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Publications (92)
Article: Evaluation of the Effect of Ammonia on Nicotine Pharmacokinetics Using Rapid Arterial Sampling[Show abstract] [Hide abstract] ABSTRACT: The nicotine bolus theory states that the dependence-producing potential of cigarettes relates to a rapid increase in nicotine at brain receptor sites. It has been suggested that ammonia, a compound typically found in tobacco products, further increases the amount of nicotine absorbed and its absorption rate. The aim of this study was to determine whether different ammonia yields in cigarettes affected the rate or amount of nicotine absorption from the lungs to arterial circulation. 34 adult smokers received 3 separate puffs from each of 2 test cigarettes with different ammonia yields (ammonia in smoke: 10.1 μg per cigarette vs. 18.9 μg per cigarette), followed by rapid radial arterial blood sampling (maximum one sample per second) with 30 min between puffs. Arterial blood samples were assayed for nicotine by liquid chromatography tandem mass spectrometry. Pharmacokinetic modeling was performed and the two test cigarettes were assessed for bioequivalence. No significant differences were found in area under the curve, C(max), or T((max)) and the 2 test cigarettes were found to be bioequivalent based on 2 one-sided tests at a significance level of 5%. In addition, the zero-order rate constant (k(0)) obtained from the initial slope of the curves and the model-dependent first-order rate constant (k(a)) were not significantly different. This study provides strong evidence that the different ammonia yields of the test cigarettes had no impact on nicotine pharmacokinetics; thus, the ammonia did not increase the rate or amount of nicotine absorption from a puff of cigarette smoke.
Article: Diazepam autoinjector intramuscular delivery system versus diazepam rectal gel: A pharmacokinetic comparison[Show abstract] [Hide abstract] ABSTRACT: Rectal administration of diazepam (DZ) has been used effectively in patients with epilepsy who experience acute repetitive seizures, but rectal gel may be difficult to administer during a seizure and is subject to variable drug absorption. An intramuscular (IM) autoinjector DZ formulation may offer a practical alternative to rectal DZ. This single-center, open-label, 3-treatment, 3-period crossover study compared the pharmacokinetic and safety profiles of 10mg DZ administered rectally in 24 healthy, fasted and fed subjects versus IM autoinjector delivery in fasted subjects. Blood samples were collected at baseline and for up to 24h postdose and plasma DZ concentrations were determined by liquid chromatography and tandem mass spectrometry. There were no significant differences between plasma concentrations for rectal administration of DZ in fasted and fed subjects at any time point. Intramuscular DZ administration resulted in more rapid and less variable drug absorption than rectal delivery. At 30min postdose and at all subsequent evaluations, IM administration resulted in significantly higher areas under the curve versus rectal administration in fasted subjects (p<0.05). This significant difference was sustained throughout the remainder of the 24-h study period (p<0.05). All reported adverse events were considered mild, and none required treatment.
- [Show abstract] [Hide abstract] ABSTRACT: We developed an automated sampling system to allow multiple, discrete blood samples from a human participant to be collected rapidly and immediately following cigarette smoke exposure. We reported the details of the sampling system along with the results of a pilot study for evaluation of the system. Components of the system include silastic tubing, solenoid pinch valves, a peristaltic pump, and a fraction collector. This system incorporates a smoking machine that allows precise delivery of cigarette smoke through a mouthpiece and intricate timing to correlate blood samples with smoke inhalation. All components are controlled via integration from a user interface and are fully customizable. We performed several tests to evaluate the equipment, including tubing dead volume, leakage tests, and sample reproducibility. We also performed a pilot study with 6 adult smokers, who received 6 controlled puffs of a research test cigarette. Each inhalation was followed by radial arterial blood collection (1 sample per second tapered to 1 sample every 4 s) for 1 min. Samples were evaluated for nicotine via liquid chromatography-tandem mass spectrometric methods. Sampling times and volumes were sufficient for nicotine analysis. No adverse effects were seen in the pilot study, and a 30-min washout period was deemed appropriate between puffs. A significant rise in plasma nicotine levels above baseline after inhalation of smoke was consistently detected in all participants. The unique advantage of this system is to allow rapid blood sampling after a puff of cigarette smoke, with the benefits of reproducibility, reduction in labor intensity, and high temporal resolution.
Article: Transitional Polytherapy: Tricks of the Trade for Monotherapy to Monotherapy AED Conversions[Show abstract] [Hide abstract] ABSTRACT: The goal of epilepsy therapy is to help patients achieve seizure freedom without adverse effects. While monotherapy is preferable in epilepsy treatment, many patients fail a first drug due to lack of efficacy or failure to tolerate an initial medication, necessitating an alteration in therapy. Sudden changes between monotherapies are rarely feasible and sometimes deleterious given potential hazards of acute seizure exacerbation or intolerable adverse effects. The preferred method for converting between monotherapies is transitional polytherapy, a process involving initiation of a new antiepileptic drug (AED) and adjusting it toward a target dose while maintaining or reducing the dose of the baseline medication. A fixed-dose titration strategy of maintaining the baseline drug dose while titrating the new medication is preferable when breakthrough seizures are occurring and no adverse effects are present. However, a flexible titration strategy involving reduction of the baseline drug dose to ensure adequate tolerability of the new adjunctive medication is preferred when patients are already experiencing adverse effects. This article reviews pharmacokinetic considerations pertinent for ensuring successful transitional polytherapy with the standard and newer antiepileptic drugs. Practical consensus recommendations "from an expect panel (SPECTRA, Study by a Panel of Experts Considerations for Therapy Replacement and Antiepileptics) for a successful monotherapy" AED conversions are then summarized. Transitional polytherapy is most successful when clinicians appropriately manage the titration strategy and consider pharmacokinetic factors germane to the baseline and new adjunctive medication.
- [Show abstract] [Hide abstract] ABSTRACT: To develop expert consensus for conversion between antiepileptic drug (AED) monotherapies, an 11-member panel used the Delphi Technique over three rounds to: (1) identify relevant issues, (2) vote on the issues, and (3) develop consensus. The panel agreed on the basic principle to taper the existing AED only after a presumably efficacious dose of the planned AED was reached. Application is modified by adverse effects possibly attributable to the existing drug, in which case earlier or more rapid tapering of the existing drug should be considered. Patients with uncontrolled seizures, as well as seizure-free patients for whom driving privileges are a consideration, may benefit from slower tapering by smaller dosage decrements of the existing AED. For 10 of the 12 AEDs considered, the panel made titration recommendations concerning initial and target doses for the planned AED, supplementing limited data in the prescribing information. This expert guidance will aid in the period of transitional polytherapy with AEDs from monotherapy to monotherapy.
- [Show abstract] [Hide abstract] ABSTRACT: To review and evaluate the medical literature concerning antiepileptic drug (AED) therapy in elderly patients. A MEDLINE search (1982-December 2004) was conducted. Bibliographies of the articles identified were also reviewed, and an Internet search engine was used to identify additional pertinent references. Clinical studies and reviews were evaluated, and relevant information was included. The elderly have the highest incidence of seizures among all age groups. Complex partial seizures are the most common, followed by primary generalized tonic-clonic seizures. An accurate diagnosis may prove difficult because of a low suspicion of epilepsy in the elderly and other diseases that may mimic seizures. Most AEDs are approved for treatment of elderly patients who have partial and tonic-clonic seizures. However, a number of age-related variables should be addressed when selecting an appropriate AED. Age-dependent differences in pharmacokinetics and pharmacodynamics of AEDs must be taken into account. Drug-drug interactions must be considered since elderly people often take multiple medications. The ultimate factor that often determines AED selection is tolerability. Numerous factors must be considered in treating elderly patients for seizures, but maximizing the ability of patients to tolerate drug therapy is often the basis for AED selection. Special consideration should be made along several lines, including elderly patients' cognitive functioning and their tendency to respond to lower AED concentrations.
