Pharmacokinetics and pharmacogenomics of once-daily raltegravir and atazanavir in healthy volunteers.

Atazanavir inhibits UDP-glucuronyl-transferase-1A1 (UGT1A1), which metabolizes raltegravir, but the magnitude of steady-state inhibition and role of the UGT1A1 genotype are unknown. Sufficient inhibition could lead to reduced-dose and -cost raltegravir regimens. Nineteen healthy volunteers, age 24 to 51 years, took raltegravir 400 mg twice daily (arm A) and 400 mg plus atazanavir 400 mg once daily (arm B), separated by ?3 days, in a crossover design. After 1 week on each regimen, raltegravir and raltegravir-glucuronide plasma and urine concentrations were measured by liquid chromatography-tandem mass spectrometry in multiple samples obtained over 12 h (arm A) or 24 h (arm B) and analyzed by noncompartmental methods. UGT1A1 promoter variants were detected with a commercially available kit and published primers. The primary outcome was the ratio of plasma raltegravir C(tau), or concentration at the end of the dosing interval, for arm B (24 h) versus arm A (12 h). The arm B-to-arm A geometric mean ratios (95% confidence interval, P value) for plasma raltegravir C(tau), area under the concentration-time curve from 0 to 12 h (AUC(0-12)), and raltegravir-glucuronide/raltegravir AUC(0-12) were 0.38 (0.22 to 0.65, 0.001), 1.32 (0.62 to 2.81, 0.45), and 0.47 (0.38 to 0.59, <0.001), respectively. Nine volunteers were heterozygous and one was homozygous for a UGT1A1 reduction-of-function allele, but these were not associated with metabolite formation. Although atazanavir significantly reduced the formation of the glucuronide metabolite, its steady-state boosting of plasma raltegravir did not render the C(tau) with a once-daily raltegravir dose of 400 mg similar to the C(tau) with the standard twice-daily dose. UGT1A1 promoter variants did not significantly influence this interaction.

Correlation of wear in vivo and six laboratory wear methods.

OBJECTIVE: We examined the correlation between clinical wear rates of restorative materials and enamel (TRAC Research Foundation, Provo, USA) and the results of six laboratory test methods (ACTA, Alabama (generalized, localized), Ivoclar (vertical, volumetric), Munich, OHSU (abrasion, attrition), Zurich). METHODS: Individual clinical wear data were available from clinical trials that were conducted by TRAC Research Foundation (formerly CRA) together with general practitioners. For each of the n=28 materials (21 composite resins for intra-coronal restorations [20 direct and 1 indirect], 5 resin materials for crowns, 1 amalgam, enamel) a minimum of 30 restorations had been placed in posterior teeth, mainly molars. The recall intervals were up to 5 years with the majority of materials (n=27) being monitored, however, only for up to 2 years. For the laboratory data, the databases MEDLINE and IADR abstracts were searched for wear data on materials which were also clinically tested by TRAC Research Foundation. Only those data for which the same test parameters (e.g. number of cycles, loading force, type of antagonist) had been published were included in the study. A different quantity of data was available for each laboratory method: Ivoclar (n=22), Zurich (n=20), Alabama (n=17), OHSU and ACTA (n=12), Munich (n=7). The clinical results were summed up in an index and a linear mixed model was fitted to the log wear measurements including the following factors: material, time (0.5, 1, 2 and 3 years), tooth (premolar/molar) and gender (male/female) as fixed effects, and patient as random effect. Relative ranks were created for each material and method; the same was performed with the clinical results. RESULTS: The mean age of the subjects was 40 (±12) years. The materials had been mostly applied in molars (81%) and 95% of the intracoronal restorations were Class II restorations. The mean number of individual wear data per material was 25 (range 14-42). The mean coefficient of variation of clinical wear data was 53%. The only significant correlation was reached by OHSU (abrasion) with a Spearman r of 0.86 (p=0.001). Zurich, ACTA, Alabama generalized wear and Ivoclar (volume) had correlation coefficients between 0.3 and 0.4. For Zurich, Alabama generalized wear and Munich, the correlation coefficient improved if only composites for direct use were taken into consideration. The combination of different laboratory methods did not significantly improve the correlation. SIGNIFICANCE: The clinical wear of composite resins is mainly dependent on differences between patients and less on the differences between materials. Laboratory methods to test conventional resins for wear are therefore less important, especially since most of them do not reflect the clinical wear.

Adjuvant early breast cancer systemic therapies according to daily used technologies.

Prognosis of early breast cancer patients is significantly improved with the use of adjuvant therapies. Various guidelines have been proposed to select patients who will derive the most benefit from such treatments. However, classifications have limited usefulness in subsets of patients such as those with node negative breast cancer. The 2007 St. Paul de Vence Clinical Practice Recommendations proposed to consider adjuvant therapy in accordance with the 10-year relapse-free survival reduction estimated by Adjuvant! Online. However, many limitations remain regarding the use of Adjuvant! Online. Among them, adverse prognostic and/or predictive factors such as vascular invasion, mitotic activity, progesterone receptor negativity, and HER-2 expression are not incorporated in the routine clinical decision process. Our group has therefore issued guidelines based on the consideration of both Adjuvant! Online calculations and the prognostic and/or predictive effects of these markers. In addition, web-accessible comprehensive tables summarizing these recommendations are provided.

