Pay attention to the metaphors by which you create your perception of reality

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BioMed CentralPage 1 of 12(page number not for citation purposes)Child and Adolescent Psychiatry and Mental HealthOpen AccessResearchDoes switching from oral extended-release methylphenidate to the methylphenidate transdermal system affect health-related quality-of-life and medication satisfaction for children with attention-deficit/hyperactivity disorder?Oscar G Bukstein*1, L Eugene Arnold2, Jeanne M Landgraf3 and Paul Hodgkins4Address: 1Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA, 2The Ohio State University, Columbus, Ohio, USA, 3HealthActCHQ Inc, Cambridge, Massachusetts, USA and 4Shire Development, Inc, Wayne, Pennsylvania, USAEmail: Oscar G Bukstein* - buksteinog@upmc.edu; L Eugene Arnold - arnold.6@embarqmail.com; Jeanne M Landgraf - jml@healthactchq.com; Paul Hodgkins - phodgkins@shire.com* Corresponding author AbstractBackground: To evaluate health-related quality of life (HRQL) and medication satisfaction after switching from a stable doseof oral extended-release methylphenidate (ER-MPH) to methylphenidate transdermal system (MTS) via a dose-transitionschedule in children with attention-deficit/hyperactivity disorder (ADHD).Methods: In a 4-week, multisite, open-label study, 171 children (164 in the intent-to-treat [ITT] population) aged 6-12 yearsdiagnosed with ADHD abruptly switched from a stable dose of oral ER-MPH to MTS nominal dosages of 10, 15, 20, and 30 mgusing a predefined dose-transition schedule. Subjects remained on the scheduled dose for the first week, after which the dosewas then titrated to an optimal effect. The ADHD Impact Module-Children (AIM-C), a disease-specific validated HRQL surveyinstrument measuring child and family impact, was used to assess the impact of ADHD symptoms on the lives of children andtheir families at baseline and study endpoint. Satisfaction with MTS use was assessed via a Medication Satisfaction Survey (MSS)at study endpoint. Both the AIM-C and MSS were completed by a caregiver (parent/legally authorized representative).Tolerability was monitored by spontaneous adverse event (AE) reporting.Results: AIM-C child and family HRQL mean scores were above the median possible score at baseline and were furtherimproved at endpoint across all MTS doses. Similar improvements were noted for behavior, missed doses, worry, and economicimpact AIM-C item scores. Overall, 93.8% of caregivers indicated a high level of satisfaction with their child's use of the studymedication. The majority of treatment-emergent AEs (> 98%) were mild to moderate in intensity, and the most commonlyreported AEs included headache, decreased appetite, insomnia, and abdominal pain. Seven subjects discontinued the study dueto intolerable AEs (n = 3) and application site reactions (n = 4).Conclusion: This study demonstrates that MTS, when carefully titrated to optimal dose, may further improve child and familyHRQL, as well as behavioral, medication worry, and economic impact item scores, as measured by the AIM-C in subjectsswitching to MTS from a stable dose of routinely prescribed oral ER-MPH after a short treatment period. Furthermore, followingthe abrupt conversion from oral ER-MPH to MTS, the majority of caregivers reported being highly satisfied with MTS as atreatment Pay attention to the metaphors by which you create your perception of reality Pay attention to the metaphors by which you create your perception of reality Bởi: Joe Tye “We have found… that metaphor is pervasive in everyday life, not just in language but in thought and action Our ordinary conceptual system, in terms of which we both think and act, is fundamentally metaphorical in nature.” George Lakoff and Mark Johnson: Metaphors We Live By A picture is worth a thousand words, and the most important pictures are those we use to create the stories by which we define reality Usually without even being aware we’re doing it we use metaphors (and similes, as when you say one person reminds you of another, which for our purposes are the same thing) define ourselves, other people, and the world around us These metaphors powerfully influence our self-identity and our beliefs If someone asks how you’re doing and you respond “I’m hanging in there,” you’ve just used a metaphor You’re not really hanging, but you’ve just told that other person – and more important you’ve just told yourself – that things are not well in your world After all, who hangs? Desperate people hang – by their fingernails at the ends of their ropes So the worst of criminals Not a very encouraging way to describe how your day is going, is it? Now, if you’ve just gotten a promotion and a big pay raise and are about to leave for a Caribbean cruise and someone asks how you’re doing, you’re probably not going to complain about just hanging in there, are you? Once when I was going through a pretty rough patch I caught myself saying that every time I came up for air it felt like a giant thumb came down from the sky and pushed me back down underwater That is obviously a metaphor – there really wasn’t a giant thumb 1/2 Pay attention to the metaphors by which you create your perception of reality and I wasn’t really drowning – it was a word picture Then it occurred to me that I could just as well have said that every time I sank beneath the waves it felt like a giant palm came up from the deeps and lifted me up to catch my breath Exact same circumstance, but the metaphor I chose to tell the story would give it a completely different interpretation 2/2 The PA-TM-RING protein RING finger protein 13 is an endosomal integral membrane E3 ubiquitin ligase whose RING finger domain is released to the cytoplasm by proteolysis Jeffrey P. Bocock 1 , Stephanie Carmicle 1 , Saba Chhotani 1 , Michael R. Ruffolo 1 , Haitao Chu 2 and Ann H. Erickson 1 1 Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC, USA 2 Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA Proteins of the PA-TM-RING