Article: The use of Monte Carlo simulations to study the effect of poor compliance on the steady state concentrations of Valproic Acid following administration of enteric-coated and extended release Divalproex Sodium formulations[Show abstract] [Hide abstract] ABSTRACT: Divalproex sodium extended-release (Depakote ER) is a once daily (QD) formulation for valproic acid that was developed to improve patient compliance and to reduce side effects compared with the standard twice-daily (BID) delayed release (DR) formulation (Depakote tablets). However, there are concerns of potential sub-therapeutic concentrations following delayed or missed doses or toxic concentrations with replacement doses for the ER and DR formulations. Simulations can be used to investigate the effect of poor compliance on drug concentrations, which may not be possible to do in a study population for ethical or practical reasons. Using Monte Carlo simulations, the effect of different patterns of poor compliance on ER QD and DR BID were systematically characterized. Non-linear binding of valproic acid to albumin was incorporated into the model, and the results were based on total and unbound VPA for comparison. The effect of poor compliance is less significant on DR BID compared with ER QD. Dosing recommendations in the case of a missed or delayed dose are both formulation and dose dependent. Since total VPA concentrations show higher inter-individual variability and tend to under-estimate the effect of poor compliance; the use of unbound VPA concentrations may offer an advantage in therapeutic monitoring.
Article: Carbamazepine extended-release capsules vs. oxcarbazepine: Computer simulations of the effect of missed doses on drug plasma concentrations[Show abstract] [Hide abstract] ABSTRACT: Plasma concentrations of antiepileptic drugs (AEDs) can vary and are not always an indication of clinical utility. However, adverse event occurrence can be correlated to fluctuations in plasma drug levels that occur with varying dosing regimens of the many AEDs. In this study, we present the results of computer simulations of plasma concentrations of the AEDs carbamazepine (CBZ) extended-release capsules (CBZ-ERC) (Carbatrol) and oxcarbazepine (OXC). A one-compartment open model with first-order absorption and elimination was generated from the results of a previous study measuring plasma concentrations following one 400 mg fasting dose of CBZ-ERC. This model was used to simulate plasma concentrations of CBZ following multiple 400 mg doses of CBZ-ERC at 12-hour intervals, and then when a missed dose is taken 3, 6, or 9 hours late; when two doses are taken at one time; and when a single dose is taken at the time of the next dosing. In comparison, similar modeling was done for monohydroxy derivative (MHD) of OXC at doses of 600 or 1200 mg. Plasma drug concentrations after 24 hours without medication were 4.1 mg/L for CBZ-ERC, 8 mg/L for 600 mg OXC, and 16 mg/L for 1200 mg OXC. If a patient was to take only a single dose 24 hours late, it would take 24 hours to reach steady-state trough values for CBZ-ERC, 36 hours for 600 mg OXC, and 2 days for 1200 mg OXC. The trough plasma concentration following a missed dose and the peak plasma concentration following a double dose (administered 12 hours after the missing of a dose) differed by a factor of two in the CBZ-ERC simulation, compared with a factor of three in both OXC simulations. The ultimate goal of antiepileptic therapy is a seizure-free state without side effects. The current computer simulation study indicates that AEDs such as CBZ-ERC and OXC, which produce relatively stable plasma concentrations, should be useful in attaining this goal. Nonetheless, simulated plasma concentrations resulting from CBZ-ERC treatment tended to oscillate less dramatically compared with simulated plasma concentrations resulting from treatment with 600 or 1200 mg OXC.
Article: Patterns of care, outcomes, and direct health plan costs of antiepileptic therapy: A pharmacoeconomic analysis of the available carbamazepine formulations[Show abstract] [Hide abstract] ABSTRACT: Although generic formulations of immediate-release carbamazepine (IR-CBZ) are available, extended-release delivery systems may offer important advantages, including the convenience of less-frequent administration and smaller peak-to-trough serum carbamazepine (CBZ) fluctuations. The aim of this study was to compare the patterns of pharmacotherapy, rates of adverse events, and the utilization costs among patients treated with the available CBZ formulations (ie, generic and branded IR-CBZ, and extended-release CBZ (ER-CBZ) capsules [Carbatrol, Shire US Inc., Wayne, Pennsylvania] and tablets [Tegretol-XR, Novartis Pharmaccuticals Corporation, East Hanover, New Jersey]). Data were retrieved from the PharMetrics patient-centric database (which contains integrated claims data for almost 36 million unique patients from 61 US health plans) for patients who were diagnosed with epilepsy and initiated CBZ between July 1999 and June 2001. Patient demographic and clinical characteristics, adverse events, discontinuations, CBZ therapy switches, and utilization and costs for related care subsequent to treatment initiation were recorded. Annual rates of adverse events and discontinuations were calculated, and the risks of these events were compared across treatment groups. Data were gathered for 1737 patients. The branded CBZ group was demographically and clinically different than the other groups (ie, migraine and cerebral palsy prevalence) and therefore was excluded from event-risk analyses. Results of the proportional hazards regression analysis indicated that Tegretol-XR patients were more likely to experience common central nervous system (CNS)-related adverse events relative to Carbatrol (hazard ratio, 1.67; P = 0.043). A lower percentage of subjects switched off ER-CBZ relative to IR-CBZ (Carbatrol, 5.2%; Tegretol-XR, 5.7%; generic IR-CBZ, 13.0%; branded IR-CBZ, 16.7%). Differences in mean payments for epilepsy-related health care services at 1 year among Carbatrol, Tegretol-XR, and branded or generic CBZ did not reach statistical significance. Among the available CBZ formulations, Carbatrol was associated with a lower incidence of common CNS adverse events. ER-CBZ formulations were also associated with reduced likelihood of therapy discontinuation or switching CBZ medications, relative to patients taking generic IR-CBZ, in this retrospective data analysis.
Article: Simulated Fluctuations in Plasma??Drug Concentrations for??Patients Receiving Oxcarbazepine??or Carbamazepine Extended-Release Capsules
Article: Lack of a Clinically Significant Effect of Zonisamide on Phenytoin Steady-State Pharmacokinetics in Patients With Epilepsy[Show abstract] [Hide abstract] ABSTRACT: This study was designed to measure the effect of the addition of zonisamide on phenytoin pharmacokinetics under steady-state conditions in patients with epilepsy. Nineteen patients stabilized under phenytoin monotherapy were included in a 3-center, open-label, 1-way drug interaction trial. Zonisamide was gradually increased to 400 mg/day, taken twice daily. Three pharmacokinetic profiles were performed: on days -7 and -1, to assess pharmacokinetic parameters of oral phenytoin administered alone, and on day 35, after 14 days of zonisamide treatment, to evaluate the effect of zonisamide on phenytoin pharmacokinetics and to characterize zonisamide pharmacokinetics in the presence of phenytoin. Fourteen patients completed the study; the coadministration of zonisamide and phenytoin was safe and well tolerated. Zonisamide did not significantly affect the mean C(min), C(max), AUC(0-12), and CL/F of phenytoin measured before and after zonisamide administration. The pharmacokinetic measures of zonisamide in the presence of phenytoin were consistent with previous reports of induction of zonisamide metabolism by phenytoin.
Article: Carbamazepine pharmacokinetics are not affected by zonisamide: In vitro mechanistic study and in vivo clinical study in epileptic patients[Show abstract] [Hide abstract] ABSTRACT: Carbamazepine is metabolized by CYP3A4 and several other cytochrome P450 enzymes. The potential effects of zonisamide on carbamazepine pharmacokinetics (PK) have not been well characterized, with contradictory literature reports. Hence, an in vitro study was designed to evaluate the cytochrome P450 inhibition spectrum of zonisamide using human liver microsomes. Further, an in vivo steady-state study was performed to measure the effect of zonisamide on carbamazepine PK in epileptic patients, and monitor zonisamide PK. In vitro human liver microsomes were incubated with zonisamide (200, 600 or 1000 microM) in the presence of appropriate probe substrates to assess selected cytochrome P450 activities. In vivo, the effect of zonisamide, up to 400 mg/day, on the steady-state PK of carbamazepine and carbamazepine-epoxide (CBZ-E) was studied in 18 epileptic patients. In vitro, zonisamide did not inhibit CYP1A2 and 2D6, and only weakly inhibited CYP2A6, 2C9, 2C19, and 2E1. The estimated Ki for zonisamide inhibition of CYP3A4 was 1076 microM, 12 times higher than typical unbound therapeutic serum zonisamide concentrations. In vivo, no statistically significant differences were observed for mean Cmax, Tmax, and AUC0-12 of total and free carbamazepine and CBZ-E measured before and after zonisamide administration (300-400 mg/day for 14 days). However, CBZ-E renal clearance was significantly (p < 0.05) reduced by zonisamide. The observed mean zonisamide t1/2 (36.3h), relative to approximately 65 h reported in subjects on zonisamide monotherapy, reflects known CYP3A4 induction by carbamazepine. Based on the lack of clinically relevant in vitro and in vivo effects, adjustment of carbamazepine dosing should not be required with concomitant zonisamide administration.
