At R.L. Voight & Son, LLC, we offer a full range of general plumbing, gas piping and hot water heating services. Whether you're dealing with an emergency, tackling a small repair job or building a new home, we can help you with all your plumbing, gas, and hot water heating needs.
We guarantee your satisfaction on every job.


text:
Q: Wrong content-type(old header sent) being received by server side I updated afnetwork to 2.0 due to 64 bit. I made a mistake at first using AFHTTPRequestSerializer, but the server side accept Json only. The wried thing was it works fine for me even I used AFHTTPRequestSerializer, so I didn't notice this problem and released the error app to public. Then I keep receiving user complain and somehow I rebuild my app on my device, and local server can catch my wrong content-type(application/x-www.form-urlencoded). After I updated the AFHTTPRequestSerializer to AFJSONRequestSerializer, it doesn't fix the problem, but the user still keep sending wrong content-type to server even they updated the app. New user has no problem, only happen on old user.
Is this related to cache problem?
Server Log:
10:22:53 AM] Mark 1 contentType is: application/x-www-form-urlencoded,      method is: POST  headers are: Connection=keep-alive&Content-Length=1880739&Content-Type=application%2fx-www-form-urlencoded&Accept=*%2f*&Accept-Encoding=gzip%2c+deflate&Accept-Language=en%3bq%3d1&Cookie=ASP.NET_SessionId%3dbby5dlk5afmsnqnoqpprvqpw&Host

10:04:56 AM]        contentType is: application/json,                       method is: POST header is: Connection=keep-alive&Content-Length=40352  4&Content-Type=application%2fjson        &Accept=*%2f*&Accept-Encoding=gzip%2c+deflate&Accept-Language=en%3bq%3d1&Cookie=ASP.NET_SessionId%3dcw3gdkg3sff1f0j50z2rnism&Host

my code is
 AFHTTPRequestOperationManager *manager = [AFHTTPRequestOperationManager manager];
manager.requestSerializer = [AFJSONRequestSerializer serializer];
manager.responseSerializer = [AFJSONResponseSerializer serializer];

AFHTTPRequestOperation *operation = [manager POST:_url parameters:requestParams success:^(AFHTTPRequestOperation *operation, id responseObject) {
    NSLog(@"operation success: %@\n %@", operation, responseObject);
    NSDictionary *decoded = [self processResponce:responseObject failureBlock:failureBlock];

                            if (!decoded) return;
                            BOOL containsError = [self checkErrorStatus:decoded failureBlock:failureBlock];
                            if (containsError) return;
                            successBlock(decoded[@"Data"]);

} failure:^(AFHTTPRequestOperation *operation, NSError *error) {
        failureBlock(FailureTypeUnknown, [error localizedDescription]);
}];

[operation setUploadProgressBlock:^(NSUInteger bytesWritten, long long totalBytesWritten, long long totalBytesExpectedToWrite) {
progressBlock(bytesWritten,totalBytesWritten,totalBytesExpectedToWrite);
}];

A: as per your response, please set your manager's content type as below
manager.responseSerializer.acceptableContentTypes = [NSSet setWithObject:@"application/json"];

redpajama_set_name: RedPajamaStackExchange


The Oil&Gas sector is a highly competitive market which demans high specialization and maximum flexibility.
The Oil & Gas sector is segmented into different development stages from exploration/extraction to transformation/distribution. With a very dynamic market and still more complex projects, key players are requested to be flexible, innovative to remain competitive.
complexity and challenging lead-time push all the stakeholders to get external support to keep flexibility and get the right expertise at the right moment.
KLB Group is able to support you all around the world at each development stages with the right expertise to allow you to keep focusing on your core business.
Furthermore, our market knowledge allows us to offer innovative and dedicated business models to fit your expectations.
KLB Group helps you to secure the availability of the right expertise, at the right moment, at the right place, allowing you to win and successfully implement your Oil&Gas projects.
In addition, we can help you to improve project performance by implementing best practices in total life cycle cost optimization, interface management, and project risk and uncertainty management.
We have developed many projects in Engineering, Procurement and Construction, together with Management. providing high flexibility at each project stage, from front end design to decommissioning, everywhere, even in the most remote and toughest regions, at home & satellite offices, fabrication yards, shipyards, supplier sites, etc.
For each project, and to succeed in this demanding market, assembling the project dream team is the number one challenge.


text:
Kate! (talk | contribs)
(→Past State Champions)
(→Past State Champions: 2018)
|2017 || [[Auburn Jr. High School]] (51) || 32nd || [[J.F. Drake Middle School]] (100) || N/A || [[Auburn High School (Alabama)|Auburn High School]] (66) || 27th || [[Randolph School]] (104) || N/A
|2018 || [[Auburn Jr. High School]] (51) || TBD || [[ASFA]] (95) || N/A || [[Auburn High School (Alabama)|Auburn High School]] (46) || TBD || [[ASFA]] (99) || N/A
|2018 || [[Auburn Jr. High School]] (51) || TBD || [[Randolph School]] (95) || N/A || [[Auburn High School (Alabama)|Auburn High School]] (46) || TBD || [[Randolph School]] (99) || N/A
Division C Champion Auburn High School
3.1 Division B
3.2 Division C
Alabama teams have continually improved, in 2014 taking their first top ten finish at the national tournament (Auburn Jr. High School). In 2000, Alabama allowed home-schooled teams to compete for the first time. In 2007, nearly 4,000 students competed in all divisions (including A divisions) on over 200 teams.
Since 1999 the Division B state champion has always been a school from the city of Auburn. Primarily this has been Auburn Junior High School, although Samford Middle School (who was removed by redistricting after than 2001 season) and J.F. Drake Middle School (grades 6-7, feeder for Auburn Junior High School) have also won the tournament.
Division C has been less constant. Auburn High dominated until St. James, then took back their title for two more years before disbanding the SO team. LAMP won the following year, and then St. James took their title back for the next three years. For the next four or five years, the Division C spot was in a state of constant flux and was a tossup before Randolph established itself as the annual winner, undefeated for four years until Auburn High came back to beat them.
1997 Auburn Junior High School 50th
1998 Samford Middle School N/A
2009 Auburn Jr. High School 22nd Our Lady of the Valley School 39th Virgil Grissom High School 46th Randolph School N/A
2014 Auburn Jr. High School 10th J.F. Drake Middle School N/A Auburn High School 47th Randolph School N/A
2015 Auburn Jr. High School 18th (510) J.F. Drake Middle School N/A Auburn High School 30th (693) LAMP High School N/A
2016 Auburn Jr. High School 20th J.F. Drake Middle School N/A Auburn High School 34th Alabama School of Fine Arts N/A
2017 Auburn Jr. High School (51) 32nd J.F. Drake Middle School (100) N/A Auburn High School (66) 27th Randolph School (104) N/A
2018 Auburn Jr. High School (51) TBD Randolph School (95) N/A Auburn High School (46) TBD Randolph School (99) N/A
Auburn University, Auburn Regional - Saturday, March 1, 2014 (B)
Spring Hill College, Mobile Regional - Saturday, February 22, 2014 (B & C)
Auburn University - April 1, 2017 (B & C)
http://www.auburn.edu/cosam/departments/outreach/programs/Science%20Olympiad/
East Samford School
Excalibur Christian School
Alabama School of Fine Arts

