78 FR 16051 - Vehicle/Track Interaction Safety Standards; High-Speed and High Cant Deficiency Operations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

...FRA is amending the Track Safety Standards and Passenger Equipment Safety Standards to promote the safe interaction of rail vehicles with the track over which they operate under a variety of conditions at speeds up to 220 m.p.h. The final rule revises standards for track geometry and safety limits for vehicle response to track conditions, enhances vehicle/track qualification procedures, and adds flexibility for permitting high cant deficiency train operations through curves at conventional speeds. The rule accounts for a range of vehicle types that are currently in operation, as well as vehicle types that may likely be used in future high-speed or high cant deficiency rail operations, or both. The rule is based on the results of simulation studies designed to identify track geometry irregularities associated with unsafe wheel/rail forces and accelerations, thorough reviews of vehicle qualification and revenue service test data, and consideration of international practices.

Transdermal and oral dl-methylphenidate-ethanol interactions in C57BL/6J mice: transesterification to ethylphenidate and elevation of d-methylphenidate concentrations.

PubMed

Bell, Guinevere H; Novak, Andrew J; Griffin, William C; Patrick, Kennerly S

2011-07-01

We tested the hypothesis that C57BL/6J mice will model human metabolic interactions between dl-methylphenidate (MPH) and ethanol, placing an emphasis on the MPH transdermal system (MTS). Specifically, we asked: (1) will ethanol increase d-MPH biological concentrations, (2) will MTS facilitate the systemic bioavailability of l-MPH, and (3) will l-MPH enantioselectively interact with ethanol to yield l-ethylphenidate (l-EPH)? Mice were dosed with MTS (¼ of a 12.5 cm(2) patch on shaved skin) or a comparable oral dl-MPH dose (7.5 mg/kg), with or without ethanol (3.0 g/kg), and then placed in metabolic cages for 3 h. MPH and EPH isomer concentrations in blood, brain, and urine were analyzed by gas chromatographic-mass spectrometry monitoring of N-(S)-prolylpiperidyl fragments. As in humans, MTS greatly facilitated the absorption of l-MPH in this mouse strain. Similarly, ethanol led to the enantioselective formation of l-EPH and to an elevation in d-MPH concentrations with both MTS and oral MPH. Although only guarded comparisons between MTS and oral MPH can be made due to route-dependent drug absorption rate differences, MTS was associated with significant MPH-ethanol interactions. Ethanol-mediated increases in circulating concentrations of d-MPH carry toxicological and abuse liability implications should this animal model hold for ethanol-consuming attention-deficit hyperactivity disorder patients or coabusers. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

Similar and Different? Subjective Effects of Methylphenidate and Cocaine in Opioid-Maintained Patients.

PubMed

Vogel, Marc; Bucher, Patricia; Strasser, Johannes; Liechti, Matthias E; Krähenbühl, Stephan; Dürsteler, Kenneth M

2016-01-01

Methylphenidate (MPH) is commonly prescribed for attention deficit hyperactivity disorder (ADHD). Recreational nonmedical use has been described and also occurs in patients on opioid maintenance treatment (OMT). MPH has been proposed for use as replacement therapy in cocaine dependence, although evidence for efficacy is inconclusive. We conducted a cross-sectional interview study on patterns of MPH use in a sample of 20 MPH-using patients on OMT with a history of cocaine use. We assessed symptoms of depression, ADHD during childhood, and retrospective subjective-effects profiles of MPH and cocaine. Risky patterns of MPH use were common, in particular illicit acquisition, use of high doses, and parenteral administration. Sixty percent of patients reported having used MPH as a substitute for cocaine. Correspondingly, the subjective-effect profiles of MPH and cocaine showed striking parallels, with overall effects of MPH being rated more positively than those of cocaine. Proportions of patients with elevated scores for depression or childhood ADHD were large, highlighting the importance of treating dual disorders in this population. Clinical studies on MPH substitution in cocaine-dependent patients on opioid maintenance treatment could benefit from consideration of the patterns of application of MPH in this population. Results are preliminary due to small sample size.

Evolution of stimulants to treat ADHD: transdermal methylphenidate

PubMed Central

Patrick, Kennerly S.; Straughn, Arthur B.; Perkins, Jeb S.; González, Mario A.

2009-01-01

Objective The following comprehensive review describes the evolution of stimulant drug formulations used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Emphasis is placed on the basic and clinical pharmacology of the dl-methylphenidate (MPH) transdermal system (MTS). Methods The pharmacokinetic and pharmacodynamic literature pertaining to MPH and amphetamine enantiomers was reviewed in the context of ADHD therapy and MTS as a treatment option. Results MTS incorporates MPH into an adhesive monolithic matrix, using the free base form of the drug to facilitate transdermal absorption. MTS technology minimizes contact dermatitis by eliminating to need for percutaneous penetration enhancers. After a lag time of approximately 2 h, plasma concentrations of the therapeutic d-MPH isomer become detectable, then continuously rise over the course of the recommended 9 h wear time. Concentrations of l-MPH typically attain 40−50% that of d-MPH (vs. 1−2% following oral MPH). Unauthorized MTS removal poses some misuse liability and over 50% of MTS drug content remains in the discarded system. Conclusions While liquid or chewable MPH formulations overcome potential swallowing difficulties, as do sprinkled once-daily extended-release (ER) MPH products, only MTS addresses swallowing difficulties while also offering a flexible individualized MPH exposure time in a once-daily MPH regimen. PMID:19051222

Comorbidities in ADHD children treated with methylphenidate: a database study

PubMed Central

2013-01-01

Background Methylphenidate (MPH) is the most common drug treatment of attention deficit / hyperactivity disorder (ADHD) in children. Treatment with MPH is contraindicated in the presence of certain psychiatric, cerebro- and cardiovascular conditions. We assessed MPH treatment prevalence and incidence and the frequency of comorbid conditions related to these contraindications in new MPH users compared to a control group without ADHD and ADHD medication. Methods We used health care data for the years 2004 to 2006 from the German Pharmacoepidemiological Research Database (GePaRD) which includes about 18% of the German population. MPH treatment prevalence and incidence was assessed based on at least one MPH prescription in the given year. In MPH users, the prevalence of psychiatric and other comorbidities was assessed in the quarter of the first MPH prescription and the three preceding quarters, whereas in controls it was assessed in the earliest four quarters of continuous insurance time starting at 01.01.2004 or the start of insurance if this was later. Differences in the presence of comorbid diagnoses between MPH users and controls were tested by logistic regression. Results In 2005, 1.5% of all children and adolescents aged 3 to 17 years (2.3% of males and 0.6% of females) received MPH in Germany. The proportion of children with a record of a psychiatric comorbidity in any of the nine ICD categories of diagnoses was substantially higher in new MPH users (83%) compared to controls (20%). Cerebro- and cardiovascular comorbidities were rare in general. Still, among new MPH users, 2% of males and females had a diagnosis of a pre-existing cardiovascular disorder but only 1.2% of controls. Conclusions Besides MPH treatment prevalence we first publish age-specific incidence rates for Germany. A high proportion of children who were started on MPH had a record of a psychiatric comorbidity preceding the first prescription. Cerebro- and cardiovascular conditions were rare in the studied age range, but still higher among children who received MPH than in the control group. Results show that in a substantial subgroup of patients, comorbidities require a thorough weighting of possible risks of MPH medication against the risks of untreated ADHD. PMID:23294623

Insights into resistance mechanism of the macrolide biosensor protein MphR(A) binding to macrolide antibiotic erythromycin by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Feng, Tingting; Zhang, Yanjun; Ding, Jing-Na; Fan, Song; Han, Ju-Guang

2015-12-01

Macrolide biosensor protein MphR(A) has been known as a key regulatory protein in metabolite sensing and genetic expression regulating. MphR(A) protein binds to macrolide antibiotic erythromycin (Ery) and releases the gene operon, thus activates expression of the mphA gene and initiates Ery resistance. The two mutant amino acid residues (V66L and V126L) might potentially disrupt Ery binding to MphR(A). In these studies, the binding of macrolide antibiotic Ery to wild type (Wt) MphR(A) and double mutant (V66L/V126L) MphR(A) are explored by molecular dynamics simulations. Compared to the Apo-MphR(A) protein and Wt-MphR(A)-Ery complex, many interesting effects owing to the double mutant (V66L/V126L) are discovered. In the case of Ery, Helix I which plays an important role in transcription shows itself a right-hand α helix in Wt-MphR(A)-Ery, whereas the activated helix is broken down in double mutant-V66L/V126L-MphR(A)-Ery. The calculated results exhibit that the double mutant V66L/V126L reduces the binding affinity of the V66L/V126L-MphR(A) to Ery, resulting in the block of Ery resistance. The binding free energy decomposition analysis reveals that the decrease of the binding affinity for the variant V66L/V126L-MphR(A)-Ery is mainly attributed to the gas phase electrostatic energies. The residue Leu66, Thr154, and Arg122 enhance the binding affinity of V66L/V126L-MphR(A) to Ery. The residues Tyr103 and His147 contributes mainly to binding energies in the Wt-MphR(A)-Ery complex, whereas the two residues have no contribution to the binding free energy inV66L/V126L-MphR(A)-Ery complex. Our study gives useful insights into the nature of amino acids mutation effect, the mechanism of blocking drug resistance at the atomic level and the characteristics in binding affinity for Ery to double mutant (V66L/V126L) MphR(A), which will contribute to the design of more effective macrolide antibiotics.

Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

PubMed

Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

2010-02-01

Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

Pharmacokinetics and therapeutic effect of OROS methylphenidate under different breakfast conditions in children with attention-deficit/hyperactivity disorder.

PubMed

Wigal, Sharon B; Gupta, Suneel; Heverin, Erica; Starr, H Lynn

2011-06-01

To examine the pharmacokinetics (PKs) and pharmacodynamics (PDs) of OROS methylphenidate (OROS MPH) dosed once daily (QD) versus an early standard regimen (immediate-release [IR] MPH dosed three times daily [TID]) under various breakfast conditions. This single-center, double-blind, double-dummy, randomized, crossover study of OROS MPH (NCT00269815) in children aged 6 to 12 years with attention-deficit/hyperactivity disorder evaluated the PKs and PDs of MPH given with different breakfast conditions: OROS MPH administered after a high-fat breakfast, after a normal breakfast, or after fasting and IR MPH administered after a normal breakfast or after fasting in the morning and at two subsequent time points during the day. To maximize information, patients were divided into two groups, each receiving three of the five treatments for 1 day in a three-period, randomized, crossover design. Patients were assigned to 1 of 3 dosage levels (OROS MPH 18, 36, and 54 mg QD, and an assumed equivalent regimen of IR MPH 5, 10, and 15 mg given TID) based on their prestudy established clinical dose of IR MPH. PD measurements included Combined-Attention and Deportment scores on a rating scale of school behavior (the Swanson, Kotkin, Agler, M-Flynn, and Pelham), global assessments of efficacy, and activity monitor levels during academic seatwork. Serial blood samples for PK analysis were taken predose, and then every 60 to 90 minutes until 11.5 hours postdose. Vital signs were assessed predose, and then every 1.5 to 2.5 hours until 11.5 hours postdose. Of the 32 patients enrolled, 31 completed the study. The PK profiles for MPH after OROS MPH administration were similar under all conditions (with normal, high-fat breakfast, or fasting). No bioequivalence tests of OROS MPH and IR MPH under various breakfast conditions were done because there were so few patients in each dose level of treatment. The two IR MPH conditions (after normal breakfast and fasting) were not compared. The drug-to-metabolite ratios (area under the curve) for all OROS MPH and IR MPH treatments were similar. OROS MPH and IR MPH provided a similar therapeutic effect, irrespective of breakfast conditions, as demonstrated by the Swanson, Kotkin, Agler, M-Flynn, and Pelham Attention and Deportment measures and global assessments. No serious adverse events, no deaths, and no clinically significant changes in vital signs were reported, except for one patient who was discontinued early because of repeated systolic blood pressure elevations on study day 1. The results of this study demonstrate that in children with attention-deficit/hyperactivity disorder, administering OROS MPH with or without food produces similar PK and PD profiles.

A Comparison of 2 Current-Issue Army Boots.

DTIC Science & Technology

2000-01-01

at 3.5 mph, mean (SD) 32 21 .Maximum heel- strike vertical force (N) while walking at 3.5 mph, mean (SD) 33 22 Maximum heel- strike braking force...while running at 6.5 mph, mean (SD) 38 34 Maximum force on the hip (N) while running at 6.5 mph, mean (SD) 38 35 Maximum vertical heel- strike force (N...during 6.5 mph running, mean (SD) 39 36. Maximum heel- strike braking force (N) while running at 6.5 mph, mean (SD) 39 37. Maximum vertical push

[Recurrent urinary tract infection].

PubMed

Ali, Adel Ben; Bagnis, Corinne Isnard

2014-09-01

Recurrent urinary tract infection involves mainly women and exhibits an ecological as well as economical risk. 4% of all urinary tract infection are recurrent and usually secondary to general or local abnormalities. A multidisciplinary medical and surgical team (urology, nephrology, bacteriology, infectious disease) best performs diagnosis and treatment as well as rules out reversible etiology. Treatment relies on behavioral changes before offering cranberry products and/or antibioprophylaxis if necessary.

Interactive effects of methylphenidate and alcohol on discrimination, conditioned place preference and motor coordination in C57BL/6J mice.

PubMed

Griffin, William C; McGovern, Robin W; Bell, Guinevere H; Randall, Patrick K; Middaugh, Lawrence D; Patrick, Kennerly S

2013-02-01

Prior research indicates methylphenidate (MPH) and alcohol (ethanol, EtOH) interact to significantly affect responses humans and mice. The present studies tested the hypothesis that MPH and EtOH interact to potentiate ethanol-related behaviors in mice. We used several behavioral tasks including: drug discrimination in MPH-trained and EtOH-trained mice, conditioned place preference (CPP), rota-rod and the parallel rod apparatus. We also used gas chromatographic methods to measure brain tissue levels of EtOH and the D- and L-isomers of MPH and the metabolite, ethylphenidate (EPH). In discrimination, EtOH (1 g/kg) produced a significant leftward shift in the MPH generalization curve (1-2 mg/kg) for MPH-trained mice, but no effects of MPH (0.625-1.25 mg/kg) on EtOH discrimination in EtOH-trained mice (0-2.5 g/kg) were observed. In CPP, the MPH (1.25 mg/kg) and EtOH (1.75 g/kg) combination significantly increased time on the drug paired side compared to vehicle (30.7 %), but this was similar to MPH (28.8 %) and EtOH (33.6 %). Footslip errors measured in a parallel rod apparatus indicated that the drug combination was very ataxic, with footslips increasing 29.5 % compared to EtOH. Finally, brain EtOH concentrations were not altered by 1.75 g/kg EtOH combined with 1.25 mg/kg MPH. However, EtOH significantly increased D-MPH and L-EPH without changing L-MPH brain concentrations. The enhanced behavioral effects when EtOH is combined with MPH are likely due to the selective increase in brain D-MPH concentrations. These studies are consistent with observations in humans of increased interoceptive awareness of the drug combination and provide new clinical perspectives regarding enhanced ataxic effects of this drug combination.

Effects of perinatal methylphenidate (MPH) treatment in male and female Sprague-Dawley offspring.

PubMed

Panos, John J; Law, C Delbert; Ferguson, Sherry A

2014-01-01

MPH is a common treatment for adult Attention Deficit Hyperactivity Disorder (ADHD). However, little information exists regarding its safety during pregnancy and thus, women with ADHD face difficult decisions regarding continued use during pregnancy. Here, Sprague-Dawley rats were orally treated 3 ×/day with 0 (control), 6 (low), 18 (mid), or 42 (high) mg MPH/kg/day (i.e., 0, 2, 6, or 14 mg/kg at each treatment time) on gestational days 6-21. On postnatal days (PNDs) 1-21, all offspring/litter were orally treated 2 ×/day with the same dose. Righting reflex (PNDs 3-6) and slant board performance (PNDs 8-11) were assessed. T3, T4, E2, testosterone, LH and corticosterone were measured at PND 22. Separate pregnant dams and resulting litters were used for serum MPH measurements. MPH treatment had mild, but significant, effects on gestational body weight and food intake. Birth weight of high MPH offspring was 5% more than controls (p<0.0500). Relative to same-sex controls on PNDs 1-22, low and mid MPH males weighed more (p<0.0094), low MPH females weighed more (p<0.0001), while high MPH females weighed less (p<0.0397). PND 22 serum E2 levels were significantly decreased (20-25%) in high MPH males and females (p<0.0500). Behavioral performance was unaffected by treatment. Serum MPH levels of the low MPH pregnant dams were within the range produced by therapeutic MPH doses in adults; however, offspring levels in all groups were substantially higher. These results indicate that developmental MPH treatment has mild effects on gestational body weight and food intake and offspring preweaning body weight. Potential functional consequences of decreased serum E2 levels are not clear, but may impact later behavior or physiology. Published by Elsevier Inc.

Plasma Methylphenidate Levels in Youths With Attention Deficit Hyperactivity Disorder Treated With OROS Formulation.

PubMed

Yorbik, Ozgur; Mutlu, Caner; Ozilhan, Selma; Eryilmaz, Gul; Isiten, Nuket; Alparslan, Serdar; Saglam, Esra

2015-06-01

There are limited studies investigating the relationship between oral release osmotic system-methylphenidate (OROS-MPH) doses and plasma methylphenidate (MPH) concentrations in children and adolescents. The aim of this study was to investigate the relationship between the doses of OROS-MPH and the plasma levels of the drug. We also examined the effects of the other drugs including aripiprazole, risperidone, fluoxetine, and sertraline on the levels of the MPH in the plasma. The files of 100 attention deficit hyperactivity disorder (ADHD) subjects (76 male, 24 female) who were diagnosed as ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria, were screened. The ages of subjects were between 6 and 18 years (mean = 11.5 ± 3.8 years). Plasma MPH levels were determined by high-performance liquid chromatography-tandem mass spectrometry assay. Daily mean OROS-MPH dose used in ADHD children was 0.7 ± 0.2 mg/kg (range: 0.3-1.3 mg/kg). The mean plasma OROS-MPH was 11.6 ± 7.3 ng/mL (range: 0.5-43.4 ng/mL). There was no group difference in the mean plasma MPH and dose-related MPH levels between the groups that used any additional drug including aripiprazole (n = 25), risperidone (n = 10), fluoxetine (n = 16), sertraline (n = 10), and did not use these drugs (P > 0.05). There was a positive correlation between the OROS-MPH doses (mg/kg) and the blood MPH levels (Pearson correlation = 0.40; P < 0.001). The plasma levels of MPH were found to be less than 13 ng/mL in 65% of the subjects. Our findings point to the fact that plasma levels of MPH show a wide range of changes at similar doses, correlate positively with the doses and, as expected, are not affected by using risperidone, sertraline, fluoxetine, and aripiprazole. Therapeutic drug monitoring may help to optimize MPH dose in patients not responding to treatment or in those experiencing serious side effects, but not in routine clinical practice. The presence of intermediate dose formulations such as 45-mg tablets for OROS-MPH may contribute to the optimization.

ABCB1 c.2677G>T variation is associated with adverse reactions of OROS-methylphenidate in children and adolescents with ADHD.

PubMed

Kim, So Won; Lee, Ji Hyun; Lee, Sung Hee; Hong, Hyun Ju; Lee, Min Goo; Yook, Ki-Hwan

2013-08-01

Osmotic-release oral system (OROS)-methylphenidate (MPH) is a safe and well-tolerated drug. Some patients cannot continue this regimen with adverse drug reactions (ADRs). As drug efflux transporters of the central nervous system, ABCB1 plays an important role in the clearance of psychotropic drugs and their metabolites from brain tissues. We hypothesized that genetic variations in the ABCB1 gene may affect ADRs to OROS-MPH. We analyzed ADRs of OROS-MPH in 134 children and adolescents with attention-deficit hyperactivity disorder who completed a 4-week trial of OROS-MPH. The ADRs of OROS-MPH were evaluated by administering the Barkley Stimulant Side Effects Rating Scale. Our study proved that MPH is a substrate for ABCB1 by using membrane vesicle assay. We analyzed the influence of ABCB1 polymorphisms on ADRs to OROS-MPH. From the association study between ABCB1 polymorphisms and ADRs of OROS-MPH, c.2677G>T (p.Ala893Ser, rs2032582) showed a strong association with OROS-MPH-related ADRs (P = 0.008; odds ratio, 5.72). Furthermore, logistic regression analysis indicated that the TT genotype at the ABCB1 2677 locus is an independent determinant of ADRs attributed to OROS-MPH. In a functional study, the 893Ser variant markedly reduced MPH transport across the cell membrane. This is the first study to demonstrate that the TT genotype at position 2677 in the ABCB1 gene is associated with ADRs to OROS-MPH.

Interaction of chronic food restriction and methylphenidate in sensation seeking of rats.

PubMed

Talishinsky, Aleksandr D; Nicolas, Celine; Ikemoto, Satoshi

2017-07-01

It is necessary to understand better how chronic food restriction (CFR) and psychostimulant drugs interact in motivated behavior unrelated to food or energy homeostasis. We examined whether CFR augments methylphenidate (MPH)-potentiated responding reinforced by visual sensation (VS) and whether repeated MPH injections or prolonged CFR further augments such responses. Before starting the following experiments, rats on a CFR diet received a limited daily ration in such a way that their body weights decreased to 85-90% of their original weights over 2 weeks. In experiment 1, rats on CFR and ad libitum diet received four injections of varying MPH doses (0, 2.5, 5, and 10 mg/kg). In experiment 2, CFR and ad libitum groups received repeated injections of MPH (2.5 mg/kg). In experiment 3, half of CFR rats received repeated injections of MPH (2.5 mg/kg), and the other half received saline, and following a 7-day abstinence, they all received the 2.5-mg/kg dose of MPH. CFR rats increased VS-reinforced responding more than ad libitum rats when they received MPH. Repeated injections of MPH with prolonged CFR further increased VS-reinforced responding. We found a double dissociation where prolonged CFR (3 vs. 6 weeks) made VS-reinforced responding, but not locomotor activity, more responsive to MPH, whereas repeated MPH injections made locomotor activity, but not VS-reinforced responding, more responsive to MPH. CFR markedly potentiates effects of MPH on VS-reinforced responding. The present study demonstrates that the longer CFR continues, the greater psychostimulant drugs augment behavioral interaction with salient stimuli.

Influence of sensitization on the discriminative stimulus effects of methylphenidate in mice.

PubMed

McGovern, Robin; Luderman, Lauryn; Knecht, Kelly; Griffin, William C

2014-12-01

Methylphenidate (MPH) remains an important therapy for attention-deficit hyperactivity disorder, but aspects of its pharmacology remain unclear. In the present study, we used a regimen of MPH (8 mg/kg daily×14 days) in C57BL/6J mice to determine whether establishing locomotor sensitization to MPH influenced the acquisition and the dose-response function of MPH in a classic drug discrimination procedure. MPH-sensitized mice (SENS group) showed enhanced locomotor activity to the 8 mg/kg exposure dose as well as a 2 mg/kg dose before discrimination training. However, the SENS mice did not acquire discrimination of either a low dose (2 mg/kg) or a higher dose (4 mg/kg) of MPH any more rapidly than the CTRL mice. Further, during generalization testing, the dose-response functions for the SENS and CTRL mice were identical. Therefore, we did not find that previous exposure to MPH, which produced a sensitized locomotor response, facilitated MPH discrimination.

Charge transfer process at the Ag/MPH/TiO2 interface by SERS: alignment of the Fermi level.

PubMed

Zhang, Xiaolei; Sui, Huimin; Wang, Xiaolei; Su, Hongyang; Cheng, Weina; Wang, Xu; Zhao, Bing

2016-11-02

A nanoscale metal-molecule-semiconductor assembly (Ag/4-mercaptophenol/TiO 2 ) has been fabricated over Au nanoparticle (NP) films as a model to study the interfacial charge transfer (CT) effects involved in Ag/MPH/TiO 2 . Due to the interaction between Au NPs and Ag NPs, some distinct differences occur in the SERS spectra. We also measured the SERS of Ag/MPH (4-mercaptophenol), Ag/MPH/TiO 2 , and Au/Ag/MPH/TiO 2 assemblies at excitation wavelengths of 477, 514, 532, 633, and 785 nm. We found that the changes in the CT process, caused by the introduction of TiO 2 and Au, can be reflected in SERS. Then in combination with other detection methods, we proposed a possible CT process involved in the Ag/MPH, Ag/MPH/TiO 2 , and Au/Ag/MPH/TiO 2 assemblies. A Pt/Ag/MPH/TiO 2 assembly was also constructed to verify our proposed CT mechanism. This work not only provides more details about CT between metal-molecule-semiconductor interfaces but also aids in constructing nanoscale models to study interfacial problems with the SERS technique.

Strain Differences in Self-Administration of Methylphenidate and Sucrose Pellets in a Rat Model of ADHD

PubMed Central

Marusich, Julie A.; McCuddy, W. Travis; Beckmann, Joshua S.; Gipson, Cassandra D.; Bardo, Michael T.

2011-01-01

Despite its abuse potential, methylphenidate (MPH) is widely prescribed for treatment of attention deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine MPH self-administration in a rat model of ADHD. Experiment 1 examined the acquisition of MPH self-administration and assessed the MPH dose-effect curve in spontaneously hypertensive rats (SHR), an inbred rat model of ADHD, Wistar Kyotos (WKY), the progenitor strain for SHR, and Sprague-Dawleys (SD), an outbred control strain. Experiment 2 replicated Experiment 1, but replaced MPH infusions with sucrose pellets. Initial acquisition of MPH self-administration was greater in SHR and SD than WKY. With extended training using an incrementing fixed ratio schedule, however, SHR and WKY did not differ in responding for MPH using the training dose (0.3 mg/kg/infusion) or other unit doses, except that SHR showed greater responding than WKY at 0.1 mg/kg/infusion. SHR also showed greater acquisition and maintenance of sucrose-reinforced responding compared to both WKY and SD. Greater initial acquisition of MPH self-administration in SHR than WKY may not be due to a strain specific difference in sensitivity to the reinforcing effect of MPH. PMID:22015805

Biochemical studies of the Saccharomyces cerevisiae Mph1 helicase on junction-containing DNA structures

PubMed Central

Kang, Young-Hoon; Munashingha, Palinda Ruvan; Lee, Chul-Hwan; Nguyen, Tuan Anh; Seo, Yeon-Soo

2012-01-01

Saccharomyces cerevisiae Mph1 is a 3–5′ DNA helicase, required for the maintenance of genome integrity. In order to understand the ATPase/helicase role of Mph1 in genome stability, we characterized its helicase activity with a variety of DNA substrates, focusing on its action on junction structures containing three or four DNA strands. Consistent with its 3′ to 5′ directionality, Mph1 displaced 3′-flap substrates in double-fixed or equilibrating flap substrates. Surprisingly, Mph1 displaced the 5′-flap strand more efficiently than the 3′ flap strand from double-flap substrates, which is not expected for a 3–5′ DNA helicase. For this to occur, Mph1 required a threshold size (>5 nt) of 5′ single-stranded DNA flap. Based on the unique substrate requirements of Mph1 defined in this study, we propose that the helicase/ATPase activity of Mph1 play roles in converting multiple-stranded DNA structures into structures cleavable by processing enzymes such as Fen1. We also found that the helicase activity of Mph1 was used to cause structural alterations required for restoration of replication forks stalled due to damaged template. The helicase properties of Mph1 reported here could explain how it resolves D-loop structure, and are in keeping with a model proposed for the error-free damage avoidance pathway. PMID:22090425

Methylphenidate and Memory and Attention Adaptation Training for Persistent Cognitive Symptoms after Traumatic Brain Injury: A Randomized, Placebo-Controlled Trial.

PubMed

McDonald, Brenna C; Flashman, Laura A; Arciniegas, David B; Ferguson, Robert J; Xing, Li; Harezlak, Jaroslaw; Sprehn, Gwen C; Hammond, Flora M; Maerlender, Arthur C; Kruck, Carrie L; Gillock, Karen L; Frey, Kim; Wall, Rachel N; Saykin, Andrew J; McAllister, Thomas W

2017-08-01

The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (P<0.05) treatment-related improvements in cognitive functioning were found for word-list learning (MAAT/placebo>ABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI.

The effect of methylphenidate on prefrontal cognitive functioning, inattention, and hyperactivity in velocardiofacial syndrome.

PubMed

Green, Tamar; Weinberger, Ronnie; Diamond, Adele; Berant, Michael; Hirschfeld, Leora; Frisch, Amos; Zarchi, Omer; Weizman, Abraham; Gothelf, Doron

2011-12-01

Methylphenidate (MPH) is commonly used to treat attention-deficit/hyperactivity disorder (ADHD) in all children, including those with velocardiofacial syndrome (VCFS). Yet concerns have been raised regarding its safety and efficacy in VCFS. The goal of this study was to examine the safety and efficacy of MPH in children with VCFS. Thirty-four children and adolescents with VCFS and ADHD participated in a randomized, controlled trial with a 2:1 ratio of MPH versus placebo. All subjects underwent a cardiological evaluation before and after MPH administration. The primary outcome measure was prefrontal cognitive performance following a single dose of MPH or placebo. A follow-up assessment was conducted after a 6-month treatment with MPH. Compared with placebo, single MPH administration was associated with a more robust improvement in prefrontal cognitive performance, including achievements in the Hearts and Flowers executive function task and the visual continuous performance task. After 6 months of treatment, a 40% reduction in severity of ADHD symptoms was reported by parents on the Revised Conners Rating Scale. All subjects treated with MPH reported at least one side effect, but it did not necessitate discontinuation of treatment. MPH induced an increase in heart rate and blood pressure that was usually minor, but was clinically significant in two cases. No differences in response to MPH were observed between catechol-O-methyltransferase Met versus Val carriers. The use of MPH in children with VCFS appears to be effective and relatively safe. A comprehensive cardiovascular evaluation for children with VCFS before and during stimulant treatment is recommended.

Protective effects of forced exercise against methylphenidate-induced anxiety, depression and cognition impairment in rat.

PubMed

Motaghinejad, Majid; Motevalian, Manijeh; Larijani, Setare Farokhi; Khajehamedi, Zohreh

2015-01-01

Methylphenidate (MPH), a neural stimulant, can cause damages to brain; the chronic neurochemical and behavioral effects of MPH remain unclear. Exercise lowers stress and anxiety and can act as non-pharmacologic neuroprotective agent. In this study protective effects of exercise in MPH-induced anxiety, depression and cognition impairment were investigated. Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control, received normal saline (0.2 ml/rat) for 21 days, group 2 and 3 (as positive controls) received MPH (10 and 20 mg/kg) for 21 days. Groups 4 and 5 concurrently were treated with MPH (10 and 20 mg/kg) and forced exercise for 21 days. On day 21, Elevated Plus Maze (EPM), Open Field Test (OFT), Forced Swim Test (FST) and Tail Suspension Test (TST) were used to investigate the level of anxiety and depression in animals. In addition between 17(th) and 21(th) days, Morris Water Maze (MWM) was applied to evaluate the effect of MPH on spatial learning and memory. MPH-treated animals indicated a reflective depression and anxiety in a dose-dependent manner in FST, EPM and TST which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT. Forced exercise by treadmill can attenuate MPH-induced anxiety, depression and motor activity alteration in OFT. MPH also can disturb learning and memory in MWM and forced exercise can neutralize this effect of MPH. We conclude that forced exercise can be protective in brain against MPH-induced anxiety, depression and cognition alteration.

32 CFR 636.22 - Speed regulations.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) of this section). (d) The following special speed limits apply: (1) When passing troop formations, 10... tactical vehicles and will obey the following off-road driving speeds: Day Driving: Trails, 16 MPH Cross County, 6 MPH Night Driving: Trails, 5 MPH (with headlights) Cross Country, 5 MPH Night Driving: Trails...

Evaluation of 70 mph speed limit in Kentucky.

DOT National Transportation Integrated Search

2008-05-01

The objective of this study was to document the change in operating speeds of cars and trucks on rural interstates and parkways as a result of the change in speed limit from 65 mph to 70 mph. The 85th percentile speed increased 1.3 mph for cars (74.6...

40 CFR Appendix V to Part 86 - The Standard Road Cycle (SRC)

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Pt. 86, App. V... engine) Idle 10 sec 0 1 Mod accel to 30 MPH 4 1 Cruise at 30 MPH for 1/4 lap 0 1 Mod. decel to 20 MPH −5 1 Mod accel to 30 MPH 4 1 Cruise at 30 MPH for 1/4 lap 0 1 Mod. decel to stop −5 1 Idle 5 sec 0 1...

40 CFR Appendix V to Part 86 - The Standard Road Cycle (SRC)

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES (CONTINUED) Pt. 86, App. V... engine) Idle 10 sec 0 1 Mod accel to 30 MPH 4 1 Cruise at 30 MPH for 1/4 lap 0 1 Mod. decel to 20 MPH −5 1 Mod accel to 30 MPH 4 1 Cruise at 30 MPH for 1/4 lap 0 1 Mod. decel to stop −5 1 Idle 5 sec 0 1...

40 CFR Appendix V to Part 86 - The Standard Road Cycle (SRC)

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) CONTROL OF EMISSIONS FROM NEW AND IN-USE HIGHWAY VEHICLES AND ENGINES Pt. 86, App. V Appendix V... engine) Idle 10 sec 0 1 Mod accel to 30 MPH 4 1 Cruise at 30 MPH for 1/4 lap 0 1 Mod. decel to 20 MPH −5 1 Mod accel to 30 MPH 4 1 Cruise at 30 MPH for 1/4 lap 0 1 Mod. decel to stop −5 1 Idle 5 sec 0 1...

Attention enhancing effects of methylphenidate are age-dependent

PubMed Central

Bhattacharya, Shevon E.; Shumsky, Jed S.; Waterhouse, Barry D.

2014-01-01

The psychostimulant methylphenidate (MPH, Ritalin®) is used to treat a variety of cognitive disorders. MPH is also popular among healthy individuals, including the elderly, for its ability to focus attention and improve concentration, but these effects have not been shown to be comparable between aged and adult subjects. Thus, we tested whether MPH would improve performance in sustained attention in both adult and aged rats. In addition, we tested the impact of visual distraction on performance in this task and the ability of MPH to mitigate the effects of distraction. Adult (6–12 months) and aged (18–22 months) male Sprague-Dawley rats were given oral MPH, and their cognitive and motor abilities were tested. Results suggest that while MPH improves task performance in adults; there is no improvement in the aged animals. These outcomes suggest that use of MPH for cognitive enhancement in elderly individuals may be ineffective. PMID:25449855

Optimal speed limits for school buses on Virginia highways : a report to Virginia's Superintendent of Public Instruction.

DOT National Transportation Integrated Search

1990-01-01

On Virginia's rural interstate highways there is a three-tiered speed limit: 45 mph for school buses, 55 mph for trucks, and 65 mph for other vehicles. On the urban interstate highways, school buses are restricted to 45 mph, but other traffic has a 5...

Better efficacy for the osmotic release oral system methylphenidate among poor adherents to immediate-release methylphenidate in the three ADHD subtypes.

PubMed

Chou, Wen-Jiun; Chou, Miao-Chun; Tzang, Ruu-Fen; Hsu, Ya-Chen; Gau, Susan Shur-Fen; Chen, Shin-Jaw; Wu, Yu-Yu; Huang, Ya-Fen; Liang, Hsin-Yi; Cheng, Helen

2009-04-01

To determine factors for switching to osmotic release oral system methylphenidate (OROS-MPH) among poor adherents to immediate-release methylphenidate (IR-MPH); and to compare the efficacy of OROS-MPH on the three attention-deficit/hyperactivity disorder (ADHD) subtypes in a multi-site prospective observational study in Taiwan. The sample included 240 children with ADHD, aged 6-16 years, who were poor adherents to IR-MPH, 137 of whom were switched to OROS-MPH. The child psychiatrists diagnosed the Diagnostic Statistical Manual of Mental Disorders (4th edition) ADHD subtypes and assessed the medical history, adherence, side-effects, global ADHD severity, and family/school effectiveness. Parents reported their child's behavioral symptoms. The determinants for an OROS-MPH switch were higher dosage, shorter treatment and thrice-daily administration of IR-MPH, and more severe inattention symptoms. Hyperactivity and oppositional symptoms were greater in the ADHD combined and hyperactive-impulsive subtypes than the inattentive subtype. Switching to OROS-MPH significantly improved behavioral symptoms and family/school measures, and this was most evident in the ADHD-combined group, followed by the ADHD-inattentive group. Inattention influenced not only academic performance, but also overall classroom behaviors and the parent-child relationship, with the latter two also influenced by oppositional symptoms. This study suggests better efficacy for the OROS-MPH among poor adherents to IR-MPH; however, its effectiveness varied across the three ADHD subtypes (ClinicalTrials.gov number NCT00460720).

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults.

PubMed

Kollins, Scott H; Schoenfelder, Erin N; English, Joseph S; Holdaway, Alex; Van Voorhees, Elizabeth; O'Brien, Benjamin R; Dew, Rachel; Chrisman, Allan K

2015-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10mg oral doses of delta-9-tetrahydocannibinol (THC); and 0mg, 10mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10mg THC+0mg, 10mg, and 40 mg MPH=89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of "Feel Drug," "Good Effects," and "Take Drug Again." THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. Copyright © 2014 Elsevier Inc. All rights reserved.

An exploratory study of the combined effects of orally administered methylphenidate and delta-9-tetrahydrocannabinol (THC) on cardiovascular function, subjective effects, and performance in healthy adults

PubMed Central

Kollins, Scott H.; Schoenfelder, Erin N.; English, Joseph S.; Holdaway, Alex; Van Voorhees, Elizabeth; O’Brien, Benjamin R.; Dew, Rachel; Chrisman, Allan K.

2014-01-01

Methylphenidate (MPH) is commonly prescribed for the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and is often used illicitly by young adults. Illicit users often coadminister MPH with marijuana. Little is known about physiologic and subjective effects of these substances used in combination. In this double-blind, cross-over experiment, sixteen healthy adult subjects free from psychiatric illness (including ADHD) and reporting modest levels of marijuana use participated in 6 experimental sessions wherein all combinations of placebo or 10 mg oral doses of delta-9-tetrahydocannibinol (THC); and 0 mg, 10 mg and 40 mg of MPH were administered. Sessions were separated by at least 48 hours. Vital signs, subjective effects, and performance measure were collected. THC and MPH showed additive effects on heart rate and rate pressure product (e.g., peak heart rate for 10 mg THC + 0 mg, 10 mg, and 40 mg MPH = 89.1, 95.9, 102.0 beats/min, respectively). Main effects of THC and MPH were also observed on a range of subjective measures of drug effects, and significant THC dose × MPH dose interactions were found on measures of “Feel Drug,” “Good Effects,” and “Take Drug Again.” THC increased commission errors on a continuous performance test (CPT) and MPH reduced reaction time variability on this measure. Effects of THC, MPH, and their combination were variable on a measure of working memory (n-back task), though in general, MPH decreased reaction times and THC mitigated these effects. These results suggest that the combination of low to moderate doses of MPH and THC produces unique effects on cardiovascular function, subjective effects and performance measures. PMID:25175495

Factors that influence full-time MPH Students' willingness in China: would You apply again for an MPH graduate degree if you had another opportunity?

PubMed

Wang, Nan; Jia, Jinzhong; Wu, Ke; Wang, Yuanyuan; Zhang, Chi; Cao, Wei; Duan, Liping; Wang, Zhifeng

2017-02-14

Current and emerging challenges to public health in the 21st century are vastly different from those faced in previous centuries. And the shortage of health personnel and their low level of educational qualifications hindered the development of Chinese public health services. In order to fulfill this requirement, the Ministry of Education initiated a full-time, Master of Public Health (MPH) graduate programme in 2009. This study aimed to evaluate the level of graduate students' satisfaction with full-time Master of Public Health (MPH) education in China, and whether they would apply again for an MPH graduate degree if they had another opportunity to do so, as well as to identify the factors influencing their decision-making process. An anonymous, web-based survey questionnaire containing 61 items was distributed to 702 MPH students in 35 universities or colleges. The questions covered the categories of student admission, training goals, lecture courses, practical training, research activities and mentorship. Levels of satisfaction were compared between MPH students who would choose MPH again as their graduate degree if they had another opportunity to do so and those who would not. Key influencing factors of training satisfaction were identified using logistic regression models. A total of 65.10% of the participants would apply again for MPH education if they had another opportunity to do so. The factors influencing students' willingness included their university type, the time since admission and their initial willingness. In addition, the four common factors (admissions & lecture courses, research activities & mentorship, practical training and training goals) emerging from factor analysis were all significantly positively correlated with student willingness (p < 0.001). Most MPH students surveyed were highly satisfied with their MPH education and, although they advocated for improvements and reforms in some aspects, they would still choose MPH as their graduate degree again if they had another opportunity to do so.

Raising the speed limit from 75 to 80mph on Utah rural interstates: Effects on vehicle speeds and speed variance.

PubMed

Hu, Wen

2017-06-01

In November 2010 and October 2013, Utah increased speed limits on sections of rural interstates from 75 to 80mph. Effects on vehicle speeds and speed variance were examined. Speeds were measured in May 2010 and May 2014 within the new 80mph zones, and at a nearby spillover site and at more distant control sites where speed limits remained 75mph. Log-linear regression models estimated percentage changes in speed variance and mean speeds for passenger vehicles and large trucks associated with the speed limit increase. Logistic regression models estimated effects on the probability of passenger vehicles exceeding 80, 85, or 90mph and large trucks exceeding 80mph. Within the 80mph zones and at the spillover location in 2014, mean passenger vehicle speeds were significantly higher (4.1% and 3.5%, respectively), as were the probabilities that passenger vehicles exceeded 80mph (122.3% and 88.5%, respectively), than would have been expected without the speed limit increase. Probabilities that passenger vehicles exceeded 85 and 90mph were non-significantly higher than expected within the 80mph zones. For large trucks, the mean speed and probability of exceeding 80mph were higher than expected within the 80mph zones. Only the increase in mean speed was significant. Raising the speed limit was associated with non-significant increases in speed variance. The study adds to the wealth of evidence that increasing speed limits leads to higher travel speeds and an increased probability of exceeding the new speed limit. Results moreover contradict the claim that increasing speed limits reduces speed variance. Although the estimated increases in mean vehicle speeds may appear modest, prior research suggests such increases would be associated with substantial increases in fatal or injury crashes. This should be considered by lawmakers considering increasing speed limits. Copyright © 2017 Elsevier Ltd and National Safety Council. All rights reserved.

Extended-release dexmethylphenidate 30 mg/d versus 20 mg/d: duration of attention, behavior, and performance benefits in children with attention-deficit/hyperactivity disorder.

PubMed

Silva, Raul R; Brams, Matthew; McCague, Kevin; Pestreich, Linda; Muniz, Rafael

2013-01-01

This study aimed to compare the effects of dexmethylphenidate (D-MPH) extended-release (ER) 30 mg and D-MPH-ER 20 mg on attention, behavior, and performance in children with attention-deficit/hyperactivity disorder. In a randomized, double-blind, 3-period-by-3-treatment, crossover study, children aged 6 to 12 years with attention-deficit/hyperactivity disorder stabilized on methylphenidate (40-60 mg/d) or D-MPH (20-30 mg/d) received D-MPH-ER 20 mg/d, 30 mg/d, and placebo for 7 days each (final dose of each treatment period administered in a laboratory classroom). Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined (Attention and Deportment) rating scale and Permanent Product Measure of Performance (PERMP) math test assessments were conducted at baseline and 3, 6, 9, 10, 11, and 12 hours postdose. A total of 165 children (94 boys; mean age, 9.6 years) were randomized (162 included in intent-to-treat analyses). Significant improvements were noted for D-MPH-ER 30 mg over D-MPH-ER 20 mg at various late time points on the SKAMP scales (Combined scores at 9, 10, 11, and 12 hours postdose; Attention scores at 10, 11, and 12 hours postdose; deportment scores at 9 and 12 hours postdose). The PERMP math test-attempted and -correct scores (change from predose) were significantly higher with D-MPH-ER 30 mg than with D-MPH-ER 20 mg at 10, 11, and 12 hours postdose. Both D-MPH-ER doses were superior to placebo at all time points. D-MPH-ER 30 mg was superior to D-MPH-ER 20 mg at later time points in the day, suggesting that higher doses of D-MPH-ER may be more effective later in the day.

Neuroimaging-Aided Prediction of the Effect of Methylphenidate in Children with Attention-Deficit Hyperactivity Disorder: A Randomized Controlled Trial.

PubMed

Ishii-Takahashi, Ayaka; Takizawa, Ryu; Nishimura, Yukika; Kawakubo, Yuki; Hamada, Kasumi; Okuhata, Shiho; Kawasaki, Shingo; Kuwabara, Hitoshi; Shimada, Takafumi; Todokoro, Ayako; Igarashi, Takashi; Watanabe, Kei-Ichiro; Yamasue, Hidenori; Kato, Nobumasa; Kasai, Kiyoto; Kano, Yukiko

2015-11-01

Although methylphenidate hydrochloride (MPH) is a first-line treatment for children with attention-deficit hyperactivity disorder (ADHD), the non-response rate is 30%. Our aim was to develop a supplementary neuroimaging biomarker for predicting the clinical effect of continuous MPH administration by using near-infrared spectroscopy (NIRS). After baseline assessment, we performed a double-blind, placebo-controlled, crossover trial with a single dose of MPH, followed by a prospective 4-to-8-week open trial with continuous MPH administration, and an ancillary 1-year follow-up. Twenty-two drug-naïve and eight previously treated children with ADHD (NAÏVE and NON-NAÏVE) were compared with 20 healthy controls (HCs) who underwent multiple NIRS measurements without intervention. We tested whether NIRS signals at the baseline assessment or ΔNIRS (single dose of MPH minus baseline assessment) predict the Clinical Global Impressions-Severity (CGI-S) score after 4-to-8-week or 1-year MPH administration. The secondary outcomes were the effect of MPH on NIRS signals after single-dose, 4-to-8-week, and 1-year administration. ΔNIRS significantly predicted CGI-S after 4-to-8-week MPH administration. The leave-one-out classification algorithm had 81% accuracy using the NIRS signal. ΔNIRS also significantly predicted CGI-S scores after 1 year of MPH administration. For secondary analyses, NAÏVE exhibited significantly lower prefrontal activation than HCs at the baseline assessment, whereas NON-NAÏVE and HCs showed similar activation. A single dose of MPH significantly increased activation compared with the placebo in NAÏVE. After 4-to-8-week administration, and even after MPH washout following 1-year administration, NAÏVE demonstrated normalized prefrontal activation. Supplementary NIRS measurements may serve as an objective biomarker for clinical decisions and monitoring concerning continuous MPH treatment in children with ADHD.

Methylphenidate effects in the young brain: friend or foe?

PubMed

Loureiro-Vieira, Sara; Costa, Vera Marisa; de Lourdes Bastos, Maria; Carvalho, Félix; Capela, João Paulo

2017-08-01

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent neuropsychiatry disorders in children and adolescents, and methylphenidate (MPH) is a first-line stimulant drug available worldwide for its treatment. Despite the proven therapeutic efficacy, concerns have been raised regarding the possible consequences of chronic MPH exposure during childhood and adolescence. Disturbances in the neurodevelopment at these crucial stages are major concerns given the unknown future life consequences. This review is focused on the long-term adverse effects of MPH to the brain biochemistry. Reports conducted with young and/or adolescent animals and studies with humans are reviewed in the context of long-term consequences after early life-exposure. MPH pharmacokinetics is also reviewed as there are differences among laboratory animals and humans that may be relevant to extrapolate the findings. Studies reveal that exposure to MPH in laboratory animals during young and/or adolescent ages can impact the brain, but the outcomes are dependent on MPH dose, treatment period, and animal's age. Importantly, the female sex is largely overlooked in both animal and human studies. Unfortunately, human reports that evaluate adults following adolescent or child exposure to MPH are very scarce. In general, human data indicates that MPH is generally safe, although it can promote several brain changes in early ages. Even so, there is a lack of long course patient evaluation to clearly establish whether MPH-induced changes are friendly or foe to the brain and more human studies are needed to assess the adult brain changes that arise from early MPH treatment. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.

Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with Attention Deficit/Hyperactivity Disorder.

PubMed

Findling, Robert L; Quinn, Declan; Hatch, Simon J; Cameron, Sara J; DeCory, Heleen H; McDowell, Michael

2006-12-01

To compare the efficacy and safety of two methylphenidate (MPH) formulations--once-daily modified-release MPH (EqXL, Equasym XL) and twice-daily immediate-release methylphenidate (MPH-IR, Ritalin)--and placebo in children with Attention Deficit/Hyperactivity Disorder (ADHD). Children aged 6-12 years on a stable dose of MPH were randomized into a double-blind, three-arm, parallel-group, multi-center study and received 3 weeks of EqXL (20, 40, or 60 mg qd), MPH-IR (10, 20, or 30 mg bid) or placebo. Non-inferiority of EqXL to MPH-IR was assessed by the difference in the inattention/overactivity component of the overall teacher's IOWA Conners' Rating Scale on the last week of treatment (per protocol population). Safety was monitored by adverse events, laboratory parameters, vital signs, physical exam, and a Side Effect Rating Scale. The lower 97.5% confidence interval bound of the difference between MPH groups fell above the non-inferiority margin (-1.5 points) not only during the last week of treatment but during all three treatment weeks. Both MPH-treatment groups experienced superior benefit when compared to placebo during all treatment weeks (P < 0.001). All treatments were well tolerated. EqXL given once-daily was non-inferior to MPH-IR given twice-daily. Both treatments were superior to placebo in reducing ADHD symptoms.

Methylphenidate-induced motor activity in rats: modulation by melatonin and vasopressin.

PubMed

Appenrodt, Edgar; Schwarzberg, Helmut

2003-04-01

Methylphenidate (MPH), a dopamine (DA) reuptake inhibitor, is well known to enhance motor activity, in part depending on the time of its application during the light-dark cycle. Moreover, after MPH administration, the hypothalamo-neurohypophysial axis including the neuropeptide vasopressin (AVP) was found influenced. Both the latter and behavioural effects of central AVP can also be modulated by the pineal gland with its light-dark-dependent activity. The present study was performed to investigate whether the pineal gland, its hormone melatonin (Mel), and AVP are involved in the MPH-evoked stimulation of activity. After application of 10 mg/kg MPH, the motor activity in pinealectomised (PE) rats was significantly higher than in sham-operated (SO) animals. After application of 250 microg Mel before MPH treatment, the stimulation of motor activity was diminished in PE rats and augmented in SO animals; however, when SO and PE rats were compared after Mel pretreatment, the reaction to MPH was nearly identical. Blocking the endogenous AVP by 25 or 1 microg of the V1a receptor antagonist d(CH(2))(5)[Tyr(Me)(2)]AVP (AAVP) before MPH treatment significantly augmented the motor activity in SO rats only and abolished the differences seen between SO and PE animals after MPH application. The present results indicate that the behavioural stimulation of MPH was modulated by both the pineal gland with its hormone Mel as well as the neuropeptide AVP.

Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus.

PubMed

Schmitz, Felipe; Pierozan, Paula; Biasibetti-Brendler, Helena; Ferreira, Fernanda Silva; Dos Santos Petry, Fernanda; Trindade, Vera Maria Treis; Pessoa-Pureur, Regina; Wyse, Angela T S

2017-12-29

Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent. Middle and high molecular weight neurofilament subunits (NF-M, NF-H) were hypophosphorylated by MPH on KSP repeat tail domains, while NFL, NFM and NFH immunocontents were not altered. MPH increased protein phosphatase 1 (PP1) and 2A (PP2A) immunocontents. MPH also decreased the total content of ganglioside and phospholipid, as well as the main brain gangliosides (GM1, GD1a, and GD1b) and the major brain phospholipids (sphingomyelin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, and phosphatidylserine). Total cholesterol content was also reduced in the hippocampi of juvenile rats treated with MPH. These results provide evidence that disruptions of cytoskeletal and lipid homeostasis in hippocampus of juvenile rats are triggers by chronic MPH treatment and present a new basis for understanding the effects and consequences associated with chronic use of this psychostimulant during the development of the central nervous system.

76 FR 31800 - Airworthiness Directives; Viking Air Limited Model DHC-3 (Otter) Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

...: ``Airspeed limitation: VMO = 144 MPH for the effective date of this land/ski plane and VMO = 134 MPH for... limit for land/ in-service (TIS) after the ski plane and 134 MPH, VMO speed limit for seaplane... land/ski the effective date of this plane and/or with a red radial at 134 MPH for a seaplane. This...

Results of baseline tests of the Lucas Limousine

NASA Technical Reports Server (NTRS)

Soltis, R. F.; Dustin, M. O.; Sargent, N. B.

1977-01-01

The Lucas Limousine, an electric vehicle, was tested to assess the state-of-the-art of electric vehicles. All tests were made without the regenerative braking system and were conducted at the gross vehicle weight of 7,700 pounds. Over a 30 mph stop and go driving cycle the vehicle went 48.4 miles. The vehicle was able to accelerate to 30 mph in about 15 seconds with a gradeability limit of 16.5 percent. As determined by coast down tests the road power and road energy consumption for the vehicle were 2.92 kilowatts and 0.146 kWh/mi, respectively, at 20 mph. At 40 mph the road power requirement was 11.12 kilowatts and the road energy requirement was 0.278 kWh/mi. The maximum energy economy measured 0.45 kilowatt hours per mile at 30 mph and increased to 0.76 kilowatt hours per mile at 50 mph. Over the 30 mph stop and go driving cycle the energy economy was 0.92 kilowatt hours per mile.

40 CFR Appendix I to Part 600 - Highway Fuel Economy Driving Schedule (Applicable to 1978 and Later Model Year Automobiles)

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 30 2011-07-01 2011-07-01 false Highway Fuel Economy Driving Schedule (Applicable to 1978 and Later Model Year Automobiles) I Appendix I to Part 600 Protection of Environment... to 1978 and Later Model Year Automobiles) [ speed (mph) vs time (sec) ] SEC MPH SEC MPH SEC MPH SEC...

Validity of the Smarthealth Watch to Measure Heart Rate during Rest and Exercise

ERIC Educational Resources Information Center

Lee, C. Matthew; Gorelick, Mark

2011-01-01

The purpose of this study was to examine the validity of the Smarthealth watch (Salutron, Inc., Fremont, California, USA), a heart rate monitor that includes a wristwatch without an accompanying chest strap. Twenty-five individuals participated in 3-min periods of standing, 2.0 mph walking, 3.5 mph walking, 4.5 mph jogging, and 6.0 mph running.…

Effects of Methylphenidate on Sleep Functioning in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Becker, Stephen P; Froehlich, Tanya E; Epstein, Jeffery N

2016-06-01

To examine the effects of stimulant medication on the sleep functioning of children with attention-deficit/hyperactivity disorder (ADHD) and identify predictors of sleep problems as a side effect of taking stimulant medication. One hundred sixty-three stimulant-naïve children (72% boys) aged 7 to 11 years diagnosed with ADHD (120 with ADHD predominantly inattentive type, 43 with ADHD combined type) participated in a 4-week, randomized, double-blind, placebo-controlled trial of once-daily (long-acting) methylphenidate (MPH). Parents completed weekly side-effect ratings including an item related to sleep problems. Ten percent of patients had parent-rated sleep problems before the initiation of medication. Rates of parent-rated sleep problems during MPH titration generally increased with increasing MPH dose (placebo: 8%; low dose: 18%; medium dose: 15%; high dose: 25%). Differences emerged between children with (n = 16) or without (n = 147) preexisting sleep problems. Although 23% of children without preexisting sleep problems went on to have sleep problems at the highest MPH dose, only 37.5% of children with preexisting sleep problems still had sleep problems at the highest MPH dose. Lower weight and lower body mass index (BMI) were associated with increased sleep problems during MPH titration. This study demonstrated a general association between increased MPH dose and increased sleep problems in children with ADHD, particularly for children of lower weight/BMI. However, a substantial proportion of children with preexisting sleep difficulties no longer had sleep problems on the highest MPH dose, which may help explain mixed findings reported to date in studies examining the impact of MPH on sleep functioning in children with ADHD and suggests that MPH dose titration should not be avoided solely on the basis of a child's premorbid sleep problems. Future research is needed to replicate and extend these findings to more specific domains of sleep functioning and to identify differences between children with persistent or improved sleep functioning as a result of MPH use.

Preparing Master of Public Health Graduates to Work in Local Health Departments.

PubMed

Hemans-Henry, Calaine; Blake, Janice; Parton, Hilary; Koppaka, Ram; Greene, Carolyn M

2016-01-01

To identify key competencies and skills that all master of public health (MPH) graduates should have to be prepared to work in a local health department. In 2011-2012, the New York City Department of Health and Mental Hygiene administered electronic surveys to 2 categories of staff: current staff with an MPH as their highest degree, and current hiring managers. In all, 312 (77%) staff members with an MPH as their highest degree and 170 (57%) hiring managers responded to the survey. Of the respondents with an MPH as their highest degree, 85% stated that their MPH program prepared them for work at the New York City Health Department. Skills for which MPH graduates most often stated they were underprepared included facility in using SAS® statistical software, quantitative data analysis/statistics, personnel management/leadership, and data collection/database management/data cleaning. Among the skills hiring managers identified as required of MPH graduates, the following were most often cited as those for which newly hired MPH graduates were inadequately prepared: quantitative data analysis, researching/conducting literature reviews, scientific writing and publication, management skills, and working with contracts/requests for proposals. These findings suggest that MPH graduates could be better prepared to work in a local health department upon graduation. To be successful, new MPH graduate hires should possess fundamental skills and knowledge related to analysis, communication, management, and leadership. Local health departments and schools of public health must each contribute to the development of the current and future public health workforce through both formal learning opportunities and supplementary employment-based training to reinforce prior coursework and facilitate practical skill development.

Current status of master of public health programmes in India: a scoping review.

PubMed

Tiwari, Ritika; Negandhi, Himanshu; Zodpey, Sanjay

2018-04-01

There is a recognized need to improve training in public health in India. Currently, several Indian institutions and universities offer the Master of Public Health (MPH) programme. However, in the absence of any formal body or council for regulating public health education in the country, there is limited information available on these programmes. This scoping review was therefore undertaken to review the current status of MPH programmes in India. Information on MPH programmes was obtained using a two-step process. First, a list of all institutions offering MPH programmes in India was compiled by use of an internet and literature search. Second, detailed information on each programme was collected via an internet and literature search and through direct contact with the institutions and recognized experts in public health education. Between 1997 and 2016-2017, the number of institutions offering MPH programmes increased from 2 to 44. The eligibility criteria for the MPH programmes are variable. All programmes include some field experience. The ratio of faculty number to students enrolled ranged from 1:0.1 to 1:42. In the 2016-2017 academic year, 1190 places were being offered on MPH programmes but only 704 students were enrolled. MPH programmes being offered in India have witnessed a rapid expansion in the past two decades. This growth in supply of public health graduates is not yet matched by an increased demand. Despite the recognized need to strengthen the public health workforce in India, there is no clearly defined career pathway for MPH graduates in the national public health infrastructure. Institutions and public health bodies must collaborate to design and deliver MPH programmes to overcome the shortage of public health professionals, such that the development goals for India might be met.

Low dopamine transporter occupancy by methylphenidate as a possible reason for reduced treatment effectiveness in ADHD patients with cocaine dependence.

PubMed

Crunelle, Cleo L; van den Brink, Wim; Veltman, Dick J; van Emmerik-van Oortmerssen, Katelijne; Dom, Geert; Schoevers, Robert A; Booij, Jan

2013-12-01

Methylphenidate (MPH) occupies brain striatal dopamine transporters (DATs) and is an effective treatment for attention deficit hyperactivity disorder (ADHD). However, patients with ADHD and comorbid cocaine dependence do not benefit significantly from treatment with MPH. To better understand the neurobiology of this phenomenon, we examined DAT availability and the effects of MPH treatment on DAT occupancy in ADHD patients with and without cocaine dependence. ADHD patients without a comorbid substance use disorder (N=16) and ADHD patients with comorbid cocaine dependence (N=8) were imaged at baseline and after two weeks MPH treatment using single photon emission computed tomography (SPECT) with the DAT tracer [(123)I]FP-CIT. Changes in ADHD symptoms were measured with the ADHD symptom rating scale (ASRS). At baseline, we observed lower striatal DAT availability in ADHD patients with cocaine dependence. Following fixed MPH treatment, MPH occupied significantly less striatal DATs in cocaine-dependent than in non-cocaine dependent ADHD patients. There were no significant correlations between baseline DAT availability or DAT occupancy by MPH and ADHD symptom improvement. However, we did find significant correlations between DAT occupancy by MPH and decreases in impulsivity scores and years of cocaine use. These preliminary findings suggest that low DAT occupancy is not the reason why ADHD patients with cocaine dependence do not benefit from MPH treatment. It also suggests that higher dosages of MPH in these patients are probably not the solution and that medications directed at other pharmacological targets should be considered in these comorbid ADHD patients. This trial is registered at the Dutch Trial Register, www.trialregister.nl, under Trial ID number NTR3127. Copyright © 2013 Elsevier B.V. and ECNP. All rights reserved.

Differentiation of rodent behavioral phenotypes and methylphenidate action in sustained and flexible attention tasks.

PubMed

Chu, Richard; Shumsky, Jed; Waterhouse, Barry D

2016-06-15

Methyphenidate (MPH) is the primary drug treatment of choice for ADHD. It is also frequently used off-label as a cognitive enhancer by otherwise healthy individuals from all age groups and walks of life. Military personnel, students, and health professionals use MPH illicitly to increase attention and improve workplace performance over extended periods of work activity. Despite the frequency of its use, the efficacy of MPH to enhance cognitive function across individuals and in a variety of circumstances is not well characterized. We sought to better understand MPH׳s cognitive enhancing properties in two different rodent models of attention. We found that MPH could enhance performance in a sustained attention task, but that its effects in this test were subject dependent. More specifically, MPH increased attention in low baseline performing rats but had little to no effect on high performing rats. MPH exerted a similar subject specific effect in a test of flexible attention, i.e. the attention set shifting task. In this test MPH increased behavioral flexibility in animals with poor flexibility but impaired performance in more flexible animals. Overall, our results indicate that the effects of MPH are subject-specific and depend on the baseline level of performance. Furthermore, good performance in in the sustained attention task was correlated with good performance in the flexible attention task; i.e. animals with better vigilance exhibited greater behavioral flexibility. The findings are discussed in terms of potential neurobiological substrates, in particular noradrenergic mechanisms, that might underlie subject specific performance and subject specific responses to MPH. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2016 Elsevier B.V. All rights reserved.

Wind tunnel test of Teledyne Geotech model 1564B cup anemometer

NASA Astrophysics Data System (ADS)

Parker, M. J.; Addis, R. P.

1991-04-01

The Department of Energy (DOE) Environment, Safety, and Health Compliance Assessment (Tiger Team) of the Savannah River Site (SRS) questioned the method by which wind speed sensors (cup anemometers) are calibrated by the Environmental Technology Section (ETS). The Tiger Team member was concerned that calibration data was generated by running the wind tunnel to only 26 miles per hour (mph) when speeds exceeding 50 mph are readily obtainable. A wind tunnel experiment was conducted and confirmed the validity of the practice. Wind speeds common to SRS (6 mph) were predicted more accurately by 0-25 mph regression equations than 0-50 mph regression equations. Higher wind speeds were slightly overpredicted by the 0-25 mph regression equations when compared to 0-50 mph regression equations. However, the greater benefit of more accurate lower wind speed predictions accuracy outweigh the benefit of slightly better high (extreme) wind speed predictions. Therefore, it is concluded that 0-25 mph regression equations should continue to be utilized by ETS at SRS. During the Department of Energy Tiger Team audit, concerns were raised about the calibration of SRS cup anemometers. Wind speed is measured by ETS with Teledyne Geotech model 1564B cup anemometers, which are calibrated in the ETS wind tunnel. Linear regression lines are fitted to data points of tunnel speed versus anemometer output voltages up to 25 mph. The regression coefficients are then implemented into the data acquisition computer software when an instrument is installed in the field. The concern raised was that since the wind tunnel at SRS is able to generate a maximum wind speed higher than 25 mph, errors may be introduced in not using the full range of the wind tunnel.

Methylphenidate clinically oral doses improved brain and heart glutathione redox status and evoked renal and cardiac tissue injury in rats.

PubMed

Loureiro-Vieira, Sara; Costa, Vera Marisa; Duarte, José Alberto; Duarte-Araújo, Margarida; Gonçalves-Monteiro, Salomé; Maria de Lourdes, Bastos; Carvalho, Félix; Capela, João Paulo

2018-04-01

Methylphenidate (MPH) is a first-line stimulant drug to treat attention deficit hyperactivity disorder (ADHD). Overdiagnosis of ADHD and MPH abuse lead to serious concerns about the possible long-term adverse consequences of MPH in healthy children and adolescents. We aimed to evaluate MPH effects in adolescent male Wistar rats (postnatal day 40) using an oral dose scheme (2 daily MPH doses 5 mg/kg in a 5% sucrose solution, 5 h apart, for 7 days) that mimics the therapeutic doses given to human adolescents. Twenty-four hours after the last MPH administration, rats were sacrificed and brain areas [cerebellum, prefrontal cortex (PFC), hippocampus, and striatum], peripheral organs (liver, heart, and kidneys), and blood were collected for biochemical and histological analysis. MPH treatment did not alter rats' body temperature or weight, neither food or water intake throughout the experiment. The ratio of reduced glutathione/oxidized glutathione (GSH/GSSG) significantly increased in the PFC and hippocampus of MPH-treated rats, meanwhile protein carbonylation remained unchanged in the brain. In the heart, the GSH/GSSG ratio and GSH levels were significantly increased, with decreased GSSG, while histology revealed significant damage, namely interstitial edema, vascular congestion, and presence of a fibrin-like material in the interstitial space. In the kidneys, MPH treatment resulted in extensive necrotic areas with cellular disorganization and cell infiltration, and immunohistochemistry analysis revealed a marked activation of nuclear factor-ĸB. This study showed that clinically relevant oral MPH doses improve the GSH redox status in the brain and heart, but evoke heart and kidney tissue damage to adolescent rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The Effect of Microporous Polysaccharide Hemospheres on Wound Healing and Scarring in Wild-Type and db/db Mice.

PubMed

Miller, Kyle J; Cao, Wei; Ibrahim, Mohamed M; Levinson, Howard

2017-04-01

Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice. The effect of MPH on scarring was evaluated by applying it to the expanded polytetrafluoroethylene tube implantation model. In wild-type mice, topically applied MPH increased epithelial thickness. Levels of α-smooth muscle actin (α-SMA) were decreased in MPH-treated wild-type wounds, whereas Rho-associated protein kinase 2 (ROCK2) and transforming growth factor β levels were increased. In db/db mice, topical wound MPH application decreased epithelial thickness and delayed wound closure. The db/db wounds displayed an increased collagen index. The ROCK2 was increased in a similar manner to wild-type mice, whereas α-SMA and transforming growth factor β levels were decreased. The MPH-treated expanded polytetrafluoroethylene tube mice showed increased α-SMA levels and depressed ROCK2 levels. There were no changes in histologic parameters of the foreign body response. The results suggest that MPH does not adversely impact wound healing in wild-type mice, both topically and around implants, but prolongs time to closure and diminishes thickness in db/db wounds. The MPH application alters contractile proteins in all wound models. These changes could have downstream effects on the wound healing process, and further investigation into the use of MPH in altered or impaired states of wound healing is warranted.