- [Show abstract] [Hide abstract] ABSTRACT: In the hospital setting, prophylactic acid suppression is an important part of care for many critically ill patients. It may also prevent rebleeding in patients admitted with acute upper gastrointestinal tract bleeding. Effective treatments for these conditions stemmed from our increased understanding of the gastric acid secretory pathway and target pH values. The late 1970s saw the introduction of histamine2-receptor antagonists (H2RAs), which partially suppress basal and meal-stimulated acid secretion. Some of these agents can induce an intragastric pH greater than 3, lasting for approximately 10 hours/day when given twice/day at recommended doses. This level of acid suppression can facilitate healing of duodenal ulcers but has limited efficacy for other indications (e.g., gastrointestinal bleed). In the late 1980s a more potent class of acid-suppressing agents was developed, proton pump inhibitors (PPIs). The PPIs can induce an intragastric pH above 3 lasting for approximately 17 hours/day, and an intragastric pH above 5 for approximately 9 hours/day after once-daily oral administration of recommended doses. It is possible to attain even higher target pH values with large doses and with continuous intravenous infusion. Thus, PPIs are agents of choice for treatment of many acid-related disorders including peptic ulcer disease and moderate-to-severe gastroesophageal reflux disease, and for prevention of rebleeding in patients with upper gastrointestinal bleeding. Availability of an intravenous formulation, pantoprazole, enables hospitalized patients for whom oral administration is not feasible to benefit from the superior potency of PPIs. Preliminary data suggest that intravenous PPIs may be more effective than H2RA prophylaxis against stress-related ulcer bleeding for intensive care patients and should facilitate healing in those with bleeding ulcers of the upper gastrointestinal tract.
Article: Tolerability and Effects on Quality of Life of Twice-Daily Extended-Release Carbamazepine in Adults with Seizure Disorders: An Open-Label, 12- To 36-Month Continuation Study[Show abstract] [Hide abstract] ABSTRACT: An earlier 6-month, multicenter, open-label study in patients with complex partial seizures found that a switch from multiple daily doses of conventional carbamazepine (CBZ) to twice-daily CBZ extended-release capsules(CBZ-ERC) was well tolerated, with maintenance of seizure control over the study period and significant improvements in quality of life (P < 0.001). The goal of the present study was to assess the tolerability and effects on quality of life of twice-daily CBZ-ERC over the longer term in patients with seizure disorders. This was a multicenter, open-label assessment of the long-term(12-36 months) tolerability and quality-of-life effects of twice-daily CBZ-ERC given at a daily dose equivalent to the daily dose of CBZ taken before study en-try. The regimen could be adjusted as clinically indicated up to a daily dose of 1600 mg. Patients could receive up to 2 other antiepileptic drugs during the study. One hundred eighteen patients were enrolled. In patients completing>12 months of study therapy, a significant decrease in the highest mean 2-day frequency of generalized tonic-clonic seizures was observed over the first 12 months (P = 0.005). The significant improvements in quality of life achieved in the earlier study were maintained during the present study. Of 37 patients who were discontinued from the study, 9 met criteria mandating withdrawal from the study due to exacerbation of seizures. Three patients were discontinued from the study for adverse events judged to be unrelated to study drug. Low incidences of rash (3.4%) and weight gain (0.8%) were reported. In this population of adults with seizure disorders, CBZ-ERC twice daily was well tolerated during 12 to 36 months of open-label treatment,with no increase in seizure frequency or decrease in quality of life.
Article: Simulation of the effect of patient nonadherence on plasma concentrations of carbamazepine from twice-daily extended-release capsules[Show abstract] [Hide abstract] ABSTRACT: Carbamazepine (CBZ) effectively treats simple, complex, and secondarily generalized partial seizures. Computer simulations were carried out to investigate the effect of missing or delaying doses of carbamazepine extended-release capsules (CBZ-ERC) on plasma CBZ levels and the optimal dosing strategy to return plasma concentrations to therapeutic levels. A one-compartment open model with first-order absorption and elimination was generated from the results of a previous study measuring plasma concentrations following one 400-mg fasting dose of CBZ-ERC. The model was used to simulate plasma CBZ concentrations following multiple doses given every 12 h to hypothetical long-term CBZ-treated patients, with the CBZ elimination half-life set to 13.7 h to account for enzymatic autoinduction. The model was then used to simulate plasma CBZ concentrations when a dose is taken 3, 6, or 9 h late, or when two doses are taken at one time. Predicted plasma CBZ concentrations in this simulation fell from a trough of approximately 6.4 microg/ml only to 4 microg/ml after 24 h without medication, and only to 2.5 microg/ml after 36 h without medication. Predicted plasma CBZ concentrations in this simulation never rose above 9 microg/ml, indicating that taking missed doses of CBZ-ERC as soon as remembered, up to two missed doses 3 h before taking the next scheduled dose, will not lead to harmful spikes in plasma concentrations of CBZ. The simulations suggest that taking a missed dose of CBZ-ERC as soon as remembered, up to two doses at one time, may be the best strategy to return plasma CBZ concentrations to steady-state levels. Since the model used in this study is a simplified model of a highly complex situation, caution should be used when relating these results to clinical practice until trials are conducted in patients.
- [Show abstract] [Hide abstract] ABSTRACT: Phenytoin is the most commonly administered antiepileptic agent for the prevention of early (< or = 7 days) posttraumatic seizures. Use of the agent, however, requires strict monitoring due to its narrow target range and nonlinear pharmacokinetics. The impact of a clinical pharmacist participating in the care of patients with head injury on posttraumatic seizure prophylaxis with regard to phenytoin dosing and monitoring, cost avoidance, and patient outcome, was measured retrospectively. Parameters from time periods before (BP) and after (AP) a clinical pharmacist participated in patient care were compared. The average number of days that phenytoin was given was 13.4 (BP) and 7.6 (AP), and the duration of phenytoin prophylaxis was 7 days or less in 35% and 65% of patients, respectively. The average number of phenytoin levels drawn from each patient was 10.3 (BP) and 3.4 (AP). Seizures occurred in 4.7% (BP) and 1.5% (AP) of patients. A cost savings of approximately $28,000 was observed for the AP group. A clinical pharmacist reduced the use of posttraumatic seizure prophylaxis and associated costs without jeopardizing patient outcomes.
- [Show abstract] [Hide abstract] ABSTRACT: Nonsteroidal antiinflammatory drugs (NSAIDs) often are prescribed to patients who are taking concomitant drugs. Cyclooxygenase (COX)-2 inhibitors (coxibs) rofecoxib and celecoxib are highly selective inhibitors of COX-2, differentiating them from nonselective NSAIDs, which substantially inhibit both COX-1 and COX-2. Like nonselective NSAIDs, coxibs are hepatically metabolized: rofecoxib primarily by reduction by cytosolic enzymes and celecoxib by the cytochrome P450 (CYP) enzyme system. Because rofecoxib is not significantly metabolized by CYP, it has fewer confirmed or potential drug interactions than celecoxib. However, potent inducers of CYP, such as rifampin, may decrease rofecoxib concentrations because of induction of general hepatic metabolic activity. Celecoxib is metabolized by CYP2C9 and may be increased or decreased by CYP2C9 modifiers. It also inhibits CYP2D6 and may affect concentrations of CYP2D6 substrates. Similar to NSAIDs, many pharmacodynamic interactions involving coxibs are related to inhibition of production of renal prostaglandins. However, coxibs have no antiplatelet activity and may be preferred to NSAIDs in patients receiving antithrombotic therapy. Nonetheless, when a potential for an interaction exists, standard monitoring is recommended when starting or discontinuing a coxib. Due to lack of data to support these interactions, which are primarily theoretical, additional studies are necessary to establish the drug interaction profiles of coxibs.
