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Pioneering longitudinal studies of boys with hyperactivity by Satterfield et al. 1 indicated that one of the most deleterious outcomes associated with attention-deficit/hyperactivity disorder (ADHD) is later antisocial behaviors. This risk grows when ADHD is accompanied by severe behavior problems.2 Though most children with ADHD will not go on to engage in criminal behavior, dimensional measures of externalizing behavior problems as well as categorical diagnoses of oppositional defiant disorder and conduct disorder have strong associations with ADHD. Moreover, cross-sectional studies of incarcerated adults indicate that 20% to 30% meet diagnostic criteria for ADHD.3 These associations between childhood ADHD, oppositional defiant disorder, and conduct disorder and later criminal behavior beg the question of whether treatment of ADHD can reduce the severity of, or in some cases prevent, criminal behavior. [ABSTRACT FROM AUTHOR]

The article focuses on the transformation of the Turkish Studies Association (TSA) into the Ottoman and Turkish Studies Association (OTSA). Topics include the challenges faced by TSA, efforts to revive the organization through publication, finding a new editor, redefining the association's identity, and its subsequent growth under the new name, reflecting a broader academic scope beyond nationalist confines.

Poor school readiness and high rates of expulsion from preschool or day care are common in very young children with attention-deficit/hyperactivity disorder (ADHD), while in cases of severe impulsivity and inadequate monitoring there is real danger of injury to the child and others. Compared to older children, preschool-age children with ADHD have more frequent and often severe ADHD symptoms and high rates of psychiatric and developmental comorbidity.1 As pediatricians are now routinely screening for ADHD in children as young as 4 years of age,2 identification will likely increase. However, once identified, far less is known about treating ADHD.3. [ABSTRACT FROM AUTHOR]

Background: ONC201 is a small molecule antagonist of DRD2, a G protein-coupled receptor overexpressed in several malignancies, that has prolonged antitumor efficacy and immunomodulatory properties in preclinical models. The first-in-human trial of ONC201 previously established a recommended phase II dose (RP2D) of 625 mg once every three weeks. Here, we report the results of a phase I study that evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of weekly ONC201. Methods: Patients ≥ 18 years old with an advanced solid tumor refractory to standard treatment were enrolled. Dose escalation proceeded with a 3 + 3 design from 375 mg to 625 mg of ONC201. One cycle, also the doselimiting toxicity (DLT) window, was 21 days. The primary endpoint was to determine the RP2D of weekly ONC201, which was confirmed in an 11-patient dose expansion cohort. Results: Twenty patients were enrolled: three at 375 mg and 17 at 625 mg of ONC201. The RP2D was defined as 625 mg with no DLT, treatment discontinuation, or dose modifications due to drug-related toxicity. PK profiles were consistent with every-three-week dosing and similar between the first and fourth dose. Serum prolactin and caspase-cleaved cytokeratin-18 induction were detected, along with intratumoral integrated stress response activation and infiltration of granzyme B+ Natural Killer cells. Induction of immune cytokines and effectors was higher in patients who received ONC201 once weekly versus once every three weeks. Stable disease of > 6 months was observed in several prostate and endometrial cancer patients. Conclusions: Weekly, oral ONC201 is well-tolerated and results in enhanced immunostimulatory activity that warrants further investigation. Trial registration: NCT02250781 (Oral ONC201 in Treating Patients With Advanced Solid Tumors), NCT02324621 (Continuation of Oral ONC201 in Treating Patients With Advanced Solid Tumors). [ABSTRACT FROM AUTHOR]

