pioglitazone increased peripheral fat more than truncal fat and decreased BMD in several regions of the body.

Systematic evaluation of validated type 2 diabetes and glycaemic trait loci for association with insulin clearance.

AIMS/HYPOTHESIS: Insulin clearance is a highly heritable trait, for which few quantitative trait loci have been discovered. We sought to determine whether validated type 2 diabetes and/or glycaemic trait loci are associated with insulin clearance. METHODS: Hyperinsulinaemic-euglycaemic clamps were performed in two Hispanic-American family cohorts totalling 1329 participants in 329 families. The Metabochip was used to fine-map about 50 previously identified loci for type 2 diabetes, fasting glucose, fasting insulin, 2 h glucose or HbA1c. This resulted in 17,930 variants, which were tested for association with clamp-derived insulin clearance via meta-analysis of the two cohorts. RESULTS: In the meta-analysis, 38 variants located within seven loci demonstrated association with insulin clearance (p < 0.001). The top signals for each locus were rs10241087 (DGKB/TMEM195 [TMEM195 also known as AGMO]) (p = 4.4 × 10(-5)); chr1:217605433 (LYPLAL1) (p = 3.25 × 10(-4)); rs2380949 (GLIS3) (p = 3.4 × 10(-4)); rs55903902 (FADS1) (p = 5.6 × 10(-4)); rs849334 (JAZF1) (p = 6.4 × 10(-4)); rs35749 (IGF1) (p = 6.7 × 10(-4)); and rs9460557 (CDKAL1) (p = 6.8 × 10(-4)). CONCLUSIONS/INTERPRETATION: While the majority of validated loci for type 2 diabetes and related traits do not appear to influence insulin clearance in Hispanics, several of these loci do show evidence of association with this trait. It is therefore possible that these loci could have pleiotropic effects on insulin secretion, insulin sensitivity and insulin clearance.

Intent to quit among daily and non-daily college student smokers.

Given the high prevalence of young adult smoking, we examined (i) psychosocial factors and substance use among college students representing five smoking patterns and histories [non-smokers, quitters, native non-daily smokers (i.e. never daily smokers), converted non-daily smokers (i.e. former daily smokers) and daily smokers] and (ii) smoking category as it relates to readiness to quit among current smokers. Of the 4438 students at six Southeast colleges who completed an online survey, 69.7% (n = 3094) were non-smokers, 6.6% (n = 293) were quitters, 7.1% (n = 317) were native non-daily smokers, 6.4% (n = 283) were converted non-daily smokers and 10.2% (n = 451) were daily smokers. There were differences in sociodemographics, substance use (alcohol, marijuana, other tobacco products) in the past 30 days and psychosocial factors among these subgroups of students (P < 0.001). Among current smokers, there were differences in cigarettes smoked per day, recent quit attempts, self-identification as a smoker, self-efficacy and motivation to quit (P < 0.001). After controlling for important factors, converted non-daily smokers were more likely to be ready to quit in the next month versus native non-daily smokers (OR = 2.15, CI 1.32-3.49, P = 0.002). Understanding differences among young adults with different smoking patterns and histories is critical in developing interventions targeting psychosocial factors impacting cessation among this population.

Insulin clearance: confirmation as a highly heritable trait, and genome-wide linkage analysis.

AIMS/HYPOTHESIS: We have previously documented a high heritability of insulin clearance in a Hispanic cohort. Here, our goal was to confirm the high heritability in a second cohort and search for genetic loci contributing to insulin clearance. METHODS: Hyperinsulinaemic-euglycaemic clamps were performed in 513 participants from 140 Hispanic families. Heritability was estimated for clamp-derived insulin clearance and a two-phase genome-wide linkage scan was conducted using a variance components approach. Linkage peaks were further investigated by candidate gene association analysis in two cohorts. RESULTS: The covariate-adjusted heritability of insulin clearance was 73%, indicating that the majority of the phenotypic variance is due to genetic factors. In the Phase 1 linkage scan, no signals with a logarithm of odds (LOD) score >2 were detected. In the Phase 2 scan, two linkage peaks with an LOD >2 for insulin clearance were identified on chromosomes 15 (LOD 3.62) and 20 (LOD 2.43). These loci harbour several promising candidate genes for insulin clearance, with 12 single nucleotide polymorphisms (SNPs) on chromosome 15 and six SNPs on chromosome 20 being associated with insulin clearance in both Hispanic cohorts. CONCLUSIONS/INTERPRETATION: In a second Hispanic cohort, we confirmed that insulin clearance is a highly heritable trait and identified chromosomal loci that harbour genes regulating insulin clearance. The identification of such genes may improve our understanding of how the body clears insulin, thus leading to improved risk assessment, diagnosis, prevention and therapy of diabetes, as well as of other hyperinsulinaemic disorders, such as the metabolic syndrome and polycystic ovary syndrome.