- [Show abstract] [Hide abstract] ABSTRACT: The role of infliximab in managing Crohn's disease (CD) is described. CD is characterized by chronic transmural inflammation at various sites of the gastrointestinal tract, particularly the ileum and colon. The major symptoms are diarrhea, abdominal pain, enterocutaneous and perianal fistulas, and weight loss. Management goals include alleviating symptoms, inducing remission, promoting healing of the intestinal mucosa and fistulas, and modifying the disease process. Drugs traditionally used to manage CD are aminosalicylates, antimicrobials, immunomodulatory agents, and corticosteroids. Infliximab is a chimeric (human-mouse) monoclonal antibody targeted at human tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine important in the pathogenesis of CD. Infliximab antagonizes the biological activity of TNF-alpha by binding to it on macrophage and T-cell surfaces. Clinical trials have shown infliximab to be effective in producing and maintaining a clinical response in patients with refractory, moderate to severe CD. Treatment helps promote healing of intestinal mucosa and closure of fistulas. Infliximab may act more rapidly than most traditional agents and produces less severe adverse effects. The most frequent adverse effects are headache, nausea, and upper-respiratory-tract infections. The recommended dosage is 5 mg/kg i.v. infused over a two-hour period. Infliximab may be given at eight-week intervals for maintenance or management of flare-ups. Infliximab appears useful in the treatment of CD and may improve patients' quality of life.
- [Show abstract] [Hide abstract] ABSTRACT: Proton pump inhibitors, the treatment of choice for acid-related disorders, are often coadministered with other medications, sometimes with potentially adverse interactions. Although all agents studied may potentially interact with one proton pump inhibitor or another, a literature review documented adverse interactions for 10 medications in particular. Furthermore, 44% of people using proton pump inhibitors received another gastrointestinal drug. Although documented interactions involving these agents have been reported infrequently, the authors advise that physicians and pharmacists should recognize this possibility and watch for potentially problematic combination therapy.
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Virginia Commonwealth University
Richmond, VA, United States
- School of Pharmacy


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Gov't leaves door open for early access to pensions
The government has concluded that early access to pensions should not be considered until evidence indicates it could benefit consumers, stating that there is only "limited evidence" that early access could boost overall pension contributions.
The Work and Pensions Committee argued in its eighth report on automatic enrolment in workplace pensions and the National Employment Savings Trust, that retirement saving through auto-enrolment may be even more attractive to individuals if it offered additional financial incentives or flexibilities.
It asked the government to consider the advantages and disadvantages, including the legal implications, of allowing individuals to withdraw pension savings to buy a first home.
The New Zealand experience may offer evidence on the extent to which savers' behaviour has been affected by this aspect of the KiwiSaver scheme, a form of workplace auto-enrolment, the committee said.
In the government's reponse to its report, published today (25 May), it said that there is "limited evidence" that early access would provide significant help to individuals facing financial hardship.
It said: "There was also a broad consensus that the extensive private pension reforms already planned, most notably the introduction of automatic enrolment, should be implemented before the government considers further reform.
"However, the government confirmed that, once automatic enrolment had been fully phased in, it would carry out research into the reasons why some people decide to opt out. If this research reveals evidence that access to pension savings is a significant factor, the government may decide to revisit the issue of early access to pensions."
In the committee's report, it argued that the government must set out its detailed plans for state pension reform as a "matter of urgency".
It its response, the government agrees that the existing state pension system needs to be simplified, admitting that it is "complex" and most people do not know with certainty how much pension they will receive at retirement or the extent to which their income will be means tested.
The government said it will publish details of its proposals for state pension reform in a White Paper in spring. However, final decisions on the detailed implementation of the policy will not be taken until the next Spending Review. The government proposes to introduce a bill "as soon as" a legislative slot becomes available.
Tom McPhail, head of pensions research at Hargreaves Lansdown, said: "The government have left the door open for early access to pensions, stating that if a case can be made for the KiwiSaver scheme, they may come back to it.
"There are interested parties in the pension world who are keen to push that issue."

subset: commoncrawl


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Weather Alerts
Neighborhoods on high alert as police search for more than 6 sexual assault suspectsUPDATED 5:56 PM CDT Mar 19, 2014
Neighborhoods in New Orleans are on high alert after several sexual assaults have been reported in the metro area.Video Transcript
FIRST AT 5--- PEOPLE ARE ON HIGH-ALERT TONIGHT... AS THE SEARCH IS ON FOR MORE THAN A HALF-DOZEN SEXUAL ASSAULT SUSPECTS. RIGHT NOW, THE N-O-P-D IS INVESTIGATING THREE SEPARATE CASES OF SEXUAL ASSAULT ACROSS THE CITY... POLICE SAY TWO WOMEN WERE ASSAULTED UPTOWN.. ANOTHER IN THE FRENCH QUARTER. THE MOST RECENT.. LED TO A CRIME ALERT FOR STUDENTS AT TULANE UNIVERSITY... WHERE A WOMAN SAYS SHE WAS ASSAULTED INSIDE A BAR AT FRERET AND BROADWAY EARLY THIS MORNING. WDSU REPORTER ANDY CUNNINGHAM LIVE IN THE STUDIO WITH DETAILS.. ON ALL THREE CASES. AT THIS POINT NO ARRESTS HAVE BEEN MADE IN ANY OF THESE SEXUAL ASSAULTS AND POLICE SAY ALL THREE CASES ARE ACTIVELY BEING INVESTIGATED. AROUND NOON WEDNESDAY, STUDENTS RECEIVED A CRIME ALERT FROM TULANE UNIVERISTY POLICE... AFTER A WOMAN REPORTED SHE WAS SEXUALLY ASSAULTED BY TWO WHITE MALES IN THEIR EARLY- TO-MID 20's INSIDE A BAR. Brenna Bossman/Tulane Student: it's really scary and it just kind of raises awareness that you have to be away careful about what you're doing... MONDAY'S REPORTED ASSAULT COMES JUST TWO WEEKS AFTER ANOTHER FEMALE REPORTED SHE AWOKE TO A MAN SEXUALLY ASSAULTING HER AT A PARTY, ALSO NEAR THE UNIVERSITY. Carl Johnson/Tulane Student: It's almost sort of difficult to conceptualize that it is an actual event that something actually happened and somebody that actually was hurt... TWO MILES AWAY, ANOTHER WOMAN REPORTED SHE WAS SEXUALLY ASSAULTED AT HER HOME IN THE 4800 BLOCK OF PRYTANIA, BY AN UNKNOWN MAN WHO IDENTIFIED HIMSELF AS "RANDY" POLICE RELEASED THIS COMPOSITE SKETCH OF THE MAN THEY'RE LOOKING FOR. Ian Phillips/Tulane Student: It's almost sort of difficult to conceptualize that it is an actual event that something actually happened and somebody that actually was hurt... IN THE FRENCH QUARTER, POLICE ARE INVESTIGATING ANOTHER ALLEGED SEXUAL ASSAULT ...OVER THE WEEKEND IN THE 700 BLOCK OF ROYAL STREET. IN THIS CASE THE VICTIM ALLEGES SHE WAS FORCED INTO AN S-U-V, TAKEN TO ANOTHER LOCATION AND ASSAULTED BY AT LEAST ONE MAN. Carl Johnson/French Quarter: I mean it's just horrible to think that we have someone like that canvassing the area, ya know, and just preying on woman, that's horrible.. THE ROYAL STREET CASE WAS THE THIRD ONE REPORTED IN AS MANY DAYS IN THE QUARTER. DETECTIVES ARE NOW REVIEWING AREA SURVIELLANCE FOOTAGE IN AN EFFORTS TO TRACK DOWN THE VEHICLE. ANYONE WITH INFORMATION ON THESE THREE SEPARATE CASES IS ASKED TO CALL CRIMESTOPPERS AT 822-11-11. SCOTT.
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The zone is just too optimistic on some guys that have physical talent but bounced around the league without ever turning their physical skills into consistent pass catching skills. Lockette, Moore, Osgood all have size and speed, but might not ever be anything but a 5th or 6th guy who makes it on ST play. On the other hand, one of the least gifted guys, Chad Hall, has been catching quite a few.