Background: Attention-deficit/hyperactivity disorder (ADHD) treatment utilization among adolescents is highly variable. This article describes pharmacological and nonpharmacological treatment utilization in a community sample of primarily Latinx and/or Black adolescents with ADHD (N = 218), followed longitudinally for 4 years, from early adolescence until approximately age 17 (M = 16.80, standard deviation = 1.65). Methods: Electronic surveys administered between 2012 and 2019 queried parent and youth reports of medication initiation, persistence, diversion, and misuse, as well as reasons for desistence. Nonpharmacological treatment utilization (including complementary and alternative treatments) was also measured. Results: Results indicated that: (1) the majority of the sample sought treatment for ADHD in their community, (2) rates of psychosocial treatment utilization were higher than medication utilization, (3) approximately half of the medicated sample discontinued community-administered ADHD medication during the follow-up period, most frequently citing tolerability issues and concerns that they were "tired of taking" medication, and (4) medication misuse consisted of youth diversion and parent utilization of teen medication, but both were reported at low rates. Race/ethnicity did not predict treatment utilization patterns, but lower family adversity and psychiatric comorbidity predicted persistence of medication use over time. Conclusions: ADHD treatment engagement efforts for Latinx and/or Black adolescents might link treatment to goals valued by the youth, address concerns related to medication tolerability, and promote secure monitoring of medication. Nonpharmacological treatments for ADHD may be more palatable to Latinx and Black youth with ADHD, and efforts to engage youth with ADHD in treatment should consider offering medication and psychosocial treatment options. [ABSTRACT FROM AUTHOR]

Low serum levels of 25-hydroxyvitamin D [25(OH)D] and low sunlight exposure are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomized 1:1:1:1 to placebo, 1000, 5000 or 10 000 international units (IU) of oral vitamin D3 daily within each study centre (n = 23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the hazard ratios (95% confidence interval) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions and use of steroids, the hazard ratios (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); and 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome. [ABSTRACT FROM AUTHOR]

There is a robust literature of predominantly cross-sectional studies demonstrating an association between attention-deficit/hyperactivity disorder (ADHD) and sleep quality in childhood and adolescence, measured by subjective as well as objective measures, dimensional and categorical variables, and controlling for a wide range of confounders such as other disorders.1 Moreover, ADHD symptoms and sleep problems are independently associated with adverse functional outcome and quality of life.2 As a result, these are viewed as common and mutually exacerbating conditions, likely mediated by common neuropathways.3-5. [ABSTRACT FROM AUTHOR]

Background: In clinical trials of medications to treat attention-deficit/hyperactivity disorder (ADHD) in children, effects on functional impairment have been less well-studied than changes in ADHD symptoms.Objective: Data regarding functional impairment were analyzed from a multicenter, double-blind, placebo-controlled study of guanfacine extended release (GXR) in children with ADHD, using the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P). The correspondence of changes in WFIRS-P scores with symptomatic and global response to GXR treatment was also examined, with treatment response defined by scores on both the ADHD Rating Scale IV (ADHD-RS-IV) and the Clinical Global Impressions-Improvement Scale (CGI-I).Methods: In this 8-week, double-blind, placebo-controlled, dose optimization study at 47 sites across the USA and Canada, children aged 6-12 years with a diagnosis of ADHD [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria, and an ADHD-RS-IV score ≥28 and CGI-Severity of Illness Scale score ≥4 at baseline], were randomized 1:1:1 into three groups: GXR AM [GXR (1-4 mg/day) in the morning, placebo in the evening], GXR PM [placebo in the morning, GXR (1-4 mg/day) in the evening], or twice-daily placebo. Parents rated their children on the WFIRS-P at screening, baseline, the end of dose optimization, and at the final on-treatment assessment.Results: The efficacy population was composed of 333 subjects (GXR AM: n = 107; GXR PM: n = 114; placebo: n = 112). At the final on-treatment assessment, there were significant improvements from baseline in the placebo-adjusted difference in least-squares (LS) mean (95 % confidence interval) WFIRS-P Total scores for both GXR treatment groups combined [GXR all-active: -0.16 (-0.25, -0.07), effect size (ES) = 0.448, P <0.001] and separately [GXR AM: -0.15 (-0.26, -0.05), ES = 0.417, P = 0.004; GXR PM: -0.18 (-0.28, -0.07), ES = 0.478, P = 0.001]. Significant improvements in WFIRS-P domain scores for Family, Learning and School (including Academic Performance and Behavior in School), Social, and Risky Behavior were found for both GXR cohorts compared with placebo. However, the Life Skills and Self-Concept domain scores of the WFIRS-P did not improve with GXR treatment. Post hoc stratification by responder status revealed that significant (P <0.001) improvements in WFIRS-P Total and all domain scores were associated with symptomatic treatment response in the GXR all-active group.Conclusions: GXR treatment in children with ADHD was associated with reductions in WFIRS-P functional impairment scores compared with placebo, regardless of time of GXR administration. Changes in WFIRS-P scores were congruent with clinical response, as determined by both ADHD symptom reduction and CGI-I scores. CLINICALTRIALS.Gov Identifier: NCT00997984. [ABSTRACT FROM AUTHOR]