redpajama_set_name: RedPajamaCommonCrawl


text:
Changes in behavior as side effects in methylphenidate treatment: review of the literature
Authors Konrad-Bindl DS, Gresser U, Richartz BM
Received 3 June 2016
Accepted for publication 24 August 2016
Published 12 October 2016 Volume 2016:12 Pages 2635—2647
Editor who approved publication: Dr Roger Pinder
Doris Susanne Konrad-Bindl,1 Ursula Gresser,1 Barbara Maria Richartz2
1Department of Internal Medicine, University of Munich, Munich, 2Clinic der Jägerwinkel, Bad Wiessee, Germany
Background: Our review of the scientific literature focused on an analysis of studies describing instances of methylphenidate treatment leading (or not) to behavioral changes in the pediatric, adolescent, and adult populations.
Materials and methods: We conducted a literature search in PubMed, Medline, and Google using the keywords "methylphenidate", "behavioral changes", "adverse effects", and "side effects". A total of 44 studies were identified as reporting on the effects and adverse effects of methylphenidate administration, and were included in the analysis.
Results: Five studies specifically set out to study, record, and discuss changes in behavior. Eight studies did not set out to study behavioral effects, but record and discuss them. A total of 28 studies recorded behavioral effects, but failed to discuss these further. Three studies did not include behavioral effects.
Conclusion: This review records what data have been published in respect of changes in behavior in association with the use of methylphenidate. While there is some evidence to suggest that methylphenidate causes changes in behavior, the majority of the studies reviewed paid little or no attention to this issue. Based on the available data, it is impossible to determine the point at which such behavioral effects occur. The frequency of occurrence of behavioral effects is also impossible to determine with certainty. Based on the available data, it is not possible to rule out whether behavioral effects may persist or not persist once treatment is discontinued. In conclusion, despite countless publications and extensive administration, especially to children, we have insufficient data to judge the long-term effects and risks of methylphenidate taking.
Keywords: methylphenidate, changes in behavior, attention-deficit/hyperactivity disorder, children, adults, adverse effects
Methylphenidate is used primarily in the treatment of children, adolescents, and adults with attention-deficit/hyperactivity disorder (ADHD). Furthermore, it is used in the treatment of narcolepsy, major depression disorder, and in patients with terminal cancer. Methylphenidate is usually prescribed for oral or transdermal use. As methylphenidate increases the ability to concentrate, it is sometimes used to enhance cognitive ability. In the treatment of ADHD, the aim of methylphenidate is to help to improve ADHD symptoms, such as difficulty paying attention or being hyperactive or impulsive. In 2012, Britton stated that until 2011, not a single study had been published on the long-term effects of treatment with methylphenidate.1 Since then, preclinical research has identified possible changes in brain structure and function, which suggest that "early pharmacotherapy can produce neuroadaptations that can persist long after drug treatment has ended".1
In rats, exposure to methylphenidate during preadolescence has been shown to lead to behavioral changes, such as increased depressive symptoms, as well as a reduction in the ability to adapt to a familiar environment.2 Adult rats treated with methylphenidate during adolescence were shown to be less responsive to positive stimuli (such as a novel environment or sex) and more susceptible to stressful situations.3 Bolaños et al stated that:
[our] findings show that developmental administration of MPH [methylphenidate] results in aberrant behavioral adaptations during adulthood, and these results underscore the need for further developmental research geared toward a better understanding of the mechanisms underlying MPH-induced behavioral plasticity.3
In a study of seven healthy adult humans, a dose of 0.25 mg/kg body weight or higher resulted in the inhibition of more than 50% of dopamine transporters.4 Long-term treatment with methylphenidate in humans led to significantly increased activity in the caudate and putamen regions. Wang et al suggested that the increased activity of dopamine transporters compensates for their pharmacological inhibition, resulting in increased inattention and the need for an increase in the dose administered.5 There are a plethora of studies investigating changes in brain structure and function, but the focus in this publication was on clinical studies.
In her review of studies investigating the neuropsychological effects of methylphenidate, Advokat concluded that the use of stimulant drugs, such as methylphenidate or amphetamine, leads to increased attention and concentration, but does not result in improved learning or academic achievements. The author explained that her review of more than 30 years of research involving children, adolescents, and students failed to show evidence of the desired effects in any of these age-groups. The author expressed concerns regarding the administration of stimulant drugs, such as methylphenidate, as these may lead to reduced impulsiveness, which in turn could result in impaired performance in cognitive tasks requiring flexibility and adaptability.6
In November 2015, a Cochrane review was published with the aim of assessing the beneficial and harmful effects of methylphenidate for children and adolescents with ADHD. The authors stated:
At the moment, the quality of the available evidence means that we cannot say for sure whether taking methylphenidate will improve the lives of children and adolescents with ADHD.7
Changes in behavior can be defined as gradual yet permanent changes affecting the defining features of an individual's personality without causing significant impairment in intellectual ability.8 For this study, we included the following symptoms as changes in behavior: abnormal behavior, accidental injury, agitation, aggression, anxiety, depression, depressed mood, disinterested in others, dizziness, drowsiness, emotional lability, euphoria, feeling jittery, irritability, mood alteration, nail biting, nervousness, nightmares, prone to crying, psychomotor hyperactivity, restlessness, sadness, staring, talks less, and tics. Methylphenidate can cause cardiovascular, abdominal, psychiatric, growth and development, and neurological side effects. For this study, the focus was on psychiatric symptoms. Methylphenidate targets the central nervous system by inhibiting the reuptake of dopamine.4,8–11 To a lesser extent, it also inhibits the reuptake of norepinephrine,9–11 and binds to the serotonin transporter, albeit with low affinity.9,11,12
Chemically speaking, methylphenidate belongs to the amphetamines.9 In 1981, it was included as part of the licensed prescription drugs listed in annex III of the newly amended German Narcotic Drugs Act (Betäubungsmittelgesetz). Amendments to the professional guidelines on the prescription of stimulant drugs (Arzneimittel-Richtline) made by the Federal Ministry of Health in 2010 meant that only "specialists in behavioral disorders of children and/or adolescents" would be allowed to prescribe stimulant drugs for use in the treatment of ADHD.13 Our review of the scientific literature focused on an analysis of studies describing instances of methylphenidate treatment leading (or not) to behavioral changes.
We conducted a literature search in PubMed, Medline, and Google using the keywords "methylphenidate", "behavioral changes", "adverse effects", and "side effects". A total of 44 studies were identified as reporting on the effects and adverse effects of methylphenidate administration, and were included in the analysis. In some studies, the results were divided among several publications. The publication period for articles was from 1990 until 2015. We did our last search on July 9, 2015. We included studies focusing on methylphenidate. We included studies with more medicines than methylphenidate if they were focusing on methylphenidate. We excluded studies with more medicines than methylphenidate if they were focusing on medicines other than methylphenidate. We excluded studies focusing only on physiological side effects like changes in blood pressure. Long-term effects of the drug were one of the main issues under consideration during the selection of studies. However, the current body of literature contains only a small number of articles on the long-term effects of methylphenidate. There was significant variation among the 44 studies reviewed, some of which were blind, others open-label. Some of the comparison groups received a placebo, while others received a different drug product. Some studies compared different forms of methylphenidate, while others compared methylphenidate at different doses.
Comparison was rendered more difficult by some of the studies involving small numbers of participants and being of limited duration: 57% of the studies lasted for less than 80 days, and patients in the shortest study14 received the drug for only 5 days. Despite its small size, Silva et al14 was judged to be of good quality, due to its randomized, double-blind, placebo-controlled, crossover trial design, and was included in the review.
Three of the studies had fewer than 30 participants. Bron et al,15 which involved 27 adult participants, was selected due to its good-quality study design, and the fact that participants had not previously been exposed to methylphenidate. Ghuman et al16 was selected due to the fact that it involved 27 very young participants (aged 3–5 years), which meant that methylphenidate was used off-label. All of the participants were methylphenidate-naïve, and treatment duration was relatively long compared to the other studies, lasting between 3 and 24 months. The study did not receive any funding, and in contrast to the other studies reviewed, did not include participants with concomitant psychiatric disorders. The smallest study selected was Maayan et al,17 which involved nine very young participants, all of whom were aged between 4 and 5 years and methylphenidate-naïve.
Some studies were included in the review despite the fact that they did not focus on side effects. One such example was Barbaresi et al,18 a retrospective cohort study, which followed participants from birth until the age of 17.2 years. While the authors described the long-term treatment with methylphenidate as effective, their conclusion was not based on the use of specific assessment tools. Assessment was by means of responses from participants and teachers, who were asked to rate the effect of treatment (positive effect, no effect, or not known). While the authors used their data to argue that long-term treatment with stimulant drugs had a positive effect, their data should be regarded as of questionable quality. Not only is it impossible to check whether the medication was administered at all, but questions regarding the effectiveness of treatment were too generic, and both students and teachers may have been overly positive in their responses.
Smith et al,19 who failed to provide any information on side effects, included results from as early as 1989. A longitudinal study conducted over 14 years, it is nonetheless worthy of mention, not only due to its sheer length but also because it showed no difference between participants receiving the drug and a comparison group from the general population. Analysis and discussion of results were modeled on Aagaard and Hansen.20 While the article by Aagaard and Hansen also included data on amphetamine, atomoxetine, and modafinil, we did not include any studies focusing on these medicines. The review by Aagaard and Hansen was published in 2011. From this paper, we included 14 studies in our review: Biederman et al,21 Arabgol et al,22 Maayan et al,17 Amiri et al,23 Findling et al,24 Newcorn et al,25 Greenhill et al,26 Gau et al,27 Silva et al,14 Kemner et al,28 Swanson et al,29 and Kratochvil et al.30 We identified and included an additional 29 studies: eleven of these included adult participants only, or participants between 4 and 65 years of age. Another ten, which involved children and adolescents, were published between 2011 and 2015. We also included an additional nine studies that had been published in 2010 or earlier. An overview of the studies is listed in Table 1.
Table 1 Overview of all 44 studies
Abbreviations: ES, extension study; G1, group 1; MPH, methylphenidate; NK, not known; SE, side effect; OL, open-label; P1, Phase I; P, placebo; Wd, withdrawal.
Studies included in the analysis differed in terms of study design, and included randomized parallel-group studies with a placebo arm (13),21–26,31–44 randomized crossover studies (ten),14,15,29,36,45–50 open-label studies (17),17,19,27,28,30,32,51–61 and retrospective studies (four).16,18,62,63
Thirteen of the studies required participants to be methylphenidate-naïve.15–17,19,23,40–42,44,45,47,53,59,60,64 In 19 of the studies, methylphenidate was discontinued between 1 and 30 days prior to the start of the study.14,22,24,25,28–33,44,48–51,61,65,66 Seven of the studies did not specify whether participants had had previous exposure to methylphenidate.18,27,34–39,46,52,57,62,63 Six of the studies included both methylphenidate-naïve participants and participants with prior exposure to methylphenidate.21,26,54–56,58
Funding arrangements
Nineteen of the studies were funded by pharmaceutical companies.18,21,24,25,27–29,31–33,44,49,51,54,56,58,61,65,66 Ten were funded using government or university funding.19,23,34–39,43,45,47,48,50,52,64 Four of the studies declared only conflict of interest,15,17,26,40–42,64 Five were not in receipt of funding,16,22,53,57,62 while six failed to provide information on funding arrangements.14,30,46,59,60,63
Comparison group
In 21 of the studies, the comparison group received a placebo.14,15,21,24–26,29,32,33,40–42,44–46,48–51,54,61,64,65 One of the studies compared methylphenidate with modafinil,23 four of the studies compared it with atomoxetine,25,28,30,57 one with reboxetine,22 three with dexamphetamine,47,52,64 and one with venlafaxine.43 Five of the studies compared different forms of methylphenidate,24,27,29,49,66 while four compared methylphenidate at different doses.33,40–42,46,50 Ten of the studies did not include a comparison group.16–18,31,53,56,58–60,62
Study duration
Seven of the studies were conducted over a period of between 11 and 21 days,14,24,28,29,48,49,59 five lasted for between 22 and 40 days,17,27,46,47,50 12 lasted for between 41 and 80 days,15,22,23,26,30,43,45,56,57,61,64,66 and 20 for more than 80 days.16,18,19,21,25,31–42,44,51–54,58,60,62,63,65
In ten of the studies, participants were adults aged between 18 and 65 years.15,31–33,45,51–55,65 Of the 2,783 participants included in these studies, 1,498 were males. In 33 of the studies, participants were aged between 3 and 17 years. Of the 6,620 included in these studies, 3,678 were males. Three of the studies did not provide any information on sex distribution among participants.34–39,48,63 In one of the studies, 590 of the 730 participants aged between 4 and 65 years were males.62
Size of studies
Three of the studies had fewer than 30 participants,15–17 16 had between 31 and 100 participants,14,22,23,26,27,43,45,46,49,50,57,59,60,61,63,64 18 between 101 and 500 participants,18,19,21,24,29,30,32,33,40–42,44,47,48,51–53,58,65,66 while seven had more than 500 participants.25,28,31,34–39,54,56,62