KSC-04pd1716

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, modules and equipment are being covered in plastic in preparation for the expected impact of Hurricane Frances on Saturday. KSC workers also have powered down the Space Shuttle orbiters, closed their payload bay doors and stowed the landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The SSPF can withstand sustained winds of 110 mph and wind gusts up to 132 mph. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

Evaluation and reformulation of the maximum peak height algorithm (MPH) and application in a hypertrophic lagoon

NASA Astrophysics Data System (ADS)

Pitarch, Jaime; Ruiz-Verdú, Antonio; Sendra, María. D.; Santoleri, Rosalia

2017-02-01

We studied the performance of the MERIS maximum peak height (MPH) algorithm in the retrieval of chlorophyll-a concentration (CHL), using a matchup data set of Bottom-of-Rayleigh Reflectances (BRR) and CHL from a hypertrophic lake (Albufera de Valencia). The MPH algorithm produced a slight underestimation of CHL in the pixels classified as cyanobacteria (83% of the total) and a strong overestimation in those classified as eukaryotic phytoplankton (17%). In situ biomass data showed that the binary classification of MPH was not appropriate for mixed phytoplankton populations, producing also unrealistic discontinuities in the CHL maps. We recalibrated MPH using our matchup data set and found that a single calibration curve of third degree fitted equally well to all matchups regardless of how they were classified. As a modification to the former approach, we incorporated the Phycocyanin Index (PCI) in the formula, thus taking into account the gradient of phytoplankton composition, which reduced the CHL retrieval errors. By using in situ biomass data, we also proved that PCI was indeed an indicator of cyanobacterial dominance. We applied our recalibration of the MPH algorithm to the whole MERIS data set (2002-2012). Results highlight the usefulness of the MPH algorithm as a tool to monitor eutrophication. The relevance of this fact is higher since MPH does not require a complete atmospheric correction, which often fails over such waters. An adequate flagging or correction of sun glint is advisable though, since the MPH algorithm was sensitive to sun glint.

Mediators of methylphenidate effects on math performance in children with attention-deficit hyperactivity disorder.

PubMed

Froehlich, Tanya E; Antonini, Tanya N; Brinkman, William B; Langberg, Joshua M; Simon, John O; Adams, Ryan; Fredstrom, Bridget; Narad, Megan E; Kingery, Kathleen M; Altaye, Mekibib; Matheson, Heather; Tamm, Leanne; Epstein, Jeffery N

2014-01-01

Stimulant medications, such as methylphenidate (MPH), improve the academic performance of children with attention-deficit hyperactivity disorder (ADHD). However, the mechanism by which MPH exerts an effect on academic performance is unclear. We examined MPH effects on math performance and investigated possible mediation of MPH effects by changes in time on-task, inhibitory control, selective attention, and reaction time variability. Children with ADHD aged 7 to 11 years (N = 93) completed a timed math worksheet (with problems tailored to each individual's level of proficiency) and 2 neuropsychological tasks (Go/No-Go and Child Attention Network Test) at baseline, then participated in a 4-week, randomized, controlled, titration trial of MPH. Children were then randomly assigned to their optimal MPH dose or placebo for 1 week (administered double-blind) and repeated the math and neuropsychological tasks (posttest). Baseline and posttest videorecordings of children performing the math task were coded to assess time on-task. Children taking MPH completed 23 more math problems at posttest compared to baseline, whereas the placebo group completed 24 fewer problems on posttest versus baseline, but the effects on math accuracy (percent correct) did not differ. Path analyses revealed that only change in time on-task was a significant mediator of MPH's improvements in math productivity. MPH-derived math productivity improvements may be explained in part by increased time spent on-task, rather than improvements in neurocognitive parameters, such as inhibitory control, selective attention, or reaction time variability.

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults

PubMed Central

Yang, Xiaoxia; Duan, John; Fisher, Jeffrey

2016-01-01

A previously presented physiologically-based pharmacokinetic model for immediate release (IR) methylphenidate (MPH) was extended to characterize the pharmacokinetic behaviors of oral extended release (ER) MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI) tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations. PMID:27723791

Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

PubMed Central

Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

2014-01-01

The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

MPH program adaptability in a competitive marketplace: the case for continued assessment.

PubMed

Caron, Rosemary M; Tutko, Holly

2010-06-01

In the last several years, the number of Master of Public Health (MPH) programs has increased rapidly in the US. As such, MPH programs, particularly smaller-sized ones, need to critically examine how their programs are meeting the needs and preferences of local public health practitioners. To assist in this necessity, the University of New Hampshire conducted a comprehensive educational assessment of its effectiveness as a smaller-sized, accredited MPH program. The aim of the assessment was to review the MPH program from the perspective of all stakeholders and then to agree on changes that would contribute to the fulfillment of the program's mission, as well as improve program quality and reach. The program's stakeholders examined the following components: policy development and implementation; target audience; marketing strategies; marketplace position; delivery model; curriculum design; and continuing education. Though assessment activities explored a wide array of program attributes, target audience, curriculum design, and delivery strategy presented significant challenges and opportunities for our smaller MPH Program to remain competitive. The effort put forth into conducting an in-depth assessment of the core components of our program also allowed for a comparison to the increasing number of MPH programs developing regionally. Since public health practice is changing and the education of public health practitioners must be adaptable, we propose that a routine assessment of an institution's MPH program could not only meet this need but also assist with keeping smaller, unbranded MPH programs competitive in a burgeoning marketplace.

Methylphenidate as a treatment for stuttering: a case report.

PubMed

Devroey, D; Beerens, G; Van De Vijver, E

2012-10-01

A randomized placebo controlled trial with methylphenidate (MPH) was set up to identify the effects of MPH on cognition in healthy young adults (ea. without attention deficit hyperactivity disorder, ADHD). Subjects repeatedly performed tests of the immediate and delayed memory and vigilance tasks after administration of placebo or 20 mg MPH. We report the case of an 18 year old man who participated in the study. He suffered from stuttering since childhood. During the study phase he reported a remarkable relief of the stuttering after the intake of 20 mg MPH. For D-amphetamine the beneficial effect on stuttering has been demonstrated but it was never implemented in clinical practice because of important adverse events. MPH, an amphetamine analogue, doesn't present these side effects. For this reason, MPH seems to merit further investigation in a randomized-controlled trial as a possible agent in the treatment of stuttering.Methylphenidate, Stuttering.

KSC-04pd1714

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers cover with plastic the Multi-Purpose Logistics Module Donatello in preparation for the expected impact of Hurricane Frances on Saturday. Other modules and equipment are being covered as well. Workers also have powered down the Space Shuttle orbiters, closed their payload bay doors and stowed the landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The SSPF can withstand sustained winds of 110 mph and wind gusts up to 132 mph. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1712

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers cover with plastic the U.S. Node 2 in preparation for the expected impact of Hurricane Frances on Saturday. Other modules and equipment are being covered as well. Workers also have powered down the Space Shuttle orbiters, closed their payload bay doors and stowed the landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The SSPF can withstand sustained winds of 110 mph and wind gusts up to 132 mph. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1713

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, workers cover with plastic the Multi-Purpose Logistics Module Raffaello in preparation for the expected impact of Hurricane Frances on Saturday. Other modules and equipment are being covered as well. Workers also have powered down the Space Shuttle orbiters, closed their payload bay doors and stowed the landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The SSPF can withstand sustained winds of 110 mph and wind gusts up to 132 mph. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1715

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, modules wrapped in plastic line one wall. The modules and equipment are being covered in preparation for the expected impact of Hurricane Frances on Saturday. KSC workers also have powered down the Space Shuttle orbiters, closed their payload bay doors and stowed the landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The SSPF can withstand sustained winds of 110 mph and wind gusts up to 132 mph. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

Effect of transitioning from extended-release methylphenidate onto osmotic, controlled-release methylphenidate in children/adolescents with ADHD: results of a 3-month non-interventional study.

PubMed

Wolff, Christian; Alfred, Adam; Lindermüller, Anton; Rettig, Klaus; Mattejat, Fritz; Gerwe, Martin; Slawik, Lara; Schäuble, Barbara

2011-01-01

To explore the clinical outcomes of children/adolescents with ADHD who transitioned from extended-release methylphenidate (ER MPH, Medikinet Retard) to osmotic release oral system (OROS) MPH (Concerta). Medikinet Retard is a registered trade name of Medice, Bad Iserlohn, Germany. Concerta is a registered trade name of Janssen-Cilag GmbH, Neuss, Germany. This prospective, non-interventional study included patients aged 6 to 18 years with a confirmed diagnosis of ADHD who experienced insufficient clinical response and/or poor tolerability on ER MPH. Patients transitioned onto OROS MPH and were followed for 12 weeks. Symptoms, functional outcome, health-related quality of life, safety and tolerability were assessed. 180 patients were included in the intention-to-treat analysis. The mean ER MPH dose before switching was 28.2 mg/day; mean OROS MPH starting dose was 38.1 mg/day, increasing to 41.2 mg/day at the final visit. Mean treatment duration was 79.49 ± 24.22 days (median 85; range 7-136). Several symptomatic and functional outcomes under OROS MPH treatment changed from baseline and included the Conners' Parent Rating Scale (CPRS; -11.7 ± 11.3; p < 0.0001), C-GAS (12.3 ± 15.2; p < 0.0001) and ILC-LQ0-28 (parents' rating 2.9 ± 4.3 and patients' rating 2.8 ± 3.8; both p < 0.0001). Improvements in social interactions, playing with other children, doing household chores, or school homework, going to bed, and behavior towards visitors/at visits were noted (p < 0.0001). Approximately 40% of patients reported better sleep quality and appetite (p < 0.0001), and 72.8% expressed satisfaction with OROS MPH therapy compared to previous ER MPH. OROS MPH was well tolerated; the most common AEs after switching, with an incidence >2% and possibly related to therapy, were involuntary muscle contractions (tics; 8.9%), insomnia (7.2%) and anorexia (5.0%). No relevant changes in body weight or vital signs were observed. Three patients reported four serious AEs, but none were considered related to OROS MPH. Limitations included those associated with the uncontrolled, open-label design, possible inclusion bias and non-validation of the CPRS in a German population. Transitioning onto OROS MPH improved functionality, symptom control and decreased burden of disease in patients with ADHD who had insufficient response to, and/or poor tolerability of ER MPH. Similarly, care givers benefited from patients' treatment and reported significant reduction in their burden of disease and improvement of their quality of life upon the child's transition onto OROS MPH.

‘Why do an MPH?’ Motivations and intentions of physicians undertaking postgraduate public health training at the University of Cape Town

PubMed Central

Zweigenthal, Virginia E.M.; Marquez, Emma; London, Leslie

2016-01-01

Background Public health (PH) approaches underpin the management and transformation of health systems in low- and middle-income countries. Despite the Master of Public Health (MPH) rarely being a prerequisite for health service employment in South Africa, many physicians pursue MPH qualifications. Objectives This study identifies their motivations and career intentions and explored MPH programme strengths and gaps in under- and post-graduate PH training. Design A cross-sectional study using an online questionnaire was completed by physicians graduating with an MPH between 2000 and 2009 and those enrolled in the programme in 2010 at the University of Cape Town. Results Nearly a quarter of MPH students were physicians. Of the 65 contactable physicians, 48% responded. They were mid-career physicians who wished to obtain research training (55%), who wished to gain broader perspectives on health (32%), and who used the MPH to advance careers (90%) as researchers, policy-makers, or managers. The MPH widened professional opportunities, with 62% changing jobs. They believed that inadequate undergraduate exposure should be remedied by applying PH approaches to clinical problems in community settings, which would increase the attractiveness of postgraduate PH training. Conclusions The MPH allows physicians to transition from pure clinical to research, policy and/or management work, preparing them to innovate changes for effective health systems, responsive to the health needs of populations. Limited local job options and incentives are important constraining factors. Advocacy for positions requiring qualifications and benchmarking exit competencies of programmes nationally may promote enrolment. PMID:27741958

Methylphenidate enhances NMDA-receptor response in medial prefrontal cortex via sigma-1 receptor: a novel mechanism for methylphenidate action.

PubMed

Zhang, Chun-Lei; Feng, Ze-Jun; Liu, Yue; Ji, Xiao-Hua; Peng, Ji-Yun; Zhang, Xue-Han; Zhen, Xue-Chu; Li, Bao-Ming

2012-01-01

Methylphenidate (MPH), commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD). Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC). To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca(2+) increase, but does not require PKA and extracellular Ca(2+) influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects.

Methylphenidate Enhances NMDA-Receptor Response in Medial Prefrontal Cortex via Sigma-1 Receptor: A Novel Mechanism for Methylphenidate Action

PubMed Central

Liu, Yue; Ji, Xiao-Hua; Peng, Ji-Yun; Zhang, Xue-Han; Zhen, Xue-Chu; Li, Bao-Ming

2012-01-01

Methylphenidate (MPH), commercially called Ritalin or Concerta, has been widely used as a drug for Attention Deficit Hyperactivity Disorder (ADHD). Noteworthily, growing numbers of young people using prescribed MPH improperly for pleasurable enhancement, take high risk of addiction. Thus, understanding the mechanism underlying high level of MPH action in the brain becomes an important goal nowadays. As a blocker of catecholamine transporters, its therapeutic effect is explained as being due to proper modulation of D1 and α2A receptor. Here we showed that higher dose of MPH facilitates NMDA-receptor mediated synaptic transmission via a catecholamine-independent mechanism, in layer V∼VI pyramidal cells of the rat medial prefrontal cortex (PFC). To indicate its postsynaptic action, we next found that MPH facilitates NMDA-induced current and such facilitation could be blocked by σ1 but not D1/5 and α2 receptor antagonists. And this MPH eliciting enhancement of NMDA-receptor activity involves PLC, PKC and IP3 receptor mediated intracellular Ca2+ increase, but does not require PKA and extracellular Ca2+ influx. Our additional pharmacological studies confirmed that higher dose of MPH increases locomotor activity via interacting with σ1 receptor. Together, the present study demonstrates for the first time that MPH facilitates NMDA-receptor mediated synaptic transmission via σ1 receptor, and such facilitation requires PLC/IP3/PKC signaling pathway. This novel mechanism possibly explains the underlying mechanism for MPH induced addictive potential and other psychiatric side effects. PMID:23284812

Methylphenidate and environmental enrichment ameliorate the deleterious effects of prenatal stress on attention functioning.

PubMed

Zubedat, Salman; Aga-Mizrachi, Shlomit; Cymerblit-Sabba, Adi; Ritter, Ami; Nachmani, Maayan; Avital, Avi

2015-01-01

Either pre- or post-natal environmental factors seem to play a key role in brain and behavioral development and to exert long-term effects. Increasing evidence suggests that exposure to prenatal stress (PS) leads to motor and learning deficits and elevated anxiety, while enriched environment (EE) shows protective effects. The dopaminergic system is also sensitive to environmental life circumstances and affects attention functioning, which serves as the preliminary gate to cognitive processes. However, the effects of methylphenidate (MPH) on the dopaminergic system and attentional functioning, in the context of these life experiences, remain unclear. Therefore, we aimed to examine the effects of EE or PS on distinct types of attention, along with possible effects of MPH exposure. We found that PS impaired selective attention as well as partial sustained attention, while EE had beneficial effects. Both EE and MPH ameliorated the deleterious effects of PS on attention functioning. Considering the possible psychostimulant effect of MPH, we examined both anxiety-like behavior as well as motor learning. We found that PS had a clear anxiogenic effect, whereas EE had an anxiolytic effect. Nevertheless, the treatment with both MPH and/or EE recovered the deleterious effects of PS. In the motor-learning task, the PS group showed superior performance while MPH led to impaired motor learning. Performance decrements were prevented in both the PS + MPH and EE + MPH groups. This study provides evidence that peripubertal exposure to EE (by providing enhanced sensory, motor, and social opportunities) or MPH treatments might be an optional therapeutic intervention in preventing the PS long-term adverse consequences.

The effect of methylphenidate on sustained attention among adolescents with attention-deficit hyperactivity disorder.

PubMed

Lufi, Dubi; Bassin-Savion, Shiry; Rubel, Lilach

2015-01-01

Twenty-seven adolescents diagnosed as having attention-deficit hyperactivity disorder (ADHD) were tested twice with a computerized MATH-CPT (mathematics continuous performance test). In one administration, the participants took medication (methylphenidate, MPH) 1.5 hr before being tested. In another administration, the MATH-CPT was administered without the medication. Treatment with MPH improved the "overall attention level" and in measures of "reaction time" and "impulsivity." MPH did not improve the performance in the four measures of sustained attention. Knowing that treatment with MPH does not improve sustained attention can be helpful in reaching a decision of whether or not a child should be treated with MPH.

Cognitive effects of methylphenidate in healthy volunteers: a review of single dose studies.

PubMed

Linssen, A M W; Sambeth, A; Vuurman, E F P M; Riedel, W J

2014-06-01

Methylphenidate (MPH), a stimulant drug with dopamine and noradrenaline reuptake inhibition properties, is mainly prescribed in attention deficit hyperactivity disorder, is increasingly used by the general population, intending to enhance their cognitive function. In this literature review, we aim to answer whether this is effective. We present a novel way to determine the extent to which MPH enhances cognitive performance in a certain domain. Namely, we quantify this by a percentage that reflects the number of studies showing performance enhancing effects of MPH. To evaluate whether the dose-response relationship follows an inverted-U-shaped curve, MPH effects on cognition are also quantified for low, medium and high doses, respectively. The studies reviewed here show that single doses of MPH improve cognitive performance in the healthy population in the domains of working memory (65% of included studies) and speed of processing (48%), and to a lesser extent may also improve verbal learning and memory (31%), attention and vigilance (29%) and reasoning and problem solving (18%), but does not have an effect on visual learning and memory. MPH effects are dose-dependent and the dose-response relationship differs between cognitive domains. MPH use is associated with side effects and other adverse consequences, such as potential abuse. Future studies should focus on MPH specifically to adequately asses its benefits in relation to the risks specific to this drug.

Prenatal exposure to methylphenidate affects the dopamine system and the reactivity to natural reward in adulthood in rats.

PubMed

Lepelletier, François-Xavier; Tauber, Clovis; Nicolas, Céline; Solinas, Marcello; Castelnau, Pierre; Belzung, Catherine; Emond, Patrick; Cortese, Samuele; Faraone, Stephen V; Chalon, Sylvie; Galineau, Laurent

2014-10-31

Methylphenidate (MPH) is a commonly-used medication for the treatment of children with Attention-Deficit/Hyperactivity Disorders (ADHD). However, its prescription to adults with ADHD and narcolepsy raises the question of how the brain is impacted by MPH exposure during pregnancy. The goal of this study was to elucidate the long-term neurobiological consequences of prenatal exposure to MPH using a rat model. We focused on the effects of such treatment on the adult dopamine (DA) system and on the reactivity of animals to natural rewards. This study shows that adult male rats prenatally exposed to MPH display elevated expression of presynaptic DA markers in the DA cell bodies and the striatum. Our results also suggest that MPH-treated animals could exhibit increased tonic DA activity in the mesolimbic pathway, altered signal-to-noise ratio after a pharmacological stimulation, and decreased reactivity to the locomotor effects of cocaine. Finally, we demonstrated that MPH rats display a decreased preference and motivation for sucrose. This is the first preclinical study reporting long-lasting neurobiological alterations of DA networks as well as alterations in motivational behaviors for natural rewards after a prenatal exposure to MPH. These results raise concerns about the possible neurobiological consequences of MPH treatment during pregnancy. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Effects of methylphenidate on body index and physical fitness in Korean children with attention deficit hyperactivity disorder.

PubMed

Kang, Kyoung Doo; Yun, Sin Weon; Chung, Unsun; Kim, Tae Ho; Park, Jeong Ha; Park, In Hui; Han, Doug Hyun

2016-03-01

The side effects of methylphenidate (MPH) on growth remain a controversial concern. This study aimed to investigate the effect of MPH on clinical symptoms, growth, and physical fitness in Korean children. Fifty male children with attention deficit hyperactivity disorder (ADHD) treated with methylphenidate (MPH-ADHD), 69 MPH-naïve male children with ADHD (Naïve-ADHD), and 60 age-matched and sex-matched healthy control subjects were recruited. Intelligence quotient (IQ), clinical symptoms of ADHD, body index (height, weight, and body mass index [BMI]), and physical fitness (muscular strength, endurance, flexibility, agility, speed, and balance) were assessed. Total IQ and performance IQ scores were significantly different among the three groups, as were mean Korean Attention Deficit Hyperactivity Disorder (K-ARS)-total, K-ARS-inattention, and K-ARS-hyperactivity scores. There was no significant difference in height, weight, or BMI among the three groups. There were significant differences in skill-related fitness scores for balance (healthy controls > MPH-ADHD > Naïve-ADHD) and agility shuttle test time (healthy controls < MPH-ADHD < Naïve-ADHD). Our findings support the effectiveness of MPH treatment for improving IQ, attention, and balance and agility measures of skill-related fitness in Korean children with ADHD. MPH was not associated with growth delays in height, weight, and BMI. Copyright © 2016 John Wiley & Sons, Ltd.

Cognitive effects of methylphenidate and levodopa in healthy volunteers.

PubMed

Linssen, A M W; Sambeth, A; Vuurman, E F P M; Riedel, W J

2014-02-01

Our previous study showed enhanced declarative memory consolidation after acute methylphenidate (MPH) administration. The primary aim of the current study was to investigate the duration of this effect. Secondary, the dopaminergic contribution of MPH effects, the electrophysiological correlates of declarative memory, and the specificity of memory enhancing effects of MPH to declarative memory were assessed. Effects of 40 mg of MPH on memory performance were compared to 100mg of levodopa (LEV) in a placebo-controlled crossover study with 30 healthy volunteers. Memory performance testing included a word learning test, the Sternberg memory scanning task, a paired associates learning task, and a spatial working memory task. During the word learning test, event-related brain potentials (ERPs) were measured. MPH failed to enhance retention of words at a 30 min delay, but it improved 24 h delayed memory recall relative to PLA and LEV. Furthermore, during encoding, the P3b and P600 ERP latencies were prolonged and the P600 amplitude was larger after LEV compared to PLA and MPH. MPH speeded response times on the Sternberg Memory Scanning task and improved performance on the Paired Associates Learning task, relative to LEV, but not PLA. Performance on the Spatial working memory task was not affected by the treatments. These findings suggest that MPH and LEV might have opposite effects on memory. © 2013 Published by Elsevier B.V. and ECNP.

Outcome and impact of Master of Public Health programs across six countries: education for change

PubMed Central

2014-01-01

Background The human resources for health crisis has highlighted the need for high-level public health education to add specific capacities to the workforce. Recently, it was questioned whether Master of Public Health (MPH) training prepared graduates with competencies relevant to low- and middle-income countries (LMICs). This study aims to examine the influence of the MPH programs geared towards LMICs offered in Vietnam, China, South Africa, Mexico, Sudan, and the Netherlands on graduates’ careers, application of acquired competencies, performance at the workplace, and their professional contribution to society. Methods A self-administered questionnaire was sent to graduates from six MPH programs. Frequency distributions of the answers were calculated, and a bivariate analysis and logistic regression of certain variables was performed. Results The response rate was 37.5%. Graduates reported change in leadership (69%), in technical position (69%), acquiring new responsibilities (80%), and increased remuneration (63%); they asserted that MPH programs contributed significantly to this. Graduates’ attribution of their application of 7 key competencies ‘substantially to the MPH program’ ranged from 33% to 48%. Of the 26 impact variables, graduates attributed the effect they had on their workplace substantially to the MPH program; the highest rated variable ranged from 31% to 73% and the lowest ranged from 9% to 43%. Of the 10 impact variables on society, graduates attributed the effect they had on society substantially to the MPH program; for the highest rated variable (13% to 71%); for the lowest rated variable (4% to 42%). Candidates’ attribution of their application of acquired competencies as well as their impact at the workplace varied significantly according to institution of study and educational background. Conclusions This study concludes that these MPH programs contribute to improving graduates’ careers and to building leadership in public health. The MPH programs contribute to graduates’ application of competencies. MPH programs contribute substantially towards impact variables on the workplace, such as development of research proposals and reporting on population health needs, and less substantially to their impact on society, such as contributing equitable access to quality services. Differences reported between MPH programs merit further study. The results can be used for curriculum reform. PMID:25099707

Clinical potential of methylphenidate in the treatment of cocaine addiction: a review of the current evidence

PubMed Central

Dürsteler, Kenneth M; Berger, Eva-Maria; Strasser, Johannes; Caflisch, Carlo; Mutschler, Jochen; Herdener, Marcus; Vogel, Marc

2015-01-01

Background Cocaine use continues to be a public health problem, yet there is no proven effective pharmacotherapy for cocaine dependence. A promising approach to treating cocaine dependence may be agonist-replacement therapy, which is already used effectively in the treatment of opioid and tobacco dependence. The replacement approach for cocaine dependence posits that administration of a long-acting stimulant medication should normalize the neurochemical and behavioral perturbations resulting from chronic cocaine use. One potential medication to be substituted for cocaine is methylphenidate (MPH), as this stimulant possesses pharmacobehavioral properties similar to those of cocaine. Aim To provide a qualitative review addressing the rationale for the use of MPH as a cocaine substitute and its clinical potential in the treatment of cocaine dependence. Methods We searched MEDLINE for clinical studies using MPH in patients with cocaine abuse/dependence and screened the bibliographies of the articles found for pertinent literature. Results MPH, like cocaine, increases synaptic dopamine by inhibiting dopamine reuptake. The discriminative properties, reinforcing potential, and subjective effects of MPH and cocaine are almost identical and, importantly, MPH has been found to substitute for cocaine in animals and human volunteers under laboratory conditions. When taken orally in therapeutic doses, its abuse liability, however, appears low, which is especially true for extended-release MPH preparations. Though there are promising data in the literature, mainly from case reports and open-label studies, the results of randomized controlled trials have been disappointing so far and do not corroborate the use of MPH as a substitute for cocaine dependence in patients without attention deficit hyperactivity disorder. Conclusion Clinical studies evaluating MPH substitution for cocaine dependence have provided inconsistent findings. However, the negative findings may be explained by specific study characteristics, among them dosing, duration of treatment, or sample size. This needs to be considered when discussing the potential of MPH as replacement therapy for cocaine dependence. Finally, based on the results, we suggest possible directions for future research. PMID:26124696

Attention-Deficit/Hyperactivity Disorder Drugs and Growth: An Italian Prospective Observational Study

PubMed Central

Germinario, Elena A.P.; Arcieri, Romano; Bonati, Maurizio; Zuddas, Alessandro; Masi, Gabriele; Vella, Stefano; Chiarotti, Flavia

2013-01-01

Abstract Objective This study was conducted to assess the long-term effect of methylphenidate (MPH) or atomoxetine (ATX) on growth in attention-deficit/hyperactivity disorder (ADHD) drug-naïve children. Design The study was an observational, post-marketing, fourth phase study. Methods Data on height and weight were collected at baseline and every 6 months up to 24 months. Results Both ATX and MPH lead to decreased height gain (assessed by means of z-scores); the effect was significantly higher for ATX than for MPH. At any time, height z-score decrease in the ATX group was higher than the corresponding decrease observed in the MPH group, but the difference was significantly relevant only during the first year of treatment. An increment of average weight was observed both in patients treated with MPH and in those treated with ATX. However, using Tanner's percentile, a subset of patients showed a degree of growth lower than expected. This negative effect was significantly higher for ATX than for MPH. Conclusions We conclude that ADHD drugs show a negative effect on linear growth in children in middle term. Such effect appears more evident for ATX than for MPH. PMID:24024538

Hurricane Darby off the Pacific Coast of Mexico

NASA Image and Video Library

2004-07-26

Hurricane Darby as observed by the Atmospheric Infrared Sounder AIRS onboard NASA Aqua in July, 2004. This daylight image of Hurricane Darby on July 28 was made with the visible sensor in the AIRS instrument suite. After reaching sustained winds on July 27 of 100 knots (115 mph) with gusts to 120 knots (138 mph), the intensity of the storm is now lowered to 75 knots (86 mph). Located in the eastern north Pacific Ocean located about 1,165 miles west-southwest of the southern tip of Baja California, the storm continues its west/northwest path at 14 knots (16mph). Figure 1 is a daylight snapshot from AIRS visible/near-infrared sensor before Darby became a tropical storm. Darby is in the upper right-hand corner. Circulation is not apparent because the storm was not organized sufficiently to allow the nascent eye to appear. At this time, winds were approximately 35 mph. Figure 2 is an AIRS infrared image. Darby falls on the edge of two AIRS data granules, which have been "stitched" together in this image. Storm intensity is lowered to 75 knots (86 mph), down from 100 knots (115 mph). http://photojournal.jpl.nasa.gov/catalog/PIA00439

Methylphenidate enhances cognitive performance in adults with poor baseline capacities regardless of attention-deficit/hyperactivity disorder diagnosis.

PubMed

Agay, Nirit; Yechiam, Eldad; Carmel, Ziv; Levkovitz, Yechiel

2014-04-01

We compare the view that the effect of methylphenidate (MPH) is selective to individuals with attention-deficit/hyperactivity disorder (ADHD) with an alternative approach suggesting that its effect is more prominent for individuals with weak baseline capacities in relevant cognitive tasks. To evaluate theses 2 approaches, we administered sustained attention, working memory, and decision-making tasks to 20 ADHD adults and 19 control subjects, using a within-subject placebo-controlled design. The results demonstrated no main effects of MPH in the decision-making tasks. In the sustained attention and working-memory tasks, MPH enhanced performance of both ADHD and non-ADHD adults to a similar extent compared with placebo. Hence, the effect of MPH was not selective to ADHD adults. In addition, those benefitting most from MPH in all 3 task domains tended to be individuals with poor task performance. However, in most tasks, individuals whose performance was impaired by MPH were not necessarily better (or worse) performers. The findings suggest that the administration of MPH to adults with ADHD should consider not only clinical diagnosis but also their functional (performance-based) profile.

Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial.

PubMed

Lanctôt, Krista L; Chau, Sarah A; Herrmann, Nathan; Drye, Lea T; Rosenberg, Paul B; Scherer, Roberta W; Black, Sandra E; Vaidya, Vijay; Bachman, David L; Mintzer, Jacobo E

2014-02-01

Little is known about the effect of methylphenidate (MPH) on attention in Alzheimer's disease (AD). MPH has shown to improve apathy in AD, and both apathy and attention have been related to dopaminergic function. The goal was to investigate MPH effects on attention in AD and assess the relationship between attention and apathy responses. MPH (10 mg PO twice daily) or placebo was administered for six weeks in a randomized, double-blind trial in mild-to-moderate AD outpatients with apathy (Neuropsychiatric Inventory (NPI) Apathy ≥ 4). Attention was measured with the Wechsler Adult Intelligence Scale--Digit Span (DS) subtest (DS forward, selective attention) and apathy with the Apathy Evaluation Scale (AES). A mixed effects linear regression estimated the difference in change from baseline between treatment groups, defined as δ (MPH (DS week 6-DS baseline)) - (placebo (DS week 6-DS baseline)). In 60 patients (37 females, age = 76 ± 8, Mini-Mental State Examination (MMSE) = 20 ± 5, NPI Apathy = 7 ± 2), the change in DS forward (δ = 0.87 (95% CI: 0.06-1.68), p = 0.03) and DS total (δ = 1.01 (95% CI: 0.09-1.93), p = 0.03) favored MPH over placebo. Of 57 completers, 17 patients had improved apathy (≥3.3 points on the AES from baseline to end point) and 40 did not. There were no significant associations between AES and NPI Apathy with DS change scores in the MPH, placebo, AES responder, or non-responder groups. DS scores did not predict apathy response to MPH treatment. These results suggest MPH can improve attention and apathy in AD; however, the effects appear independent in this population.

Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.

PubMed

Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

2017-04-01

Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α 2 -adrenergic receptors. © 2016 Société Française de Pharmacologie et de Thérapeutique.

Extinction memory is facilitated by methylphenidate and regulated by dopamine and noradrenaline receptors.

PubMed

Furini, Cristiane R G; Behling, Jonny A K; Zinn, Carolina G; Zanini, Mara Lise; Assis Brasil, Eduardo; Pereira, Luiza Doro; Izquierdo, Ivan; de Carvalho Myskiw, Jociane

2017-05-30

Extinction is defined as the learned inhibition of retrieval and is the mainstay of exposure therapy, which is widely used to treat drug addiction, phobias and fear disorders. The psychostimulant, methylphenidate (MPH) is known to increase extracellular levels of noradrenaline and dopamine by blocking their reuptake and studies have demonstrated that MPH can modulate hippocampal physiology and/or functions including long-term potentiation (LTP), learning and memory. However, the influence of MPH on fear extinction memory has been insufficiently studied. Here we investigate the effect of MPH infused into the CA1 region of the hippocampus on extinction memory in animals normally incapable of showing contextual fear conditioning (CFC) extinction because of weak training, and the possible mechanisms through which it acts during this process. For this, male Wistar rats with infusion cannulae stereotaxically implanted in the CA1 region were submitted to a weak extinction protocol in a CFC apparatus. Animals that received intra-CA1 infusion of MPH (12.5μg/side) 20min before the extinction training (Ext Tr) expressed less freezing behavior than Veh-treated animals during both Ext Tr and extinction retention Test (Ext Test). Additionally, the administration of MPH+Timolol (1μg/side) or MPH+SCH23390 (1.5μg/side) intra-CA1 20min before the Ext Tr blocked the enhancing effect of the MPH on extinction learning. These results suggest that MPH in the CA1 region of the hippocampus is able to induce the consolidation of extinction memory and this process occurs through both β-adrenergic and D1/D5 dopaminergic receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

Wind tunnel test of Teledyne Geotech model 1564B cup anemometer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Parker, M.J.; Addis, R.P.

1991-04-04

The Department of Energy (DOE) Environment, Safety and Health Compliance Assessment (Tiger Team) of the Savannah River Site (SRS) questioned the method by which wind speed sensors (cup anemometers) are calibrated by the Environmental Technology Section (ETS). The Tiger Team member was concerned that calibration data was generated by running the wind tunnel to only 26 miles per hour (mph) when speeds exceeding 50 mph are readily obtainable. A wind tunnel experiment was conducted and confirmed the validity of the practice. Wind speeds common to SRS (6 mph) were predicted more accurately by 0--25 mph regression equations than 0--50 mphmore » regression equations. Higher wind speeds were slightly overpredicted by the 0--25 mph regression equations when compared to 0--50 mph regression equations. However, the greater benefit of more accurate lower wind speed predictions accuracy outweight the benefit of slightly better high (extreme) wind speed predictions. Therefore, it is concluded that 0--25 mph regression equations should continue to be utilized by ETS at SRS. During the Department of Energy Tiger Team audit, concerns were raised about the calibration of SRS cup anemometers. Wind speed is measured by ETS with Teledyne Geotech model 1564B cup anemometers, which are calibrated in the ETS wind tunnel. Linear regression lines are fitted to data points of tunnel speed versus anemometer output voltages up to 25 mph. The regression coefficients are then implemented into the data acquisition computer software when an instrument is installed in the field. The concern raised was that since the wind tunnel at SRS is able to generate a maximum wind speed higher than 25 mph, errors may be introduced in not using the full range of the wind tunnel.« less

The effect of multiple primary rules on cancer incidence rates and trends

PubMed Central

Weir, Hannah K.; Johnson, Christopher J.; Ward, Kevin C.; Coleman, Michel P.

2018-01-01

Purpose An examination of multiple primary cancers can provide insight into the etiologic role of genes, the environment, and prior cancer treatment on a cancer patient’s risk of developing a subsequent cancer. Different rules for registering multiple primary cancers (MP) are used by cancer registries throughout the world making data comparisons difficult. Methods We evaluated the effect of SEER and IARC/IACR rules on cancer incidence rates and trends using data from the SEER Program. We estimated age-standardized incidence rate (ASIR) and trends (1975–2011) for the top 26 cancer categories using joinpoint regression analysis. Results ASIRs were higher using SEER compared to IARC/IACR rules for all cancers combined (3 %) and, in rank order, melanoma (9 %), female breast (7 %), urinary bladder (6 %), colon (4 %), kidney and renal pelvis (4 %), oral cavity and pharynx (3 %), lung and bronchus (2 %), and non-Hodgkin lymphoma (2 %). ASIR differences were largest for patients aged 65+ years. Trends were similar using both MP rules with the exception of cancers of the urinary bladder, and kidney and renal pelvis. Conclusions The choice of multiple primary coding rules effects incidence rates and trends. Compared to SEER MP coding rules, IARC/IACR rules are less complex, have not changed over time, and report fewer multiple primary cancers, particularly cancers that occur in paired organs, at the same anatomic site and with the same or related histologic type. Cancer registries collecting incidence data using SEER rules may want to consider including incidence rates and trends using IARC/IACR rules to facilitate international data comparisons. PMID:26809509

Impact of the 65 mph speed limit on Virginia's rural interstate highways, 1989-1992.

DOT National Transportation Integrated Search

1994-01-01

In April of 1987, Congress passed the Surface Transportation and Uniform Relocation Assistance Act (STURAA), which permitted states to raise their maximum speed limit on rural interstate highways to 65 mph. Virginia's 65 mph speed limit went into eff...

The impact of the 65 MPH speed limit on Virginia's rural interstate highways through 1990.

DOT National Transportation Integrated Search

1992-01-01

In April of 1987, Congress passed the Surface Transportation and Uniform Relocation Assistance Act (STURAA), which permitted states to raise their maximum speed limit on rural interstate highways (rural interstates) to 65 mph. Virginia's 65 mph speed...

Evolution of the Study of Methylphenidate and Its Actions on the Adult Versus Juvenile Brain.

PubMed

Urban, Kimberly R; Gao, Wen-Jun

2015-07-01

Methylphenidate (MPH) is the most often prescribed medication for treatment of ADHD. However, many of its specific cellular and molecular mechanisms of action, as well as developmental consequences of treatment, are largely unknown. This review provides an overview of current understanding of MPH efficacy, safety, and dosage in adult and pediatric ADHD patients, as well as adult animal studies and pioneering studies in juvenile animals treated with MPH. A thorough review of the current literature on MPH efficacy and safety in children, adults, and animal models was included. Results of studies were compared and contrasted. While MPH is currently considered safe, there is a lack of knowledge of potential developmental consequences of early treatment, as well as differences in drug actions in the developing versus mature brain system. This review emphasizes the need for further research into the age-dependent activities and potency of MPH, and a need for tighter control and clinical relevance in future studies. © 2012 SAGE Publications.

Effects of methylphenidate on working memory components: influence of measurement.

PubMed

Bedard, Anne-Claude; Jain, Umesh; Johnson, Sheilah Hogg; Tannock, Rosemary

2007-09-01

To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in attention-deficit hyperactivity disorder (ADHD) and determine the responsiveness of WM measures to MPH. Participants were a clinical sample of 50 children and adolescents with ADHD, aged 6 to 16 years old, who participated in an acute randomized, double-blind, placebo-controlled, crossover trial with single challenges of three MPH doses. Four components of WM were investigated, which varied in processing demands (storage versus manipulation of information) and modality (auditory-verbal; visual-spatial), each of which was indexed by a minimum of two separate measures. MPH improved the ability to store visual-spatial information irrespective of instrument used, but had no effects on the storage of auditory-verbal information. By contrast, MPH enhanced the ability to manipulate both auditory-verbal and visual-spatial information, although effects were instrument specific in both cases. MPH effects on WM are selective: they vary as a function of WM component and measurement.

KSC-04pd1717

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Space Station Processing Facility, a worker wraps equipment in plastic in preparation for the expected impact of Hurricane Frances on Saturday. The various modules in the SSPF, such as the Japanese Experiment Module, U.S. Node 2 and Multi-Purpose Logistics Modules, are being covered as well. KSC workers also have powered down the Space Shuttle orbiters, closed their payload bay doors and stowed the landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The SSPF can withstand sustained winds of 110 mph and wind gusts up to 132 mph. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

Twin-arginine signal peptide of Bacillus subtilis YwbN can direct Tat-dependent secretion of methyl parathion hydrolase.

PubMed

Liu, Ruihua; Zuo, Zhenqiang; Xu, Yingming; Song, Cunjiang; Jiang, Hong; Qiao, Chuanling; Xu, Ping; Zhou, Qixing; Yang, Chao

2014-04-02

The twin-arginine translocation (Tat) pathway exports folded proteins across the cytoplasmic membranes of bacteria and archaea. Two parallel Tat pathways (TatAdCd and TatAyCy systems) with distinct substrate specificities have previously been discovered in Bacillus subtilis. In this study, to secrete methyl parathion hydrolase (MPH) into the growth medium, the twin-arginine signal peptide of B. subtilis YwbN was used to target MPH to the Tat pathway of B. subtilis. Western blot analysis and MPH assays demonstrated that active MPH was secreted into the culture supernatant of wild-type cells. No MPH secretion occurred in a total-tat2 mutant, indicating that the observed export in wild-type cells was mediated exclusively by the Tat pathway. Export was fully blocked in a tatAyCy mutant. In contrast, the tatAdCd mutant was still capable of secreting MPH. These results indicated that the MPH secretion directed by the YwbN signal peptide was specifically mediated by the TatAyCy system. The N-terminal sequence of secreted MPH was determined as AAPQVR, demonstrating that the YwbN signal peptide had been processed correctly. This is the first report of functional secretion of a heterologous protein via the B. subtilis TatAyCy system. This study highlights the potential of the TatAyCy system to be used for secretion of other heterologous proteins in B. subtilis.

MPH-M, AODV-M and DSR-M Performance Evaluation under Jamming Attacks.

PubMed

Del-Valle-Soto, Carolina; Mex-Perera, Carlos; Monroy, Raul; Nolazco-Flores, Juan A

2017-07-05

In this work, we present the design of a mitigation scheme for jamming attacks integrated to the routing protocols MPH, AODV, and DSR. The resulting protocols are named MPH-M (Multi-Parent Hierarchical - Modified), AODV-M (Ad hoc On Demand Distance Vector - Modified), and DSR-M (Dynamic Source Routing - Modified). For the mitigation algorithm, if the detection algorithm running locally in each node produces a positive result then the node is isolated; second, the routing protocol adapts their paths avoiding the isolated nodes. We evaluated how jamming attacks affect different metrics for all these modified protocols. The metrics we employ to detect jamming attack are number of packet retransmissions, number of CSMA/CA (Carrier Sense Multiple Access with Collision Avoidance) retries while waiting for an idle channel and the energy wasted by the node. The metrics to evaluate the performance of the modified routing protocols are the throughput and resilience of the system and the energy used by the nodes. We evaluated all the modified protocols when the attacker position was set near, middle and far of the collector node. The results of our evaluation show that performance for MPH-M is much better than AODV-M and DSR-M. For example, the node energy for MPH-M is 138.13% better than AODV-M and 126.07% better than DSR-M. Moreover, we also find that MPH-M benefits much more of the mitigation scheme than AODV-M and DSR-M. For example, the node energy consumption is 34.61% lower for MPH-M and only 3.92% and 3.42% for AODV-M and DSR-M, respectively. On throughput, the MPH protocol presents a packet reception efficiency at the collector node of 16.4% on to AODV and DSR when there is no mitigation mechanism. Moreover, MPH-M has an efficiency greater than 7.7% with respect to AODV-M and DSR-M when there is a mitigation scheme. In addition, we have that with the mitigation mechanism AODV-M and DSR-M do not present noticeable modification. However, MPH-M improves its efficiency by 8.4%. We also measure the resilience of these algorithms from the average packet re-transmissions perspective, and we find that MPH-M has around a 15% lower change rate than AODV-M and DSR-M. The MPH-M recovery time is 5 s faster than AODV-M and 2 s faster than DSR-M.

MPH-M, AODV-M and DSR-M Performance Evaluation under Jamming Attacks

PubMed Central

Del-Valle-Soto, Carolina

2017-01-01

In this work, we present the design of a mitigation scheme for jamming attacks integrated to the routing protocols MPH, AODV, and DSR. The resulting protocols are named MPH-M (Multi-Parent Hierarchical - Modified), AODV-M (Ad hoc On Demand Distance Vector - Modified), and DSR-M (Dynamic Source Routing - Modified). For the mitigation algorithm, if the detection algorithm running locally in each node produces a positive result then the node is isolated; second, the routing protocol adapts their paths avoiding the isolated nodes. We evaluated how jamming attacks affect different metrics for all these modified protocols. The metrics we employ to detect jamming attack are number of packet retransmissions, number of CSMA/CA (Carrier Sense Multiple Access with Collision Avoidance) retries while waiting for an idle channel and the energy wasted by the node. The metrics to evaluate the performance of the modified routing protocols are the throughput and resilience of the system and the energy used by the nodes. We evaluated all the modified protocols when the attacker position was set near, middle and far of the collector node. The results of our evaluation show that performance for MPH-M is much better than AODV-M and DSR-M. For example, the node energy for MPH-M is 138.13% better than AODV-M and 126.07% better than DSR-M. Moreover, we also find that MPH-M benefits much more of the mitigation scheme than AODV-M and DSR-M. For example, the node energy consumption is 34.61% lower for MPH-M and only 3.92% and 3.42% for AODV-M and DSR-M, respectively. On throughput, the MPH protocol presents a packet reception efficiency at the collector node of 16.4% on to AODV and DSR when there is no mitigation mechanism. Moreover, MPH-M has an efficiency greater than 7.7% with respect to AODV-M and DSR-M when there is a mitigation scheme. In addition, we have that with the mitigation mechanism AODV-M and DSR-M do not present noticeable modification. However, MPH-M improves its efficiency by 8.4%. We also measure the resilience of these algorithms from the average packet re-transmissions perspective, and we find that MPH-M has around a 15% lower change rate than AODV-M and DSR-M. The MPH-M recovery time is 5 s faster than AODV-M and 2 s faster than DSR-M. PMID:28678180

Methylphenidate Enhances Extinction of Contextual Fear

ERIC Educational Resources Information Center

Abraham, Antony D.; Cunningham, Christopher L.; Lattal, K. Matthew

2012-01-01

Methylphenidate (MPH, Ritalin) is a norepinephrine and dopamine transporter blocker that is widely used in humans for treatment of attention deficit disorder and narcolepsy. Although there is some evidence that targeted microinjections of MPH may enhance fear acquisition, little is known about the effect of MPH on fear extinction. Here, we show…

Small Arms - Hand and Shoulder Weapons and Machine Guns

DTIC Science & Technology

2016-06-24

temperature with a wind speed less than 8 kilometers per hour (km/hr) (5 miles per hour (mph)) with no sunlight on the barrel or receiver. e...the aiming of the mount/weapon system. d. Meteorological Conditions. (1) Ensure that the velocity of the transverse wind is no greater than 8...km/hr (5 mph) or varies by more than 4 km/hr (2.5 mph); wind parallel to the LOF should not exceed 16 km/hr (10 mph) or vary by more than 8 km/hr (5

Dream Chaser Rolls Through Tow Tests at NASA Armstrong

NASA Image and Video Library

2017-05-20

In this 2-minute, 41-second video, Sierra Nevada Corporation (SNC) puts its Dream Chaser engineering test vehicle through a series of ground tests at NASA's Armstrong Flight Research Center at Edwards Air Force Base, CA, to prepare for upcoming captive-carry and free-flight tests later this year. During this 60-mph tow test, a pickup truck pulled the Dream Chaser test vehicle on Edward’s runway to validate the performance of the spacecraft's nose skid, brakes, tires, and other systems. The company has performed the tests at 10 mph, 20 mph, and 40 mph over the last few months to lead up to the 60-mph runway test. Range and taxi tow tests are standard for winged vehicles that touchdown on a runway to prove the overall spacecraft handling post-landing.

Remission in children and adolescents diagnosed with attention-deficit/hyperactivity disorder via an effective and tolerable titration scheme for osmotic release oral system methylphenidate.

PubMed

Chou, Wen-Jiun; Chen, Shin-Jaw; Chen, Ying-Sheue; Liang, Hsin-Yi; Lin, Chih-Chien; Tang, Ching-Shu; Huang, Yu-Shu; Yeh, Chin-Bin; Chou, Miao-Chun; Lin, Dai-Yueh; Hou, Po-Hsun; Wu, Yu-Yu; Liu, Hung-Jen; Huang, Ya-Fen; Hwang, Kai-Ling; Chan, Chin-Hong; Pan, Chia-Ho; Chang, Hsueh-Ling; Huang, Chi-Fen; Hsu, Ju-Wei

2012-06-01

The purpose of this study was to identify the optimal dose of osmotic release oral system methylphenidate (OROS-MPH) using a dosage forced-titration scheme to achieve symptomatic remission in children with attention- deficit/hyperactivity disorder (ADHD). We also evaluated the efficacy and safety of, and patient and parent satisfaction with, the change in therapy from immediate-release methylphenidate (IR-MPH) to OROS-MPH over 10 weeks. We recruited 521 children and adolescents aged 6-18 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of ADHD, who had received IR-MPH treatments (<70 mg/day) for at least 1 month. The treatment, switched from IR-MPH to OROS-MPH according to a conversion scheme, started with a 6-week forced-titration phase of OROS-MPH to achieve symptomatic remission (defined as a score of 0 or 1 for each of the first 18 ADHD items in the Chinese version of the Swanson, Nolan, and Pelham, Version IV [SNAP-IV]), followed by a 4-week maintenance phase. The global ADHD severity and drug side effects of the participants were evaluated. Parents completed the ratings scales for the ADHD-related symptoms. Patient and parent satisfaction for the OROS-MPH treatment was also assessed. Among the 439 participants with ADHD who completed the trial, 290 participants (66.1%) achieved symptomatic remission. The mean dose of OROS-MPH among participants in remission was 36.7 mg (1.08 mg/kg) per day. Increased efficacy, superior satisfaction, and safety equivalent to that of IR-MPH were demonstrated in intra-individual comparisons from the baseline to the end of study. Determinants for remission included less severe ADHD symptoms (SNAP-IV score < 40), no family history of ADHD, and an appropriate dosage of medication according to the patient's weight. The findings suggest remission as a treatment goal for ADHD therapy by providing an optimal dosage of medication for children and adolescents with ADHD through using an effective and tolerable forced-titration scheme.

Using business plan development as a capstone project for MPH programs in Canada: validation through the student perspective.

PubMed

Papadopoulos, Andrew; Britten, Nicole; Hatcher, Meghan; Rainville, Keira

2013-10-01

Master of Public Health (MPH) programs have been developed across Canada as a response to the need for adequately trained individuals to work in the public health sector. Educational institutions that deliver MPH programs have a responsibility to ensure that graduates of their program have the essential knowledge, skills and attitudes to begin a successful career in public health. The Public Health Agency of Canada has created the core competencies for public health to guide the development, delivery and evaluation of MPH programs. In Canada, a capstone project is the recommended method of evaluating the MPH graduate's ability to demonstrate proficiency in the public health core competencies. A business plan that develops the framework for a public health program is an ideal capstone project currently used in practice within the University of Guelph MPH program. This group assignment incorporates all 36 of the public health core competencies while providing students with a real-world public health experience, and should be considered for inclusion within MPH programs across Canada. Business planning provides students the opportunity to engage in practice-based learning, applying theoretical knowledge to practice. Further, the ability to develop realistic but financially feasible public health problems is an invaluable skill for MPH graduates. As the development of programs becomes more restricted and the continuation of other programs are under constant threat, the ability to develop a sound business plan is a required skill for individuals entering the public health sector, and will ensure students are able to maximize outcomes given tight fiscal budgets and limited resources.

Disagreements with implications: diverging discourses on the ethics of non-medical use of methylphenidate for performance enhancement

PubMed Central

Forlini, Cynthia; Racine, Eric

2009-01-01

Background There is substantial evidence that methylphenidate (MPH; Ritalin), is being used by healthy university students for non-medical motives such as the improvement of concentration, alertness, and academic performance. The scope and potential consequences of the non-medical use of MPH upon healthcare and society bring about many points of view. Methods To gain insight into key ethical and social issues on the non-medical use of MPH, we examined discourses in the print media, bioethics literature, and public health literature. Results Our study identified three diverging paradigms with varying perspectives on the nature of performance enhancement. The beneficial effects of MPH on normal cognition were generally portrayed enthusiastically in the print media and bioethics discourses but supported by scant information on associated risks. Overall, we found a variety of perspectives regarding ethical, legal and social issues related to the non-medical use of MPH for performance enhancement and its impact upon social practices and institutions. The exception to this was public health discourse which took a strong stance against the non-medical use of MPH typically viewed as a form of prescription abuse or misuse. Wide-ranging recommendations for prevention of further non-medical use of MPH included legislation and increased public education. Conclusion Some positive portrayals of the non-medical use of MPH for performance enhancement in the print media and bioethics discourses could entice further uses. Medicine and society need to prepare for more prevalent non-medical uses of neuropharmaceuticals by fostering better informed public debates. PMID:19580661

Methylphenidate DAT binding in adolescents with Attention-Deficit/ Hyperactivity Disorder comorbid with Substance Use Disorder--a single photon emission computed tomography with [Tc(99m)]TRODAT-1 study.

PubMed

Szobot, Claudia M; Shih, Ming Chi; Schaefer, Thais; Júnior, Neivo; Hoexter, Marcelo Q; Fu, Ying Kai; Pechansky, Flávio; Bressan, Rodrigo A; Rohde, Luis A P

2008-04-15

Attention-Deficit/Hyperactivity Disorder (ADHD) is highly prevalent among adolescents with Substance Use Disorders (SUD). Effects of methylphenidate (MPH) on ADHD are attributed to its properties of blocking the dopamine transporter (DAT) in the striatum. However, it has been demonstrated that drug addiction is associated with dopaminergic system changes that may affect MPH brain effects, emphasizing the need to better understand MPH actions in subjects with ADHD+SUD. To evaluate the effect of an extended release formulation of MPH (MPH-SODAS) on DAT availability in 17 stimulant-naive ADHD adolescents with comorbid SUD (cannabis and cocaine). Subjects underwent two single photon emission computed tomography (SPECT) scans with [Tc(99m)]TRODAT-1, at baseline and after 3 weeks on MPH-SODAS. Clinical assessment for ADHD relied on the Swanson, Nolan and Pelham Scale - version IV (SNAP-IV). Caudate and putamen DAT binding potential (BP) was calculated. After 3 weeks on MPH-SODAS, there was a significant reduction of SNAP-IV total scores (p<0.001), and approximately 52% reductions of DAT BP at the left and right caudate. Similar decreases were found at the left and right putamen (p<0.001 for all analyses). This study shows that the magnitude of DAT blockade induced by MPH in this population is similar to what is found in ADHD patients without SUD comorbidity, providing neurobiological support for trials with stimulants in adolescents with ADHD+SUD, an important population excluded from studies.

Methylphenidate does not improve interference control during a working memory task in young patients with attention-deficit hyperactivity disorder.

PubMed

Prehn-Kristensen, Alexander; Krauel, Kerstin; Hinrichs, Hermann; Fischer, Jochen; Malecki, Ulrike; Schuetze, Hartmut; Wolff, Stephan; Jansen, Olav; Duezel, Emrah; Baving, Lioba

2011-05-04

Patients with attention-deficit/hyperactivity disorder (ADHD) show deficits in working memory (WM) which may be related to prefrontal dysfunction. Methylphenidate (MPH) can restore WM deficits in ADHD by enhancing prefrontal activity. At the same time, changes in striatal activation could cause ADHD patients to be more interference-sensitive during working memory tasks. However, it is unclear whether MPH reduces WM distractibility in ADHD. In this fMRI study, 12 ADHD patients and 12 healthy controls participated on two separate days in a delayed-match-to-sample test. During the delay interval, a distractor stimulus was presented in half of the trials. Children and adolescents with ADHD received MPH only on one of the two sessions. Behavioral data analyses revealed that MPH normalized WM in ADHD. However, MPH did not improve WM performance when a distractor was presented during the delay interval. Functional images showed that MPH enhanced prefrontal activity during the delay in ADHD patients when no distractor was present. If the delay was interrupted by a distractor, only healthy controls showed activation of the caudate. In patients with ADHD, however, in line with behavioral data, MPH did not enhance caudate activity. In healthy youth, caudate activity is involved in interference control allowing the successful maintenance of information in working memory even in the presence of distraction. Our findings suggest that interference control, linked to caudate activity, is not adequately enhanced by MPH in ADHD. Copyright © 2011 Elsevier B.V. All rights reserved.

Animal model of methylphenidate's long-term memory-enhancing effects.

PubMed

Carmack, Stephanie A; Howell, Kristin K; Rasaei, Kleou; Reas, Emilie T; Anagnostaras, Stephan G

2014-01-16

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01-10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1-10 mg/kg, i.p.), bupropion (0.5-20 mg/kg, i.p.), and citalopram (0.01-10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development.

Animal model of methylphenidate's long-term memory-enhancing effects

PubMed Central

Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

2014-01-01

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a critical target of therapeutic intervention in ADHD. We examined the effects of a wide range of doses of MPH (0.01–10 mg/kg, i.p.) on Pavlovian fear learning, a leading model of memory. MPH's effects were then compared to those of atomoxetine (0.1–10 mg/kg, i.p.), bupropion (0.5–20 mg/kg, i.p.), and citalopram (0.01–10 mg/kg, i.p.). At low, clinically relevant doses, MPH enhanced fear memory; at high doses it impaired memory. MPH's memory-enhancing effects were not confounded by its effects on locomotion or anxiety. Further, MPH-induced memory enhancement seemed to require both dopamine and norepinephrine transporter inhibition. Finally, the addictive potential of MPH (1 mg/kg and 10 mg/kg) was compared to those of two other psychostimulants, amphetamine (0.005 mg/kg and 1.5 mg/kg) and cocaine (0.15 mg/kg and 15 mg/kg), using a conditioned place preference and behavioral sensitization paradigm. We found that memory-enhancing effects of psychostimulants observed at low doses are readily dissociable from their reinforcing and locomotor activating effects at high doses. Together, our data suggest that fear conditioning will be an especially fruitful platform for modeling the effects of psychostimulants on LTM in drug development. PMID:24434869

Methylphenidate and Cocaine Self-Administration Produce Distinct Dopamine Terminal Alterations

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Melchior, James R.; Bermejo, Kristel; Salahpour, Ali; Roberts, David C. S.; Jones, Sara R.

2012-01-01

Methylphenidate (MPH) is a commonly abused psychostimulant prescribed for the treatment of attention deficit hyperactivity disorder. MPH has a mechanism of action similar to cocaine (COC) and is commonly characterized as a dopamine transporter (DAT) blocker. While there has been extensive work aimed at understanding dopamine (DA) nerve terminal changes following COC self-administration, very little is known about the effects of MPH self-administration on the DA system. We used fast scan cyclic voltammetry in nucleus accumbens core slices from animals with a five-day self-administration history of 40 injections/day of either MPH (0.56 mg/kg) or COC (1.5 mg/kg) to explore alterations in baseline DA release and uptake kinetics as well as alterations in the interaction of each compound with the DAT. Although MPH and COC have similar behavioral effects, the consequences of self-administration on DA system parameters were found to be divergent. We show that COC self-administration reduced DAT levels and maximal rates of DA uptake, as well as reducing electrically stimulated release, suggesting decreased DA terminal function. In contrast, MPH self-administration increased DAT levels, DA uptake rates, and DA release, suggesting enhanced terminal function, which was supported by findings of increased metabolite/DA tissue content ratios. Tyrosine hydroxylase mRNA, protein and phosphorylation levels were also assessed in both groups. Additionally, COC self-administration reduced COC-induced DAT inhibition, while MPH self-administration increased MPH-induced DAT inhibition, suggesting opposite pharmacodynamic effects of these two drugs. These findings suggest that the factors governing DA system adaptations are more complicated than simple DA uptake blockade. PMID:22458761

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity

PubMed Central

Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD. PMID:28740389

Methylphenidate dose optimization for ADHD treatment: review of safety, efficacy, and clinical necessity.

PubMed

Huss, Michael; Duhan, Praveen; Gandhi, Preetam; Chen, Chien-Wei; Spannhuth, Carsten; Kumar, Vinod

2017-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic psychiatric disorder characterized by hyperactivity and/or inattention and is often associated with a substantial impact on psychosocial functioning. Methylphenidate (MPH), a central nervous system stimulant, is commonly used for pharmacological treatment of adults and children with ADHD. Current practice guidelines recommend optimizing MPH dosage to individual patient needs; however, the clinical benefits of individual dose optimization compared with fixed-dose regimens remain unclear. Here we review the available literature on MPH dose optimization from clinical trials and real-world experience on ADHD management. In addition, we report safety and efficacy data from the largest MPH modified-release long-acting Phase III clinical trial conducted to examine benefits of dose optimization in adults with ADHD. Overall, MPH is an effective ADHD treatment with a good safety profile; data suggest that dose optimization may enhance the safety and efficacy of treatment. Further research is required to establish the extent to which short-term clinical benefits of MPH dose optimization translate into improved long-term outcomes for patients with ADHD.

Structure and Function of the Macrolide Biosensor Protein, MphR(A), with and without Erythromycin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Jianting; Sagar, Vatsala; Smolinsky, Adam

2009-09-02

The regulatory protein MphR(A) has recently seen extensive use in synthetic biological applications, such as metabolite sensing and exogenous control of gene expression. This protein negatively regulates the expression of a macrolide 2{prime}-phosphotransferase I resistance gene (mphA) via binding to a 35-bp DNA operator upstream of the start codon and is de-repressed by the presence of erythromycin. Here, we present the refined crystal structure of the MphR(A) protein free of erythromycin and that of the MphR(A) protein with bound erythromycin at 2.00- and 1.76-{angstrom} resolutions, respectively. We also studied the DNA binding properties of the protein and identified mutants ofmore » MphR(A) that are defective in gene repression and ligand binding in a cell-based reporter assay. The combination of these two structures illustrates the molecular basis of erythromycin-induced gene expression and provides a framework for additional applied uses of this protein in the isolation and engineered biosynthesis of polyketide natural products.« less

Cardiac mesothelial papillary hyperplasia in four dogs.

PubMed

Kirejczyk, Shannon G; Burnum, Anne L; Brown, Corrie C; Sakamoto, Kaori; Rissi, Daniel R

2018-05-01

Mesothelial papillary hyperplasia (MPH) has been described as an incidental finding on the epicardial surface of clinically normal laboratory Beagle dogs. We describe MPH in 4 dogs diagnosed with acute cardiac tamponade (1 case) or chronic cardiac disease (3 cases). Cardiac MPH appeared as distinct, soft, irregular villous plaques on the epicardial surface of the auricles and occasionally the ventricles. Histologically, areas of MPH were composed of multiple papillary fronds arising from the epicardial surface and projecting into the pericardial space. Fronds were covered by cuboidal and occasionally vacuolated mesothelial cells and were supported by loose fibrovascular stroma with various degrees of edema and inflammation. Although these may represent incidental findings with no clinical significance, the gross appearance warrants differentiation from other conditions. Additional insight into the pathogenesis of MPH is needed to fully understand its significance in the face of concurrent cardiac disease.

Flow cytometric detection of Pig-A mutant red blood cells using an erythroid-specific antibody: application of the method for evaluating the in vivo genotoxicity of methylphenidate in adolescent rats.

PubMed

Dobrovolsky, Vasily N; Boctor, Sherin Y; Twaddle, Nathan C; Doerge, Daniel R; Bishop, Michelle E; Manjanatha, Mugimane G; Kimoto, Takafumi; Miura, Daishiro; Heflich, Robert H; Ferguson, Sherry A

2010-03-01

A modified flow cytometry assay for Pig-A mutant rat red blood cells (RBCs) was developed using an antibody that positively identifies rat RBCs (monoclonal antibody HIS49). The assay was used in conjunction with a flow cytometric micronucleus (MN) assay to evaluate gene mutation and clastogenicity/aneugenicity in adolescent male and female rats treated with methylphenidate hydrochloride (MPH). Sprague-Dawley rats were treated orally with 3 mg/kg MPH (70/sex) or water (40/sex) 3 x /day on postnatal days (PNDs) 29-50. Eight additional rats (4/sex) were injected i.p. with N-ethyl-N-nitrosourea (ENU) on PND 28. Blood was collected on PNDs 29, 50, and 90, and used for determining serum MPH levels and/or conducting genotoxicity assays. On the first and last days of MPH treatment (PNDs 29 and 50), serum MPH levels averaged 21 pg/microl, well within the clinical treatment range. Relative to our previously published method (Miura et al. [2008]; Environ Mol Mutagen 49: 614-629), the HIS49 Pig-A mutation assay significantly reduced the background RBC mutant frequency; in the experiments with ENU-treated rats, the modification increased the overall sensitivity of the assay 2-3 fold. Even with the increased assay sensitivity, the 21 consecutive days of MPH treatment produced no evidence of Pig-A mutation induction (measured at PND 90); in addition, MPH treatment did not increase MN frequency (measured at PND 50). These results support the consensus view that the genotoxicity of MPH in pediatric patients reported earlier (El-Zein et al. [2005]: Cancer Lett 230: 284-291) cannot be reproduced in animal models, suggesting that MPH at clinically relevant levels may be nongenotoxic in humans. Published 2009 by Wiley-Liss, Inc.

Development and validation of an UFLC-MS/MS method for enantioselectivity determination of d,l-thero-methylphenidate, d,l-thero-ethylphenidate and d,l-thero-ritalinic acid in rat plasma and its application to pharmacokinetic study.

PubMed

Zhang, Chenghao; Luo, Huafei; Wu, Yubo; Zhang, Junyun; Zhang, Furong; Lin, Guobei; Wang, Hao

2016-02-01

A chiral UFLC-MS/MS method was established and validated for quantifying d-threo-methylphenidate (d-threo-MPH), l-threo-methylphenidate (l-threo-MPH), d-threo-ethylphenidate (d-threo-EPH), l-threo-ethylphenidate (l-threo-EPH) and d,l-threo-ritalinic acid (d,l-threo-RA) in rat plasma over the linearity range of 1-500ng/mL. Chiral separation was performed on an Astec Chirobiotic V2 column (5μm, 250×2.1mm) with isocratic elution using methanol containing 0.003% ammonium acetate (w/v) and 0.003% trifluoroacetic acid (v/v) at a flow of 0.3mL/min. All analytes and IS were extracted from rat plasma by a one-step liquid-liquid extraction (LLE) method. The intra- and inter-run accuracies were within 85-115%, and the intra- and inter-run precision were <10% for all analytes. Extraction recoveries were 55-62% for d-threo-MPH, 54-60% for l-threo-MPH, 55-60% for d-threo-EPH, 53-57% for l-threo-EPH and 25-30% for d,l-threo-RA. The validated UFLC-MS/MS method successfully applied to the pharmacokinetic interaction study of oral d-threo-MPH and l-threo-MPH (alone or in combination) in female Sprague Dawley rats. The EPH was not detected in rat plasma following oral administrated MPH without EtOH. As far as it is known to the authors, this study is the first one step liquid-liquid extraction method to extract and UFLC-MS/MS method to quantify d-threo-MPH, l-threo-MPH, d-threo-EPH, l-threo-EPH and d,l-threo-RA simultaneously. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of Aptensio XR (Methylphenidate HCl Extended-Release) Capsules on Sleep in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Owens, Judith; Weiss, Margaret; Nordbrock, Earl; Mattingly, Greg; Wigal, Sharon; Greenhill, Laurence L; Chang, Wei-Wei; Childress, Ann; Kupper, Robert J; Adjei, Akwete

2016-12-01

To evaluate measures of sleep (exploratory endpoints) in two pivotal studies of a multilayer bead extended-release methylphenidate (MPH-MLR) treatment of attention-deficit/hyperactivity disorder in children. Study 1 evaluated the time course of response to MPH-MLR (n = 26) patients in an analog classroom setting through four phases: screening (≤28 days), open label (OL) dose optimization (4 weeks), double-blind (DB) crossover (2 weeks; placebo vs. optimized dose), and follow-up call. Study 2 was a forced-dose parallel evaluation of MPH-MLR (n = 230) in four phases: screening (≤28 days), DB (1 week; placebo or MPH-MLR 10, 15, 20, or 40 mg/day), OL dose optimization (11 weeks), and follow-up call. Sleep was evaluated by parents using the Children's or Adolescent Sleep Habits Questionnaire (CSHQ or ASHQ) during the DB and OL phases. DB analysis: Study 1 (crossover), analysis of variance; Study 2, analysis of covariance. OL analysis: paired t-test. DB: treatments were significantly different in Study 1 only for CSHQ Sleep Onset Delay (MPH-MLR, 1.90 vs. placebo, 1.34; p = 0.0046, placebo was better), and Study 2 for CSHQ Parasomnias (treatment, p = 0.0295), but no MPH-MLR treatment was different from placebo (pairwise MPH-MLR treatment to placebo, all p ≥ 0.170). OL: CSHQ total and Bedtime Resistance, Sleep Duration, Sleep Anxiety, Night Wakings, Parasomnias, and Sleep-disordered Breathing subscales decreased (improved, Study 1) significant only for CSHQ Night Wakings (p < 0.05); in Study 2 CSHQ total and Bedtime Resistance, Sleep Duration, Night Wakings, Parasomnias, and Daytime Sleepiness, and ASHQ total, Bedtime, Sleep Behavior, and Morning Waking all significantly improved (p < 0.05). In both studies, there was minimal negative impact of MPH-MLR on sleep during the brief DB phase and none during the longer duration OL phase. Some measures of sleep improved with optimized MPH-MLR dose.