Patients with primary immunodeficiency disease (PIDD) typically require life-long intravenous (IV) or subcutaneous (SC) immunoglobulin (Ig) replacement therapy to prevent recurrent infections. The efficacy, safety, and pharmacokinetics of a highly concentrated (20 %) Ig preparation for SC administration (IGSC 20 %) were evaluated in a prospective trial in patients with PIDD. A total of 74 patients (aged 3-83 years) received 4327 IGSC 20 % infusions over a median of 380.5 days. The rate of validated serious bacterial infections was 0.012 event/patient-year ( p < 0.0001 compared with the historical control), and the annualized rate of infection was 2.41 events/patient. Median IgG trough levels were >14.5 g/l. The median maximum infusion rate was 60 ml/h/site (range 4.4-180), resulting in a median infusion duration of 0.95 h. A volume ≥30 ml was infused per site in 74.8 % of IGSC 20 % infusions. Most (84.9 %) infusions were administered using ≤2 infusion sites; for 99.8 % of infusions, there was no need to interrupt/stop administration or reduce the infusion rate. No related serious adverse event (AE) occurred during IGSC 20 % treatment; related non-serious AEs occurred at a rate of 0.036 event/infusion. The incidence of related local AEs was 0.015 event/infusion and of related systemic AEs was 0.021 event/infusion; most were mild in severity, none severe. Increased infusion rates or volumes were not associated with higher AE rates. The investigated IGSC 20 % treatment was shown to be effective and safe, enabling higher infusion rates and volumes per site compared to conventional SC treatments, resulting in fewer infusion sites and shorter infusion durations. [ABSTRACT FROM AUTHOR]

Under-recruitment into clinical trials is a common and costly problem that undermines medical research. To better understand barriers to recruitment into clinical trials in our region, we conducted a multimethod descriptive study. We initially surveyed investigators who had conducted or were currently conducting studies that utilized an adult or pediatric clinical research center (n = 92). We then conducted focus groups and key informant interviews with investigators, coordinators, and other stakeholders in clinical and translational research (n = 32 individuals). Only 41% of respondents reported that they had or were successfully meeting recruitment goals and 24% of the closed studies actually met their targeted recruitment goals. Varied reasons were identified for poor recruitment but there was not a single investigator or study "phenotype" that predicted enrollment outcome. Investigators commonly recruited from their own practice or clinic, and 29% used a manual electronic medical record search. The majority of investigators would utilize a service that provides recruitment advice, including feasibility assessment and consultation, easier access to the electronic health record and assistance with institutional review board and other regulatory requirements. Our findings suggest potential benefits providing assistance across a range of services that can be individualized to the varied needs of clinical and translational investigators. [ABSTRACT FROM AUTHOR]

Background This study examined the effects of atomoxetine ( ATX) and OROS methylphenidate ( MPH) on laboratory measures of inhibitory control and attention in youth with attention-deficit/hyperactivity disorder ( ADHD). It was hypothesized that performance would be improved by both treatments, but response profiles would differ because the medications work via different mechanisms. Methods One hundred and two youth (77 male; mean age = 10.5 ± 2.7 years) with ADHD received ATX (1.4 ± 0.5 mg/kg) and MPH (52.4 ± 16.6 mg) in a randomized, double-blind, crossover design. Medication was titrated in 4-6-week blocks separated by a 2-week placebo washout. Inhibitory control and attention measures were obtained at baseline, following washout, and at the end of each treatment using Conners' Continuous Performance Test II ( CPT- II), which provided age-adjusted T-scores for reaction time ( RT), reaction time variability ( RT variability), and errors. Repeated-measures analyses of variance were performed, with Time (premedication, postmedication) and Treatment type ( ATX, MPH) entered as within-subject factors. Data from the two treatment blocks were checked for order effects and combined if order effects were not present. Clinical trial registration: Clinicaltrials.gov: NCT00183391. Results Main effects for Time on RT ( p = .03), RTSD ( p = .001), and omission errors ( p = .01) were significant. A significant Drug × Time interaction indicated that MPH improved RT, RTSD, and omission errors more than ATX ( p < .05). Changes in performance with treatment did not correlate with changes in ADHD symptoms. Conclusions MPH has greater effects than ATX on CPT measures of sustained attention in youth with ADHD. However, the dissociation of cognitive and behavioral change with treatment indicates that CPT measures cannot be considered proxies for symptomatic improvement. Further research on the dissociation of cognitive and behavioral endpoints for ADHD is indicated. [ABSTRACT FROM AUTHOR]