Given that Jenkins and Patton aren't going to be able to grow if they can't even get on the practice field, they pulled the trigger on trying a couple of guys that could be a third or fourth receiver that you wouldn't be afraid of the throwing the ball too.


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Climatological averages tell us that a typical hurricane season sees 10 tropical storms, and six of those storms will become hurricanes.
Dr. William Gray has been issuing forecasts for hurricane seasons for years, and on Wednesday he and his team of forecasters from Colorado State University issued their updated 2008 forecast at the National Hurricane Conference in the Bahamas. Their updated forecast is not what most people want to hear.
They say the season will be very active. Their forecast calls for 15 tropical storms. They say seven of those 15 storms become strong enough to be called hurricanes, and three of those hurricanes will reach major hurricane status - meaning they are of category 3, 4, or 5 intensity with winds over 110 mph.
Dr. Gray told Miami CBS affiliate WFOR that cooler-than-average water temperatures in the equatorial Pacific Ocean - a pattern called La Nina - as well as warmer-than-average water temperatures in the Atlantic Ocean are major contributing factors to the increase in storms forecast.
A record 28 storms formed in 2005 - the season that included deadly Hurricane Katrina. In 2006 saw only 10 storms, while 2007 saw 14 storms. While no hurricanes have made landfall in the U.S. since 2005, several tropical storms did hit the U.S.
Dr. Gray's forecasts do not indicate whether or not storms will actually the the U.S. coast, nor do they indicate where along the U.S. coast storms will hit. His forecast, however, does show the probability of a storm hitting regions of the coast. The overall U.S. coast has a 69% probability of being hit by at least one major hurricane. The average for the last century is 52%. For the Florida Peninsula and the U.S. East Coast, the probability is 45% while the 100-year average is 31%. The Gulf Coast from Brownsville, Texas to the Florida Panhandle has a 44% probability of being impacted. That 100-year average is 30%.
What does this mean? It means that based on past hurricanes seasons with similar pre-season weather patterns, odds are greater than in most seasons that at least one major storm will impact the U.S. Coast.
Now is the best time to start preparing for hurricanes to strike. The start of the hurricane season is June 1, and the season lasts through November 30.
Here are the storm names for the 2008 Atlantic Hurricane Season:


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What are the differences in use between 'sort', 'kind' and 'type' (nouns) ?
Also, between 'sort of' and 'kind of' is there any difference in use? (both are for informal use)
2 answers
In practice, these words are synonymous. The trick is to learn the phrases where only one word is acceptable.
"What kind/sort/type of breakfast cereal do you like?" (any word will do).
"He's not my type." (idiom, can't be changed without changing meaning.)
Also, 'kind of' and 'sort of' are practically the same.
|link comment
|answered May 25 '11 at 16:35 Kimberly Expert
Sort of is used for character : what sort of person he is; To show one's doubt: He might be sort of alive; or to show negative feeling: He is that sort of guy.
Type is used for distinguishing among widely different entities from a general category such as Car. There are several type of cars such as two doors, four doors, etc. What TYPE of transportation will include trucks, Bikes, planes etc. Type is used for Generally distinguishing between wider areas such as Animals (4 legged), Birds (flightless), House (movable)
Kind is a sub category of type. One you know what Type of car someone drives such as two door, you ask what kind of two door car he/drives such as sedan, suzuki, camry etc. Similarly what KIND of seal is this mean there are already a big category of seals present, of that category we are furthur categorizing seals based on color, features etc.
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|answered Jul 19 '15 at 01:33 Bilal Abdullah New member
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Tag Archives: summerdrags
Rotary Overload: New Zealand Summerdrags 2010
Listen up, Mazdafarians! If you want to see over 300 pics of vintage kiwi-style rotaries at the recent 2010 Summerdrags, click right here and braap your brains out.
Mazda Rotaries at New Zealand Summerdrags
Hey Mazdafarians, we just got this in from Kiwi Bureau: photos from last weekend's Mazda Rotary Summerdrags in New Zealand. Yes, while we're huddled by the fireplace for warmth in the dead of winter, Nee Zeelanders are enjoying nice warm … Continue reading


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October 18, 2012, 12:19 AM
Sure Shot Mc Gee
Senior Member
Join Date: January 2, 2012
Posts: 2,766
Deja vu: With the large population of wolves we have. A coyote would have to be invisible to stay alive in wolf habitat here. Wolves they are indeed moving and spreading out to the South and East. Wisconsin has had many more sightings these last few years than usual as Michigan also. Back in the early 70s that Endangered Species Act. Those in charge. Their plan or idea was to protect the Gray Wolf and not inhibit them in any way in hopes to bring there population back up to 12-1400 max for the available habitat here in Northern MN. Well after 30 plus years. The Gray Wolf was recently removed from (The List) at the behest of our Sen. Amy Klobuchar. Apparently the re-population plan exceeded the Agency's desires and we now have 3 to 5000 and as many as 7000 possibly. You just got to love them politicians. lol
"Do not follow where the path leads, rather go where there is no path and leave a trail for others to follow."
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Organizers prepare for busy Mayor's CupUPDATED 5:36 PM EDT Jun 18, 2014
Art Center to play prominent roleVideo Transcript
THE MAYOR'S CUP IN PLATTSBURGH IS ONLY A FEW WEEKS AWAY. ORGANIZERS MET AT DOCK STREET LANDING THIS AFTERNOON FILLED WITH EXCITEMENT ABOUT THE ANNUAL TRADITION. WPTZ'S ALISON CAREY JOINS US LIVE WITH MORE. ALISON? GEORGE, THE SLOGAN FOR THE MAYO'RS CUP REGATA IS FREE FAMILY FUN -- and ORGANIZERS SAY THIS YEAR'S LINE UP WILL NOT DISSAPPOINT. EVENTS INCLUDE EVERYTHING FROM LIVE MUSIC TO A PARADE OF BOATS AND REGATA TO ARTS and KIDS ACTIVITIES. NEW THIS YEAR -- THE STRAND THEATER IS TAKING ON A MORE PROMINENT ROLE. THERE WILL BE JUMPIN IN JULY MUSIC FESTIVAL ON THE ARTS CENTER LAWN DOWNTOWN. THEN THE STOWAWAYS -- AN AWARD WINNING LOCAL BAND -- WILL PERFORM AT THE DOCK STREET WATEFRONT. JESSICA DULLE DIRECTOR STRAND CENTER OF THE ARTS we do like doing the community involvement but we also want to highlight what's going on for the strand center of the arts. It's very exciting. We're going to be launching our very first season in 2015, so this is kind of a sneak peak of what's to come. LOCAL ARTISTS WILL ALSO EXHIBIT THEIR WORK THROUGHOUT THE WEEKEND THE FESTIVITES KICK OFF ON THURSDAY JULY TENTH and WILL CONTINUE THROUGH SUNDAY JULY 13TH. FOR THOSE WHO CAN'T WAIT. THERE WILL BE A PRACTICE FIREWORKS DISPLAY TOMORROW NIGHT FROM 9:15 TO 9:30 WHICH WILL BE VISIBLE FROM DOWNTOWN WE HAVE MORE ON ALL OF THESE EVENTS ON WPTZ.COM I'M ALISON CAREY WPTZ NEWS
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A Quote by Ray Davies (the Kinks)
I think I'm sophisticated 'cause I'm living my life like a good homo sapiens But all around me everybody's multiplying and they're walking round like flies man So I'm no better than the animals sitting in the cages in the zoo man Cause compared to the flowers and the birds and the trees I am an apeman.
I think I'm so educated and I'm so civilized 'cause I'm a strict vegetarian But with the over-population and inflation and starvation and the crazy politicians I don't feel safe in this world no more, I don't want to die in a nuclear war. I want to sail away to a distant shore and make like an apeman.
Contributed by: Alexa


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Police said they found two teenagers who were reported missing on Thursday.
Officers said 14-year old Christina "Tia" Farrington and 15-year old Kate Picard were found in Montpelier and returned home to Chittenden County.
The views expressed are not those of this site, this station or its affiliated companies. By posting your comments you agree to accept our terms of use.blog comments powered by Disqus


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Do any of you knows if it is available yet?
I couldnt find much info about where to get it from..
Dont even know if its been released...