Dopaminergic and Noradrenergic Contributions to Functionality in ADHD: The Role of Methylphenidate

PubMed Central

Engert, Veronika; Pruessner, Jens C

2008-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood psychiatric condition characterized by severe impulsiveness, inattention and overactivity. Methylphenidate (MPH), a psychostimulant affecting both the dopaminergic and the noradrenergic systems, is one of the most frequently prescribed treatments for ADHD. Despite the widespread use of MPH and its proven effectiveness, its precise neurochemical mechanisms of action are under debate. For the most part, MPH’s influence on subcortical dopamine neurotransmission is thought to play a crucial role in its behavioral and cognitive effects. In their hypothesis of biphasic MPH action, Seeman and Madras [42, 43] suggest that therapeutic doses of MPH elevate tonic dopamine while inhibiting phasic transmitter release in subcortical structures, leading to reduced postsynaptic receptor stimulation and psychomotor activation in response to salient stimuli. Volkow and colleagues [56] suggest that by amplifying a weak striatal dopamine signal, MPH increases the perception of a stimulus or task as salient. The enhanced interest for the task is thought to increase attention and improve performance. Recent animal studies have however shown that when administered at doses producing clinically relevant drug plasma levels and enhancing cognitive function, MPH preferentially activates dopamine and noradrenaline efflux within the prefrontal cortex relative to the subcortical structures [5]. Overall, we suggest that the delineated theories of MPH therapeutic action should not be discussed as exclusive. Studies are outlined that allow integrating the different findings and models. PMID:19587853

The effect of methylphenidate on very low frequency electroencephalography oscillations in adult ADHD.

PubMed

Cooper, Ruth E; Skirrow, Caroline; Tye, Charlotte; McLoughlin, Grainne; Rijsdijk, Fruhling; Banaschweski, Tobias; Brandeis, Daniel; Kuntsi, Jonna; Asherson, Philip

2014-04-01

Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02-0.2Hz) during a cued continuous performance task. 41 untreated adults with ADHD and 47 controls were assessed, and 21 cases followed up after MPH treatment, with a similar follow-up for 38 controls (mean follow-up=9.4months). Cases had enhanced frontal and parietal VLF-EEG and increased omission errors. In the whole sample, increased parietal VLF-EEG correlated with increased omission errors. After controlling for subthreshold comorbid symptoms, VLF-EEG case-control differences and treatment effects remained. Post-treatment, a time by group interaction emerged; VLF-EEG and omission errors reduced to the same level as controls, with decreased inattentive symptoms in cases. Reduced VLF-EEG following MPH treatment provides preliminary evidence that changes in VLF-EEG may relate to MPH treatment effects on ADHD symptoms; and that VLF-EEG may be an intermediate phenotype of ADHD. Further studies of the treatment effect of MPH in larger controlled studies are required to formally evaluate any causal link between MPH, VLF-EEG and ADHD symptoms. Copyright © 2014 Elsevier Inc. All rights reserved.

Urinary retention and syndrome of inappropriate antidiuretic hormone secretion (SIADH) secondary to impacted gravid uterus.

PubMed

Irani, M; Fisher, N; Mor, A; Bensinger, G

2016-06-01

Urinary retention is an emergency that rarely occurs during pregnancy. Previous case reports have suggested multiple risk factors that can cause the gravid uterus to become impacted in the pelvis leading to lower bladder or urethral compression with subsequent urinary retention. However, no cases of urinary obstruction in a pregnancy that was complicated with severe electrolyte imbalance have been reported. To our knowledge, we report the first case of a 31-year-old woman presenting at 8 weeks' gestation with acute urinary retention caused by a retroflexed, retroverted uterus with a 6-cm posterior uterine fibroid leading to syndrome of inappropriate antidiuretic hormone secretion and severe hyponatremia requiring intensive care unit admission. The cornerstones of effective management of urinary retention should include: (i) urgent bladder catheterization; (ii) assessment of sodium levels to rule out syndrome of inappropriate antidiuretic hormone secretion, and prompt treatment before neurological damage occurs; (iii) reduction of the impacted uterus; and (iv) monitoring for post-obstructive diuresis. © 2016 Japan Society of Obstetrics and Gynecology.

A Status report to the Superintendent of Public Instruction on a study of optimal school bus speed limits on Virginia highways.

DOT National Transportation Integrated Search

1988-01-01

The study was prompted by the fact that on Virginia's rural interstate highways there is a three-tiered speed limit: 45 mph for school buses, 55 mph for other buses and trucks, and 65 mph for passenger vehicles. On the urban interstate system, school...

A Randomized, Single-Blind, Substitution Study of OROS Methylphenidate (Concerta) in ADHD Adults Receiving Immediate Release Methylphenidate

ERIC Educational Resources Information Center

Spencer, Thomas J.; Mick, Eric; Surman, Craig B. H.; Hammerness, Paul; Doyle, Robert; Aleardi, Megan; Kotarski, Meghan; Williams, Courtney G.; Biederman, Joseph

2011-01-01

Objective: The main aim of this study was to examine the efficacy, tolerability, and compliance of an extended-release formulation of methylphenidate (OROS-MPH) in adults with ADHD receiving immediate-release methylphenidate (IR-MPH). Method: Participants were outpatient adults with ADHD who were stable on IR-MPH-administered TID. Participants…

A Preliminary Study on the Effect of Methylphenidate on Motor Performance in Children with Comorbid DCD and ADHD

ERIC Educational Resources Information Center

Bart, Orit; Podoly, Tamar; Bar-Haim, Yair

2010-01-01

Attention Deficit Hyperactive Disorder (ADHD) and Developmental Coordination Disorder (DCD) are two developmental disorders with considerable comorbidity. The impact of Methylphenidate (MPH) on ADHD symptoms is well documented. However, the effects of MPH on motor coordination are less studied. We assessed the influence of MPH on motor performance…

Recurrent urinary tract infections in young children: role of DMSA scintigraphy in detecting vesicoureteric reflux.

PubMed

Awais, Muhammad; Rehman, Abdul; Zaman, Maseeh Uz; Nadeem, Naila

2015-01-01

Performing micturiting cystourethrography (MCUG) in young children with recurrent urinary tract infections is controversial with discrepancy among the major guidelines. Previous studies have shown that a normal dimercaptosuccinic acid (DMSA) scintigraphy may avoid the need of performing MCUG for detecting vesicoureteric reflux in children with first febrile urinary tract infection. However, the role of DMSA for ruling out vesicoureteric reflux in children with recurrent urinary tract infections has not been studied. Approval from institutional ethical review committee was sought and the requirement of informed consent was waived. A total of 50 children under the age of 10 years with recurrent urinary tract infections underwent MCUG scan within 3 months of DMSA scan from January 2011 to September 2012 at our institution. Diagnosis of recurrent urinary tract infections and grading of vesicoureteric reflux was according to previously established standards. Abnormalities on DMSA scan - scarring, hydronephrosis and reduced differential renal function - were compared with presence of vesicoureteric reflux on MCUG. High-grade vesicoureteric reflux was noted on MCUG in 22 (44%) cases. The findings on DMSA included hydronephrosis and scarring in 25 (50%) and 25 (50%) cases, respectively. Abnormalities on DMSA scan for detecting the presence of high-grade vesicoureteric reflux on MCUG examination had sensitivity, specificity, positive and negative predictive values of 95.45%, 35.71%, 53.85% and 90.91%, respectively. The positive and negative likelihood ratios were 1.48 and 0.13 respectively. DMSA scan had high overall sensitivity and negative predictive value with a low negative likelihood ratio for ruling out high-grade vesicoureteric reflux on MCUG, which may obviate the need of invasive MCUG along with its associated drawbacks.

Suicide risk reduction in youths with attention-deficit/hyperactivity disorder prescribed methylphenidate: A Taiwan nationwide population-based cohort study.

PubMed

Liang, Sophie Hsin-Yi; Yang, Yao-Hsu; Kuo, Ting-Yu; Liao, Yin-To; Lin, Tzu-Chin; Lee, Yena; McIntyre, Roger S; Kelsen, Brent A; Wang, Tsu-Nai; Chen, Vincent Chin-Hung

2018-01-01

Attention-deficit/hyperactivity disorder (ADHD) youths have increased suicide risk. Nevertheless, the beneficial effects of methylphenidate (MPH) on suicide attempt have received relatively little attention. To investigate the MPH usage and the risk of suicide attempt among ADHD youths. We identified 84,898 youths less than 18 years old with ADHD diagnosis between 1997 and 2013 from National Health Insurance, and examined whether MPH use affected suicide attempt risk using Cox proportional-hazards models. Among ADHD youths, reduction of suicide risk was found in patients prescribed 90-180days of MPH after adjusting for confounding factors (hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.19-0.90) and a greater reduction in those prescribed more than 180days of MPH (HR: 0.28, 95% CI: 0.17-0.48). We observed a 59% suicide attempt risk reduction among ADHD youths prescribed between 90 and 180days and a 72% risk reduction in those prescribed more than 180days of MPH. The protective benefit observed by the group prescribed MPH for longer duration underscores the importance of psychoeducation and compliance enhancement as part of ADHD management. Indication bias is identified as a limitation of this study, and future self-case control study to investigate the association between suicide attempt and ADHD medication is suggested. This nationwide population-based cohort study showed that among ADHD youths, reduction of suicide risk was observed in patients prescribed MPH for duration 90days and longer, underscoring the importance of appropriate ADHD pharmacotherapy and enhancing drug compliance. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Methylphenidate increases glucose uptake in the brain of young and adult rats.

PubMed

Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

2015-10-01

Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Randomized Controlled Trial of Osmotic-Release Methylphenidate with CBT in Adolescents with ADHD and Substance Use Disorders

PubMed Central

Riggs, Paula D.; Winhusen, Theresa; Davies, Robert D.; Leimberger, Jeffrey D.; Mikulich-Gilbertson, Susan; Klein, Constance; Macdonald, Marilyn; Lohman, Michelle; Bailey, Genie L.; Haynes, Louise; Jaffee, William B.; Hodgkins, Candace; Whitmore, Elizabeth; Trello-Rishel, Kathlene; Tamm, Leanne; Acosta, Michelle C.; Royer-Malvestuto, Charlotte; Subramaniam, Geetha; Fishman, Marc; Holmes, Beverly W.; Kaye, Mary Elyse; Vargo, Mark A.; Woody, George E.; Nunes, Edward V.; Liu, David

2011-01-01

Objective To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared to placebo for attention deficit hyperactivity disorder (ADHD) and impact on substance treatment outcomes in adolescents concurrently receiving cognitive behavioral therapy (CBT) for substance use disorders (SUD). Method 16-week randomized controlled multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13-18), meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcomes: (1) ADHD- clinician-administered ADHD Rating Scale (ADHD-RS), adolescent informant; (2) Substance- adolescent reported days of use in the past 28 days. Secondary outcome measures included parent ADHD-RS and weekly urine drug screens (UDS). Results There were no group differences on reduction in ADHD-RS scores (OROS-MPH: −19.2, 95% confidence interval [CI], −17.1 to −21.2; placebo,−21.2, 95% CI, −19.1 to −23.2) or reduction in days of substance use (OROS-MPH: −5.7 days, 95% CI, 4.0-7.4; placebo: −5.2 days, 95% CI, 3.5-7.0). Some secondary outcomes favored OROS-MPH including lower parent ADHD-RS scores at 8 (mean difference [md]=4.4, 95% CI, 0.8-7.9) and 16 weeks (md=6.9; 95% CI, 2.9-10.9) and more negative UDS in OROS-MPH (mean=3.8) compared to placebo (mean=2.8; P=0.04). Conclusions OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD. However, OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures. PMID:21871372

Switch in Therapy from Methylphenidate to Atomoxetine in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: An Analysis of Patient Records.

PubMed

Warrer, Pernille; Thomsen, Per Hove; Dalsgaard, Søren; Hansen, Ebba Holme; Aagaard, Lise; Wallach Kildemoes, Helle; Rasmussen, Henrik Berg

2016-05-01

The purpose of this study was to investigate therapy switching from methylphenidate (MPH) to atomoxetine (ATX) in a clinical sample of Danish children and adolescents with attention-deficit/hyperactivity disorder (ADHD); specifically, to determine the duration of MPH treatment before switching to ATX, and the reasons leading to a switch in therapy. We included 55 patients with ADHD who switched from first-line MPH to second-line ATX during January 01, 2012 and May 15, 2014. Patient and treatment characteristics along with clinical reasons for switching therapy were extracted from individual patients' records. Mean duration of MPH treatment until switch to ATX was 11.2 months (range = 0.3-28.5 months); 36% of the patients switched within the first 6 months, 56% within the first year, and 76% within 1.5 years of initiating MPH; 24% continued MPH treatment for up to 2.5 years prior to switching. Most common reasons for switching were "adverse events" (AEs) (78%), "wish for more optimal day coverage" (24%), and "lack of efficacy" (16%). Other reasons for switching included "patient/parental request" (13%) and "noncompliance" (2%). Most common AEs leading to switch were psychiatric disorders (insomnia, aggression, tic, depression, anxiety) and decreased appetite. Our findings highlight the importance of continuous evaluation of the need for prescription switch to ATX in children and adolescents treated with MPH, taking into consideration various factors including potential AEs, non-optimal day coverage, lack of efficacy, patient/parental preferences, and noncompliance. These factors should be considered, not only at the initial stage of MPH treatment but throughout the whole treatment course.

Efficacy of hemostatic matrix and microporous polysaccharide hemospheres.

PubMed

Lewis, Kevin M; Atlee, Holly; Mannone, Angela; Lin, Lawrence; Goppelt, Andreas

2015-02-01

Microporous Polysaccharide Hemospheres (MPH) are a new plant-derived polysaccharide powder hemostat. Previous studies investigated MPH as a replacement to nonflowable hemostatic agents of different application techniques (e.g., oxidized cellulose, collagen); therefore, the purpose of this study was to determine if MPH is a surrogate for flowable hemostatic agents of similar handling and application techniques, specifically a flowable thrombin-gelatin hemostatic matrix. Hemostatic efficacy was compared using a heparinized porcine abrasion model mimicking a capsular tear of a parenchymal organ. MPH (ARISTA, 1 g) and hemostatic matrix (Floseal, 1 mL) were applied, according to a randomized scheme, to paired hepatic abrasions (40 lesions per group). Hemostatic success, control of bleeding, and blood loss were assessed 2, 5, and 10 min after treatment. Hemostatic success and control of bleeding were analyzed using odds ratios and blood loss using mean differences. Hemostatic matrix provided superior hemostatic success relative to MPH at 5 (odds ratio: 0.035, 95% confidence interval: 0.004-0.278) and 10 min (0.032, 0.007-0.150), provided superior control of bleeding at 5 (0.006, <0.001-0.037) and 10 min (0.009, 0.001-0.051), and had significantly less blood loss at 5 (mean difference: 0.3118 mL/min, 95% confidence interval: 0.0939-0.5296) and 10 min (0.5025, 0.2489-0.7561). These findings corroborate other MPH investigations regarding its low-level efficacy and suggest that MPH is not an appropriate surrogate for hemostatic matrix despite similar application techniques. The lack of a procoagulant within MPH may likely be the reason for its lower efficacy and need for multiple applications. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Dosage Mutator Genes in Saccharomyces cerevisiae: A Novel Mutator Mode-of-Action of the Mph1 DNA Helicase.

PubMed

Ang, J Sidney; Duffy, Supipi; Segovia, Romulo; Stirling, Peter C; Hieter, Philip

2016-11-01

Mutations that cause genome instability are considered important predisposing events that contribute to initiation and progression of cancer. Genome instability arises either due to defects in genes that cause an increased mutation rate (mutator phenotype), or defects in genes that cause chromosome instability (CIN). To extend the catalog of genome instability genes, we systematically explored the effects of gene overexpression on mutation rate, using a forward-mutation screen in budding yeast. We screened ∼5100 plasmids, each overexpressing a unique single gene, and characterized the five strongest mutators, MPH1 (mutator phenotype 1), RRM3, UBP12, PIF1, and DNA2 We show that, for MPH1, the yeast homolog of Fanconi Anemia complementation group M (FANCM), the overexpression mutator phenotype is distinct from that of mph1Δ. Moreover, while four of our top hits encode DNA helicases, the overexpression of 48 other DNA helicases did not cause a mutator phenotype, suggesting this is not a general property of helicases. For Mph1 overexpression, helicase activity was not required for the mutator phenotype; in contrast Mph1 DEAH-box function was required for hypermutation. Mutagenesis by MPH1 overexpression was independent of translesion synthesis (TLS), but was suppressed by overexpression of RAD27, a conserved flap endonuclease. We propose that binding of DNA flap structures by excess Mph1 may block Rad27 action, creating a mutator phenotype that phenocopies rad27Δ. We believe this represents a novel mutator mode-of-action and opens up new prospects to understand how upregulation of DNA repair proteins may contribute to mutagenesis. Copyright © 2016 by the Genetics Society of America.

The role of dopamine D₁ and D₂ receptors in adolescent methylphenidate conditioned place preference: sex differences and brain-derived neurotrophic factor.

PubMed

Cummins, Elizabeth D; Griffin, Stephen B; Duty, Chase M; Peterson, Daniel J; Burgess, Katherine C; Brown, Russell W

2014-01-01

This study analyzed the role of dopamine D1 and D2 receptors in methylphenidate (MPH) conditioned place preference (CPP) in adolescent male and female rats, in addition to the role of these receptors in the effects of MPH on brain-derived neurotrophic factor (BDNF) in the dorsal striatum and nucleus accumbens. Using a nonbiased CPP procedure, the animals were conditioned from postnatal day (PD) 33 to 37. On conditioning trials, animals were first administered saline or their respective antagonist (0.1 or 0.2 mg/kg SCH-23390; 0.01 or 0.03 mg/kg eticlopride HCl), followed by MPH (5 mg/kg). Approximately 10 min after MPH administration, the rats were placed into the paired context for a 10-min trial. One day after conditioning on PD38, a preference test was administered with dividers removed. One day following the preference test on PD39, brain tissue was removed, and the nucleus accumbens and striatum were analyzed for BDNF. Results revealed that MPH conditioning resulted in an increased preference that was blocked by either dose of SCH-23390, but generally not affected by either dose of eticlopride. Further, the higher dose of SCH-23390 resulted in a conditioned place aversion in males, presumably due to an increased number of dopamine D1 receptors in adolescent males. MPH produced a significant increase of striatal and accumbal BDNF alleviated by SCH-23390 or eticlopride. These results show that MPH results in CPP in adolescent male and female rats and these effects appear to be mediated by the dopamine D1 receptor, but the effects of MPH on BDNF appear to be mediated by both dopamine receptor families. © 2014 S. Karger AG, Basel.

Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder and Substance Use Disorders.

PubMed

Simon, Nicolas; Rolland, Benjamin; Karila, Laurent

2015-01-01

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopment disorder occurring during childhood. However, ADHD persists into adulthood in 45.7% of cases. The global prevalence of adult ADHD is estimated to 5.3%, with no difference between Europe and North America. ADHD is often comorbid with substance use disorder (SUD), with Odds Ratio ranges from 1.5 to 7.9, depending on the substance and the dependence level. Conversely, the prevalence of ADHD among patients with SUD is 10.8%, versus 3.8% for patients without SUD. Methylphenidate (MPH) alleviates ADHD symptoms and, as such, is currently considered as a first choice medication. MPH blocks the dopamine and norepinephrine transporters leading to an increase in extracellular dopamine. It should be noted that its subjective effects are highly dependent on the pharmacokinetic and especially on the rate of input, which highlights the importance of choosing a sustained-release formulation. Meanwhile, prescribing MPH to patients with comorbid SUD has always been challenging for clinicians. The aim of this review is to address the benefits and pitfalls of using MPH in adults with ADHD comorbid SUD, depending on each of the following types of SUD: amphetamine, cocaine, nicotine, alcohol, cannabis and opiates. Overall, due to the prevalence of ADHD in SUD and to the benefits of MPH observed in this population, and considering the mild or low side effects observed, the response to MPH treatment should be evaluated individually in adults with comorbid ADHD and SUD. The choice of the formulation should favor sustained- release MPH over immediate release MPH. Cardiovascular parameters also have to be monitored during long-term use.

Effects of methylphenidate on acute math performance in children with attention-deficit hyperactivity disorder.

PubMed

Grizenko, Natalie; Cai, Emmy; Jolicoeur, Claude; Ter-Stepanian, Mariam; Joober, Ridha

2013-11-01

Examine the short-term (acute) effects of methylphenidate (MPH) on math performance in children with attention-deficit hyperactivity disorder (ADHD) and what factors predict improvement in math performance. One hundred ninety-eight children with ADHD participated in a double-blind, placebo-controlled, randomized crossover MPH trial. Math response to MPH was determined through administration of math problems adjusted to their academic level during the Restricted Academic Situation Scale (RASS). Student t tests were conducted to assess change in math performance with psychostimulants. Correlation between change on the RASS and change on the math performance was also examined. Linear regression was performed to determine predictor variables. Children with ADHD improved significantly in their math with MPH (P < 0.001). The degree of improvement on the RASS (which evaluates motor activity and orientation to task) and on math performance on MPH was highly correlated. A child's age at baseline and Wechsler Individual Achievement Test (WIAT)-Numerical Operations standard scores at baseline accounted for 15% of variances for acute math improvement. MPH improves acute math performance in children with ADHD. Younger children with lower math scores (as assessed by the WIAT) improved most on math scores when given psychostimulants. NCT00483106.

The dual DVM/MPH degree at the University of Wisconsin--Madison: a uniquely interdisciplinary collaboration.

PubMed

Olsen, Christopher W; Remington, Patrick L

2008-01-01

The University of Wisconsin-Madison (UWM) launched a new Master of Public Health (MPH) degree program in 2005. This 42-credit MPH degree consists of 18 core and 14 elective course credits, two seminar credits, and eight field project/culminating experience credits. Unique strengths of the program include its strongly interdisciplinary philosophy, encompassing both health science (human medicine, veterinary medicine, pharmacy, nursing) and social science units on campus, and its emphasis on service learning through instructional and field project ties to the public-health community of the state and beyond. To date, the program has admitted 87 students, including full-time students as well as part-time students who continue to work in the health care and/or public-health sectors. The program is currently proceeding with the process for accreditation through the Council for Education in Public Health. In 2007, a formal dual DVM/MPH program was approved to allow students to integrate DVM and MPH training and complete both degrees in a total of five years. Nine MPH students over the first three years of admissions have been individuals affiliated with veterinary medicine (five DVM students and four post-graduate veterinarians).

Hospitalization for community-acquired febrile urinary tract infection: validation and impact assessment of a clinical prediction rule.

PubMed

Stalenhoef, Janneke E; van der Starre, Willize E; Vollaard, Albert M; Steyerberg, Ewout W; Delfos, Nathalie M; Leyten, Eliane M S; Koster, Ted; Ablij, Hans C; Van't Wout, Jan W; van Dissel, Jaap T; van Nieuwkoop, Cees

2017-06-06

There is a lack of severity assessment tools to identify adults presenting with febrile urinary tract infection (FUTI) at risk for complicated outcome and guide admission policy. We aimed to validate the Prediction Rule for Admission policy in Complicated urinary Tract InfeCtion LEiden (PRACTICE), a modified form of the pneumonia severity index, and to subsequentially assess its use in clinical practice. A prospective observational multicenter study for model validation (2004-2009), followed by a multicenter controlled clinical trial with stepped wedge cluster-randomization for impact assessment (2010-2014), with a follow up of 3 months. Paricipants were 1157 consecutive patients with a presumptive diagnosis of acute febrile UTI (787 in validation cohort and 370 in the randomized trial), enrolled at emergency departments of 7 hospitals and 35 primary care centers in the Netherlands. The clinical prediction rule contained 12 predictors of complicated course. In the randomized trial the PRACTICE included guidance on hospitalization for high risk (>100 points) and home discharge for low risk patients (<75 points), in the control period the standard policy regarding hospital admission was applied. Main outcomes were effectiveness of the clinical prediction rule, as measured by primary hospital admission rate, and its safety, as measured by the rate of low-risk patients who needed to be hospitalized for FUTI after initial home-based treatment, and 30-day mortality. A total of 370 patients were included in the randomized trial, 237 in the control period and 133 in the intervention period. Use of PRACTICE significantly reduced the primary hospitalization rate (from 219/237, 92%, in the control group to 96/133, 72%, in the intervention group, p < 0.01). The secondary hospital admission rate after initial outpatient treatment was 6% in control patients and 27% in intervention patients (1/17 and 10/37; p < 0.001). Although the proposed PRACTICE prediction rule is associated with a lower number of hospital admissions of patients presenting to the ED with presumptive febrile urinary tract infection, futher improvement is necessary to reduce the occurrence of secondary hospital admissions. NTR4480 http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4480 , registered retrospectively 25 mrt 2014 (during enrollment of subjects).

Cognitive and emotional behavioural changes associated with methylphenidate treatment: a review of preclinical studies.

PubMed

Britton, Gabrielle B

2012-02-01

There is evidence from animal studies that repeated exposure to methylphenidate (MPH), a widely used psychostimulant for the treatment of attention deficit hyperactivity disorder (ADHD), produces behavioural, structural and neurochemical changes that persist long after drug administration has ended. However, the translational utility of much of this work is compromised by the use of drug doses and routes of administration that produce plasma and brain MPH levels that fall outside the clinical range, i.e. experimental parameters more relevant to drug abuse than ADHD. We used PubMed to identify pre-clinical studies that employed repeated MPH administration at low doses in young rodents and examined long-term effects on cognition, emotion, and brain structure and function. A review of this work suggests that repeated MPH treatment during early development can modify a number of cognitive, behavioural and brain processes, but these are reduced when low therapeutic doses are employed. Moreover, MPH sites of action extend beyond those implicated in ADHD. Studies that combined neurobiological and behavioural approaches provide important insights into the mechanisms underlying MPH-produced effects on cognitive and behavioural processes, which may be relevant to MPH therapeutic efficacy. There is an emerging consensus that pharmacological treatment of childhood psychiatric disorders produces persistent neuroadaptations, highlighting the need for studies that assess long-term effects of early developmental pharmacotherapy. In this regard, studies that mimic clinical therapy with rodents are useful experimental approaches for defining the behavioural and neural plasticity associated with stimulant therapy in paediatric populations.

Reinforcement and Stimulant Medication Ameliorate Deficient Response Inhibition in Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Rosch, Keri S; Fosco, Whitney D; Pelham, William E; Waxmonsky, James G; Bubnik, Michelle G; Hawk, Larry W

2016-02-01

This study examined the degree to which reinforcement, stimulant medication, and their combination impact response inhibition in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Across three studies, participants with ADHD (n = 111, 25 girls) and typically-developing (TD) controls (n = 33, 6 girls) completed a standard version of the stop signal task (SST) and/or a reinforcement-manipulation SST with performance-contingent points. In two of these studies, these tasks were performed under placebo or 0.3 and 0.6 mg/kg methylphenidate (MPH) conditions. Cross-study comparisons were conducted to test hypotheses regarding the separate and combined effects of reinforcement and methylphenidate on response inhibition among children with ADHD relative to TD controls. Baseline response inhibition was worse among children with ADHD compared to controls. MPH produced dose-related improvements in response inhibition in children with ADHD; compared to non-medicated TD controls, 0.3 mg/kg MPH normalized deficient response inhibition, and 0.6 mg/kg MPH resulted in better inhibition in children with ADHD. Reinforcement improved response inhibition to a greater extent for children with ADHD than for TD children, normalizing response inhibition. The combination of MPH and reinforcement improved response inhibition among children with ADHD compared to reinforcement alone and MPH alone, also resulting in normalization of response inhibition despite repeated task exposure. Deficient response inhibition commonly observed in children with ADHD is significantly improved with MPH and/or reinforcement, normalizing inhibition relative to TD children tested under standard conditions.

Reinforcement and stimulant medication ameliorate deficient response inhibition in children with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Rosch, Keri S.; Fosco, Whitney D.; Pelham, William E.; Waxmonsky, James G.; Bubnik, Michelle G.; Hawk, Larry W.

2015-01-01

This study examined the degree to which reinforcement, stimulant medication, and their combination impact response inhibition in children with Attention-Deficit/Hyperactivity Disorder (ADHD). Across three studies, participants with ADHD (n=111, 25 girls) and typically-developing (TD) controls (n=33, 6 girls) completed a standard version of the stop signal task (SST) and/or a reinforcement-manipulation SST with performance-contingent points. In two of these studies, these tasks were performed under placebo or 0.3 and 0.6 mg/kg methylphenidate (MPH) conditions. Cross-study comparisons were conducted to test hypotheses regarding the separate and combined effects of reinforcement and methylphenidate on response inhibition among children with ADHD relative to TD controls. Baseline response inhibition was worse among children with ADHD compared to controls. MPH produced dose-related improvements in response inhibition in children with ADHD; compared to non-medicated TD controls, 0.3 mg/kg MPH normalized deficient response inhibition, and 0.6 mg/kg MPH resulted in better inhibition in children with ADHD. Reinforcement improved response inhibition to a greater extent for children with ADHD than for TD children, normalizing response inhibition. The combination of MPH and reinforcement improved response inhibition among children with ADHD compared to reinforcement alone and MPH alone, also resulting in normalization of response inhibition despite repeated task exposure. Deficient response inhibition commonly observed in children with ADHD is significantly improved with MPH and/or reinforcement, normalizing inhibition relative to TD children tested under standard conditions. PMID:25985978

Early postnatal exposure to methylphenidate alters stress reactivity and increases hippocampal ectopic granule cells in adult rats

PubMed Central

Torres-Reveron, Annelyn; Gray, Jason D.; Melton, Jay T.; Punsoni, Michael; Tabori, Nora E.; Ward, Mary J.; Frys, Kelly; Iadecola, Costantino; Milner, Teresa A.

2009-01-01

To mimic clinical treatment with methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), rat pups were injected with MPH (5 mg/kg, I.P.) or placebo twice daily during their nocturnal active phase from postnatal day (PND) 7 to 35. Thirty-nine days after the last MPH administration (PND76), four litters of rats experienced stressful conditions during the 2003 New York City blackout. MPH-treated rats that endured the blackout lost more weight and regained it at a slower pace than controls (p<0.05; N=7–11/group). Furthermore, MPH-treated rats had elevated systolic arterial blood pressure (from 115.6 ± 1.2 to 126 ± 1.8 mmHg; p<0.05), assessed on PND130 by tail cuff plethysmography. Immunocytochemical studies of transmitter systems in the brain demonstrated rearrangements of catecholamine and neuropeptide Y fibers in select brain regions at PND135, which did not differ between blackout and control groups. However, MPH-treated rats that endured the blackout had more ectopic granule cells in the hilus of the dorsal hippocampal dentate gyrus compared to controls at PND 135 (p<0.05; N=6/group). These findings indicate that early postnatal exposure to high therapeutic doses of MPH can have long lasting effects on the plasticity of select brain regions and can induce changes in the reactivity to stress that persist into adulthood. PMID:19100815

Validation of the OMNI RPE Seven Day Exertional Recall Questionnaire

ERIC Educational Resources Information Center

Schafer, Mark A.; Robertson, Robert J.; Thekkada, Savitha J.; Gallagher, Michael, Jr.; Hunt, Sarah E.; Goss, Fredric L.; Aaron, Deborah J.

2013-01-01

Purpose: The present study examined the validity of the Seven Day Recall Questionnaire among recreationally active men and women. Method: Initially, participants completed a level walk (2.5 mph [4.0 kph]), hill walk (3.5 mph [5.6 kph], 5% grade), and run (5.0 mph [8.0 kph], 2.5% grade). Seven days later, participants were given the Seven Day…

PAIRED-CITY STUDY TO DETERMINE THE CONTRIBUTION OF SOURCE WATER TYPE TO THE ENDEMIC LEVEL OF MICROBIAL DISEASE

EPA Science Inventory

Paired-City Study to Determine the Contribution of Source Water Type to the Endemic Level of Microbial Disease

F Frost PhD, T Kunde MPH, L Harter PhD, T Muller MS, GF Craun PE MPH, RL Calderon MPH PhD

ABSTRACT

Context: The effectiveness of current drinking...

Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder.

PubMed

Cao, Ai-hua; Yu, Lin; Wang, Yu-wei; Wang, Jun-mei; Yang, Le-jin; Lei, Ge-Fei

2012-02-28

Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose.

Effects of methylphenidate on attentional set-shifting in a genetic model of attention-deficit/hyperactivity disorder

PubMed Central

2012-01-01

Background Although deficits of attentional set-shifting have been reported in individuals with attention deficit/hyperactivity disorder (ADHD), it is rarely examined in animal models. Methods This study compared spontaneously hypertensive rats (SHRs; a genetic animal model of ADHD) and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats (normoactive control strains), on attentional set-shifting task (ASST) performance. Furthermore, the dose-effects of methylphenidate (MPH) on attentional set-shifting of SHR were investigated. In experiment 1, ASST procedures were conducted in SHR, WKY and SD rats of 8 each at the age of 5 weeks. Mean latencies at the initial phase, error types and numbers, and trials to criteria at each stage were recorded. In experiment 2, 24 SHR rats were randomly assigned to 3 groups of 8 each-- MPH-L (lower dose), MPH-H (higher dose), and SHR-vehicle groups. From 3 weeks, they were administered 2.5 mg/kg or 5 mg/kg MPH or saline respectively for 14 consecutive days. All rats were tested in the ASST at the age of 5 weeks. Results The SHRs generally exhibited poorer performance on ASST than the control WKY and SD rats. Significant strain effects on mean latency [F (2, 21) = 639.636, p < 0.001] and trials to criterion [F (2, 21) = 114.118, p < 0.001] were observed. The SHRs were found to have more perseverative and regressive errors than the control strains (p < 0.001). After MPH treatment, the two MPH treated groups exhibited significantly longer latency and fewer trials to reach criterion than the SHR-vehicle group and the MPH-L group exhibited fewer trials to reach criterion in more stages compared with the MPH-H group. Significant main effects of treatment [F (2, 21) = 52.174, p < 0.001] and error subtype [F (2, 42) = 221.635, p < 0.01] were found. Conclusions The SHR may be impaired in discrimination learning, reversal learning and attentional set-shifting. Our study provides evidence that MPH may improve the SHR's performance on attentional set-shifting and lower dose is more effective than higher dose. PMID:22369105

Rule-Mining for the Early Prediction of Chronic Kidney Disease Based on Metabolomics and Multi-Source Data

PubMed Central

Luck, Margaux; Bertho, Gildas; Bateson, Mathilde; Karras, Alexandre; Yartseva, Anastasia; Thervet, Eric

2016-01-01

1H Nuclear Magnetic Resonance (NMR)-based metabolic profiling is very promising for the diagnostic of the stages of chronic kidney disease (CKD). Because of the high dimension of NMR spectra datasets and the complex mixture of metabolites in biological samples, the identification of discriminant biomarkers of a disease is challenging. None of the widely used chemometric methods in NMR metabolomics performs a local exhaustive exploration of the data. We developed a descriptive and easily understandable approach that searches for discriminant local phenomena using an original exhaustive rule-mining algorithm in order to predict two groups of patients: 1) patients having low to mild CKD stages with no renal failure and 2) patients having moderate to established CKD stages with renal failure. Our predictive algorithm explores the m-dimensional variable space to capture the local overdensities of the two groups of patients under the form of easily interpretable rules. Afterwards, a L2-penalized logistic regression on the discriminant rules was used to build predictive models of the CKD stages. We explored a complex multi-source dataset that included the clinical, demographic, clinical chemistry, renal pathology and urine metabolomic data of a cohort of 110 patients. Given this multi-source dataset and the complex nature of metabolomic data, we analyzed 1- and 2-dimensional rules in order to integrate the information carried by the interactions between the variables. The results indicated that our local algorithm is a valuable analytical method for the precise characterization of multivariate CKD stage profiles and as efficient as the classical global model using chi2 variable section with an approximately 70% of good classification level. The resulting predictive models predominantly identify urinary metabolites (such as 3-hydroxyisovalerate, carnitine, citrate, dimethylsulfone, creatinine and N-methylnicotinamide) as relevant variables indicating that CKD significantly affects the urinary metabolome. In addition, the simple knowledge of the concentration of urinary metabolites classifies the CKD stage of the patients correctly. PMID:27861591

Norepinephrine transporter -3081(A/T) and alpha-2A-adrenergic receptor MspI polymorphisms are associated with cardiovascular side effects of OROS-methylphenidate treatment.

PubMed

Cho, Soo-Churl; Kim, Bung-Nyun; Cummins, Tarrant D R; Kim, Jae-Won; Bellgrove, Mark A

2012-03-01

The purpose of this study was to investigate a possible association between norepinephrine genes and cardiovascular side effects of the Osmotic Controlled-Release Oral Delivery System-methylphenidate (OROS-MPH) in Korean children with attention-deficit/hyperactivity disorder (ADHD). One hundred and one children with ADHD (8.7 ± 1.7 years) were recruited from child psychiatric centers at six university hospitals in South Korea. All participants were drug-naive ADHD children treated with OROS-MPH for 12 weeks. During the treatment period the investigators titrated the OROS-MPH dosage on the basis of symptom severity and side effects. Resting heart rate (HR), diastolic blood pressure (DBP), and systolic blood pressure (SBP) were examined before and after treatment. The percentage change score (post-treatment - pretreatment/pretreatment × 100) of each parameter was calculated. Genotyping of SLC6A2 -3081(A/T) and G1287A, and alpha-2A-adrenergic receptor (ADRA2A) MspI and DraI polymorphisms was performed. Clinically significant changes were not found in cardiovascular monitoring during the course of treatment. An increase of HR after OROS-MPH treatment was found to be statistically significant (t = 3.54, p = 0.001). Changes in SBP and DBP were not significant and no specific change was found in the ECGs. However, an additive regression analysis demonstrated a significant association between SLC6A2 -3081(A/T) and percentage change in HR post-treatment (p = 0.01) after controlling for age, gender, dosage of MPH and response and baseline pulse rate. Children with ADHD having the T/T genotype of SLC6A2 showed a 12.5% increase in HR compared to baseline, whereas children with the A/T or A/A genotype showed a 3.5% and 2.5% increase after OROS-MPH treatment, respectively. There was also a significant association between the ADRA2A MspI genotype and percentage change of DBP post-treatment after controlling for age, gender, dosage of MPH and response and baseline DBP (p = 0.009). Children with ADHD having the C/C genotype of ADRA2A MspI showed an 18.5% increase in DBP compared to baseline, but children with the G/G or G/C genotype showed a 0.2% decrease after OROS-MPH treatment. The overall cardiovascular effects of OROS-MPH were modest. However, our findings show a positive association between norepinephrine-related gene polymorphisms and cardiovascular response induced by MPH in Korean children with ADHD. Consideration must be given to such children or adults with specific norepinephrine-related genotypes, especially if they show significant changes in HR or DBP after OROS-MPH administration.

PROBABILISTIC HAZARD ASSESSMENT FOR TORNADOES, STRAIGHT-LINE WIND, AND EXTREME PRECIPITATION AT THE SAVANNAH RIVER SITE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werth, D.; NOEMAIL), A.; Shine, G.

Recent data sets for three meteorological phenomena with the potential to inflict damage on SRS facilities - tornadoes, straight winds, and heavy precipitation - are analyzed using appropriate statistical techniques to estimate occurrence probabilities for these events in the future. Summaries of the results for DOE-mandated return periods and comparisons to similar calculations performed in 1998 by Weber, et al., are given. Using tornado statistics for the states of Georgia and South Carolina, we calculated the probability per year of any location within a 2⁰ square area surrounding SRS being struck by a tornado (the ‘strike’ probability) and the probabilitymore » that any point will experience winds above set thresholds. The strike probability was calculated to be 1.15E-3 (1 chance in 870) per year and wind speeds for DOE mandated return periods of 50,000 years, 125,000 years, and 1E+7 years (USDOE, 2012) were estimated to be 136 mph, 151 mph and 221 mph, respectively. In 1998 the strike probability for SRS was estimated to be 3.53 E-4 and the return period wind speeds were 148 mph every 50,000 years and 180 mph every 125,000 years. A 1E+7 year tornado wind speed was not calculated in 1998; however a 3E+6 year wind speed was 260 mph. The lower wind speeds resulting from this most recent analysis are largely due to new data since 1998, and to a lesser degree differences in the models used. By contrast, default tornado wind speeds taken from ANSI/ANS-2.3-2011 are somewhat higher: 161 mph for return periods of 50,000 years, 173 mph every 125,000 years, and 230 mph every 1E+7 years (ANS, 2011). Although the ANS model and the SRS models are very similar, the region defined in ANS 2.3 that encompasses the SRS also includes areas of the Great Plains and lower Midwest, regions with much higher occurrence frequencies of strong tornadoes. The SRS straight wind values associated with various return periods were calculated by fitting existing wind data to a Gumbel distribution, and extrapolating the values for any return period from the tail of that function. For the DOE mandated return periods, we expect straight winds of 123 mph every 2500 years, and 132mph every 6250 years at any point within the SRS. These values are similar to those from the W98 report (which also used the Gumbel distribution for wind speeds) which gave wind speeds of 115mph and 122 mph for return periods of 2500 years and 6250 years, respectively. For extreme precipitation accumulation periods, we compared the fits of three different theoretical extreme-value distributions, and in the end decided to maintain the use of the Gumbel distribution for each period. The DOE mandated 6-hr accumulated rainfall for return periods of 2500 years and 6250 years was estimated as 7.8 inches and 8.4 inches, respectively. For the 24- hr rainfall return periods of 10,000 years and 25,000 years, total rainfall estimates were 10.4 inches and 11.1 inches, respectively. These values are substantially lower than comparable values provided in the W98 report. This is largely a consequence of the W98 use of a different extreme value distribution with its corresponding higher extreme probabilities.« less

The effect of methylphenidate on postural stability under single and dual task conditions in children with attention deficit hyperactivity disorder - a double blind randomized control trial.

PubMed

Jacobi-Polishook, Talia; Shorer, Zamir; Melzer, Itshak

2009-05-15

To investigate the effects of Methylphenidate (MPH) on postural stability in attention deficit hyperactivity disorder (ADHD) children in single and dual task conditions. A randomized controlled double-blind study analyzing postural stability in 24 ADHD children before and after MPH vs. placebo treatments, in three task conditions: (1) Single task, standing still; (2) dual task, standing still performing a memory-attention demanding task; (3) standing still listening to music. MPH resulted in a significant improvement in postural stability during the dual task condition and while listening to music, with no equivalent improvement in placebo controls. MPH improves postural stability in ADHD, especially when an additional task is performed. This is probably due to enhanced attention abilities, thus contributing to improved balance control during performance of tasks that require attention. MPH remains to be studied as a potential drug treatment to improve balance control and physical functioning in other clinical populations.

Novelty-seeking trait predicts the effect of methylphenidate on creativity.

PubMed

Gvirts, Hila Z; Mayseless, Naama; Segev, Aviv; Lewis, D Yael; Feffer, Kfir; Barnea, Yael; Bloch, Yuval; Shamay-Tsoory, Simon G

2017-05-01

In recent years the use of psychostimulants for cognitive enhancement in healthy individuals with no psychiatric disorders has been on the rise. However, it is still unclear whether psychostimulants improve certain cognitive functions at the cost of others, and how these psychostimulants interact with individual personality differences. In the current study, we investigated whether the effect of one common stimulant, methylphenidate (MPH), on creativity is associated with novelty seeking. Thirty-six healthy adults, without attention-deficit hyperactivity disorder (ADHD) symptomology, were assigned randomly in a double-blind fashion to receive MPH or placebo. We found that the effect of MPH on creativity was dependent on novelty-seeking (NS) personality characteristics of the participants. MPH increased creativity in individuals with lower NS, while it reduced creativity levels in individuals with high NS. These findings highlight the role of the dopaminergic system in creativity, and indicate that among healthy individuals NS can be seen as a predictor of the effect of MPH on creativity.

A Double-Blind, Placebo-Controlled Trial of Dexmethylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in Children with Attention-Deficit-Hyperactivity Disorder

ERIC Educational Resources Information Center

Wigal, Sharon; Swanson, James M.; Feifel, David; Sangal, R. Bart; Elia, Josephine; Casat, Charles D.; Zeldis, Jerome B.; Conners, C. Keith

2004-01-01

Objective: To evaluate the efficacy and safety of dexmethylphenidate hydrochloride (d-MPH, Focalin[TM]) for the treatment of attention-deficit/hyperactivity disorder (ADHD) and to test an a priori hypothesis that d-MPH would have a longer duration of action than d,l-threo-methylphenidate (d,l-MPH). Method: This was a randomized, double-blind study…

Predicting methylphenidate response in attention deficit hyperactivity disorder: a preliminary study.

PubMed

Johnston, Blair A; Coghill, David; Matthews, Keith; Steele, J Douglas

2015-01-01

Methylphenidate (MPH) is established as the main pharmacological treatment for patients with attention deficit hyperactivity disorder (ADHD). Whilst MPH is generally a highly effective treatment, not all patients respond, and some experience adverse reactions. Currently, there is no reliable method to predict how patients will respond, other than by exposure to a trial of medication. In this preliminary study, we sought to investigate whether an accurate predictor of clinical response to methylphenidate could be developed for individual patients, using sociodemographic, clinical and neuropsychological measures. Of the 43 boys with ADHD included in this proof-of-concept study, 30 were classed as responders and 13 as non-responders to MPH, with no significant differences in age nor verbal intelligence quotient (IQ) between the groups. Here we report the application of a multivariate analysis approach to the prediction of clinical response to MPH, which achieved an accuracy of 77% (p = 0.005). The most important variables to the classifier were performance on a 'go/no go' task and comorbid conduct disorder. This preliminary study suggested that further investigation is merited. Achieving a highly significant accuracy of 77% for the prediction of MPH response is an encouraging step towards finding a reliable and clinically useful method that could minimise the number of children needlessly being exposed to MPH. © The Author(s) 2014.

Verbal working memory-related functional connectivity alterations in boys with attention-deficit/hyperactivity disorder and the effects of methylphenidate.

PubMed

Wu, Zhao-Min; Bralten, Janita; An, Li; Cao, Qing-Jiu; Cao, Xiao-Hua; Sun, Li; Liu, Lu; Yang, Li; Mennes, Maarten; Zang, Yu-Feng; Franke, Barbara; Hoogman, Martine; Wang, Yu-Feng

2017-08-01

Few studies have investigated verbal working memory-related functional connectivity patterns in participants with attention-deficit/hyperactivity disorder (ADHD). Thus, we aimed to compare working memory-related functional connectivity patterns in healthy children and those with ADHD, and study effects of methylphenidate (MPH). Twenty-two boys with ADHD were scanned twice, under either MPH (single dose, 10 mg) or placebo, in a randomised, cross-over, counterbalanced placebo-controlled design. Thirty healthy boys were scanned once. We used fMRI during a numerical n-back task to examine functional connectivity patterns in case-control and MPH-placebo comparisons, using independent component analysis. There was no significant difference in behavioural performance between children with ADHD, treated with MPH or placebo, and healthy controls. Compared with controls, participants with ADHD under placebo showed increased functional connectivity within fronto-parietal and auditory networks, and decreased functional connectivity within the executive control network. MPH normalized the altered functional connectivity pattern and significantly enhanced functional connectivity within the executive control network, though in non-overlapping areas. Our study contributes to the identification of the neural substrates of working memory. Single dose of MPH normalized the altered brain functional connectivity network, but had no enhancing effect on (non-impaired) behavioural performance.

Effectiveness of atomoxetine and methylphenidate for problematic online gaming in adolescents with attention deficit hyperactivity disorder.

PubMed

Park, Jeong Ha; Lee, Young Sik; Sohn, Ji Hyun; Han, Doug Hyun

2016-11-01

There is a high prevalence of problematic online gaming in adolescents with attention deficit hyperactivity disorder (ADHD). In the current study, we compared the effectiveness of atomoxetine (ATM) and methylphenidate (MPH) on problematic online gaming in adolescents with ADHD. We recruited 86 adolescents diagnosed with ADHD together with Internet gaming disorder. These participants were divided into two treatment groups: 44 participants were treated with MPH for 12 weeks, and 42 participants were treated with ATM for 12 weeks. During the 3-month study period, the MPH group showed greater improvement in Korean ADHD rating scale scores than the ATM group. The ATM group showed greater improvement in Child Depression Inventory scores than the MPH group. However, Young Internet Addiction Scale and Behavioral Inhibition & Activation Scales score changes did not differ significantly between the MPH and ATM groups. In both groups, changes in Young Internet Addiction Scale scores were positively correlated with the changes in Behavioral Inhibition & Activation Scales scores. Both MPH and ATM reduced the severity of Internet gaming disorder symptoms, and this reduction was correlated with impulsivity reduction, which also resulted from both ADHD medications. These findings suggest impulsivity plays a critical role in the development of problematic online gaming. Copyright © 2016 John Wiley & Sons, Ltd.

Cross-validation of oxygen uptake prediction during walking in ambulatory persons with multiple sclerosis.

PubMed

Agiovlasitis, Stamatis; Motl, Robert W

2016-01-01

An equation for predicting the gross oxygen uptake (gross-VO2) during walking for persons with multiple sclerosis (MS) has been developed. Predictors included walking speed and total score from the 12-Item Multiple Sclerosis Walking Scale (MSWS-12). This study examined the validity of this prediction equation in another sample of persons with MS. Participants were 18 persons with MS with limited mobility problems (42 ± 13 years; 14 women). Participants completed the MSWS-12. Gross-VO2 was measured with open-circuit spirometry during treadmill walking at 2.0, 3.0, and 4.0 mph (0.89, 1.34, and 1.79 m·s(-1)). Absolute percent error was small: 8.3 ± 6.1% , 8.0 ± 5.6% , and 12.2 ± 9.0% at 2.0, 3.0, and 4.0 mph, respectively. Actual gross-VO2 did not differ significantly from predicted gross-VO2 at 2.0 and 3.0 mph, but was significantly higher than predicted gross-VO2 at 4.0 mph (p <  0.001). Bland-Altman plots indicated nearly zero mean difference between actual and predicted gross-VO2 with modest 95% confidence intervals at 2.0 and 3.0 mph, but there was some underestimation at 4.0 mph. Speed and MSWS-12 score provide valid prediction of gross-VO2 during treadmill walking at slow and moderate speeds in ambulatory persons with MS. However, there is a possibility of small underestimation for walking at 4.0 mph.

Plasma level-dependent effects of methylphenidate on task-related functional magnetic resonance imaging signal changes.

PubMed

Müller, Ulrich; Suckling, J; Zelaya, F; Honey, G; Faessel, H; Williams, S C R; Routledge, C; Brown, J; Robbins, T W; Bullmore, E T

2005-08-01

Methylphenidate (MPH) is a dopamine and noradrenaline enhancing drug used to treat attentional deficits. Understanding of its cognition-enhancing effects and the neurobiological mechanisms involved, especially in elderly people, is currently incomplete. The aim of this study was to investigate the relationship between MPH plasma levels and brain activation during visuospatial attention and movement preparation. Twelve healthy elderly volunteers were scanned twice using functional magnetic resonance imaging (fMRI) after oral administration of MPH 20 mg or placebo in a within-subject design. The cognitive paradigm was a four-choice reaction time task presented at two levels of difficulty (with and without spatial cue). Plasma MPH levels were measured at six time points between 30 and 205 min after dosing. FMRI data were analysed using a linear model to estimate physiological response to the task and nonparametric permutation tests for inference. Lateral premotor and medial posterior parietal cortical activation was increased by MPH, on average, over both levels of task difficulty. There was considerable intersubject variability in the pharmacokinetics of MPH. Greater area under the plasma concentration-time curve was positively correlated with strength of activation in motor and premotor cortex, temporoparietal cortex and caudate nucleus during the difficult version of the task. This is the first pharmacokinetic/pharmacodynamic study to find an association between plasma levels of MPH and its modulatory effects on brain activation measured using fMRI. The results suggest that catecholaminergic mechanisms may be important in brain adaptivity to task difficulty and in task-specific recruitment of spatial attention systems.

Assessment of potential cardiovascular risks of methylphenidate in comparison with sibutramine: do we need a SCOUT (trial)?

PubMed

Antel, Jochen; Albayrak, Özgür; Heusch, Gerd; Banaschewski, Tobias; Hebebrand, Johannes

2015-04-01

With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1 years of follow-up in children and adolescents and mean duration of 0.33 years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH.

Effect of methylphenidate treatment during adolescence on norepinephrine transporter function in orbitofrontal cortex in a rat model of Attention Deficit Hyperactivity Disorder

PubMed Central

Somkuwar, Sucharita S.; Kantak, Kathleen M.; Dwoskin, Linda P.

2015-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is associated with hypofunctional medial prefrontal cortex (mPFC) and orbitofrontal cortex (OFC). Methylphenidate (MPH) remediates ADHD, in part, by inhibiting the norepinephrine transporter (NET). MPH also reduces ADHD-like symptoms in Spontaneously Hypertensive Rats (SHRs), a model of ADHD. However, effects of chronic MPH treatment on NET function in mPFC and OFC in SHR have not been reported. In the current study, long-term effects of repeated treatment with a therapeutically relevant oral dose of MPH during adolescence on NET function in subregions of mPFC (cingulate gyrus, prelimbic cortex and infralimbic cortex) and in the OFC of adult SHR, Wistar-Kyoto (WKY, inbred control) and Wistar (WIS, outbred control) rats were determined using in vivo voltammetry. Following local ejection of norepinephrine (NE), uptake rate was determined as peak amplitude (Amax) x first-order rate constant (k-1). In mPFC subregions, no strain or treatment effects were found in NE uptake rate. In OFC, NE uptake rate in vehicle-treated adult SHR was greater than in adult WKY and WIS administered vehicle. MPH treatment during adolescence normalized NE uptake rate in OFC in SHR. Thus, the current study implicates increased NET function in OFC as an underlying mechanism for reduced noradrenergic transmission in OFC, and consequently, the behavioral deficits associated with ADHD. MPH treatment during adolescence normalized NET function in OFC in adulthood, suggesting that the therapeutic action of MPH persists long after treatment cessation and may contribute to lasting reductions in deficits associated with ADHD. PMID:25680322

Factors Associated With Adherence to Methylphenidate Treatment in Adult Patients With Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders.

PubMed

Skoglund, Charlotte; Brandt, Lena; Almqvist, Catarina; DʼOnofrio, Brian M; Konstenius, Maija; Franck, Johan; Larsson, Henrik

2016-06-01

Adherence to treatment is one of the most consistent factors associated with a favorable addiction treatment outcome. Little is known about factors associated with treatment adherence in individuals affected with comorbid attention-deficit/hyperactivity disorder and substance use disorders (SUD). This study aimed to explore whether treatment-associated factors, such as the prescribing physician's (sub)specialty and methylphenidate (MPH) dose, or patient-related factors, such as sex, age, SUD subtype, and psychiatric comorbidity, were associated with adherence to MPH treatment. Swedish national registers were used to identify adult individuals with prescriptions of MPH and medications specifically used in the treatment of SUD or a diagnosis of SUD and/or coexisting psychiatric diagnoses. Primary outcome measure was days in active MPH treatment in stratified dose groups (≤36 mg, ≥37 mg to ≤54 mg, ≥55 mg to ≤72 mg, ≥73 mg to ≤90 mg, ≥91 mg to ≤108 mg, and ≥109 mg). Lower MPH doses (ie, ≤36 mg day 100) were associated with treatment discontinuation between days 101 and 830 (HR≤36 mg, 1.67; HR37-54mg, 1.37; HR55-72mg, 1.36; HR73-90mg, 1.19; HR≥108mg, 1.09). The results showed a linear trend (P < 0.0001) toward decreased risk of treatment discontinuation along with increase of MPH doses. In conclusion, this study shows that higher MPH doses were associated with long-term treatment adherence in individuals with attention-deficit/hyperactivity disorder and SUD.

Methylphenidate alleviates manganese-induced impulsivity but not distractibility

PubMed Central

Beaudin, Stephane A.; Strupp, Barbara J.; Uribe, Walter; Ysais, Lauren; Strawderman, Myla; Smith, Donald R.

2017-01-01

Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50 mg Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107 – 115) on an attention task that specifically tapped selective attention and impulse control. Animals were treated with oral MPH (2.5 mg/kg/d) throughout testing on the attention task. Our findings show that lifelong postnatal Mn exposure impaired impulse control and selective attention in young adulthood, and that a therapeutically relevant oral MPH regimen alleviated the Mn-induced dysfunction in impulse control, but not selective attention, and actually impaired focused attention in the Mn group. In addition, the effect of MPH was qualitatively different for the Mn-exposed versus control animals across a range of behavioral measures of inhibitory control and attention, as well as dendritic spine density in the mPFC, suggesting that postnatal Mn exposure alters catecholaminergic systems modulating these behaviors. Collectively these findings suggest that MPH may hold promise for treating the behavioral dysfunction caused by developmental Mn exposure, although further research is needed with multiple MPH doses to determine whether a dose can be identified that ameliorates the dysfunction in both impulse control and selective attention, without impairing focused attention. PMID:28363668

Methylphenidate alleviates manganese-induced impulsivity but not distractibility.

PubMed

Beaudin, Stephane A; Strupp, Barbara J; Uribe, Walter; Ysais, Lauren; Strawderman, Myla; Smith, Donald R

2017-05-01

Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107-115) on an attention task that specifically tapped selective attention and impulse control. Animals were treated with oral MPH (2.5mg/kg/d) throughout testing on the attention task. Our findings show that lifelong postnatal Mn exposure impaired impulse control and selective attention in young adulthood, and that a therapeutically relevant oral MPH regimen alleviated the Mn-induced dysfunction in impulse control, but not selective attention, and actually impaired focused attention in the Mn group. In addition, the effect of MPH was qualitatively different for the Mn-exposed versus control animals across a range of behavioral measures of inhibitory control and attention, as well as dendritic spine density in the mPFC, suggesting that postnatal Mn exposure alters catecholaminergic systems modulating these behaviors. Collectively these findings suggest that MPH may hold promise for treating the behavioral dysfunction caused by developmental Mn exposure, although further research is needed with multiple MPH doses to determine whether a dose can be identified that ameliorates the dysfunction in both impulse control and selective attention, without impairing focused attention. Copyright © 2017 Elsevier Inc. All rights reserved.

Subjective Effects, Misuse, and Adverse Effects of Osmotic-Release Methylphenidate Treatment in Adolescent Substance Abusers with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Lewis, Daniel F.; Riggs, Paula D.; Davies, Robert D.; Adler, Lenard A.; Sonne, Susan; Somoza, Eugene C.

2011-01-01

Abstract Objective Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non–substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. Method Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13–18) with at least one non-nicotine SUD and one with 255 adult smokers (18–55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). Results Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. Conclusions With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence. PMID:22040190

Subjective effects, misuse, and adverse effects of osmotic-release methylphenidate treatment in adolescent substance abusers with attention-deficit/hyperactivity disorder.

PubMed

Winhusen, Theresa M; Lewis, Daniel F; Riggs, Paula D; Davies, Robert D; Adler, Lenard A; Sonne, Susan; Somoza, Eugene C

2011-10-01

Psychostimulants are effective treatments for attention-deficit/hyperactivity disorder (ADHD) but may be associated with euphoric effects, misuse/diversion, and adverse effects. These risks are perceived by some clinicians to be greater in substance-abusing adolescents relative to non-substance-abusing adults. The present study evaluates the subjective effects, misuse/diversion, and adverse effects associated with the use of osmotic-release oral system methylphenidate (OROS-MPH), relative to placebo, for treating ADHD in adolescents with a substance use disorder (SUD) as a function of substance use severity and compared these risks with those associated with the treatment of ADHD in adults without a non-nicotine SUD. Datasets from two randomized placebo-controlled trials of OROS-MPH for treating ADHD, one conducted with 303 adolescents (13-18) with at least one non-nicotine SUD and one with 255 adult smokers (18-55), were analyzed. Outcome measures included the Massachusetts General Hospital Liking Scale, self-reported medication compliance, pill counts, and adverse events (AEs). Euphoric effects and misuse/diversion of OROS-MPH were not significantly affected by substance use severity. The euphoric effects of OROS-MPH did not significantly differ between the adolescent and adult samples. Adults rated OROS-MPH as more effective in treating ADHD, whereas adolescents reported feeling more depressed when taking OROS-MPH. The adolescents lost more pills relative to the adults regardless of treatment condition, which suggests the importance of careful medication monitoring. Higher baseline use of alcohol and cannabis was associated with an increased risk of experiencing a treatment-related AE in OROS-MPH, but baseline use did not increase the risk of serious AEs or of any particular category of AE and the adolescents did not experience more treatment-related AEs relative to the adults. With good monitoring, and in the context of substance abuse treatment, OROS-MPH can be safely used in adolescents with an SUD despite non-abstinence.

The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast.

PubMed

Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi

2016-01-01

The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1.

Components of a Fanconi-like pathway control Pso2-independent DNA interstrand crosslink repair in yeast.

PubMed

Ward, Thomas A; Dudášová, Zuzana; Sarkar, Sovan; Bhide, Mangesh R; Vlasáková, Danuša; Chovanec, Miroslav; McHugh, Peter J

2012-01-01

Fanconi anemia (FA) is a devastating genetic disease, associated with genomic instability and defects in DNA interstrand cross-link (ICL) repair. The FA repair pathway is not thought to be conserved in budding yeast, and although the yeast Mph1 helicase is a putative homolog of human FANCM, yeast cells disrupted for MPH1 are not sensitive to ICLs. Here, we reveal a key role for Mph1 in ICL repair when the Pso2 exonuclease is inactivated. We find that the yeast FANCM ortholog Mph1 physically and functionally interacts with Mgm101, a protein previously implicated in mitochondrial DNA repair, and the MutSα mismatch repair factor (Msh2-Msh6). Co-disruption of MPH1, MGM101, MSH6, or MSH2 with PSO2 produces a lesion-specific increase in ICL sensitivity, the elevation of ICL-induced chromosomal rearrangements, and persistence of ICL-associated DNA double-strand breaks. We find that Mph1-Mgm101-MutSα directs the ICL-induced recruitment of Exo1 to chromatin, and we propose that Exo1 is an alternative 5'-3' exonuclease utilised for ICL repair in the absence of Pso2. Moreover, ICL-induced Rad51 chromatin loading is delayed when both Pso2 and components of the Mph1-Mgm101-MutSα and Exo1 pathway are inactivated, demonstrating that the homologous recombination stages of ICL repair are inhibited. Finally, the FANCJ- and FANCP-related factors Chl1 and Slx4, respectively, are also components of the genetic pathway controlled by Mph1-Mgm101-MutSα. Together this suggests that a prototypical FA-related ICL repair pathway operates in budding yeast, which acts redundantly with the pathway controlled by Pso2, and is required for the targeting of Exo1 to chromatin to execute ICL repair.

The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast

PubMed Central

Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi

2016-01-01

ABSTRACT The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1. PMID:26900649

Bladder rupture caused by postpartum urinary retention.

PubMed

Dueñas-García, Omar Felipe; Rico, Hugo; Gorbea-Sanchez, Viridiana; Herrerias-Canedo, Tomas

2008-08-01

Postpartum bladder rupture is an uncommon surgical emergency and a diagnostic challenge. A primigravida delivered a healthy newborn without complications at 39.4 weeks of gestation. The patient was admitted 80 hours postpartum with abdominal pain, oliguria, hematuria, and pain that worsened during the previous 4 hours. An inserted Foley catheter drained only a small amount of urine, and serum creatinine was elevated (3.5 mg/dL). A laparotomy was performed and revealed a 10-cm hole in the urinary bladder. The bladder was repaired and the patient was discharged 15 days after surgery. The follow-up cystoscopy revealed adequate healing of the bladder. Urinary retention can lead to serious complications, including bladder rupture. Postpartum bladder rupture due to urinary retention should be ruled out if there is a history of abdominal pain, oliguria, and elevated of serum creatinine.

Grumman WS33 wind system: prototype construction and testing, Phase II technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adler, F.M.; Henton, P.; King, P.W.

1980-11-01

The prototype fabrication and testing of the 8 kW small wind energy conversion system are reported. The turbine is a three-bladed, down-wind machine designed to interface directly with an electrical utility network. The machine as finally fabricated is rated at 15 kW at 24 mpH and peak power of 18 kW at 35 mph. Utility compatible electrical power is generated in winds between a cut-in speed of 9 mph and a cut-out speed of 35 mph by using the torque characteristics of the unit's induction generator combined with the rotor aerodynamics to maintain essentially constant speed. Inspection procedures, pre-delivery testing,more » and a cost analysis are included.« less

Hurricane Celia off the Pacific Coast of Mexico

NASA Image and Video Library

2004-07-23

Hurricane Celia as observed by NASA's spaceborne Atmospheric Infrared Sounder (AIRS). This image shows Celia on July 23 in visible light, as you would perceive it from space. Located in the eastern north Pacific Ocean off the coast of Mexico, Celia's winds have now dissipated to highs of 40 mph. Celia was the first hurricane of the eastern north Pacific season. Figure 1 is a daylight snapshot taken on July 19; Celia as tropical storm, winds at 50mph. Figure 2 is a daylight snapshot taken on July 21; Celia has a small eye with an 80-90% closed eyewall; sustained winds at 75mph with gusts reaching 92mph; Celia is upgraded to hurricane status. http://photojournal.jpl.nasa.gov/catalog/PIA00438

KSC-04pd1697

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, workers prepare to close the payload bay doors on Atlantis in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1692

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare to stow the landing gear on the orbiter Atlantis in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, and closing their payload bay doors. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1694

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare the wheel bay to stow Atlantis’ landing gear in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, and closing their payload bay doors. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1711

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility finish Hurricane preparations on the payload bay doors of Atlantis. Preparing for the expected impact of Hurricane Frances on Saturday, workers also powered down the Space Shuttle orbiters, and stowed the landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1691

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare to close the nose wheel doors on Atlantis in preparation for the expected impact of Hurricane Frances on Saturday. Preparations at KSC include powering down the Space Shuttle orbiters, closing their payload bay doors and stowing their landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1688

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare the orbiter Atlantis and related equipment for the expected impact of Hurricane Frances on Saturday. Preparations at KSC include powering down the Space Shuttle orbiters, closing their payload bay doors and stowing their landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1703

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, the payload bay doors on Atlantis are being closed in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1710

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility cover up areas of Atlantis with plastic, preparing for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, closing the payload bay doors and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1693

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare to stow the landing gear on the orbiter Atlantis in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, and closing their payload bay doors. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1699

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, Atlantis’ payload bay doors are being closed in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1698

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, workers prepare to close the payload bay doors on Atlantis in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1690

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare to close the nose wheel doors on Atlantis in preparation for the expected impact of Hurricane Frances on Saturday. Preparations at KSC include powering down the Space Shuttle orbiters, closing their payload bay doors and stowing their landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1689

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility prepare to close the nose wheel doors on Atlantis in preparation for the expected impact of Hurricane Frances on Saturday. Preparations at KSC include powering down the Space Shuttle orbiters, closing their payload bay doors and stowing their landing gear. They are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1708

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility cover up areas of Atlantis, preparing for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, closing the payload bay doors and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1702

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, the payload bay doors on Atlantis are being closed in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1700

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, the payload bay doors on Atlantis are being closed in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1696

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, Atlantis’ wheels are raised into their wheel bays in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, and closing their payload bay doors. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1704

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, the payload bay doors on Atlantis are being closed in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1701

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, a worker checks out part of Atlantis after payload bay doors were closed in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1695

NASA Image and Video Library

2004-08-31

KENNEDY SPACE CENTER, FLA. - In the Orbiter Processing Facility, Atlantis’ wheels are raised into their wheel bays in preparation for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, and closing their payload bay doors. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

KSC-04pd1709

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility cover up areas of Atlantis with plastic, preparing for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, closing the payload bay doors and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

Effects of developmental methylphenidate (MPH) treatment on monoamine neurochemistry of male and female rats.