Racial and ethnic disparities in diabetes risk after gestational diabetes mellitus.

AIMS/HYPOTHESIS: To investigate racial/ethnic disparities in diabetes risk after gestational diabetes mellitus (GDM). METHODS: This is a retrospective cohort study of women enrolled in the Kaiser Permanente Southern California health plan from 1995 to 2009. GDM status was identified on the basis of plasma glucose levels during pregnancy. The incidence of diabetes after the first delivery complicated by GDM before 31 December 2009 (n = 12,998) was compared with the experience for women without GDM (n = 64,668) matched on maternal age at delivery, race/ethnicity and year of delivery (1:5 ratio). Matched Cox regression was used to compare the RRs of diabetes associated with GDM within and across racial/ethnic groups. RESULTS: Compared with the women without GDM, the HRs (95% CI) of diabetes for women after GDM were 6.5 (5.2, 8.0) in non-Hispanic white, 7.7 (6.8, 8.7) in Hispanic, 9.9 (7.5, 13.1) in black and 6.3 (5.0, 7.9) in Asian/Pacific Islanders after adjustment for parity, maternal education, comorbidity and number of outpatient visits before the index pregnancy. The HR of diabetes for black women was significantly higher than that for non-Hispanic white women (p = 0.032). Further adjustment for prepregnancy BMI reduced the diabetes risk association with GDM for each racial/ethnic group, but did not explain the risk differences across groups. CONCLUSIONS/INTERPRETATIONS: Racial/ethnic disparities exist in risk of diabetes after GDM. Black women with GDM had the highest risk of developing diabetes. This highlights the importance of developing an effective diabetes screening and prevention programme in women with GDM, particularly black women with GDM.

High-density baiting with ONRAB® rabies vaccine baits to control Arctic-variant rabies in striped skunks in Ontario, Canada.

The Arctic variant of rabies virus has been maintained in striped skunks in small foci in southwestern Ontario, Canada, despite the control of the disease in red foxes. To control the disease in skunks, high-density baiting with ONRAB(®) oral rabies vaccine baits was conducted by air and by hand distribution of baits in the vicinity of skunk cases. During 2009, antibody prevalences in skunks were higher in areas baited at a density of 300 baits/km(2) and flight-line spacing of 0.25 km than at 0.5-km spacing. Once an area containing Arctic-variant cases was treated with high densities of ONRAB baits, the disease did not reoccur in skunks in those areas. During 2009, only eight skunks were diagnosed with the Arctic variant of rabies virus in Ontario.

Hair MDMA samples are consistent with reported ecstasy use: findings from a study investigating effects of ecstasy on mood and memory.

AIMS: Our group has conducted several Internet investigations into the biobehavioural effects of self-reported recreational use of MDMA (3,4-methylenedioxymethamphetamine or Ecstasy) and other psychosocial drugs. Here we report a new study examining the relationship between self-reported Ecstasy use and traces of MDMA found in hair samples. METHODS: In a laboratory setting, 49 undergraduate volunteers performed an Internet-based assessment which included mood scales and the University of East London Drug Use Questionnaire, which asks for history and current drug use. They also provided a hair sample for determination of exposure to MDMA over the previous month. RESULTS: Self-report of Ecstasy use and presence in hair samples were consistent (p < 0.00001). Both subjective and objective measures predicted lower self-reported ratings of happiness and higher self-reported stress. Self-reported Ecstasy use, but not presence in hair, was also associated with decreased tension. CONCLUSION: Different psychoactive drugs can influence long-term mood and cognition in complex and dynamically interactive ways. Here we have shown a good correspondence between self-report and objective assessment of exposure to MDMA. These data suggest that the Internet has potentially high utility as a useful medium to complement traditional laboratory studies into the sequelae of recreational drug use.

Acute treatment of migraine.