family have a protease- associated (PA) domain and a RING finger domain separated by a transmembrane (TM) domain. PA domains are 120–210 amino acid sequences located in the noncatalytic regions of diverse proteases [1,2]. They are found in multiple members of MEROPS peptidase Keywords E3 ubiquitin ligase; neurite outgrowth; protease-associated domain; proteolysis; RNF13 Correspondence A. Erickson, Department of Biochemistry and Biophysics, CB 7260 GM, University of North Carolina, Chapel Hill, NC 27599, USA Fax: +1 929 966 2852 Tel: +1 919 966 4694 E-mail: ann_erickson@med.unc.edu (Received 1 November 2008, revised 23 December 2008, accepted 20 January 2009) doi:10.1111/j.1742-4658.2009.06913.x PA-TM-RING proteins have an N-terminal protease-associated domain, a structure found in numerous proteases and implicated in protein binding, and C-terminal RING finger and PEST domains. Homologous proteins include GRAIL (gene related to anergy in leukocytes), which controls T-cell anergy, and AtRMR1 (receptor homology region-transmembrane domain-RING-H2 motif protein), a plant protein storage vacuole sorting receptor. Another family member, chicken RING zinc finger (C-RZF), was identified as being upregulated in embryonic chicken brain cells grown in the presence of tenascin-C. Despite algorithm predictions that the cDNA encodes a signal peptide and transmembrane domain, the protein was found in the nucleus. We showed that RING finger protein 13 (RNF13), the murine homolog of C-RZF, is a type I integral membrane protein localized in the endosomal ⁄ lysosomal system. By quantitative real-time RT-PCR analysis, we demonstrated that expression of RNF13 is increased in adult relative to embryonic mouse tissues and is upregulated in B35 neu- roblastoma cells stimulated to undergo neurite outgrowth. We found that RNF13 is very labile, being subject to extensive proteolysis that releases both the protein-associated domain and the RING domain from the mem- brane. By analyzing microsomes, we showed that the ectodomain is shed into the lumen of vesicles, whereas the C-terminal half, which possesses the RING finger, is released to the cytoplasm. This C-terminal fragment of RNF13 has the ability to mediate ubiquitination. Proteolytic release of RNF13 from a membrane anchor thus provides unique spatial and tempo- ral regulation that has not been previously described for an endosomal E3 ubiquitin ligase. Abbreviations APP, Alzheimer’s precursor protein; AtRMR1, Arabidopsis thaliana receptor homology region-transmembrane domain-RING-H2 motif protein; CHO, Chinese hamster ovary; C-RZF, chicken RING zinc finger; CTF, cytoplasmic C-terminal fragment; EEA1, early endosomal antigen 1; ER, endoplasmic reticulum; GRAIL, gene related to anergy in leukocytes; HA, hemagglutinin; HAF, hemagglutinin and 3· FLAG epitopes; HRP, horseradish peroxidase; ICD, intracellular domain; LAMP2, lysosomal-associated membrane protein 2; MPR, mannose [...]... federal air quality standards that are even more stringent than the California standards Except for the standard on nitrogen dioxide, the federal standards are not to be exceeded more than once a year These standards must be attained within three years of the date of final approval of the state plan, except that an extension of up to two years may be granted by the Administrator Thus, the South Coast Air... Air Basin is required to meet the new federal ambient air quality standards by 1975, except in the case of photochemical oxidants, for which the EPA granted a two-year extension If the state agencies do not prepare a satisfactory implementation plan, the Act empowers the Administrator of EPA to develop such a plan, and if ~~~~~~~~~~~~~~~~~ broad authority to the Administrator Even if the Administrator... is an exacting federal statute which requires every state to develop an adequate air pollution abatement plan by 30 January, 1972 The plan must provide for the implementation, enforcement and maintenance of national ambient air quality standards promulgated by the Administrator of the EPA (Table 2) These air quality standards must be attained within three years of the date of approval of such plan... "management standards," based on technical, economic and social feasibility, that would serve as milestones enroute to the clean air required by both the California and federal ambient air quality standards These management standards would set a first "target date," by which time significant percentage reductions are to be achieved in the number of days per year that ambient air quality standards are... (as amended) appears to give the Administrator of the EPA discretionary authority to approve such an approach by a state during the period in which a time extension is in effect Such extensions can be granted when (among other reasons) the necessary technology is unavailable; when the state has implemented reasonable alternatives (as would be the case if a strategy similar to EQL Strategy # 1 were adopted);... Environmental Protection Agency (EPA) in February, 1972 'California State ambient air quality standard '''Health Warning" level recommended by Los Angeles County Medical Association for persons with coronary artery diseases or chronic respiratory diseases 6 Recommended Ambient Air Quality Standards Applicable to All Air Basins, a report to the California Air Resources Board by the Technical Advisory... social and economic incentives, modes of transportation and patterns of land use and development in an attempt to formulate a long-range strategy LESTER LEES Director, Environmental Quality Laboratory Pasadena, California June 15, 1972 12 SMOG A REPORT TO THE [...]