Rates of withdrawal due to side effects
Among the studies reviewed, withdrawal rates due to side effects were found to be between 0 and 27%. Eight of the studies had a zero withdrawal rate14,23,26,27,29,45,49,60 (one of these recorded an early withdrawal by one participant allocated to the placebo group).14 Seven of the studies did not provide information on either the number of withdrawals or withdrawal rate due to side effects.18,19,48,50,58,62,63
Classification of side effects
Of the studies, 27 did not provide information on the methods or definitions employed in the reporting of side effects. In one of the studies, side effects were reported if experienced by at least 1% of participants,28 in four studies the cutoff was at least 2% of participants,26,29,32,49 in one study at least 3% of participants,24 in seven studies at least 5%,25,30,33,44,54,55,61,65 and in two studies at least 10%.31,66 Two of the studies recorded the most commonly observed side effects only.51,40–42
Frequency of side effects
Frequency of side effects varied enormously between studies. In Haertling et al, 13.7% of participants reported experiencing side effects.58 In Khajehpiri et al, the figure was 100%.60 Sixteen studies failed to provide this information.17,19,23,27,29,30,40–44,47,49,50,59,63
Behavioral changes
Side effects associated with changes in behavior are listed in Table 2. Five studies specifically addressed the issue of behavioral changes, and duly recorded and described these.40–42,51,59,63,64 Cherland and Fitzpatrick focused on the psychotic side effects of methylphenidate.63 The other studies addressed behavioral changes in relation to the long-term safety of methylphenidate,51 its short-term side effects,63 its safety and tolerability,40–42 and its use in minimizing adverse events.64
Table 2 Overview of behavioral changes observed in persons treated with methylphenidate
Notes: *1) "most frequently recorded". *2) 5 (recorded in open-label), 4 (recorded in withdrawal); *3) 15 most frequently recorded adverse events.
The most frequently recorded symptoms were "irritability" (0%–80%), "prone to crying" (1%–71%), "staring" (21%–62%), "anxiety" (2%–61%), "sadness" (0%–56%), "nail biting" (22%–45%), "euphoria" (16%–43%), and "talks less" (27%–42%). Among studies with adult participants, the most commonly recorded symptoms were "drowsiness" (0%–32%) and "nervousness" (3%–23%).
Table 2 does not include individual cases of severe side effects. Casas et al33 and Huss et al54,55 mentioned one attempted suicide each. Fredriksen et al53 explained that the suicidal thoughts reported by one of the participants in their study were classed as not drug-induced, as they occurred several months after methylphenidate had been discontinued. Adler et al31 listed side effects reported by more than 10% of participants; 1.8% of their participants were reported as experiencing psychiatric symptoms, such as mania, aggression, and paranoia. Bejerot et al52 reported that three of their participants with concomitant psychiatric disorders developed such symptoms as hallucinations, agitation, and aggression, or seizures. Kemner et al28 reported that participants treated with methylphenidate developed severe side effects, such as mania, paranoia, crying/fear/aggression, and kicking the table. Symptoms ceased once treatment was discontinued.
Three studies mentioned when the symptoms started. Adler et al51 reported that most of the symptoms occurred within the first month of therapy. In Adler et al,31 82.4% of symptoms were reported during the first 30 days. Arabgol et al reported that the symptoms occurred 1–2 weeks after the medication was started.22 None of the studies provided information on when the side effects started exactly, except Robb et al, who reported two severe side effects: one at 18 days, and one at 9 days.61 Biederman et al stated that the same side effects were reported in treatment and in placebo washout.21 Three studies failed to offer any information about the time the symptoms occurred.19,24,34–39
Are the reported side effects reversible?
Most of the studies failed to provide information on whether side effects persisted following discontinuation of the drug. In seven of the studies, patients were followed up after the end of the medication.18,19,25,33–42 However, none of these allowed conclusions to be drawn regarding the reversibility of reported side. Cherland and Fitzpatrick were vague in this respect, stating simply that "most" participants improved following withdrawal of the medication.63 Adler et al describes the symptoms experienced by some of the participants as reversible.31 In three of the studies, all reported side effects disappeared following withdrawal of the medication.17,46,47 Two of the studies report that the side effects persisted until the end of the study.56,58
Study design and selection of studies
Does methylphenidate cause changes in behavior? Current prescribing practices mean that many patients start taking methylphenidate as children and continue treatment until they reach adulthood. Five of the studies selected specifically recorded and discussed changes in behavior.31,40–42,59,63,64 Unfortunately, these studies cannot be compared in terms of quality (Table 3).
Table 3 Studies that recorded and discussed changes in behavior
Notes: For Adler et al, changes in behavior were mentioned in the article, but are not shown in the tables.31 For Cherland and Fitzpatrick, it was impossible to determine with certainty whether the behavioral changes observed were reversible.63 The Karabekiroglu et al study was specifically designed to study short-term effects.59 Subjects in the PATS group studies used methylphenidate off-label because of their age.40–42 In Ramtvedt et al, methylphenidate treatment was limited to 2 weeks.64
In 29 of the studies, participants withdrew early because of side effects. Withdrawal rates ranged from 0 to 27%, and six of the studies failed to provide this information at all. Three of the studies27,29,49 – two with a partial focus on the safety of methylphenidate27,29 – stipulated that participants had to be receiving a stable dose of methylphenidate prior to entry into the study. All three reported zero withdrawal rates. Inclusion criteria for 13 of the studies stipulated that participants had to be methylphenidate-naïve. Three of these23,45,60 reported zero withdrawal rates, while one19 failed to report this information. Maayan et al recorded the highest withdrawal rate – 27%.17 However, the study's eleven participants did not constitute a representative sample. For studies that included only methylphenidate-naïve participants, the mean withdrawal rate was 6.7%. Studies that included only participants able to tolerate methylphenidate or that did not establish whether participants had prior exposure to the drug recorded a mean withdrawal rate of 7.4%. The reviewed data would thus suggest that there is no link between prior exposure to methylphenidate and early withdrawal due to side effects.
Changes in behavior
The occurrence of recorded changes in behavior differ widely. The symptom "irritability" was recorded by no subjects14 to 80% of subjects.47 In every case of the most frequently recorded symptoms, Efron et al recorded the highest percentages: "prone to crying" (71%), "staring" (62%), "anxiety" (61%), "sadness" (56%), "nail biting" (45%), "euphoria" (43%), and "talks less" (42%).47
Occurrence of side effects
While Khajehpiri et al reported side effects for all their participants,60 Haertling et al reported the lowest rate of occurrence of side effects (13.7%).58 Studies with methylphenidate-naïve participants reported side effects in 67.7% of participants. Studies that did not require participants to be methylphenidate-naïve or required them to be able to tolerate methylphenidate recorded a side effect rate of 57.7%. What was the reason for the low rate of occurrence reported in Haertling et al?58 The study was similar to the other studies in terms of age distribution and number of participants. Nineteen percent of participants received methylphenidate for the first time. The remaining participants were already using methylphenidate, but in a different form. The study was funded by the pharmaceutical industry. If both the comparability of studies and the evaluation of side effects are to be improved, future studies will need to exclude participants with prior exposure to methylphenidate.
Barkley et al posited that any behavioral changes observed during their study had to be linked to the condition under study.46 They supported this assertion by stating that the same symptoms occurred during initial testing and during the placebo phase of the trial, and that the physiological effects of methylphenidate disappeared within 24 hours of administration. The authors' assertion should be treated with caution. Participants were aged between 5 and 13 years. Inclusion criteria stipulated that participants had to have developed ADHD symptoms before the age of 7 years. While no such information was provided in the article, it must be assumed that some of the participants would have been receiving drug-based treatment for a number of years prior to enrollment. The assertion that side effects cease completely 24 hours after administration directly contradicts results from animal studies, which suggest that exposure leads to structural changes inside the brain, as well as clear changes in behaviors displayed by adult rats.2,3
Study funding and its impact on results
Some of the articles mentioned relevant results, but failed to discuss these further. Adler et al mentioned specifically instructing participants to report psychotic side effects, and that participants reported mania, aggression, and paranoia.51 However, during their presentation of results, the authors introduced the rule that only "symptoms occurring in at least 10% of participants" were to be classed as side effects. As psychiatric side effects only occurred in 1.8% of participants, these were not discussed any further. The study was conducted in conjunction with the pharmaceutical industry. The study's first author declared a conflict of interest. Casas et al reported that one participant attempted to commit suicide, but failed to provide any further details.33 It is impossible to establish whether side effects occurred during the washout period. The authors merely observed that no more than three participants from each arm of the study reported any side effects in the week between outcome measurements and follow-up visit. This rather vague statement leaves room for speculation. The study was funded by the pharmaceutical industry.
Are reported side effects reversible once administration is discontinued? Only a few of the details provided in the studies can be verified. Even studies aimed at testing the safety of methylphenidate did not provide information on the cessation of side effects. Both Döpfner et al and Haertling et al reported side effects as not reversible until the end of the study.56,58 Only Barkley et al and Efron et al provided clear information in support of the statement that side effects were completely reversible.46,47 The other studies failed to provide information on this issue.
Lack of data
With the exception of the studies mentioned earlier, none of the studies discussed the issue of behavioral change. While many of the articles listed instances of behavioral change, the tables provided only listed side effects reported by a certain percentage of respondents (up to 10%). This of course raises the question of how many examples of behavioral change remain undetected among studies that only list side effects above a certain minimum frequency. Whether behavioral side effects are particularly common is of no real relevance. The fact that there is a real risk of such side effects developing should be reason enough to instill a sense of caution when prescribing methylphenidate. What is more, data from the reviewed studies do not rule out the possibility that the observed side effects may be irreversible. The MTA study may be able to provide some indirect answers.34–39 When compared with children from the control group, children enrolled in the MTA study were ten times more likely to be admitted to psychiatric institutions.
With the exception of Cherland and Fitzpatrick, which was retrospective in design, none of the studies set out specifically and exclusively to study changes in behavior.63 What is more, most of the studies were too short to allow inferences to be made regarding the drug's long-term effects. As the majority of the studies did not include follow-up examinations, it is impossible to determine whether behavioral symptoms were reversible.
It would therefore be desirable if future studies were to meet the required quality criteria as determined by study design (multicenter, randomized, double-blind, placebo-controlled), and if they were designed to ensure a study duration long enough to permit the study of long-term effects. It would also be desirable if future studies were to include a follow-up phase, as this would allow conclusions to be drawn regarding the reversibility or irreversibility of behavioral effects. In terms of inclusion criteria, it would be desirable if studies were to be limited to participants not previously exposed to methylphenidate. This would allow potential side effects to be evaluated with regard to both frequency and severity. Future studies should set out to study changes in behavior or at the very least side effects in general. The use of assessment tools would improve comparability between studies by allowing side effects to be both recorded and evaluated. Funding by pharmaceutical companies should always be treated with caution.
The question of whether methylphenidate treatment is associated with behavioral effects remains to be fully elucidated. What is clear, however, is that children and adolescents continue to be treated with substances regulated by the Narcotics Drug Act, and that they are often exposed to these drugs for many years, and at a time when their brains are still growing and therefore vulnerable. The fact that the long-term safety of these drugs remains to be fully elucidated means that there is an urgent need for further research. In April 2016, Inglis et al published the study protocol of the ADDUCE study, a prospective observational study to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD, funded by the European Commission. Hopefully, this study can offer some security for the further use of methylphenidate.67
In Germany, the use of methylphenidate is regulated by the Narcotic Drugs Act (Betäubungsmittelgesetz). Among other disorders, methylphenidate is used in the treatment of children and adolescents with ADHD. Since 2011, the drug has been licensed for use in adults with ADHD.
The fact that methylphenidate is often used over many years raises the following questions. Does methylphenidate lead to changes in behavior either during or after treatment? At what point do changes in behavior occur? Has there been sufficient research into the side effects of treatment with methylphenidate, and does this research include the period after treatment is discontinued?
An analysis of the articles included in the list of references provides the following answers. Seven studies specifically set out to study, record, and discuss changes in behavior.31,40–42,59,63,64 Eight studies did not set out to study behavioral effects, but recorded and discussed them.16,32,45,46,48,50,52,61 A total of 28 studies recorded behavioral effects, but failed to discuss these further.14,15,17,19,21–30,32–39,44,47,49,51,53–58,60,66 Three studies did not include behavioral effects.18,43,62