Background: Patients with immunodeficiency diseases require lifelong treatment with immunoglobulin (Ig), yet few studies have vetted dosing strategies and effectiveness of Ig in older patient populations. Patients requiring subcutaneous (SC) Ig (SCIG) typically start with intravenous dosing before transitioning to SCIG weekly maintenance. In this retrospective review, we investigated an alternate strategy with higher initial SC doses among an older patient population with antibody deficiency syndromes. Findings: Records of 13 patients (mean age, 70 years) with antibody deficiencies who were naive to treatment with Ig were assessed. SCIG (Vivaglobin® [Immune Globulin Subcutaneous (Human), 16% Liquid] or Hizentra® [Immune Globulin Subcutaneous (Human), 20% Liquid]) was given twice weekly (100 mg/kg) for 2 weeks, followed by weekly (100 mg/kg) administration The mean pretreatment IgG level was 460 mg/dL; at 1, 3, and 6 months after SCIG initiation, mean IgG serum levels were 852, 907, and 943 mg/dL, respectively. Maintenance doses were unchanged during 6 months of follow-up. All patients remain on SCIG (median, 44 months). One patient developed sepsis/cholangitis unrelated to treatment 3 months after starting SCIG; no other serious bacterial infections were reported. Conclusions: Initiation of SCIG by doubling the maintenance dose over 2 weeks may be a well-tolerated and effective option for patients with antibody deficiencies requiring Ig replacement, especially among older patients. [ABSTRACT FROM AUTHOR]

Objectives: This study seeks to determine if variation in the dopamine transporter gene (SLC6A3/DAT1) moderates the dose-response effects of long-acting dexmethylphenidate (D-MPH) and mixed amphetamine salts (MAS) in children with attention-deficit/hyperactivity disorder (ADHD). Methods: Fifty-six children and adolescents (mean age=11.7±2.2) participated in a double-blind, two period crossover, dose-response study with a randomized placebo week in each 4 week drug period. Each period consisted of sequential week-long exposures to three dose levels (10, 20, 25-30 mg, depending upon weight) of D-MPH or MAS. Results: Doses of 10-20 mg of either D-MPH or MAS had little to no effect on hyperactivity-impulsivity and total ADHD symptom scores in subjects with the 9/9 genotype; this was in contrast to the dose-response curves of subjects with either the 10/10 or 10/9 genotype. Conclusions: ADHD youth with the 9/9 genotype may require higher stimulant doses to achieve adequate symptom control. [ABSTRACT FROM AUTHOR]

Objective: To examine the efficacy and tolerability of guanfacine extended release (GXR) administered in the morning or evening in children with attention-deficit/hyperactivity disorder (ADHD). Method: In this multicenter, double-blind, placebo-controlled, dose-optimization study, children 6 to 12 years of age with ADHD were randomized to receive GXR (1-4 mg/d) in the morning and placebo in the evening (GXR AM), placebo in the morning and GXR in the evening (GXR PM), or twice-daily placebo. The primary efficacy measure was the ADHD Rating Scale-IV (ADHD-RS-IV). Results: A total of 333 child participants received study drug in the following cohorts: GXR AM (n = 107), GXR PM (n = 114), or placebo (n = 112). Mean (standard deviation) changes from baseline to week 8 (visit 10 or last observation carried forward) in ADHD-RS-IV total scores were significant for both GXR treatment groups combined (GXR all-active: -20.0 [12.97]) and separately (GXR AM: -19.8 [12.95]; GXR PM: -20.1 [13.04]) compared with placebo (-11.0 [12.93]; p < .001 for all). Most spontaneously-elicited treatment-emergent adverse events were mild or moderate in severity; the most common was somnolence (GXR all-active: 44.3%; GXR AM: 46.7%; GXR PM: 42.1%; placebo: 12.5%). Conclusions: GXR administered either in the morning or evening was associated with significant and clinically meaningful improvements in ADHD symptoms. The levels of response and tolerability observed with GXR were similar regardless of time of dosing (morning versus evening), indicating that once-daily GXR monotherapy is effective whether administered in the morning or evening. Clinical trial registration information--Tolerability and Efficacy of AM and PM Once Daily Dosing With Extended-release Guanfacine Hydrochloride in Children 6-12 With Attention-Deficit/Hyperactivity Disorder (ADHD) (The ADHD Tempo Study); http://clinicaltrials.gov/; NCT00997984. [ABSTRACT FROM AUTHOR]