Chest pain in daily practice: occurrence, causes and management

QUESTIONS UNDER STUDY: We assessed the occurrence and aetiology of chest pain in primary care practice. These features differ between primary and emergency care settings, where most previous studies have been performed. METHODS: 59 GPs in western Switzerland recorded all consecutive cases presenting with chest pain. Clinical characteristics, laboratory tests and other investigations as well as the diagnoses remaining after 12 months of follow-up were systematically registered. RESULTS: Among 24,620 patients examined during a total duration of 300 weeks of observation, 672 (2.7%) presented with chest pain (52% female, mean age 55 +/- 19(SD)). Most cases, 442 (1.8%), presented new symptoms and in 356 (1.4%) it was the reason for consulting. Over 40 ailments were diagnosed: musculoskeletal chest pain (including chest wall syndrome) (49%), cardiovascular (16%), psychogenic (11%), respiratory (10%), digestive (8%), miscellaneous (2%) and without diagnosis (3%). The three most prevalent diseases were: chest wall syndrome (43%), coronary artery disease (12%) and anxiety (7%). Unstable angina (6), myocardial infarction (4) and pulmonary embolism (2) were uncommon (1.8%). Potentially serious conditions including cardiac, respiratory and neoplasic diseases accounted for 20% of cases. A large number of laboratory tests (42%), referral to a specialist (16%) or hospitalisation (5%) were performed. Twentyfive patients died during follow-up, of which twelve were for a reason directly associated with thoracic pain [cancer (7) and cardiac causes (5)]. CONCLUSIONS: Thoracic pain was present in 2.7% of primary care consultations. Chest wall syndrome pain was the main aetiology. Cardio - vascular emergencies were uncommon. However chest pain deserves full consideration because of the occurrence of potentially serious conditions.

Physico-chemical characterization and oxidative reactivity evaluation of aged brake wear particles

Brake wear dust is a significant component of traffic emissions and has been linked to adverse health effects. Previous research found a strong oxidative stress response in cells exposed to freshly generated brake wear dust. We characterized aged dust collected from passenger vehicles, using microscopy and elemental analyses. Reactive oxygen species (ROS) generation was measured with acellular and cellular assays using 2′7-dichlorodihydrofluorescein dye. Microscopy analyses revealed samples to be heterogeneous particle mixtures with few nanoparticles detected. Several metals, primarily iron and copper, were identified. High oxygen concentrations suggested that the elements were oxidized. ROS were detected in the cell-free fluorescent test, while exposed cells were not dramatically activated by the concentrations used. The fact that aged brake wear samples have lower oxidative stress potential than fresh ones may relate to the highly oxidized or aged state of these particles, as well as their larger size and smaller reactive surface area.

1965 Womens Wear Campaign

Highlights from the creative presentation made to Lightning Fastener for the 1965 Womens Wear campaign.

A physical activity intervention in a workplace setting

Physical inactivity poses a huge burden on Canada's health care system and is detrimental to the health of Canadians (Katzmarzyk & Janssen, 2004). Walking is a viable option for individuals to become physically active on a daily basis and is in fact the most commonly reported leisure time physical activity. It has been associated with many health benefits including weight loss/weight control, reduced risk of coronary artery disease and diabetes, lowered blood pressure, and improved psychological wellbeing (Brisson & Tudor-Locke, 2004). Specifically, individuals' stage of change, selfefficacy and health related quality of life (HRQL) are three psychological constructs that can be greatly improved with increased physical activity (Dishman, 1991; Penedo & Dahn, 2005; Poag & McAuley, 1992). Public health physical activity recommendations exist but many individuals find these difficult to meet due to overly busy lifestyles (Public Health Agency of Canada, 2003). Pedometers are inexpensive devices that can monitor individual bouts of walking so that the incorporation of physical activity into one's daily life is more plausible. They are also excellent tools for motivation, goalsetting, and immediate feedback (Brisson & Tudor-Locke, 2004). Since many people spend a large proportion of their time at their places of employment, workplaces have begun to be a common site for the development of physical activity interventions. These programs have been growing in popUlarity and have shown numerous benefits for both employees and employers (Voit, 2001). The purpose of the current study was to implement and evaluate the use of a pedometer-based physical activity intervention incorporating goal-setting and physical activity logs in a workplace setting, and to examine the relationship between different types of self-efficacy (task, barrier, and scheduling) and different phases of the intervention. Twenty male participants from a local steel manufacturing plant who exhibited health risk factors (e.g. hypertension, diabetes, etc.) were assigned to one of two groups (group A or group B). All participants were asked to wear pedometers on their waists, record their daily steps, set goals that were outlined on a step-tracking sheet (detennined by their baseline number of steps), and keep track of their work days, wakelbed time, sedentary time, and time spent doing other physical activity. Group A began the intervention immediately following the baseline measures, whereas group B continued with their regular routine for 4 weeks before beginning. Physiological measures (height, weight, blood pressure, relative body fat, waist and hip circumference, and body mass index) were taken and a battery of questionnaires that assessed barrier, task and scheduling self-efficacy, HRQL, and stage of change administered at baseline, week 5 (end of intervention for group A), week 9 (end of intervention for group B; follow-up for group A) and week 13 (follow-up for both groups). Results showed that this workplace physical activity intervention was successful at increasing the participants' daily steps, that task self-efficacy is a significant predictor of participants' exercise adherence during the initial stages of participation (intervention phase), and that the participants felt that this intervention was effective. Finally, further exploratory analyses showed that this intervention was effective for all participants, but most valuable for participants most in need of improvement - that is, those who were most sedentary prior to the intervention. This intervention is an inexpensive use of simple and effective tools (e.g. pedometers), has the potential to attract a wide variety of participants and become a pennanent part of any health promotion initiative.