Findings from our review of the selected studies can be summarized as follows. While there is some evidence to suggest that methylphenidate causes changes in behavior, the majority of the studies reviewed paid little or no attention to this issue. Based on the available data, it is impossible to determine the point at which such behavioral effects occur. The frequency of occurrence of behavioral effects is also impossible to determine with certainty. Based on the available data, it is not possible to rule out whether behavioral effects may persist or not persist once treatment is discontinued.
There is a relative dearth of studies dealing with the long-term outcomes of methylphenidate treatment and the issue of posttreatment follow-up. As a result, this literature review was unable to establish a good safety profile for the drug. Further studies are needed, which in order to provide meaningful data will need to meet certain quality criteria. Aside from being randomized, placebo-controlled, and double-blind multicenter studies, they will need to include a sufficient number of participants. They will also need to be of sufficient duration to allow conclusions regarding the long-term effects of methylphenidate. Participants should be methylphenidate-naïve. A follow-up phase must be included if the reversibility of behavioral effects is to be studied. In conclusion, despite countless publications and extensive administration, especially to children, we have insufficient data to judge the long-term effects and risks of taking methylphenidate.
This paper contains results from a thesis by Doris S Konrad-Bindl – "Führt Methylphenidat zu Wesensänderungen? Eine Literaturstudie" – submitted to the Faculty of Medicine of Ludwig-Maximilians-Universität München in fulfillment of the requirement for a medicine degree.
Britton GB. Cognitive and emotional behavioral changes associated with methylphenidate treatment: a review of preclinical studies. Int J Neuropsychopharmacol. 2012;15(1):41–53.
Carlezon WA, Mague SD, Andersen SL. Enduring behavioral effects of early exposure to methylphenidate in rats. Biol Psychiatry. 2003;54(12):1330–1337.
Bolaños CA, Barrot M, Berton O, Wallace-Black D, Nestler EJ. Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood. Biol Psychiatry. 2003;54(12):1317–1329.
Volkow ND, Wang GJ, Fowler JS, et al. Dopamine transporter occupancies in the human brain induced by therapeutic doses of oral methylphenidate. Am J Psychiatry. 1998;155(10):1325–1331.
Wang GJ, Volkow ND, Wigal T, et al. Long-term stimulant treatment affects brain dopamine transporter level in patients with attention deficit hyperactive disorder. PLoS One. 2013;8(5):1–6.
Advokat C. What are the cognitive effects of stimulant medications? Emphasis on adults with attention-deficit/hyperactivity disorder (ADHD). Neurosci Biobehav Rev. 2010;34(8):1256–1266.
Storebø OJ, Ramstad E, Krogh HB, et al. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev. 2015;(11):CD009885.
Reiche D. Roche Lexikon Medizin [Medical Encyclopedia]. 4th ed. Munich: Urban & Fischer; 2003.
Challman T, Lipsky JJ. Methylphenidate: its pharmacology and uses. Mayo Clin Proc. 2000;75(7):711–721.
Kuczenski R, Segal D. Effects of methylphenidate on extracellular dopamine, serotonin, and norepinephrine: comparison with amphetamine. J Neurochem. 1997;68(5):2032–2037.
Gatley SJ, Pan D, Chen R, Chaturvedi G, Ding YS. Affinities of methylphenidate derivatives for dopamine, norepinephrine and serotonin transporters. Life Sci. 1996;58(12):231–239.
Gray JD, Punsoni M, Tabori NE, et al. Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress. J Neurosci. 2007;27(27):7196–7207.
Germany Federal Ministry of Health. Bekanntmachung eines Beschlusses des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie [Declaration of a resolution of the Federal Joint Committee about a modification of the guideline for medicine]. Berlin: Bundesministerium für Gesundheit; 2010.
Silva RR, Muniz R, Pestreich L, et al. Efficacy and duration of effect of extended-release dexmethylphenidate versus placebo in schoolchildren with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol. 2006;16(3):239–251.
Bron TI, Bijlenga D, Boonstra AM, et al. OROS-methylphenidate efficacy on specific executive functioning deficits in adults with ADHD: a randomized, placebo-controlled cross-over study. Eur Neuropsychopharmacol. 2014;24(4):519–528.
Ghuman JK, Ginsburg GS, Subramaniam G, Human HS, Kau AS, Riddle MA. Psychostimulants in preschool children with attention-deficit/hyperactivity disorder: clinical evidence from a developmental disorders institution. J Am Acad Child Adolesc Psychiatry. 2001;40(5):516–524.
Maayan L, Paykina N, Fried J, Strauss T, Gugga SS, Greenhill L. The open-label treatment of attention-deficit/hyperactivity disorder in 4- and 5-year-old children with beaded methylphenidate. J Child Adolesc Psychopharmacol. 2009;19(2):147–153.
Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Leibson CL, Jacobsen SJ. Long-term stimulant medication treatment of attention-deficit/hyperactivity disorder: results from a population-based study. J Dev Behav Pediatr. 2006;27(1):1–10.
Smith G, Jongeling B, Hartmann P. Raine ADHD Study: Long-Term Outcomes Associated with Stimulant Medication in the Treatment of ADHD in Children. Perth: Government of Western Australia Department of Health; 2010.
Aagaard L, Hansen EH. The occurrence of adverse drug reactions reported for attention deficit hyperactivity disorder (ADHD) medications in the pediatric population: a qualitative review of empirical studies. Neuropsychiatr Dis Treat. 2011;7:729–744.
Biederman J, Quinn D, Weiss M, et al. Efficacy and safety of Ritalin LA, a new, once daily, extended-release dosage form of methylphenidate, in children with attention deficit hyperactivity disorder. Paediatr Drugs. 2003;5(12):833–841.
Arabgol F, Panaghi L, Hebrani P. Reboxetine versus methylphenidate in treatment of children and adolescents with attention deficit-hyperactivity disorder. Eur Child Adolesc Psychiatry. 2009;18(1):53–59.
Amiri S, Mohammadi MR, Mohammadi M, Neuroozinejad GH, Kahbazi M, Akhondzadeh S. Modafinil as a treatment for attention-deficit/hyperactivity disorder in children and adolescents: a double blind, randomized clinical trial. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(1):145–149.
Findling RL, Quinn D, Hatch SJ, Cameron SJ, DeCory HH, McDowell M. Comparison of the clinical efficacy of twice-daily Ritalin and once-daily Equasym XL with placebo in children with attention deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. 2006; 15(8):450–459.
Newcorn JH, Kratochvil CJ, Allen AJ. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: acute comparison and differential response. Am J Psychiatry. 2008;165(6):721–730.
Greenhill L, Muniz R, Ball RR, Levine A, Pestreich L, Jiang H. Efficacy and safety of dexmethylphenidate extended-release capsules in children with attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2006;45(7):817–823.
Gau SS, Shen HY, Soong WT, Gau CS. An open-label, randomized, active-controlled equivalent trial of osmotic release oral system methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Child Adolesc Psychopharmacol. 2006;16(4):441–455.
Kemner JE, Starr HL, Ciccone PE, Hooper-Wood CG, Crockett RS. Outcomes of OROS methylphenidate compared with atomoxetine in children with ADHD: a multicenter, randomized prospective study. Adv Ther. 2005;22(5):498–512.
Swanson JM, Wigal SB, Wigal T, et al. A comparison of once-daily extended-release methylphenidate formulations in children with attention-deficit/hyperactivity disorder in the laboratory school (the COMACS study). Pediatrics. 2004;113(3 Pt 1):e206–e216.
Kratochvil CJ, Heiligenstein JH, Dittmann R, et al. Atomoxetine and methylphenidate treatment in children with ADHD: a prospective, randomized, open-label trial. J Am Acad Child Adolesc Psychiatry. 2002;41(7):776–784.
Adler LA, Orman C, Starr HL, et al. Long-term safety of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder: an open-label, dose-titration, 1-year study. J Clin Psychopharmacol. 2011;31(1):108–114.
Buitelaar JK, Ramos-Quiroga A, Casas M, et al. Safety and tolerability of flexible dosages of prolonged-release OROS methylphenidate in adults with attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2009;5:457–466.
Casas M, Rösler M, Kooij JJ, et al. Efficacy and safety of prolonged-release OROS methylphenidate in adults with attention deficit/hyperactivity disorder: a 13-week, randomized, double-blind, placebo-controlled, fixed-dose study. World J Biol Psychiatry. 2013;14(4): 268–281.
The MTA Cooperative Group. A 14-month randomized clinical trial of treatment strategies for attention-deficit/hyperactivity disorder. Arch Gen Psychiatry. 1999;56(12):1073–1086.
Arnold LE, Howard BA, Cantwell DP, et al. National Institute of Mental Health collaborative multimodal treatment study of children with ADHD (the MTA). Arch Gen Psychiatry. 1997;54(9):865–870.
MTA Cooperative Group. National Institute of Mental Health multimodal treatment study of ADHD follow-up: 24-month outcomes of treatment strategies for attention-deficit/hyperactivity disorder. Pediatrics. 2004;113(4):754–761.
MTA Cooperative Group. National Institute of Mental Health multimodal treatment study of ADHD follow-up: changes in effectiveness and growth after the end of treatment. Pediatrics. 2004;113(4):762–769.
Jensen PS, Arnold LE, Swanson JM, et al. 3-Year follow-up of the NIMH MTA study. J Am Acad Child Adolesc Psychiatry. 2007;6(8):989–1002.
Molina BS, Hinshaw SP, Swanson JM, et al. The MTA at 8 years: prospective follow-up of children treated for combined type ADHD in a multisite study. J Am Acad Child Adolesc Psychiatry. 2009;48(5):484–500.
Greenhill L, Kollins S, Abikoff H, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry. 2006;45(11):1284–1293.
Wigal T, Greenhill L, Chuang S, et al. Safety and tolerability of methylphenidate in preschool children with ADHD. J Am Acad Child Adolesc Psychiatry. 2006;45(11):1294–1303.
Riddle MA, Yershova K, Lazzaretto D, et al. The Preschool Attention-Deficit/Hyperactivity Disorder Treatment Study (PATS) 6-year follow-up. J Am Acad Child Adolesc Psychiatry. 2013;52(3):264–278.
Zarinara AR, Mohammadi MR, Hazrati N, et al. Venlafaxine versus methylphenidate in pediatric outpatients with attention deficit hyperactivity disorder: a randomized, double-blind comparison trial. Hum Psychopharmacol. 2010;25(7–8):530–535.
Wigal SB, Nordbrock E, Adjei AL, Childress A, Kupper RJ, Greenhill L. Efficacy of methylphenidate hydrochloride extended-release capsules (Aptensio XR) in children and adolescents with attention-deficit/hyperactivity disorder: a phase III, randomized, double-blind study. CNS Drugs. 2015;29(4):331–340.
Kooij JJ, Burger H, Boonstra AM, Van der Linden PD, Kalma LE, Buitelaar JK. Efficacy and safety of methylphenidate in 45 adults with attention-deficit/hyperactivity disorder: a randomized placebo-controlled double-blind cross-over trial. Psychol Med. 2004;34(6):973–982.
Barkley RA, McMurray MB, Edelbrock CS, Robbins K. Side effects of methylphenidate in children with attention deficit hyperactivity disorder: a systemic-placebo-controlled evaluation. Pediatrics. 1990;86(2):184–192.
Efron D, Jarman F, Barker M. Side effects of methylphenidate and dexamphetamine in children with attention deficit hyperactivity disorder: a double-blind, crossover trial. Pediatrics. 1997;100(4):662–666.
Lee J, Grizenko N, Bhat V, Sengputa S, Polotskaia A, Joober R. Relation between therapeutic response and side effects induced by methylphenidate as observed by parents and teachers of children with ADHD. BMC Psychiatry. 2011;11:70.
Pelham WE, Gnagy EM, Burrows-Maclean L, et al. Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics. 2001;107(6):E105.
Stein MA, Sarampote CS, Waldman ID, et al. A dose-response study of OROS methylphenidate in children with attention-deficit/hyperactivity disorder. Pediatrics. 2003;112(5):e404–e413.
Adler LA, Spencer T, McGough JJ, Jiang H, Muniz R. Long-term effectiveness and safety of dexmethylphenidate extended-release capsules in adult ADHD. J Atten Disord. 2009;12(5):449–459.
Bejerot S, Rydén EM, Arlinde CM. Two-year outcome of treatment with central stimulant medication in adult attention-deficit/hyperactivity disorder: a prospective study. J Clin Psychiatry. 2010;71(12): 1590–1597.
Fredriksen M, Dahl AA, Martinsen EW, Klungsoyr O, Haavik J, Peleikis DE. Effectiveness of one-year pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD): an open-label prospective study of time in treatment, dose, side-effects and comorbidity. Eur Neuropsychopharmacol. 2014;24(12):1873–1884.
Huss M, Ginsberg Y, Tvedten T, et al. Methylphenidate hydrochloride modified-release in adults with attention deficit hyperactivity disorder: a randomized double-blind placebo-controlled trial. Adv Ther. 2014;31(1):44–65.
Huss M, Ginsberg Y, Arngrim T, et al. 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. Clin Drug Investig. 2014;34(9):639–649.
Döpfner M, Görtz-Dorten A, Breuer D, Rothenberger A. An observational study of once-daily modified release methylphenidate in ADHD: effectiveness on symptoms and impairment, and safety. Eur Child Adolesc Psychiatry. 2011;20(2):243–255.
Garg J, Arun P, Chavan BS. Comparative short term efficacy and tolerability of methylphenidate and atomoxetine in attention deficit hyperactivity disorder. Indian Pediatr. 2014;51(7):550–554.
Haertling F, Mueller B, Bilke-Hentsch O. Effectiveness and safety of a long-acting, once-daily, two-phase release formulation of methylphenidate (Ritalin LA) in school children under daily practice conditions. Atten Defic Hyperact Disord. 2015;7(2):157–164.
Karabekiroglu K, Yazgan YM, Dedeoglu C. Can we predict short-term side effects of methylphenidate immediate-release? Int J Psychiatry Clin Pract. 2008;12(1):48–54.
Khajehpiri Z, Mahmoudi-Gharaei J, Faghihi T, Karimzadeh I, Khalili H, Mohammadi M. Adverse reactions of methylphenidate in children with attention deficit-hyperactivity disorder: report from a referral center. J Res Pharm Pract. 2015;3(4):130–136.
Robb AS, Findling RL, Childress AC, Berry SA, Belden HW, Wigal SB. Efficacy, safety, and tolerability of a novel methylphenidate extended-release oral suspension (MEROS) in ADHD. J Atten Disord. Epub 2014 May 29.
Valdizán-Usón JR, Cánovas-Martínez A, De Lucas-Taracena MT, et al. A response to methylphenidate by adult and pediatric patients with attention-deficit/hyperactivity disorder: the Spanish multicenter DIHANA study. Neuropsychiatr Dis Treat. 2013;9:211–218.
Cherland E, Fitzpatrick R. Psychotic side effects of psychostimulants: a 5-year review. Can J Psychiatry. 1999;44(8):811–813.
Ramtvedt BE, Aabech HS, Sundet K. Minimizing adverse events while maintaining clinical improvement in a pediatric attention-deficit/hyperactivity disorder crossover trial with dextroamphetamine and methylphenidate. J Child Adolesc Psychopharmacol. 2014;24(3):130–139.
Buitelaar JK, Trott GE, Hofecker M, et al. Long-term efficacy and safety outcomes with OROS-MPH in adults with ADHD. Int J Neuropsychopharmacol. 2012;15(1):1–13.
Steele M, Weiss M, Swanson J, Wang J, Prinzo RS, Binder CE. A randomized, controlled, effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder. Can J Clin Pharmacol. 2006;13(1):e50–e62.
Inglis SK, Carucci S, Garas P, et al. Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) Study. BMJ Open. 2016;6(4):e010433.