Film-"Looking for ancient tibet"
A place to post videos, pictures, and any other sort of Buddhist or non-Buddhist media.
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Mike Doyle's In-Game Commentary at Edmonton
Wednesday, 11.30.2011 / 3:19 PM CT / Minnesota Wild | Features
By Mike Doyle - Manager of Digital Content
This page will automatically refresh every 60 seconds.
How you doing State of Hockey legion? This day in rock 'n' roll history, "Love Child" by Diana Ross and the Supremes topped the charts. Also topping the charts is Sun Country Airlines with its supreme service. I'm sure that Ms. Ross chooses Sun Country and I know she follows In-Game Commentary because it keeps her hangin' on to all of the Wild's on-ice action.
Speaking of Wild action, I'm subbing in for Glen Andresen tonight from the Central Minnesota Hockey Tavern a.k.a. my living room, as the Wild travels to the frozen plains of Edmonton to drill the Oilers.
The last time these two teams met, the Wild's 17-game home winning streak against the Oil was snapped in a 5-2 loss. Everybody gets luck sometimes – even you Edmonton – and my guess is that the Wild extracts a little road revenge tonight.
One thing the Wild has going in its favor is Niklas Backstrom and he'll be in net tonight. He seals the Oilers tighter than the Alyeska Pipeline's welded double joints. Backstrom plays against Edmonton, just like the pipeline runs for 800 mile, without a leak.
Head Coach Mike Yeo is inserting Colton Gillies back into the lineup and is looking for him to respond after being the healthy scratch last game. Guillaume Latendresse and Marek Zidlicky are out tonight with concussions, and Justin Falk didn't travel with the team because of an upper body injury. The lone healthy scratch will be Casey Wellman.
For those of you who like watching hockey because of the uniforms, the Wild is skating in the road whites and the Oilers are outfitted in blue with its oil drip logo.
It's the last game in Movember, so next time you see the Wild, the players will be clean-shaven. It's also the last time you can help defeat the Oil off the ice in the MoBro Faceoff by donating to Nick Schultz's Mo Bros page. After you're done being charitable, come right back and join the commentary.
Period 1
17:46 – We had a feeling this was going to happen as Brad Staubitz and Darcy Hordichuk toss the gloves to the ice then toss their fists into each others faces. We all know what happened last game and this was obviously in response to those dustups. Pretty even bout with both large men landing a couple of good shots.
17:07 – First power play of the game coming for the Oilers as Mike Lundin is called for holding. Ales Hemskey has a partial break and tries to shield Lundin while on the backhand. Hemskey gets a weak shot on Backstrom but Lundin gets called for a hold.
14:43 – First big save for Backstrom as he stones Ryan Nugent-Hopkins in the low slot. The Oilers rookie takes a pass from veteran Ryan Smyth as he breaks off the wall and snaps a low wrist shot, but Back is out challenging and makes a kick save.
10:02 – MIN 0 – EDM 1 – Someone card Nugent-Hopkins, no way is he old enough to score 11 goals this early in the year. He takes a nice feed from Andy Sutton and buries a one-timer; Backstrom didn't have a chance. Don't worry folks, the Wild has been in this position before and I have a feeling we have another comeback brewing.
7:44 – Wild with a shorthanded opportunity. Recent call-up David McIntyre is on a two-on-one with Colton Gillies. McIntyre waits before releasing a shot, but Ryan Whitney waits just a bit longer and blocks the attempt with his stick.
6:02 – One of these times the Heatley high-slot tip is going to pay dividens. Mikko Koivu makes a nifty move at the blue line and finds Marco Scandella on the right point. Scandella fires a low shot to Heatley, who tips the puck through Nikolai Khabibulin's legs, but Bulin gets just enough to deflect it wide.
4:28 – Minnesota with another great opportunity. Colton Gillies steals the puck off of an Oiler turnover at the blue line. Gillies walks down the slot and winds up for a half-slapper. The puck was rolling and Khabibulin was out to cut down the angle and makes a pad save.
2:58 – Wild on the power play, Heatley takes a redirected shot and puts it on Bulin. Cal Clutterbuck is standing by the crease like a dog waiting for table scraps but there is no rebound. The Oilers take exception and Ladislav Smid cross checks Clutterbuck in the face, taking a penalty. I wonder what @Clutterstache has to say about that play.
0:00 – With seconds remaining, Clutterbuck circles low in the Oilers' zone and takes a knee-on-knee hit from Ryan Whitney. He is shaken up on the play, but if I were Whitney, I'd grow an extra set of eyes because you know Cal isn't going to take that collision lightly. Actually, the entire Oiler team better watch out, because I feel the Wild is going to be brining the pain in the second period.
Period 2
17:03 - With the game getting as physical as Olivia Newton-John in leg warmers, Gillies lays the hit of the game, thus far. Yeo likes players to respond and Gillies is flying around laying the body on anyone in his path, this time Sutton was in his way.
14:50 – MIN 0 – EDM 2 – Score another one for the bad guys. This time, Jordan Eberle takes a cross-ice pass from Nugent-Hopkins on the power play. Eberle corrals the pass then flips a backhander over Backstrom's shoulder. Time for the Wild to get back to work.
12:36 – Wild with its best chance of the period. After a neutral zone regroup that looked like it was drawn on the white board, Matt Cullen takes the puck at the blue line. He feeds the puck across to Devin Setoguchi, who takes the puck with his skate on the off wing and kicks it up to his stick. Setoguchi starts to run out of room but fires a shot that Bulin swallows up.
10:20 – Typically when someone opens the door for you, you thank them. Unless it is your opponent on a line change and his buddy knocks you into the open gate. That's what just happened to Darroll Powe as Eric Belanger knocks him into the open Oilers door. That one hurt me.
8:29 – MIN 1 – EDM 2 – That's what I'm talking about Minnesota. Setoguchi, back on a line with Koivu and Heatley because Clutterbuck has gone to the locker room, puts home a backhand goal. Koivu throws the puck towards the net from the half-wall and Seto bangs home his eight goal on the year.
5:09 - MIN 2 - EDM 2 – The Oilers want to start playing dirty? Well, the Wild can play dirty too: On the score sheet. Kyle Brodziak takes an initial shot on the power play that gets blocked. The puck bounces back to him and he takes another whack at it. This one gets on goal but Bulin makes the save. Brodziak stays persistent and it pays off. The puck bounces off some part of his body and goes through Khabibulin's legs. Woooo!
1:24 – Gillies gets another scoring chance with hard work and a well-placed dump. Bouchard has the puck at the red line and flips it high into the air behind the Oilers D-men. They lose sight of it, but Gillies doesn't. He splits the D and chips a puck on goal but Bulin turns it away.
0:00 – One word to describe that period: Response. Down two, the Wild didn't quit and tied the game with two hard-working goals. You can only guess where we're going in the third. It's going to be physical, it's going to be fast and I'm betting it will be a Wild W.
Period 3
14:47 – Not to state the obvious, but Pierre-Marc Bouchard has a nice set of hands. This time, he only uses one to knock the puck out of the air to keep the puck in at the blue line. He then finds Jared Spurgeon on the other point, who rips a slapper on Bulin.
12:41 – Poke check! Backstrom demonstrates a perfect poke check on Shawn Horcoff, who was sprung on a breakaway. The Oiler captain is in alone with a full head of steam, but a little too much steam because Backs saw the situation and dove out with the big goal stick and pokes the puck off Horcoff's stick.
9:23 – Horcoff must be getting pretty sick of Niklas Backstrom. The Wild netminder stones Horcoff again, this time a little more traditionally as Horcoff has the puck in the slot, but Backstrom is out, on top of the crease and turns away the wrister.
6:53 – Backstrom keeps the game tied at two, but this time has a little help from an unusual suspect: Dany Heatley. Hemskey takes a shot on the right side and Backs makes the save. The rebound goes into the slot to Gagner but Heatley is there and goes down to block the shot. Heatley is known for goal scoring, but in Minnesota he is starting to be know for his D-play.
5:40 – Nick Johnson, now playing on a line with Cullen and Bouchard, almost puts the Wild up one. Johnson picks up a loose puck near the blue line. He makes a shifty move on an Oilers player and releases a dangerous wrist shot that Bulin has to make a save on.