Given the high heritability of the disorder, attention-deficit hyperactivity disorder (ADHD) is common among parents of children with ADHD. Parental ADHD is associated with maladaptive parenting, negative parent-child interaction patterns and a diminished response to behavioural parent training. We describe our previous research demonstrating that stimulant medications for mothers with ADHD are associated with reductions in maternal ADHD symptoms. Although limited beneficial effects on self-reported parenting were also found in our study, the impact of ADHD medications on functional outcomes related to parenting and family interactions may not be sufficient for many families. Many questions remain with regard to how best to treat multiplex ADHD families in which a parent and child have ADHD. In particular, future studies are needed: (1) to evaluate how best to sequence pharmacotherapy, psychosocial treatment for adult ADHD and behavioural parenting interventions; (2) to determine the best approach to maintaining treatment effects over the long term for both parents and children; and (3) to identify individual predictors of treatment response. [ABSTRACT FROM AUTHOR]

Poor vitamin D nutrition is linked with dementia, but vitamin D has not been tested in a randomized controlled trial (RCT) in Alzheimer's disease (AD). Nasal insulin acutely improves cognition and vitamin D upregulates insulin receptor expression and enhances insulin action. In an RCT we examined the effect of high-dose vitamin D followed by nasal insulin on memory and disability in mild-moderate AD. 63 community-dwelling individuals aged > 60 were recruited; 32 with mild-moderate disease (Folstein Mini-Mental State Examination [MMSE] score 12-24) met entry criteria and were randomized. All took low-dose vitamin D (1000IU/day) throughout. After run-in (8 weeks), they were randomized to additional high-dose D/placebo for 8 weeks, followed immediately by randomization to nasal insulin (60 IU qid)/placebo for 48 h. Primary outcome measures were Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) and Disability Assessment in Dementia (after high-dose D) and ADAS-cog and Wechsler Memory Scale-Revised Logical memory (WMS-R LM) for immediate and delayed recall (after nasal insulin). Baseline median (interquartile range, IR) age, MMSE, and ADAS-cog were 77.5 (69-80), 19.5 (17-22), and 25.5 (20-31), respectively. Median 25OHD increased from 49 to 60 nM (p < 0.01) after run-in and was 187 nM after high-dose vitamin D and 72 nM after placebo (p < 0.001). Neither cognition nor disability changed significantly after high-dose D. ADAS-cog improved by a median (IR) of 9 (1-11) with nasal insulin after placebo high-dose vitamin D (p = 0.02), but may represent regression to the mean as WLS-R LM did not change. We conclude that high-dose vitamin D provides no benefit for cognition or disability over low-dose vitamin D in mild-moderate AD. [ABSTRACT FROM AUTHOR]