PubMed

Panos, John J; O'Callaghan, James P; Miller, Diane B; Ferguson, Sherry A

2014-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is estimated to affect 4-5% of the adult human population (Kessler et al., 2006; Willcutt, 2012). Often prescribed to attenuate ADHD symptoms (Nair and Moss, 2009), methylphenidate hydrochloride (MPH) can have substantial positive effects. However, there is a paucity of literature regarding its use during pregnancy. Thus, adult women with ADHD face a difficult decision when contemplating pregnancy. In this study, pregnant Sprague-Dawley rats were orally treated a total of 0 (water), 6 (low), 18 (medium), or 42 (high) mg MPH/kg body weight/day (divided into three doses) on gestational days 6-21 (i.e., the low dose received 2 mg MPH/kg body weight 3×/day). Offspring were orally treated with the same daily dose as their dam (divided into two doses) on postnatal days (PNDs) 1-21. One offspring/sex/litter was sacrificed at PND 22 or PND 104 (n=6-7/age/sex/treatment group) and the striatum was quickly dissected and frozen. High Performance Liquid Chromatography (HPLC) coupled to a Photo Diode Array detector (PDA) was used to analyze monoamine content in the striatum of one side while a sandwich ELISA was used to analyze tyrosine hydroxylase (TH) from the other side. Age significantly affected monoamine and metabolite content as well as turnover ratios (i.e., DA, DOPAC, HVA, DOPAC/DA, HVA/DA, 5-HT and 5-HIAA); however, there were no significant effects of sex. Adult rats of the low MPH group had higher DA levels than control adults (p<0.05). At both ages, subjects of the low MPH group had higher TH levels than controls (p<0.05), although neither effect (i.e., higher DA or TH levels) exhibited an apparent dose-response. PND 22 subjects of the high MPH treatment group had higher ratios of HVA/DA and DOPAC/DA than same-age control subjects (p<0.05). The increased TH levels of the low MPH group may be related to the increased DA levels of adult rats. While developmental MPH treatment appears to have some effects on monoamine system development, further studies are required to determine if these alterations manifest as functional changes in behavior. Published by Elsevier Inc.

Optimization of Methylphenidate Extended-Release Chewable Tablet Dose in Children with ADHD: Open-Label Dose Optimization in a Laboratory Classroom Study.

PubMed

Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi W; Chappell, Phillip; Wajsbrot, Dalia B; Nagraj, Praneeta; Abbas, Richat; Palumbo, Donna

2018-06-01

To examine methylphenidate extended-release chewable tablets (MPH ERCT) dose patterns, attention-deficit/hyperactivity disorder (ADHD) symptom scores, and safety during the 6-week, open-label (OL) dose-optimization period of a phase 3, laboratory classroom study. Boys and girls (6-12 years) diagnosed with ADHD were enrolled. MPH ERCT was initiated at 20 mg/day; participants were titrated in 10-20 mg/day increments weekly based on efficacy and tolerability (maximum dose, 60 mg/day). Dose-optimization period efficacy assessments included the ADHD Rating Scale (ADHD-RS-IV), analyzed by week in a post hoc analysis using a mixed-effects model for repeated measures with final optimized dose (20, 30/40, or 50/60 mg), visit, final optimized dose and visit interaction, and baseline score as terms. Adverse events (AEs) and concomitant medications were collected throughout the study. Mean MPH ERCT daily dose increased weekly from 29.4 mg/day after the first dose adjustment at week 1 (n = 90) to 42.8 mg/day after the final adjustment at week 5 (n = 86). Final optimized MPH ERCT dose ranged from 20 to 60 mg/day. Mean final optimized MPH ERCT dose ranged from 40.0 mg/day in 6-8 year-old participants to 44.8 mg/day for 11-12 year-old participants. There was a progressive decrease in mean (standard deviation) ADHD-RS-IV total score from 40.1 (8.72) at baseline to 12.4 (7.88) at OL week 5, with similar improvement patterns for hyperactivity/impulsivity and inattentiveness subscale scores. Participants optimized to MPH ERCT 50/60 mg/day had a significantly higher mean (standard error) ADHD-RS-IV score at baseline compared with participants optimized to MPH ERCT 20 mg/day (42.4 [1.34] vs. 35.1 [2.55]; p = 0.013). Treatment-emergent AEs were reported by 65/90 (72.2%) participants in the dose-optimization period. Dose-optimization period results describing relationships between change in ADHD symptom scores and final optimized MPH ERCT dose will be valuable for clinicians optimizing MPH ERCT dose.

Urinary metabolic profiling of asymptomatic acute intermittent porphyria using a rule-mining-based algorithm.

PubMed

Luck, Margaux; Schmitt, Caroline; Talbi, Neila; Gouya, Laurent; Caradeuc, Cédric; Puy, Hervé; Bertho, Gildas; Pallet, Nicolas

2018-01-01

Metabolomic profiling combines Nuclear Magnetic Resonance spectroscopy with supervised statistical analysis that might allow to better understanding the mechanisms of a disease. In this study, the urinary metabolic profiling of individuals with porphyrias was performed to predict different types of disease, and to propose new pathophysiological hypotheses. Urine 1 H-NMR spectra of 73 patients with asymptomatic acute intermittent porphyria (aAIP) and familial or sporadic porphyria cutanea tarda (f/sPCT) were compared using a supervised rule-mining algorithm. NMR spectrum buckets bins, corresponding to rules, were extracted and a logistic regression was trained. Our rule-mining algorithm generated results were consistent with those obtained using partial least square discriminant analysis (PLS-DA) and the predictive performance of the model was significant. Buckets that were identified by the algorithm corresponded to metabolites involved in glycolysis and energy-conversion pathways, notably acetate, citrate, and pyruvate, which were found in higher concentrations in the urines of aAIP compared with PCT patients. Metabolic profiling did not discriminate sPCT from fPCT patients. These results suggest that metabolic reprogramming occurs in aAIP individuals, even in the absence of overt symptoms, and supports the relationship that occur between heme synthesis and mitochondrial energetic metabolism.

Neuroprotective effects of various doses of topiramate against methylphenidate-induced oxidative stress and inflammation in isolated rat amygdala: the possible role of CREB/BDNF signaling pathway.

PubMed

Motaghinejad, Majid; Motevalian, Manijeh; Falak, Reza; Heidari, Mansour; Sharzad, Mahshid; Kalantari, Elham

2016-12-01

Methylphenidate (MPH) abuse damages brain cells. The neuroprotective effects of topiramate (TPM) have been reported previously, but its exact mechanism of action still remains unclear. This study investigated the in vivo role of various doses of TPM in the protection of rat amygdala cells against methylphenidate-induced oxidative stress and inflammation. Seventy adult male rats were divided into seven groups. Groups 1 and 2 received normal saline (0.7 ml/rat) and MPH (10 mg/kg), respectively, for 21 days. Groups 3, 4, 5, 6, and 7 were concurrently treated with MPH (10 mg/kg) and TPM (10, 30, 50, 70, and 100 mg/kg), respectively, for 21 days. elevated plus maze (EPM) was used to assess motor activity disturbances. In addition, oxidative, antioxidantand inflammatory factors and CREB, Ak1, CAMK4, MAPK3, PKA, BDNF, and c FOS gene levels were measured by RT-PCR, and also, CREB and BDNF protein levels were measured by WB in isolated amygdalae. MPH significantly disturbed motor activity and TPM (70 and 100 mg/kg) neutralized its effects. MPH significantly increased lipid peroxidation, mitochondrial GSSG levels and IL-1β and TNF-α level and CAMK4 gene expression in isolated amygdala cells. In contrast, superoxide dismutase, glutathione peroxidase, and glutathione reductase activities and CREB, BDNF Ak1, MAPK3, PKA, BDNF, and c FOS expression significantly decreased. The various doses of TPM attenuated these effects of MPH. It seems that TPM can be used as a neuroprotective agent and is a good candidate against MPH-induced neurodegeneration.

Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders.

PubMed

McCracken, J T; Badashova, K K; Posey, D J; Aman, M G; Scahill, L; Tierney, E; Arnold, L E; Vitiello, B; Whelan, F; Chuang, S Z; Davies, M; Shah, B; McDougle, C J; Nurmi, E L

2014-06-01

Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P<0.02), COMT (P<0.04), DRD3 (P<0.05), DRD4 (P<0.05), SLC6A3 (P<0.05) and SLC6A4 (P<0.05) genotypes were found for responders versus non-responders. Variants in DRD2 (P<0.001) and DRD3 (P<0.04) were associated with tolerability in the 14 subjects who discontinued the trial. For this first MPH pharmacogenetic study in children with ASD, multiple monoaminergic gene variants may help explain individual differences in MPH's efficacy and tolerability.

Methylphenidate treatment of attention deficit hyperactivity disorder in young people with learning disability and difficult-to-treat epilepsy: evidence of clinical benefit.

PubMed

Fosi, Tangunu; Lax-Pericall, Maria T; Scott, Rod C; Neville, Brian G; Aylett, Sarah E

2013-12-01

To establish the efficacy and safety of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) in a group of children and young people with learning disability and severe epilepsy. This retrospective study systematically reviewed the case notes of all patients treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center between 1998 and 2005. Treatment efficacy was ascertained using clinical global impressions (CGI) scores, and safety was indexed by instances of >25% increase in monthly seizure count within 3 months of starting MPH. Eighteen (18) patients were identified with refractory epilepsies (14 generalized, 4 focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was diagnosed at a median age of 11.5 years (range 6–18 years). With use of a combination of a behavioral management program and MPH 0.3–1 mg/kg/day, ADHD symptoms improved in 61% of patients (11/18; type A intraclass correlation coefficient of CGI 0.85, 95% confidence interval [CI] 0.69–0.94). Daily MPH dose, epilepsy variables, and psychiatric comorbidity did not relate to treatment response across the sample. MPH adverse effects led to treatment cessation in three patients (dysphoria in two, anxiety in one). There was no statistical evidence for a deterioration of seizure control in this group with the use of MPH. Methylphenidate with behavioral management was associated with benefit in the management of ADHD in more than half of a group of children with severe epilepsy and additional cognitive impairments. Eighteen percent had significant side effects but no attributable increase in seizures. Methylphenidate is useful in this group and is likely to be under employed.

Comparative efficacy and safety of methylphenidate and atomoxetine for attention-deficit hyperactivity disorder in children and adolescents: Meta-analysis based on head-to-head trials.

PubMed

Liu, Qiang; Zhang, Hong; Fang, Qingqing; Qin, Lili

2017-11-01

Comparative efficacy and safety are important issues for appropriate drug selection for attention-deficit hyperactivity disorder (ADHD) treatment. Therefore we conducted a meta-analysis, where we compared atomoxetine (ATX) and methylphenidate (MPH) for ADHD treatment in children and adolescents. Literature retrieval was conducted in relevant databases from their inception to April 2016 to select head-to-head trials that compared ATX and MPH in children and adolescents. Outcomes like response rate, ADHD Rating Scale (ADHD-RS) score, and adverse events were compared between ATX and MPH treatments. The standardized mean difference (SMD) and risk ratio (RR) with their corresponding 95% confidence intervals (CIs) were used as the effect size for continuous data or dichotomous data, respectively. Eleven eligible randomized-controlled trials were included, and two of them were double-blind, while the remaining were open-label. Compared to ATX, MPH showed a higher response rate (RR = 1.14, 95% CI [1. 09, 1.20]), decreased inattention (SMD = -0.13, 95% CI [-0.25, -0.01]) and lower risk of adverse events (drowsiness: RR = 0.17, 95% CI [0.11, 0.26; nausea: RR = 0.49; 95% CI [0.29, 0.85; vomiting: RR = 0.41, 95% CI [0.27, 0.63]). However, MPH presented a higher risk of insomnia than ATX (RR = 2.27, 95% CI [1.63, 3.15], p < .01). Results of the meta-analysis add additional evidence of the effectiveness of both ATX and MPH and suggest that MPH should be a first treatment option in most patients with ADHD.

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats

PubMed Central

Izquierdo, Alicia; Pozos, Hilda; De La Torre, Adrianna; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra

2016-01-01

Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. PMID:27091300

Sex differences, learning flexibility, and striatal dopamine D1 and D2 following adolescent drug exposure in rats.

PubMed

Izquierdo, Alicia; Pozos, Hilda; Torre, Adrianna De La; DeShields, Simone; Cevallos, James; Rodriguez, Jonathan; Stolyarova, Alexandra

2016-07-15

Corticostriatal circuitry supports flexible reward learning and emotional behavior from the critical neurodevelopmental stage of adolescence through adulthood. It is still poorly understood how prescription drug exposure in adolescence may impact these outcomes in the long-term. We studied adolescent methylphenidate (MPH) and fluoxetine (FLX) exposure in rats and their impact on learning and emotion in adulthood. In Experiment 1, male and female rats were administered MPH, FLX, or saline (SAL), and compared with methamphetamine (mAMPH) treatment beginning in postnatal day (PND) 37. The rats were then tested on discrimination and reversal learning in adulthood. In Experiment 2, animals were administered MPH or SAL also beginning in PND 37 and later tested in adulthood for anxiety levels. In Experiment 3, we analyzed striatal dopamine D1 and D2 receptor expression in adulthood following either extensive learning (after Experiment 1) or more brief emotional measures (after Experiment 2). We found sex differences in discrimination learning and attenuated reversal learning after MPH and only sex differences in adulthood anxiety. In learners, there was enhanced striatal D1, but not D2, after either adolescent MPH or mAMPH. Lastly, also in learners, there was a sex x treatment group interaction for D2, but not D1, driven by the MPH-pretreated females, who expressed significantly higher D2 levels compared to SAL. These results show enduring effects of adolescent MPH on reversal learning in rats. Developmental psychostimulant exposure may interact with learning to enhance D1 expression in adulthood, and affect D2 expression in a sex-dependent manner. Copyright © 2016 Elsevier B.V. All rights reserved.

SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A systematic review and meta-analysis.

PubMed

Soleimani, Robabeh; Salehi, Zivar; Soltanipour, Soheil; Hasandokht, Tolou; Jalali, Mir Mohammad

2018-04-01

Methylphenidate (MPH) is the most commonly used treatment for attention-deficit hyperactivity disorder (ADHD) in children. However, the response to MPH is not similar in all patients. This meta-analysis investigated the potential role of SLC6A3 polymorphisms in response to MPH in children with ADHD. Clinical trials or naturalistic studies were selected from electronic databases. A meta-analysis was conducted using a random-effects model. Cohen's d effect size and 95% confidence intervals (CIs) were determined. Sensitivity analysis and meta-regression were performed. Q-statistic and Egger's tests were conducted to evaluate heterogeneity and publication bias, respectively. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to assess the quality of evidence. Sixteen studies with follow-up periods of 1-28 weeks were eligible. The mean treatment acceptability of MPH was 97.2%. In contrast to clinical trials, the meta-analysis of naturalistic studies indicated that children without 10/10 repeat carriers had better response to MPH (Cohen's d: -0.09 and 0.44, respectively). The 9/9 repeat polymorphism had no effect on the response rate (Cohen's d: -0.43). In the meta-regression, a significant association was observed between baseline severity of ADHD, MPH dosage, and combined type of ADHD in some genetic models. Sensitivity analysis indicated the robustness of our findings. No publication bias was observed in our meta-analysis. The GRADE evaluations revealed very low levels of confidence for each outcome of response to MPH. The results of clinical trials and naturalistic studies regarding the effect size between different polymorphisms of SLC6A3 were contradictory. Therefore, further research is recommended. © 2017 Wiley Periodicals, Inc.

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task.

PubMed

Goldstein, Rita Z; Woicik, Patricia A; Maloney, Thomas; Tomasi, Dardo; Alia-Klein, Nelly; Shan, Juntian; Honorio, Jean; Samaras, Dimitris; Wang, Ruiliang; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D

2010-09-21

Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.

Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function)more » in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.« less

Exposure to methylphenidate during peri-adolescence affects endocrine functioning and sexual behavior in female Long-Evans rats.

PubMed

Guarraci, Fay A; Holifield, Caroline; Morales-Valenzuela, Jessica; Greene, Kasera; Brown, Jeanette; Lopez, Rebecca; Crandall, Christina; Gibbs, Nicole; Vela, Rebekah; Delgado, Melissa Y; Frohardt, Russell J

2016-03-01

The present study was designed to test the effects of methylphenidate (MPH) exposure on the maturation of endocrine functioning and sexual behavior. Female rat pups received either MPH (2.0mg/kg, i.p.) or saline twice daily between postnatal days 20-35. This period of exposure represents the time just prior to puberty as well as puberty onset. Approximately five weeks after the last injection of MPH or saline, female subjects were hormone-primed and tested during their first sexual experience. Subjects were given the choice to interact with a sexually active male or a sexually receptive female rat (i.e., the partner-preference test). The partner-preference paradigm allows us to assess multiple aspects of female sexual behavior. MPH exposure during peri-adolescence delayed puberty and, when mated for the first time, affected sexual behavior (e.g., increased time spent with the male stimulus and decreased the likelihood of leaving after mounts) during the test of partner preference. When monitoring estrous cyclicity, female subjects treated with MPH during peri-adolescence frequently experienced irregular estrous cycles. The results of the present study suggest that chronic exposure to a therapeutic dose of MPH around the onset of puberty alters long-term endocrine functioning, but with hormone priming, increases sensitivity to sexual stimuli. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-Melanogenic Activity and Cytotoxicity of Pistacia vera Hull on Human Melanoma SKMEL-3 Cells.

PubMed

Sarkhail, Parisa; Salimi, Mona; Sarkheil, Pantea; Mostafapour Kandelous, Hirsa

2017-07-01

Pistacia vera seed is a common food and medicinal seed in Iran. It's hull (outer skin) as a significant byproduct of pistachio, is traditionally used as tonic, sedative and antidiarrheal and has been shown to be a rich source of antioxidants. The aim of the present study is to evaluate the anti-melanogenic activity of the pistachio hulls in order to discover a new alternative herbal agent to treat skin hyperpigmentation disorders. In this work, antioxidant and anti-tyrosinase activity of MeOH extract from Pistacia vera hull (MPH) were evaluated in vitro, respectively, by DPPH radical scavenging and mushroom tyrosinase activity assays. Then the effect of MPH on the melanin content, cellular tyrosinase activity and cytotoxicity (MTT assay) on human melanoma SKMEL-3 cell were determined followed by 72 h incubation. The results indicated that MPH had valuable DPPH radical scavenging effect and weak anti-tyrosinase activity when compared to the well-known antioxidant (BHT) and tyrosinase inhibitor (kojic acid), respectively. MPH, at a high dose (0.5 mg/mL), showed significant cytotoxic activity (~63%) and strong anti-melanogenic effect (~57%) on SKMEL-3 cells. The effect of MPH in the reduction of melanin content may be related to its cytotoxicity. The results obtained suggest that MPH can be used as an effective agent in the treatment of some skin hyperpigmentation disorders such as melanoma.

The effect of methylphenidate on decision making in patients with borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Gvirts, Hila Z; Lewis, Yael D; Dvora, Shira; Feffer, Kfir; Nitzan, Uriel; Carmel, Ziv; Levkovitz, Yechiel; Maoz, Hagai

2018-07-01

Impaired decision making in patients with borderline personality disorder (BPD) has been reported in several studies. Although methylphenidate (MPH) is known to ameliorate impaired decision making in patients with attention-deficit/hyperactivity disorder (ADHD), it has not yet been examined in patients with BPD. We therefore assessed the efficacy of a single dose of MPH on cognitive functions and decision making in patients with BPD. Twenty-two patients diagnosed with BPD participated in the study. The study was a randomized, double-blind placebo-controlled, random block order cross-over trial. Patients participated in two sessions and performed the Test of Variables of Attention, a digit-span test, and the computerized Iowa Gambling Task, after they had been administered either the MPH or a placebo. ADHD symptoms were assessed using the Adult ADHD Self-Report Scale-18. Lower scores on the inattention symptoms scale were associated with a greater improvement in decision making following the administration of MPH when compared with improvements in patients with higher ADHD scores [F(1,17)=5.63, P=0.030]. We conclude that MPH may improve decision making in patients with BPD, although this effect is mediated by the level of ADHD symptoms. Further studies are needed to assess whether a prolonged beneficial effect of MPH on decision making in patients with BPD might also be present in 'real life'.

Influence of Methylphenidate on the Frequency of Stuttering: A Randomized Controlled Trial.

PubMed

Rabaeys, Henk; Bijleveld, Henny-Annie; Devroey, Dirk

2015-10-01

Recently, a case report described a decrease in frequency of stuttering after intake of methylphenidate (MPH). This study was undertaken to investigate if this effect could again be reproduced in a population of young healthy male adult persons with developmental stuttering. A double-blind randomized crossover trial, with a 2-week washout period, including 15 Dutch-speaking young healthy persons with developmental stuttering, assessed the effects of a single dose of 20 mg MPH compared with placebo on stuttering. Dependent and 1-sample t tests were used to detect significant differences. The end point was the number of stutter moments and self-perceived improvement. MPH yielded a significant decrease in the number of stutter moments when reading and speaking (P = 0.002), which was not the case with placebo (P = 0.090). There was a significant improvement from baseline after intake of MPH as compared with placebo (P = 0.003). Self-perceived improvement with MPH was not significantly better as compared with placebo (P = 0.28). This study showed that the participants had an objective statistically significant decrease in the frequency of stuttering with MPH, and this was not the case with placebo. This was also the case for a reduction in stutter moments when reading out loud and speaking spontaneously. However, this result was not subjectively perceived by the participants. © The Author(s) 2015.

Methylphenidate treatment in children with attention deficit hyperactivity disorder and comorbid social phobia.

PubMed

Golubchik, Pavel; Sever, Jonathan; Weizman, Abraham

2014-07-01

The aim of this study was to assess the response of social phobia (SP) symptoms to methylphenidate (MPH) treatment in children with attention deficit hyperactivity disorder (ADHD). Twenty-one ADHD patients with SP, aged between 8 and 18 years, received 12 weeks of MPH treatment. The severity of SP symptoms were assessed by the Liebowitz Social Anxiety Scale for Children and Adolescents (LSAS-CA), and the severity of ADHD symptoms was assessed by the ADHD Rating Scale at baseline and at endpoint. MPH treatment was associated with a significant decrease in the ADHD Rating Scale scores (P<0.0001) and in the total LSAS-CA scores (P=0.013), as well as the school-related items of LSAS-CA (P=0.011). A significant correlation was found between the reductions in ADHD score and total LSAS-CA score (P=0.038), especially in school-related SP. The improvement in ADHD symptoms because of MPH treatment correlates with a parallel improvement in SP. MPH treatment appears to be safe and effective in ADHD/SP children.

Cytogenetic Effects of Chronic Methylphenidate Treatment and Chronic Social Stress in Adults with Attention-Deficit/Hyperactivity Disorder.

PubMed

Kittel-Schneider, S; Spiegel, S; Renner, T; Romanos, M; Reif, A; Reichert, S; Heupel, J; Schnetzler, L; Stopper, H; Jacob, C

2016-07-01

Methylphenidate (MPH) is widely used to treat childhood and adult attention-deficit/hyperactivity disorder (ADHD). However, there are still safety concerns about side effects in long-term treatment. The aim of this study was to assess cytogenetic effects of chronic MPH treatment in adult ADHD and to find out if chronic social stress is attenuated by medication and to investigate whether chronic psychosocial stress leads to mutagenic effects by itself. Lymphocytes for micronucleus assay and saliva samples for cortisol measurement were collected from adult ADHD patients and healthy controls. Stress exposure of the last 3 months was assessed by TICS (Trier Inventory for Chronic Stress). We could not detect an influence of MPH treatment on cytogenetic markers. ADHD patients displayed significantly higher chronic stress levels measured by TICS compared to healthy controls which were influenced by duration of MPH treatment. ADHD patients also showed significantly lower basal cortisol levels. We could corroborate that there are neither cytogenetic effects of chronic stress nor of chronic MPH intake even after several years of treatment. © Georg Thieme Verlag KG Stuttgart · New York.

Evaluating effects of methylphenidate on brain activity in cocaine addiction: a machine-learning approach

NASA Astrophysics Data System (ADS)

Rish, Irina; Bashivan, Pouya; Cecchi, Guillermo A.; Goldstein, Rita Z.

2016-03-01

The objective of this study is to investigate effects of methylphenidate on brain activity in individuals with cocaine use disorder (CUD) using functional MRI (fMRI). Methylphenidate hydrochloride (MPH) is an indirect dopamine agonist commonly used for treating attention deficit/hyperactivity disorders; it was also shown to have some positive effects on CUD subjects, such as improved stop signal reaction times associated with better control/inhibition,1 as well as normalized task-related brain activity2 and resting-state functional connectivity in specific areas.3 While prior fMRI studies of MPH in CUDs have focused on mass-univariate statistical hypothesis testing, this paper evaluates multivariate, whole-brain effects of MPH as captured by the generalization (prediction) accuracy of different classification techniques applied to features extracted from resting-state functional networks (e.g., node degrees). Our multivariate predictive results based on resting-state data from3 suggest that MPH tends to normalize network properties such as voxel degrees in CUD subjects, thus providing additional evidence for potential benefits of MPH in treating cocaine addiction.

Prediction of High-Grade Vesicoureteral Reflux after Pediatric Urinary Tract Infection: External Validation Study of Procalcitonin-Based Decision Rule

PubMed Central

Leroy, Sandrine; Bouissou, François; Fernandez-Lopez, Anna; Gurgoze, Metin K.; Karavanaki, Kyriaki; Ulinski, Tim; Bressan, Silvia; Vaos, Geogios; Leblond, Pierre; Coulais, Yvon; Cubells, Carlos Luaces; Aygun, A. Denizmen; Stefanidis, Constantinos J.; Bensman, Albert; DaDalt, Liviana; Gardikis, Stefanos; Bigot, Sandra; Gendrel, Dominique; Bréart, Gérard; Chalumeau, Martin

2011-01-01

Background Predicting vesico-ureteral reflux (VUR) ≥3 at the time of the first urinary tract infection (UTI) would make it possible to restrict cystography to high-risk children. We previously derived the following clinical decision rule for that purpose: cystography should be performed in cases with ureteral dilation and a serum procalcitonin level ≥0.17 ng/mL, or without ureteral dilatation when the serum procalcitonin level ≥0.63 ng/mL. The rule yielded a 86% sensitivity with a 46% specificity. We aimed to test its reproducibility. Study Design A secondary analysis of prospective series of children with a first UTI. The rule was applied, and predictive ability was calculated. Results The study included 413 patients (157 boys, VUR ≥3 in 11%) from eight centers in five countries. The rule offered a 46% specificity (95% CI, 41–52), not different from the one in the derivation study. However, the sensitivity significantly decreased to 64% (95%CI, 50–76), leading to a difference of 20% (95%CI, 17–36). In all, 16 (34%) patients among the 47 with VUR ≥3 were misdiagnosed by the rule. This lack of reproducibility might result primarily from a difference between derivation and validation populations regarding inflammatory parameters (CRP, PCT); the validation set samples may have been collected earlier than for the derivation one. Conclusions The rule built to predict VUR ≥3 had a stable specificity (ie. 46%), but a decreased sensitivity (ie. 64%) because of the time variability of PCT measurement. Some refinement may be warranted. PMID:22216314

Grantee Spotlight: Katherine Briant, MPH, CHES

Cancer.gov

Katherine Briant, MPH, CHES, is Community Health Educator in NCI’s National Outreach Network links NCI-supported outreach and community education efforts and cancer health disparities research and training programs.

KSC-04pd1707

NASA Image and Video Library

2004-09-01

KENNEDY SPACE CENTER, FLA. - Workers in the Orbiter Processing Facility unwrap plastic for use in covering equipment as part of preparations for the expected impact of Hurricane Frances on Saturday. Other preparations at KSC include powering down the Space Shuttle orbiters, closing the payload bay doors and stowing the landing gear. Workers are also taking precautions against flooding by moving spacecraft hardware off the ground and sandbagging facilities. The Orbiter Processing Facility is constructed of concrete and steel and was designed to withstand winds of 105 mph. The Vehicle Assembly Building is constructed of concrete and steel and was designed to withstand winds of 125 mph. Other payload and flight hardware support facilities can endure winds of 110 mph. Launch pads and the Payload Hazardous Servicing Facility can withstand 125-mph winds.

The effect of using different competence frameworks to audit the content of a masters program in public health.

PubMed

Harrison, Roger A; Gemmell, Isla; Reed, Katie

2015-01-01

(1) To quantify the effect of using different public health competence frameworks to audit the curriculum of an online distance learning MPH program, and (2) to measure variation in the outcomes of the audit depending on which competence framework is used. Retrospective audit. We compared the teaching content of an online distance learning MPH program against each competence listed in different public health competence frameworks relevant to an MPH. We then compared the number of competences covered in each module in the program's teaching curriculum and in the program overall, for each of the competence frameworks used in this audit. A comprehensive search of the literature identified two competence frameworks specific to MPH programs and two for public health professional/specialty training. The number of individual competences in each framework were 32 for the taught aspects of the UK Faculty of Public Health Specialist Training Program, 117 for the American Association of Public Health, 282 for the exam curriculum of the UK Faculty of Public Health Part A exam, and 393 for the European Core Competencies for MPH Education. This gave a total of 824 competences included in the audit. Overall, the online MPH program covered 88-96% of the competences depending on the specific framework used. This fell when the audit focused on just the three mandatory modules in the program, and the variation between the different competence frameworks was much larger. Using different competence frameworks to audit the curriculum of an MPH program can give different indications of its quality, especially as it fails to capture teaching considered to be relevant, yet not included in an existing competence framework. The strengths and weaknesses of using competence frameworks to audit the content of an MPH program have largely been ignored. These debates are vital given that external organizations responsible for accreditation specify a particular competence framework to be used. Our study found that each of four different competence frameworks suggested different levels of quality in our teaching program, at least in terms of the competences included in the curriculum. Relying on just one established framework missed some aspects of the curriculum included in other frameworks used in this study. Conversely, each framework included items not covered by the others. Thus, levels of agreement with the content of our MPH and established areas of competence were, in part, dependent on the competence framework used to compare its' content. While not entirely a surprising finding, this study makes an important point and makes explicit the challenges of selecting an appropriate competence framework to inform MPH programs, and especially one which recruits students from around the world.

Drug Treatment Patterns of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents in Germany: Results from a Large Population-Based Cohort Study

PubMed Central

Mikolajczyk, Rafael T.; Banaschewski, Tobias; Petermann, Ulrike; Petermann, Franz; Kraut, Angela A.; Langner, Ingo

2012-01-01

Abstract Objective Despite a substantial increase in total methylphenidate (MPH) prescriptions in Germany over the last 20 years, and the introduction of modified release MPH (MR MPH) and atomoxetine (ATX), remarkably little is known about treatment patterns of attention- deficit/hyperactivity disorder (ADHD) in individual patients. Methods Usage patterns of ADHD drugs in children and adolescents in Germany were analyzed using data from one large German health insurance including >7,200,000 members. Of those, 6210 ADHD patients newly diagnosed in 2005 were followed for a maximum of 4 years. Kaplan–Meier estimates were calculated for onset and discontinuation of ADHD drug treatment. Predictors of time until drug treatment initiation were assessed by Cox regression. Results During follow-up, 52.0% of ADHD subjects (53.4% of boys, 47.5% of girls) received ADHD drug treatment. The majority of them (91.6%) were started on MPH, with immediate release MPH (IR MPH) being the initial treatment choice in 75.3%. In these subjects, change to drug treatment with MR MPH in the first year occurred in 48% by switch or addition. Significant predictors of drug treatment were behavioral and emotional disorders (HR=1.13; 95% CI 1.03–1.24) and a diagnosis of ADHD with conduct disorder (HR=1.21, 95% CI 1.12–1.32), whereas young age showed a protective effect. After 6, 12, and 24 months of treatment initiation, 22.4%, 43.4%, and 66.3% of treated girls, and 17.8%, 36.1%, and 54.1% of treated boys had discontinued ADHD treatment. Conclusion Drug treatment of ADHD was relatively common in Germany and more frequent in boys than in girls. IR MPH was the predominant treatment choice at treatment initiation. Approximately 20% of treated subjects discontinued drug treatment within the first 6 months, with girls stopping drug treatment earlier than boys. The reasons for early drug discontinuation need to be further explored. PMID:23234588

Inter- and Intraindividual Variation of Methylphenidate Concentrations in Serum and Saliva of Patients with Attention-Deficit/Hyperactivity Disorder.

PubMed

Preiskorn, Joshua; Studer, Sophie; Rauh, Reinhold; Lukačin, Richard; Geffert, Christoph; Fleischhaker, Christian; Clement, Hans-Willi; Schulz, Eberhard; Biscaldi, Monica

2018-05-03

BackgroundTherapeutic drug monitoring (TDM) is becoming increasingly important in psychiatric therapy; especially in children. However, for several reasons, it cannot yet be implemented as a daily routine in clinical or outpatient settings. To evaluate new, non-invasive procedures; blood and saliva (oral fluid) samples were collected from patients with attention-deficit/hyperactivity disorder (ADHD) who were also being administered methylphenidate (MPH). The study's main purposes were to correlate MPH concentrations in serum and saliva between subjects; and to analyze intraindividual variation of serum concentration.MethodsThirty-six ADHD patients (27 children and 9 adults) on methylphenidate medication were included for drug analysis. MPH and its major metabolite ritalinic acid (RA) were quantified using LC-MS/MS measurements. The following correlations were investigated: 1) between drug concentrations in serum and saliva, and 2) between pH value and saliva to serum concentration ratio. Furthermore, the mean intraindividual MPH-concentration fluctuation in saliva under constant frame conditions was analyzed.ResultsAfter quantification, MPH concentrations were approximately 5 times higher in the saliva than in the serum, while the concentrations of RA were much lower in saliva. We found significant correlations between concentrations of MPH in serum and saliva (r=0.51, p<0.05). Saliva MPH measures, compared to serum, were pH-dependent(r=-0.56, p<0.01). Daily coefficient of variance of saliva concentration in children taking constant medication was 27.3% (11%-42 %), while the coefficient of variance for the ratio of saliva to serum was 122% (2%-2060%).ConclusionsOur data indicates that the interindividual variation in saliva to serum concentrations is rather high, while the intraindividual variation is fairly low, as already shown in the literature for repeated citalopram serum measurements. Saliva may well serve as an alternative matrix for TDM of MPH in ADHD patients, especially for follow-up examinations. Future research should focus on analyzing the relationship between drug levels in saliva and clinical effects; as well as on understanding the mechanisms that generate saliva drug concentrations. These are essential steps prior to potential clinical use.

The effect of economic status on height, insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in healthy Turkish children.

PubMed

Turan, S; Bereket, A; Furman, A; Omar, A; Berber, M; Ozen, A; Akbenlioglu, C; Haklar, G

2007-06-01

The effect of economic status (ES) on growth, insulin-like growth factor (IGF)-I and IGF-binding protein (IGFBP)-3 in healthy children is not well characterized. We aimed to study the interrelationship between height, weight, IGF-I, IGFBP-3, mid-parental height (MPH) and ES. Eight hundred and fourteen healthy children (428 boys, 386 girls; age 3-18 years) were classified according to income of the families as low, middle and high. Standard deviation scores (SDSs) of height, weight, MPH, IGF-I and IGFBP-3 were compared between the groups. The combined effect of these parameters and ES on height SDS was investigated with complex statistical models. There was a significant trend for height and weight SDSs to increase with higher income levels in boys, but not in girls. Body mass index (BMI) SDSs were similar in three groups. There was a general trend for MPH SDS to increase with income levels in both sexes. In boys, IGF-I SDS was significantly higher in high ES group than low ES. In girls, IGFBP-3 SDSs were significantly higher in high ES group than in middle ES group. For both genders, height SDS was highly correlated with weight SDS and moderately correlated with BMI SDS, MPH SDS and IGF-1 SDS. All correlations were significant and positive. Complex models showed that MPH (19%), IGF-I (13%) and ES (3%) in boys, and MPH (16%) and IGF-I (7%) in girls have significant contribution to height SDSs. ES per se, independent of overt malnutrition, affects height, weight, IGF-I and IGFBP-3 with some gender differences in healthy children. Influence of income on height and weight show sexual dimorphism, a slight but significant effect is observed only in boys. MPH is the most prominent variable effecting height in healthy children. Higher height and MPH SDSs observed in higher income groups suggest that secular trend in growth still exists, at least in boys, in a country of favorable economic development.

Efficacy, Safety, and Tolerability of an Extended-Release Orally Disintegrating Methylphenidate Tablet in Children 6-12 Years of Age with Attention-Deficit/Hyperactivity Disorder in the Laboratory Classroom Setting.

PubMed

Childress, Ann C; Kollins, Scott H; Cutler, Andrew J; Marraffino, Andrea; Sikes, Carolyn R

2017-02-01

Methylphenidate extended-release orally disintegrating tablets (MPH XR-ODTs) represent a new technology for MPH delivery. ODTs disintegrate in the mouth without water and provide a pharmacokinetic profile that is consistent with once-daily dosing. This study sought to determine the efficacy, safety, and tolerability of this novel MPH XR-ODT formulation in school-age children with attention-deficit/hyperactivity disorder (ADHD) in a laboratory classroom setting. Children aged 6-12 years with ADHD (n = 87) were enrolled in this randomized, multicenter, double-blind, placebo-controlled, parallel, laboratory classroom study. The MPH XR-ODT dose was titrated to an optimized dose during a 4-week open-label period and maintained on that dose for 1 week. Participants (n = 85) were then randomized to receive their optimized dose of MPH XR-ODT or placebo once daily for 1 week (double blind), culminating in a laboratory classroom testing day. Efficacy was evaluated using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Attention, Deportment, and Combined scores along with Permanent Product Measure of Performance (PERMP; Attempted and Correct) assessments. Onset and duration of drug action were also evaluated as key secondary endpoints. Safety assessments included adverse events (AEs), physical examinations, electrocardiograms (ECGs), and the Columbia Suicide Severity Rating Scale (C-SSRS). The average SKAMP-Combined score on the classroom study day was significantly better for the MPH XR-ODT group (n = 43) than for the placebo group (n = 39; p < 0.0001). The effect was evident at 1 hour and lasted through 12 hours postdose. The average SKAMP-Attention, SKAMP-Deportment, PERMP-A, and PERMP-C scores were indicative of significantly greater ADHD symptom control for the MPH XR-ODT group. The most common AEs reported were decreased appetite, upper abdominal pain, headache, insomnia, upper respiratory tract infection, affect lability, irritability, cough, and vomiting. MPH XR-ODT was effective and well tolerated for the treatment of children with ADHD in a laboratory classroom setting. Clinical Trial Registry: NCT01835548 ( ClinicalTrials.gov ).

Cancer Data and Statistics Tools

MedlinePlus

... Joseph Jacqueline W. Miller Mona Saraiya Judith Lee Smith Sherri L. Stewart Mary C. White Debra Younginer ... MD, MPH Simple Singh, MD, MPH Judith Lee Smith, PhD Sherri L. Stewart, PhD Eric Tai, MD, ...

Ashley Felix, Ph.D., M.P.H.

Cancer.gov

NCI Cancer Prevention Fellowship Program (CPFP) alumna, Ashley Felix, Ph.D., M.P.H., details her transition from pre-med student to an epidemiologist who focuses on studying the causes and prevention of disease.

Assessing the interplay between the shoulders and low back during manual patient handling techniques in a nursing setting.

PubMed

Belbeck, Alicia; Cudlip, Alan C; Dickerson, Clark R

2014-01-01

The purpose of this research was to quantify shoulder demands during freestyle manual patient handling (MPH) tasks and determine whether approaches intended to prevent low back injury increased shoulder demands. Twenty females completed 5 MPH tasks found commonly in hospital settings before and after a training session using current workplace MPH guidelines. Most normalized muscle activity indices and ratings of perceived exertion decreased following training at both the low back and shoulders, but were more pronounced at the low back. There was little evidence to suggest that mechanical demands were transferred from the low back to the shoulders following the training session. The study generally supports continued use of the recommended MPH techniques, but indicates that several tasks generate high muscular demands and should be avoided if possible.

Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants

PubMed Central

Stage, C; Bergmann, TK; Ferrero‐Milliani, L; Bjerre, D; Thomsen, R; Dalhoff, KP; Rasmussen, HB; Jürgens, G

2016-01-01

The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d‐MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two‐compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d‐MPH plasma exposure. PMID:27754602

The Africanization of poverty: a retrospective on "Make Poverty History".

PubMed

Harrison, Graham

2010-01-01

This article explores the ways in which the British campaign coalition Make Poverty History represented Africa throughout 2005. Focusing particularly on the G8 Gleneagles summit, Make Poverty History (MPH) asserted a series of justice claims which had no geographical reference. Nevertheless, as a result of internal tensions within the coalition, and especially as a result of the ways in which MPH interacted with other political agencies as the summit approached, MPH's messages became increasingly interpolated by references to Africa as a result of the emergence of government, media, and celebrity involvement. The result of this was that global poverty increasingly became an African issue. As 2005 became the "Year of Africa," the justice messages that constituted MPH were largely effaced by the more familiar imperial legacy which represents Africa as a place of indigence in need of outside assistance.

Methylphenidate Induced Lip and Tongue Biting.

PubMed

Gokcen, Cem; Karadag, Mehmet; Aksoy, Ihsan

2018-05-31

Attention deficit hyperactivity disorder (ADHD) is a life-long neurodevelopmental disorder and treatment depends on pharmacotherapy because of its biological origin. Stimulant drugs are the most commonly used treatment for ADHD and they have various side effects. Herein, we report a case who bit off the tip of her tongue with Osmotic Release Oral System methylphenidate (OROS MPH) 36 mg/day, bit the tip of her lower lip with immediate release (IR) MPH 10 mg/day and lateral part of her tongue with IR MPH 20 mg/day. A diagnosis of epilepsy was unlikely because of the normal neurological examination and electroencephalography findings. This case was considered as an atypical side effect of MPH such as perseverative/compulsive behaviours and movement disorders. Clinicians should be aware of that stimulant medications may cause lip and tongue biting behavior and this may effect treatment compliance tremendously.

Molecular imaging genetics of methylphenidate response in ADHD and substance use comorbidity.

PubMed

Szobot, Claudia M; Roman, Tatiana; Hutz, Mara H; Genro, Júlia P; Shih, Ming Chi; Hoexter, Marcelo Q; Júnior, Neivo; Pechansky, Flávio; Bressan, Rodrigo A; Rohde, Luis A P

2011-02-01

Attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. The goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs. Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc(99m) ]TRODAT-1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype. The combination of both DRD4 7-repeat allele (7R) and homozygosity for the DAT1 10-repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P ≤ 0.02; R² from 0.50 to 0.56). In patients with ADHD/SUDs, combined DRD4 7R and DAT1 10/10 could index MPH reduced DAT occupancy. This might be important for clinical trials, in terms of better understanding individual variability in treatment response. Copyright © 2010 Wiley-Liss, Inc.

The role of gender in MPH graduates' salaries.

PubMed

Bradley, E H; White, W; Anderson, E; Mattocks, K; Pistell, A

2000-01-01

Several studies have demonstrated that workforce roles and salaries differ substantially between men and women in administrative positions within the health care industry. Recent studies of graduates with masters of business administration (MBA) and masters of health administration (MHA) degrees have indicated that women tend to experience lower salaries, given like responsibilities. However, the impact of gender on salary has been less studied among masters of public health (MPH) graduates in the health care field. Our objective was to assess the impact of gender on salary among MPH degree graduates. Using a cross-sectional survey of all graduates from the MPH program at Yale University between 1991-1997 (n = 201, response rate = 51%), we ascertained graduates' reported salary in the first job post-graduation and reported salary in their current position. Bivariate and multivariate analyses were used to assess the unadjusted and adjusted associations between gender and salary. Salaries in both the first job post-graduation and in the current job differed significantly by gender, with women earning less than men (p-values < .05). Moreover, these differences persisted after controlling for a set of human capital measures including pre-MPH work experience, age at graduation, years since graduation, area of specialization within the MPH degree, and type of work site (governmental or nonprofit versus for-profit). Unlike studies of MBA and MHA graduates, however, this study did not find evidence that the gender-related salary gap widened as the years since graduation increased, although the sample size did not allow comprehensive testing of this trend.

The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design.

PubMed

Bottelier, Marco A; Schouw, Marieke L J; Klomp, Anne; Tamminga, Hyke G H; Schrantee, Anouk G M; Bouziane, Cheima; de Ruiter, Michiel B; Boer, Frits; Ruhé, Henricus G; Denys, Damiaan; Rijsman, Roselyne; Lindauer, Ramon J L; Reitsma, Hans B; Geurts, Hilde M; Reneman, Liesbeth

2014-02-19

Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of different approaches to determine whether there are related findings in humans. Animal studies were carried out to investigate age-related effects of psychotropic drugs and to validate new neuroimaging techniques. In addition, we set up two double-blind placebo controlled clinical trials with MPH in 50 boys (10-12 years) and 50 young men (23-40 years) suffering from ADHD (ePOD-MPH) and with FLX in 40 girls (12-14 years) and 40 young women (23-40 years) suffering from depression and anxiety disorders (ePOD-SSRI). Trial registration numbers are: Nederlands Trial Register NTR3103 and NTR2111. A cross-sectional cohort study on age-related effects of these psychotropic medications in patients who have been treated previously with MPH or FLX (ePOD-Pharmo) is also ongoing. The effects of psychotropic drugs on the developing brain are studied using neuroimaging techniques together with neuropsychological and psychiatric assessments of cognition, behavior and emotion. All assessments take place before, during (only in case of MPH) and after chronic treatment. The combined results of these approaches will provide new insight into the modulating effect of MPH and FLX on brain development.

The effects of Psychotropic drugs On Developing brain (ePOD) study: methods and design

PubMed Central

2014-01-01

Background Animal studies have shown that methylphenidate (MPH) and fluoxetine (FLX) have different effects on dopaminergic and serotonergic system in the developing brain compared to the developed brain. The effects of Psychotropic drugs On the Developing brain (ePOD) study is a combination of different approaches to determine whether there are related findings in humans. Methods/Design Animal studies were carried out to investigate age-related effects of psychotropic drugs and to validate new neuroimaging techniques. In addition, we set up two double-blind placebo controlled clinical trials with MPH in 50 boys (10–12 years) and 50 young men (23–40 years) suffering from ADHD (ePOD-MPH) and with FLX in 40 girls (12–14 years) and 40 young women (23–40 years) suffering from depression and anxiety disorders (ePOD-SSRI). Trial registration numbers are: Nederlands Trial Register NTR3103 and NTR2111. A cross-sectional cohort study on age-related effects of these psychotropic medications in patients who have been treated previously with MPH or FLX (ePOD-Pharmo) is also ongoing. The effects of psychotropic drugs on the developing brain are studied using neuroimaging techniques together with neuropsychological and psychiatric assessments of cognition, behavior and emotion. All assessments take place before, during (only in case of MPH) and after chronic treatment. Discussion The combined results of these approaches will provide new insight into the modulating effect of MPH and FLX on brain development. PMID:24552282

Methylphenidate-induced improvements of various measures of attention in adults with attention deficit hyperactivity disorder.

PubMed

Tucha, O; Mecklinger, L; Laufkötter, R; Klein, H E; Walitza, S; Lange, K W

2006-10-01

The present study examined the effect of the stimulant medication methylphenidate (MPH) on attentional functioning of adults with ADHD. Sixteen adults with a diagnosed ADHD without comorbidity were assessed twice, at baseline off MPH and following MPH treatment. The assessment battery consisted of reaction time tasks of low complexity, including measures of alertness--subdivided into tonic and phasic alertness, vigilance, divided attention, flexibility and such aspects of selective attention as including focused attention, inhibition and integration of sensory information. In addition, 16 healthy participants who were matched to adults with ADHD according to sex, age, education level and intellectual functions were also assessed twice using the same test battery. The results of the present study suggest that adults with ADHD off stimulant medication are seriously impaired in various components of attention including vigilance, divided attention, selective attention and flexibility. These impairments of attention were observed primarily in regard to reaction time and its variability. Treatment of adults with ADHD using individually tailored doses of MPH has a positive effect on measures of alertness, vigilance, selective attention, divided attention and flexibility. However, even on MPH adults with ADHD displayed considerable deficits in vigilance and integration of sensory information. The present findings indicate that adults with ADHD are not differentially impaired in attentional processes but may suffer from a more global deficit of attention. Although MPH treatment has been found to be effective in the treatment of the attention deficit of adults with ADHD, additional treatment appears to be necessary.

Exploring longitudinal course and treatment-baseline severity interactions in secondary outcomes of smoking cessation treatment in individuals with attention-deficit hyperactivity disorder.

PubMed

Luo, Sean X; Wall, Melanie; Covey, Lirio; Hu, Mei-Chen; Scodes, Jennifer M; Levin, Frances R; Nunes, Edward V; Winhusen, Theresa

2018-01-25

A double blind, placebo-controlled randomized trial (NCT00253747) evaluating osmotic-release oral system methylphenidate (OROS-MPH) for smoking-cessation revealed a significant interaction effect in which participants with higher baseline ADHD severity had better abstinence outcomes with OROS-MPH while participants with lower baseline ADHD severity had worse outcomes. This current report examines secondary outcomes that might bear on the mechanism for this differential treatment effect. Longitudinal analyses were conducted to evaluate the effect of OROS-MPH on three secondary outcomes (ADHD symptom severity, nicotine craving, and withdrawal) in the total sample (N = 255, 56% Male), and in the high (N = 134) and low (N = 121) baseline ADHD severity groups. OROS-MPH significantly improved ADHD symptoms and nicotine withdrawal symptoms in the total sample, and exploratory analyses showed that in both higher and lower baseline severity groups, OROS-MPH statistically significantly improved these two outcomes. No effect on craving overall was detected, though exploratory analyses showed statistically significantly decreased craving in the high ADHD severity participants on OROS-MPH. No treatment by ADHD baseline severity interaction was detected for the outcomes. Methylphenidate improved secondary outcomes during smoking cessation independent of baseline ADHD severity, with no evident treatment-baseline severity interaction. Our results suggest divergent responses to smoking cessation treatment in the higher and lower severity groups cannot be explained by concordant divergence in craving, withdrawal and ADHD symptom severity, and alternative hypotheses may need to be identified.

COMPARING STIMULANT EFFECTS IN YOUTH WITH ADHD SYMPTOMS AND EPILEPSY

PubMed Central

Gonzalez-Heydrich, Joseph; Hsin, Olivia; Gumlak, Sarah; Kimball, Kara; Rober, Ashley; Azeem, Muhammad W.; Hickory, Meredith; Mrakotsky, Christine; Torres, Alcy; Mezzacappa, Enrico; Bourgeois, Blaise; Biederman, Joseph

2014-01-01

To retrospectively examine response to stimulant treatment in patients with epilepsy and ADHD symptoms as predicted by seizure freedom for six months, use of methylphenidate (MPH) versus amphetamine (AMP) preparations, and cognitive level, medical records were searched for patients under age 18 with epilepsy and ADHD symptoms treated with MPH or AMP (n = 36, age 10.4±3.5; 67% male). “Responders” had a CGI-Improvement score of ≤2 and did not stop medication due to adverse effects. “Worsened” patients discontinued medication due to agitation/emotional lability. Seizure freedom did not predict treatment response. Lower cognitive level was associated with increased rate of worsening (p=0.048). No patients who were seizure-free at start of the medication trial experienced an increase in seizures. Of the patients having seizures at the start of trial, one patient on MPH and two on AMP had increased seizures during the trial. Seizures returned to baseline frequency or less after stimulant discontinuation or anticonvulsant adjustment. MPH was associated with a higher response rate, with 12 of 19 given MPH 0.62±0.28mg/kg/day compared to 4 of 17 given AMP 0.37±0.26mg/kg/day responding (p=0.03). MPH treatment and higher cognitive level were associated with improved treatment outcome while seizure freedom had no clear effect. Confidence in these findings is limited by the study’s small, open label, and uncontrolled nature. PMID:24907495

The role of Homer 1a in increasing locomotor activity and non-selective attention, and impairing learning and memory abilities.

PubMed

Yang, Lei; Hong, Qin; Zhang, Min; Liu, Xiao; Pan, Xiao-Qin; Guo, Mei; Fei, Li; Guo, Xi-Rong; Tong, Mei-Ling; Chi, Xia

2013-06-17

The current study aimed to investigate the possible role of Homer 1a in the etiology and pathogenesis of attention deficit hyperactivity disorder (ADHD). We divided 32 rats into four groups. The rats in the RNAi-MPH group were given the lentiviral vector containing Homer 1a-specific miRNA (Homer 1a-RNAi-LV) by intracerebroventricular injection, and 7 days later they were given three daily doses of methylphenidate (MPH) by intragastric gavage. The RNAi-SAL group was given Homer 1a-RNAi-LV and saline later. The NC-MPH group was given the negative control lentiviral vector (NC-LV) and MPH later. The NC-SAL group was given NC-LV and saline later. Rats that were given Homer 1a RNAi exhibited increased locomotor activity and non-selective attention, and impaired learning and memory abilities, which is in line with the behavioral findings of animal models of ADHD. However, MPH ameliorated these abnormal behaviors. All findings indicated that Homer 1a may play an important role in the etiology and pathogenesis of ADHD. Copyright © 2013 Elsevier B.V. All rights reserved.

An evaluation of the pharmacokinetics of methylphenidate for the treatment of attention-deficit/ hyperactivity disorder.

PubMed

Frölich, Jan; Banaschewski, Tobias; Döpfner, Manfred; Görtz-Dorten, Anja

2014-08-01

Methylphenidate (MPH) plays a principal role in the multimodal treatment of attention-deficit/hyperactivity disorder (ADHD). Controlled studies have demonstrated an effective reduction in the core symptoms of the disorder following MPH therapy, although long-term studies also demonstrate that the therapeutic benefits dissipate in the absence of combined psychosocial interventions. This review article focuses on the pharmacological characteristics of MPH, examining its effects on brain metabolism and the neurotransmitter system. Neuropsychological and clinical effects of different immediate and extended release MPH formulations are discussed to aid clinicians in choosing the appropriate formulation. The drug's addictive potency and abuse potential is also discussed. Data came from a literature search of relevant studies performed using the PubMed database up to June 2013. MPH is effective in the treatment of the core symptoms of ADHD. Considerable clinical expertise is required to identify an individually well-adapted dosage which will produce the optimal clinical effects with potential side effects minimized. Due to low adherence to medication, especially in adolescents, motivation to treatment and attentive clinical monitoring is mandatory, as is the consideration of risks of abuse or the presence of a comorbid addictive disorder.

Factors influencing publication of scientific articles derived from masters theses in public health.

PubMed

Hollmann, Malen; Borrell, Carme; Garin, Olatz; Fernández, Esteve; Alonso, Jordi

2015-05-01

To evaluate theses of a Masters program in Public Health (MPH), in terms of the students' and theses' characteristics that influence publication of the thesis as a scientific article. Longitudinal study of students who successfully completed the MPH at Universitat Pompeu Fabra and Universitat Autònoma de Barcelona (Spain) from 2006 to 2010. Participants completed an electronic survey and additional data were gathered from university files. 162 students participated in the study (83 % response rate). 60.5 % had already published an article derived from their thesis at the time of the study or were in process of publishing it. The likelihood of publishing in a peer-reviewed journal was greater among women (aRR = 1.41), among those who had a bachelor's degree in sciences other than health (aRR = 1.40), had completed the MPH on time (aRR = 2.10), had enrolled in a doctoral program after the MPH (aRR = 1.44) or had a masters thesis score of ≥7 (aRR = 1.61). The majority of MPH students published their thesis in a peer-reviewed journal. The strongest predictors of successful publication were related to academic performance.

The Possible Effect of Methylphenidate Treatment on Empathy in Children Diagnosed with Attention-Deficit/Hyperactivity Disorder, Both With and Without Comorbid Oppositional Defiant Disorder.

PubMed

Golubchik, Pavel; Weizman, Abraham

2017-06-01

To assess the Empathizing Quotient (EQ) of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD) only or comorbid with oppositional defiant disorder (ODD) and compare the two groups' responses to methylphenidate (MPH) treatment. Fifty-two children (8-18 years) diagnosed with ADHD, 26 of whom were also diagnosed with comorbid ODD (ADHD/ODD), were treated with MPH for 12 weeks. The level of EQ was assessed with the Children's version of the Empathizing Quotient (EQ-C) and the severity of ADHD symptoms with the ADHD Rating Scale (ADHD-RS). Assessments were done at baseline and at end point. A significant increase in EQ scores was obtained in both groups following MPH treatment (p = 0.003 for ADHD/ODD; p = 0.002 for ADHD). Significant correlation was found in the ADHD group between the changes in ADHD-RS and those in EQ, following MPH treatment (p = 0.015), but not in the ADHD/ODD group (p = 0.48). A correlation exists between MPH-related improvement in ADHD symptoms and between more empathy in children with ADHD not comorbid with ODD.

Methylphenidate treatment of attention deficit hyperactivity disorder in young people with learning disability and difficult-to-treat epilepsy: Evidence of clinical benefit

PubMed Central

Fosi, Tangunu; Lax-Pericall, Maria T; Scott, Rod C; Neville, Brian G; Aylett, Sarah E

2013-01-01

Purpose To establish the efficacy and safety of methylphenidate (MPH) treatment for attention deficit hyperactivity disorder (ADHD) in a group of children and young people with learning disability and severe epilepsy. Methods This retrospective study systematically reviewed the case notes of all patients treated with methylphenidate (MPH) for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) ADHD at a specialist epilepsy center between 1998 and 2005. Treatment efficacy was ascertained using clinical global impressions (CGI) scores, and safety was indexed by instances of >25% increase in monthly seizure count within 3 months of starting MPH. Key Findings Eighteen (18) patients were identified with refractory epilepsies (14 generalized, 4 focal), IQ <70, and ADHD. Male patients predominated (13:5) and ADHD was diagnosed at a median age of 11.5 years (range 6–18 years). With use of a combination of a behavioral management program and MPH 0.3–1 mg/kg/day, ADHD symptoms improved in 61% of patients (11/18; type A intraclass correlation coefficient of CGI 0.85, 95% confidence interval [CI] 0.69–0.94). Daily MPH dose, epilepsy variables, and psychiatric comorbidity did not relate to treatment response across the sample. MPH adverse effects led to treatment cessation in three patients (dysphoria in two, anxiety in one). There was no statistical evidence for a deterioration of seizure control in this group with the use of MPH. Significance Methylphenidate with behavioral management was associated with benefit in the management of ADHD in more than half of a group of children with severe epilepsy and additional cognitive impairments. Eighteen percent had significant side effects but no attributable increase in seizures. Methylphenidate is useful in this group and is likely to be under employed. PMID:24304474

Comparative treatment patterns, healthcare resource utilization and costs of atomoxetine and long-acting methylphenidate among children and adolescents with attention-deficit/hyperactivity disorder in Germany.

PubMed

Greven, Peter; Sikirica, Vanja; Chen, Yaozhu J; Curtice, Tammy G; Makin, Charles

2017-09-01

Attention-deficit/hyperactivity disorder (ADHD) imposes a substantial burden on patients and their families. A retrospective, propensity score-matched cohort study compared treatment patterns, healthcare resource utilization (HRU) and costs among children/adolescents with ADHD aged 6-17 years at treatment initiation (index) in Germany who received atomoxetine (ATX) or long-acting methylphenidate (LA-MPH) monotherapy. Patients received at least one prescription for their index medication (ATX/LA-MPH) during 2006-2010; the first prescription marked the index date. ATX- and LA-MPH-indexed cohorts were matched 1:1 (n = 737); a patient subset was identified that had not received ADHD-indicated medications in 12 months prior to index (novel initiators: ATX, n = 486; LA-MPH, n = 488). Treatment patterns were evaluated among novel initiators, and HRU and costs among the matched cohorts in the 12 months after index. No significant differences in baseline characteristics were found between the novel initiator patient subsets. ATX-indexed novel initiators had significantly longer persistence to index medication [mean (standard deviation; SD) days: 222.0 (133.9) vs 203.2 (135.0), P = 0.029) but higher switching rates (8.8 vs 5.5 %, P = 0.045) than LA-MPH-indexed novel initiators. The total ATX-indexed cohort required more prescriptions [any medication; mean (SD): 20.9 (11.5) vs 15.7 (9.0), P < 0.001] and outpatient visits [mean (SD): 10.1 (6.3) vs 8.3 (5.3), P < 0.001], and incurred significantly higher total median healthcare costs (€1144 vs €541, P < 0.001) versus matched LA-MPH patients. These real-world data indicate that, among children/adolescents with ADHD in Germany, ATX-indexed patients may require more prescriptions and physician visits, and incur higher total healthcare costs, than matched LA-MPH patients.

Alumni survey of Masters of Public Health (MPH) training at the Hanoi School of Public Health

PubMed Central

Le, Linh Cu; Bui, Quyen Tu; Nguyen, Ha Thanh; Rotem, Arie

2007-01-01

Background 1) To elicit the opinions of the Public Health alumni of the MPH program; 2) To assess the applicability of the knowledge and skills acquired; 3) To identify the frequency of the public health competencies that the alumni performed. Methods We requested 187 graduates to complete a self-administered questionnaire and conducted in-depth interviews with 8 alumni as well as a focus group discussion with 14 alumni. Results In total 79.1% (148) of the MPH graduates completed and returned the questionnaire. Most alumni (91%) agreed that the MPH curriculum corresponded with the working requirements of public health professionals; and nearly all were satisfied with what they have learnt (96%). Most respondents said that the MPH program enabled them to develop relevant professional skills (95%) and that they were satisfied with the curriculum (90%). Notably fewer respondents (73%) felt that the MPH program structure was balanced and well designed. Most alumni (64.3%) were satisfied with Hanoi School of Public Health (HSPH) full-time lecturers; but even more (83%) were satisfied with visiting lecturers. The most commonly selected of the 34 pre-identified public health competencies were: applying computer skills (66.4%), planning and managing health programs (47.9%), communicating with the community and/or mobilizing the community to participate in health care (43.2%). Overall, the MPH alumni felt that HSPH emphasized research methods at the expense of some management and operational competencies. The most important challenges at work identified by the alumni were insufficient skills in: data analysis, decision making, inter-sectoral cooperation development, English language and training. Conclusion The training program should be reviewed and revised to meet the needs of its graduates who enter diverse situations and positions. English language skills were identified as top priority for further emphasis. The training program should comply with a more advanced accreditation system and standards. PMID:17949491

The Mixed Opioid Receptor Antagonist Naltrexone Mitigates Stimulant-Induced Euphoria: A Double-Blind, Placebo-Controlled Trial of Naltrexone.

PubMed

Spencer, Thomas J; Bhide, Pradeep; Zhu, Jinmin; Faraone, Stephen V; Fitzgerald, Maura; Yule, Amy M; Uchida, Mai; Spencer, Andrea E; Hall, Anna M; Koster, Ariana J; Feinberg, Leah; Kassabian, Sarah; Storch, Barbara; Biederman, Joseph

Supratherapeutic doses of methylphenidate activate μ-opioid receptors, which are linked to euphoria. This study assessed whether naltrexone, a mixed μ-opioid antagonist, may attenuate the euphoric effects of stimulants, thereby minimizing their abuse potential in subjects with attention-deficit/hyperactivity disorder (ADHD). We conducted a 6-week, double-blind, placebo-controlled, randomized clinical trial of naltrexone in adults with DSM-IV ADHD receiving open treatment with a long-acting formulation of methylphenidate (January 2013 to June 2015). Spheroidal Oral Drug Absorption System methylphenidate (SODAS-MPH) was administered twice daily, was titrated to ~1 mg/kg/d over 3 weeks, and was continued for 3 additional weeks depending on response and adverse effects. Subjects were adults with ADHD preselected for having experienced euphoria with an oral test dose of 60 mg of immediate-release methylphenidate (IR-MPH). The primary outcome measure was Question 2 (Liking a Drug Effect) on the Drug Rating Questionnaire, Subject version, which was assessed after oral test doses of 60 mg of IR-MPH were administered after the third and sixth weeks of treatment with SODAS-MPH. Thirty-seven subjects who experienced stimulant-induced (mild) euphoria at a baseline visit were started in the open trial of SODAS-MPH and randomized to naltrexone 50 mg/d or placebo. Thirty-one subjects completed through week 3, and 25 completed through week 6. Naltrexone significantly diminished the euphoric effect of IR-MPH during the heightened-risk titration phase (primary outcome; first 3 weeks) (χ² = 5.07, P = .02) but not the maintenance phase (weeks 4-6) (χ² = 0.22, P = .64) of SODAS-MPH treatment. Preclinical findings are extended to humans showing that naltrexone may mitigate stimulant-associated euphoria. Our findings provide support for further studies combining opioid receptor antagonists with stimulants to reduce abuse potential. ClinicalTrials.gov identifier: NCT01673594. © Copyright 2018 Physicians Postgraduate Press, Inc.

76 FR 62423 - National Institute on Deafness and Other Communication Disorders; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-07

...., Rockville, MD 20852, (Telephone Conference Call). Contact Person: Melissa Stick, PhD, MPH, Chief, Scientific...., Rockville, MD 20852, (Telephone Conference Call). Contact Person: Melissa Stick, PhD, MPH, Chief, Scientific...

Acute Effects of MPH on the Parent-Teen Interactions of Adolescents With ADHD.

PubMed

Pelham, William E; Meichenbaum, David L; Smith, Bradley H; Sibley, Margaret H; Gnagy, Elizabeth M; Bukstein, Oscar

2017-01-01

This study explored the nature of interactions between adolescent males with ADHD and their mothers, and the effects of methylphenidate (MPH) on an analogue parent-teen interaction task. Twenty-five adolescent males with ADHD ( M = 13.6 years) and their mothers and 14 non-ADHD adolescent males ( M = 13.4 years) and their mothers completed ratings of perceived dyadic conflict. Behavioral observations of dyads during 10-min conflict-resolution tasks were also collected. The ADHD dyads completed these tasks twice, with adolescents receiving either 0.3 mg/kg MPH or placebo. Videotaped sessions were coded using the Parent-Adolescent Interaction Rating Scale. Following the conflict-resolution task, participants rated their perceived conflict and affect during the interaction. Findings indicated higher conflict in the ADHD dyads, and minimal MPH effects on parent-teen interactions during the analogue task. Results suggest that stimulant medication does not produce meaningful acute effects on parent-teen interactions.