0:00 – The only thing better than hockey on a Wednesday night? Extra hockey. We're headed to overtime and you know what happens when the Wild get into extra time with the Oilers.
4:45 – Bouchard nearly ends it right away. Bouchard is sprung by a neutral zone pass from Schultz. He has Bulin in his sights, beats the goalie high, but rings one off the post.
1:53 - To the dismay of Oiler fans, Smyth takes a penalty. I usually don't agree with people from Canada, but this time they have a reason to be upset. Smyth takes a hooking penalty on Spurgeon that might have been more of a lost edge than a vicious hook.
0:00 - Zam that ice, we're going to a shootout. It looks like it needs a fresh shave, much like many of your Wild players. The puck was bouncing around for the entirety of the last WIld power play.
Eberle starts things off with a backhand five-hole goal.
"Anything you can do I can do better," says Bouchard as he uses nearly the same move to beat Bulin.
Hemsky is denied by Backstrom.
What a move by Koivu as he drops the shoulder and takes it to the roof.
Gagner keeps the Oilers alive...just barely.
Cullen has a chance to end the game and hits the post.
Nugent-Hopkins hits the post as well.
Setoguchi tries to go five-hole but is denied.
Horcoff gets revenge on Backstrom with a nifty backhand.
Heatley scores with a diving move that was unorthadox to say the least. Still, tie shootout.
Smyth goes with a backhand move into the pad of Backstrom.
Boom. Brodziak ends it against his former team. Wild set a franchise record for wins in a month with 11. Happy Movember everyone!


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Man loses appeal in Hinds County murder case
Harrell serving life sentence
The state Court of Appeals has upheld the capital murder conviction of a Holmes County man in the death of a Jackson man.
Christopher Harrell was sentenced to life in prison without parole in 2010 in Hinds County.
Harrell was convicted of capital murder in the 2008 slaying of Frank Damico in Jackson. Authorities said Harrell dumped Damico's body in rural Holmes County.
Prosecutors said Damico's body was found nine days after he was reported missing from Jackson. A Holmes County public works employee found Damico's decomposed body near a creek on April 15, 2008.
Prosecutors said Harrell killed Damico to take his car because he was wanted for other crimes.
The Appeals Court on Tuesday rejected Harrell's challenge to jury instructions.
Copyright 2012 by The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.


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The Office of Research Integrity (ORI) provides broad oversight, resources and education for integrity and compliance issues relating to the conduct of research at the University of California, Riverside. We strive to promote excellence in research while ensuring compliance with federal and state regulations. The Office of Research Integrity has oversight and responsibility over:
Institutional review boards (IRBs) which required by federal regulations to review all human subjects research conducted on behalf of the institution. The function of the IRBs is to ensure adherence to all federal, state, local, and institutional regulations concerning the protection of human subjects. UCR IRB review is required for both funded and non-funded human subjects research.
Administer and support Institutional Biosafety Committee (IBC) functions as the local review body responsible for oversight of research activities, including teaching laboratories, involving the use, storage and handling of biohazardous materials
Administer and support functions of Institutional Animal Care and Use Committee (IACUC) which has authority over all vertebrate animal and care
Promoting Research Objectivity (PRO) is charged with reviewing Investigator statements of financial interest related to their sponsored research activities and determining whether a conflict of interest management plan is warranted after review of all the facts and circumstances.
Stem Cell Research Oversight (SCRO) Committee reviews activities involving human stem cell research, regardless of the type of stem cells or whether the stem cells are adult or embryonic
Educating and training researchers on research compliance;
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You know that phrase, "Ignorance is bliss"? There's a reason it's stuck around all these years. Because having the upper hand in intelligence might give you an advantage in some areas, like crossword puzzle solving and quantum physics-ing, but it also might just screw up your lifeforever.
For instance, if you're smart ...
#5. You're Probably a Night Owl -- And That's a Bad Thing
Recently, scientists discovered a quirky side effect to having a high IQ: You tend to stay up until later hours and get up later in the morning. That's right -- the more intelligent are also much more likely to be night owls. Which isn't such a surprise when you consider that intelligent people are infamous for burning the midnight oil to cram for tests, write papers, touch up those earnings reports, etc
It appears to just be evolution -- the more intelligent members of a species are, in general, the first to change habits (their big brains are wired to seek out novelty). Since humans have been day-dwellers during most of their existence, it's primarily the smarties who prefer to habitually stay up until the wee hours and to do the types of tasks that are easier to accomplish when you don't have the day-dwellers hanging around and distracting you. Stuff that requires concentration, in other words.
So let the early birds keep their measly worms. The nights owls get to feast on the juicy field mice of accomplishment!
So What's the Problem?
Well, being a night owl does have some negative side effects. And by "some" we mean, "You're pretty much screwed."
For starters, studies have found that "eveningness" is associated with a high degree of emotional instability. That means you tend to be less agreeable and conscientious than the average Joe. Oh, and you don't just make others' lives miserable. Thanks to your late-night habits, likely brought on by high intelligence, you're also three times more likely to suffer symptoms of depression.
And the fun doesn't end there, geniuses! Turns out that, short of becoming a competitive asbestos eater, staying up late at night is about the worst thing you could do for your physical health. According to a number of studies, night owls are at higher risk for heart disease and suffer more arterial stiffness than those who go to bed early.
The direct cause might have less to do with the fact that you stay up than with some of the other things you're doing while your eyes get all nice and bloodshot. You see, people who tend to stay up late also tend to do other unhealthy things at night, such as overeating. Then, once they do eventually hit the hay, they experience more sleep interruptions when those pesky morning larks get up and start noisying about.
All this adds up to some nasty artery stress and whacked-out circadian rhythms, a nice recipe for a massive coronary. So be sure to thank those dumbass early risers and your high intelligence for your inevitable heart attack.
#4. You're Less Likely to Pass On Your Genes
Another unfortunate stereotype of smart people is that they're socially awkward nerds who are doomed to lives of celibacy until they get out of high school hell. Unfortunately, that one turns out to be totally true.
But it's not all bad news. There's evidence that the highly educated get more enjoyment out of sex than the dumb jocks and that really, all the lovin' you need to be happy comes from having sex with just one partner per year. So even the nerdlingers among us can find one person to get along with, then have highly enjoyable loser-geek sex, eventually leading to populating the planet with loser-geek children, right?
So What's the Problem?
Smart boy, please. Those genes you're carrying aren't going any-goddamn-where. Unbeknownst to the smarties, their education levels and IQ are conspiring to keep them childless and perhaps leading them to adopt 30 cats when they're in their late 70s.
It all starts with the smart ladies. A 2008 national census reported that women who had dropped out of high school had the most children on average. And the more education women achieved, the fewer children they were likely to have, with the fewest children being born to women who had finished graduate school.
The explanation, according to the Census Bureau, is simple: Women wanted to finish school before they were saddled with nine months of fetus-carrying. Then, for smart people of both sexes, there's the career to think about, and promotions, and who has time for a needy mini-human during all that? And of course, IQ plays a direct role here, since it has also been found that women with lower IQs are less likely to know how to use birth control properly, leading to more unplanned pregnancies.
But that's just the ladies. The smart fellas must be picking up the slack somehow, right? Maybe by getting a little dumb-girl nookie on the side? Not so. Research shows that countries with high national IQs tend to have lower childbirth rates in general compared with countries that can't collectively tie their shoelaces together. That's right -- entire nations are missing the evolutionary point of fucking as their IQs rise.
#3. You're More Likely to Lie
The problem with being the smartest guy in the room is that you usually know you're the smartest guy in the room. For some people, that's not a big deal. They can relate to others just fine and know how to navigate around everyone else's deficiencies without being complete pricks. Others, however, know they have an intellectual edge and can't help but abuse it.
So What's the Problem?
In addition to giving you an advantage in brainpower, IQ apparently also bestows the gift of deception.
After all, in order to lie and get away with it, you also have to keep the truth in mind and manipulate it, and you might even have to cover up your lies upon further questioning. All of this involves integrating several brain processes in much the same way that you would solve a complex calculus problem. This means that the age at which you start lying, and the effectiveness with which you do it throughout your life, are controlled by how smart you are.
