Circadian genomics of the chick pineal gland in vitro

<p>Abstract</p> <p>Background</p> <p>Chick pinealocytes exhibit all the characteristics of a complete circadian system, comprising photoreceptive inputs, molecular clockworks and an easily measured rhythmic output, melatonin biosynthesis. These properties make the <it>in vitro </it>pineal a particularly useful model for exploring circadian control of gene transcription in a pacemaker tissue, as well as regulation of the transcriptome by primary inputs to the clock (both photic and noradrenergic).</p> <p>Results</p> <p>We used microarray analysis to investigate the expression of approximately 8000 genes within cultured pinealocytes subjected to both LD and DD. We report that a reduced subset of genes was rhythmically expressed <it>in vitro </it>compared to those previously published <it>in vivo</it>, and that gene expression rhythms were lower in amplitude, although the functional distribution of the rhythmic transcriptome was largely similar. We also investigated the effects of 6-hour pulses of light or of norepinephrine on gene expression in free-running cultures during both subjective day and night. As expected, both light and norepinephrine inhibited melatonin production; however, the two treatments differentially enhanced or suppressed specific sets of genes in a fashion that was dependent upon time of day.</p> <p>Conclusion</p> <p>Our combined approach of utilizing a temporal, photic and pharmacological microarray experiment allowed us to identify novel genes linking clock input to clock function within the pineal. We identified approximately 30 rhythmic, light-responsive, NE-insensitive genes with no previously known clock function, which may play a role in circadian regulation of the pineal. These are candidates for future functional genomics experiments to elucidate their potential role in circadian physiology. Further, we hypothesize that the pineal circadian transcriptome is reduced but functionally conserved <it>in vitro</it>, and supports an endogenous role for the pineal in regulating local rhythms in metabolism, immune function, and other conserved pathways.</p

Accuracy of physician-estimated probability of brain injury in children with minor head trauma

Objective: To evaluate the accuracy of physician estimates of the probability of intracranial injury in children with minor head trauma. Methods: This is a subanalysis of a large prospective multicentre cohort study performed from July 2001 to November2005. During data collection for the derivation of a clinical prediction rule for children with minor head trauma, physicians indicated their estimate of the probability of brain injury visible on computed tomography (P-Injury) and the probability of injury requiring intervention (P-Intervention) by choosing one of the following options: 0%, 1%, 2%, 3%, 4%, 5%, 10%, 20%, 30%, 40%, 50%, 75%, 90%, and 100%. We compared observed frequencies to expected frequencies of injury using Pearson’s χ2-test in analyses stratified by the level of each type of predicted probability and by year of age. Results: In 3771 eligible subjects, the mean predicted risk was 4.6% (P-Injury) and 1.4% (P-Intervention). The observed frequency of injury was 4.1% (any injury) and 0.6% (intervention). For all levels of P-Injury from 1% to 40%, the observed frequency of injury was consistent with the expected frequency. The observed frequencies for the 50%, 75%, and 90% levels were lower than expected (p\u3c0.05). For estimates of P-Intervention, the observed frequency was consistently higher than the expected frequency. Physicians underestimated risk for infants (mean P-Intervention 6.2%, actual risk 12.3%, p\u3c0.001). Conclusions: Physician estimates of probability of any brain injury in children were collectively accurate for children with low and moderate degrees of predicted risk. Risk was underestimated in infants

Scalp Hematoma Characteristics Associated with Intracranial Injury in Pediatric Minor Head Injury