O'reilly's - Irish whiskey, 70 cl.
Teeling - Single grain, 70 cl.
Teeling - Single malt, 70 cl.
Teeling - Small batch, 70 cl.
Redbreast - 15 års, 70 cl.
Redbreast 12 års, 70 cl.
Paddy - Irish whiskey, 70 cl.
Jameson - Master Selection, 18 års, 70 cl.


Crackpottery: BBC journalists told to stop interviewing science deniers.
BBC Journalists Told to Stop Giving Airtime to Crackpots. Finally.
Photo by Teach the Controversy T-shirts, which are fantastic.
In very welcome news, BBC journalists have been told to stop inviting crackpots on news shows in the name of balance.
Oh, I do so love this. It's precisely the right thing to do, sorely needed and sorely overdue. In this specific case, back in 2012 the BBC was criticized for news shows inviting on people with fringe views, especially when the science being discussed was solidly understood.
Obviously, the topic most abused in this way was the reality of global warming. That should come as no surprise to anyone who has been paying any attention at all.
But more broadly, most TV news shows do this, especially when they are done with a talk show format. It's all too easy for a news program or other venue with a biased ideological objective (cough cough Fox News cough Wall Street Journal cough) to bring on people who sound authoritative, but who are in fact simply cranks or contrarians with outlandish claims. This sort of bias sows doubt, which is far easier to do than to debunk it.
News shows don't put on a flat-earther whenever they show a map. They don't get an opposing opinion from a young-Earth creationist when a new dinosaur fossil is found. They don't interview an astrologer when a new exoplanet is discovered. So why put on a climate change denier when we're talking about our planet heating up?
As you (Energy & Environment Cabinet official) sit there in your chair with your data, we sit up here in ours with our data and our constituents and stuff behind us. I don't want to get into the debate about climate change, but I will simply point out that I think in academia we all agree that the temperature on Mars is exactly as it is here. Nobody will dispute that. Yet there are no coal mines on Mars. There are no factories on Mars that I'm aware of.
If your brain survived that onslaught, then I'll dispute that. The average temperature on Earth is very roughly 14° C (57°F). The average temperature of Mars is -55°C (-67° F). Not really "exactly the same".
Ironically, if Mars ever did have the same temperature as Earth, it would be due to global warming from the greenhouse effect. The atmosphere of the Red Planet is less than 1 percent as thick as Earth's, but it's mostly carbon dioxide. That gas raises the planet's temperature a few degrees. On Earth, given our distance from the Sun and other factors, the average temperature should hover around freezing. Thanks to greenhouse gases like CO2, it's far more clement … but since we're adding huge amounts of carbon dioxide to our air, it won't stay that way for much longer.
People would actually be a whole lot better off if those coal mines were on Mars.
Just as we'd be a whole lot better off if all our politicians acknowledged the reality of reality and our media kicked folks who think otherwise to the curb. I applaud the BBC for its stance (as well as the L. A. Times and other venues), and hope to see a lot, lot more of this in the near future.