... have them believe in our truss; but, by being so suspicious, they lose far more than we; they lose the chance to get better, and probably the chance to get well We sometimes speak of the Cluthe Truss as the Cluthe Automatic Massager; both names are necessary if we would do our truss full justice But we have decided never to give up the word truss; in spite of the fact that its use makes it harder to. .. probably disarm much of the suspicion many people have against the word truss But we don't want to adopt any subterfuges And there are now so many people wearing Cluthe Automatic Massaging Trusses, or who have worn them until cured, that simply by one man recommending the Cluthe Truss to another the prejudice against the word truss is bound to be overcome in time ... the chance to get farther along; robbed them of money they might have made For no man can be at his best in any capacity if his rupture is bothering him the drain on the strength is too great It has interfered with the pleasures of thousands Deprived them of recreation, kept them from taking part in athletics, kept them from getting proper exercise because they have known of no way to escape the danger... to get people to believe our advertisements We don't want to fly under false colors We don't want to do any of the things done by those who have worthless trusses to sell; those who have cheap contraptions which they call "appliances," "methods," etc., in order to deceive ruptured people If we were willing to call the Cluthe Truss by some other name, we would probably disarm much of the suspicion many... the one aim of his life That led, later on, to the founding of the Cluthe Rupture Institute And there are now five of us—father and four sons For as we sons grew up, we were trained in our father's work in the field of rupture; and have become Members of the Institute We four sons have all had the benefit of our father's forty years of experience And the youngest of us has now had seventeen years of... article of some other kind— like clothing or shoes—they don't condemn everything similar This fear of anything called a truss has kept lots of people from answering our advertisements; lots of people, because of disappointing experience with other trusses, won't even take the trouble to investigate; give themselves no chance to find out about the merits of the Cluthe Truss We would like to have these people... made the lives of many women a burden; made it hard for them to do their work or to enjoy social affairs; deprived many of them of the blessings of motherhood It has seized upon countless children; filled their days with suffering, robbed them of childhood's happiness But in spite of all that, when taken in time, rupture is no longer a hard thing to get rid of Not Hard To Get Rid Of So easy to overcome... has ruined the health of hundreds of thousands, simply because they couldn't find anything that would do any good Kept them from The getting much enjoyment out of life, sapped their strength Misery [...]... have them believe in our truss; but, by being so suspicious, they lose far more than we; they lose the chance to get better, and probably the chance to get well We sometimes speak of the Cluthe Truss as the Cluthe Automatic Massager; both names are necessary if we would do our truss full justice But we have decided never to give up the word truss; in spite of the fact that its use makes it harder to. .. probably disarm much of the suspicion many people have against the word truss But we don't want to adopt any subterfuges And there are now so many people wearing Cluthe Automatic Massaging Trusses, or who have worn them until cured, that simply by one man recommending the Cluthe Truss to another the prejudice against the word truss is bound to be overcome in time ... the chance to get farther along; robbed them of money they might have made For no man can be at his best in any capacity if his rupture is bothering him the drain on the strength is too great It has interfered with the pleasures of thousands Deprived them of recreation, kept them from taking part in athletics, kept them from getting proper exercise because they have known of no way to escape the danger... to get people to believe our advertisements We don't want to fly under false colors We don't want to do any of the things done by those who have worthless trusses to sell; those who have cheap contraptions which they call "appliances," "methods," etc., in order to deceive ruptured people If we were willing to call the Cluthe Truss by some other name, we would probably disarm much of the suspicion many... the one aim of his life That led, later on, to the founding of the Cluthe Rupture Institute And there are now five of us—father and four sons For as we sons grew up, we were trained in our father's work in the field of rupture; and have become Members of the Institute We four sons have all had the benefit of our father's forty years of experience And the youngest of us has now had seventeen years of... article of some other kind— like clothing or shoes—they don't condemn everything similar This fear of anything called a truss has kept lots of people from answering our advertisements; lots of people, because of disappointing experience with other trusses, won't even take the trouble to investigate; give themselves no chance to find out about the merits of the Cluthe Truss We would like to have these people... made the lives of many women a burden; made it hard for them to do their work or to enjoy social affairs; deprived many of them of the blessings of motherhood It has seized upon countless children; filled their days with suffering, robbed them of childhood's happiness But in spite of all that, when taken in time, rupture is no longer a hard thing to get rid of Not Hard To Get Rid Of So easy to overcome... has ruined the health of hundreds of thousands, simply because they couldn't find anything that would do any good Kept them from The getting much enjoyment out of life, sapped their strength Misery .. .Pay attention to the metaphors by which you create your perception of reality and I wasn’t really drowning – it was a word picture Then it occurred to me that I could just... time I sank beneath the waves it felt like a giant palm came up from the deeps and lifted me up to catch my breath Exact same circumstance, but the metaphor I chose to tell the story would give it