Music and video as distractors for boys with ADHD in the classroom: comparison with controls, individual differences, and medication effects.

PubMed

Pelham, William E; Waschbusch, Daniel A; Hoza, Betsy; Gnagy, Elizabeth M; Greiner, Andrew R; Sams, Susan E; Vallano, Gary; Majumdar, Antara; Carter, Randy L

2011-11-01

This study examined the effects of music and video on the classroom behavior and performance of boys with and without attention deficit hyperactivity disorder (ADHD) and examined the effects of 0.3 mg/kg methylphenidate (MPH). In one study, 41 boys with ADHD and 26 controls worked in the presence of no distractor, music, or video. Video produced significant distraction, particularly for the boys with ADHD, and MPH improved the performance of boys with ADHD across distractor conditions.There were individual differences in response to the music such that some boys were adversely affected and others benefited relative to no-distractor.In a second study, music and MPH were assessed in an additional 86 boys with ADHD to examine further the music results. In the presence or absence of music, MPH improved performance relative to placebo. Similar individual differences were found as in Experiment 1.

KSC-06pd1980

NASA Image and Video Library

2006-08-29

KENNEDY SPACE CENTER, FLA. - A serene scene surrounds Space Shuttle Atlantis as it begins rolling off Launch Pad 39B to return to the Vehicle Assembly Building. First motion off the pad was at 10:04 a.m. EDT. The crawler is 131 feet long, 113 feet wide and 20 feet high. It weights 5.5 million pounds unloaded. The combined weight of crawler, mobile launcher platform and a space shuttle is 12 million pounds. Unloaded, the crawler moves at 2 mph. Loaded, the snail's pace slows to 1 mph. The rollback is a safety precaution as the area waits for the arrival of Tropical Storm Ernesto. The storm is forecast to be bringing 58-mph to 70-mph winds in the next 24 hours. The shuttle will be moved into high bay 2, on the southwest side of the VAB, for protection from the storm. Photo credit: NASA/Ken Thornsley

Artificial neural network, genetic algorithm, and logistic regression applications for predicting renal colic in emergency settings.

PubMed

Eken, Cenker; Bilge, Ugur; Kartal, Mutlu; Eray, Oktay

2009-06-03

Logistic regression is the most common statistical model for processing multivariate data in the medical literature. Artificial intelligence models like an artificial neural network (ANN) and genetic algorithm (GA) may also be useful to interpret medical data. The purpose of this study was to perform artificial intelligence models on a medical data sheet and compare to logistic regression. ANN, GA, and logistic regression analysis were carried out on a data sheet of a previously published article regarding patients presenting to an emergency department with flank pain suspicious for renal colic. The study population was composed of 227 patients: 176 patients had a diagnosis of urinary stone, while 51 ultimately had no calculus. The GA found two decision rules in predicting urinary stones. Rule 1 consisted of being male, pain not spreading to back, and no fever. In rule 2, pelvicaliceal dilatation on bedside ultrasonography replaced no fever. ANN, GA rule 1, GA rule 2, and logistic regression had a sensitivity of 94.9, 67.6, 56.8, and 95.5%, a specificity of 78.4, 76.47, 86.3, and 47.1%, a positive likelihood ratio of 4.4, 2.9, 4.1, and 1.8, and a negative likelihood ratio of 0.06, 0.42, 0.5, and 0.09, respectively. The area under the curve was found to be 0.867, 0.720, 0.715, and 0.713 for all applications, respectively. Data mining techniques such as ANN and GA can be used for predicting renal colic in emergency settings and to constitute clinical decision rules. They may be an alternative to conventional multivariate analysis applications used in biostatistics.

Children with ADHD and symptoms of oppositional defiant disorder improved in behavior when treated with methylphenidate and adjuvant risperidone, though weight gain was also observed - Results from a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Jahangard, Leila; Akbarian, Shahrokh; Haghighi, Mohammad; Ahmadpanah, Mohammad; Keshavarzi, Amir; Bajoghli, Hafez; Sadeghi Bahmani, Dena; Holsboer-Trachsler, Edith; Brand, Serge

2017-05-01

Children with ADHD often show symptoms of oppositional defiant disorders (ODD). We investigated the impact of adjuvant risperidone (RISP) to a standard treatment with methylphenidate (MPH) in children with ADHD and symptoms of ODD. Eighty-four children with ADHD and ODD (age: M=8.55; range: 7.28-9.95 years; 73.8% males) took part in a double-blind, randomized, placebo-controlled, clinical trial lasting eight weeks. Participants were randomly assigned either to the MPH+RISP (1mg/kg/d+0.5mg/d) or to the MPH+PLCO (1mg/kg/d+placebo) condition. Symptoms of ADHD, weight, height, and blood pressure were assessed at baseline, and at weeks 2, 4, 6 and 8. Symptoms of ADHD decreased over time, but more so in the MPH+RISP than in the MPH only condition. In the MPH+RISP condition weight, waist circumference and prolactine levels increased over time. Data suggest that adjuvant RISP improved symptoms in children with ADHD and ODD, but weight gain and higher prolactine levels were also observed, which are two alarming side effects. This may become an issue, once children become adolescents, a period of life in which body shape and body self-image are closely linked to self-confidence and peer acceptance. Health care professionals should carefully balance the short-term and long-term costs and benefits of administration of RISP. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Impact of negative media publicity on attention-deficit/hyperactivity disorder medication in Taiwan.

PubMed

Wang, Liang-Jen; Lee, Sheng-Yu; Yuan, Shin-Sheng; Yang, Chun-Ju; Yang, Kang-Chung; Lee, Tung-Liang; Shyu, Yu-Chiau

2016-01-01

This study explores trends in attention-deficit/hyperactivity disorder (ADHD) medications in Taiwan from 2000 to 2011 and whether negative media coverage of Ritalin in January 2010 impacted ADHD prescriptions throughout the country. Patients throughout Taiwan who had been newly diagnosed with ADHD (n = 145,269) between January 2000 and December 2011 were selected from Taiwan's National Health Insurance database as subjects for this study. We analyzed monthly and yearly data on person-days of treatment with immediate-release methylphenidate (IR-MPH), osmotic controlled-release formulation of methylphenidate (OROS-MPH), and atomoxetine (ATX) using linear models of curve estimation and the time series expert modeler. Of our sample, 57.8%, 28.9%, and 4.3% had been prescribed one or more doses of IR-MPH, OROS-MPH, or ATX, respectively. The annual person-days of IR-MPH use increased regularly from 2000 to 2009, dropped abruptly in 2010, and then increased again the next year. Furthermore, the person-days of OROS-MPH prescriptions did not reach their expected goal in 2010; however, the person-days of ATX prescriptions have increased constantly since entering the market in 2007. Compared with patients newly diagnosed with ADHD in 2009, those newly diagnosed in 2010 were less likely to be treated with medication. These findings suggest that negative publicity affected the writing of stimulant prescriptions for ADHD patients throughout Taiwan. Media reporting has a vital role in influencing children with ADHD, their parents, and their willingness to accept pharmacotherapy as treatment. Copyright © 2015 John Wiley & Sons, Ltd.

70 mph study : final report.

DOT National Transportation Integrated Search

2016-06-30

In July and August 2014, the Pennsylvania Department of Transportation (PennDOT) and Pennsylvania Turnpike Commission : (PTC) raised the posted speed limit on rural sections of Interstates 80, 380, and 76 from 65 to 70 mph. The purpose of this study ...

Speed limit recommendation in vicinity of signalized, high-speed intersection.

DOT National Transportation Integrated Search

2012-04-01

We evaluated the traffic operations and safety effects of 5 mph and 10 mph speed limit reductions in the vicinity of highspeed, : signalized intersections with advance warning flashers (AWF). Traffic operational effects of the reduced speed : limits ...

Alternative Fuels Data Center

Science.gov Websites

a maximum speed of 35 miles per hour (mph) and that must comply with the safety standards in Title have a posted speed limit of 45 mph or less except to cross at an intersection. A county, municipality

Genetic imaging study with [Tc-99m] TRODAT-1 SPECT in adolescents with ADHD using OROS-methylphenidate.

PubMed

Akay, Aynur Pekcanlar; Kaya, Gamze Çapa; Kose, Samet; Yazıcıoğlu, Çiğdem Eresen; Erkuran, Handan Özek; Güney, Sevay Alşen; Oğuz, Kaya; Keskin, Duygu; Baykara, Burak; Emiroğlu, Neslihan İnal; Eren, Mine Şencan; Kızıldağ, Sefa; Ertay, Türkan; Özsoylu, Dua; Miral, Süha; Durak, Hatice; Gönül, Ali Saffet; Rohde, Luis Augusto

2018-04-20

To examine theeffects on the brain of 2-month treatment withamethylphenidate extended-release formulation (OROS-MPH) using [Tc- 99m ] TRODAT-1SPECT in a sample of treatment-naïve adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). In addition, to assess whether risk alleles (homozygosity for 10-repeat allele at the DAT1 gene were associated with alterations in striatal DAT availability. Twenty adolescents with ADHD underwent brain single-photon emission computed tomography (SPECT) scans with [Tc- 99m ] TRODAT-1 at baseline and two months after starting OROS-MPH treatment with dosages up to 1 mg/kg/day. Severity of illness was estimated using the Clinical Global Impression Scale (CGI-S) and DuPaul ADHD Rating Scale-Clinician version (ARS) before treatment,1 month and 2 months after initiating OROS-MPH treatment. Decreased DAT availability was found in both the right caudate (pretreatment DAT binding: 224.76 ± 33.77, post-treatment DAT binding: 208.86 ± 28.75, p = 0.02) and right putamen (pre-treatment DAT binding: 314.41 ± 55.24, post-treatment DAT binding: 285.66 ± 39.20, p = 0.05) in adolescents with ADHD receiving OROS-MPH treatment. Adolescents with ADHD who showed a robust response to OROS-MPH (n = 7) had significantly greater reduction of DAT density in the right putamen than adolescents who showed less robust response to OROS-MPH (n = 13) (p = 0.02). However, between-group differences by treatment responses were not related with DAT density in the right caudate. Risk alleles (homozygosity for the 10-repeat allele of DAT1 gene) in the DAT1 gene were not associated with alterations in striatal DAT availability. Two months of OROS-MPH treatment decreased DAT availability in both the right caudate and putamen. Adolescents with ADHD who showed a robust response to OROS-MPH had greater reduction of DAT density in the right putamen. However,our findings did not support an association between homozygosity for a 10-repeat allele in the DAT1 gene and DAT density, assessedusing[Tc- 99m ] TRODAT-1SPECT. Copyright © 2018 Elsevier Inc. All rights reserved.

Windthrow a hazard in Virginia pine strip cuttings

Treesearch

Richard H. Fenton

1955-01-01

The eye of Hurricane Hazel passed to the west of the Beltsville Experimental Forest in Maryland on the afternoon of October 15, 1954. Sustained wind velocities of 66 mph (from the SE), with maximum gusts of 98 mph, were recorded nearby.

Reducing Carbon Dioxide Emissions: Using the Mole Concept.

ERIC Educational Resources Information Center

Myers, Alan

2002-01-01

Provides an application of quantitative chemistry concepts in the context of motor vehicle emissions. Shows how carbon dioxide emissions from cars may be reduced by up to 25% by reducing motorway speeds from 70-75 mph to 60 mph. (Author/MM)

Executive Impairment Determines ADHD Medication Response: Implications for Academic Achievement

ERIC Educational Resources Information Center

Hale, James B.; Reddy, Linda A.; Semrud-Clikeman, Margaret; Hain, Lisa A.; Whitaker, James; Morley, Jessica; Lawrence, Kyle; Smith, Alex; Jones, Nicole

2011-01-01

Methylphenidate (MPH) often ameliorates attention-deficit/hyperactivity disorder (ADHD) behavioral dysfunction according to "indirect" informant reports and rating scales. The standard of care behavioral MPH titration approach seldom includes "direct" neuropsychological or academic assessment data to determine treatment…

Alternative Fuels Data Center

Science.gov Websites

Low-Speed Vehicle Definition A low-speed vehicle is defined as a four wheeled vehicle that has a maximum speed greater than 20 miles per hour (mph) but not more than 25 mph and has a gross vehicle weight

A Comparison of 2 Current-Issue Army Boots, 5 Prototype Military Boots, and 5 Commercial Hiking Boots: Performance, Efficiency, Biomechanics, Comfort and Injury

DTIC Science & Technology

1999-11-01

Maximum force (N) on the ankle, knee and hip while walking at 3.5 mph 51 23. Maximum heel- strike force (N) while walking at 3.5 mph ^.ർ 24...to first force peak while running at 6.5 mph ’.""."..62 34. Variables relating to force low point between the heel- strike and push-off peak...was lower peak deceleration and lower peak pressure at the heel than at the forefoot . In the second phase of their research, Hamill and Bensel (7, 8

Strain actuated aeroelastic control

NASA Technical Reports Server (NTRS)

Lazarus, Kenneth B.

1992-01-01

Viewgraphs on strain actuated aeroelastic control are presented. Topics covered include: structural and aerodynamic modeling; control law design methodology; system block diagram; adaptive wing test article; bench-top experiments; bench-top disturbance rejection: open and closed loop response; bench-top disturbance rejection: state cost versus control cost; wind tunnel experiments; wind tunnel gust alleviation: open and closed loop response at 60 mph; wind tunnel gust alleviation: state cost versus control cost at 60 mph; wind tunnel command following: open and closed loop error at 60 mph; wind tunnel flutter suppression: open loop flutter speed; and wind tunnel flutter suppression: closed loop state cost curves.

Comparison of analytical methods for calculation of wind loads

NASA Technical Reports Server (NTRS)

Minderman, Donald J.; Schultz, Larry L.

1989-01-01

The following analysis is a comparison of analytical methods for calculation of wind load pressures. The analytical methods specified in ASCE Paper No. 3269, ANSI A58.1-1982, the Standard Building Code, and the Uniform Building Code were analyzed using various hurricane speeds to determine the differences in the calculated results. The winds used for the analysis ranged from 100 mph to 125 mph and applied inland from the shoreline of a large open body of water (i.e., an enormous lake or the ocean) a distance of 1500 feet or ten times the height of the building or structure considered. For a building or structure less than or equal to 250 feet in height acted upon by a wind greater than or equal to 115 mph, it was determined that the method specified in ANSI A58.1-1982 calculates a larger wind load pressure than the other methods. For a building or structure between 250 feet and 500 feet tall acted upon by a wind rangind from 100 mph to 110 mph, there is no clear choice of which method to use; for these cases, factors that must be considered are the steady-state or peak wind velocity, the geographic location, the distance from a large open body of water, and the expected design life and its risk factor.

Accuracy of an infrared LED device to measure heart rate and energy expenditure during rest and exercise.

PubMed

Lee, C Matthew; Gorelick, Mark; Mendoza, Albert

2011-12-01

The purpose of this study was to examine the accuracy of the ePulse Personal Fitness Assistant, a forearm-worn device that provides measures of heart rate and estimates energy expenditure. Forty-six participants engaged in 4-minute periods of standing, 2.0 mph walking, 3.5 mph walking, 4.5 mph jogging, and 6.0 mph running. Heart rate and energy expenditure were simultaneously recorded at 60-second intervals using the ePulse, an electrocardiogram (EKG), and indirect calorimetry. The heart rates obtained from the ePulse were highly correlated (intraclass correlation coefficients [ICCs] ≥0.85) with those from the EKG during all conditions. The typical errors progressively increased with increasing exercise intensity but were <5 bpm only during rest and 2.0 mph. Energy expenditure from the ePulse was poorly correlated with indirect calorimetry (ICCs: 0.01-0.36) and the typical errors for energy expenditure ranged from 0.69-2.97 kcal · min(-1), progressively increasing with exercise intensity. These data suggest that the ePulse Personal Fitness Assistant is a valid device for monitoring heart rate at rest and low-intensity exercise, but becomes less accurate as exercise intensity increases. However, it does not appear to be a valid device to estimate energy expenditure during exercise.

Sex differences in attentional performance and their modulation by methylphenidate in children with attention-deficit/hyperactivity disorder.

PubMed

Günther, Thomas; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2010-06-01

Still little is known about neuropsychological differences between boys and girls with attention-deficit/hyperactivity disorder (ADHD) and whether there are sex-specific differences in the modulation of attentional performance by methylphenidate (MPH). In this study, 27 males and 27 females between 8-12 years old and with ADHD were investigated in a double-blind, placebo-controlled trial on five computerized attention tests (0.25 vs. 0.5 mg/kg MPH as a single dose, versus placebo). Boys and girls with ADHD did not differ with respect to age, intelligence quotient (IQ), symptom severity, co-morbidity patterns, and ADHD subtype. However, ADHD boys were more impulsive on a sustained attention task, whereas girls with ADHD had more deficits on tasks measuring selective attention. Attentional performance increased differentially as a function of MPH dose, with some tasks showing linear improvement with higher dosage whereas more complex tasks in particular showed inverse U-shaped patterns of MPH effects. However, these effects were comparable between girls and boys. Our data suggest that there are some gender differences in attentional performance in subjects with ADHD in a clinical sample, even if symptom severity and co-morbidity are controlled; however, modulation of attention by MPH does not seem to differ between sexes.

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

PubMed

Mulder, Erik J; Anderson, George M; Kemperman, Ramses F J; Oosterloo-Duinkerken, Alida; Minderaa, Ruud B; Kema, Ido P

2010-01-01

A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production. (c) 2009 S. Karger AG, Basel.

Examination of media coverage of increasing the speed limit to 65 mph

DOT National Transportation Integrated Search

1988-09-01

Heightened newspaper and television coverage of the proposed 65 mph limit may have encouraged increased travel speeds which in turn could have produced an increase in fatalities prior to passage of the national legislation. To pursue this further, NH...

Evaluating the impacts of proposed speed limit increases in Michigan : research spotlight.

DOT National Transportation Integrated Search

2014-07-01

Recent proposed speed limit legislation led MDOT to evaluate the : states current speed limit policies and potential alternatives. Currently, : Michigan freeways have a maximum speed limit of 70 mph for passenger : vehicles and 60 mph for trucks a...

High-speed rail aerodynamic assessment and mitigation report : final report.

DOT National Transportation Integrated Search

2015-12-01

This report advances the current state of knowledge, as well as shared understanding and evaluation of present procedures used to : mitigate the impacts effects from high-speed trains (HST) operating at speeds between 110 mph and 250 mph. This work g...

Engineering studies in support of the development of high-speed track geometry specifications

DOT National Transportation Integrated Search

1997-03-01

The Federal Railroad Administration has been directing engineering studies to support the development of high speed track geometry standards. These standards are intended to cover train operating speeds from 110 mph to 200 mph. The studies conducted ...

65 mph speed limit : analysis of fatal accident injury severity

DOT National Transportation Integrated Search

1989-11-01

Several studies of the fatality experience in the 38 states that implemented a65 mph speed : limit on Rural Interstate highways in 1987 concluded that the higher speed limit has : caused fatalities to increase. This relationship between the speed lim...

Passenger vehicles sustain huge damage in 5 Mph tests

DOT National Transportation Integrated Search

2000-04-15

Seventeen new cars, all 1999 and 2000 models, turned in mostly disappointing results in 5 mph crash tests conducted to assess how well the bumpers resist costly damage in the kinds of impacts that frequently occur in commuter traffic and parking lots...

Growth hormone (GH) dosing during catch-up growth guided by individual responsiveness decreases growth response variability in prepubertal children with GH deficiency or idiopathic short stature.

PubMed

Kriström, Berit; Aronson, A Stefan; Dahlgren, Jovanna; Gustafsson, Jan; Halldin, Maria; Ivarsson, Sten A; Nilsson, Nils-Osten; Svensson, Johan; Tuvemo, Torsten; Albertsson-Wikland, Kerstin

2009-02-01

Weight-based GH dosing results in a wide variation in growth response in children with GH deficiency (GHD) or idiopathic short stature (ISS). The hypothesis tested was whether individualized GH doses, based on variation in GH responsiveness estimated by a prediction model, reduced variability in growth response around a set height target compared with a standardized weight-based dose. A total of 153 short prepubertal children diagnosed with isolated GHD or ISS (n = 43) and at least 1 SD score (SDS) below midparental height SDS (MPH(SDS)) were included in this 2-yr multicenter study. The children were randomized to either a standard (43 microg/kg.d) or individualized (17-100 microg/kg.d) GH dose. We measured the deviation of height(SDS) from individual MPH(SDS) (diffMPH(SDS)). The primary endpoint was the difference in the range of diffMPH(SDS) between the two groups. The diffMPH(SDS) range was reduced by 32% in the individualized-dose group relative to the standard-dose group (P < 0.003), whereas the mean diffMPH(SDS) was equal: -0.42 +/- 0.46 and -0.48 +/- 0.67, respectively. Gain in height(SDS) 0-2 yr was equal for the GH-deficient and ISS groups: 1.31 +/- 0.47 and 1.36 +/- 0.47, respectively, when ISS was classified on the basis of maximum GH peak on the arginine-insulin tolerance test or 24-h profile. Individualized GH doses during catch-up growth significantly reduce the proportion of unexpectedly good and poor responders around a predefined individual growth target and result in equal growth responses in children with GHD and ISS.

Aboriginal and Torres Strait Islander Public Health: Online and Integrated into Core Master of Public Health Subjects

PubMed Central

Angus, Lynnell; Ewen, Shaun; Coombe, Leanne

2016-01-01

The Master of Public Health (MPH) is an internationally recognised post-graduate qualification for building the public health workforce. In Australia, MPH graduate attributes include six Indigenous public health (IPH) competencies. The University of Melbourne MPH program includes five core subjects and ten specialisation streams, of which one is Indigenous health. Unless students complete this specialisation or electives in Indigenous health, it is possible for students to graduate without attaining the IPH competencies. To address this issue in a crowded and competitive curriculum an innovative approach to integrating the IPH competencies in core MPH subjects was developed. Five online modules that corresponded with the learning outcomes of the core public health subjects were developed, implemented and evaluated in 2015. This brief report outlines the conceptualisation, development, and description of the curriculum content; it also provides preliminary student evaluation and staff feedback on the integration project. Significance for public health This approach to a comprehensive, online, integrated Indigenous public health (IPH) curriculum is significant, as it ensures that all University of Melbourne Master of Public Health (MPH) graduates will have the competencies to positively contribute to Indigenous health status. A workforce that is attuned not only to the challenges of IPH, but also to the principles of self-determination, Indigenous agency and collaboration is better equipped to be comprised of ethical and judgment-safe practitioners. Additionally, the outlined approach of utilizing IPH content and examples into core MPH subjects ensures both the Australian relevance for an Australian-based health professional course and international appeal through the modules inclusion of International Indigenous case-studies and content. Furthermore, approaches learned in a challenging Indigenous Australian context are transferable and applicable to other IPH challenges in a local, national and global context. PMID:27190981

Oral methylphenidate alleviates the fine motor dysfunction caused by chronic postnatal manganese exposure in adult rats.

PubMed

Beaudin, Stéphane A; Strupp, Barbara J; Lasley, Stephen M; Fornal, Casimir A; Mandal, Shyamali; Smith, Donald R

2015-04-01

Developmental manganese (Mn) exposure is associated with motor dysfunction in children and animal models, but little is known about the underlying neurochemical mechanisms or the potential for amelioration by pharmacotherapy. We investigated whether methylphenidate (MPH) alleviates fine motor dysfunction due to chronic postnatal Mn exposure, and whether Mn exposure impairs brain extracellular dopamine (DA) and norepinephrine (NE) in the prefrontal cortex (PFC) and striatum in adult animals. Rats were orally exposed to 0 or 50 mg Mn/kg/day from postnatal day 1 until the end of the study (PND 145). The staircase test was used to assess skilled forelimb function. Oral MPH (2.5 mg/kg/day) was administered daily 1 h before staircase testing for 16 days. DA and NE levels were measured by dual probe microdialysis. Results show that Mn exposure impaired reaching and grasping skills and the evoked release of DA and NE in the PFC and striatum of adult rats. Importantly, oral MPH treatment fully alleviated the fine motor deficits in the Mn-exposed animals, but did not affect forelimb skills of control rats not exposed to Mn. These results suggest that catecholaminergic hypofunctioning in the PFC and striatum may underlie the Mn-induced fine motor dysfunction, and that oral MPH pharmacotherapy is an effective treatment approach for alleviating this dysfunction in adult animals. The therapeutic potential of MPH for the treatment of motor dysfunction in Mn-exposed children and adults appears promising pending further characterization of MPH efficacy in other functional areas (eg, attention) believed to be affected by developmental Mn exposure. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: a randomized, placebo-controlled cross-over study.

PubMed

Bron, Tannetje I; Bijlenga, Denise; Boonstra, A Marije; Breuk, Minda; Pardoen, Willem F H; Beekman, Aartjan T F; Kooij, J J Sandra

2014-04-01

Attention-deficit/hyperactivity disorder (ADHD) is linked to impaired executive functioning (EF). This is the first study to objectively investigate the effects of a long-acting methylphenidate on neurocognitive test performance of adults with ADHD. Twenty-two adults with ADHD participated in a 6-weeks study examining the effect of osmotic-release oral system methylphenidate (OROS-mph) on continuous performance tests (CPTs; objective measures), and on the self-reported ADHD rating scale (subjective measure) using a randomized, double-blind, placebo-controlled cross-over design. OROS-mph significantly improved reaction time variability (RTV), commission errors (CE) and d-prime (DP) as compared to baseline (Cohen's d>.50), but did not affect hit reaction time (HRT) or omission errors (OE). Compared to placebo, OROS-mph only significantly influenced RTV on one of two CPTs (p<.050). Linear regression analyses showed predictive ability of more beneficial OROS-mph effects in ADHD patients with higher EF severity (RTV: β=.670, t=2.097, p=.042; omission errors (OE): β=-.098, t=-4.759, p<.001), and with more severe ADHD symptoms (RTV: F=6.363, p=.019; HRT: F=3.914, p=.061). Side effects rates were substantially but non-significantly greater for OROS-mph compared to placebo (77% vs. 46%, p=.063). OROS-mph effects indicated RTV as the most sensitive parameter for measuring both neuropsychological and behavioral deficits in adults with ADHD. These findings suggest RTV as an endophenotypic parameter for ADHD symptomatology, and propose CPTs as an objective method for monitoring methylphenidate titration. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Association Between 5-HTTLPR Polymorphism and Tics after Treatment with Methylphenidate in Korean Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Park, Seo Yeon; Kim, Eun Joo; Cheon, Keun-Ah

2015-10-01

The purpose of this study is to examine the relationship between 5-HTTLPR polymorphism (44-bp insertion/deletion polymorphism of serotonin transporter gene) and methylphenidate (MPH) treatment response, as well as the association between the adverse events of MPH treatment and 5-HTTLPR polymorphism in children with attention-deficit/hyperactivity disorder (ADHD). A total of 114 children with ADHD (mean age 9.08 ± 1.94 years) were recruited from the child psychiatric clinic in a hospital in South Korea. We have extracted the genomic DNA of the subjects from their blood lymphocytes and analyzed 5-HTTLPR polymorphism of the SLC6A4 gene. All children were treated with MPH for 8 weeks, with clinicians monitoring both the improvement of ADHD symptoms and the side effects. We compared the response to MPH treatment and adverse events among those with the genotype of 5-HRRLPR polymorphism. There was no significant association between the 5-HTTLPR genotype and the response to MPH treatment in children with ADHD. Subjects with the S/L+L/L genotype tended to have tics and nail biting (respectively, p < 0.001, p = 0.017). The results of this study do not support the association between the 5-HTTLPR polymorphism and treatment response with MPH in ADHD. However, our findings suggest the association between 5-HTTLPR polymorphism and the occurrence of tics and nail-biting as an adverse event of methylphenidate. This may aid in our understanding of the genetic contribution and genetic susceptibility of a particular allele in those ADHD patients with tics or nail biting.

Treatment with a Clinically-Relevant Dose of Methylphenidate Alters NMDA Receptor Composition and Synaptic Plasticity in the Juvenile Rat Prefrontal Cortex

PubMed Central

Urban, Kimberly R.; Li, Yan-Chun; Gao, Wen-Jun

2013-01-01

Methylphenidate (Ritalin, MPH) is the most commonly prescribed psychoactive drug for children. Used to treat attention-deficit/hyperactivity disorder (ADHD) and for cognitive enhancement in healthy individuals, its cellular mechanisms of action and potential long-term effects are poorly understood. We recently reported that a clinically relevant (1 mg/kg i.p., single injection) dose of MPH significantly decreased neuronal excitability in the juvenile rat prefrontal cortical neurons. Here we further explore the actions of acute treatment with MPH on the level of NMDA receptor subunits and NMDA receptor-mediated short- and long-term synaptic plasticity in the juvenile rat prefrontal cortical neurons. We found that a single dose of MPH treatment (1 mg/kg, intraperitoneal) significantly decreased the surface and total protein levels of NMDA receptor subunits NR1 and NR2B, but not NR2A, in the juvenile prefrontal cortex. In addition, the amplitude, decay time and charge transfer of NMDA receptor-mediated EPSCs were significantly decreased whereas the amplitude and short-term depression of AMPA receptor-mediated EPSCs were significantly increased in the prefrontal neurons. Furthermore, MPH treatment also significantly increased the probability and magnitude of LTP induction, but had only a small effect on LTD induction in juvenile rat prefrontal cortical neurons. Our data thus present a novel mechanism of action of MPH, i.e., changes in glutamatergic receptor-mediated synaptic plasticity following early-life treatment. Furthermore, since a single dosage resulted in significant changes in NMDA receptors, off-label usage by healthy individuals, especially children and adolescents, may result in altered potential for plastic learning. PMID:23333502

Association Between 5-HTTLPR Polymorphism and Tics after Treatment with Methylphenidate in Korean Children with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Park, Seo Yeon; Kim, Eun Joo

2015-01-01

Abstract Objectives: The purpose of this study is to examine the relationship between 5-HTTLPR polymorphism (44-bp insertion/deletion polymorphism of serotonin transporter gene) and methylphenidate (MPH) treatment response, as well as the association between the adverse events of MPH treatment and 5-HTTLPR polymorphism in children with attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 114 children with ADHD (mean age 9.08 ± 1.94 years) were recruited from the child psychiatric clinic in a hospital in South Korea. We have extracted the genomic DNA of the subjects from their blood lymphocytes and analyzed 5-HTTLPR polymorphism of the SLC6A4 gene. All children were treated with MPH for 8 weeks, with clinicians monitoring both the improvement of ADHD symptoms and the side effects. We compared the response to MPH treatment and adverse events among those with the genotype of 5-HRRLPR polymorphism. Results: There was no significant association between the 5-HTTLPR genotype and the response to MPH treatment in children with ADHD. Subjects with the S/L+L/L genotype tended to have tics and nail biting (respectively, p < 0.001, p = 0.017). Conclusions: The results of this study do not support the association between the 5-HTTLPR polymorphism and treatment response with MPH in ADHD. However, our findings suggest the association between 5-HTTLPR polymorphism and the occurrence of tics and nail-biting as an adverse event of methylphenidate. This may aid in our understanding of the genetic contribution and genetic susceptibility of a particular allele in those ADHD patients with tics or nail biting. PMID:26402385

Designing the framework for competency-based master of public health programs in India.

PubMed

Sharma, Kavya; Zodpey, Sanjay; Morgan, Alison; Gaidhane, Abhay; Syed, Zahiruddin Quazi; Kumar, Rajeev

2013-01-01

Competency in the practice of public health is the implicit goal of education institutions that offer master of public health (MPH) programs. With the expanding number of institutions offering courses in public health in India, it is timely to develop a common framework to ensure that graduates are proficient in critical public health. Steps such as situation assessment, survey of public health care professionals in India, and national consultation were undertaken to develop a proposed competency-based framework for MPH programs in India. The existing curricula of all 23 Indian MPH courses vary significantly in content with regard to core, concentration, and crosscutting discipline areas and course durations. The competency or learning outcome is not well defined. The findings of the survey suggest that MPH graduates in India should have competencies ranging from monitoring of health problems and epidemics in the community, applying biostatistics in public health, conducting action research, understanding social and community influence on public health developing indicators and instruments to monitor and evaluate community health programs, developing proposals, and involving community in planning, delivery, and monitoring of health programs. Competency statements were framed and mapped with domains including epidemiology, biostatistics, social and behavioral sciences, health care system, policy, planning, and financing, and environmental health sciences and a crosscutting domain that include health communication and informatics, health management and leadership, professionalism, systems thinking, and public health biology. The proposed competency-based framework for Indian MPH programs can be adapted to meet the needs of diverse, unique programs. The framework ensures the uniqueness and diversity of individual MPH programs in India while contributing to measures of overall program success.

Development and Validation of a Monte Carlo Simulation Tool for Multi-Pinhole SPECT

PubMed Central

Mok, Greta S. P.; Du, Yong; Wang, Yuchuan; Frey, Eric C.; Tsui, Benjamin M. W.

2011-01-01

Purpose In this work, we developed and validated a Monte Carlo simulation (MCS) tool for investigation and evaluation of multi-pinhole (MPH) SPECT imaging. Procedures This tool was based on a combination of the SimSET and MCNP codes. Photon attenuation and scatter in the object, as well as penetration and scatter through the collimator detector, are modeled in this tool. It allows accurate and efficient simulation of MPH SPECT with focused pinhole apertures and user-specified photon energy, aperture material, and imaging geometry. The MCS method was validated by comparing the point response function (PRF), detection efficiency (DE), and image profiles obtained from point sources and phantom experiments. A prototype single-pinhole collimator and focused four- and five-pinhole collimators fitted on a small animal imager were used for the experimental validations. We have also compared computational speed among various simulation tools for MPH SPECT, including SimSET-MCNP, MCNP, SimSET-GATE, and GATE for simulating projections of a hot sphere phantom. Results We found good agreement between the MCS and experimental results for PRF, DE, and image profiles, indicating the validity of the simulation method. The relative computational speeds for SimSET-MCNP, MCNP, SimSET-GATE, and GATE are 1: 2.73: 3.54: 7.34, respectively, for 120-view simulations. We also demonstrated the application of this MCS tool in small animal imaging by generating a set of low-noise MPH projection data of a 3D digital mouse whole body phantom. Conclusions The new method is useful for studying MPH collimator designs, data acquisition protocols, image reconstructions, and compensation techniques. It also has great potential to be applied for modeling the collimator-detector response with penetration and scatter effects for MPH in the quantitative reconstruction method. PMID:19779896

Effects of wind speed on aerosol spray penetration in adult mosquito bioassay cages.

PubMed

Hoffmann, W Clint; Fritz, Bradley K; Farooq, Muhammad; Cooperband, Miriam F

2008-09-01

Bioassay cages are commonly used to assess efficacy of insecticides against adult mosquitoes in the field. To correlate adult mortality readings to insecticidal efficacy and/or spray application parameters properly, it is important to know how the cage used in the bioassay interacts with the spray cloud containing the applied insecticide. This study compared the size of droplets, wind speed, and amount of spray material penetrating cages and outside of cages in a wind tunnel at different wind speeds. Two bioassay cages, Center for Medical, Agricultural and Veterinary Entomology (CMAVE) and Circle, were evaluated. The screen materials used on these cages reduced the size of droplets, wind speed, and amount of spray material inside the cages as compared to the spray cloud and wind velocity outside of the cages. When the wind speed in the dispersion tunnel was set at 0.6 m/sec (1.3 mph), the mean wind speed inside of the CMAVE Bioassay Cage and Circle Cage was 0.045 m/sec (0.10 mph) and 0.075 m/sec (0.17 mph), respectively. At air velocities of 2.2 m/sec (4.9 mph) in the dispersion tunnel, the mean wind speed inside of the CMAVE Bioassay Cage and Circle Cage was 0.83 m/sec (1.86 mph) and 0.71 m/sec (1.59 mph), respectively. Consequently, there was a consistent 50-70% reduction of spray material penetrating the cages compared to the spray cloud that approached the cages. These results provide a better understanding of the impact of wind speed, cage design, and construction on ultra-low-volume spray droplets.

Early long-term exposure with caffeine induces cross-sensitization to methylphenidate with involvement of DARPP-32 in adulthood of rats.

PubMed

Boeck, Carina R; Marques, Virgínia B; Valvassori, Samira S; Constantino, Leandra C; Rosa, Daniela V F; Lima, Fabrício F; Romano-Silva, Marco A; Quevedo, João

2009-09-01

Chronic ingestion of caffeine causes dependence and sleep disturbance in children and adolescents. In rodents, the administration of caffeine may produce behavioral cross-sensitization to some psychostimulants, such as dopaminergic psychoactive drugs. Methylphenidate (MPH; Ritalin) is a psychostimulant used in pediatric- and adult human populations to manage the symptoms associated with attention-deficit hyperactivity disorder (ADHD). Previous studies have suggested that dopamine- and cAMP-regulated phosphoproteins of 32 kDa (DARPP-32) participate in the manifestation of behavioral activity following ingestion of caffeine or MPH. The aim of the present study was to evaluate whether long-term administration of low doses of caffeine in rodents during their adolescence induces cross-sensitization to MPH challenge in their adulthood and investigate the involvement of DARPP-32 in this model. Young rats (P25) consumed water or caffeine (0.3 g/L; mean consumption was 7.5 mg/day/kg) for 28 days. The caffeine consumption was then suspended for 14 days (washout period) when the animals received saline solution or MPH (1, 2, or 10 mg/kg) (P67) intraperitoneally. The locomotor activity of these rats was assessed using the open-field test, following which the immunocontent of DARPP-32 was evaluated in samples of their prefrontal cortex, striatum, or hippocampus. Rats chronically exposed to caffeine in their adolescent period and to inactive doses of MPH (1mg/kg) in adulthood showed augmented locomotor activity. The behavioral effect observed was accompanied by increased levels of DARPP-32 in the striatum and prefrontal cortex compared to control groups (saline or caffeine). However, no alteration caused by these treatments was noted in the hippocampus. In conclusion, chronic caffeine exposure induces likely long-term cross-sensitization to MPH in a DARPP-32-dependent pathway.

The role of the polymorphic efflux transporter P-glycoprotein on the brain accumulation of d-methylphenidate and d-amphetamine.

PubMed

Zhu, Hao-Jie; Wang, Jun-Sheng; DeVane, C Lindsay; Williard, Robin L; Donovan, Jennifer L; Middaugh, Lawrence D; Gibson, Brian B; Patrick, Kennerly S; Markowitz, John S

2006-07-01

The psychostimulant medications methylphenidate (MPH) and amphetamine (AMP), available in various ratios or enantiopure formulations of their respective active dextrorotary isomers, constitute the majority of agents used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Substantial interindividual variability occurs in their pharmacokinetics and tolerability. Little is known regarding the potential role of drug transporters such as P-glycoprotein (P-gp) in psychostimulant pharmacokinetics and response. Therefore, experiments were carried out in P-gp knockout (KO) mice versus wild-type (WT) mice after intraperitoneal dosing (2.5 mg/kg) of d-MPH or (3.0 mg/kg) of d-AMP. After the administration of each psychostimulant, locomotor activity was assessed at 30-min intervals for 2 h. Total brain-to-plasma drug concentration ratios were determined at 10-, 30-, and 80-min postdosing time-points. The results showed no statistically supported genotypic difference in d-AMP-induced locomotor activity stimulation or in brain-to-plasma ratio of d-AMP. As for d-MPH, the P-gp KO mice had 33% higher brain concentrations (p < 0.05) and 67.5% higher brain-to-plasma ratios (p < 0.01) than WT controls at the 10-min postdosing timepoint. However, in spite of elevated brain concentrations, d-MPH-induced locomotor activity increase was attenuated for P-gp compared with that for WT mice. These data indicate that P-gp has no apparent effect on the pharmacokinetics and pharmacodynamics of d-AMP. In addition, d-MPH is a relatively weak P-gp substrate, and its entry into the brain may be limited by P-gp. Furthermore, the mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO mice remains to be elucidated.

Effects of Raising Speed Limits on Motor Vehicle Emissions

DOT National Transportation Integrated Search

1997-03-01

In 1974 the Federal government introduced a national speed limit of 55 miles per hour (mph) in response to the Arab oil embargo and subsequent energy crisis. This limit was raised to 65 mph for rural interstate freeways in 1987. In November of 1995, ...

The impact of the 65 mph speed limit on Virginia's rural interstate highways through 1989.

DOT National Transportation Integrated Search

1990-01-01

In April 1987, Congress passed the Surface Transportation and Uniform Relocation Assistance Act (STURAA) which permitted states to raise their maximum speed limit on rural interstate highways (rural interstates) to 65 mph. Since then, 40 states, incl...

Evaluating the impacts of speed limit policy alternatives.

DOT National Transportation Integrated Search

2014-07-01

As of June 2014, Michigan is one of eight states with a differential speed limit in place on its rural : freeways, which sets a maximum speed of 70 mph for passenger vehicles and 60 mph for trucks and : buses. In select urban environments, these spee...

A flexible approach to training veterinarians in public health: an overview and early assessment of the DVM/MPH dual-degree program at the University of Minnesota.

PubMed

Minicucci, Larissa A; Hanson, Kate A; Olson, Debra K; Hueston, William D

2008-01-01

As a result of the growing need for public-health veterinarians, novel educational programs are essential to train future public-health professionals. The University of Minnesota School of Public Health, in collaboration with the College of Veterinary Medicine, initiated a dual DVM/MPH program in 2002. This program provides flexibility by combining distance learning and on-campus courses offered through a summer public-health institute. MPH requirements are completed through core courses, elective courses in a focus area, and an MPH project and field experience. Currently, more than 100 students representing 13 veterinary schools are enrolled in the program. The majority of initial program graduates have pursued public-practice careers upon completion of the program. Strengths of the Minnesota program design include accessibility and an environment to support multidisciplinary training. Continued assessment of program graduates will allow for evaluation and adjustment of the program in the coming years.

Physicochemical and flavor characteristics of flavoring agent from mungbean protein hydrolyzed by bromelain.

PubMed

Sonklin, Chanikan; Laohakunjit, Natta; Kerdchoechuen, Orapin

2011-08-10

Enzymatic bromelain mungbean meal protein hydrolysate (eb-MPH) was produced from mungbean meal protein isolate (MPI). Enzymatic bromelain, with a known protease activity of 98,652 (unit/g), was used at concentrations of 0, 2, 6, 10, 14 and 18% (w/w) and with hydrolysis times of 0.5, 3, 6, 12, and 24 h. The pH and temperature were controlled at 6.0 and 50 °C, respectively. It was found that the best treatment combination for eb-MPH production by response surface methodology (RSM) was 18% bromelain and a hydrolysis time of 3 h, resulting in the greatest degree of hydrolysis (% DH) and percent yield, with values of 61.04 and 45.63%, respectively. Results also showed that the phenylalanine, tyrosine and leucine contents of the optimally produced eb-MPH were 20.88, 14.50 and 10.93%, respectively. Twelve volatile compounds were identified using gas chromatography mass spectrometry in eb-MPH; benzaldehyde, 2-pentylfuran and furfural were the predominant odorants.

Validation of public health competencies and impact variables for low- and middle-income countries.

PubMed

Zwanikken, Prisca Ac; Alexander, Lucy; Huong, Nguyen Thanh; Qian, Xu; Valladares, Laura Magana; Mohamed, Nazar A; Ying, Xiao Hua; Gonzalez-Robledo, Maria Cecilia; Linh, Le Cu; Wadidi, Marwa Se Abuzaid; Tahir, Hanan; Neupane, Sunisha; Scherpbier, Albert

2014-01-20

The number of Master of Public Health (MPH) programmes in low- and middle-income countries (LMICs) is increasing, but questions have been raised regarding the relevance of their outcomes and impacts on context. Although processes for validating public health competencies have taken place in recent years in many high-income countries, validation in LMICs is needed. Furthermore, impact variables of MPH programmes in the workplace and in society have not been developed. A set of public health competencies and impact variables in the workplace and in society was designed using the competencies and learning objectives of six participating institutions offering MPH programmes in or for LMICs, and the set of competencies of the Council on Linkages Between Academia and Public Health Practice as a reference. The resulting competencies and impact variables differ from those of the Council on Linkages in scope and emphasis on social determinants of health, context specificity and intersectoral competencies. A modified Delphi method was used in this study to validate the public health competencies and impact variables; experts and MPH alumni from China, Vietnam, South Africa, Sudan, Mexico and the Netherlands reviewed them and made recommendations. The competencies and variables were validated across two Delphi rounds, first with public health experts (N = 31) from the six countries, then with MPH alumni (N = 30). After the first expert round, competencies and impact variables were refined based on the quantitative results and qualitative comments. Both rounds showed high consensus, more so for the competencies than the impact variables. The response rate was 100%. This is the first time that public health competencies have been validated in LMICs across continents. It is also the first time that impact variables of MPH programmes have been proposed and validated in LMICs across continents. The high degree of consensus between experts and alumni suggests that these public health competencies and impact variables can be used to design and evaluate MPH programmes, as well as for individual and team assessment and continuous professional development in LMICs.

Association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients.

PubMed

Angyal, Nora; Horvath, Erzsebet Zsofia; Tarnok, Zsanett; Richman, Mara J; Bognar, Emese; Lakatos, Krisztina; Sasvari-Szekely, Maria; Nemoda, Zsofia

2018-06-08

Methylphenidate (MPH) is the most frequently prescribed drug in Attention Deficit Hyperactivity Disorder (ADHD). Hitherto mostly the dopamine transporter gene has been studied in MPH-response and only a few studies analyzed the norepinephrine transporter (NET, SLC6A2) gene, although MPH is a potent inhibitor of both dopamine and norepinephrine transporters. We aimed to analyze this monoamine transporter gene in relation to ADHD per se and MPH-response in particular to gain further knowledge in ADHD pharmacogenetics using a Caucasian sample. Six single nucleotide polymorphisms (rs28386840, rs2242446, rs3785143, rs3785157, rs5569, rs7194256 SNP) were studied across the NET gene in 163 ADHD children (age: 9.3±2.6; 86.5% male) using ADHD-RS hyperactivity-impulsivity and inattention scales. For case-control analysis 486 control subjects were also genotyped. At the MPH-response analysis responders had minimum 25% decrease of ADHD-RS total score after 2months of treatment, and chi-square test compared 90 responders and 32 non-responders, whereas ANOVA was used to assess symptom improvement after the first month among the 122 ADHD patients. The classical case-control analysis did not yield any association with ADHD diagnosis, which was supported by meta-analysis conducted on the available genetic data (combining previously published and the present studies). On the other hand, the intronic rs3785143 showed nominal association with inattention symptoms (p=0.01). The haplotype analysis supported this association, and indicated the importance of the first haploblock encompassing the intronic and 2 promoter SNPs. With MPH-response only the promoter rs28386840 showed nominal association: Those with at least one T-allele were overrepresented in the responder group (42% vs 19%, p=0.08), and they had better improvement on the hyperactivity-impulsivity scale compared to the AA genotype (p=0.04). Although none of our single SNP findings remained significant after correcting for multiple testing, our results from the MPH-response analysis indicate the potential importance of promoter variants in the NET gene. Copyright © 2018 Elsevier Inc. All rights reserved.

Validation of public health competencies and impact variables for low- and middle-income countries

PubMed Central

2014-01-01

Background The number of Master of Public Health (MPH) programmes in low- and middle-income countries (LMICs) is increasing, but questions have been raised regarding the relevance of their outcomes and impacts on context. Although processes for validating public health competencies have taken place in recent years in many high-income countries, validation in LMICs is needed. Furthermore, impact variables of MPH programmes in the workplace and in society have not been developed. Method A set of public health competencies and impact variables in the workplace and in society was designed using the competencies and learning objectives of six participating institutions offering MPH programmes in or for LMICs, and the set of competencies of the Council on Linkages Between Academia and Public Health Practice as a reference. The resulting competencies and impact variables differ from those of the Council on Linkages in scope and emphasis on social determinants of health, context specificity and intersectoral competencies. A modified Delphi method was used in this study to validate the public health competencies and impact variables; experts and MPH alumni from China, Vietnam, South Africa, Sudan, Mexico and the Netherlands reviewed them and made recommendations. Results The competencies and variables were validated across two Delphi rounds, first with public health experts (N = 31) from the six countries, then with MPH alumni (N = 30). After the first expert round, competencies and impact variables were refined based on the quantitative results and qualitative comments. Both rounds showed high consensus, more so for the competencies than the impact variables. The response rate was 100%. Conclusion This is the first time that public health competencies have been validated in LMICs across continents. It is also the first time that impact variables of MPH programmes have been proposed and validated in LMICs across continents. The high degree of consensus between experts and alumni suggests that these public health competencies and impact variables can be used to design and evaluate MPH programmes, as well as for individual and team assessment and continuous professional development in LMICs. PMID:24438672

How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition.

PubMed

Hawk, Larry W; Fosco, Whitney D; Colder, Craig R; Waxmonsky, James G; Pelham, William E; Rosch, Keri S

2018-05-07

Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments. © 2018 Association for Child and Adolescent Mental Health.

Injuries to the urethra and urinary bladder associated with fractures of the pelvis.

PubMed

Morehouse, D D

1988-03-01

The posterior urethra or urinary bladder may be injured in patients who sustain fractures of the bony pelvis. It is important to assess the urethra radiologically by retrograde urethrography before introducing a urethral catheter to avoid missing a urethral injury or causing further damage. The author's approach to the immediate management of urethral injury is suprapubic cystostomy. The urethra may be repaired later after other injuries have healed. With this approach the incidence of permanent impotence and incontinence will be low and the stricture cure rate high. If the urethra has not been injured, a catheter is introduced and cystography performed to rule out bladder injuries. If the bladder is ruptured, the area is explored, the perivesical space drained and urinary drainage is provided by either a suprapubic cystostomy or a urethral catheter.

Implementing speed reductions at specific interstate work zones from 65 mph to 35 mph : final report.

DOT National Transportation Integrated Search

2013-02-01

Interstate preservation projects are commonly conducted at night and often require working in close proximity to ongoing traffic. Vehicle speed and speed variability in work zones is inextricably connected to the work zone design and the selected tra...

Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies

PubMed Central

2013-01-01

Background The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed. The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection. Methods A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included. Results Of 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study. Conclusions Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation. No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment. For patients achieving suboptimal symptom control, switching long-acting MPH formulations may be beneficial. When switching formulations, it is usually appropriate to titrate the immediate-release component of the formulation; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components. Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response. PMID:24074240

Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies.

PubMed

Coghill, David; Banaschewski, Tobias; Zuddas, Alessandro; Pelaz, Antonio; Gagliano, Antonella; Doepfner, Manfred

2013-09-27

The stimulant methylphenidate (MPH) has been a mainstay of treatment for attention-deficit/hyperactivity disorder (ADHD) for many years. Owing to the short half-life and the issues associated with multiple daily dosing of immediate-release MPH formulations, a new generation of long-acting MPH formulations has emerged. Direct head-to-head studies of these long-acting MPH formulations are important to facilitate an evaluation of their comparative pharmacokinetics and efficacy; however, to date, relatively few head-to-head studies have been performed.The objective of this systematic review was to compare the evidence available from head-to-head studies of long-acting MPH formulations and provide information that can guide treatment selection. A systematic literature search was conducted in MEDLINE and PsycINFO in March 2012 using the MeSH terms: attention deficit disorder with hyperactivity/drug therapy; methylphenidate/therapeutic use and All Fields: Concerta; Ritalin LA; OROS and ADHD; Medikinet; Equasym XL and ADHD; long-acting methylphenidate; Diffucaps and ADHD; SODAS and methylphenidate. No filters were applied and no language, publication date or publication status limitations were imposed. Articles were selected if the title indicated a comparison of two or more long-acting MPH preparations in human subjects of any age; non-systematic review articles and unpublished data were not included. Of 15,295 references returned in the literature search and screened by title, 34 articles were identified for inclusion: nine articles from pharmacokinetic studies (nine studies); nine articles from laboratory school studies (six studies); two articles from randomized controlled trials (two studies); three articles from switching studies (two studies) and three articles from one observational study. Emerging head-to-head studies provide important data on the comparative efficacy of the formulations available. At a group level, efficacy across the day generally follows the pharmacokinetic profile of the MPH formulation. No formulation is clearly superior to another; careful consideration of patient needs and subtle differences between formulations is required to optimize treatment. For patients achieving suboptimal symptom control, switching long-acting MPH formulations may be beneficial. When switching formulations, it is usually appropriate to titrate the immediate-release component of the formulation; a limitation of current studies is a focus on total daily dose rather than equivalent immediate-release components. Further studies are necessary to provide guidance in clinical practice, particularly in the treatment of adults and pre-school children and the impact of comorbidities and symptom severity on treatment response.

Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Childress, Ann; Berry, Sally A.; Belden, Heidi; Walters, Faith; Chappell, Phillip; Sherman, Nancy; Orazem, John; Palumbo, Donna

2017-01-01

Abstract Objective: This phase 3, laboratory classroom study assessed the efficacy and safety of methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD). Methods: Following a 6-week, open-label, dose-optimization period, children 6–12 years of age (n = 90) with ADHD were randomly assigned to double-blind MPH ERCT at the final optimized dose (20–60 mg/day) or placebo. After 1 week of double-blind treatment, efficacy was assessed predose and 0.75, 2, 4, 8, 10, 12, and 13 hours postdose in a laboratory classroom setting. The primary efficacy measure was the average of postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores, analyzed using a mixed-model, repeated-measures analysis. Secondary efficacy measures included Permanent Product Measure of Performance (PERMP) total number of problems attempted and total number of problems correct. Safety assessments included adverse event (AE) monitoring and the Columbia-Suicide Severity Rating Scale (C-SSRS). Results: MPH ERCT treatment statistically significantly reduced the average of all postdose SKAMP-Combined scores versus placebo (least-squares mean difference [95% confidence interval], −7.0 [−10.9, −3.1]; p < 0.001). Statistically significant treatment differences in SKAMP-Combined scores were observed at 2 hours postdose through 8 hours postdose (p-values <0.001). Statistically significant differences between MPH ERCT and placebo in PERMP total number of problems attempted and total number of problems correct were observed at 0.75 hours postdose through 8 hours postdose (p-values ≤0.049). Common AEs in the open-label period (≥5%) were decreased appetite, upper abdominal pain, mood swings, irritability, insomnia, upper respiratory tract infection (URTI), dysgeusia, and headache; URTI was the only AE reported by >1 subject receiving MPH ERCT in the double-blind period (placebo: URTI, contusion, wound, and initial insomnia). No suicidal ideation or behavior was reported on the C-SSRS at baseline or at any postbaseline assessment. Conclusions: MPH ERCT 20–60 mg significantly improved ADHD symptoms compared with placebo at 2 hours postdose through at least 8 hours postdose. MPH ERCT was generally safe and well tolerated, with a safety profile consistent with other MPH ER formulations. ClinicalTrials.gov Identifier: NCT01654250. www.clinicaltrials.gov/ct2/show/NCT01654250. PMID:28557548

Osmotic Release Oral System Methylphenidate Versus Atomoxetine for the Treatment of Attention-Deficit/Hyperactivity Disorder in Chinese Youth: 8-Week Comparative Efficacy and 1-Year Follow-Up.

PubMed

Su, Yi; Yang, Li; Stein, Mark A; Cao, Qingjiu; Wang, Yufeng

2016-05-01

The purpose of this study was to compare the short-term efficacy, tolerability, and 1-year adherence in Chinese children and adolescents with attention-deficit/hyperactivity disorder (ADHD) treated with either osmotic release oral system methylphenidate (OROS MPH) or atomoxetine (ATX). Children and adolescents meeting Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for ADHD were randomly assigned to receive either OROS MPH (n = 119) or ATX (n = 118). Participants underwent a 1-4 week dose titration period to determine optimal dose, and then were maintained on that dose for 4 weeks (maintenance period). Assessment for efficacy was conducted every week over the titration period and at the end of the maintenance period. The primary efficacy measure was the investigator-rated total ADHD Rating Scale-IV (ADHD-RS-IV) score. Response was further classified as remission (ADHD-RS-IV [18 or 9 items] average score ≤1), robust improvement (ADHD-RS-IV ≥40% decrease in total score), or improvement (≥ 25% decrease in total score) at the end of maintenance period. Medication adherence (taking medication at least 5 days in 1 week) and reasons for nonadherence were evaluated every week over the titration period, at the end of maintenance period, and then at 3, 6, and 12 months. At the end of maintenance period, both OROS MPH and ATX were associated with significant and similar reductions from baseline in ADHD symptoms. Percentages achieving remission, robust improvement, and improvement were comparable for OROS MPH and ATX treatment (35.3% vs. 37.1%, 45.4% vs. 44.8%, 65.5% vs. 66.4%). Medication use decreased over time for both treatments; however, at end of maintenance period, 3 month, 6 month, and 1 year follow-ups, subjects in the OROS MPH group were more likely to be compliant with treatment (74.8%, 50.4%, 38.7%, and 21.8% for OROS MPH vs. 52.5%, 33.9%, 12.7%, and 3.4% for ATX) ( p < 0.05). The most common reasons for nonadherence were adverse events and lack of efficacy. Both OROS MPH and ATX resulted in similar reductions in ADHD symptoms in Chinese children and adolescents with ADHD. Long-term adherence with medication was poor in general, although somewhat better with OROS MPH than with ATX. ClinicalTrials.gov , Identifier: NCT01065259.

Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea

PubMed Central

Duszenko, Nikolas

2017-01-01

ABSTRACT Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found in Methanosarcina species that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studied Methanosarcina species, Methanosarcina acetivorans C2A and Methanosarcina barkeri Fusaro, to the quinone pool size in the bacterium Escherichia coli. We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher in M. acetivorans than in M. barkeri. The concentration of MPh suggests the cell membrane of M. acetivorans, but not of M. barkeri, is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing) E. coli cells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate of M. barkeri three times that of M. acetivorans. Our work suggests electron flux through MPh is naturally higher in M. acetivorans than in M. barkeri and that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh. IMPORTANCE Can we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggest Methanosarcina acetivorans, but not Methanosarcina barkeri, has electrically quantized membranes. Escherichia coli, a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale. PMID:28710268

Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea.

PubMed

Duszenko, Nikolas; Buan, Nicole R

2017-09-15

Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found in Methanosarcina species that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studied Methanosarcina species, Methanosarcina acetivorans C2A and Methanosarcina barkeri Fusaro, to the quinone pool size in the bacterium Escherichia coli We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher in M. acetivorans than in M. barkeri The concentration of MPh suggests the cell membrane of M. acetivorans , but not of M. barkeri , is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing) E. coli cells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate of M. barkeri three times that of M. acetivorans Our work suggests electron flux through MPh is naturally higher in M. acetivorans than in M. barkeri and that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh. IMPORTANCE Can we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggest Methanosarcina acetivorans , but not Methanosarcina barkeri , has electrically quantized membranes. Escherichia coli , a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale. Copyright © 2017 American Society for Microbiology.

Diagnosis and treatment of urinary tract infections across age groups.

PubMed

Chu, Christine M; Lowder, Jerry L

2018-01-02

Urinary tract infections are the most common outpatient infections, but predicting the probability of urinary tract infections through symptoms and test results can be complex. The most diagnostic symptoms of urinary tract infections include change in frequency, dysuria, urgency, and presence or absence of vaginal discharge, but urinary tract infections may present differently in older women. Dipstick urinalysis is popular for its availability and usefulness, but results must be interpreted in context of the patient's pretest probability based on symptoms and characteristics. In patients with a high probability of urinary tract infection based on symptoms, negative dipstick urinalysis does not rule out urinary tract infection. Nitrites are likely more sensitive and specific than other dipstick components for urinary tract infection, particularly in the elderly. Positive dipstick testing is likely specific for asymptomatic bacteriuria in pregnancy, but urine culture is still the test of choice. Microscopic urinalysis is likely comparable to dipstick urinalysis as a screening test. Bacteriuria is more specific and sensitive than pyuria for detecting urinary tract infection, even in older women and during pregnancy. Pyuria is commonly found in the absence of infection, particularly in older adults with lower urinary tract symptoms such as incontinence. Positive testing may increase the probability of urinary tract infection, but initiation of treatment should take into account risk of urinary tract infection based on symptoms as well. In cases in which the probability of urinary tract infection is moderate or unclear, urine culture should be performed. Urine culture is the gold standard for detection of urinary tract infection. However, asymptomatic bacteriuria is common, particularly in older women, and should not be treated with antibiotics. Conversely, in symptomatic women, even growth as low as 10 2 colony-forming unit/mL could reflect infection. Resistance is increasing to fluoroquinolones, beta-lactams, and trimethoprim-sulfamethoxazole. Most uropathogens still display good sensitivity to nitrofurantoin. First-line treatments for urinary tract infection include nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole (when resistance levels are <20%). These antibiotics have minimal collateral damage and resistance. In pregnancy, beta-lactams, nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole can be appropriate treatments. Interpreting the probability of urinary tract infection based on symptoms and testing allows for greater accuracy in diagnosis of urinary tract infection, decreasing overtreatment and encouraging antimicrobial stewardship. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of MPH-OROS on the organizational, time management, and planning behaviors of children with ADHD.

PubMed

Abikoff, Howard; Nissley-Tsiopinis, Jenelle; Gallagher, Richard; Zambenedetti, Maurizio; Seyffert, Michael; Boorady, Roy; McCarthy, John

2009-02-01

To evaluate the effects of stimulant medication on organizational, time management, and planning (OTMP) in children with attention-deficit/hyperactivity disorder (ADHD) and ascertain whether OTMP is normalized with medication. Participants included 19 stimulant-naïve children with ADHD (aged 8-13 years) and impaired OTMP functioning, defined as greater than 1 SD below norms on the Children's Organizational Skills Scale. A double-blind, placebo-controlled, crossover design, with 4 weeks of each condition, evaluated medication (methylphenidate-osmotic-release oral system [MPH-OROS]) effects on OTMP, based on the parent and teacher versions of the Children's Organizational Skills Scale. The parent and teacher Swanson, Nolan, and Pelham, Version IV, rating scales assessed ADHD symptoms. "Not impaired" in OTMP was defined as no longer meeting study entry criteria, and "not impaired" in ADHD symptoms was defined as having mean Swanson, Nolan, and Pelham, Version IV, scores of < or = 1.0. MPH-OROS significantly improved children's OTMP behaviors. These improvements were correlated with significant reductions in ADHD symptoms. However, most of the children (61%) continued to show significant OTMP impairments on MPH-OROS. The MPH-OROS reduced children's OTMP deficits, and these improvements were associated with improvements in ADHD symptoms. Some children remained impaired in OTMP even after effective stimulant treatment of ADHD symptoms. These youngsters may require other treatments that target OTMP deficits.

Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder.

PubMed

Bottelier, Marco A; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G H; Bouziane, Cheima; Kooij, J J Sandra; de Ruiter, Michiel B; Reneman, Liesbeth

2017-11-30

In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90min after an acute oral challenge with MPH (0.5mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

A pilot study: differential effects of methylphenidate-OROS on working memory and attention functions in children with attention-deficit/hyperactivity disorder with and without behavioural comorbidities.

PubMed

Rubio, Belén; Hernández, Sergio; Verche, Emilio; Martín, Raquel; González-Pérez, Pedro

2011-03-01

To examine the effects of methylphenidate-OROS (MPH-OROS) on working memory (WM) and attention functions in children with attention-deficit hyperactivity disorder (ADHD), and to investigate whether there is a differential effect in ADHD children with (ADHD+) and without (ADHD-) behavioural comorbidities. Participants included a clinic referred sample of 12 stimulant naïve school-aged children with a diagnosis of combined ADHD according to the DSM-IV criteria (6 ADHD+, 6 ADHD-), and 11 healthy children. A neuropsychological protocol was applied at three different moments: before treatment, after one those of MPH-OROS, and after one month of MPH-OROS daily treatment. The protocol was simultaneously administered to the control group. Initial differences in attention parameters between naïve children with ADHD and the control group disappeared after the first dose of MPH-OROS. For WM, one month of daily treatment was necessary to achieve this pattern of results. Both ADHD groups (ADHD+ and ADHD-) showed these differences, but there was a greater improvement in (ADHD-). MPH-OROS had an immediate effect on attention deficits, but long-term treatment was needed to improve WM to the level of healthy subjects. The presence of comorbid behavioural conditions determined a less robust response in neuropsychological performance to stimulant treatment.

Effects of concomitant methylphenidate and ethanol administration on working and reference memory in rats.

PubMed

Sloan, Anthony R; McGovern, Robin; Buffalari, Deanne M

Recent studies have suggested that college students are heavily engaged in non-medical use of stimulant drugs prescribed to treat attention deficit hyperactivity disorder. This age group is also at high risk for alcohol use. Despite their potential co-abuse, little work has examined how these drugs interact to affect cognitive abilities. In fact, these drugs have opposing effects on working memory, which brings into question how they may interact to affect this particular behavior. The purpose of this research was to examine the concomitant effects of methylphenidate (MPH) and ethanol (EtOH) on working and reference memory. Rats were first trained on the radial arm maze task to establish a baseline performance rate measured as average number of reference and working memory errors. Performance was then assessed after injections of saline, MPH alone, EtOH alone, and MPH+EtOH combined. While both doses of MPH caused nonsignificant improvements in working memory, when combined with EtOH, there was an overall impairment in working and reference memory compared to other conditions. EtOH alone also decreased memory. These data indicate increased impairment of memory function with combined MPH and EtOH use. By understanding how the combination of methylphenidate and alcohol affects memory, we can better assess the risks of taking both substances simultaneously. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Interaction Between DRD4 Methylation and Prenatal Maternal Stress on Methylphenidate-Induced Changes in Continuous Performance Test Performance in Youth with Attention-Deficit/Hyperactivity Disorder.

PubMed

Kim, Johanna Inhyang; Kim, Jae-Won; Shin, Inkyung; Kim, Bung-Nyun

2018-06-15

Environmental factors may interact with genetic factors via the epigenetic process, and this interaction can contribute to inter-individual variability in the treatment response. The purpose of this study was to investigate the interaction effects between dopamine receptor D4 (DRD4) methylation and prenatal maternal stress on the methylphenidate (MPH) response of youth with attention-deficit/hyperactivity disorder (ADHD). This study was an 8-week open-label trial of MPH that included 74 ADHD youth. We investigated the associations between MPH treatment response, which was defined as a score ≤2 on the Clinical Global Impressions-Improvement (CGI-I) scale, and the methylation of 28 cytosine-guanine dinucleotide (CpG) sites of DRD4. Additionally, the interaction effects between DRD4 methylation and prenatal maternal stress on changes in Continuous Performance Test (CPT) scores after MPH treatment were investigated. Although there were no significant sites that showed significant association with treatment response, there was a significant interaction effect of the methylation of CpG7 and prenatal maternal stress on changes in omission errors of the CPT following treatment (p = 0.0001). The present findings indicate that the interaction between methylation of CpG7 of DRD4 and prenatal maternal stress may be predictive of the treatment response to MPH in youth with ADHD.

Effect of methylphenidate and/or levodopa combined with physiotherapy on mood and cognition after stroke: a randomized, double-blind, placebo-controlled trial.