text:
Invest in Open Infrastructure
# Charter of the Community Oversight Council [//]: <> (Source content to copy-and-paste into HackMD: [//]: <> https://docs.google.com/document/d/1iPuq4544AayywEfc10O0iC-QRcScagITu-c0l2-WVZo/edit) Status: Adopted Charter, last updated 2022-04-07. URL for this page: https://hackmd.io/@investinopen/COC-charter URL for this site: https://hackmd.io/@investinopen/how-we-work ## Council Description & Purpose The Invest in Open Infrastructure (IOI) Community Oversight Council (COC) was established to further transparency and accountability of open infrastructure services, providers, funders and supporters. The purpose of the COC is to surface themes, trends and issues in the open research and scholarship infrastructure sector and adjacent spaces, to provide a collaborative, safe forum for discussions, and to advise and inform IOI staff and Steering Committee on mechanisms to ensure that IOI's work is serving our community. The COC is an independent, non-voting governing body of IOI. ## Key responsibilities & Duties The following are activities of the COC designed to promote the fulfillment of its purposes as described in this Charter. These activities are set forth as a guide with the understanding that the COC may diverge from this guide as appropriate should the need arise. COC responsibilities may include the following: - Help surface developments in technology, policy changes and ethical concerns related to research and scholarship infrastructure - Hold safe, inclusive fora for practitioners in the broader sector (research & scholarship, librarianship, higher education) to discuss the implications of these developments and changes - Provide thoughtful, constructive reflection and insight on IOI's strategic vision and key research and engagement work Specific tasks: - Develop or review the COC's values and principles statement - Scope, develop and facilitate quarterly public community meetings - Support IOI staff in assessing and responding to changes in the sector (e.g. mergers, acquisitions, and policy changes) on an as-needed basis - Assist in the review and implementation of IOI's recommendations to open infrastructure funders, supporters, services, providers and users ## Council Membership & Structure The COC is composed of 5-6 Core Council members who are actively involved in discussions around tools and technologies and their implications as they relate to IOI's mission, vision and values. The COC is chaired by two Co-Chairs, who are Core Council members. Where possible, there should be a staggered overlap between the terms of Co-Chairs to ensure continuity in the COC's work. Core Council members' term of service is 1 year, with the possibility to renew for one term. ## Procedures ### Meetings The COC Core members will meet at a minimum, monthly. COC Core members should work with IOI's Engagement Lead to identify a suitable recurring meeting time. Additional meetings may be scheduled on an as-needed basis. The COC Core members are also responsible for scoping and facilitating quarterly public meetings to ensure an open dialogue with the open research community, adjacent sectors, and interested stakeholders in IOI's work. IOI's Engagement Lead will support the COC in scheduling and documenting these gatherings. ### Recruitment Community members can apply to become COC Core members via annual open calls. ### Communications A meeting agenda and all materials required to prepare for an upcoming COC Core members meeting will be provided at least a week in advance. COC can choose to invite IOI staff members to join a meeting when it is helpful, e.g. to answer questions about specific aspects of IOI's work. Following each meeting of the COC, a summary detailing decisions made and key topics discussed will be forwarded to COC Core Council members and IOI staff. Meeting summaries will be posted online on IOI's website as documentation. ### Periodic Review This charter, any additional governing documents, and the make-up of the Council will be reviewed at least annually to determine if any changes are needed to any aspects of the Council's structure, membership, or operating procedures. --- ## See also * Archived copy of this page (via the Internet Archive's Wayback Machine): https://web.archive.org/web/*/https://hackmd.io/@investinopen/COC-charter --- This page first published: 2022-04-06 ###### tags: `community-council` `governance` ---
This work is made available under a Creative Commons Attribution 4.0 International License. Users are free to share, remix, and adapt this work. (Please attribute [Invest in Open Infrastructure](https://investinopen.org/) in any derivative work).
IOI jargon
This page is under construction. :hammer_and_wrench: This page is meant to list and explain evolving terms, acronyms, and nicknames used by IOI staff in internal communications. Arcadia = Arcadia, a charitable fund of Lisbet Rausing and Peter Baldwin; one of IOI's philanthropic funders. B + O = Weekly business and operations meeting. Civi = CiviCRM, IOI's internal database for tracking contact information of collaborators and stakeholders.
[Internal] Invited review process
Last updated: 2023-01-30 URL for this page: https://hackmd.io/@investinopen/invited-review URL for this site: https://hackmd.io/@investinopen/how-we-work What is this? An internal process to faciltiate the invited review process for research outputs, including preliminary investigations, analytic memos, and other works. Not to be confused with the Reviewer guide, which is a complementary piece of documentation shared with reviewers with instructions and guidelines for reviewers participating in this reviewing process. Background
Last updated: 2023-01-30 URL for this page: https://hackmd.io/@investinopen/meetings URL for this site: https://hackmd.io/@investinopen/how-we-work Our team meets virtually online several times per week. We use synchronous face-to-face meetings to coordinate our individual and group tasks and projects, to plan ahead, to review our past work, and to discuss other relevant issues. Our online synchronous sessions supplement our asynchronous communication channels (Slack, Trello, Google Workspace, and email). Norms We strive to respect one another's time by
Trello guide
Last updated: 2023-01-30 URL for this page: https://hackmd.io/@investinopen/trello URL for this site: https://hackmd.io/@investinopen/how-we-work We use Trello to keep track of what we're currently working on, and to plan what we'll be working on in the near future. Internal access only. Purpose Coordinating + tracking tasks :dizzy: Planning complex tasks :boom: Ideating + brainstorming :bulb:
Read more from Invest in Open Infrastructure


There will likely be a lot of traffic congestion on the first day of school. Families are encouraged to avoid driving their student to school if possible (please have them walk or take public transportation if you can). There is very limited parking in the neighborhood surrounding the school, so if you must drive you should plan to park several blocks away.


Errors happen, and they are not always caused by the person who coded the application. Sometimes your application will generate an error because of an action that was initiated by the end user of your application or it might be simply due to the environmental context in which your code is running. In any case, you should anticipate errors occurring in your applications and code accordingly.
The .NET Framework has enhanced the ways in which you deal with errors. C#'s mechanism for handling error conditions allows you to provide custom handling for each type of error condition as well as to separate code that identifies errors from the code that handles them.
By the end of the chapter, you will have a good grasp on advanced exception handling in your C# applications.


The basic premise for the stochastic indicator is that the market tends to close higher in its range during a bull market, up move and lower during a bear market, down move.
The indicator is made up of two lines, generally posted below the bar chart. These lines are referred to as %K and %D lines and are calculated as shown below.
There are two types of stochastic, the fast stochastic indicator (calculations shown above) and the slow stochastic. The fast stochastic is extremely sensitive to price, while the slow stochastic is merely the result of smoothing the fast stochastic, using a moving average calculation.
Therefore the fast stochastic %K line is actually the %D line from the slow stochastic and the new %D line is a smoothed moving average of the faster stochastic, %D line. A three period moving average is most common.
The indicator is bound by the parameters of 0 and 100. Most charting packages will place a horizontal line at 20 and 80, which may reflect an oversold or overbought condition, respectively. Some packages will allow a little more and place these indicator lines at 25 and 75. It can be dangerous to use these indicator lines solely, as a trading signal, without more information to support it.
There are several ways one can use this indicator.
As a simple overbought / oversold oscillating index. In which case, a sell signal is generated when the stochastic rises above the 80 level and a buy signal generated when the indicator falls below 20.
Stochastic cross - when the fast moving line %K crosses above the slower moving %D line a buy signal is generated. There is even more credence to this signal if it occurs below the 20 level. Conversely when the fast moving line %K falls below the slow moving line %D, a sell signal is generated. Again this is a much better signal if it occurs above the 80 line.
Divergence - when price rises to new highs and the indicator fails to make new highs the market is said to be diverging. This produces a sell signal. Conversely if the market makes new lows in price, but the indicator fails to make a new low, then a buy signal may be generated.
The strongest signal occurs when we have all three patterns converging. That is when the stochastic crosses in the buy or sell zone above or below 80 or 20 respectively and we have divergence.
Something that should be pointed out is that a market that is topping will be closing at the upper extreme of the range and a market that is at a bottom will probably be closing at its lower extreme. This situation could exists for some time, which gives rise to a condition known as stochastic crawl an example of which can be seen in the chart example below.
In the example below the stochastic indicator first pushed above the 80 line in early March when price was trading around 9450. This condition remained while price moved higher to 9470. It wasn't until they finally crossed with a smidgen of divergence that the signal became valid and price fell away accordingly.