Acute treatment of migraine has benefited first from major advances in pharmacological science followed in short order, sometimes preceded, by an improved understanding of pathogenesis, especially of headache. This chapter reviews the mechanisms of migraine that provide an understanding of the pharmacology and therapeutic targets for acute migraine medications. General clinical approaches to acute therapy are reviewed, and indices of acceptable acute therapeutic outcomes are discussed. Currently the serotonin (5-HT) 1B/1D agonist group of drugs, triptans, forms the mainstay of acute therapeutic regimens. Other approaches to acute treatment such as simple analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), ergots, and combination medications are reviewed. Finally, the newest acute treatments that are currently exploratory or under clinical investigation are discussed.

Field evaluation of an inactivated vaccine to control raccoon rabies in Ontario, Canada.

Since raccoon rabies first appeared in Ontario in 1999, >90,000 raccoons (Procyon lotor) have received IMRAB3 inactivated rabies vaccine via intramuscular (IM) injection and were released at the point of capture as part of a multiyear rabies control program, trap-vaccinate-release (TVR). Of the 132 confirmed cases infected with raccoon-variant rabies virus in Ontario between 1999 and 2005, two were from that vaccinated group, as indicated by the presence of identifying ear tags. During ongoing rabies control programs in 2003, sera were collected from 172 wild raccoons that had received IMRAB3 and tested for rabies-virus antibodies. Raccoons had one of three histories: 1) vaccinated in the current year only (to examine the response to primary vaccination), 2) vaccinated in the previous year only (to determine the duration of the primary antibody response), and 3) vaccinated in the previous year and current year (to examine antibody response to booster vaccination). Seroconversion in primary vaccinates could be detected as early as 1 wk postvaccination when sera were measured with the use of a competitive enzyme-linked immunosorbent assay (C-ELISA) with a cutoff value established to correspond to a neutralizing titer of 0.5 IU/ml. During weeks three and four postvaccination, 94% of sampled raccoons had detectable antibodies to rabies virus and 31% were still antibody positive the following year. Differences in the kinetics of the immune response were found in raccoons sampled from the two different TVR areas of the province. A strong anamnestic response was detected after booster vaccinations. IMRAB3 by IM injection was found to be an efficacious vaccine for rabies control in raccoons.

Determinants of glucose tolerance in impaired glucose tolerance at baseline in the Actos Now for Prevention of Diabetes (ACT NOW) study.

AIMS/HYPOTHESIS: The aim of the study was to examine the determinants of oral glucose tolerance in 602 persons with impaired glucose tolerance (IGT) who participated in the Actos Now for Prevention of Diabetes (ACT NOW) study. METHODS: In addition to the 602 IGT participants, 115 persons with normal glucose tolerance (NGT) and 50 with impaired fasting glucose (IFG) were identified during screening and included in this analysis. Insulin secretion and insulin sensitivity indices were derived from plasma glucose and insulin during an OGTT. The acute insulin response (AIR) (0-10 min) and insulin sensitivity (S(I)) were measured with the frequently sampled intravenous glucose tolerance test (FSIVGTT) in a subset of participants. RESULTS: At baseline, fasting plasma glucose, 2 h postprandial glucose (OGTT) and HbA(1c) were 5.8 +/- 0.02 mmol/l, 10.5 +/- 0.05 mmol/l and 5.5 +/- 0.04%, respectively, in participants with IGT. Participants with IGT were characterised by defects in early (DeltaI (0-30)/DeltaG (0-30) x Matsuda index, where DeltaI is change in insulin in the first 30 min and DeltaG is change in glucose in the first 30 min) and total (DeltaI(0-120)/DeltaG(0-120) x Matsuda index) insulin secretion and in insulin sensitivity (Matsuda index and S(I)). Participants with IGT in whom 2 h plasma glucose was 7.8-8.3 mmol/l had a 63% decrease in the insulin secretion/insulin resistance (disposition) index vs participants with NGT and this defect worsened progressively as 2 h plasma glucose rose to 8.9-9.94 mmol/l (by 73%) and 10.0-11.05 mmol/l (by 80%). The Matsuda insulin sensitivity index was reduced by 40% in IGT compared with NGT (p < 0.005). In multivariate analysis, beta cell function was the primary determinant of glucose AUC during OGTT, explaining 62% of the variance. CONCLUSION: Our results strongly suggest that progressive beta cell failure is the main determinant of progression of NGT to IGT.