PubMed

Delbari, Ahmad; Salman-Roghani, Reza; Lokk, Johan

2011-01-01

Stimulant medications can enhance mood and cognition in stroke rehabilitation, but human clinical trial results are inconclusive. We sought to prospectively study the effects of levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy on mood and cognition following stroke in human subjects. Ischemic stroke patients were enrolled in our study 15 to 180 days after stroke onset. The patients were randomized into four medication groups (MPH, LD, MPH + LD, or placebo) and received a 15-day course of medication therapy (1 dose daily) and 45-min standard physiotherapy treatment daily. Mood and cognitive function were assessed at the study onset and 15, 90 and 180 days after study enrollment. The strongest improvement of mood and cognition was found between baseline and the first follow-up immediately after the intervention. A significant improvement in mood was also found in the combined treatment group (MPH + LD) at 90 and 180 days, compared to the placebo group. A 15-day course of daily MPH + LD combined with physiotherapy over a 3-week period was safe and significantly improved mood status in ischemic stroke patients. Future studies are needed which determine the optimal therapeutic window for and dosage of psychostimulants as well as identify those stroke patients who might benefit the most from treatment. Copyright © 2011 S. Karger AG, Basel.

Family Medicine or Primary Care Residency Selection: Effects of Family Medicine Interest Groups, MD/MPH Dual Degrees, and Rural Medical Education.

PubMed

Wei McIntosh, Elizabeth; Morley, Christopher P

2016-05-01

If medical schools are to produce primary care physicians (family medicine, pediatrics, or general internal medicine), they must provide educational experiences that enable medical students to maintain existing or form new interests in such careers. This study examined three mechanisms for doing so, at one medical school: participation as an officer in a family medicine interest group (FMIG), completion of a dual medical/public health (MD/MPH) degree program, and participation in a rural medical education (RMED) clinical track. Specialty Match data for students who graduated from the study institution between 2006 and 2015 were included as dependent variables in bivariate analysis (c2) and logistic regression models, examining FMIG, MD/MPH, and RMED participation as independent predictors of specialty choice (family medicine yes/no, or any primary care (PC) yes/no), controlling for student demographic data. In bivariate c2 analyses, FMIG officership did not significantly predict matching with family medicine or any PC; RMED and MD/MPH education were significant predictors of both family medicine and PC. Binary logistic regression analyses replicated the bivariate findings, controlling for student demographics. Dual MD/MPH and rural medical education had stronger effects in producing primary care physicians than participation in a FMIG as an officer, at one institution. Further study at multiple institutions is warranted.

The role of urinary fractionated metanephrines in the diagnosis of phaeochromocytoma

PubMed Central

Jeyaraman, Kanakamani; Natarajan, Vasanthi; Thomas, Nihal; Jacob, Paul Mazhuvanchary; Nair, Aravindan; Shanthly, Nylla; Oommen, Regi; Varghese, Gracy; Joseph, Fleming Jude; Seshadri, Mandalam Subramaniam; Rajaratnam, Simon

2013-01-01

Background & objectives: Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma. Methods: Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit. Results: Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 μg/day had a low sensitivity and uNMN >600 μg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent. Interpretation & conclusions: ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population. PMID:23563375

The role of urinary fractionated metanephrines in the diagnosis of phaeochromocytoma.

PubMed

Jeyaraman, Kanakamani; Natarajan, Vasanthi; Thomas, Nihal; Jacob, Paul Mazhuvanchary; Nair, Aravindan; Shanthly, Nylla; Oommen, Regi; Varghese, Gracy; Joseph, Fleming Jude; Seshadri, Mandalam Subramaniam; Rajaratnam, Simon

2013-02-01

Plasma and urinary metanephrines are used as screening tests for the diagnosis of phaeochromocytoma. The recommended cut-off levels are not standardized. This study was conducted to identify a cut-off level for 24 h urinary fractionated metanephrines viz. metanephrine (uMN) and normetanephrine (uNMN) using enzyme immunoassay for the diagnosis of phaeochromocytoma. Consecutive patients suspected to have phaeochromocytoma were included in the study. uMN and uNMN in 24 h urinary sample were measured using a commercial ELISA kit. Overall, 72 patients were included over a period of 18 months. Twenty patients had histopathologically confirmed phaeochromocytoma and in 52 patients phaeochromocytoma was ruled out. Using the upper limit of normal stated by the assay manufacturer as the cut-off, uMN >350 μg/day had a low sensitivity and uNMN >600 μg/day had a poor specificity. By increasing the cut-off value of uNMN to twice the upper limit, specificity increased significantly without much loss in sensitivity. Combining uMN and uNMN using a cut-off twice the upper limit improved the diagnostic performance - sensitivity (95%); specificity (92.3%); positive predictive value (PPV - 82.6%); negative predictive value (NPV - 98%). In subsets of patients with a variable pretest probability for phaeochromocytoma, the PPV correlates well with the occurred of these tumors decreased, while the NPV remained at 100 per cent. ELISA is a simple and reliable method for measuring uMN and uNMN. The test has a good NPV and can be used as an initial screening test for ruling out phaeochromocytoma. Each hospital will have to define the cut-off value for the assay being used, choosing a proper control population.

The effectiveness of the 55 MPH national maximum speed limit as a life saving benefit

DOT National Transportation Integrated Search

1980-10-01

The report contains an analysis of the life saving benefits resulting from the 55 mph NMSL from 1974-1979. Monthly fatality data from 1970-1979 was used in a time series model to arrive at the estimated safety benefits (lives saved). The time series ...

40 CFR 610.64 - Track test procedures.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 31 2012-07-01 2012-07-01 false Track test procedures. 610.64 Section 610.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL... necessary to limit testing to times when the wind velocity is less than 5 mph, with gusts less than 10 mph...

40 CFR 610.64 - Track test procedures.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 31 2013-07-01 2013-07-01 false Track test procedures. 610.64 Section 610.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) ENERGY POLICY FUEL... necessary to limit testing to times when the wind velocity is less than 5 mph, with gusts less than 10 mph...

Spray spectrum modifications through changes in airspeed to minimize drift

USDA-ARS?s Scientific Manuscript database

Management of droplet size is one of the key components to minimizing spray drift, which can be accomplished in-flight by changing airspeed. Studies were conducted measuring spray droplet spectra parameters across airspeeds ranging from 100-140 mph (in 5 mph increments). In general the volume medi...

Implementing speed reductions at specific interstate work zones from 65 mph to 35 mph : appendices to final report.

DOT National Transportation Integrated Search

2013-02-01

Interstate preservation projects are commonly conducted at night and often require working in close proximity to ongoing traffic. Vehicle speed and speed variability in work zones is inextricably connected to the work zone design and the selected tra...

The effect of multiple primary rules on population-based cancer survival

PubMed Central

Weir, Hannah K.; Johnson, Christopher J.; Thompson, Trevor D.

2015-01-01

Purpose Different rules for registering multiple primary (MP) cancers are used by cancer registries throughout the world, making international data comparisons difficult. This study evaluates the effect of Surveillance, Epidemiology, and End Results (SEER) and International Association of Cancer Registries (IACR) MP rules on population-based cancer survival estimates. Methods Data from five US states and six metropolitan area cancer registries participating in the SEER Program were used to estimate age-standardized relative survival (RS%) for first cancers-only and all first cancers matching the selection criteria according to SEER and IACR MP rules for all cancer sites combined and for the top 25 cancer site groups among men and women. Results During 1995–2008, the percentage of MP cancers (all sites, both sexes) increased 25.4 % by using SEER rules (from 14.6 to 18.4 %) and 20.1 % by using IACR rules (from 13.2 to 15.8 %). More MP cancers were registered among females than among males, and SEER rules registered more MP cancers than IACR rules (15.8 vs. 14.4 % among males; 17.2 vs. 14.5 % among females). The top 3 cancer sites with the largest differences were melanoma (5.8 %), urinary bladder (3.5 %), and kidney and renal pelvis (2.9 %) among males, and breast (5.9 %), melanoma (3.9 %), and urinary bladder (3.4 %) among females. Five-year survival estimates (all sites combined) restricted to first primary cancers-only were higher than estimates by using first site-specific primaries (SEER or IACR rules), and for 11 of 21 sites among males and 11 of 23 sites among females. SEER estimates are comparable to IACR estimates for all site-specific cancers and marginally higher for all sites combined among females (RS 62.28 vs. 61.96 %). Conclusion Survival after diagnosis has improved for many leading cancers. However, cancer patients remain at risk of subsequent cancers. Survival estimates based on first cancers-only exclude a large and increasing number of MP cancers. To produce clinically and epidemiologically relevant and less biased cancer survival estimates, data on all cancers should be included in the analysis. The multiple primary rules (SEER or IACR) used to identify primary cancers do not affect survival estimates if all first cancers matching the selection criteria are used to produce site-specific survival estimates. PMID:23558444

Virulence of Macrophomina phaseolina isolates in common bean (Phaseolus vulgaris) genotypes

USDA-ARS?s Scientific Manuscript database

Charcoal rot caused by Macrophomina phaseolina (Tassi) Goid, is an important disease in common beans (Phaseolus vulgaris) in the dry and warmer areas of Puerto Rico and in much of the tropics and subtropics worldwide. The virulence of three isolates from Isabela (Mph-ISA-TARS), Juana Diaz (Mph-JD) a...

The effectiveness of the 55 MPH national maximum speed limit as a life saving benefit : executive summary

DOT National Transportation Integrated Search

1981-01-01

The following report contains an analysis of the life saving benefits resulting from the 55 mph NMSL from 1974-1979. Monthly fatality data from 1970-1979 was used in a time series model to arrive at the estimated safety benefits (lives saved). The ti...

Animal Model of Methylphenidate's Longterm Memory-Enhancing Effects

ERIC Educational Resources Information Center

Carmack, Stephanie A.; Howell, Kristin K.; Rasaei, Kleou; Reas, Emilie T.; Anagnostaras, Stephan G.

2014-01-01

Methylphenidate (MPH), introduced more than 60 years ago, accounts for two-thirds of current prescriptions for attention deficit hyperactivity disorder (ADHD). Although many studies have modeled MPH's effect on executive function, almost none have directly modeled its effect on long-term memory (LTM), even though improvement in LTM is a…

Effects of Methylphenidate on Working Memory Components: Influence of Measurement

ERIC Educational Resources Information Center

Bedard, Anne-Claude; Jain, Umesh; Hogg-Johnson, Sheilah; Tannock, Rosemary

2007-01-01

Background: To investigate the effects of methylphenidate (MPH) on components of working memory (WM) in attention-deficit hyperactivity disorder (ADHD) and determine the responsiveness of WM measures to MPH. Methods: Participants were a clinical sample of 50 children and adolescents with ADHD, aged 6 to 16 years old, who participated in an acute…

A revolution in preventing fatal craniovertebral junction injuries: lessons learned from the Head and Neck Support device in professional auto racing.

PubMed

Kaul, Anand; Abbas, Ahmed; Smith, Gabriel; Manjila, Sunil; Pace, Jonathan; Steinmetz, Michael

2016-12-01

Fatal craniovertebral junction (CVJ) injuries were the most common cause of death in high-speed motor sports prior to 2001. Following the death of a mutual friend and race car driver, Patrick Jacquemart (1946-1981), biomechanical engineer Dr. Robert Hubbard, along with race car driver and brother-in-law Jim Downing, developed the concept for the Head and Neck Support (HANS) device to prevent flexion-distraction injuries during high-velocity impact. Biomechanical testing showed that neck shear and loading forces experienced during collisions were 3 times the required amount for a catastrophic injury. Crash sled testing with and without the HANS device elucidated reductions in neck tension, neck compression, head acceleration, and chest acceleration experienced by dummies during high-energy crashes. Simultaneously, motor sports accidents such as Dale Earnhardt Sr.'s fatal crash in 2001 galvanized public opinion in favor of serious safety reform. Analysis of Earnhardt's accident demonstrated that his car's velocity parallel to the barrier was more than 150 miles per hour (mph), with deceleration upon impact of roughly 43 mph in a total of 0.08 seconds. After careful review, several major racing series such as the National Association for Stock Car Auto Racing (NASCAR) and Championship Auto Racing Team (CART) made major changes to ensure the safety of drivers at the turn of the 21st century. Since the rule requiring the HANS device in professional auto racing series was put in place, there has not been a single reported case of a fatal CVJ injury.

Effects of Extended Release Methylphenidate Treatment on Ratings of Attention-Deficit/Hyperactivity Disorder (ADHD) and Associated Behavior in Children with Autism Spectrum Disorders and ADHD Symptoms

PubMed Central

Santos, Cynthia W.; Aman, Michael G.; Arnold, L. Eugene; Casat, Charles D.; Mansour, Rosleen; Lane, David M.; Loveland, Katherine A.; Bukstein, Oscar G.; Jerger, Susan W.; Factor, Perry; Vanwoerden, Salome; Perez, Evelyn; Cleveland, Lynne A.

2013-01-01

Abstract Objective The purpose of this study was to examine the behavioral effects of four doses of psychostimulant medication, combining extended-release methylphenidate (MPH) in the morning with immediate-release MPH in the afternoon. Method The sample comprised 24 children (19 boys; 5 girls) who met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age=8.8 years, SD=1.7; mean intelligence quotient [IQ]=85; SD=16.8). Effects of four dose levels of MPH on parent and teacher behavioral ratings were investigated using a within-subject, crossover, placebo-controlled design. Results MPH treatment was associated with significant declines in hyperactive and impulsive behavior at both home and school. Parents noted significant declines in inattentive and oppositional behavior, and improvements in social skills. No exacerbation of stereotypies was noted, and side effects were similar to those seen in typically developing children with ADHD. Dose response was primarily linear in the dose range studied. Conclusions The results of this study suggest that MPH formulations are efficacious and well-tolerated for children with ASD and significant ADHD symptoms. PMID:23782128

The effect of methylphenidate and rearing environment on behavioral inhibition in adult male rats.

PubMed

Hill, Jade C; Covarrubias, Pablo; Terry, Joel; Sanabria, Federico

2012-01-01

The ability to withhold reinforced responses-behavioral inhibition-is impaired in various psychiatric conditions including Attention Deficit Hyperactivity Disorder (ADHD). Methodological and analytical limitations have constrained our understanding of the effects of pharmacological and environmental factors on behavioral inhibition. To determine the effects of acute methylphenidate (MPH) administration and rearing conditions (isolated vs. pair-housed) on behavioral inhibition in adult rats. Inhibitory capacity was evaluated using two response-withholding tasks, differential reinforcement of low rates (DRL) and fixed minimum interval (FMI) schedules of reinforcement. Both tasks made sugar pellets contingent on intervals longer than 6 s between consecutive responses. Inferences on inhibitory and timing capacities were drawn from the distribution of withholding times (interresponse times, or IRTs). MPH increased the number of intervals produced in both tasks. Estimates of behavioral inhibition increased with MPH dose in FMI and with social isolation in DRL. Nonetheless, burst responding in DRL and the divergence of DRL data relative to past studies, among other limitations, undermined the reliability of DRL data as the basis for inferences on behavioral inhibition. Inhibitory capacity was more precisely estimated from FMI than from DRL performance. Based on FMI data, MPH, but not a socially enriched environment, appears to improve inhibitory capacity. The highest dose of MPH tested, 8 mg/kg, did not reduce inhibitory capacity but reduced the responsiveness to waiting contingencies. These results support the use of the FMI schedule, complemented with appropriate analytic techniques, for the assessment of behavioral inhibition in animal models.

Mixed-Effects Modeling of Neurofeedback Self-Regulation Performance: Moderators for Learning in Children with ADHD.

PubMed

Zuberer, Agnieszka; Minder, Franziska; Brandeis, Daniel; Drechsler, Renate

2018-01-01

Neurofeedback (NF) has gained increasing popularity as a training method for children and adults with attention deficit hyperactivity disorder (ADHD). However, it is unclear to what extent children learn to regulate their brain activity and in what way NF learning may be affected by subject- and treatment-related factors. In total, 48 subjects with ADHD (age 8.5-16.5 years; 16 subjects on methylphenidate (MPH)) underwent 15 double training sessions of NF in either a clinical or a school setting. Four mixed-effects models were employed to analyze learning: training within-sessions, across-sessions, with continuous feedback, and with transfer in which performance feedback is delayed. Age and MPH affected the NF performance in all models. Cross-session learning in the feedback condition was mainly moderated by age and MPH, whereas NF learning in the transfer condition was mainly boosted by MPH. Apart from IQ and task types, other subject-related or treatment-related effects were unrelated to NF learning. This first study analyzing moderators of NF learning in ADHD with a mixed-effects modeling approach shows that NF performance is moderated differentially by effects of age and MPH depending on the training task and time window. Future studies may benefit from using this approach to analyze NF learning and NF specificity. The trial name Neurofeedback and Computerized Cognitive Training in Different Settings for Children and Adolescents With ADHD is registered with NCT02358941.

Neurotrophin 3 genotype and emotional adverse effects of osmotic-release oral system methylphenidate (OROS-MPH) in children with attention-deficit/hyperactivity disorder.

PubMed

Park, Subin; Kim, Bung-Nyun; Kim, Jae-Won; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

2014-03-01

Neurotrophin 3 (NTF3) has been studied in relation to the pathophysiology of attention-deficit/hyperactivity disorder (ADHD) and mood disorders as well as psychostimulant action. We hypothesized that the risk of an emotional side effect to methylphenidate (MPH) treatment may be associated with NTF3 genotypes. Ninety-six medication-naïve children with ADHD (mean age 8.70, standard deviation 1.41 years, 79 males) were genotyped and treated with MPH. At baseline, which was prior to MPH treatment, and after two weeks of medication, investigators asked children and their parents or caregivers about adverse events using a symptom rating scale. ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Emotionality' and 'Over-focus/euphoria' factor scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.042 and p=0.045, respectively). ADHD subjects with the A/A genotype at the NTF3 rs6332 polymorphism showed the highest 'Proneness to crying' and 'Nail biting' item scores, followed by those with the G/A genotype and those with the G/G genotype (p=0.047 and p=0.017, respectively). These data provide preliminary evidence that genetic variation in the NTF3 gene is related to susceptibility to emotional side effects in response to MPH treatment in Korean children with ADHD.

Effects of extended release methylphenidate treatment on ratings of attention-deficit/hyperactivity disorder (ADHD) and associated behavior in children with autism spectrum disorders and ADHD symptoms.

PubMed

Pearson, Deborah A; Santos, Cynthia W; Aman, Michael G; Arnold, L Eugene; Casat, Charles D; Mansour, Rosleen; Lane, David M; Loveland, Katherine A; Bukstein, Oscar G; Jerger, Susan W; Factor, Perry; Vanwoerden, Salome; Perez, Evelyn; Cleveland, Lynne A

2013-06-01

The purpose of this study was to examine the behavioral effects of four doses of psychostimulant medication, combining extended-release methylphenidate (MPH) in the morning with immediate-release MPH in the afternoon. The sample comprised 24 children (19 boys; 5 girls) who met American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) criteria for an autism spectrum disorder (ASD) on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS), and had significant symptoms of attention-deficit/hyperactivity disorder (ADHD). This sample consisted of elementary school-age, community-based children (mean chronological age=8.8 years, SD=1.7; mean intelligence quotient [IQ]=85; SD=16.8). Effects of four dose levels of MPH on parent and teacher behavioral ratings were investigated using a within-subject, crossover, placebo-controlled design. MPH treatment was associated with significant declines in hyperactive and impulsive behavior at both home and school. Parents noted significant declines in inattentive and oppositional behavior, and improvements in social skills. No exacerbation of stereotypies was noted, and side effects were similar to those seen in typically developing children with ADHD. Dose response was primarily linear in the dose range studied. The results of this study suggest that MPH formulations are efficacious and well-tolerated for children with ASD and significant ADHD symptoms.

Methylphenidate and emotional-motivational processing in attention-deficit/hyperactivity disorder.

PubMed

Conzelmann, Annette; Woidich, Eva; Mucha, Ronald F; Weyers, Peter; Müller, Mathias; Lesch, Klaus-Peter; Jacob, Christian P; Pauli, Paul

2016-08-01

In line with the assumption that emotional-motivational deficits are one core dysfunction in ADHD, in one of our previous studies we observed a reduced reactivity towards pleasant pictures in adult ADHD patients as compared to controls. This was indicated by a lack of attenuation of the startle reflex specifically during pleasant pictures in ADHD patients. The first choice medical agents in ADHD, methylphenidate (MPH), is discussed to normalize these dysfunctions. However, experimental evidence in the sense of double-blind placebo-controlled study designs is lacking. Therefore, we investigated 61 adult ADHD patients twice, one time with placebo and one time with MPH with the same experimental design as in our study previously and assessed emotion processing during the presentation of pleasant, neutral and unpleasant pictures. We obtained startle reflex data as well as valence and arousal ratings in association with the pictures. As previously shown, ADHD patients showed a diminished startle attenuation during pleasant pictures while startle potentiation during unpleasant pictures was normal. Valence and arousal ratings unsuspiciously increased with increasing pleasantness and arousal of the pictures, respectively. There were no significant influences of MPH. The study replicates that ADHD patients show a reduced reactivity towards pleasant stimuli. MPH did not normalize this dysfunction. Possibly, MPH only influences emotions during more complex behavioural tasks that involve executive functions in adults with ADHD. Our results emphasize the importance for the use of double-blind placebo-controlled designs in psychopharmacological research.

On the MAC/network/energy performance evaluation of Wireless Sensor Networks: Contrasting MPH, AODV, DSR and ZTR routing protocols.

PubMed

Del-Valle-Soto, Carolina; Mex-Perera, Carlos; Orozco-Lugo, Aldo; Lara, Mauricio; Galván-Tejada, Giselle M; Olmedo, Oscar

2014-12-02

Wireless Sensor Networks deliver valuable information for long periods, then it is desirable to have optimum performance, reduced delays, low overhead, and reliable delivery of information. In this work, proposed metrics that influence energy consumption are used for a performance comparison among our proposed routing protocol, called Multi-Parent Hierarchical (MPH), the well-known protocols for sensor networks, Ad hoc On-Demand Distance Vector (AODV), Dynamic Source Routing (DSR), and Zigbee Tree Routing (ZTR), all of them working with the IEEE 802.15.4 MAC layer. Results show how some communication metrics affect performance, throughput, reliability and energy consumption. It can be concluded that MPH is an efficient protocol since it reaches the best performance against the other three protocols under evaluation, such as 19.3% reduction of packet retransmissions, 26.9% decrease of overhead, and 41.2% improvement on the capacity of the protocol for recovering the topology from failures with respect to AODV protocol. We implemented and tested MPH in a real network of 99 nodes during ten days and analyzed parameters as number of hops, connectivity and delay, in order to validate our Sensors 2014, 14 22812 simulator and obtain reliable results. Moreover, an energy model of CC2530 chip is proposed and used for simulations of the four aforementioned protocols, showing that MPH has 15.9% reduction of energy consumption with respect to AODV, 13.7% versus DSR, and 5% against ZTR.

A novel HPLC fluorescence method for the quantification of methylphenidate in human plasma

PubMed Central

Zhu, Hao-Jie; Wang, Jun-Sheng; Patrick, Kennerly S.; Donovan, Jennifer L.; DeVane, C. Lindsay; Markowitz, John S.

2007-01-01

A number of analytical methods have been established to quantify methylphenidate (MPH). However, to date no HPLC methods are applicable to human pharmacokinetic studies without the use of mass spectrometry (MS) detection. We developed a sensitive and reliable HPLC-fluorescence method for the determination of MPH in human plasma using 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride (DIB-Cl) as the derivatizing agent. An established GC-MS method was adopted in this study as a comparator assay. MPH was derivatized DIB-Cl, and separated isocratically on a C18 column using a HPLC system with fluorescence detection (λex: 330 nm, λem: 460 nm). The lower limit of determination was found to be 1 ng/mL. A linear calibration curve was obtained over the concentrations ranging from 1 to 80 ng/mL (r=0.998). The relative standard deviations of intra-day and inter-day variations were ≤ 9.10 % and ≤ 7.58 %, respectively. The accuracy ranged between 92.59 % and 103.06 %. The method was successfully applied to the pharmacokinetic study of a subject who received a single oral dose (0.3 mg/kg) of immediate-release MPH and yielded consistent results with that of the GC-MS method. This method is the first HPLC assay with non-MS detection providing sufficient reliability and sensitivity for both pre-clinical and clinical studies of MPH. PMID:17804308

Methylphenidate, cognition, and epilepsy

PubMed Central

Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J.; Loring, David W.; Meador, Kimford

2017-01-01

Objective: To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. Methods: This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Results: Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20–62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive “fogginess” (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. Conclusions: This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. ClinicalTrials.gov identifier: NCT02178995. Classification of evidence: This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. PMID:28031390

Methylphenidate, cognition, and epilepsy: A double-blind, placebo-controlled, single-dose study.

PubMed

Adams, Jesse; Alipio-Jocson, Valerie; Inoyama, Katherine; Bartlett, Victoria; Sandhu, Saira; Oso, Jemima; Barry, John J; Loring, David W; Meador, Kimford

2017-01-31

To evaluate the potential efficacy of immediate-release methylphenidate (MPH) for treating cognitive deficits in epilepsy. This was a double-blind, randomized, single-dose, 3-period crossover study in patients with epilepsy and chronic cognitive complaints comparing the effects of placebo and MPH 10 and 20 mg given 1 week apart. Cognitive outcome was evaluated on the basis of an omnibus z score calculated from performance on the Conners Continuous Performance Test 3 (ability to discriminate between target and nontarget stimuli [d'] and hit reaction time standard deviation), Symbol-Digit Modalities Test, and Medical College of Georgia Paragraph Memory Test. Adverse events and seizure frequency were monitored. An open-label follow-up is reported elsewhere. Thirty-five adult patients with epilepsy participated, of whom 31 finished. Demographics included the following: mean age = 35.3 years (range 20-62 years), 13 men and 18 women, and baseline seizure frequency of 2.8 per month. Epilepsy types were focal (n = 24), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.5 years. A statistically significant performance benefit was present at both 10-mg (p = 0.030) and 20-mg (p = 0.034) MPH doses. No seizures were associated with either MPH dose. Adverse effects leading to withdrawal included cognitive "fogginess" (n = 1 on 20 mg), anxiety/agitation (n = 1 on 10 mg), and tachycardia (n = 1). One participant was lost to follow-up after one 20-mg dose without side effect. This single-dose study suggests that MPH may be effective in ameliorating some cognitive deficits in patients with epilepsy. Additional studies are required. NCT02178995. This study provides Class II evidence that single doses of MPH improve cognitive performance on some measures of attention and processing speed in patients with epilepsy and cognitive complaints. © 2016 American Academy of Neurology.

Social reinforcement as alternative to sucrose reinforcement is increased by nicotine and methylphenidate in male Fischer-344 rats.

PubMed

Martin, Connor D; Bool, Heather M; George, Anthony M; Carr, Katelyn A; Epstein, Leonard H; Hawk, Larry W; Richards, Jerry B

2018-04-24

Stimulant drugs such as nicotine (NIC) and methylphenidate (MPH) are hypothesized to increase the reinforcing value of sensory stimuli, thus increasing the effectiveness of such reinforcers as alternatives to sucrose reinforcers. Inbred Fischer-344 rats (n = 30) were assigned to three groups: saline (SAL; n = 10), nicotine (NIC; n = 10), or methylphenidate (MPH; n = 10). Testing was done in three phases: sucrose only, (SUC), sucrose and drug (SUC/DRUG), and sucrose, drug, and social reinforcement (SUC/DRUG/SOC). During the SUC phase, rats were trained on a progressive ratio 5 (PR5) reinforcement schedule for sucrose (20% solution). In the SUC/DRUG phase, animals were treated with SAL, NIC (0.4 mg/kg, n = 10 SC), or MPH (2.0 mg/kg, n = 10 IP) 30 min prior to testing. In the SUC/DRUG/SOC phase, animals continued receiving drug treatment, and social reinforcement was introduced concurrently with the sucrose reinforcer. The progressive ratio for each reinforcer ran independently of the others. Reinforcing value was measured as break point (BP), the highest number of responses resulting in a reinforcer. SAL-treated animals showed no significant change in sucrose BP. MPH-treated animals showed decreased sucrose BP in the SUC/DRUG phase, with a further reduction in the SUC/DRUG/SOC phase. NIC-treated animals decreased sucrose BP only when a social alternative was offered. Both NIC and MPH reduce the sucrose BP in the presence of a social alternative. The decrease in sucrose responding, coupled with increased social responding, suggests that the social alternative acted as an effective alternative reinforcer to sucrose. From a translational perspective, these results suggest that stimulant drugs such as NIC and MPH may increase the effectiveness of treatments that use alternative social reinforcers to decrease eating.

Impact of attention-deficit/hyperactivity disorder (ADHD) treatment on smoking cessation intervention in ADHD smokers: a randomized, double-blind, placebo-controlled trial.

PubMed

Winhusen, Theresa M; Somoza, Eugene C; Brigham, Gregory S; Liu, David S; Green, Carla A; Covey, Lirio S; Croghan, Ivana T; Adler, Lenard A; Weiss, Roger D; Leimberger, Jeffrey D; Lewis, Daniel F; Dorer, Emily M

2010-12-01

High smoking rates in adults with attention-deficit/hyperactivity disorder (ADHD) and nicotine's amelioration of ADHD suggest that effective ADHD treatment might facilitate abstinence in smokers with ADHD. The present study evaluated if using osmotic-release oral system methylphenidate (OROS-MPH) to treat ADHD enhances response to smoking cessation treatment in smokers with ADHD. A randomized, double-blind, placebo-controlled, 11-week trial with a 1-month follow-up was conducted at 6 clinical sites between December 2005 and January 2008. Adults (aged 18-55 years) meeting DSM-IV criteria for ADHD and interested in quitting smoking were randomly assigned to OROS-MPH titrated to 72 mg/d (n = 127) or placebo (n = 128). All participants received brief weekly individual smoking cessation counseling for 11 weeks and 21 mg/d nicotine patches starting on the smoking quit day (day 27) through study week 11. Outcome measures included prolonged smoking abstinence and DSM-IV ADHD Rating Scale (ADHD-RS) score. Of 255 randomly assigned participants, 204 (80%) completed the trial. Prolonged abstinence rates, 43.3% and 42.2%, for the OROS-MPH and placebo groups, respectively, did not differ significantly (OR = 1.1; 95% CI, 0.63-1.79; P = .81). Relative to placebo, OROS-MPH evidenced a greater reduction in DSM-IV ADHD-RS score (P < .0001) and in cigarettes per day during the post-quit phase (P = .016). Relative to placebo, OROS-MPH increased blood pressure and heart rate to a statistically, but not clinically, significant degree (P < .05); medication discontinuation did not differ significantly between treatments. Treatment for ADHD did not improve smoking cessation success; OROS-MPH, relative to placebo, effectively treated ADHD and was safe and generally well tolerated in this healthy sample of adult ADHD smokers. clinical trials.gov Identifier: NCT00253747. © Copyright 2010 Physicians Postgraduate Press, Inc.

Six months methylphenidate treatment improves emotion dysregulation in adolescents with attention deficit/hyperactivity disorder: a prospective study.

PubMed

Suzer Gamli, Ipek; Tahiroglu, Aysegul Yolga

2018-01-01

Individuals with attention deficit/hyperactivity disorder (ADHD) may suffer from emotional dysregulation (ED), although this symptom is not listed among the diagnostic criteria. Methylphenidate (MPH) is useful in reducing emotional symptoms in ADHD. The aim of the present study was to determine both psychosocial risk factors and presence of ED in adolescents with ADHD before and after MPH treatment. Eighty-two patients aged 12-18 years with ADHD were included as participants. The Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime, the Difficulties in Emotion Regulation Scale (DERS), sociodemographic form, and the Inventory of Statements About Self-Injury were administered. Results were compared before and after 6 months MPH treatment. A significant improvement was detected on DERS for impulsivity (15.9±6.8 initial vs 14.2±6.5 final test, p <0.01) and total score (88.4±23.3 initial vs 82.4±2.7 final test, p <0.05) across all patients taking MPH regardless of subtype and sex. Despite treatment, a significant difference remained for impulsivity, strategies, and total score in patients with comorbid oppositional defiant disorder (ODD) compared with those without ODD, but no difference was detected for conduct disorder comorbidity. In patients who self-harm, scores for goals, impulsivity, strategies, clarity, and total score were higher before treatment: furthermore, impulsivity and total score remained high after treatment. In maltreated patients, goals, impulsivity, strategies, and total scores were significantly higher before treatment; however, their symptoms were ameliorated after treatment with MPH. Individuals with severe ED may "self-medicate" by smoking and/or self-harming. MPH led to significant improvements in ED possibly owing, in part, to a decrease in impulsivity, so that individuals felt more able to supervise their emotions and engage in goal-directed behaviors. ED should be considered particularly in patients with additional psychosocial factors and ODD comorbidity, and included in the treatment plan.

A Randomized Placebo-Controlled Double-Blind Study Evaluating the Time Course of Response to Methylphenidate Hydrochloride Extended-Release Capsules in Children with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Greenhill, Laurence L.; Nordbrock, Earl; Connor, Daniel F.; Kollins, Scott H.; Adjei, Akwete; Childress, Ann; Stehli, Annamarie; Kupper, Robert J.

2014-01-01

Abstract Objective: The purpose of this study was to assess the time of onset and time course of efficacy over 12.0 hours of extended-release multilayer bead formulation of methylphenidate (MPH-MLR) compared with placebo in children 6–12 years of age with attention-deficit/hyperactivity disorder (ADHD) in a laboratory school setting. Methods: This randomized double-blind placebo-controlled study included children 6–12 years of age with ADHD. Enrolled children went through four study phases: 1) Screening period (≤4 weeks) and a 2 day medication washout period; 2) open-label period with dose initiation of MPH-MLR 15 mg daily and individual dose optimization treatment period (2–4 weeks); 3) double-blind crossover period in which participants were randomized to sequences (1 week each) of placebo and the optimized MPH-MLR dose given daily; and 4) follow-up safety call. Analog classroom time course evaluations were performed at the end of each double-blind week. The primary efficacy end-point was the mean of the on-treatment/postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)-Total scores over time points collected 1.0–12.0 hours after dosing. End-points were evaluated using a mixed-effects analysis of covariance. Results: The evaluable population included 20 participants. The least-squares mean postdose SKAMP-Total score was higher for placebo than for MPH-MLR (2.18 vs. 1.32, respectively; p=0.0001), indicating fewer symptoms with MPH-MLR therapy than with placebo. No difference in SKAMP-Total score between participants who received sequence 1 or sequence 2 was noted. From each of hours 1.0–12.0, least-squares mean SKAMP-Total score was significantly lower for those receiving MPH-MLR than for those receiving placebo (p≤0.0261). Neither serious adverse events nor new or unexpected safety findings were noted during the study. Conclusions: MPH-MLR showed a significant decrease in SKAMP scores compared with placebo in children with ADHD 6–12 years of age, indicating a decrease in ADHD symptoms. The estimated onset was observed within 1.0 hour, and duration was measured to 12.0 hours postdose. Trial registration: ClinicalTrials.gov Identifier: NCT01269463 PMID:25470572

Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review.

PubMed

Whiting, Penny; Westwood, Marie; Watt, Ian; Cooper, Julie; Kleijnen, Jos

2005-04-05

Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture. We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age. The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful. Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation.

Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review

PubMed Central

Whiting, Penny; Westwood, Marie; Watt, Ian; Cooper, Julie; Kleijnen, Jos

2005-01-01

Background Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture. Methods We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age. Results The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful. Conclusion Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation. PMID:15811182

Unique Stealth Unmanned Aerial Vehicle (UAV) Houck Aircraft Design Program. Volume 2: Prototype Report

DTIC Science & Technology

2008-11-01

Configuration ................................ 23 Figure 18: Wake at 15 MPH for AOA = 6, 20 degrees...27 Figure 19: Wake at 35 MPH for AOA = 6, 20 degrees ............................................................... 28 Figure 20: Wake ...several different manners beginning with alpha (angle of attack) sweeps, then Q (velocity) sweeps, and finally randomized testing. Solid and wake

Hala Azzam, PhD, MPH | Division of Cancer Prevention

Cancer.gov

Dr. Hala Azzam is a Cancer Epidemiologist in the Cancer Prevention Fellowship Program (CPFP) in the Division of Cancer Prevention within the National Cancer Institute. She received her Bachelor's degree in molecular biology from Kings College London University, her PhD in anatomy and cell biology from Georgetown University Lombardi Cancer Center, and her MPH in epidemiology

49 CFR 325.35 - Ambient conditions; highway operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... test site at the time of testing. (b) Wind. The wind velocity at the test shall be measured at the... established that the wind velocity is essentially constant. Once this fact has been established, wind velocity... wind velocity is 12 mph (19.3 kph) or less. Gust wind measurements of up to 20 mph (33.2 kph) are...

49 CFR 325.55 - Ambient conditions; stationary test.

Code of Federal Regulations, 2012 CFR

2012-10-01

... site at the time of testing. (b) Wind. The wind velocity at the test site shall be measured at the... established that the wind velocity is essentially constant. Once this fact has been established, wind velocity... wind velocity is 12 mph (19.3 kph) or less. Gust wind measurements of up to 20 mph (33.2 kph) are...

Using COMSOL Software on the Peregrine System | High-Performance Computing

Science.gov Websites

the following command: lmstat.comsol COMSOL can be used by starting the COMSOL GUI that allows one to compute node, the following will bring up the COMSOL interface. module purge module load comsol/5.3 comsol following command comsol batch -inputfile myinputfile.mph -outputfile out.mph Running a Parallel COMSOL Job

Impact of Methylphenidate Delivery Profiles on Driving Performance of Adolescents with Attention-Deficit/hyperactivity Disorder: A Pilot Study

ERIC Educational Resources Information Center

Cox, Daniel J.; Merkel, R. Lawrence; Penberthy, Jennifer Kim; Kovatchev, Boris; Hankin, Cheryl S.

2004-01-01

Objective: Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at high risk for driving accidents. One dose of methylphenidate (MPH) improves simulator driving performances of ADHD-diagnosed adolescents at 1.5 hours post-dose. However, little is known about the effects of different MPH delivery profiles on driving performance…

Earth observations taken by the Expedition Seven crew

NASA Image and Video Library

2003-09-03

ISS007-E-14419 (4 September 2003) --- This view featuring Hurricane Fabian was taken by one of the Expedition 7 crewmembers onboard the International Space Station (ISS) while it was in orbit over Hispaniola. At the time this photo was taken, Fabian had maximum sustained winds of 120 mph and was moving to the north-northwest at 12 mph.

49 CFR 325.35 - Ambient conditions; highway operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... test site at the time of testing. (b) Wind. The wind velocity at the test shall be measured at the... established that the wind velocity is essentially constant. Once this fact has been established, wind velocity... wind velocity is 12 mph (19.3 kph) or less. Gust wind measurements of up to 20 mph (33.2 kph) are...

49 CFR 325.55 - Ambient conditions; stationary test.

Code of Federal Regulations, 2011 CFR

2011-10-01

... site at the time of testing. (b) Wind. The wind velocity at the test site shall be measured at the... established that the wind velocity is essentially constant. Once this fact has been established, wind velocity... wind velocity is 12 mph (19.3 kph) or less. Gust wind measurements of up to 20 mph (33.2 kph) are...

49 CFR 325.55 - Ambient conditions; stationary test.

Code of Federal Regulations, 2010 CFR

2010-10-01

... site at the time of testing. (b) Wind. The wind velocity at the test site shall be measured at the... established that the wind velocity is essentially constant. Once this fact has been established, wind velocity... wind velocity is 12 mph (19.3 kph) or less. Gust wind measurements of up to 20 mph (33.2 kph) are...

49 CFR 325.35 - Ambient conditions; highway operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... test site at the time of testing. (b) Wind. The wind velocity at the test shall be measured at the... established that the wind velocity is essentially constant. Once this fact has been established, wind velocity... wind velocity is 12 mph (19.3 kph) or less. Gust wind measurements of up to 20 mph (33.2 kph) are...

49 CFR 213.137 - Frogs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... than 10 m.p.h. (c) If the tread portion of a frog casting is worn down more than three-eighths inch below the original contour, operating speed over that frog shall not be more than 10 m.p.h. (d) Where... 49 Transportation 4 2011-10-01 2011-10-01 false Frogs. 213.137 Section 213.137 Transportation...

Effects of MPH-OROS on the Organizational, Time Management, and Planning Behaviors of Children with ADHD

ERIC Educational Resources Information Center

Abikoff, Howard; Nissley-Tsiopinis, Jenelle; Gallagher, Richard; Zambenedetti, Maurizio; Seyffert, Michael; Boorady, Roy; McCarthy, John

2009-01-01

A double-blind, placebo-controlled, crossover design study was done to evaluate the effects of methylphenidate-osmotic-release oral systems (MPH-OROS) on the organization, time management, and planning (OTMP) of children with attention deficit hyperactivity disorder (ADHD). Results show significant improvements on the OTMP of children with ADHD in…

A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.

PubMed

Benson, Constance A; Currier, Judith S; Del Rio, Carlos; Gallant, Joel E; Gulick, Roy M; Marrazzo, Jeanne M; Richman, Douglas D; Saag, Michael S; Schooley, Robert T; Volberding, Paul A

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD.

Objective and subjective cure rates after trans-obturator tape (OBTAPE) treatment of female urinary incontinence.

PubMed

Deval, Bruno; Ferchaux, Jérome; Berry, Richard; Gambino, Sandro; Ciofu, Calin; Rafii, Arash; Haab, François

2006-02-01

To evaluate the safety and efficacy of a thermally bonded nonwoven polypropylene mesh in a transobturator suburethral tape procedure (OBTAPE), Mentor-Porges, Le Plessis Robinson, France) for women with stress urinary incontinence. Between January 2003 and January 2005, 129 consecutive women (mean age 57.2 years) underwent OBTAPE) in two academic centers. All the patients had stress urinary incontinence preoperatively. Detrusor instability was ruled out by cystometry. The women were evaluated 1, 6 and 12 months postoperatively. The objective cure rate was evaluated by clinical examination and the subjective cure rate was assessed using the KHQ and BFLUTS questionnaire. Mean follow-up was 17.2+/-4.7 months (range 4 to 28 months). The objective and subjective cure rates were respectively 89.9% and 77.5%. Most of the patients received general anesthesia (85.3%). Urinary retention was observed in two women (1.5%), necessitating tape adjustment. Voiding difficulties were observed in 7 cases (5.4%) necessitating intermittent self-catheterization for 4.2+/-2.4 days (range 1 to 7 days). Seven patients developed vaginal erosion (one with vaginal extrusion, and two with an obturator abscess). Complete mesh removal was necessary in 6 patients, four of whom had recurrent stress urinary incontinence. Our results suggest that the OBTAPE) is an effective treatment for women with stress urinary incontinence. However, vaginal mesh erosion occurred in 6.2% of women, and this implies the need for careful follow-up.

[Urinary tract infections in pregnancy: when to treat, how to treat, and what to treat with].

PubMed

Kladenský, J

2012-04-01

Urinary tract infections (UTI) in pregnant women are a relatively frequent occurrence and the spectrum of these infections ranges from lower urinary tract disease (asymptomatic bacteriuria, acute cystitis) to upper urinary tract disease (acute pyelonephritis). Anatomical and functional changes in the urinary tract in pregnancy result in significantly higher susceptibility to progression of the infection from asymptomatic bacteriuria to the stage of acute pyelonephritis. Untreated asymptomatic bacteriuria in pregnancy leads, in as much as 40%, to the development of acute pyelonephritis with all the subsequent negative effects not only for the woman herself, but particularly for the fetus. Bacteriuria in pregnancy accounts for a significantly higher number of newborns with a low birth weight, low gestational age and higher neonatal mortality rate. Therefore, it is necessary to perform screening for bacteriuria in pregnant women and, when the finding is positive, to treat this bacteriuria. The selection of an appropriate antimicrobial agent to treat urinary tract infection in pregnancy is limited by the safety of a given drug not only for the woman, but particularly for the fetus. The article provides an overview of medications that can be safely used throughout the pregnancy or only in certain stages of pregnancy. The selection of an appropriate antibiotic should always be preceded by the result of urine culture. The article presents the principles and rules for treating asymptomatic bacteriuria, acute cystitis and acute pyelonephritis in pregnant women.

Dynamic hyperinflation after metronome-paced hyperventilation in COPD--a 2 year follow-up.

PubMed

Hannink, Jorien; Lahaije, Anke; Bischoff, Erik; van Helvoort, Hanneke; Dekhuijzen, Richard; Schermer, Tjard; Heijdra, Yvonne

2010-11-01

In contrast to the decline in FEV(1), the behavior of dynamic hyperinflation (DH) over time is unknown in patients with COPD. Metronome-paced hyperventilation (MPH) is a simple applicable surrogate for exercise to detect DH. To evaluate changes in MPH-induced DH during two years follow-up in mild-to-severe COPD patients. Additionally, influence of smoking status on DH and the relation between DH and other lung function parameters were assessed. Patients were recruited from a randomized controlled trial conducted in general practice. Measurements of lung function and DH were performed at baseline and after 12 and 24 months. DH was assessed by MPH with breathing frequency set at twice the baseline rate. Change in inspiratory capacity after MPH was used to reflect change in end-expiratory lung volume and therefore DH, presuming constant total lung capacity. During follow-up, 68 patients completed all measurements. DH increased by 0.23±0.06L (p≤0.001). No significant changes in FEV(1) %pred were seen. Smokers had lower FEV(1) and a more rapid decline than non-smokers. DH in smokers increased more over time compared to non-smokers. The amount of DH correlated positively with resting inspiratory capacity. After two years, a significant increase in MPH-induced DH in COPD patients was demonstrated, which was not accompanied by a decline in FEV(1). It might be that DH is a sensitive measure to track consequences of changes in airflow obstruction. Copyright © 2010 Elsevier Ltd. All rights reserved.

Public health and social work: training dual professionals for the contemporary workplace.

PubMed

Ruth, Betty J; Sisco, Sarah; Wyatt, Jamie; Bethke, Christina; Bachman, Sara S; Piper, Tinka Markham

2008-01-01

The emergence of new, complex social health concerns demands that the public health field strengthen its capacity to respond. Academic institutions are vital to improving the public health infrastructure. Collaborative and transdisciplinary practice competencies are increasingly viewed as key components of public health training. The social work profession, with its longstanding involvement in public health and emphasis on ecological approaches, has been a partner in many transdisciplinary community-based efforts. The more than 20 dual-degree programs in public health and social work currently offered reflect this collaborative history. This study represents an exploratory effort to evaluate the impact of these programs on the fields of public health and social work. This study explored motivations, perspectives, and experiences of 41 graduates from four master of social work/master of public health (MSW/ MPH) programs. Four focus groups were conducted using traditional qualitative methods during 2004. Findings suggest that MSW/MPH alumni self-selected into dual programs because of their interest in the missions, ethics, and practices of both professions. Participants highlighted the challenges and opportunities of dual professionalism, including the struggle to better define public health social work in the workplace. Implications for academic public health focus on how schools can improve MSW/MPH programs to promote transdisciplinary collaboration. Increased recognition, better coordination, and greater emphasis on marketing to prospective employers were suggested. A national evaluation of MSW/MPH graduates could strengthen the roles and contributions of public health social work to the public health infrastructure. A conceptual framework, potentially based on developmental theory, could guide this evaluation of the MSW/MPH training experience.

The effects of methylphenidate and propranolol on the interplay between induced-anxiety and working memory

PubMed Central

Ernst, Monique; Lago, Tiffany; Davis, Andrew; Grillon, Christian

2016-01-01

Rationale Research documents a reciprocal impact of anxiety on working memory (WM), although its strength and direction depend on factors like task difficulty. A better understanding of these factors may generate insights into cognitive mechanisms of action involved in anxiety, culminating into treatment implications. By blocking the physiological effects of anxiety, propranolol might also block anxiety interference on WM. Conversely, by improving task-directed attention, methylphenidate might reduce anxiety, or, alternatively, by improving cognitive efficiency and free up processing resources to compute anxiety. Objectives To investigate the interplay between induced anxiety and WM, we pharmacologically manipulated either anxiety or cognition, using single doses of 40 mg propranolol (PRO), 20 mg methylphenidate (MPH), or placebo (PLA). In this double-blind parallel-group design study, 60 healthy volunteers (20/drug group) performed a verbal WM task under three loads, 1-, 2- and 3-back, and in two conditions, threat of shock and safety. Startle electromyography (EMG) was used to measure anxiety. Results Findings were twofold: (1) MPH blocked anxiety interference only on the 3-back WM performance, while PRO or PLA had no effects on anxiety-WM interference, and (2) drugs had no effects on anxiety, but, after controlling for baseline anxiety, MPH enhanced anxiety-potentiated startle during the 3-back task. Conclusions These findings support that MPH-related improvement of cognitive efficiency permits anxiety to be processed and expressed. In conclusion, MPH may be a useful tool to investigate the mechanisms of interaction between anxiety and WM, particularly those under catecholaminergic control. PMID:27492789

The effects of methylphenidate and propranolol on the interplay between induced-anxiety and working memory.

PubMed

Ernst, Monique; Lago, Tiffany; Davis, Andrew; Grillon, Christian

2016-10-01

Research documents a reciprocal impact of anxiety on working memory (WM), although its strength and direction depend on factors like task difficulty. A better understanding of these factors may generate insights into cognitive mechanisms of action involved in anxiety, culminating into treatment implications. By blocking the physiological effects of anxiety, propranolol might also block anxiety interference on WM. Conversely, by improving task-directed attention, methylphenidate might reduce anxiety, or, alternatively, by improving cognitive efficiency and free up processing resources to compute anxiety. To investigate the interplay between induced anxiety and WM, we pharmacologically manipulated either anxiety or cognition, using single doses of 40 mg propranolol (PRO), 20 mg methylphenidate (MPH), or placebo (PLA). In this double-blind parallel-group design study, 60 healthy volunteers (20/drug group) performed a verbal WM task under three loads, 1-, 2- and 3-back, and in two conditions, threat of shock and safety. Startle electromyography (EMG) was used to measure anxiety. Findings were twofold: (1) MPH blocked anxiety interference only on the 3-back WM performance, while PRO or PLA had no effects on anxiety-WM interference, and (2) drugs had no effects on anxiety, but, after controlling for baseline anxiety, MPH enhanced anxiety-potentiated startle during the 3-back task. These findings support that MPH-related improvement of cognitive efficiency permits anxiety to be processed and expressed. In conclusion, MPH may be a useful tool to investigate the mechanisms of interaction between anxiety and WM, particularly those under catecholaminergic control.

Effect of visual attention on postural control in children with attention-deficit/hyperactivity disorder.

PubMed

Bucci, Maria Pia; Seassau, Magali; Larger, Sandrine; Bui-Quoc, Emmanuel; Gerard, Christophe-Loic

2014-06-01

We compared the effect of oculomotor tasks on postural sway in two groups of ADHD children with and without methylphenidate (MPH) treatment against a group of control age-matched children. Fourteen MPH-untreated ADHD children, fourteen MPH-treated ADHD children and a group of control children participated to the study. Eye movements were recorded using a video-oculography system and postural sway measured with a force platform simultaneously. Children performed fixation, pursuits, pro- and anti-saccades. We analyzed the number of saccades during fixation, the number of catch-up saccades during pursuits, the latency of pro- and anti-saccades; the occurrence of errors in the anti-saccade task and the surface and mean velocity of the center of pressure (CoP). During the postural task, the quality of fixation was significantly worse in both groups of ADHD children with respect to control children; in contrast, the number of catch-up saccades during pursuits, the latency of pro-/anti-saccades and the rate of errors in the anti-saccade task did not differ in the three groups of children. The surface of the CoP in MPH-treated children was similar to that of control children, while MPH-untreated children showed larger postural sway. When performing any saccades, the surface of the CoP improved with respect to fixation or pursuits tasks. This study provides evidence of poor postural control in ADHD children, probably due to cerebellar deficiencies. Our study is also the first to show an improvement on postural sway in ADHD children performing saccadic eye movements. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Dietary patterns in patients with attention deficit hyperactivity disorder].

PubMed

Durá Travé, T; Diez Bayona, V; Yoldi Petri, M E; Aguilera Albesa, S

2014-04-01

To evaluate the dietary patterns in a group of patients diagnosed with attention deficit hyperactivity disorder (ADHD) and under treatment with extended-release methylphenidate (MPH-ER). A nutrition survey (food intake recall for three consecutive days) was carried out on 100 patients diagnosed with ADHD and under treatment with MPH-ER, and in 150 healthy children (control group). Calorie and nutrient intake, as well as nutrition status, were evaluated and compared in both groups. The mean MPH-ER dose was 1.02 mg/kg/day. Nutritional status in the ADHD group was significantly lower (P < .05) than in control group. The consumption of cereals, meat, pulses and fruits in the control group was significantly higher (P < .05) than in ADHD group. Calorie intake in the mid-morning snack, lunch and afternoon snack was significantly higher (P < .05) in the control group. Calorie intake at supper was significantly higher (P < .05) in the ADHD group. Total calorie intake, as well as protein, carbohydrates, fat, fibre, calcium, iron, magnesium, zinc, selenium and phosphorous, thiamine, niacin, vitamin B6 and folate intake in the control group was significantly higher than in ADHD group. Treatment with MPH-ER substantially modifies the percentage distribution of calorie intake of the different meals. The daily calorie and nutrients intake in patients under treatment with MPH-ER is, generally, lower than in the healthy population of a similar age. Nutrition education should be provided, along with multimodal treatment, to the patients and/or their families. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Short-term efficacy and tolerability of methylphenidate in children with traumatic brain injury and attention problems.

PubMed

Ekinci, Ozalp; Direk, Meltem Çobanoğulları; Gunes, Serkan; Teke, Halenur; Ekinci, Nuran; Yıldırım, Fatma; Okuyaz, Çetin

2017-04-01

This study aims to investigate the short-term efficacy and tolerability of immediate-release methylphenidate (IR-MPH) in children with a history of traumatic brain injury (TBI). Twenty children with TBI (mean age: 12.7±3.1years) who had clinically significant attention deficit and/or hyperactivity-impulsivity symptoms and twenty children with primary Attention Deficit Hyperactivity Disorder (ADHD) (mean age: 12.3±3.05years) were included. Study measures, which included the Turgay DSM-IV based ADHD rating Scale (T-DSM-IV-S), Conners' Parent Rating Scale (CPRS), Conners' Teacher Rating Scale (CTRS-R) and Clinical Global Impression-Improvement Scale (CGI-I), were completed at the baseline for both of the groups. For the TBI group, study measures and an adverse effect scale developed by the authors were completed 8weeks after IR-MPH treatment (10mg dose t.i.d). No significant difference was found regarding the baseline scale scores between the study groups. Among children with TBI, most of the scores on T-DSM-IV-S, CPRS and CTRS-R were found to improve significantly after MPH treatment, (p<0.05). 70% (N=14) of the sample were much improved at the endpoint. MPH was generally well-tolerated (95% had either no adverse effect or mild adverse effects). In this preliminary open-label study, IR-MPH was found as a safe and effective treatment option for ADHD symptoms after TBI. However, future controlled studies are needed to confirm our findings. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Effectiveness of Neurofeedback Versus Medication in Treatment of ADHD.

PubMed

Sudnawa, Khemika Khemakanok; Chirdkiatgumchai, Vilawan; Ruangdaraganon, Nichara; Khongkhatithum, Chaiyos; Udomsubpayakul, Umaporn; Jirayucharoensak, Suwicha; Israsena, Pasin

2018-06-22

Neurofeedback (NF) is an operant conditioning procedure that trains participants for self-regulation of brain activity. Previous studies have shown that NF is a promising treatment of ADHD. However, there have been only a few RCT studies comparing effectiveness of NF with medication with various NF protocol and results. The aim of this study was to evaluate theeffectiveness of unipolar electrodeneurofeedback (NF) using theta/beta protocol compared with methylphenidate (MPH) in the treatment of ADHD. Children with newly diagnosed ADHD were randomly organised into NF and MPH groups. Each of children in NF group received 30 sessions of NF. Children in MPH group were prescribed methylphenidate for 12 weeks. Vanderbilt ADHD rating scales were completed by parents and teachers to evaluate ADHD symptoms pre- and post-treatment. Student's t-tests and Cohen's dwere used to compare symptoms between groups and evaluate effect size (ES) of each treatment respectively. Forty children participated in the study. No differences in ADHD baseline symptoms between groups were found. Post-treatment, teachers reported significantly lower ADHD symptoms in the MPH group (p = 0.01), but parents reported no differences betweenthe groups (p = 0.55). MPH demonstrated large ES (Cohen's d 1.30 - 1.69), while NF showed moderate ES (Cohen's d 0.49 - 0.68) for treatment of ADHD symptoms. This study supports NF as a promising alternative treatment for ADHD in children who do not respond or experience significant adverse effects to ADHD medications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Methylphenidate and the risk of trauma.

PubMed

Man, Kenneth K C; Chan, Esther W; Coghill, David; Douglas, Ian; Ip, Patrick; Leung, Ling-Pong; Tsui, Matthew S H; Wong, Wilfred H S; Wong, Ian C K

2015-01-01

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) are prone to sustaining trauma that requires emergency department (ED) admission. Methylphenidate (MPH) can reduce ADHD symptoms and may thus theoretically reduce the risk of trauma-related ED admission, but previous studies do not make this association clear. This study examines this association. A total of 17 381 patients aged 6 to 19 years who received MPH prescriptions were identified by using the Clinical Data Analysis & Reporting System (2001-2013). Using a self-controlled case series study design, the relative incidence of trauma-related ED admissions was compared with periods of patient exposure and nonexposure to MPH. Among 17 381 patients prescribed MPH, 4934 had at least 1 trauma-related ED admission. The rate of trauma-related ED admission was lower during exposed periods compared with nonexposed periods (incidence rate ratio [IRR]: 0.91 [95% confidence interval (CI): 0.86-0.97]). The findings were similar only when the incident trauma episode was assessed (IRR: 0.89 [95% CI: 0.82-0.96]). A similar protective association was found in both genders. In validation analysis using nontrauma-related ED admissions as a negative control outcome, no statistically significant association was found (IRR: 0.99 [95% CI: 0.95-1.02]). All sensitivity analyses demonstrated consistent results. This study supports the hypothesis that MPH is associated with a reduced risk of trauma-related ED admission in children and adolescents. A similar protective association was found in both male and female patients. This protective association should be considered in clinical practice. Copyright © 2015 by the American Academy of Pediatrics.

Teaching Note--Educating Public Health Social Work Professionals: Results from an MSW/MPH Program Outcomes Study

ERIC Educational Resources Information Center

Ruth, Betty J.; Marshall, Jamie Wyatt; Velásquez, Esther E. M.; Bachman, Sara S.

2015-01-01

Dual-degree programs in public health and social work continue to proliferate, yet there has been little research on master's of social work (MSW)/master's of public health (MPH) graduates. The purpose of this study was to describe and better understand the self-reported professional experiences, identities, roles, and outcomes associated with 1…

Safety and Tolerability of Methylphenidate in Preschool Children with ADHD

ERIC Educational Resources Information Center

Wigal, Tim; Greenhill, Laurence; Chuang, Shirley; McGough, James; Vitiello, Benedetto; Skrobala, Anne; Swanson, James; Wigal, Sharon; Abikoff, Howard; Kollins, Scott; McCracken, James; Riddle, Mark; Posner, Kelly; Ghuman, Jaswinder; Davies, Mark; Thorp, Ben; Stehli, Annamarie

2006-01-01

Objective: To report on the safety and tolerability of methylphenidate (MPH) 3- to 5-year-old children with attention-deficit/hyperactivity disorder (ADHD) during 1 year of treatment. Method: Exactly 183 children (3-5 years old) entered a treatment study of MPH, consisting of a 1-week open-label lead-in (n = 183); a 5-week placebo-controlled,…

Efficacy of a Methylphenidate Transdermal System versus t.i.d. Methylphenidate in a Laboratory Setting

ERIC Educational Resources Information Center

Pelham, William E.; Waxmonsky, James G.; Schentag, Jerome; Ballow, Charles H.; Panahon, Carlos J.; Gnagy, Elizabeth M.; Hoffman, Martin T.; Burrows-MacLean, Lisa; Meichenbaum, David L.; Forehand, Gregory L.; Fabiano, Gregory A.; Tresco, Katy E.; Lopez-Williams, Andy; Coles, Erika K.; Gonzalez, Mario A.

2011-01-01

Objective: To test the efficacy and tolerability of the methylphenidate transdermal formulation (MTS) against immediate-release methylphenidate (IR MPH) and placebo in a 12-hr analog classroom setting. Method: A total of nine boys ages 6 to 9 years, medicated with MPH for ADHD, complete a within-subject, double-blind study. For the purpose of the…

Disability Evaluation System Analysis and Research Annual Report 2017

DTIC Science & Technology

2017-11-20

Amanda L. Kelley, MPH Program Manager, AMSARA Deputy Program Manager, AMSARA Contractor, ManTech Health Contractor, ManTech Health Christine...Toolin, MS Cordie K. Campbell, MPH Public Health Analyst, AMSARA Public Health Analyst, AMSARA Contractor, ManTech Health Contractor...ManTech Health Preventive Medicine Branch Walter Reed Army Institute of Research 503 Robert Grant Road, Forest Glen Annex Silver

Using Mandated Speed Limits to Measure the Value of a Statistical Life

ERIC Educational Resources Information Center

Ashenfelter, Orley; Greenstone, Michael

2004-01-01

In 1987 the federal government permitted states to raise the speed limit on their rural interstate roads, but not on their urban interstate roads, from 55 mph to 65 mph. Since the states that adopted the higher speed limit must have valued the travel hours they saved more than the fatalities incurred, this institutional change provides an…

Comparative Effects of Methylphenidate and Mixed Salts Amphetamine on Height and Weight in Children with Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Pliszka, Steven R.; Matthews, Thomas L.; Braslow, Kenneth J.; Watson, Melissa A.

2006-01-01

Objective: To determine whether methylphenidate (MPH) and mixed salts amphetamine (MSA) have different effects on growth in children with attention-deficit/hyperactivity disorder. Method: Patients treated for at least 1 year with MPH or MSA were identified. A linear regression was performed to determine the effect of stimulant type, patient…

Alternative Fuels Data Center

Science.gov Websites

Low-Speed Vehicle Access to Roadways Low-speed vehicles are only permitted on highways with speed limits up to 35 miles per hour (mph) or up to 45 mph in some municipalities or boroughs. Low-speed highway that allows low-speed vehicle use. Operators of low-speed vehicles are subject to all traffic laws

Social Work and Public Health: Comparing Graduates from a Dual-Degree Program

ERIC Educational Resources Information Center

Ruth, Betty J.; Wyatt, Jamie; Chiasson, Emily; Geron, Scott Miyake; Bachman, Sally

2006-01-01

This study compared dual-degree master of social work/master of public health (MSW/MPH) and MSW-only graduates with 3 or more years of postgraduate experience. Thirty graduates from an MSW/MPH program were matched with 30 MSW-only graduates. All subjects were randomly selected from the alumni directory and interviewed via telephone. Results showed…

Self-Regulation of Visual Attention and Facial Expression of Emotions in ADHD Children

ERIC Educational Resources Information Center

Kuhle, Hans J.; Kinkelbur, Jorg; Andes, Kerstin; Heidorn, Fridjof M.; Zeyer, Solveigh; Rautzenberg, Petra; Jansen, Fritz

2007-01-01

Objective: To test if visual focusing and mimic display as features of self-regulation in ADHD children show a curvilinear relation to rising methylphenidate (MPH) doses. To test if small dose steps of 2.5mg MPH cause significant changes in behavior. And to test the relation of these features to intellectual performance, parents' ratings, and…

Master of Public Health | Cancer Prevention Fellowship Program

Cancer.gov

One of the unique features of the CPFP is the opportunity to receive formal, academic training in public health. By pursuing an MPH or equivalent degree, fellows learn about the current role and historical context of cancer prevention in public health. The MPH provides individuals with a strong foundation population health sciences, particularly the quantitative sciences of epidemiology and biostatistics.

The Acute Effect of Methylphenidate in Brazilian Male Children and Adolescents with ADHD: A Randomized Clinical Trial

ERIC Educational Resources Information Center

Szobot, C. M.; Ketzer, C.; Parente, M. A.; Biederman, J.; Rohde, L. A.

2004-01-01

Objective: To evaluate the acute efficacy of methylphenidate (MPH) in Brazilian male children and adolescents with ADHD. Method: In a 4-day, double-blind, placebo-controlled, randomized, fix dose escalating, parallel-group trial, 36 ADHD children and adolescents were allocated to two groups: MPH (n = 19) and placebo (n = 17). Participants were…

Effects of Air Conditioner Use on Real-World Fuel Economy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huff, Shean P; West, Brian H; Thomas, John F

2013-01-01

Vehicle data were acquired on-road and on a chassis dynamometer to assess fuel consumption under several steady cruise conditions and at idle. Data were gathered for various air conditioner (A/C) settings and with the A/C off and the windows open. Two vehicles were used in the comparisonstudy: a 2009 Ford Explorer and a 2009 Toyota Corolla. At steady speeds between 64.4 and 112.7 kph (40 and 70 mph), both vehicles consumed more fuel with the A/C on at maximum cooling load (compressor at 100% duty cycle) than when driving with the windows down. The Explorer maintained this trend beyond 112.7more » kph (70 mph), while the Corolla fuel consumption with the windows down matched that of running the A/C at 120.7 kph (75 mph), and exceeded it at 128.7 kph (80 mph). The largest incremental fuel consumption rate penalty due to air conditioner use occurred was nearly constant with a weakslight trend of increasing consumption with increasing compressor (and vehicle) speed. Lower consumption is seenobserved at idle for both vehicles, likely due to the low compressor speed at this operating point« less

Evaluation of advanced air bag deployment algorithm performance using event data recorders.

PubMed

Gabler, Hampton C; Hinch, John

2008-10-01

This paper characterizes the field performance of occupant restraint systems designed with advanced air bag features including those specified in the US Federal Motor Vehicle Safety Standard (FMVSS) No. 208 for advanced air bags, through the use of Event Data Recorders (EDRs). Although advanced restraint systems have been extensively tested in the laboratory, we are only beginning to understand the performance of these systems in the field. Because EDRs record many of the inputs to the advanced air bag control module, these devices can provide unique insights into the characteristics of field performance of air bags. The study was based on 164 advanced air bag cases extracted from NASS/CDS 2002-2006 with associated EDR data. In this dataset, advanced driver air bags were observed to deploy with a 50% probability at a longitudinal delta-V of 9 mph for the first stage, and at 26 mph for both inflator stages. In general, advanced air bag performance was as expected, however, the study identified cases of air bag deployments at delta-Vs as low as 3-4 mph, non-deployments at delta-Vs over 26 mph, and possible delayed air bag deployments.

Evaluation of Advanced Air Bag Deployment Algorithm Performance using Event Data Recorders

PubMed Central

Gabler, Hampton C.; Hinch, John

2008-01-01

This paper characterizes the field performance of occupant restraint systems designed with advanced air bag features including those specified in the US Federal Motor Vehicle Safety Standard (FMVSS) No. 208 for advanced air bags, through the use of Event Data Recorders (EDRs). Although advanced restraint systems have been extensively tested in the laboratory, we are only beginning to understand the performance of these systems in the field. Because EDRs record many of the inputs to the advanced air bag control module, these devices can provide unique insights into the characteristics of field performance of air bags. The study was based on 164 advanced air bag cases extracted from NASS/CDS 2002-2006 with associated EDR data. In this dataset, advanced driver air bags were observed to deploy with a 50% probability at a longitudinal delta-V of 9 mph for the first stage, and at 26 mph for both inflator stages. In general, advanced air bag performance was as expected, however, the study identified cases of air bag deployments at delta-Vs as low as 3-4 mph, non-deployments at delta-Vs over 26 mph, and possible delayed air bag deployments. PMID:19026234

Engaging Key Stakeholders to Assess and Improve the Professional Preparation of MPH Health Educators

PubMed Central

Steckler, Allan; Maman, Suzanne; Ellenson, Meg; French, Elizabeth; Blanchard, Lynn; Bowling, Mike; Yamanis, Nina; Succop, Stacey; Davenport, Amy; Moracco, Beth

2010-01-01

Objectives. We described the process of engaging key stakeholders in a systematic review of requirements for a master of public health (MPH) degree within the Department of Health Behavior and Health Education, University of North Carolina Gillings School of Global Public Health, and summarized resulting changes. Methods. A benchmarking study of 11 peer institutions was completed. Key stakeholders (i.e., current students, alumni, faculty, staff, employers, and practicum preceptors) received online or print surveys. A faculty retreat was convened to process results and reach consensus on program revisions. Results. MPH program changes included (1) improved advising and mentoring program, (2) elimination of research and practice track options, (3) increased elective and decreased required credit hours, (4) replacement of master's paper requirement with “deliverables” (written products such as reports, documents, and forms) produced as part of the required “Capstone” course, (5) extended community field experience to 2 semesters and moved it to year 2 of the program, and (6) allowed practica of either 200, 300, or 400 hours. Conclusions. Engaging key stakeholders in the program review process yielded important changes to the MPH degree program requirements. Others may consider this approach when undertaking curriculum reviews. PMID:20395575

Innovating in Health Care Management Education: Development of an Accelerated MBA and MPH Degree Program at Yale

PubMed Central

Forman, Howard P.; Pistell, Anne F.; Nembhard, Ingrid M.