Discussion in 'Tech/Mech General' started by Suzy, Jul 29, 2007.
We don't have a spare wheel. I wonder where we would get one and how much such a thing would be. Then having got it where do you store it?
Hi Suzy I would imagine you have 22.5" wheels which is a standard lorry size so you might be able to get some rims from commercial garage, they would need to have the same offset, PCD for the studs and centre hole, failing that Linda at stateside would be a good bet.
No idea on the price £100 maybe?? As for location, mines in the bedroom slide locker, Shanes is in a carrier underneath. Scotjimland was talking about getting a carrier made up for his spare, so he could fit it underneath, I think he had a quote of over £200.
Thanks for the info, as you say ours are 22.5". Hopefully Linda will respond with price. The carrier slung underneath sounds a good solution but very expensive need to look around and see what we can do. I may ask Scotjimland if he had a drawing or something.
Not sure where you would get one in the UK. I believe that ScotJimLand shipped a wheel rim in from the US as the stud spacing and offset are quite different to those in Europe. You could quickly check with one of your Volvos?
The tyres will be easy as they are European sized and we have ours on a carrier underneath the rear, of course with yours being a "pusher", you cannot fit it in the same area so will need to find another location. Maybe in one of the belly lockers???
Mines in a locker and takes up a lot of space.
Interested in the under slung frame.
Still looking for a price for the spare wheel?
That looks cool, I need something that we can retrofit as there is no housing or spare wheel and I need one before we go to Morocco !!!! I think I can get he tyre its just a lorry tyre I think.
I could do with one taking off a damaged or old RV and fitting to mine, they must have lots of scrap yards in the US, how can I get one over here?
A spare wheel will not be cheap Suzy - Its the weight that kills it due to the shipping cost.
I shipped Jim's wheel for him, it was not easy to get hold of but I still have the contact somewhere in my archives.
Because we have a year to get it I was kinda hoping that someone who was shipping an RV over could put it in. I wonder what the chances are of that?
My guess is £300 cos I think i saw it somewhere.
I think once you brought up a subject and thinking about it events will happen that without it you WILL suddenly need it.
Sorry for being gloomy Suzy.
RR John isn't a mile out on cost but they will vary depending on size and manufacturer.
Wow, thats a lot of money! Wish they had a breakers yard for RV's in this country!
Suzy surely with the haulage business you have contacts who could look around for you?
You would have thought so wouldn't you? I've made enquiries and its a no, they are different to ours apparently.


You are currently browsing the category archive for the 'Fetus' category.
How does the physical growth of the fetal brain relate to pain function? Addressing this question is not just of research interest, but has profound consequences in guiding clinical use of analgesic and anesthetic intervention for in utero surgery. Adult brains appear structurally and functionally specialized for types of pain; for example, acute pain preferentially engages medial prefrontal cortical and subcortical limbic regions [1,2]. However, the question of the relationship between such specializations and pain is still controversial in the debate concerning fetal pain [3, for review]. One 'maturational' perspective is that brain growth and pain function co-develop through innate genetic and molecular mechanisms, and that postnatal experience merely has a role in the final 'fine tuning' [4,5,6,7]. Evidence concerning the differential neuroanatomical development of brain regions is used to determine a lower gestational age when particular regions likely become functional for pain. Several authors claim that maturation within subcortical brain regions enables pain function as early as 20 weeks gestation [6,7], others claim expansion of thalamocortical regions at 24 weeks is necessary and sufficient. An alternative 'expertise' view is that brain development and pain function involve a prolonged process of co-specialization that is shaped by postnatal experience [3,8,9,10]. Based on this approach, some authors argue that the fetal brain is not functional for pain at any gestational stage because skills such as sense of self and mind-reading learnt in postnatal life are necessary for pain [3,8,9,10].
Maturational views of functional brain development assume that brain growth and the appearance of functions are equivalent or the same thing, in the way that water and H2O are equivalent or the same thing, which implies that concerning the question of fetal pain, the sequential coming 'on-line' of specific brain regions during fetal development is identical with the appearance of pain function. That is, pain function numerically shares all its properties or qualities with the brain. Things with qualitative identity share properties, so things can be more or less qualitatively identical. Apples and oranges are qualitatively identical because they share the quality of being a fruit, but two apples have greater qualitative identity. Maturational views of fetal pain demand more than this, however, since they imply numerical identity. Numerical identity implies total qualitative identity, and can only hold between a thing and itself. This means that a maturational view of fetal pain makes a very strong demand about pain capacity: specific brain regions and pain function co-develop in the fetus because they are numerically identical, one and the very same thing. Pain is in the brain.
3. Pain is not numerically identical to the brain.
1. Pains are knowable to me by direct personal experience.
2. Brain events are not knowable to me by direct personal experience.
3. My pain is not numerically identical to my brain.
1. Ibuprofen is known by me to relieve pain.
2. Iso-butyl-propanoic-phenolic acid is not known by me to relieve pain.
3. Ibuprofen cannot be identical to iso-butyl-propanoic-phenolic acid.
The premises in the example are true, but the conclusion is known to be false. The argument is fallacious because its core assumption – 'fundamental divergence' – is mistaken: it mistakenly assumes that a thing must be known by somebody somewhere. But the property 'being known by somebody' is not a necessary feature of anything, much less a property that might establish its identity or non-identity with something otherwise known. The truth of the premises may be due to nothing else but my ignorance of what turns out to be identical with what. This point entails that 'being known by somebody' is not a necessary feature of pain that might explain its identity or non-identity with the brain. The non-identity of fetal brain development and pain function cannot be established by this argument.
The argument needs to produce independent evidence for the idea of 'fundamental divergence', since it is not self-evident. To illustrate this point, consider the argument for pain-brain numerical identity that personal pain would have no influence on mammalian behaviour were it not numerically identical with brain events . This apparently simple argument wasn't established until fairly recently because a crucial premise was not available. This is the premise that physical effects like pain are determined by prior physical causes. This is an empirical premise, and one which scientific theories of pain didn't take to be fully evidenced until the middle and late twentieth century [12, for review]. It is this evidential shift, and not the apparently obvious, which is responsible for the argument's persuasive power. It remains to be seen if stronger evidence for pain-brain identity in the fetus is forthcoming.
Of course, the failure of this particular argument to establish its conclusion does not thereby abolish the expertise perspective and self-guarantee its opposite, the maturational perspective, or even prove that the two perspectives are mutually exclusive. Rather, what the failure of the argument shows is that apparently obvious logic is sometimes a poor guide to reality. Whether pain-brain identity is true or false is impossible to tell simply by arguing personal appearances.
 Apkarian AV, Hashmi JA, Baliki MN. Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 2011; 152(3 Suppl): S49–S64.
 Wager TD, Atlas LY, Lindquist MA, Roy M, Woo CW, Kross E. An fMRI-based neurologic signature of physical pain. New England Journal of Medicine 2013; 368(15): 1388–1397.
 Derbyshire SWG, Raja A. On the development of painful experience. Journal of Consciousness Studies 2011; 18: 9–10.
 Anand KJ, Hickey PR. Pain and its effects in the human neonate and fetus. New England Journal of Medicine 1987; 317(21): 1321–1329.
 Anand KJ. Consciousness, cortical function, and pain perception in nonverbal humans. Behavioral and Brain Sciences 2007; 30(1): 82–83.
 Lowery CL, Hardman MP, Manning N, Clancy B, Whit Hall R, Anand KJS. Neurodevelopmental changes of fetal pain. Seminars in Perinatology 2007; 31(5): 275–282.
 Brusseau RR, Mashour GA. Subcortical consciousness: Implications for fetal anesthesia and analgesia. Behavioral and Brain Sciences 2007; 30(01): 86–87.
 Derbyshire SWG. Controversy: Can fetuses feel pain? BMJ: British Medical Journal 2006; 332(7546): 909–912.
 Derbyshire SWG. Fetal analgesia: where are we now? Future Neurology 2012; 7(4): 367–369.
 Szawarski Z. Do fetuses feel pain? Probably no pain in the absence of "self". BMJ: British Medical Journal 1996; 313(7060): 796–797.
 Papineau D. Thinking about consciousness. Oxford: Oxford University Press; 2002.
 Perl ER. Pain mechanisms: a commentary on concepts and issues. Progress in Neurobiology 2011; 94(1): 20–38.
The trend in the literature on fetal pain is to approach the question of consciousness in the fetus in terms of conscious states of pain. That is, first define what makes a pain a conscious mental state, and then determine being a conscious fetus in terms of having such a state. Thus, the possibility of a conscious fetus is thought to rely on theories of conscious pain states. Call this the state approach to fetal pain.
Two state approaches to fetal pain are present in the literature. One approach looks at the brain structure(s), pathways and circuits necessary for conscious pain states and then seeks to establish whether this substrate is present and functional in the fetus. There is broad agreement among researchers that the minimal necessary neural pathways for pain are in the human fetus by 24 weeks gestation [1, for review]. Some researchers argue that the fetus can feel pain earlier than 24 weeks because pain is enabled by subcortical brain structures [4,5,6].
Another phenomenal approach is to consider the subjective content of a conscious experience of pain, and to ask whether that content might be available to the fetus [1,2,3]. Based on this approach, some researchers argue that the fetus cannot feel pain at any stage because it lacks developmental abilities and concepts such as sense of self necessary for pain [1,2,3].
Although both state approaches are presented as opposites in the literature, they share the determination of fetal pain based on specific levels or degrees of complexity, whether of the brain structures and the relationship they have to the conscious state of pain, or of the subjective contents that constitute that state.
An alternate approach to understanding fetal consciousness that has not been explored in the literature on fetal pain is the extent to which pain is based on the arrangement of certain brain structures (or experiential contents), rather than a result of maturation or increase in complexity achieved by growth of the brain substrate which below a certain size does not enable consciousness [7,8]. Thus, whether the fetus is excluded in this regard is not due to its simplicity, but because its lack of certain brain arrangements necessary to enable consciousness.
The possibilities in this consciousness scale range from simply experienced sensation ('This'; 'This is so') to self-consciousness ('I am affected by this which is so'; 'So this is I who am affected by this which is so'). Each stage in this scale presupposes consciousness. Any experience, whatever its degree of complexity, is conscious. It follows that to see, to hear, and to feel is to be conscious, irrespective of whether in addition a creature is self-conscious that it is seeing, hearing, and feeling . To feel pain is to be conscious of that experience regardless of whether in addition one is self-conscious of being in pain. Self-consciousness is just one of many contents of consciousness available to big-brained living creatures with complex capacities: it is not definitive of consciousness [7,8]. The point of saying this is that it circumvents the logical mistake of misidentifying attributes unique to a specialized form of consciousness (e.g., self-consciousness) as general features of consciousness itself.
With this alternate view of consciousness now sketched in, we should determine where the fetus and where pain fall in the Indian scale of sentience. The possibilities in the scale extend from mere sensation to self-consciousness–where does the fetus fall in?
 Derbyshire S, Raja A. (2011). On the development of painful experience.Journal of Consciousness Studies, 18, 9–10.
 Derbyshire SW. (2006). Controversy: Can fetuses feel pain?. BMJ: British Medical Journal, 332(7546), 909.
 Szawarski Z. (1996). Do fetuses feel pain? Probably no pain in the absence of "self". BMJ: British Medical Journal, 313(7060), 796–797.
 Anand KJ, Hickey PR. (1987). Pain and its effects in the human neonate and fetus. New England Journal of Medicine, 317(21), 1321–1329.
 Anand KJ. (2007). Consciousness, cortical function, and pain perception in nonverbal humans. Behavioral and Brain Sciences, 30(01), 82–83.
 Lowery CL, Hardman MP, Manning N, Clancy B, Whit Hall R, Anand KJS. (2007). Neurodevelopmental changes of fetal pain. In Seminars in perinatology (Vol. 31, No. 5, pp. 275–282).
 Merker B. (1997). The common denominator of conscious states: Implications for the biology of consciousness. Available at: http://cogprints.soton.ac.uk.
for neuroscience and medicine. Target article with peer commentary and author's response. Behavioral and Brain Sciences, 30, 63–134.
There is broad agreement among researchers that the minimal necessary neural pathways for pain are in the human fetus by 24 weeks gestation [1, for review]. However, some argue that the fetus can feel pain earlier than 24 weeks because pain can be enabled by subcortical brain structures [2,3,4,5]. Other researchers argue that the fetus cannot feel pain at any stage of gestation because the fetus is sustained in a state of unconsciousness . Finally, others argue that the fetus cannot feel pain at any stage because the fetus lacks the conceptual postnatal development necessary for pain [7,8,9]. If a behavioral and neural reaction to a noxious stimulus is considered sufficient for pain then pain is possible from 24 weeks and probably much earlier. If a conceptual subjectivity is considered necessary for pain, however, then pain is not possible at any gestational age. According to , much of the disagreement concerning fetal pain rests on the understanding of key terms such as 'wakefulness', 'conscious' and 'pain'.
1. Pain experiences are subjective.
2. Brain events are objective.
3. Pain experiences are not identical to brain events.
1. Pain experiences are knowable to me by introspection.
2. Brain events are not knowable to me by introspection.
3. My pain experiences are not identical to any of my brain events.
1. Ibuprofen is known to me to relieve pain.
The premises in the example are true, but the conclusion is known to be false. The argument is fallacious because the core idea of the argument – 'fundamental divergence' – makes an erroneous assumption; namely, it assumes that a thing must be known by somebody. But the property 'being known by somebody' is not a necessary feature of any thing, much less a property that might establish its identity or non-identity with some thing otherwise known. The truth of the premises may be due to nothing else but my ignorance of what turns out to be identical with what. These considerations challenge the assumed epistemology in the conceptual subjectivity view of pain.
They also challenge the related claim made by proponents of conceptual subjectivity that any description of a pain given in objective scientific terms will necessarily always exclude the personal experience of that pain [7,8,9]. The argument made here is by now familiar: since descriptions of pain in personal subjective terms are different from scientific descriptions of pain, it follows that a pain and its private subjectivity cannot be identical with a brain event and its public objectivity. Only persons can feel pain – brain cells and protein channels can't. Clearly, the argument begs the issue in question: whether or not the subjective features of a pain I personally experience are identical with some objective features of my brain that might be discovered by neuroscience is precisely the question at issue [10,11].
Besides, in order to understand a scientific explanation of pain, neuroscience does not require of a person that he both understands the explanation and feels pain as a condition of understanding. Neuroscience aims to explain pain, that is its main purpose. Too much is demanded of neuroscience if, in addition to formulating an explanation of pain, it is meant to re-create pain in somebody as a requirement of understanding [10,11]. This expectation is therefore much too strong.
 Derbyshire SWG, Raja A. (2011). On the development of painful experience.Journal of Consciousness Studies, 18, 9–10.
 Anand KJ. (2007). Consciousness, cortical function, and pain perception in nonverbal humans. Behavioral and Brain Sciences, 30(1), 82–83.
 Lowery CL, Hardman MP, Manning N, Clancy B, Whit Hall R, Anand KJS. (2007). Neurodevelopmental changes of fetal pain. In Seminars in perinatology, 31(5), 275–282.
 Mellor DJ, Diesch TJ, Gunn AJ, Bennet L. (2005). The importance of 'awareness' for understanding fetal pain. Brain research reviews, 49(3), 455-471.
 Derbyshire SWG. (2012). Fetal analgesia: where are we now? Future Neurology, 7(4), 367-369.
 Derbyshire SWG. (2006). Controversy: Can fetuses feel pain? BMJ: British Medical Journal, 332(7546), 909.
 Churchland PS. (2002). Brain-wise: V: Studies in Neurophilosophy. MIT press.
 van Rysewyk S. (2013). Pain is Mechanism. PhD Dissertation, University of Tasmania.