Objectives Minor head trauma accounts for a significant proportion of pediatric emergency department (ED) visits. In children younger than 24 months, scalp hematomas are thought to be associated with the presence of intracranial injury (ICI). We investigated which scalp hematoma characteristics were associated with increased odds of ICI in children less than 17 years who presented to the ED following minor head injury and whether an underlying linear skull fracture may explain this relationship. Methods This was a secondary analysis of 3,866 patients enrolled in the Canadian Assessment of Tomography of Childhood Head Injury (CATCH) study. Information about scalp hematoma presence (yes/no), location (frontal, temporal/parietal, occipital), and size (small and localized, large and boggy) was collected by emergency physicians using a structured data collection form. ICI was defined as the presence of an acute brain lesion on computed tomography. Logistic regression analyses were adjusted for age, sex, dangerous injury mechanism, irritability on examination, suspected open or depressed skull fracture, and clinical signs of basal skull fracture. Results ICI was present in 159 (4.1%) patients. The presence of a scalp hematoma (n = 1,189) in any location was associated with significantly greater odds of ICI (odds ratio [OR] = 4.4, 95% confidence interval [CI] = 3.06 to 6.02), particularly for those located in temporal/parietal (OR = 6.0, 95% CI = 3.9 to 9.3) and occipital regions (OR = 5.6, 95% CI = 3.5 to 8.9). Both small and localized and large and boggy hematomas were significantly associated with ICI, although larger hematomas conferred larger odds (OR = 9.9, 95% CI = 6.3 to 15.5). Although the presence of a scalp hematoma was associated with greater odds of ICI in all age groups, odds were greatest in children aged 0 to 6 months (OR = 13.5, 95% CI = 1.5 to 119.3). Linear skull fractures were present in 156 (4.0%) patients. Of the 111 patients with scalp hematoma and ICI, 57 (51%) patients had a linear skull fracture and 54 (49%) did not. The association between scalp hematoma and ICI attenuated but remained significant after excluding patients with linear skull fracture (OR = 3.3, 95% CI = 2.1 to 5.1). Conclusions Large and boggy and nonfrontal scalp hematomas had the strongest association with the presence of ICI in this large pediatric cohort. Although children 0 to 6 months of age were at highest odds, the presence of a scalp hematoma also independently increased the odds of ICI in older children and adolescents. The presence of a linear skull fracture only partially explained this relation, indicating that ruling out a skull fracture beneath a hematoma does not obviate the risk of intracranial pathology

Model development of the Aquistore CO2 storage project

AbstractThe Plains CO2 Reduction (PCOR) Partnership, through the Energy & Environmental Research Center, is collaborating with Petroleum Technology Research Centre in site characterization; risk assessment; public outreach; and monitoring, verification, and accounting activities at the Aquistore project. The PCOR Partnership constructed a static geological model to assess the potential volumetric storage capacity of the Aquistore site and provide the foundation for dynamic simulation for the dynamic CO2 storage capacity. Results of the predictive simulations will be used in the risk assessment process to define an overall monitoring plan and assure stakeholders that the injected CO2 will remain safely stored

CATCH: A clinical decision rule for the use of computed tomography in children with minor head injury

Background: There is controversy about which children with minor head injury need to undergo computed tomography (CT). We aimed to develop a highly sensitive clinical decision rule for the use of CT in children with minor head injury. Methods: For this multicentre cohort study, we enrolled consecutive children with blunt head trauma presenting with a score of 13-15 on the Glasgow Coma Scale and loss of consciousness, amnesia, disorientation, persistent vomiting or irritability. For each child, staff in the emergency department completed a standardized assessment form before any CT. The main outcomes were need for neurologic intervention and presence of brain injury as determined by CT. We developed a decision rule by using recursive partitioning to combine variables that were both reliable and strongly associated with the outcome measures and thus to find the best combinations of predictor variables that were highly sensitive for detecting the outcome measures with maximal specificity. Results: Among the 3866 patients enrolled (mean age 9.2 years), 95 (2.5%) had a score of 13 on the Glasgow Coma Scale, 282 (7.3%) had a score of 14, and 3489 (90.2%) had a score of 15. CT revealed that 159 (4.1%) had a brain injury, and 24 (0.6%) underwent neurologic intervention. We derived a decision rule for CT of the head consisting of four high-risk factors (failure to reach score of 15 on the Glasgow coma scale within two hours, suspicion of open skull fracture, worsening headache and irritability) and three additional medium-risk factors (large, boggy hematoma of the scalp; signs of basal skull fracture; dangerous mechanism of injury). The high-risk factors were 100.0% sensitive (95% CI 86.2%-100.0%) for predicting the need for neurologic intervention and would require that 30.2% of patients undergo CT. The medium-risk factors resulted in 98.1% sensitivity (95% CI 94.6%-99.4%) for the prediction of brain injury by CT and would require that 52.0% of patients undergo CT. Interpretation: The decision rule developed in this study identifies children at two levels of risk. Once the decision rule has been prospectively validated, it has the potential to standardize and improve the use of CT for children with minor head injury. © 2010 Canadian Medical Association