2015-01-01

Increasingly, there is recognition of the need for individuals with expertise in both management and public health to help health care organizations deliver high-quality and cost-effective care. The Yale School of Public Health and Yale School of Management began offering an accelerated Master of Business Administration (MBA) and Master of Public Health (MPH) joint degree program in the summer of 2014. This new program enables students to earn MBA and MPH degrees simultaneously from 2 fully accredited schools in 22 months. Students will graduate with the knowledge and skills needed to become innovative leaders of health care organizations. We discuss the rationale for the program, the developmental process, the curriculum, benefits of the program, and potential challenges. PMID:25706023

Community wind electrical power case study: Muir Beach. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bluhm, R.; Freebairn-Smith, R.

1979-10-01

Muir Beach experiences relatively steady northwest coastal winds. Recordings at anemometer stations have indicated wind speeds averaging 10 to 12 mph over the year. This compares favorably with the minimum of 8 to 9 mph generally considered necessary for feasible wind-electric generation. Given the town's wind environment, a 100 kW wind turbine of the kind planned could provide an annual output of about 150,000 kWh, or about one-eighth of Muir Beach's projected need. Especially promising for Muir Beach are other potential sites at higher elevations on neighboring Mt. Tamalpais, where federal records indicate annual average speeds of 18 mph. Eachmore » 100 kW wind turbine sited there could conservatively yield at least double and perhaps triple the output of the first system.« less

Innovating in health care management education: development of an accelerated MBA and MPH degree program at Yale.

PubMed

Pettigrew, Melinda M; Forman, Howard P; Pistell, Anne F; Nembhard, Ingrid M

2015-03-01

Increasingly, there is recognition of the need for individuals with expertise in both management and public health to help health care organizations deliver high-quality and cost-effective care. The Yale School of Public Health and Yale School of Management began offering an accelerated Master of Business Administration (MBA) and Master of Public Health (MPH) joint degree program in the summer of 2014. This new program enables students to earn MBA and MPH degrees simultaneously from 2 fully accredited schools in 22 months. Students will graduate with the knowledge and skills needed to become innovative leaders of health care organizations. We discuss the rationale for the program, the developmental process, the curriculum, benefits of the program, and potential challenges.

Saturn Northern Hemisphere

NASA Image and Video Library

1998-12-05

This false color picture of Saturn’s northern hemisphere was assembled from ultraviolet, violet and green images obtained Aug. 19 by Voyager 2 from a range of 7.1 million kilometers (4.4 million miles). The several weather patterns evident include three spots flowing westward at about 15 meters-per-second (33 mph). Although the cloud system associated with the western-most spot is part of this flow, the spot itself moves eastward at about 30 meters-per-second (65 mph). Their joint flow shows the anti-cyclonic rotation of the spot, which is about 3,000 km. (1,900 mi.) in diameter. The ribbon- like feature to the north marks a high-speed jet where wind speeds approach 150 meters-per-second (330 mph). http://photojournal.jpl.nasa.gov/catalog/PIA01365

Cost-benefit analysis of the 55-mph speed limit

DOE Office of Scientific and Technical Information (OSTI.GOV)

Forester, T.H.; McNown, R.F.; Singell, L.D.

1984-01-01

This article presents the results of an empirical study which estimates the number of reduced fatalities as a result of the imposed 55-mph speed limit. Time series data for the US from 1952 to 1979 is employed in a regression model capturing the relation between fatalities, average speed, variability of speed, and the speed limit. Also discussed are the alternative approaches to valuing human life and the value of time. Provided is a series of benefit-cost ratios based on alternative measures of the benefits and costs from life saving. The paper concludes that the 55-mph speed limit is not costmore » efficient unless additional time on the highway is valued significantly below levels estimated in the best reasearch on the value of time. 12 references, 1 table.« less

[Phytotherapy in urology. Current scientific evidence of its application in urolithiasis, chronic pelvic pain, erectile dysfunction and urinary tract infections].

PubMed

Morán, E; Budía, A; Broseta, E; Boronat, F

2013-03-01

To assess the usefulness of phytotherapy in urolitiasis, urinary tract infections, erectile dysfunction (ED) and chronic prostatitis/chronic pelvic pain (CP/CPP). Systematic review of the evidence published until January 2011 using the following scientific terms:phytotherapy, urinary lithiasis, Chronic prostatitis, chronic pelvic pain, erectile dysfunction, urinary tract infection, cystitis and the scientific names of compounds following the rules of the International Code of Botanical Nomenclature. The databases used were Medline and The Cochrane Library.We included articles published until January 2011 written in English and Spanish. We included studies in Vitro/in vivo on animal models or human beings. Exclusion criteria were literature not in English and Spanish or articles with serious methodological flaws. We included 86 articles selecting 40 that met the inclusion criteria. In Urolitiasis there are few works in humans. The phytate has its main use as prevention and in reducing the growth of residual fragments after extracorporeal shock wave lithotripsy (ESWL). In CP/CPP the only compound that has shown effectiveness was the extract of pollen in a field of multimodal treatment. In DE ther is no evidence for the use of herbal medicine.Most of the works have limitations in the design or low sample size. In urinary tract infections most of the products are diuretics .There is only evidence for the cranberry as prevention in young or pregnant women. It must not be used as a treatment for urinary tract infections. Phytotherapy is usefull in repeat urinary tract infections and the CP/CPP. It has some role in the urolitiasis and lacks useful in the DE. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

Long-Term Effectiveness and Safety of Dexmethylphenidate Extended-Release Capsules in Adult ADHD

ERIC Educational Resources Information Center

Adler, Lenard A.; Spencer, Thomas; McGough, James J.; Jiang, Hai; Muniz, Rafael

2009-01-01

Objective: This study evaluates dexmethylphenidate extended release (d-MPH-ER) in adults with ADHD. Method: Following a 5-week, randomized, controlled, fixed-dose study of d-MPH-ER 20 to 40 mg/d, 170 adults entered a 6-month open-label extension (OLE) to assess long-term safety, with flexible dosing of 20 to 40 mg/d. Exploratory effectiveness…

Teaching Science and Technology via Online Distance Learning: The Experience of Teaching Biostatistics in an Online Master of Public Health Programme

ERIC Educational Resources Information Center

Gemmell, Isla; Sandars, John; Taylor, Stewart; Reed, Katie

2011-01-01

This paper describes the development and teaching of a biostatistics module within a fully online distance learning Master of Public Health (MPH) programme at the University of Manchester. The MPH programme caters for students from over 40 countries worldwide and all materials are delivered via the Blackboard virtual learning environment. In this…

Atomoxetine and Methylphenidate Treatment in Children with ADHD: The Efficacy, Tolerability and Effects on Executive Functions

ERIC Educational Resources Information Center

Yildiz, Ozlem; Sismanlar, Sahika G.; Memik, Nursu Cakin; Karakaya, Isik; Agaoglu, Belma

2011-01-01

The aim of this study was to compare the safety, efficacy, tolerability, and the effects of atomoxetine and OROS-MPH on executive functions in children with ADHD. This study was an open-label study that only included two medication groups. Children were randomized to open-label atomoxetine or OROS-MPH for 12 weeks. Primary efficacy measures were…

Design of a Multi-Pinhole Collimator for I-123 DaTscan Imaging on Dual-Headed SPECT Systems in Combination with a Fan-Beam Collimator.

PubMed

King, Michael A; Mukherjee, Joyeeta M; Könik, Arda; Zubal, I George; Dey, Joyoni; Licho, Robert

2016-02-01

For the 2011 FDA approved Parkinson's Disease (PD) SPECT imaging agent I-123 labeled DaTscan, the volume of interest (VOI) is the interior portion of the brain. However imaging of the occipital lobe is also required with PD for calculation of the striatal binding ratio (SBR), a parameter of significance in early diagnosis, differentiation of PD from other disorders with similar clinical presentations, and monitoring progression. Thus we propose the usage of a combination of a multi-pinhole (MPH) collimator on one head of the SPECT system and a fan-beam on the other. The MPH would be designed to provide high resolution and sensitivity for imaging of the interior portion of the brain. The fan-beam collimator would provide lower resolution but complete sampling of the brain addressing data sufficiency and allowing a volume-of-interest to be defined over the occipital lobe for calculation of SBR's. Herein we focus on the design of the MPH component of the combined system. Combined reconstruction will be addressed in a subsequent publication. An analysis of 46 clinical DaTscan studies was performed to provide information to define the VOI, and design of a MPH collimator to image this VOI. The system spatial resolution for the MPH was set to 4.7 mm, which is comparable to that of clinical PET systems, and significantly smaller than that of fan-beam collimators employed in SPECT. With this set, we compared system sensitivities for three aperture array designs, and selected the 3 × 3 array due to it being the highest of the three. The combined sensitivity of the apertures for it was similar to that of an ultra-high resolution fan-beam (LEUHRF) collimator, but smaller than that of a high-resolution fan-beam collimator (LEHRF). On the basis of these results we propose the further exploration of this design through simulations, and the development of combined MPH and fan-beam reconstruction.

Switching from oral extended-release methylphenidate to the methylphenidate transdermal system: continued ADHD symptom control and tolerability after abrupt conversion

PubMed Central

Arnold, L. E.; Hodgkins, P.; McKay, M.; Beckett-Thurman, L.; Greenbaum, M.; Bukstein, O.; Patel, A.; Bozzolo, D. R.

2013-01-01

Objective To evaluate symptom control and tolerability after abrupt conversion from oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transition schedule in children with attention-deficit/hyperactivity disorder (ADHD). Methods In a 4-week, prospective, multisite, open-label study, 171 children (164 intent-to-treat) with diagnosed ADHD aged 6–12 years abruptly switched from a stable dose of oral ER-MPH to MTS in nominal dosages of 10, 15, 20, and 30 mg using a predefined dose-transition schedule. After the first week on the scheduled dose, the dose was titrated to optimal effect. The primary effectiveness outcome was the change from baseline (while taking ER-MPH) to week 4 in ADHD-Rating Scale-IV (ADHD-RS-IV) total scores. Adverse events (AEs) were assessed throughout the study. Results Most subjects (58%) remained on the initial MTS dose defined by the dose-transition schedule; 38% increased and 4% decreased their MTS dose for optimization. MTS dose optimization resulted in significantly better ADHD-RS-IV total (mean ± SD) scores at week 4 than at baseline (9.9±7.47 vs 14.1±7.48; p<0.0001). The most commonly reported AEs included headache, decreased appetite, insomnia, and upper abdominal pain. Four subjects (2.3%) discontinued because of application site reactions and 3 discontinued because of other AEs. Conclusions Abrupt conversion from a stable dose of oral ER-MPH to MTS was accomplished using a predefined dose-transition schedule without loss of symptom control; however, careful titration to optimal dose is recommended. Most AEs were mild to moderate and, with the exception of application site reactions, were similar to AEs typically observed with oral MPH. Limitations of this study included its open-label sequential design without placebo, which could result in spurious attribution of improvement to the study treatment and precluded superiority determinations of MTS over baseline ER-MPH treatment. The apparent superiority of MTS was likely due to more careful titration and clinical monitoring rather than the product itself. NCT NCT00151983 PMID:19916704

Norepinephrine genes predict response time variability and methylphenidate-induced changes in neuropsychological function in attention deficit hyperactivity disorder.

PubMed

Kim, Bung-Nyun; Kim, Jae-Won; Cummins, Tarrant D R; Bellgrove, Mark A; Hawi, Ziarih; Hong, Soon-Beom; Yang, Young-Hui; Kim, Hyo-Jin; Shin, Min-Sup; Cho, Soo-Churl; Kim, Ji-Hoon; Son, Jung-Woo; Shin, Yun-Mi; Chung, Un-Sun; Han, Doug-Hyun

2013-06-01

Noradrenergic dysfunction may be associated with cognitive impairments in attention-deficit/hyperactivity disorder (ADHD), including increased response time variability, which has been proposed as a leading endophenotype for ADHD. The aim of this study was to examine the relationship between polymorphisms in the α-2A-adrenergic receptor (ADRA2A) and norepinephrine transporter (SLC6A2) genes and attentional performance in ADHD children before and after pharmacological treatment.One hundred one medication-naive ADHD children were included. All subjects were administered methylphenidate (MPH)-OROS for 12 weeks. The subjects underwent a computerized comprehensive attention test to measure the response time variability at baseline before MPH treatment and after 12 weeks. Additive regression analyses controlling for ADHD symptom severity, age, sex, IQ, and final dose of MPH examined the association between response time variability on the comprehensive attention test measures and allelic variations in single-nucleotide polymorphisms of the ADRA2A and SLC6A2 before and after MPH treatment.Increasing possession of an A allele at the G1287A polymorphism of SLC6A2 was significantly related to heightened response time variability at baseline in the sustained (P = 2.0 × 10) and auditory selective attention (P = 1.0 × 10) tasks. Response time variability at baseline increased additively with possession of the T allele at the DraI polymorphism of the ADRA2A gene in the auditory selective attention task (P = 2.0 × 10). After medication, increasing possession of a G allele at the MspI polymorphism of the ADRA2A gene was associated with increased MPH-related change in response time variability in the flanker task (P = 1.0 × 10).Our study suggested an association between norepinephrine gene variants and response time variability measured at baseline and after MPH treatment in children with ADHD. Our results add to a growing body of evidence, suggesting that response time variability is a viable endophenotype for ADHD and suggesting its utility as a surrogate end point for measuring stimulant response in pharmacogenetic studies.

Accuracy of Automated Flow Cytometry-Based Leukocyte Counts To Rule Out Urinary Tract Infection in Febrile Children: a Prospective Cross-Sectional Study

PubMed Central

Duong, Hong Phuoc; Wissing, Karl Martin; Tram, Nathalie; Mascart, Georges; Lepage, Philippe

2016-01-01

Automated flow cytometry of urine remains an incompletely validated method to rule out urinary tract infection (UTI) in children. This cross-sectional analytical study was performed to compare the predictive values of flow cytometry and a dipstick test as initial diagnostic tests for UTI in febrile children and prospectively included 1,106 children (1,247 episodes). Urine culture was used as the gold standard test for diagnosing UTI. The performance of screening tests to diagnose UTI were established using receiver operating characteristic (ROC) analysis. Among these 1,247 febrile episodes, 221 UTIs were diagnosed (17.7% [95% confidence interval {CI}, 15.6 to 19.8%]). The area under the ROC curve for flow cytometry white blood cell (WBC) counts (0.99 [95% CI, 0.98 to 0.99]) was significantly superior to that for red blood cell (0.74 [95% CI, 0.70 to 0.78]) and bacterial counts (0.89 [95% CI, 0.87 to 0.92]) (P < 0.001). Urinary WBC counts also had a significantly higher area under the ROC curve than that of the leukocyte esterase (LE) dipstick (0.92 [95% CI, 0.90 to 0.94]), nitrite dipstick (0.83 [95% CI, 0.80 to 0.87]), or the combination of positive LE and/or nitrite dipstick (0.91 [95% CI, 0.89 to 0.93]) test (P < 0.001). The presence of ≥35 WBC/μl of urine was the best cutoff point, yielding both a high sensitivity (99.5% [95% CI, 99 to 100%]) and an acceptable specificity (80.6% [95% CI, 78 to 83%]). Using this cutoff point would have reduced the number of samples sent to the laboratory for culture by 67%. In conclusion, the determination of urinary WBC counts by flow cytometry provides optimal performance as an initial diagnostic test for UTI in febrile children. PMID:27682127

[Recurrent and catheter-associated urinary tract infections : Prophylaxis and prevention].

PubMed

Piechota, H

2017-06-01

Urinay tract infection (UTI) as one of the most frequent bacterial infections in humans is of utmost relevance. Because of the rising prevalence of antimicrobial resistance, urinalysis should always include urine culture and a resistogram in order to avoid an unspecific selection and overuse of antibiotics. Prevention of recurrent UTI must first of all rule out predisposing uropathogenic conditions. Nowadays, a great variety of drugs, behavioral, and supportive treatment options can effectively minimize UTI recurrence. The growing importance of vaccines (immunotherapy), probiotics (lactobacilli), and standardized herbal preparations meets the need of reducing antibiotic use and the development of antimicrobial resistance. Around 80% of all nosocomial UTIs (nUTIs) are associated with indwelling urinary catheters. It is estimated that up to 70% of all nUTIs occurring in Germany may be avoided by using appropriate preventative measures. Therefore, profound knowledge about the basics of catheter-associated nUTIs and the correct management of urinary catheters are of utmost individual and socioeconomic importance.

No. 127-The Evaluation of Stress Incontinence Prior to Primary Surgery.

PubMed

Farrell, Scott A

2018-02-01

To provide clinical guidelines for the evaluation of women with stress urinary incontinence prior to primary anti-incontinence surgery. The modalities of evaluation range from basic pelvic examination through to the use of adjuncts including ultrasound and urodynamic testing. These guidelines provide a comprehensive approach to the preoperative evaluation of urinary incontinence to ensure that excessive evaluation is avoided without sacrificing diagnostic accuracy. Published opinions of experts, supplemented by evidence from clinical trials, where appropriate. The quality of the evidence is rated using the criteria described by the Canadian Task Force on the Periodic Health Examination. Comprehensive evaluation of women considering surgery to treat urinary incontinence is essential to rule out causes of incontinence that may not be amenable to surgical treatment. Simplifying the evaluation minimizes the discomfort and embarrassment potentially experienced by women. VALIDATION: These guidelines have been approved by the Urogynaecology Committee and the Executive and Council of The Society of Obstetricians and Gynaecologists of Canada. Copyright © 2018. Published by Elsevier Inc.

Lower Urinary Tract Dysfunction in Elementary School Children: Results of a Cross-Sectional Teacher Survey.

PubMed

Ko, Lauren N; Chuang, Kai-wen; Champeau, Angelique; Allen, I Elaine; Copp, Hillary L

2016-04-01

Lower urinary tract dysfunction in school-aged children is common and yet data are lacking on current teacher practice regarding bathroom use and daytime incontinence during classroom hours. We determined the prevalence of elementary school teachers who promote lower urinary tract health and identified predictors for and against such behavioral promotion. We performed an electronic cross-sectional survey among self-identified teachers using targeted social media advertisement during a 1-week period in July 2014. The empirical survey tool consisted of 27 questions and collected data on 5 principal domains, including 1) teacher demographics, 2) rules and regulations on water intake and bathroom use during classroom hours, 3) characteristics of school bathrooms in terms of safety, supervision and suitability for use, 4) experience with and management of students with daytime incontinence and 5) training on the topic of lower urinary tract health. Predictors for promoting lower urinary tract health were identified by multivariable logistic regression. Of the 4,166 teachers who completed the survey 88% indicated that they encourage students to hold urine. Despite strict bathroom protocols 81% of teachers allowed children unlimited access to water. Of the teachers 82% reported never having undergone any professional development on bathroom regulations for children. Overall only 24% of surveyed teachers met criteria for promoting lower urinary tract health. The odds of promoting lower urinary tract health decreased with ascending grade level (OR 0.80, 95% CI 0.76-0.84). Conversely it increased if teaching experience was greater than 5 years (OR 1.66, 95% CI 1.39-1.98) or professional development on the subject had been received (OR 1.42, 95% CI 1.18-1.70). Of elementary school teachers 76% are not promoting lower urinary tract health in school-aged children. Professional development training on the topics of lower urinary tract dysfunction and/or lower urinary tract health may be beneficial, particularly for educators who teach higher grades and those with less teaching experience. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Auditory Processing Assessment in Children with Attention Deficit Hyperactivity Disorder: An Open Study Examining Methylphenidate Effects

PubMed Central

Lanzetta-Valdo, Bianca Pinheiro; Oliveira, Giselle Alves de; Ferreira, Jane Tagarro Correa; Palacios, Ester Miyuki Nakamura

2016-01-01

Introduction Children with Attention Deficit Hyperactivity Disorder can present Auditory Processing (AP) Disorder. Objective The study examined the AP in ADHD children compared with non-ADHD children, and before and after 3 and 6 months of methylphenidate (MPH) treatment in ADHD children. Methods Drug-naive children diagnosed with ADHD combined subtype aging between 7 and 11 years, coming from public and private outpatient service or public and private school, and age-gender-matched non-ADHD children, participated in an open, non-randomized study from February 2013 to December 2013. They were submitted to a behavioral battery of AP tests comprising Speech with white Noise, Dichotic Digits (DD), and Pitch Pattern Sequence (PPS) and were compared with non-ADHD children. They were followed for 3 and 6 months of MPH treatment (0.5 mg/kg/day). Results ADHD children presented larger number of errors in DD (p < 0.01), and less correct responses in the PPS (p < 0.0001) and in the SN (p < 0.05) tests when compared with non-ADHD children. The treatment with MPH, especially along 6 months, significantly decreased the mean errors in the DD (p < 0.01) and increased the correct response in the PPS (p < 0.001) and SN (p < 0.01) tests when compared with the performance before MPH treatment. Conclusions ADHD children show inefficient AP in selected behavioral auditory battery suggesting impaired in auditory closure, binaural integration, and temporal ordering. Treatment with MPH gradually improved these deficiencies and completely reversed them by reaching a performance similar to non-ADHD children at 6 months of treatment. PMID:28050211

Auditory Processing Assessment in Children with Attention Deficit Hyperactivity Disorder: An Open Study Examining Methylphenidate Effects.

PubMed

Lanzetta-Valdo, Bianca Pinheiro; Oliveira, Giselle Alves de; Ferreira, Jane Tagarro Correa; Palacios, Ester Miyuki Nakamura

2017-01-01

Introduction  Children with Attention Deficit Hyperactivity Disorder can present Auditory Processing (AP) Disorder. Objective  The study examined the AP in ADHD children compared with non-ADHD children, and before and after 3 and 6 months of methylphenidate (MPH) treatment in ADHD children. Methods  Drug-naive children diagnosed with ADHD combined subtype aging between 7 and 11 years, coming from public and private outpatient service or public and private school, and age-gender-matched non-ADHD children, participated in an open, non-randomized study from February 2013 to December 2013. They were submitted to a behavioral battery of AP tests comprising Speech with white Noise, Dichotic Digits (DD), and Pitch Pattern Sequence (PPS) and were compared with non-ADHD children. They were followed for 3 and 6 months of MPH treatment (0.5 mg/kg/day). Results  ADHD children presented larger number of errors in DD ( p  < 0.01), and less correct responses in the PPS ( p  < 0.0001) and in the SN ( p  < 0.05) tests when compared with non-ADHD children. The treatment with MPH, especially along 6 months, significantly decreased the mean errors in the DD ( p  < 0.01) and increased the correct response in the PPS ( p  < 0.001) and SN ( p  < 0.01) tests when compared with the performance before MPH treatment. Conclusions  ADHD children show inefficient AP in selected behavioral auditory battery suggesting impaired in auditory closure, binaural integration, and temporal ordering. Treatment with MPH gradually improved these deficiencies and completely reversed them by reaching a performance similar to non-ADHD children at 6 months of treatment.

Effect of Methylphenidate on Emotional Dysregulation in Children With Attention-Deficit/Hyperactivity Disorder + Oppositional Defiant Disorder/Conduct Disorder.

PubMed

Kutlu, Ayse; Akyol Ardic, Ulku; Ercan, Eyup Sabri

2017-04-01

Emotional dysregulation (ED) is a frequent feature of attention-deficit/hyperactivity disorder (ADHD). It can be observed as a dysregulation profile or a deficient emotional self-regulation (DESR) profile. Oppositional defiant disorder/conduct disorder (ODD/CD) comorbidity is prevalent in ADHD and known to be related with ED. The first-line treatment of ADHD includes psychostimulants, but their effects on ED are not well studied. This study aimed to evaluate the outcomes of methylphenidate (MPH) treatment on ED in ADHD + ODD/CD cases. A total of 118 ADHD + ODD/CD patients with a mean age of 9.0 ± 1.9 years were treated with MPH for 1 year. Also, parents of cases were recruited for a parent-training program, which initiated after first month of MPH treatment. Symptom severity was assessed at baseline and 12th month by Turgay Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-Based Child and Adolescent Behavior Disorders Screening and Rating Scale-Parent Form, Children Depression Inventory, Child Behavior Checklist 4-18 years, and Parental Acceptance and Rejection Questionnaire-Mother Form. Emotional dysregulation (DESR + DP) was present in 85.6% of cases. Conduct disorder was significantly higher in patients with DP, whereas ODD was significantly higher in the DESR and non-ED groups (P < 0.0001). Symptoms of ADHD and ED were significantly improved with 1-year of MPH treatment (P < 0.05). The improvement in ED was independent of improvement in ADHD symptoms and parent training (P < 0.05). Emotional dysregulation is highly prevalent in disruptive behavioral disorders as ODD and CD, which are comorbid with ADHD. The MPH treatment is effective on ED independently from other clinical determinants.

Open-label dose optimization of methylphenidate modified release long acting (MPH-LA): a post hoc analysis of real-life titration from a 40-week randomized trial.

PubMed

Huss, Michael; Ginsberg, Ylva; Arngrim, Torben; Philipsen, Alexandra; Carter, Katherine; Chen, Chien-Wei; Gandhi, Preetam; Kumar, Vinod

2014-09-01

In the management of attention-deficit hyperactivity disorder (ADHD) in adults it is important to recognize that individual patients respond to a wide range of methylphenidate doses. Studies with methylphenidate modified release long acting (MPH-LA) in children have reported the need for treatment optimization for improved outcomes. We report the results from a post hoc analysis of a 5-week dose optimization phase from a large randomized, placebo-controlled, multicenter 40-week study (9-week double-blind dose confirmation phase, 5-week open-label dose optimization phase, and 26-week double-blind maintenance of effect phase). Patients entering the open-label dose optimization phase initiated treatment with MPH-LA 20 mg/day; up/down titrated to their optimal dose (at which there was balance between control of symptoms and side effects) of 40, 60, or 80 mg/day in increments of 20 mg/week by week 12 or 13. Safety was assessed by monitoring the adverse events (AEs) and serious AEs. Efficacy was assessed by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, Attention-Deficit Hyperactivity Disorder Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores. At the end of the dose confirmation phase, similar numbers of patients were treated optimally with each of the 40, 60, and 80 mg/day doses (152, 177, and 160, respectively) for MPH-LA. Mean improvement from baseline in the dose confirmation phase in total scores of DSM-IV ADHD RS and SDS were 23.5 ± 9.90 and 9.7 ± 7.36, respectively. Dose optimization with MPH-LA (40, 60, or 80 mg/day) improved treatment outcomes and was well-tolerated in adult ADHD patients.

Tropical Cyclone Glenda in the Indian Ocean

NASA Image and Video Library

2015-03-03

Tropical Cyclone Glenda took a five day tour of the Southern Indian Ocean in late February, 2015. The storm formed from a low pressure system, System 90S on February 24, when maximum sustained winds reached 40 mph (64 km/h). The Moderate Resolution Imaging Spectroradiometer (MODIS) aboard NASA’s Aqua satellite captured this true-color image of Tropical Storm Glenda on February 25 at 08:55 UTC (3:55 a.m. EST). At that time bands of thunderstorms wrapped into the low-level center of circulation. An eye was beginning to form. At 0900 UTC (4 a.m. EST) on February 25, Glenda's maximum sustained winds were near 63.2 mph (102 km/h). It was centered near 17.6 south latitude and 69.1 east longitude, about 760 miles (1,224 km) south-southwest of Diego Garcia. Glenda was moving to the west-southwest at 8 mph (13 km/h). At that time, the Joint Typhoon Warning Center expect Glenda to strengthen to near 109 mph (176 km/h) before beginning to weaken. However, strong wind shear began to affect the storm. By the afternoon of February 26 Tropical Cyclone Glenda’s winds had dropped to about 58 mph (93 km/h), and by February 28 the storm had transitioned to an extra-tropical storm. Credit: NASA/GSFC/Jeff Schmaltz/MODIS Land Rapid Response Team NASA image use policy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Like us on Facebook Find us on Instagram

Effects of methylphenidate on quality of life in children with both developmental coordination disorder and ADHD.

PubMed

Flapper, Boudien C T; Schoemaker, Marina M

2008-04-01

Measurement of health-related quality of life (HRQOL) in attention-deficit-hyperactivity disorder (ADHD) gives a more complete picture of day-to-day functioning and treatment effects than behavioural rating alone. The aim of this pilot study was to investigate the impact of the combined diagnoses of developmental coordination disorder (DCD) and ADHD on HRQOL, and the effectiveness of methylphenidate (MPH) on HRQOL. HRQOL was established using the Dutch-Child-AZL-TNO-Quality-of-Life (DUX-25) and the TNO-AZL-Child-Quality-of-Life (TACQOL) questionnaires, completed by children and parents. HRQOL of these children was compared with that of 23 age- and sex-matched healthy controls. Twenty-three children (21 males, two females; mean age 8 y 6 mo, [SD 3 mo] range 7 y-10 y 8 mo) with ADHD/DCD entered a 4-week, open-label MPH study, after MPH-sensitivity was established, in a double-blind, placebo-controlled trial. In these children's self- and proxy reports, impact of both DCD and ADHD was reflected in lower general well-being (self and proxy report p=0.001) due to lower functioning in motor (selfp=0.026; proxy 0.001), autonomic (self p<0.001; proxy p=0.047), cognitive (self p=0.001; proxy p=0.01), and social (self and proxy p<0.001) domains. HRQOL scores improved in 18 children receiving MPH (p=0.001) versus controls. The ADHD /DCD group also demonstrated a significant improvement in ADHD symptoms (p<0.001) and motor functioning (p<0.001). Additional motor therapy will still be needed in about half of the children with ADHD/DCD receiving MPH, within multimodal treatment including educational and psychosocial assistance.

Comparison of Objective and Subjective Changes Induced by Multiple-Pinhole Glasses and Single-Pinhole Glasses

PubMed Central

2017-01-01

Multiple-pinhole (MPH) glasses are currently sold in many countries with unproven advertisements; however, their objective and subjective effects have not been investigated. Therefore, to investigate the effects of MPH glasses excluding the single-pinhole (SPH) effect, we compared the visual functional changes, reading speed, and ocular discomfort after reading caused by MPH and SPH glasses. Healthy 36 participants with a mean age of 33.1 years underwent examinations of pupil size, visual acuity (VA), depth of focus (DOF), and near point accommodation (NPA); tests for visual field (VF), contrast sensitivity (CS), stereopsis, and reading speed; and a survey of ocular discomfort after reading. Both types of pinhole glasses enlarged pupil diameter and improved VA, DOF, and NPA. However, CS, stereopsis, and VF parameters deteriorated. In comparison with SPH glasses, MPH glasses induced smaller pupil dilation (5.3 and 5.9 mm, P < 0.001) and showed better VF parameters with preserved peripheral VF. However, no significant difference was observed for VA, DOF, NPA, stereopsis, and CS. Reading speed using pinhole glasses was significantly slower than baseline; SPH glasses showed the slowest reading speed. Both types of glasses caused significant ocular discomfort after reading compared with baseline, and symptoms were worst with MPH glasses. In conclusion, both types of pinhole glasses had positive effects due to the pinhole effect; however, they had negative effects on VF, CS, stereopsis, reading speed, and ocular discomfort. In spite of the increased luminance and preserved peripheral VF with MPHs, these glasses caused more severe ocular discomfort than SPH glasses. This clinical trial was registered at www.ClinicalTrials.gov (Identifier: NCT02572544). PMID:28378561

A review of OROS methylphenidate (Concerta(®)) in the treatment of attention-deficit/hyperactivity disorder.

PubMed

Katzman, Martin A; Sternat, Tia

2014-11-01

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioural disorder with onset during childhood. It affects a child's development, both at home and at school, and impacts on social, emotional and cognitive functioning, in both the home and the school environment. Untreated ADHD is very often associated with poor academic achievement, low occupational status, increased risk of substance abuse and delinquency. Current practice guidelines recommend a multimodal approach in the treatment of ADHD, which includes educational, behavioural and mental health interventions, and pharmacological management. Stimulant medications, including methylphenidate (MPH) and amphetamine products, are recommended as first-line pharmacotherapy in the treatment of ADHD. The choice of stimulant is influenced by several factors; the most influential factor is the duration of action. Long-acting medication provides benefits long after school and work. It also increases the likelihood of once-daily dosing, thereby eliminating the need for mid-day dosing, making the treatment more private, avoiding stigma and improving adherence to medication. MPH is the most widely used psychotropic medication in child psychiatry. It was first developed for use in children as an oral, immediate-release formulation and more recently as various extended-release formulations. These latter formulations include the 12 h preparation Concerta(®) (osmotic-release oral system [OROS] MPH), which utilizes an osmotic pump system, designed to overcome the difficulties of multiple daily dosing. Since it received approval from the US Food and Drug Administration in August 2000, OROS MPH has been quickly and widely accepted as one of the preferred treatments for ADHD because of its once-daily dosing. This paper reviews the data in support of long-acting OROS MPH in children, adolescents and adults, both in ADHD and in association with its comorbidities.

Improvements in Irritability with Open-Label Methylphenidate Treatment in Youth with Comorbid Attention Deficit/Hyperactivity Disorder and Disruptive Mood Dysregulation Disorder.

PubMed

Winters, Drew E; Fukui, Sadaaki; Leibenluft, Ellen; Hulvershorn, Leslie A

2018-06-01

The purpose of this open-label study was to examine the effects of long-acting methylphenidate (MPH) treatment on irritability and related emotional symptoms associated with disruptive mood dysregulation disorder (DMDD) in youth with comorbid attention-deficit/hyperactivity disorder (ADHD). The sample included 22 medication-free male and female subjects (ages 9-15) who met criteria for both DMDD and ADHD. Participants underwent a 4-week trial of long-acting MPH treatment (Concerta ® ), with weekly dosing increases until a therapeutic dose was reached. Repeated measures t-tests were used to compare pre- and posttreatment ratings of primary and secondary measures. The primary outcome was self-report irritability. Secondary outcomes included parent and child ratings of emotional frequency, emotional lability, and negative affect (NA). Multiple regression was used to examine the impact baseline hyperactivity, age, gender, race, socioeconomic status, or comorbid diagnosis had on treatment outcomes. Significant improvements (medium to large effect sizes) in child-rated irritability as well as parent and child ratings of emotional lability, NA, and anger were found. As anticipated, ADHD symptoms also improved. While a majority of the sample saw improvement in child-rated irritability (71%), symptoms worsened a small proportion (19%), and an even smaller portion experienced no change (10%). No demographics, psychiatric comorbidities, or severity of ADHD symptoms influenced treatment outcomes. Study findings suggest that MPH treatment significantly improved mood and emotional symptoms associated with DMDD comorbid with ADHD. These findings, coupled with good tolerability in this open-label pilot study supports further research into the use of MPH as a first-line treatment for DMDD. Future work examining MPH treatment of youth with DMDD with and without comorbid ADHD is needed.

Attention-deficit hyperactivity disorder, its treatment with medication and the probability of developing a depressive disorder: A nationwide population-based study in Taiwan.

PubMed

Lee, Min-Jing; Yang, Kang-Chung; Shyu, Yu-Chiau; Yuan, Shin-Sheng; Yang, Chun-Ju; Lee, Sheng-Yu; Lee, Tung-Liang; Wang, Liang-Jen

2016-01-01

The purpose of this study is to determine the risk of developing depressive disorders by evaluating children with attention-deficit/hyperactivity disorder (ADHD) in comparison to controls that do not have ADHD, as well as to analyze whether the medications used to treat ADHD, methylphenidate (MPH) and atomoxetine (ATX), influence the risk of depression. A group of patients newly diagnosed with ADHD (n=71,080) and age- and gender-matching controls (n=71,080) were chosen from Taiwan's National Health Insurance database during the period of January 2000 to December 2011. Both the patients and controls were monitored through December 31, 2011. We also explore the potential influence of the length of MPH and ATX treatment on developing depressive disorders. The ADHD patients showed a significantly increased probability of developing a depressive disorder when compared to the control group (ADHD: 5.3% vs. 0.7%; aHR, 7.16, 99% CI: 6.28-8.16). Regarding treatment with MPH, a longer MPH use demonstrates significant protective effects against developing a depressive disorder (aOR, 0.91, 99%CI: 0.88-0.94). However, the duration of ATX treatment could not be significantly correlated with the probability of developing a depressive disorder. The database employed in this study lacks of comprehensive clinical information for the patients with ADHD. Potential moderating factors between ADHD and depression were not considered in-depth in this study. The results of this study reveal that youths diagnosed with ADHD have a greater risk of developing depressive disorders. Long-term treatment with MPH correlated to the reduced probability of developing a depressive disorder among youths with ADHD. Copyright © 2015 Elsevier B.V. All rights reserved.

Quantifying the causal effects of 20mph zones on road casualties in London via doubly robust estimation.

PubMed

Li, Haojie; Graham, Daniel J

2016-08-01

This paper estimates the causal effect of 20mph zones on road casualties in London. Potential confounders in the key relationship of interest are included within outcome regression and propensity score models, and the models are then combined to form a doubly robust estimator. A total of 234 treated zones and 2844 potential control zones are included in the data sample. The propensity score model is used to select a viable control group which has common support in the covariate distributions. We compare the doubly robust estimates with those obtained using three other methods: inverse probability weighting, regression adjustment, and propensity score matching. The results indicate that 20mph zones have had a significant causal impact on road casualty reduction in both absolute and proportional terms. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Critical Care Trained Flight Paramedics on Casualty Survival During Helicopter Evacuation in the Current War in Afghanistan

DTIC Science & Technology

2012-01-01

survival during helicopter evacuation in the current war in Afghanistan Robert L . Mabry ...MD, MC, Amy Apodaca , MS, Jason Penrod , PharmD, Jean A . Orman , ScD, MPH, Robert T. Gerhardt , MD, MPH, and Warren C. Dorlac, MD, Fort Sam Houston...GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Mabry R. L ., Apodaca A ., Penrod J.,

Prior Health Care Utilization as a Potential Determinant of Enrollment in a 21-Year Prospective Study, the Millennium Cohort Study

DTIC Science & Technology

2008-01-10

studies Military medicine Military personnel Response bias Veterans Abbreviations CI Confidence interval ICD-9- CM International...DVM, MPH and Tomoko I Hooper, MD MPH (Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences...hospitalization. In contrast, the decision to seek outpatient care may be a personal decision to seek con- sultation, preventive medicine , or medical

Supertyphoon Yuri, Western Pacific Ocean

NASA Image and Video Library

1991-12-01

Supertyphoon Yuri began development approximately 1000 miles east of the Philippine Islands. At the time this photo was taken, Yuri was about 1000 nautical miles in diameter and had estimated maximum sustained wind speeds of 145 mph, gusting to 170 mph. This oblique view shows the well formed eye of Yuri and the raised segment of clouds at the cusp of the eye indicating very high wind speeds within the vortex.

40 CFR 86.161-00 - Air conditioning environmental test facility ambient requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... each point of a 0.5 meter grid over the entire footprint of the test vehicle at the elevation of one... impractical, air flow of 2 mph or less will be allowed at 0 mph vehicle speed. (3) The fan air flow velocity..., within the test cell, during all phases of the air conditioning test sequence to 95 ±2 °F on average and...

MYOCARDIAL INJURY FROM INHALED COMBUSTION PARTICLES: IS THERE A ROLE FOR ZINC?

EPA Science Inventory

Myocardial injury from inhaled combustion particles: Is there a role for zinc?
U.P.Kodavanti, PhD 1, C.F.Moyer, PhD, DVM 2, A.D.Ledbetter, BS 1, M.C.Schladweiler, BS
1, P.S.Gilmour, PhD 1, R.Hauser, ScD, MPH 3, D.C.Christiani, MPH, MS 3, D.L.Costa, ScD
1 and A.Ny...

A chloroplast thylakoid lumen protein is required for proper photosynthetic acclimation of plants under fluctuating light environments

PubMed Central

2017-01-01

Despite our increasingly sophisticated understanding of mechanisms ensuring efficient photosynthesis under laboratory-controlled light conditions, less is known about the regulation of photosynthesis under fluctuating light. This is important because—in nature—photosynthetic organisms experience rapid and extreme changes in sunlight, potentially causing deleterious effects on photosynthetic efficiency and productivity. Here we report that the chloroplast thylakoid lumenal protein MAINTENANCE OF PHOTOSYSTEM II UNDER HIGH LIGHT 2 (MPH2; encoded by At4g02530) is required for growth acclimation of Arabidopsis thaliana plants under controlled photoinhibitory light and fluctuating light environments. Evidence is presented that mph2 mutant light stress susceptibility results from a defect in photosystem II (PSII) repair, and our results are consistent with the hypothesis that MPH2 is involved in disassembling monomeric complexes during regeneration of dimeric functional PSII supercomplexes. Moreover, mph2—and previously characterized PSII repair-defective mutants—exhibited reduced growth under fluctuating light conditions, while PSII photoprotection-impaired mutants did not. These findings suggest that repair is not only required for PSII maintenance under static high-irradiance light conditions but is also a regulatory mechanism facilitating photosynthetic adaptation under fluctuating light environments. This work has implications for improvement of agricultural plant productivity through engineering PSII repair. PMID:28874535

Methylphenidate does not enhance visual working memory but benefits motivation in macaque monkeys.

PubMed

Oemisch, Mariann; Johnston, Kevin; Paré, Martin

2016-10-01

Working memory is a limited-capacity cognitive process that retains relevant information temporarily to guide thoughts and behavior. A large body of work has suggested that catecholamines exert a major modulatory influence on cognition, but there is only equivocal evidence of a direct influence on working memory ability, which would be reflected in a dependence on working memory load. Here we tested the contribution of catecholamines to working memory by administering a wide range of acute oral doses of the dopamine and norepinephrine reuptake inhibitor methylphenidate (MPH, 0.1-9 mg/kg) to three female macaque monkeys (Macaca mulatta), whose working memory ability was measured from their performance in a visual sequential comparison task. This task allows the systematic manipulation of working memory load, and we therefore tested the specific hypothesis that MPH modulates performance in a manner that depends on both dose and memory load. We found no evidence of a dose- or memory load-dependent effect of MPH on performance. In contrast, significant effects on measures of motivation were observed. These findings suggest that an acute increase in catecholamines does not seem to affect the retention of visual information per se. As such, these results help delimit the effects of MPH on cognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Paleoparasitological Hybridization Approach as Effective Tool for Diagnosing Human Intestinal Parasites from Scarce Archaeological Remains

PubMed Central

Jaeger, Lauren Hubert; Iñiguez, Alena Mayo

2014-01-01

Paleoparasitology is the science that uses parasitological techniques for diagnosing parasitic diseases in the past. Advances in molecular biology brought new insights into this field allowing the study of archaeological material. However, due to technical limitations a proper diagnosis and confirmation of the presence of parasites is not always possible, especially in scarce and degraded archaeological remains. In this study, we developed a Molecular Paleoparasitological Hybridization (MPH) approach using ancient DNA (aDNA) hybridization to confirm and complement paleoparasitological diagnosis. Eight molecular targets from four helminth parasites were included: Ascaris sp., Trichuris trichiura, Enterobius vermicularis, and Strongyloides stercoralis. The MPH analysis using 18th century human remains from Praça XV cemetery (CPXV), Rio de Janeiro, Brazil, revealed for the first time the presence E. vermicularis aDNA (50%) in archaeological sites of Brazil. Besides, the results confirmed T. trichiura and Ascaris sp. infections. The prevalence of infection by Ascaris sp. and E. vermicularis increased considerably when MPH was applied. However, a lower aDNA detection of T. trichiura (40%) was observed when compared to the diagnosis by paleoparasitological analysis (70%). Therefore, based on these data, we suggest a combination of Paleoparasitological and MPH approaches to verify the real panorama of intestinal parasite infection in human archeological samples. PMID:25162694

Environmental consequences of postulate plutonium releases from Atomics International's Nuclear Materials Development Facility (NMDF), Santa Susana, California, as a result of severe natural phenomena

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jamison, J.D.; Watson, E.C.

1982-02-01

Potential environmental consequences in terms of radiation dose to people are presented for postulated plutonium releases caused by severe natural phenomena at the Atomics International's Nuclear Materials Development Facility (NMDF), in the Santa Susana site, California. The severe natural phenomena considered are earthquakes, tornadoes, and high straight-line winds. Plutonium deposition values are given for significant locations around the site. All important potential exposure pathways are examined. The most likely 50-year committed dose equivalents are given for the maximum-exposed individual and the population within a 50-mile radius of the plant. The maximum plutonium deposition values likely to occur offsite are alsomore » given. The most likely calculated 50-year collective committed dose equivalents are all much lower than the collective dose equivalent expected from 50 years of exposure to natural background radiation and medical x-rays. The most likely maximum residual plutonium contamination estimated to be deposited offsite following the earthquake, and the 150-mph and 170-mph tornadoes are above the Environmental Protection Agency's (EPA) proposed guideline for plutonium in the general environment of 0.2 ..mu..Ci/m/sup 2/. The deposition values following the 110-mph and the 130-mph tornadoes are below the EPA proposed guideline.« less

Effect of methylphenidate and/or levodopa coupled with physiotherapy on functional and motor recovery after stroke--a randomized, double-blind, placebo-controlled trial.

PubMed

Lokk, J; Salman Roghani, R; Delbari, A

2011-04-01

Amphetamine-like drugs are reported to enhance motor recovery and activities of daily living (ADL) in stroke rehabilitation, but results from trials with humans are inconclusive. This study is aimed at investigating whether levodopa (LD) and/or methylphenidate (MPH) in combination with physiotherapy could improve functional motor recovery and ADL in patients with stroke. A randomized, double-blind, placebo-controlled trial with ischemic stroke patients randomly allocated to one of four treatment groups of either MPH, LD or MPH+LD or placebo combined with physiotherapy was performed. Motor function, ADL, and stroke severity were assessed by Fugl-Meyer (FM), Barthel index (BI), and National Institute of Health Stroke Scale (NIHSS) at baseline, 15, 90, and 180 days respectively. All participants showed recovery of motor function and ADL during treatment and at 6-month follow-up. There were slightly but significant differences in BI and NIHSS compared to placebo at the 6-month follow-up. Ischemic chronic stroke patients having MPH and/or LD in combination with physiotherapy showed a slight ADL and stroke severity improvement over time. Future studies should address the issue of the optimal therapeutic window and dosage of medications to identify those patients who would benefit most. © 2010 John Wiley & Sons A/S.

A chloroplast thylakoid lumen protein is required for proper photosynthetic acclimation of plants under fluctuating light environments.

PubMed

Liu, Jun; Last, Robert L

2017-09-19

Despite our increasingly sophisticated understanding of mechanisms ensuring efficient photosynthesis under laboratory-controlled light conditions, less is known about the regulation of photosynthesis under fluctuating light. This is important because-in nature-photosynthetic organisms experience rapid and extreme changes in sunlight, potentially causing deleterious effects on photosynthetic efficiency and productivity. Here we report that the chloroplast thylakoid lumenal protein MAINTENANCE OF PHOTOSYSTEM II UNDER HIGH LIGHT 2 (MPH2; encoded by At4g02530 ) is required for growth acclimation of Arabidopsis thaliana plants under controlled photoinhibitory light and fluctuating light environments. Evidence is presented that mph2 mutant light stress susceptibility results from a defect in photosystem II (PSII) repair, and our results are consistent with the hypothesis that MPH2 is involved in disassembling monomeric complexes during regeneration of dimeric functional PSII supercomplexes. Moreover, mph2 -and previously characterized PSII repair-defective mutants-exhibited reduced growth under fluctuating light conditions, while PSII photoprotection-impaired mutants did not. These findings suggest that repair is not only required for PSII maintenance under static high-irradiance light conditions but is also a regulatory mechanism facilitating photosynthetic adaptation under fluctuating light environments. This work has implications for improvement of agricultural plant productivity through engineering PSII repair.

Adhesion of lactobacilli to urinary catheters and diapers: effect of surface properties.

PubMed

Reid, G; Lam, D; Bruce, A W; van der Mei, H C; Busscher, H J

1994-06-01

Thirteen strains of lactobacilli were tested for their ability to adhere to commercial devices used in the urinary tract. Although it appeared that the most hydrophilic organisms adhered in highest numbers, there was no significant correlation between water contact angle and adhesiveness to catheters. Five organisms tested were found to be highly adherent to Huggies commercial diapers. Loss in hydrophobicity upon serial culture of Lactobacillus fermentum B-54 was not due to a proteinaceous S layer, although protein involvement per se cannot be ruled out. It was evident that, not only can members of the normal female urogenital flora adhere to commonly used commercial prostheses, but their ability to attach is related to hydrophilic as well as hydrophobic surface components.

Protecting Health and Saving Lives: The Part-Time/Internet-Based Master of Public Health Program at the Johns Hopkins Bloomberg School of Public Health

ERIC Educational Resources Information Center

Bruce, Linda; Gresh, Kathy; Vanchiswaran, Rohini; Werapitiya, Deepthi

2007-01-01

This article discusses the part-time/Internet-based Master of Public Health (MPH) program at the Johns Hopkins Bloomberg School of Public Health (JHSPH). The Johns Hopkins Bloomberg School of Public Health was the first school of public health in the United States to offer a Master of Public Health program via the Internet. The JHSPH MPH Program…

A Multicenter, Open-Label Trial to Evaluate the Quality of Life in Adults with ADHD Treated with Long-Acting Methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) Study

ERIC Educational Resources Information Center

Mattos, Paulo; Rodrigues Louza, Mario; Fernandes Palmini, Andre Luis; de Oliveira, Irismar Reis; Lopes Rocha, Fabio

2013-01-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. Objective: To assess the effectiveness of Methyphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. Method: A 12-week, multicenter, open-label trial involving 60 patients was used. The…

Journal of Special Operations Medicine, Volume 6, Edition 1, Winter 2006

DTIC Science & Technology

2006-01-01

Mark A. Antonacci, MD; Paul L. Link, NC Stress Fracture and Attrition in Basic Underwater Demolition SEAL Trainees Daniel W. Trone, MA; Adriana ...Special Operations Medicine32 Stress Fracture and Attrition in Basic Underwater Demolition SEAL Trainees Daniel W. Trone, MA; Adriana Villaseñor, MPH...effects of physical activity, with a focus on functional decline and injuries in recreational and military populations. Adriana Villaseñor, MPH, is

Novel Influenza A (H1N1) Outbreak at the U.S. Air Force Academy: Epidemiology and Viral Shedding Duration (American Journal of Preventive Medicine, Volume 20, Number 10, 2009)

DTIC Science & Technology

2009-01-01

and Viral Shedding Duration atherine Takacs Witkop, MD, MPH, Mark R. Duffy, DVM, MPH, Elizabeth A. Macias, PhD, homas F. Gibbons, PhD, James D. Escobar...oseltami- ir two times daily for 5 days if the patients indicated onset of ymptoms no more than 72 hours prior to presentation. pper-class cadets

Calculation of wind speeds required to damage or destroy buildings

NASA Astrophysics Data System (ADS)

Liu, Henry

Determination of wind speeds required to damage or destroy a building is important not only for the improvement of building design and construction but also for the estimation of wind speeds in tornadoes and other damaging storms. For instance, since 1973 the U.S. National Weather Service has been using the well-known Fujita scale (F scale) to estimate the maximum wind speeds of tornadoes [Fujita, 1981]. The F scale classifies tornadoes into 13 numbers, F-0 through F-12. The wind speed (maximum gust speed) associated with each F number is given in Table 1. Note that F-6 through F-12 are for wind speeds between 319 mi/hr (mph) and the sonic velocity (approximately 760 mph; 1 mph = 1.6 km/kr). However, since no tornadoes have been classified to exceed F-5, the F-6 through F-12 categories have no practical meaning [Fujita, 1981].

Roadside tree/pole crash barrier field test

NASA Technical Reports Server (NTRS)

Wilson, A. H.

1979-01-01

A series of tests was carried out to evaluate the performance of a crash barrier designed to protect the occupants of an automobile from serious injury. The JPL barrier design is a configuration of empty aluminum beverage cans contained in a tear-resistant bag which, in turn, is encased in a collapsible container made of plywood and steel. Tests were conducted with a driven vehicle impacting the barrier. The basic requirements of NCHRP Report 153 were followed except that speeds of 30 mph rather than 60 mph were used. Accelerometer readings on the driver's helmet showed that the driver was never subjected to dangerous decelerations, and never experienced more than temporary discomfort. Also, all of the requirements of the cited report were met. An extrapolation of data indicated that the JPL barrier installed in front of a tree or telephone pole along a roadside would also have met the requirements at a speed of 40 mph.

Effective methylphenidate treatment of an adult Aspergers Syndrome and a comorbid ADHD: a clinical investigation with fMRI.

PubMed

Roy, Mandy; Dillo, Wolfgang; Bessling, Svenja; Emrich, Hinderk M; Ohlmeier, Martin D

2009-01-01

Aspergers Syndrome can present as comorbid with attention-deficit/hyperactivity disorder (ADHD). Very few cases of the assessment and treatment of this comorbidity in adulthood are described in the research literature. A 26-year-old patient as suffering from ADHD in combination with Aspergers Syndrome is diagnosed. Treatment is started with methylphenidate (MPH), and the patient's clinical response is observed, psychological tests concerning attention are analyzed, and a functional magnetic resonance imaging (fMRI) examination is performed during an attention-task. On the functional magnetic resonance imaging, a reduction of cerebral activity bilaterally in the parietal lobe under the influence of MPH is detected. Besides the neurophysiological findings, this case reports the complex impairment caused by the combination of AD/HD with Aspergers Syndrome and the broad social and behavioral benefits of treatment with MPH for this comorbidity.

Use of Stimulants in Bipolar Disorder.

PubMed

Perugi, Giulio; Vannucchi, Giulia; Bedani, Fulvio; Favaretto, Ettore

2017-01-01

Several international guidelines indicate stimulants, including methylphenidate (MPH), amphetamines and derivatives, modafinil, and armodafinil among the second-third-line choices for bipolar depression. Efficacy of stimulants has been also reported for the management of residual depressive symptoms such as fatigue and sleepiness and for the management of affective, cognitive, and behavioral symptoms in children and adult bipolar patients with comorbid ADHD. Few case reports show positive results with MPH in the treatment of resistant mania. Finally, MPH might be an option in some bipolar forms observed in psychiatric presentations of frontotemporal dementia and traumatic brain injury. In spite of these preliminary observations, the use of stimulants in bipolar patients is still controversial. Potential of misuse and abuse and mood destabilization with induction of (hypo)manic switches, mixed states, and rapid cycling are the concerns most frequently reported. Our aims are to summarize available literature on this topic and discuss practical management implications.

Theory of Mind and Empathy in Children With ADHD.

PubMed

Maoz, Hagai; Gvirts, Hila Z; Sheffer, Maya; Bloch, Yuval

2017-05-01

The current study compared empathy and theory of mind (ToM) between children with ADHD and healthy controls, and assessed changes in ToM among children with ADHD following administration of methylphenidate (MPH). Twenty-four children with ADHD (mean age = 10.3 years) were compared with 36 healthy controls. All children completed the interpersonal reactivity index (IRI), a self-reported empathy questionnaire, and performed the "faux-pas" recognition task (FPR). Children with ADHD performed the task with and without MPH. Children with ADHD showed significantly lower levels of self-reported empathy on most IRI subscales. FPR scores were significantly lower in children with ADHD and were improved, following the administration of MPH, to a level equal to that found in healthy controls. Children with ADHD show impaired self-reported empathy and FPR when compared with healthy controls. Stimulants improve FPR in children with ADHD to a level equal to that in healthy controls.

Evidence-based rules from family practice to inform family practice; the learning healthcare system case study on urinary tract infections.

PubMed

Soler, Jean K; Corrigan, Derek; Kazienko, Przemyslaw; Kajdanowicz, Tomasz; Danger, Roxana; Kulisiewicz, Marcin; Delaney, Brendan

2015-05-16

Analysis of encounter data relevant to the diagnostic process sourced from routine electronic medical record (EMR) databases represents a classic example of the concept of a learning healthcare system (LHS). By collecting International Classification of Primary Care (ICPC) coded EMR data as part of the Transition Project from Dutch and Maltese databases (using the EMR TransHIS), data mining algorithms can empirically quantify the relationships of all presenting reasons for encounter (RfEs) and recorded diagnostic outcomes. We have specifically looked at new episodes of care (EoC) for two urinary system infections: simple urinary tract infection (UTI, ICPC code: U71) and pyelonephritis (ICPC code: U70). Participating family doctors (FDs) recorded details of all their patient contacts in an EoC structure using the ICPC, including RfEs presented by the patient, and the FDs' diagnostic labels. The relationships between RfEs and episode titles were studied using probabilistic and data mining methods as part of the TRANSFoRm project. The Dutch data indicated that the presence of RfE's "Cystitis/Urinary Tract Infection", "Dysuria", "Fear of UTI", "Urinary frequency/urgency", "Haematuria", "Urine symptom/complaint, other" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection" . The Maltese data indicated that the presence of RfE's "Dysuria", "Urinary frequency/urgency", "Haematuria" are all strong, reliable, predictors for the diagnosis "Cystitis/Urinary Tract Infection". The Dutch data indicated that the presence of RfE's "Flank/axilla symptom/complaint", "Dysuria", "Fever", "Cystitis/Urinary Tract Infection", "Abdominal pain/cramps general" are all strong, reliable, predictors for the diagnosis "Pyelonephritis" . The Maltese data set did not present any clinically and statistically significant predictors for pyelonephritis. We describe clinically and statistically significant diagnostic associations observed between UTIs and pyelonephritis presenting as a new problem in family practice, and all associated RfEs, and demonstrate that the significant diagnostic cues obtained are consistent with the literature. We conclude that it is possible to generate clinically meaningful diagnostic evidence from electronic sources of patient data.

[Clinical, ureteroscopic and photodynamic diagnosis of urothelial carcinomas of the upper tract: state-of-the art review for the yearly scientific report of the French National Association of Urology].

PubMed

Nison, L; Bozzini, G; Rouprêt, M; Traxer, O; Colin, P

2014-11-01

To propose a state-of-the art of current knowledge about clinical, ureteroscopic and photodynamic for the diagnosis of the upper urinary tract cancer (UTUC). A systematic review of the literature search was performed from the database Medline (NLM, Pubmed), focused on the following keywords: urothelial carcinomas; upper urinary tract; ureter; renal pelvis; diagnosis; fluorescence; ureteroscopy; photodynamic technique; biopsy; cytology. Gross hematuria and flank pain are the two main clinical symptoms revealing a UTUC in daily clinical practice. Urinary cystoscopy and cystoscopy are mandatory to rule out a concomittant synchronous bladder tumour. Flexible ureteroscopy has revolutionized the management of UTUC by allowing a full exploration of upper urinary tract, an endoscopi vizualization of the tumour and assessment of grade with biopsies. A flexible ureteroscopy is mandatory in diagnostic evaluation of UTUC as soon as a conservative management is being considered. New investigation technologies such as fluorescence, narrow band imaging and optical coherence tomography (± combined with ultra sound), are promising for a near future. It has to be understood that the diagnostic work-up of a UTUC has to be exhaustive and particularly the search of another urothelial carcinoma within the urinary tract. Flexible ureterosocopy has revolutionized the diagnosis and management of UTUC and belongs fully to its initial evaluation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Association Between Early Idiopathic Neonatal Jaundice and Urinary Tract Infections

PubMed Central

Özcan, Murat; Sarici, S Ümit; Yurdugül, Yüksel; Akpinar, Melis; Altun, Demet; Özcan, Begüm; Serdar, Muhittin A; Sarici, Dilek

2017-01-01

Background and purpose: Etiologic role, incidence, demographic, and response-to-treatment characteristics of urinary tract infection (UTI) among neonates, its relationship with significant neonatal hyperbilirubinemia, and abnormalities of the urinary system were studied in a prospective investigation in early (≤10 days) idiopathic neonatal jaundice in which all other etiologic factors of neonatal hyperbilirubinemia were ruled out. Patients and methods: Urine samples for microscopic and bacteriologic examination were obtained with bladder catheterization from 155 newborns with early neonatal jaundice. Newborns with a negative urine culture and with a positive urine culture were defined as group I and group II, respectively, and the 2 groups were compared with each other. Results: The incidence of UTI in whole of the study group was 16.7%. Serum total and direct bilirubin levels were statistically significantly higher in group II when compared with group I (P = .005 and P = .001, respectively). Decrease in serum total bilirubin level at the 24th hour of phototherapy was statistically significantly higher in group I compared with group II (P = .022). Conclusions: Urinary tract infection should be investigated in the etiologic evaluation of newborns with significant hyperbilirubinemia. The possibility of UTI should be considered in jaundiced newborns who do not respond to phototherapy well or have a prolonged duration of phototherapy treatment. PMID:28469520

Validating and updating a prediction rule for serious bacterial infection in patients with fever without source.

PubMed

Bleeker, S E; Derksen-Lubsen, G; Grobbee, D E; Donders, A R T; Moons, K G M; Moll, H A

2007-01-01

To externally validate and update a previously developed rule for predicting the presence of serious bacterial infections in children with fever without apparent source. Patients, 1-36 mo, presenting with fever without source, were prospectively enrolled. Serious bacterial infection included bacterial meningitis, sepsis, bacteraemia, pneumonia, urinary tract infection, bacterial gastroenteritis, osteomyelitis/ethmoiditis. The generalizability of the original rule was determined. Subsequently, the prediction rule was updated using all available data of the patients with fever without source (1996-1998 and 2000-2001, n = 381) using multivariable logistic regression. the generalizability of the rule appeared insufficient in the new patients (n = 150). In the updated rule, independent predictors from history and examination were duration of fever, vomiting, ill clinical appearance, chest-wall retractions and poor peripheral circulation (ROC area (95%CI): 0.69 (0.63-0.75)). Additional independent predictors from laboratory were serum white blood cell count and C-reactive protein, and in urinalysis > or = 70 white bloods (ROC area (95%CI): 0.83 (0.78-0.88). A previously developed prediction rule for predicting the presence of serious bacterial infection in children with fever without apparent source was updated. Its clinical score can be used as a first screening tool. Additional laboratory testing may specify the individual risk estimate (range: 4-54%) further.

Prostate Cancer Research Training in Health Disparities for Undergraduates (PCaRT)

DTIC Science & Technology

2010-03-01

management Program Mentors Carlton Adams, M.D. LaMonica Stewart, Ph.D. Ben Ogunkua, M.D., Ph.D. Alphonse Pasipanodya, M.D. Jay Fowke, Ph.D., MPH...African-Americans Alphonse Pasipanodya, MD. (Primary Mentor) Flora A. M. Ukoli, MD., MPH. (Principal Investigator) Derrick Beech, M.D. (Co-PI...my goals is to be a successful black woman influencing and touching the lives of all those I come in contact with daily. Alphonse Pasipanodya

KSC-04PD-1803

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Fire and Rescue team members clean up the vehicles after Hurricane Frances, which passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph.

KSC-04pd1803

NASA Image and Video Library

2004-09-14

KENNEDY SPACE CENTER, FLA. - Fire and Rescue team members clean up the vehicles after Hurricane Frances, which passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph.

The Anatomy of a Pitch: Doing Physics with PITCHf/x Data

ERIC Educational Resources Information Center

Kagan, David

2009-01-01

On Aug. 7, 2007, Barry Bonds of the San Francisco Giants was at bat waiting for a 3-2 pitch from Mike Bacsik of the Washington Nationals. The ball left the pitcher's hand at 84.7 mph and arrived at home plate traveling 77.2 mph. It was within 0.2 in of the center of home plate and 3.213 ft above the ground when Bonds swung and hit his 756th home…

Baseline test data for the EVA electric vehicle. [low energy consumption automobiles

NASA Technical Reports Server (NTRS)

Harhay, W. C.; Bozek, J.

1976-01-01

Two electric vehicles from Electric Vehicle Associates were evaluated for ERDA at the Transportation Research Center of Ohio. The vehicles, loaded to a gross vehicle weight of 3750 pounds, had a range of 56.3 miles at a steady speed of 25 mph and a 27.4 miles range during acceleration-deceleration tests to a top speed of 30 mph. Energy consumption varied from 0.48 kw-hr/mi. to 0.59 kw-hr/mi.

Intermittent Cocaine Self-Administration Produces Sensitization of Stimulant Effects at the Dopamine Transporter

PubMed Central

Calipari, Erin S.; Ferris, Mark J.; Siciliano, Cody A.; Zimmer, Benjamin A.

2014-01-01

Previous literature investigating neurobiological adaptations following cocaine self-administration has shown that high, continuous levels of cocaine intake (long access; LgA) results in reduced potency of cocaine at the dopamine transporter (DAT), whereas an intermittent pattern of cocaine administration (intermittent access; IntA) results in sensitization of cocaine potency at the DAT. Here, we aimed to determine whether these changes are specific to cocaine or translate to other psychostimulants. Psychostimulant potency was assessed by fast-scan cyclic voltammetry in brain slices containing the nucleus accumbens following IntA, short access, and LgA cocaine self-administration, as well as in brain slices from naive animals. We assessed the potency of amphetamine (a releaser), and methylphenidate (a DAT blocker, MPH). MPH was selected because it is functionally similar to cocaine and structurally related to amphetamine. We found that MPH and amphetamine potencies were increased following IntA, whereas neither was changed following LgA or short access cocaine self-administration. Therefore, whereas LgA-induced tolerance at the DAT is specific to cocaine as shown in previous work, the sensitizing effects of IntA apply to cocaine, MPH, and amphetamine. This demonstrates that the pattern with which cocaine is administered is important in determining the neurochemical consequences of not only cocaine effects but potential cross-sensitization/cross-tolerance effects of other psychostimulants as well. PMID:24566123

Observer assessment of multi-pinhole SPECT geometries for prostate cancer imaging: a simulation study

NASA Astrophysics Data System (ADS)

Kalantari, Faraz; Sen, Anando; Gifford, Howard C.

2014-03-01

SPECT imaging using In-111 ProstaScint is an FDA-approved method for diagnosing prostate cancer metastases within the pelvis. However, conventional medium-energy parallel-hole (MEPAR) collimators produce poor image quality and we are investigating the use of multipinhole (MPH) imaging as an alternative. This paper presents a method for evaluating MPH designs that makes use of sampling-sensitive (SS) mathematical model observers for tumor detectionlocalization tasks. Key to our approach is the redefinition of a normal (or background) reference image that is used with scanning model observers. We used this approach to compare different MPH configurations for the task of small-tumor detection in the prostate and surrounding lymph nodes. Four configurations used 10, 20, 30, and 60 pinholes evenly spaced over a complete circular orbit. A fixed-count acquisition protocol was assumed. Spherical tumors were placed within a digital anthropomorphic phantom having a realistic Prostascint biodistribution. Imaging data sets were generated with an analytical projector and reconstructed volumes were obtained with the OSEM algorithm. The MPH configurations were compared in a localization ROC (LROC) study with 2D pelvic images and both human and model observers. Regular and SS versions of the scanning channelized nonprewhitening (CNPW) and visual-search (VS) model observers were applied. The SS models demonstrated the highest correlations with the average human-observer results

The effect of methylphenidate treatment on suspiciousness in children with ADHD alone or comorbid with ODD.