Hi – Vikram from Yatra Tea Company. Trust you all had a nice weekend.
This week through Saturday we're offering Free Standard Shipping in the US for orders of $25 or higher.
Our stock is dwindling – last week we bid goodbye to Puttabong and Singbulli, two gems from Darjeeling. We have some excellent teas still in stock – browse our shop and have a look see.
- We have 4 new teas arriving this week – 3 beautiful Nilgiri winter teas from Glendale, Craigmore, and Kodanad Estates (January harvests), and a Mao Feng green tea produced in the Autumn from Darjeeling's Gopaldhara Estate. These teas will be on the site in the next two days!
We're keen to keep dwindling our stocks – that will help free up some cash for the First Flush 2019 teas!
Thanks for reading, and have a great week ahead!
Thinking of placing two orders. I have never tried any teas from Nepal so this would be first on my list. As for the Darjeelings, which would you recommend? You know my preferences for Darjeeling tea.
Hey – personally, I love the Sakhira from Nepal, so much so that I've requested the producer to make me something similar this spring. Hoping that materialises!
Given your preference for later invoice Spring Darjeelings, go for the Thurbo (DJ 39). I personally like the DJ 5 Goomtee, but I like the early invoice Darjeelings even though I find them more finicky. Whichever you order, I'll send you a sample of the other.
Thanks – keen to hear what you think of the teas!
Hey - personally, I love the Sakhira from Nepal, so much so that I've requested the producer to make me something similar this spring. Hoping that materialises! Given your preference for later invoice Spring Darjeelings, go for the Thurbo (DJ 39). I personally like the DJ 5 Goomtee, but I like the early invoice Darjeelings even though I find them more finicky. Whichever you order, I'll send you a sample of the other. Thanks - keen to hear what you think of the teas!
Login or sign up to post a message.
OK. Placed my order for the Sakhira and Thurbo.
Thanks for giving us a try! Given your in depth knowledge of Spring Darjeelings, I'm curious to hear your thoughts on the Thurbo. Hopefully you will also enjoy your first foray into the world of Nepali teas through the Sakhira!
Thanks for giving us a try! Given your in depth knowledge of Spring Darjeelings, I'm curious to hear your thoughts on the Thurbo. Hopefully you will also enjoy your first foray into the world of Nepali teas through the Sakhira!
Teas are on their way!
The First Flush Thurbo Estate, 2017 Darjeeling was very good.
Hits all the flavor notes of a Spring Flush Darjeeling. Good balance of flavor and astringency. Just a little light on depth and body. It's a Spring Flush Darjeeling, so the depth and body may not be a concern. The taste is good and the tea is all the better with the low cost. Yes, depending on preferences, you can buy a better Darjeeling. The thing is marginal gains. Would you be willing to pay more than 3 times the price to get that last ounce of body and depth?
The teas come packaged in ziplock Mylar bas and the customer support is very good. Lots of other retailers offer Darjeeling teas. I especially like retailers trying to up their game by really reaching out and listening to customer comments.
I am not employed by Yatra. I am not a fake customer. I am a real consumer enjoying the taste of the Yatra teas. I can go on and on write a clinical analysis but I won't.
Give their teas a try.
The First Flush Thurbo Estate, 2017 Darjeeling was very good. Hits all the flavor notes of a Spring Flush Darjeeling. Good balance of flavor and astringency. Just a little light on depth and body. It's a Spring Flush Darjeeling, so the depth and body may not be a concern. The taste is good and the tea is all the better with the low cost. Yes, depending on preferences, you can buy a better Darjeeling. The thing is marginal gains. Would you be willing to pay more than 3 times the price to get that last ounce of body and depth? The teas come packaged in ziplock Mylar bas and the customer support is very good. Lots of other retailers offer Darjeeling teas. I especially like retailers trying to up their game by really reaching out and listening to customer comments. I am not employed by Yatra. I am not a fake customer. I am a real consumer enjoying the taste of the Yatra teas. I can go on and on write a clinical analysis but I won't. Give their teas a try.
Many thanks for the kind words. One thing I have discovered is how much I like interacting with people over the topic of tea.
I am glad you enjoyed the Thurbo! And I hope you give us the opportunity to send you more tea in the future!
Many thanks for the kind words. One thing I have discovered is how much I like interacting with people over the topic of tea. I am glad you enjoyed the Thurbo! And I hope you give us the opportunity to send you more tea in the future!
Curious as to why this thread keeps getting bumped with no new replies.
In an effort to maintain just one dedicated thread for my company's sales and promotions, I edit the main body of the thread on a weekly basis, or whenever I offer a new promotion. If you scroll up you will notice an edit date. Every time I edit the thread gets bumped up.
This way I do not flood the forum with a new thread every week.
In an effort to maintain just one dedicated thread for my company's sales and promotions, I edit the main body of the thread on a weekly basis, or whenever I offer a new promotion. If you scroll up you will notice an edit date. Every time I edit the thread gets bumped up. This way I do not flood the forum with a new thread every week.
:) no, just the opposite, you're quite observant.
I think there may have been a discussion at the very start of the year about companies promoting their teas. I was guilty of multiple threads in 2017 and figured just one dedicated thread updated on a weekly basis would suffice.