Cigarette smoking, cytochrome P4501A1 polymorphisms, and breast cancer among African-American and white women

INTRODUCTION: Previous epidemiologic studies suggest that women with variant cytochrome P4501A1 (CYP1A1) genotypes who smoke cigarettes are at increased risk for breast cancer. METHODS: We evaluated the association of breast cancer with CYP1A1 polymorphisms and cigarette smoking in a population-based, case–control study of invasive breast cancer in North Carolina. The study population consisted of 688 cases (271 African Americans and 417 whites) and 702 controls (285 African Americans and 417 whites). Four polymorphisms in CYP1A1 were genotyped using PCR/restriction fragment length polymorphism analysis: M1 (also known as CYP1A1*2A), M2 (CYP1A1*2C), M3 (CYP1A1*3), and M4 (CYP1A1*4) RESULTS: No associations were observed for CYP1A1 variant alleles and breast cancer, ignoring smoking. Among women who smoked for longer than 20 years, a modest positive association was found among women with one or more M1 alleles (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.2–3.5) but not among women with non-M1 alleles (OR = 1.2, 95% CI = 0.9–1.6). Odds ratios for smoking longer than 20 years were higher among African-American women with one or more M3 alleles (OR = 2.5, 95% CI = 0.9–7.1) compared with women with non-M3 alleles (OR = 1.3, 95% CI = 0.8–2.2). ORs for smoking in white women did not differ appreciably based upon M2 or M4 genotypes. CONCLUSIONS: Cigarette smoking increases breast cancer risk in women with CYP1A1 M1 variant genotypes and in African-American women with CYP1A1 M3 variant genotypes, but the modifying effects of the CYP1A1 genotype are quite weak

What patients think doctors know: Beliefs about provider knowledge as barriers to safe medication use

We examined patient beliefs about provider awareness of medication use, patient-reported prevalence and nature of provider counseling about medications, and the impact of health literacy on these outcomes

Take-Wait-stop: A Patient-Centered Strategy for Writing PRN Medication Instructions

Recent studies have linked patient misunderstanding of label instructions for as needed (PRN) medications to dosing errors. This study conducted a preliminary field test of patient-centered PRN label instructions. Patients participated in a hypothetical dosing experiment and were randomized to a patient-centered label (referred to as “Take-Wait-Stop”) or standard label. Participants were asked to demonstrate dosing the medicine over 24 hours. Three types of independent dosing errors were measured: (a) taking more than two pills at one time, (b) exceeding the maximum daily dose, and (c) waiting fewer than 4 hours between doses. Generalized linear models were used to assess the association between label type, health literacy, and sociodemographic characteristics. Participants' mean age was 39.8 years, 62.1% were female, 43.7% were White, and 72.4% had adequate literacy. Of participants, 31.8% who were shown the standard label demonstrated taking in excess of 6 pills in 24 hours compared with only 14.0% of participants who were shown the Take-Wait-Stop label (p = .05). Overall, only 1 person demonstrated he would take more than 2 pills in a single dose. Of the standard label group, 20.5% demonstrated dosing intervals of fewer than 4 hours compared with 23.3% of the Take-Wait-Stop label group (p = .75). In a multivariate model, participants who were exposed to the standard label were 2.5 times more likely to exceed the recommended maximum daily dose (95% CI [1.05, 7.70], p = .03). The Take-Wait-Stop label was beneficial in preventing participants from exceeding the maximum dose in 24 hours, although it did not significantly reduce other dosing errors