In one study, scientists put people in brain-imaging machines and found that the regions of the brain that light up when a person metaphorically sets his pants on fire are the same that control "executive functioning." These are high-order thinking and reasoning abilities that include working memory, which, you guessed it, is the single biggest component of your IQ.
Another study simply tracked the tendency of children to lie as they got older (that is, as that aforementioned part of their brains developed). The researchers simply placed young kids in a room with a toy Barney under a cloth and told the kids not to peek at the toy when the researchers left the room.
Of course, 9 out of 10 kids totally peeked, but the percentage of kids who lied about whether they peeked grew as the kids got older. At age 2, 25 percent of the kids lied about peeking; at age 3, half lied; and by age 4, 90 percent of the kids who peeked at the purple dinosaur refused to admit their guilt. That would also seem to imply that the 25 percent of kids who fibbed at age 2 possessed higher cognitive abilities than their peers.
In other words, if you want to know whether your kid is gifted, simply track the specific age at which he starts trying to bullshit you. Speaking of which ...
#2. You're More Likely to Believe Bullshit
We're sure that at some point, someone has told you that you can't get anywhere without an education, and for the most part, they're right. And you're much more likely to pursue that education if you're starting out with a high IQ. According to renowned intelligenceologists who painstakingly measured every goddamn thing that you can associate with IQ, test scores were "the best single predictor of an individual's years of education."
Why? Well, their theory goes that smarter students do better in school (Cracked breaks new ground yet again!), which leads to more encouragement from teachers and parents, which in turn leads to more motivation to stay in school, then yadda yadda yadda, bingo-bango, master's degree in economics!
So What's the Problem?
It turns out that all this book learnin' is teaching you more than just the Pythagorean theorem -- it's also making it easier for you to believe some laughably wrong and even seriously weird stuff.
One problem is that education leads to one overall inaccurate belief: You think you're smarter than you are. Three studies have found that people who fall for investment scams are better-educated than the average person but don't seek advice because they think they're immune to making mistakes. In one study, researchers found that 94 percent of college professors think their work is superior to their peers'. These fellows fail to realize that intelligence doesn't always translate to real-world ability, and thus they tend to overestimate the quality of their work.
It seems to go back to the old saying about how the wisest man is the one who realizes he knows nothing. Or, as Michael Shermer, the author of Why People Believe Weird Things, puts it: "Smart people believe weird things because they are skilled at defending beliefs they arrived at for non-smart reasons."
That's why the more education you get, the more likely you are to believe in, say, ghosts and the supernatural. One study found that 23 percent of college freshman believed in the paranormal, compared with 31 percent of seniors and 34 percent of graduate students. Which leads us to wonder ... what the fuck are schools teaching these days?
#1. You're More Likely to Be Self-Destructive
On one hand, it seems like the smarter you are, the greater your ability to know the dangers of, say, shooting heroin. So self-destructive habits are traits of the low-class and stupid, right? Eh, not really...
The thing is, the great minds have something in common with proverbial death-prone kitties: curiosity. Researchers have finally begun to understand the link between curiosity and intelligence on the molecular level, thanks to scientists from the University of Toronto and Mount Sinai Hospital who discovered a protein in an under-explored part of the brain that controls both traits.
Makes sense. Weird shit like monkey-powered time machines can be invented only by people with enough brain smarts to make them work and enough curiosity to want to see such awesomeness in the first place.
So What's the Problem?
Extra-curious people are also extra-likely to be substance abusers.
British scientists published the results of a long-term study showing that smart people were more likely to be drunks. People who fell into the "very bright" category (IQs of 125 or greater) were not only more likely to experiment with alcohol but also were more likely to drink excessively and binge drink than their dimwitted counterparts.
And yeah, they pretty much found the same link between high intelligence and psychoactive drug use. It also turns out that intelligent people are much more likely to indulge in illicit substances such as marijuana, Ecstasy, cocaine and heroin. The smarter you are, the more likely you are to be tripping balls at any given moment
As for why, remember when we said earlier that smart people's brains seek out novelty and thus are the first to experiment with any new habit? Well, one theory explaining the link between substance abuse and intelligence is that both alcohol and drugs are novel substances, in evolutionary terms. Humans have been consuming alcohol for only about 10,000 years, and the earliest recorded drug was only 5,000 years ago. So when something is novel, the curiouser and most intelligent among us are more likely to want to try it out.
You know. For science.
By: Noobium
In: WTF, Science and Technology
Tags: intelligence, downside, science
Views: 6125 | Comments: 29 | Votes: 6 | Favorites: 7 | Shared: 22 | Updates: 0 | Times used in channels: 2
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text:
Vance Gerald Apple, Sr., 75, of Marlow died Sunday, June 30, 2013, at his home.
No services are scheduled at this time.
Vance was born Tuesday, March 1, 1938, in Louisville, Ky., to Etheridge D. and Edna Merle (White) Apple. He attended school in Louisville and later attended college. He had lived in Marlow for the past 34 years. On July 17, 1973, Vance married the former Linda Kaye Spyres in Las Vegas, Nev. He was employed as a carpenter for many years. Vance enjoyed riding horses, riding bucking horses, team-roping and calf-roping.
Vance was preceded in death by his parents.
Survivors include his wife, Linda Kaye Apple, of the home; two sons, Vance Apple, Jr., and Adam David Apple, both of Marlow; two daughters and sons-in-law, Candice Kaye and Charles Barkley of Quinton, Va., and Jamie and Greg Moon of Ralston; three grandchildren, Samuel Wade Barkley, Madison Kaye Barkley and Carson Moon; a brother, Phil Apple of Marlow; and a cousin, Ken Apple and wife Linda of Marlow.
Online condolences smay be sent to the family at www.callawaysmithcobb.com.
From MarlowReview.com
Vance Gerald Apple, Sr.
Posted in: Obituaries
Jul 1, 2013 - 4:36:24 PM
Jul 1, 2013 - 4:36:24 PM
© Copyright 2013 by MarlowReview.com


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text:
This is a discussion on Re: Areca vs. ZFS performance testing. - FreeBSD ; > Its probably worth playing with vfs.zfs.cache_flush_disable when using > the hardware RAID. > > By default, ZFS will flush the entire hardware cache just to make sure > the ZFS Intent Log (ZIL) has been written. > > This ...
> Its probably worth playing with vfs.zfs.cache_flush_disable when using
> the hardware RAID.
> By default, ZFS will flush the entire hardware cache just to make sure
> the ZFS Intent Log (ZIL) has been written.
> This isn't so bad on a group of hard disks with small caches, but bad if
> you have 256mb of controller write cache.
Flushing the cache to constituent drives also has a direct impact on
latency, even without any dirty data (save what you just written) in
the cache. If you're doing anything that does frequent fsync():s,
you're likely to not want to wait for actual persistence to disk (with
battery backed cache).
In any case, why would the actual RAID controller cache be flushed,
unless someone expliclitly configured it such? I would expect a
regular BIO_FLUSH (that's all ZFS is going right?) to be satisfied by
the data being contained in the controller cache, under the assumption
that it is battery backed, and that the storage volume/controller has
not been explicitly configured otherwise to not rely on the battery
for persistence.
Please correct me if I'm wrong, but if synchronous writing to your
RAID device results in actually waiting for underlying disks to commit
the data to platters, that sounds like a driver/controller
problem/policy issue rather than anything that should be fixed by
tweaking ZFS.
Or is it the case that ZFS does both a "regular" request to commit
data (which I thought was the purpose of BIO_FLUSH, even though the
"FLUSH" sounds more specific) and separately does a "flush any actual
caches no matter what" type of request that ends up bypassing
controller policy (because it is needed on stupid SATA drives or
/ Peter Schuller
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iEYEARECAAYFAkkNwqQACgkQDNor2+l1i30+tQCfYKIGEHETqN g1gfwi9XwBuFuq


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|Choose foods with fiber
|Stabilize your blood sugar by eating fiber from whole grains, beans and other legumes, vegetables, and fruit in small, frequent meals.
|Try a high-protein, low-carb diet
|Some doctors have seen good results with high-protein (more meat or soy), low-carbohydrate diets (less pasta, breads, and pastries), particularly among people who do not improve with a high-fiber, high-complex-carbohydrate diet.
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