PubMed

Golubchik, Pavel; Weizman, Abraham

2018-06-01

To assess the level of the suspiciousness in children with attention deficit/hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD) in comparison to ADHD alone and the response of suspiciousness symptoms to methylphenidate (MPH) treatment. In this open-label comparative study, children with DSM-IV-TR ADHD, aged 8-18 years, with (N = 30) or without (N = 30) ODD received MPH treatment for 12 weeks. The severity of ODD symptoms was assessed by the Kiddie-Schedule for Affective Disorders and Schizophrenia. The severity of ADHD symptoms was assessed by the ADHD-Rating-Scale-IV and suspiciousness was assessed at baseline and at endpoint by a scale designed especially for assessment of suspiciousness and named Suspiciousness Rating Scale (SRS). Significant reductions in SRS scores were detected in both groups following MPH treatment (before and after: p = .0012 and p = .0273, respectively). Only in the ADHD/ODD group a significant correlation was found between the rate of improvement in ADHD, as assessed by the ADHD-RS, and the reduction in suspiciousness, as assessed by the SRS (Spearman r = 0.48, p =  .0066). In addition to the beneficial effect of MPH treatment on ADHD and ODD symptoms it also diminishes suspiciousness. However, due to the small sample size further studies are needed to confirm the present results.

No association between catechol-O-methyltransferase (COMT) genotype and attention deficit hyperactivity disorder (ADHD) in Japanese children.

PubMed

Yatsuga, Chiho; Toyohisa, Daiki; Fujisawa, Takashi X; Nishitani, Shota; Shinohara, Kazuyuki; Matsuura, Naomi; Ikeda, Shinobu; Muramatsu, Masaaki; Hamada, Akinobu; Tomoda, Akemi

2014-08-01

This study ascertained the association between attention deficit/hyperactivity disorder (ADHD) in Japanese children and a polymorphism of catechol-O-methyltransferase (COMT), a dopamine-control gene. The secondary aim of the study was the evaluation of a putative association between methylphenidate (MPH) effect/adverse effects and the COMT genotype. To ascertain the distribution of the Val158Met variant of COMT, 50 children meeting ADHD inclusion criteria were compared with 32 healthy children. Clinical improvement and the occurrence of adverse effects were measured before and 3 months after MPH administration in children with ADHD, and analyzed for genotype association. Wechsler Intelligence Scale for Children-Third Edition (WISC-III), age, MPH dose were included as co-variables. The occurrence of the COMT Val/Val genotype was significantly higher in children with ADHD (χ(2)(1)=7.13, p<0.01). However, there was no significant difference in the Val/Val genotype according to disorder, and WISC and ADHD rating scale scores, after correcting for the interaction between disorder and COMT genotype. Furthermore, no significant difference in MPH effect/adverse effects was observed in association with the COMT genotype in the ADHD group. These results showed a lack of association between the COMT Val/Val genotype and ADHD in Japan. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Characteristics of good supervision: a multi-perspective qualitative exploration of the Masters in Public Health dissertation.

PubMed

Katikireddi, Srinivasa Vittal; Reilly, Jacqueline

2017-09-01

A dissertation is often a core component of the Masters in Public Health (MPH) qualification. This study aims to explore its purpose, from the perspective of both students and supervisors, and identify practices viewed as constituting good supervision. A multi-perspective qualitative study drawing on in-depth one-to-one interviews with MPH supervisors (n = 8) and students (n = 10), with data thematically analysed. The MPH dissertation was viewed as providing generic as well as discipline-specific knowledge and skills. It provided an opportunity for in-depth study on a chosen topic but different perspectives were evident as to whether the project should be grounded in public health practice rather than academia. Good supervision practice was thought to require topic knowledge, generic supervision skills (including clear communication of expectations and timely feedback) and adaptation of supervision to meet student needs. Two ideal types of the MPH dissertation process were identified. Supervisor-led projects focus on achieving a clearly defined output based on a supervisor-identified research question and aspire to harmonize research and teaching practice, but often have a narrower focus. Student-led projects may facilitate greater learning opportunities and better develop skills for public health practice but could be at greater risk of course failure. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health.

A S-Layer Protein of Bacillus anthracis as a Building Block for Functional Protein Arrays by In Vitro Self-Assembly.

PubMed

Wang, Xu-Ying; Wang, Dian-Bing; Zhang, Zhi-Ping; Bi, Li-Jun; Zhang, Ji-Bin; Ding, Wei; Zhang, Xian-En

2015-11-18

S-layer proteins create a cell-surface layer architecture in both bacteria and archaea. Because S-layer proteins self-assemble into a native-like S-layer crystalline structure in vitro, they are attractive building blocks in nanotechnology. Here, the potential use of the S-layer protein EA1 from Bacillus anthracis in constructing a functional nanostructure is investigated, and apply this nanostructure in a proof-of-principle study for serological diagnosis of anthrax. EA1 is genetically fused with methyl parathion hydrolase (MPH), to degrade methyl parathion and provide a label for signal amplification. EA1 not only serves as a nanocarrier, but also as a specific antigen to capture anthrax-specific antibodies. As results, purified EA1-MPH forms a single layer of crystalline nanostructure through self-assembly. Our chimeric nanocatalyst greatly improves enzymatic stability of MPH. When applied to the detection of anthrax-specific antibodies in serum samples, the detection of our EA1-MPH nanostructure is nearly 300 times more sensitive than that of the unassembled complex. Together, it is shown that it is possible to build a functional and highly sensitive nanosensor based on S-layer protein. In conclusion, our present study should serve as a model for the development of other multifunctional nanomaterials using S-layer proteins. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The value of formal clinical research training in initiating a career as a clinical investigator.

PubMed

Kapoor, Karan; Wu, Bechien U; Banks, Peter A

2011-12-01

The aim of this study was to determine whether formal clinical research training is of value in the initiation of a successful career as a clinical investigator. We conducted a retrospective review of the career choices of all 25 fellows who entered the Academic Clinical Research Track at Brigham and Women's Hospital since its inception in 1995 and examined the impact of formal clinical research training during their fellowship on their career choice. The primary measure of a successful career as a clinical investigator was the obtainment of external funding for clinical research within 3 years of completion of fellowship. Thirteen of the 25 fellows (52%) received a Master of Public Health (MPH) degree at the Harvard School of Public Health during their fellowship. Ten of these 13 fellows (77%) obtained external funding for clinical research within 3 years of completion of their fellowship. None of the 5 fellows who had already obtained an MPH degree prior to their fellowship and none of the 7 fellows who completed a 7-week summer Program in Clinical Effectiveness but did not complete an MPH degree attempted to receive external funding for clinical research within 3 years of completion of their fellowship. We conclude that formal clinical research training culminating in an MPH degree was extremely valuable in the initiation of a successful career as a clinical investigator.

Topiramate via NMDA, AMPA/kainate, GABAA and Alpha2 receptors and by modulation of CREB/BDNF and Akt/GSK3 signaling pathway exerts neuroprotective effects against methylphenidate-induced neurotoxicity in rats.

PubMed

Motaghinejad, Majid; Motevalian, Manijeh; Fatima, Sulail; Beiranvand, Tabassom; Mozaffari, Shiva

2017-11-01

Chronic abuse of methylphenidate (MPH) often causes neuronal cell death. Topiramate (TPM) carries neuroprotective effects, but its exact mechanism of action remains unclear. In the present study, the role of various doses of TPM and its possible mechanisms, receptors and signaling pathways involved against MPH-induced hippocampal neurodegeneration were evaluated in vivo. Thus, domoic acid (DOM) was used as AMPA/kainate receptor agonist, bicuculline (BIC) as GABA A receptor antagonist, ketamine (KET) as NMDA receptor antagonist, yohimbine (YOH) as α 2 adrenergic receptor antagonist and haloperidol (HAL) was used as dopamine D 2 receptor antagonist. Open field test (OFT) was used to investigate the disturbances in motor activity. Hippocampal neurodegenerative parameters were evaluated. Protein expressions of CREB/BDNF and Akt/GSK3 signaling pathways were also evaluated. Cresyl violet staining was performed to show and confirm the changes in the shape of the cells. TPM (70 and 100 mg/kg) reduced MPH-induced rise in lipid peroxidation, oxidized form of glutathione (GSSG), IL-1β and TNF-α levels, Bax expression and motor activity disturbances. In addition, TPM treatment increased Bcl-2 expression, the level of reduced form of glutathione (GSH) and the levels and activities of superoxide dismutase, glutathione peroxidase and glutathione reductase enzymes. TPM also inhibited MPH-induced hippocampal degeneration. Pretreatment of animals with DOM, BIC, KET and YOH inhibited TPM-induced neuroprotection and increased oxidative stress, neuroinflammation, neuroapoptosis and neurodegeneration while reducing CREB, BDNF and Akt protein expressions. Also pretreatment with DOM, BIC, KET and YOH inhibited TPM-induced decreases in GSK3. It can be concluded that the mentioned receptors by modulation of CREB/BDNF and Akt/GSK3 pathways, are involved in neuroprotection of TPM against MPH-induced neurodegeneration.

A randomized controlled trial into the effects of neurofeedback, methylphenidate, and physical activity on EEG power spectra in children with ADHD.

PubMed

Janssen, Tieme W P; Bink, Marleen; Geladé, Katleen; van Mourik, Rosa; Maras, Athanasios; Oosterlaan, Jaap

2016-05-01

The clinical and neurophysiological effects of neurofeedback (NF) as treatment for children with ADHD are still unclear. This randomized controlled trial (RCT) examined electroencephalogram (EEG) power spectra before and after NF compared to methylphenidate (MPH) treatment and physical activity (PA) - as semi-active control group - during resting and active (effortful) task conditions to determine whether NF can induce sustained alterations in brain function. Using a multicentre three-way parallel group RCT design, 112 children with a DSM-IV diagnosis of ADHD, aged between 7 and 13 years, were initially included. NF training consisted of 30 sessions of theta/beta training at Cz over a 10-week period. PA training was a semi-active control group, matched in frequency and duration. Methylphenidate was titrated using a double-blind placebo controlled procedure in 6 weeks, followed by a stable dose for 4 weeks. EEG power spectra measures during eyes open (EO), eyes closed (EC) and task (effortful) conditions were available for 81 children at pre- and postintervention (n = 29 NF, n = 25 MPH, n = 27 PA). Train Your Brain? Exercise and Neurofeedback Intervention for ADHD, https://clinicaltrials.gov/show/;NCT01363544, Ref. No. NCT01363544. Both NF and MPH resulted in comparable reductions in theta power from pre- to postintervention during the EO condition compared to PA (ηp (2)  = .08 and .12). For NF, greater reductions in theta were related to greater reductions in ADHD symptoms. During the task condition, only MPH showed reductions in theta and alpha power compared to PA (ηp (2)  = .10 and .12). This study provides evidence for specific neurophysiological effects after theta/beta NF and MPH treatment in children with ADHD. However, for NF these effects did not generalize to an active task condition, potentially explaining reduced behavioural effects of NF in the classroom. © 2016 Association for Child and Adolescent Mental Health.

Differential impact of methylphenidate and atomoxetine on sustained attention in youth with attention-deficit/hyperactivity disorder.

PubMed

Bédard, Anne-Claude V; Stein, Mark A; Halperin, Jeffrey M; Krone, Beth; Rajwan, Estrella; Newcorn, Jeffrey H

2015-01-01

This study examined the effects of atomoxetine (ATX) and OROS methylphenidate (MPH) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder (ADHD). It was hypothesized that performance would be improved by both treatments, but response profiles would differ because the medications work via different mechanisms. One hundred and two youth (77 male; mean age = 10.5 ± 2.7 years) with ADHD received ATX (1.4 ± 0.5 mg/kg) and MPH (52.4 ± 16.6 mg) in a randomized, double-blind, crossover design. Medication was titrated in 4-6-week blocks separated by a 2-week placebo washout. Inhibitory control and attention measures were obtained at baseline, following washout, and at the end of each treatment using Conners' Continuous Performance Test II (CPT-II), which provided age-adjusted T-scores for reaction time (RT), reaction time variability (RT variability), and errors. Repeated-measures analyses of variance were performed, with Time (premedication, postmedication) and Treatment type (ATX, MPH) entered as within-subject factors. Data from the two treatment blocks were checked for order effects and combined if order effects were not present. Clinicaltrials.gov: NCT00183391. Main effects for Time on RT (p = .03), RTSD (p = .001), and omission errors (p = .01) were significant. A significant Drug × Time interaction indicated that MPH improved RT, RTSD, and omission errors more than ATX (p < .05). Changes in performance with treatment did not correlate with changes in ADHD symptoms. MPH has greater effects than ATX on CPT measures of sustained attention in youth with ADHD. However, the dissociation of cognitive and behavioral change with treatment indicates that CPT measures cannot be considered proxies for symptomatic improvement. Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated. © 2014 The Authors. Journal of Child Psychology and Psychiatry. © 2014 Association for Child and Adolescent Mental Health.

Long-term effects of short-acting methylphenidate on growth rates of children with attention deficit hyperactivity disorder at Queen Sirikit National Institute of Child Health.

PubMed

Moungnoi, Pranee; Maipang, Prinyaporn

2011-08-01

Methylphenidate (MPH) is generally considered to be first-line treatment for the core symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Long-term administration of MPH in childhood may have adverse effects on growth. To determine the effect of long-term, short-acting MPH medication on growth. A retrospective descriptive study was employed by gathering the data of patients who were diagnosed as ADHD by child psychiatrists at the child and adolescent clinic, Queen Sirikit National Institute of Child Health. Subjects were patients received the first dose of short-acting methylphenidate from January 1st 2000 to December 31st 2007 and continued medication for at least 1 year. Data about height and weight were reviewed at the beginning of short-acting MPH medication, 6 months (mo), 1 yr, 2 yr, 3 yr, 4 yr, 5 yr, 6 yr and 7 yr interval. Collecting data was interpreted with INMU-Nutri Stat software program. Paired t-test was used to compare Z score of height and weight at different time points. There were 96 cases in the present study; the ratio of male to female was 3.6: 1. The first dose of short-acting methylphenidate was started at an average age of 8.62 +/- 1.70 years. Average drug dose ranged from 0.41-0.49 mg/kg/day. The data evaluated at 6 mo, 1 year 2 years, 3 years, 4 years and 5 years after drug use found that weight was not affected. Height decreased at 6 mo. after drug use (p < 0.05) but long-term treatment was not statistically significant. Prolonged medication with short-acting MPH has shown to have minimal impact on height only at the first 6 months; however, catch up growth was detected during adolescent period.

Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin.

PubMed

Taylor, C A; Overstreet, J W; Samuels, S J; Boyers, S P; Canfield, R E; O'Connor, J F; Hanson, F W; Lasley, B L

1992-06-01

To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA.

Urinary concentrations of dichlorophenol pesticides and obesity among adult participants in the U.S. National Health and Nutrition Examination Survey (NHANES) 2005-2008.

PubMed

Wei, Yudan; Zhu, Jianmin; Nguyen, An

2014-03-01

Accumulating evidence from recent studies has suggested a possible link between exposure to environmental pesticides and obesity. In this study, we assessed the potential associations between exposure to dichlorophenol pesticides and obesity in adults. Study participants aged 20-85 years were selected from the 2005 to 2006 and 2007 to 2008 U.S. National Health and Nutrition Examination Survey, and were categorized as obese and non-obese based on body mass index. Creatinine-corrected urinary concentrations of dichlorophenols were determined to assess level of exposure to environmental pesticides. Multivariate logistic regression was performed using SAS 9.3 to assess the association between 2,4-dichlorophenol (2,4-DCP) and 2,5-dichlorophenol (2,5-DCP) levels in urine and obesity with adjustment for potential confounders. Significantly higher geometric means of urinary concentrations of both 2,5-DCP (p<0.0001) and 2,4-DCP (p=0.0170) were seen in obese adults, compared to that in non-obese adults. A dose-dependent increase in the prevalence of obesity was observed in the study participants across increasing levels of urinary 2,5-DCP (p-trend<0.0001). Urinary concentrations of 2,5-DCP were significantly associated with obesity among the second (AOR: 1.47, 95% CI: 1.12, 1.93), third (AOR: 1.41, 95% CI: 1.07, 1.87), and fourth (AOR: 1.62, 95% CI: 1.21, 2.17) inter-quartiles after adjustment for age, gender, race, education, total fat intake, and physical activity. A statistically significant association was not seen between urinary 2,4-DCP and obesity. Our findings suggest a potential relationship between exposure to the fumigant insecticide paradichlorobenzene, measured as urinary concentrations of 2,5-DCP, and obesity in adults. Because we cannot rule out the possibility of reverse causality in our study, prospective studies measuring exposure during etiologically relevant periods are warranted. Copyright © 2013 Elsevier GmbH. All rights reserved.

Implementation of the updated 2015 Commission for Hospital Hygiene and Infection Prevention (KRINKO) recommendations "Prevention and control of catheter-associated urinary tract infections" in the hospitals in Frankfurt/Main, Germany.

PubMed

Heudorf, Ursel; Grünewald, Miriam; Otto, Ulla

2016-01-01

The Commission for Hospital Hygiene and Infection Prevention (KRINKO) updated the recommendations for the prevention of catheter-associated urinary tract infections in 2015. This article will describe the implementation of these recommendations in Frankfurt's hospitals in autumn, 2015. In two non-ICU wards of each of Frankfurt's 17 hospitals, inspections were performed using a checklist based on the new KRINKO recommendations. In one large hospital, a total of 5 wards were inspected. The inspections covered the structure and process quality (operating instructions, training, indication, the placement and maintenance of catheters) and the demonstration of the preparation for insertion of a catheter using an empty bed and an imaginary patient, or insertion in a model. Operating instructions were available in all hospital wards; approximately half of the wards regularly performed training sessions. The indications were largely in line with the recommendations of the KRINKO. Alternatives to urinary tract catheters were available and were used more often than the urinary tract catheters themselves (15.9% vs. 13.5%). In accordance with the recommendations, catheters were placed without antibiotic prophylaxis or the instillation of antiseptic or antimicrobial substances or catheter flushing solutions. The demonstration of catheter placement was conscientiously performed. Need for improvement was seen in the daily documentation and the regular verification of continuing indication for a urinary catheter, as well as the omission of regular catheter change. Overall, the recommendations of the KRINKO on the prevention of catheter-associated urinary tract infections were adequately implemented. However, it cannot be ruled out that in situations with time pressure and staff shortage, the handling of urinary tract catheters may be of lower quality than that observed during the inspections, when catheter insertion was done by two nurses. Against this background, a sufficient number of qualified staff and regular ward rounds by the hygiene staff appear recommendable.

A Fixed-Point Phase Lock Loop in a Software Defined Radio

DTIC Science & Technology

2002-09-01

code from a simulation model. This feature will allow easy implementation on an FPGA as C can be easily converted to VHDL , the language required...this is equivalent to the MATLAB code implementation in Appendix A. The PD takes the input signal 40 and multiplies it by the in-phase and...stop to 60 mph in 3.1 seconds (the fastest production car ever built is the Porsche Carrera twin turbo which was tested at 0-60 mph in 3.1 seconds

Realistic Bomber Training Initiative Supplemental Environmental Impact Statement

DTIC Science & Technology

2007-03-01

mph at the surface and 27 mph at 22 feet AGL; e ) A pull-up maneuver by the B-1B, which may be executed once or twice per sortie- operation, can...avoid resources, where feasible. ( e ) Developing and implementing site-specifi.c mitigation measures, if required. (3) The Air Force will avoid or...form a complete MOA, the LancerMOA. (2) Concerns were expressed about the structw~ e of the proposed MTR, IR 178. The Air Force reduced noise

Prospective Study of Respiratory Infections at the U.S. Naval Academy

DTIC Science & Technology

2001-09-01

conducting the .findings were significant in demonstrating infection cause and study at the U.S. Naval Academy: Tomoko Hooper, MD MPH; Richard Jhe large...leven M, Ursi D, Van Bever H, Quint W, Niesters HG, Goossens H: Detection of disease. J Infect Dis 1992; 166: 365-73. Mycoplasmapneumoniaeby two...6. AUTHORS 5d. Project Number: Gregory C. Gray, MD, MPH; Robert G. Schultz, MD; Gary D. Gackstetter, DVM, 5e. Task Number: PhD; Richard Thomas, MD

Tropical Storm Bonnie as Observed by NASA Spaceborne Atmospheric Infrared Sounder AIRS

NASA Image and Video Library

2004-08-12

Tropical storm Bonnie, Gulf of Mexico, captured on August 11 at 1:30am CDT. Located in the Gulf of Mexico, the center of the storm is positioned about 280 miles south-southwest of the mouth of the Mississippi River. Bonnie is a small tropical storm with wind speeds sustained at 45 mph and extending 30 miles from the storm center. It is moving northward at 5 mph. http://photojournal.jpl.nasa.gov/catalog/PIA00441

Within-year Exertional Heat Illness Incidence in U.S. Army Soldiers, 2008-2012

DTIC Science & Technology

2015-06-01

index (MDI;(17)) were created. Wind speed (in kph) was calculated as wind speed (in mph)*1.61. Wind chill was calculated for all climate samples...downloaded from the NOAA website, new variables for wind speed (converted from mph to kph), wind chill , minimum temperature, and modified discomfort...Windspeed_Kph** 0.16 + 0.3965 * DryBulbCelsius * Windspeed_Kph ** 0.16. Dry bulb temperatures (in °C) and wind chill temperatures (in °C) were

Traumatic Brain Injury Screening: Preliminary Findings in a US Army Brigade Combat Team

DTIC Science & Technology

2009-01-01

Screening: Preliminary Findings in a US Army Brigade Combat Team Heidi Terrio, MD, MPH; Lisa A. Brenner, PhD; Brian J. Ivins, MS; John M. Cho, MD; Katherine...Sheila Saliman and Lisa Betthauser is greatly appreciated. Corresponding author: Heidi Terrio, MD, MPH, 1853 O’Connell Blvd, Bldg 1042, Room 107, Fort...more mild TBI symptoms among injured soldiers with and without TBI (n = 1208)∗,† Parameter Adjusted 95% CI adjusted Variable estimate (β) SE β Wald P

History and physical examination plus laboratory testing for the diagnosis of adult female urinary tract infection.

PubMed

Meister, Lisa; Morley, Eric J; Scheer, Diane; Sinert, Richard

2013-07-01

Emergency physicians often encounter females presenting with symptoms suggestive of urinary tract infections (UTIs). The diagnostic accuracy of history, physical examination, and bedside laboratory tests for female UTIs in emergency departments (EDs) have not been quantitatively described. This was a systematic review to determine the utility of history and physical examination (H&P) and urinalysis in diagnosing uncomplicated female UTI in the ED. The medical literature was searched from January 1965 through October 2012 in PUBMED and EMBASE using the following criteria: Patients were females greater than 18 years of age in the ED suspected of having UTIs. Interventions were H&P and urinalysis used to diagnose a UTI. The comparator was UTI confirmed by a positive urine culture. The outcome was operating characteristics of the interventions in diagnosing a UTI. Study quality was assessed using Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS-2). Sensitivity, specificity, and likelihood ratios (LRs) were calculated using Meta-DiSc. Four studies (pooled n = 948) were included with UTI prevalence ranging from 40% to 60%. H&P variables all had positive LRs (+LR, range = 0.8 to 2.2) and negative LRs (-LR, range = 0.7 to 1.0) that are insufficient to significantly alter pretest probability of UTI. Only a positive nitrite reaction (+LR = 7.5 to 24.5) was useful to rule in a UTI. To rule out UTI, only a negative leukocyte esterase (LE; -LR = 0.2) or blood reaction on urine dipstick (-LR = 0.2) were significantly accurate. Increasing pyuria directly correlated with +LR, and moderate pyuria (urine white blood cells [uWBC] > 50 colony-forming units [CFUs]/ml) and moderate bacteruria were good predictors of UTI (+LR = 6.4 and 15.0, respectively). No single H&P finding can accurately rule in or rule out UTI in symptomatic women. Urinalysis with a positive nitrite or moderate pyuria and/or bacteruria are accurate predictors of a UTI. If the pretest probability of UTI is sufficiently low, a negative urinalysis can accurately rule out the diagnosis. © 2013 by the Society for Academic Emergency Medicine.

Environmental consequences of postulated plutonium releases from Westinghouse PFDL, Cheswick, Pennsylvania, as a result of severe natural phenomena

DOE Office of Scientific and Technical Information (OSTI.GOV)

McPherson, R.B.; Watson, E.C.

1979-06-01

Potential environmental consequences in terms of radiation dose to people are presented for postulated accidents due to earthquakes, tornadoes, high straight-line winds, and floods. Maximum plutonium deposition values are given for significant locations around the site. All important potential exposure pathways are examined. The most likely calculated 50-year collective committed dose equivalents are all much lower than the collective dose equivalent expected from 50 years of exposure to natural background radiation and medical x-rays except Earthquake No. 4 and the 260-mph tornado. The most likely maximum residual plutonium contamination estimated to be deposited offsite following Earthquake No. 4, and themore » 200-mph and 260-mph tornadoes are above the Environmental Protection Agency's (EPA) proposed guideline for plutonium in the general environment of 0.2 ..mu..Ci/m/sup 2/. The deposition values following the other severe natural phenomena are below the EPA proposed guideline.« less

Association of the GRIN2B rs2284411 polymorphism with methylphenidate response in attention-deficit/hyperactivity disorder.

PubMed

Kim, Johanna I; Kim, Jae-Won; Park, Jong-Eun; Park, Subin; Hong, Soon-Beom; Han, Doug Hyun; Cheong, Jae Hoon; Choi, Jae-Won; Lee, Sumin; Kim, Bung-Nyun

2017-08-01

We investigated the possible association between two NMDA subunit gene polymorphisms (GRIN2B rs2284411 and GRIN2A rs2229193) and treatment response to methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). A total of 75 ADHD patients aged 6-17 years underwent 6 months of MPH administration. Treatment response was defined by changes in scores of the ADHD-IV Rating Scale (ADHD-RS), clinician-rated Clinical Global Impression-Improvement (CGI-I), and Continuous Performance Test (CPT). The association of the GRIN2B and GRIN2A polymorphisms with treatment response was analyzed using logistic regression analyses. The GRIN2B rs2284411 C/C genotype showed significantly better treatment response as assessed by ADHD-RS inattention ( p=0.009) and CGI-I scores ( p=0.009), and there was a nominally significant association in regard to ADHD-RS hyperactivity-impulsivity ( p=0.028) and total ( p=0.023) scores, after adjusting for age, sex, IQ, baseline Clinical Global Impression-Severity (CGI-S) score, baseline ADHD-RS total score, and final MPH dose. The GRIN2B C/C genotype also showed greater improvement at the CPT response time variability ( p<0.001). The GRIN2A G/G genotype was associated with a greater improvement in commission errors of the CPT compared to the G/A genotype ( p=0.001). The results suggest that the GRIN2B rs2284411 genotype may be an important predictor of MPH response in ADHD.

Anti-gravity treadmills are effective in reducing knee forces.

PubMed

Patil, Shantanu; Steklov, Nikolai; Bugbee, William D; Goldberg, Timothy; Colwell, Clifford W; D'Lima, Darryl D

2013-05-01

Lower body positive pressure (LBPP) treadmills permit significant unweighting of patients and have the potential to enhance recovery following lower limb surgery. We determined the efficacy of an LBPP treadmill in reducing knee forces in vivo. Subjects, implanted with custom electronic tibial prostheses to measure forces in the knee, were tested on a treadmill housed within a LBPP chamber. Tibiofemoral forces were monitored at treadmill speeds from 1.5 mph (0.67 m/s) to 4.5 mph (2.01 m/s), treadmill incline from -10° to +10°, and four treadmill chamber pressure settings adjusted to decrease net treadmill reaction force from 100% to 25% of the subject's body weight (BW). The peak axial tibiofemoral force ranged from 5.1 times BW at a treadmill speed of 4.5 mph (2.01 m/s) and a pressure setting of 100% BW to 0.8 times BW at 1.5 mph (0.67 m/s) and a pressure setting of 25% BW. Peak knee forces were significantly correlated with walking speed and treadmill reaction force (R(2)  = 0.77, p = 0.04). The LBPP treadmill might be an effective tool in the rehabilitation of patients following lower-extremity surgery. The strong correlation between tibiofemoral force and walking speed and treadmill reaction forces allows for more precisely achieving the target knee forces desired during early rehabilitation. Copyright © 2012 Orthopaedic Research Society.

Caloric and nutrient intake in children with attention deficit hyperactivity disorder treated with extended-release methylphenidate: analysis of a cross-sectional nutrition survey.

PubMed

Durá-Travé, Teodoro; Gallinas-Victoriano, Fidel

2014-02-01

To study calorie and nutrients intake in a group of patients diagnosed with attention deficit hyperactivity disorder (ADHD) under treatment with extended-release methylphenidate (MPH-ER), and to analyse the need to design nutrition intervention strategies. Observational (case-control). Navarra Hospital Complex, Pamplona, Spain. A total of 100 patients diagnosed with ADHD under treatment with MPH-ER and 100 healthy children (control group). A nutrition survey was carried out (food intake registration of 3 consecutive school days). Calorie and nutrient intake, as well as nutrition status, were evaluated and compared in both groups. Nutritional status in ADHD group was significantly lower (p < 0.05) than in control group. Calorie intake in mid-morning snack, lunch and afternoon snack was significantly higher (p < 0.05) in the control group. Calorie intake in supper was significantly higher (p < 0.05) in the ADHD group. There were no significant differences in breakfast. Total calorie intake, as well as protein, carbohydrates, fat, fibre, calcium, iron, magnesium, zinc, selenium and phosphorous, thiamine, niacin, vitamin B6 and folate intake, in control group was significantly higher than in ADHD group. The daily calorie and nutrients intake in patients under treatment with MPH-ER is, generally, lower than in healthy population of similar age. The need to impart programmes of nutrition education simultaneously with multimodal treatment in order to avoid the nutrition consequences of treatment with MPH should be considered.

Urinary tract infections in infants and children: Diagnosis and management

PubMed Central

Robinson, Joan L; Finlay, Jane C; Lang, Mia Eileen; Bortolussi, Robert

2014-01-01

Recent studies have resulted in major changes in the management of urinary tract infections (UTIs) in children. The present statement focuses on the diagnosis and management of infants and children >2 months of age with an acute UTI and no known underlying urinary tract pathology or risk factors for a neurogenic bladder. UTI should be ruled out in preverbal children with unexplained fever and in older children with symptoms suggestive of UTI (dysuria, urinary frequency, hematuria, abdominal pain, back pain or new daytime incontinence). A midstream urine sample should be collected for urinalysis and culture in toilet-trained children; others should have urine collected by catheter or by suprapubic aspirate. UTI is unlikely if the urinalysis is completely normal. A bagged urine sample may be used for urinalysis but should not be used for urine culture. Antibiotic treatment for seven to 10 days is recommended for febrile UTI. Oral antibiotics may be offered as initial treatment when the child is not seriously ill and is likely to receive and tolerate every dose. Children <2 years of age should be investigated after their first febrile UTI with a renal/bladder ultrasound to identify any significant renal abnormalities. A voiding cystourethrogram is not required for children with a first UTI unless the renal/bladder ultrasound reveals findings suggestive of vesicoureteral reflux, selected renal anomalies or obstructive uropathy. PMID:25332662

Urinary tract infections in infants and children: Diagnosis and management.

PubMed

Robinson, Joan L; Finlay, Jane C; Lang, Mia Eileen; Bortolussi, Robert

2014-06-01

Recent studies have resulted in major changes in the management of urinary tract infections (UTIs) in children. The present statement focuses on the diagnosis and management of infants and children >2 months of age with an acute UTI and no known underlying urinary tract pathology or risk factors for a neurogenic bladder. UTI should be ruled out in preverbal children with unexplained fever and in older children with symptoms suggestive of UTI (dysuria, urinary frequency, hematuria, abdominal pain, back pain or new daytime incontinence). A midstream urine sample should be collected for urinalysis and culture in toilet-trained children; others should have urine collected by catheter or by suprapubic aspirate. UTI is unlikely if the urinalysis is completely normal. A bagged urine sample may be used for urinalysis but should not be used for urine culture. Antibiotic treatment for seven to 10 days is recommended for febrile UTI. Oral antibiotics may be offered as initial treatment when the child is not seriously ill and is likely to receive and tolerate every dose. Children <2 years of age should be investigated after their first febrile UTI with a renal/bladder ultrasound to identify any significant renal abnormalities. A voiding cystourethrogram is not required for children with a first UTI unless the renal/bladder ultrasound reveals findings suggestive of vesicoureteral reflux, selected renal anomalies or obstructive uropathy.

Predicting who will undergo surgery after physiotherapy for female stress urinary incontinence.

PubMed

Labrie, J; Lagro-Janssen, A L M; Fischer, K; Berghmans, L C M; van der Vaart, C H

2015-03-01

To predict who will undergo midurethral sling surgery (surgery) after initial pelvic floor muscle training (physiotherapy) for stress urinary incontinence in women. This was a cohort study including women with moderate to severe stress incontinence who were allocated to the physiotherapy arm from a previously reported multicentre trial comparing initial surgery or initial physiotherapy in treating stress urinary incontinence. Crossover to surgery was allowed. Data from 198/230 women who were randomized to physiotherapy was available for analysis, of whom 97/198 (49 %) crossed over to surgery. Prognostic factors for undergoing surgery after physiotherapy were age <55 years at baseline (OR 2.87; 95 % CI 1.30-6.32), higher educational level (OR 3.28; 95 % CI 0.80-13.47), severe incontinence at baseline according to the Sandvik index (OR 1.77; 95 % CI 0.95-3.29) and Urogenital Distress Inventory; incontinence domain score (OR 1.03; per point; 95 % CI 1.01-1.65). Furthermore, there was interaction between age <55 years and higher educational level (OR 0.09; 95 % CI 0.02-0.46). Using these variables we constructed a prediction rule to estimate the risk of surgery after initial physiotherapy. In women with moderate to severe stress incontinence, individual prediction for surgery after initial physiotherapy is possible, thus enabling shared decision making for the choice between initial conservative or invasive management of stress urinary incontinence.

iss009e18123

NASA Image and Video Library

2004-08-12

ISS009-E-18123 (21:08:33 GMT, 12 August 2004) --- This panoramic view of Hurricane Charley was taken by the Expedition 9 crew of the International Space Station just after 5PM (EDT), August 12, 2004. The Category Two Hurricane was in the northwest Caribbean Sea, 140 miles south-southeast of Havana, Cuba moving north-northwest at 18mph packing winds of 105mph. In this view looking southeast, the newly formed eye of the storm is just visible and the west coast of Florida from Naples to Tampa Bay may be seen on the right.

Earth Science

NASA Image and Video Library

2004-08-13

This panoramic view of Hurricane Charley was photographed by the Expedition 9 crew aboard the International Space Station (ISS) on August 13, 2004, at a vantage point just north of Tampa, Florida. The small eye was not visible in this view, but the raised cloud tops near the center coincide roughly with the time that the storm began to rapidly strengthen. The category 2 hurricane was moving north-northwest at 18 mph packing winds of 105 mph. Crew Earth Observations record Earth surface changes over time, as well as more fleeting events such as storms, floods, fires, and volcanic eruptions.

Comparative Pharmacodynamics and Plasma Concentrations of D-Threo-Methylphenidate Hydrochloride after Single Doses of D-Threo-Methylphenidate Hydrochloride and D,l-Threo-Methylphenidate Hydrochloride in a Double-Blind, Placebo-Controlled, Crossover Laboratory School Study in Children with Attention-Deficit/hyperactivity Disorder

ERIC Educational Resources Information Center

Quinn, Declan; Wigal, Sharon; Swanson, James; Hirsch, Sharon; Ottolini, Yvonne; Dariani, Maghsoud; Roffman, Mark; Zeldis, Jerome; Cooper, Thomas

2004-01-01

Objective: Methylphenidate has four optical isomers due to two asymmetries (erythro-threo and dextro-levo). The initial commercial formulation eliminated the erythro isomer, but the dextro-levo asymmetry was racemic, with equal amounts of d and l-threo isomers (d,l-MPH). Previous work has suggested that the d-threo isomer methylphenidate (d-MPH)…

The Diagnosis of Urinary Tract Infection in Young Children (DUTY) Study Clinical Rule: Economic Evaluation.

PubMed

Hollingworth, William; Busby, John; Butler, Christopher C; O'Brien, Kathryn; Sterne, Jonathan A C; Hood, Kerenza; Little, Paul; Lawton, Michael; Birnie, Kate; Thomas-Jones, Emma; Harman, Kim; Hay, Alastair D

2017-04-01

To estimate the cost-effectiveness of a two-step clinical rule using symptoms, signs and dipstick testing to guide the diagnosis and antibiotic treatment of urinary tract infection (UTI) in acutely unwell young children presenting to primary care. Decision analytic model synthesising data from a multicentre, prospective cohort study (DUTY) and the wider literature to estimate the short-term and lifetime costs and healthcare outcomes (symptomatic days, recurrent UTI, quality adjusted life years) of eight diagnostic strategies. We compared GP clinical judgement with three strategies based on a 'coefficient score' combining seven symptoms and signs independently associated with UTI and four strategies based on weighted scores according to the presence/absence of five symptoms and signs. We compared dipstick testing versus laboratory culture in children at intermediate risk of UTI. Sampling, culture and antibiotic costs were lowest in high-specificity DUTY strategies (£1.22 and £1.08) compared to clinical judgement (£1.99). These strategies also approximately halved urine sampling (4.8% versus 9.1% in clinical judgement) without reducing sensitivity (58.2% versus 56.4%). Outcomes were very similar across all diagnostic strategies. High-specificity DUTY strategies were more cost-effective than clinical judgement in the short- (iNMB = £0.78 and £0.84) and long-term (iNMB =£2.31 and £2.50). Dipstick tests had poorer cost-effectiveness than laboratory culture in children at intermediate risk of UTI (iNMB = £-1.41). Compared to GPs' clinical judgement, high specificity clinical rules from the DUTY study could substantially reduce urine sampling, achieving lower costs and equivalent patient outcomes. Dipstick testing children for UTI is not cost-effective. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Decreased dopamine activity predicts relapse in methamphetamine abusers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang G. J.; Wang, G.-J.; Smith, L.

2011-01-20

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [{sup 11}C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested withinmore » 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.« less

Decreased dopamine activity predicts relapse in methamphetamine abusers.

PubMed

Wang, G J; Smith, L; Volkow, N D; Telang, F; Logan, J; Tomasi, D; Wong, C T; Hoffman, W; Jayne, M; Alia-Klein, N; Thanos, P; Fowler, J S

2012-09-01

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [(11)C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes.

Quantification of Methylphenidate, Dexamphetamine, and Atomoxetine in Human Serum and Oral Fluid by HPLC With Fluorescence Detection.

PubMed

Stegmann, Benedikt; Dörfelt, Anett; Haen, Ekkehard

2016-02-01

For psychostimulants, a marked individual variability in the dose-response relationship and large differences in plasma concentrations after similar doses are known. Therefore, optimizing the efficacy of these drugs is at present the most promising way to exploit their full pharmacological potential. Moreover, it seems important to examine oral fluid as less invasive biological matrix for its benefit in therapeutic drug monitoring for patients with hyperkinetic disorder. A high-performance liquid chromatography method for quantification of methylphenidate (MPH), dexamphetamine (DXA), and atomoxetine in serum and oral fluid has been developed and validated. The analytical procedure involves liquid-liquid extraction, derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride as a label and chromatographic separation on a Phenomenex Gemini-NX C18 analytical column using gradient elution with water-acetonitrile. The derivatized analytes were detected at 330 nm (excitation wavelength) and 440 nm (emission wavelength). To examine the oral fluid/serum ratios, oral fluid samples were collected simultaneously to blood samples from patients with hyperkinetic disorder. The method allows quantification of all analytes in serum and oral fluid within 16 minutes under the same or similar conditions. Oral fluid/serum ratios for MPH and DXA were highly variable and showed an accumulation of these drugs in oral fluid. The developed method covers the determination of MPH, DXA, and atomoxetine concentrations in serum and oral fluid after the intake of therapeutic doses. Oral fluid samples are useful for the qualitative detection of MPH and DXA.

Right prefrontal activation as a neuro-functional biomarker for monitoring acute effects of methylphenidate in ADHD children: An fNIRS study☆

PubMed Central

Monden, Yukifumi; Dan, Haruka; Nagashima, Masako; Dan, Ippeita; Tsuzuki, Daisuke; Kyutoku, Yasushi; Gunji, Yuji; Yamagata, Takanori; Watanabe, Eiju; Momoi, Mariko Y.

2012-01-01

An objective biomarker is a compelling need for the early diagnosis of attention deficit hyperactivity disorder (ADHD), as well as for the monitoring of pharmacological treatment effectiveness. The advent of fNIRS, which is relatively robust to the body movements of ADHD children, raised the possibility of introducing functional neuroimaging diagnosis in younger ADHD children. Using fNIRS, we monitored the oxy-hemoglobin signal changes of 16 ADHD children (6 to 13 years old) performing a go/no-go task before and 1.5 h after MPH or placebo administration, in a randomized, double-blind, placebo-controlled, crossover design. 16 age- and gender-matched normal controls without MPH administration were also monitored. Relative to control subjects, unmedicated ADHD children exhibited reduced activation in the right inferior frontal gyrus (IFG) and middle frontal gyrus (MFG) during go/no-go tasks. The reduced right IFG/MFG activation was acutely normalized after MPH administration, but not after placebo administration. The MPH-induced right IFG/MFG activation was significantly larger than the placebo-induced activation. Post-scan exclusion rate was 0% among 16 right-handed ADHD children with IQ > 70. We revealed that the right IFG/MFG activation could serve as a neuro-functional biomarker for monitoring the acute effects of methylphenidate in ADHD children. fNIRS-based examinations were applicable to ADHD children as young as 6 years old, and thus would contribute to early clinical diagnosis and treatment of ADHD children. PMID:24179746

Rapid quantitative analysis of methylphenidate and ritalinic acid in oral fluid by liquid chromatography triple quadrupole mass spectrometry (LC-QqQ-MS).

PubMed

Mulet, Carmen T; Arroyo-Mora, Luis E; Leon, Lorena A; Gnagy, Elizabeth; DeCaprio, Anthony P

2018-06-20

Methylphenidate (MPH), which is metabolized into ritalinic acid (RA), is an amphetamine derivative largely used in the treatment of attention-deficit hyperactivity disorder, a neurological condition commonly diagnosed in early childhood. Ensuring that patients comply with clinical treatment is crucial and compliance is generally monitored in blood or urine specimens which, especially in the case of children, can be challenging to obtain on a repetitive basis. Here we report validation of a specific, non-invasive, and rapid dilute-and-shoot analytical method for the detection and quantitation of MPH and RA in oral fluid (OF). The method is based on liquid chromatography coupled to triple quadrupole MS with electrospray ionization utilizing dynamic MRM mode. Subject OF specimens were collected using a Quantisal™ device, processed, and diluted for analysis with seven-point quadratic calibration curves (weighting of 1/x) using MPH-d 9 and (±)-threo-RA-d 10 as internal standards. QC samples and diluted specimens showed intra- and inter-day bias and imprecision values no greater than ±12%. The LOD and LOQ for MPH were 0.1 and 0.5 ng/mL, respectively, and 0.2 ng/mL and 0.5 ng/mL for RA, respectively, indicating the validity of the method for identification and confirmation at low concentrations. Selectivity was specific for the analytes of interest and matrix effects were minimized through the use of internal standard based quantitation. Copyright © 2018 Elsevier B.V. All rights reserved.

Methylphenidate administration determines enduring changes in neuroglial network in rats.

PubMed

Cavaliere, Carlo; Cirillo, Giovanni; Bianco, Maria Rosaria; Adriani, Walter; De Simone, Antonietta; Leo, Damiana; Perrone-Capano, Carla; Papa, Michele

2012-01-01

Repeated exposure to psychostimulant drugs induces complex molecular and structural modifications in discrete brain regions of the meso-cortico-limbic system. This structural remodeling is thought to underlie neurobehavioral adaptive responses. Administration to adolescent rats of methylphenidate (MPH), commonly used in attention deficit and hyperactivity disorder (ADHD), triggers alterations of reward-based behavior paralleled by persistent and plastic synaptic changes of neuronal and glial markers within key areas of the reward circuits. By immunohistochemistry, we observe a marked increase of glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expression and a down-regulation of glial glutamate transporter GLAST in dorso-lateral and ventro-medial striatum. Using electron microscopy, we find in the prefrontal cortex a significant reduction of the synaptic active zone length, paralleled by an increase of dendritic spines. We demonstrate that in limbic areas the MPH-induced reactive astrocytosis affects the glial glutamatergic uptake system that in turn could determine glutamate receptor sensitization. These processes could be sustained by NO production and synaptic rearrangement and contribute to MPH neuroglial induced rewiring. Copyright © 2011. Published by Elsevier B.V.

A multicenter, open-label trial to evaluate the quality of life in adults with ADHD treated with long-acting methylphenidate (OROS MPH): Concerta Quality of Life (CONQoL) study.

PubMed

Mattos, Paulo; Louzã, Mário Rodrigues; Palmini, André Luís Fernandes; de Oliveira, Irismar Reis; Rocha, Fábio Lopes

2013-07-01

The available literature provides few studies on the effectiveness of methylphenidate in improving quality of life in individuals with ADHD. To assess the effectiveness of methylphenidate OROS formulation (OROS MPH) through QoL in adults with ADHD. A 12-week, multicenter, open-label trial involving 60 patients was used. The measures used were Adult Self-Rating Scale, Adult ADHD Quality of Life Scale (AAQoL), State and Trait Anxiety Inventory (STAI), Hamilton Depression Rating Scale (HAM-D), Clinical Global Impression (CGI), and safety measures. A significance statistic level of 5% was adopted. Analyses included 60 patients (66.7% male; M age = 31.1 years) for safety and 58 patients for effectiveness. All AAQoL subscales improved from baseline to Week 12 (p < .0001), as well as the Total AAQoL (p < .0001). A significant reduction on Clinical Global Impression-Improvement (CGI-I), HAM-D, STAI, and ASRS scores was observed (p < .0001). No serious adverse event was reported. Treatment of adult ADHD patients with OROS MPH improves QoL.

The effect of methylphenidate on anxiety and depression symptoms in patients with Asperger syndrome and comorbid attention deficit/hyperactivity disorder.

PubMed

Golubchik, Pavel; Rapaport, Michal; Weizman, Abraham

2017-09-01

The objective of this study was to assess the response of anxiety and depression symptoms to methylphenidate (MPH) treatment in patients with Asperger syndrome (AS) combined with attention deficit/hyperactivity disorder (ADHD). A group of 12 patients with AS/ADHD, aged 8-18 years, received 12 weeks of MPH treatment. The severities of ADHD, anxiety, and depression symptoms were assessed by means of the ADHD Rating Scale (ADHD-RS), Screen for Child Anxiety Related Emotional Disorders, and the Children's Depression Inventory. The severity of ADHD and depression symptoms was reduced significantly (P<0.0003 and P=0.046, respectively). No improvement in total anxiety symptoms was found, but a significant reduction was obtained in the school-related subscale of the Screen for Child Anxiety Related Emotional Disorders (P=0.0054). A positive correlation was found between the reductions in ADHD-RS and Children's Depression Inventory scores (r=0.59, P=0.039). MPH treatment may be safe, tolerable, and effective in alleviating depression and school-related anxiety symptoms in patients with AS and ADHD.

Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/hyperactivity disorder treated with methylphenidate.

PubMed

Bruxel, E M; Salatino-Oliveira, A; Genro, J P; Zeni, C P; Polanczyk, G V; Chazan, R; Rohde, L A; Hutz, M H

2013-10-01

Carboxylesterase 1 is the enzyme involved in methylphenidate (MPH) metabolism. The aim of this study was to evaluate the association between a -75 T>G polymorphism and appetite reduction in children with attention-deficit/hyperactivity disorder (ADHD). A sample of 213 children with ADHD was investigated. The primary outcome was appetite reduction measured by the Barkley Stimulant Side Effect Rating Scale applied at baseline, at 1 and 3 months of treatment. MPH doses were augmented until no further clinical improvement or significant adverse events occurred. The G allele presented a trend for association with appetite reduction scores (P=0.05). A significant interaction between the G allele and treatment over time for appetite reduction scores was also observed (P=0.03). The G allele carriers presented a higher risk for appetite reduction worsening when compared with T allele homozygotes (odds ratio=3.47, P=0.01). The present results suggest an influence of carboxylesterase 1 -75 T>G polymorphism on the worsening of appetite reduction with MPH treatment in youths with ADHD.

Improved SCR ac Motor Controller for Battery Powered Urban Electric Vehicles

NASA Technical Reports Server (NTRS)

Latos, T. S.

1982-01-01

An improved ac motor controller, which when coupled to a standard ac induction motor and a dc propulsion battery would provide a complete electric vehicle power train with the exception of the mechanical transmission and drive wheels was designed. In such a system, the motor controller converts the dc electrical power available at the battery terminals to ac electrical power for the induction motor in response to the drivers commands. The performance requirements of a hypothetical electric vehicle with an upper weight bound of 1590 kg (3500 lb) were used to determine the power rating of the controller. Vehicle acceleration capability, top speed, and gradeability requisites were contained in the Society of Automotive Engineers (SAE) Schedule 227a(d) driving cycle. The important capabilities contained in this driving cycle are a vehicle acceleration requirement of 0 to 72.4 kmph (0 to 45 mph) in 28 seconds a top speed of 88.5 kmph (55 mph), and the ability to negotiate a 10% grade at 48 kmph (30 mph). A 10% grade is defined as one foot of vertical rise per 10 feet of horizontal distance.

Magnetic particle hyperthermia—a promising tumour therapy?

NASA Astrophysics Data System (ADS)

Dutz, Silvio; Hergt, Rudolf

2014-11-01

We present a critical review of the state of the art of magnetic particle hyperthermia (MPH) as a minimal invasive tumour therapy. Magnetic principles of heating mechanisms are discussed with respect to the optimum choice of nanoparticle properties. In particular, the relation between superparamagnetic and ferrimagnetic single domain nanoparticles is clarified in order to choose the appropriate particle size distribution and the role of particle mobility for the relaxation path is discussed. Knowledge of the effect of particle properties for achieving high specific heating power provides necessary guidelines for development of nanoparticles tailored for tumour therapy. Nanoscale heat transfer processes are discussed with respect to the achievable temperature increase in cancer cells. The need to realize a well-controlled temperature distribution in tumour tissue represents the most serious problem of MPH, at present. Visionary concepts of particle administration, in particular by means of antibody targeting, are far from clinical practice, yet. On the basis of current knowledge of treating cancer by thermal damaging, this article elucidates possibilities, prospects, and challenges for establishment of MPH as a standard medical procedure.

Reinforcement Enhances Vigilance Among Children With ADHD: Comparisons to Typically Developing Children and to the Effects of Methylphenidate

PubMed Central

Bubnik, Michelle G.; Hawk, Larry W.; Pelham, William E.; Waxmonsky, James G.; Rosch, Keri S.

2014-01-01

Sustained attention and reinforcement are posited as causal mechanisms in Attention-Deficit/Hyperactivity Disorder (ADHD), but their interaction has received little empirical study. In two studies, we examined the impact of performance-based reinforcement on sustained attention over time, or vigilance, among 9- to 12-year-old children. Study 1 demonstrated the expected vigilance deficit among children with ADHD (n=25; 12% female) compared to typically developing (TD) controls (n=33; 22% female) on a standard continuous performance task (CPT). During a subsequent visit, reinforcement improved attention more among children with ADHD than controls. Study 2 examined the separate and combined effects of reinforcement and acute methylphenidate (MPH) on CPT performance in children with ADHD (n=19; 21% female). Both reinforcement and MPH enhanced overall target detection and attenuated the vigilance decrement that occurred in no-reinforcement, placebo condition. Cross-study comparisons suggested that the combination of MPH and reinforcement eliminated the vigilance deficit in children with ADHD, normalizing sustained attention. This work highlights the clinically and theoretically interesting intersection of reinforcement and sustained attention. PMID:24931776

Prediction of methylphenidate treatment outcome in adults with attention-deficit/hyperactivity disorder (ADHD).

PubMed

Retz, Wolfgang; Retz-Junginger, Petra

2014-11-01

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent mental disorder of childhood, which often persists in adulthood. Methylphenidate (MPH) is one of the most effective medications to treat ADHD, but also few adult patients show no sufficient response to this drug. In this paper, we give an overview regarding genetic, neuroimaging, clinical and other studies which have tried to reveal the reasons for non-response in adults with ADHD, based on a systematic literature search. Although MPH is a well-established treatment for adults with ADHD, research regarding the prediction of treatment outcome is still limited and has resulted in inconsistent findings. No reliable neurobiological markers of treatment response have been identified so far. Some findings from clinical studies suggest that comorbidity with substance use disorders and personality disorders has an impact on treatment course and outcome. As MPH is widely used in the treatment of adults with ADHD, much more work is needed regarding positive and negative predictors of long-term treatment outcome in order to optimize the pharmacological treatment of adult ADHD patients.

Urinary biomarkers in hexachloro-1:3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression.

PubMed

Swain, Aubrey; Turton, John; Scudamore, Cheryl L; Pereira, Ines; Viswanathan, Neeti; Smyth, Rosemary; Munday, Michael; McClure, Fiona; Gandhi, Mitul; Sondh, Surjit; York, Malcolm

2011-05-01

Hexachloro-1:3-butadiene (HCBD) causes kidney injury specific to the pars recta of the proximal tubule. In the present studies, injury to the nephron was characterized at 24 h following a single dose of HCBD, using a range of quantitative urinary measurements, renal histopathology and gene expression. Multiplexed renal biomarker measurements were performed using both the Meso Scale Discovery (MSD) and Rules Based Medicine platforms. In a second study, rats were treated with a single nephrotoxic dose of HCBD and the time course release of a range of traditional and newer urinary biomarkers was followed over a 25 day period. Urinary albumin (a marker of both proximal tubular function and glomerular integrity) and α-glutathione S-transferase (α-GST, a proximal tubular cell marker of cytoplasmic leakage) showed the largest fold change at 24 h (day 1) after dosing. Most other markers measured on either the MSD or RBM platforms peaked on day 1 or 2 post-dosing, whereas levels of kidney injury molecule-1 (KIM-1), a marker of tubular regeneration, peaked on day 3/4. Therefore, in rat proximal tubular nephrotoxicity, the measurement of urinary albumin, α-GST and KIM-1 is recommended as they potentially provide useful information about the function, degree of damage and repair of the proximal tubule. Gene expression data provided useful confirmatory information regarding exposure of the kidney and liver to HCBD, and the response of these tissues to HCBD in terms of metabolism, oxidative stress, inflammation, and regeneration and repair. Copyright © 2011 John Wiley & Sons, Ltd.

Impact of prenatal exposure to cadmium on cognitive development at preschool age and the importance of selenium and iodine.

PubMed

Kippler, Maria; Bottai, Matteo; Georgiou, Vaggelis; Koutra, Katerina; Chalkiadaki, Georgia; Kampouri, Mariza; Kyriklaki, Andriani; Vafeiadi, Marina; Fthenou, Eleni; Vassilaki, Maria; Kogevinas, Manolis; Vahter, Marie; Chatzi, Leda

2016-11-01

The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.

KSC-04pd1799

NASA Image and Video Library

2004-09-14

KENNEDY SPACE CENTER, FLA. - Repair crews clean up debris left behind after Hurricane Frances as it passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph. Hurricane damage sustained at KSC included the south wall and roof of the Vehicle Assembly Building plus the roof of the Thermal Protection System Facility.

KSC-04PD-1800

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. Repair crews clean up debris left behind after Hurricane Frances as it passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph. KSC sustained damage to the south wall and roof of the Vehicle Assembly Building plus the roof of the Thermal Protection System Facility.

KSC-04PD-1798

NASA Technical Reports Server (NTRS)

2004-01-01

KENNEDY SPACE CENTER, FLA. A repair crew replaces a light fixture damaged by Hurricane Frances as it passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph. Hurricane damage sustained at KSC included the south wall and roof of the Vehicle Assembly Building plus the roof of the Thermal Protection System Facility.

KSC-04pd1801

NASA Image and Video Library

2004-09-14

KENNEDY SPACE CENTER, FLA. - A repair crew replaces a light fixture damaged by Hurricane Frances as it passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph. KSC sustained damage to the south wall and roof of the Vehicle Assembly Building plus the roof of the Thermal Protection System Facility.

KSC-04pd1800

NASA Image and Video Library

2004-09-14

KENNEDY SPACE CENTER, FLA. - Repair crews clean up debris left behind after Hurricane Frances as it passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph. KSC sustained damage to the south wall and roof of the Vehicle Assembly Building plus the roof of the Thermal Protection System Facility.

KSC-04pd1798

NASA Image and Video Library

2004-09-14

KENNEDY SPACE CENTER, FLA. - A repair crew replaces a light fixture damaged by Hurricane Frances as it passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph. Hurricane damage sustained at KSC included the south wall and roof of the Vehicle Assembly Building plus the roof of the Thermal Protection System Facility.

KSC-04pd1802

NASA Image and Video Library

2004-09-14

KENNEDY SPACE CENTER, FLA. - Repair crews clean up debris at the railroad yard left behind after Hurricane Frances as it passed over Central Florida during the Labor Day weekend. The maximum wind at the surface from Hurricane Frances was 94 mph from the northeast at 6:40 a.m. on Sunday, September 5. It was recorded at a weather tower located on the east shore of the Mosquito Lagoon near the Cape Canaveral National Seashore. The highest sustained wind at KSC was 68 mph. KSC sustained damage to the south wall and roof of the Vehicle Assembly Building plus the roof of the Thermal Protection System Facility.

Low Ultraviolet B and Increased Risk of Brain Cancer: An Ecological Study of 175 Countries

DTIC Science & Technology

2009-07-01

strong impact on risk of brain cancer . However, there was now way to directly assess this in the current model given the data available to the...8217 . ’ . · ’ · ’ ’ . ’ . ’ ’ ’ Low. U/Jraviolet Band Increased . . . Ri$-k. of Brain . cancer :’ . .. A~ :Ec(!logical Study of 175 CiJun~ries...B and increased risk of brain cancer : an ecological study of 175 countries Sharif B. Mohr, M.P.H. 1,2, Edward D. Gorham1, M.P.H., Ph.D. 1,2

Dose-Response Effects of Long-Acting Liquid Methylphenidate in Children with Attention Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD): A Pilot Study.

PubMed

Kim, Soo-Jeong; Shonka, Sophia; French, William P; Strickland, Jennifer; Miller, Lindsey; Stein, Mark A

2017-08-01

Attention deficit/hyperactivity disorder (ADHD) symptoms are common in youth with autism spectrum disorders (ASD) and are frequently treated with stimulant medications. Twenty-seven children were randomized to different dose titration schedules, and ADHD symptoms, tolerability, and aberrant behaviors were assessed weekly during a 6-week trial with long-acting liquid methylphenidate (MPH). MPH at low to moderate doses was effective in reducing ADHD symptoms and was well tolerated in young children with ASD and ADHD. Future studies are needed to assess generalization and maintenance of efficacy.

45 MPH 6,000-Pound and 10,000-Pound Rough Terrain Fork Lift Truck Feasibility Study.

DTIC Science & Technology

1986-06-24

Airport Post Office Box 66911 Chicago, IL 60666 NPN Security Classification of This Page REPORT DOCUMENTATION PAGE la . Report Security Classification...HOP Unausended Duadin., 20 - I: - 1 1.8 Inch RMS Road 14 la -3 * Clam C (0.93 Inch RMS) Rod w 12 10 10 Per~cent 9 P 7 U. 3 Percent 3 2 0 20 40 SPM...elm 10 67- * * 3 o *" - .2 0 20 40 W (mph) 4/2/ SOJA Figure 75. Rear Wheel Hop on Four Road Surfaces (10K RTFLT Unsuspended Baseline) " Page 93 Adding

Inficon Transpector MPH Mass Spectrometer Random Vibration Test Report

NASA Technical Reports Server (NTRS)

Santiago-Bond, Jo; Captain, Janine

2015-01-01

The purpose of this test report is to summarize results from the vibration testing of the INFICON Transpector MPH100M model Mass Spectrometer. It also identifies requirements satisfied, and procedures used in the test. As a payload of Resource Prospector, it is necessary to determine the survivability of the mass spectrometer to proto-qualification level random vibration. Changes in sensitivity of the mass spectrometer can be interpreted as a change in alignment of the instrument. The results of this test will be used to determine any necessary design changes as the team moves forward with flight design.

Can routine automated urinalysis reduce culture requests?

PubMed

Kayalp, Damla; Dogan, Kubra; Ceylan, Gozde; Senes, Mehmet; Yucel, Dogan

2013-09-01

There are a substantial number of unnecessary urine culture requests. We aimed to investigate whether urine dipstick and microscopy results could accurately rule out urinary tract infection (UTI) without urine culture. The study included a total of 32,998 patients (11,928 men and 21,070 women, mean age: 39 ± 32 years) with a preliminary diagnosis of UTI and both urinalysis and urinary culture were requested. All urine cultures were retrospectively reviewed; association of culture positivity with a positive urinalysis result for leukocyte esterase (LE) and nitrite in chemical analysis and pyuria (WBC) and bacteriuria in microscopy was determined. Diagnostic performance of urinalysis parameters for detection of UTI was evaluated. In total, 758 (2.3%) patients were positive by urine culture. Out of these culture positive samples, ratios of positive dipstick results for LE and nitrite were 71.0% (n=538) and 17.7% (n=134), respectively. The positive microscopy results for WBC and bacteria were 68.2% (n=517) and 78.8% (n=597), respectively. Negative predictive values for LE, nitrite, bacteriuria and WBC were very close to 100%. Most of the samples have no or insignificant bacterial growth. Urine dipstick and microscopy can accurately rule out UTI. Automated urinalysis is a practicable and faster screening test which may prevent unnecessary culture requests for majority of patients. © 2013. Published by Elsevier Inc. All rights reserved.

Prediction of vesico-ureteric reflux in childhood urinary tract infection: a multivariate approach.

PubMed

Oostenbrink, R; van der Heijden, A J; Moons, K G; Moll, H A

2000-07-01

In this study, independent predictors obtained from patient history, physical examination and laboratory results for vesico-ureteric reflux (VUR) in children of 0-5 y with a first urinary tract infection (UTI) were assessed and the added value of renal ultrasound (US) investigated. Information was collected from children visiting the paediatric outpatient department with a first proven UTI, defined as a urine monoculture with > or = 10(5) organism/ml, with clinical symptoms and possible white cell count > or = 20 per high-power field of spun fresh urine. Children with neurologic bladder dysfunction were excluded. VUR was determined by voiding cystourethrography (VCUG) and graded from I to V. The diagnostic value of predictors was judged using multivariate logistic modelling with the area under the receiver operating characteristic (ROC area). A risk score was derived based on the regression coefficients of the independent predictors in the logistic model. In 140 children (51 boys and 89 girls) VUR was diagnosed in 37. Independent predictors for VUR were male gender, age, family history for uropathology, serum C-reactive protein level (CRP) and dilatation of the urinary tract on US. The ROC area of this model was 0.78 (95% CI: 0.69-0.87). This prediction model identified 12% (95% CI: 7-18) of the patients without VUR without missing one case of VUR. If we used VUR > or = grade 3 as a threshold, the model assessed VUR to be absent in 34% (95% CI: 26-42). A prediction rule based on age, gender, family history, CRP and US results is useful in assessing the probability of VUR in the individual child with a first UTI and may help the physician to make decisions about performing additional imaging techniques. Prospective validation of the model in future patients, however, will be necessary before applying the rule in practice.

Gait pattern alteration by functional sensory substitution in healthy subjects and in diabetic subjects with peripheral neuropathy.

PubMed

Walker, S C; Helm, P A; Lavery, L A

1997-08-01

To evaluate the ability of diabetic and nondiabetic individuals to learn to use a lower extremity sensory substitution device to cue gait pattern changes. Case-control study. Gait laboratory. Thirty diabetic persons and 20 age- and education-matched nondiabetic controls responded to advertisements for study participation. Participants walked on a treadmill at three speeds (1, 2, and 2.5mph) with auditory sensory feedback to cue ground contact greater than 80% duration of baseline. The variables measured included gait cycle (steps per minute) and number of times per minute that any step during a trial exceeded 80% duration of ground contacted compared with a measured baseline step length for each speed. Persons in both groups were able to rapidly and significantly alter their gait patterns in response to signals from the sensory substitution device, by changing their gait cycles (nondiabetic group, F(17,124) = 5.27, p < .001; diabetic group, F(5,172) = 3.45, p < .001). Post hoc analyses showed early gait cycle modification and error reduction among both groups. The nondiabetic group learned to use the device significantly more quickly than the diabetic group during the slow (1mph, t = 3.57, p < .001) and average (2mph, t = 2.97, p < .05) trials. By the fast (2.5mph) ambulation trial, both groups were performing equally, suggesting a rapid rate of adjustment to the device. No technical failures from gait trainer malfunction occurred during the study. Diabetic persons with neuropathy effectively used lower extremity sensory substitution, and the technology is now available to manufacture a durable, effective lower extremity sensory substitution system.

Anxiety and depressed mood decline following smoking abstinence in adult smokers with Attention Deficit Hyperactivity Disorder

PubMed Central

Covey, Lirio S.; Hu, Mei-Chen; Winhusen, Theresa; Lima, Jennifer; Berlin, Ivan; Nunes, Edward

2015-01-01

Introduction A preponderance of relevant research has indicated reduction in anxiety and depressive symptoms following smoking abstinence. This secondary analysis investigated whether the phenomenon extends to smokers with attention deficit hyperactivity disorder (ADHD). Methods The study setting was an 11-Week double-blind placebo-controlled randomized trial of osmotic release oral system methylphenidate (OROS-MPH) as a cessation aid when added to nicotine patch and counseling. Participants were 255 adult smokers with ADHD. The study outcomes are: anxiety (Beck Anxiety Inventory (BAI)) and depressed mood (Beck Depression Inventory II (BDI)) measured one Week and six Weeks after a target quit day (TQD). The main predictor is point - prevalence abstinence measured at Weeks 1 and 6 after TQD. Covariates are treatment (OROS-MPH vs placebo), past major depression, past anxiety disorder, number of cigarettes smoked daily, demographics (age, gender, education, marital status) and baseline scores on the BAI, BDI, and the DSM-IV ADHD Rating Scale. Results Abstinence was significantly associated with lower anxiety ratings throughout the post-quit period (p<0.001). Depressed mood was lower for abstainers than non-abstainers at Week 1 (p<0.05), but no longer at Week 6 (p=0.83). Treatment with OROS-MPH relative to placebo showed significant reductions at Week 6 after TQD for both anxiety (p<0.05) and depressed mood (p<0.001), but not at Week 1. Differential abstinence effects of gender were observed. Anxiety and depression ratings at baseline predicted increased ratings of corresponding measures during the post-quit period. Conclusion Stopping smoking yielded reductions in anxiety and depressed mood in smokers with ADHD treated with nicotine patch and counseling. Treatment with OROS-MPH yielded mood reductions in delayed manner. PMID:26272693