The condition of Niagara Falls, and the measures needed to preserve them : eight letters published in the New York Evening post, the New York tribune, and the Boston daily advertiser, during the summer of 1882 /

Appendix: Extracts from Harper's weekly, New York herald, New York tribune and the Nation.

Role of family eating practices on daily nutrient intakes, dietary patterns and measures of body composition in peri-adolescents

Although family eating practices (FEPs) playa role in the formation of eating practices in children, there is a lack of evidence regarding the role of FEPs on obesity (DB) risk. The purpose of this thesis was to assess the role of child, mother 'and father eating practices (CEPs; MEPS; FaEPs) on nutrient intakes, dietary patterns and body composition. Data were collected on approximately 2,400 peri-adolescents (s250 with complete covariate data). Dietary patterns were assessed using scores that reflected how closely participants followed DASH and Health Canada (HC) recommendations. In girls, poor CEPs, MEPs and FaEPs were associated with increased BMI and risk of overweight and poor dietary patterns according to DASH, and DASH and HC, respectively. In boys, poor CEPs and FaEPs were associated with increased monounsaturated and trans fat, and Vitamin C intakes, respectively. These findings suggest FEPs are associated with DB risk, particularly in girls.

Daily Physical Activity as an Intervention Strategy for Anxious Elementary Students

The focus of this project was twofold: a comprehensive examination of provincially mandated, school-based physical activity programming beyond physical education, as well as an exploration of the potential relationship between school-based physical activity and student anxiety. The data were collected using a descriptive research methodology consisting of a qualitative document analysis of provincial government publications pertaining to school-based physical activity programming and the literature on the relationship between physical activity and student anxiety. The findings revealed inconsistencies between the Canadian provinces and territories in providing mandated school-based physical activity beyond physical education. It was also revealed that regular school-based physical activity has the potential to make a positive impact on students’ lives in many ways. Students are living more sedentary lives, and evidence shows that regular physical activity could prevent and treat student anxiety.

Alexandria Daily Gazette, 9 September 1812 (vol. 12, no. 3744) - Newspaper

Volumes of interest were published in 1812 with articles about the War of 1812. Issue for Sept. 9, 1812 includes a proclamation by Major General Isaac Brock.

Does bracing affect bone health in women with adolescent idiopathic scoliosis?

Purpose: Adolescent idiopathic scoliosis (AIS) is often associated with low bone mineral content and density (BMC, BMD). Bracing, used to manage spine curvature, may interfere with the growth-related BMC accrual, resulting in reduced bone strength into adulthood. The purpose of this study was to assess the effects of brace treatment on BMC in adult women, diagnosed with AIS and braced in early adolescence. Methods: Participants included women with AIS who: (i) underwent brace treatment (AIS-B, n = 15, 25.6 ± 5.8 yrs), (ii) underwent no treatment (AIS, n = 15, 24.0 ± 4.0 yrs), and (iii) a healthy comparison group (CON, n = 19, 23.5 ± 3.8 yrs). BMC and body composition were assessed using dual-energy X-ray absorptiometry. Differences between groups were examined using a oneway ANOVA or ANCOVA, as appropriate. Results: AIS-B underwent brace treatment 27.9 ± 21.6 months, for 18.0 ± 5.4 h/d. Femoral neck BMC was lower (p = 0.06) in AIS-B (4.54 ± 0.10 g) compared with AIS (4.89 ± 0.61 g) and CON (5.07 ± 0.58 g). Controlling for lean body mass, calcium and vitamin D daily intake, and strenuous physical activity, femoral neck BMC was statistically different (p = 0.02) between groups. A similar pattern was observed at other lower extremity sites (p < 0.05), but not in the spine or upper extremities. BMC and BMD did not correlate with duration of brace treatment, duration of daily brace wear, or overall physical activity. Conclusion: Young women with AIS, especially those who were treated with a brace, have significantly lower BMC in their lower limbs compared to women without AIS. However, the lack of a relationship between brace treatment duration during adolescence and BMC during young adulthood, suggests that the brace treatment is not the likely mechanism of the low BMC.

Daily Journals of Louis J. Cahill, 1946-2006

41 hardcover and soft cover journals containing handwritten entries