BACKGROUND: On the basis of potential additive or synergistic immunostimulatory antitumor effects, in this phase 1 study, the authors evaluated the combination of sunitinib and tremelimumab (CP-675206; an antibody against cytotoxic T-lymphocyte--associated antigen 4 [CTLA4]) in patients with metastatic renal cell carcinoma (mRCC) was evaluated. METHODS: Adult patients with mRCC who had received ≤1 previous systemic treatment received tremelimumab (6 mg/kg, 10 mg/kg, or 15 mg/kg) intravenously once every 12 weeks and oral sunitinib (50 mg daily for 4 weeks then 2 weeks off or 37.5 mg daily as a continuous dose). The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives were to assess antitumor activity, safety, and pharmacokinetics. RESULTS: Twenty-eight patients were enrolled. Two of 5 patients who received 50 mg sunitinib plus tremelimumab 6 mg/kg experienced dose-limiting toxicities (DLTs), and no further enrollment to the combination with sunitinib 50 mg dosing was pursued. Among patients who received continuous sunitinib 37.5 mg daily, 1 of 7 patients who received tremelimumab 10 mg/kg plus sunitinib suffered a sudden death, and 3 of 6 patients who received tremelimumab 15 mg/kg plus sunitinib experienced DLTs. An expansion cohort (n = 7) was enrolled at tremelimumab 10 mg/kg plus sunitinib 37.5 mg daily; 3 of those patients experienced DLTs. Overall, rapid-onset renal failure was the most common DLT. Nine of 21 patients who were evaluable for response achieved partial responses (43%; 95% confidence interval, 22%-66%), and 4 of those responses were ongoing at the time of the current report. CONCLUSIONS: In this study of tremelimumab plus sunitinib, rapid-onset acute renal failure was observed unexpectedly, and further investigation of tremelimumab doses >6 mg/kg plus sunitinib 37.5 mg daily is not recommended. Preclinical investigation may be warranted to understand the mechanism of renal toxicity. Cancer 2011;117:758-67. [ABSTRACT FROM AUTHOR]

The authors discuss a phase II study examining the safety, tolerability, and impact of insulin-like growth factor 1 (IGF-1) on autism specific impairments in 18 children with 22q13 deletion or Phelan-McDermid syndrome. They stresses the ethical participatien of patients in the said study. The authors suggest that the study subjects must either reside in the geographic area or have the economic ability to relocate in the duration of research.

This Essay offers a utilitarian perspective on Martha Nussbaum's theory of justice. Nussbaum believes that society should guarantee to every individual a threshold level of central human capabilities. Although Nussbaum's approach has considerable appeal, it is implausible and unappealing when it diverges greatly from utilitarianism. Nussbaum's theory requires that enormous sums of money be devoted to people who receive very little benefit from efforts to raise them toward a capability threshold. Moreover, Nussbaum refuses to take a principled position on how conflicts among below-threshold interests should be resolved, even when one alternative would produce enormously more good than another alternative. Nussbaum mitigates these problems through an implicit incorporation of utilitarianism to address conflicts among below-threshold interests, but this partial adoption of utilitarianism cannot completely cure her theory. In addition to critiquing Nussbaum's theory, this Essay responds to some of Nussbaum's criticisms of utilitarianism. It rejects Nussbaum's claim that utilitarianism is wrong to give weight to adaptive preferences. It also demonstrates that Nussbaum misstates the relationship between her theory and the doctrine of incommensurability: features of her theory that she attributes to a denial of commensurability actually reflect a commitment to commensurability across the capability threshold. [ABSTRACT FROM AUTHOR]

The article focuses on the use of stimulants to treat adults with attention-deficit/hyperactivity disorder (ADHD). It states that U.S. Food and Drug Administration approved long-acting stimulants such as Adderall and Concerta to ADHD patients to provide a daily dose in controlling the symptoms and avoiding the need to repeat the dose. However, it also states that several side effects may be commonly experienced by patients including headache, insomnia and agitation.

The article reports on the relationship between ADHD, stimulant medication, and sleep. Sleep problems such as insomnia are associated with stimulant medications but can be distinguished from bedtime resistance that is associated with ADHD and comorbid disorders such as anxiety and delayed sleep phase syndrome.

Stimulant medications, such as methylphenidate (MPH), are the most commonly used, effective treatment for ADHD. MPH acts primarily by inhibiting the dopamine transporter (DAT), a protein responsible for the reuptake of dopamine from the synapse into presynaptic terminals. We sought to evaluate the relationship between DATI 3'-untranslated region (3'-UTR) variable number tandem repeats (VNTR) genotypes and dose response to MPH. Children with ADHD (n = 47), ages 5-16 years (mean = 9.07 years), underwent a 4-week, double-blinded, crossover trial with forced weekly dosage changes. Children were genotyped for the DATI VNTR and evaluated on placebo and three dosage levels of OROS® MPH. Parents and clinicians who were blind to genotype and medication status rated ADHD symptoms, impairment, and stimulant side effects each week. Children who were homozygous for the less common, 9repeat DATI 3'-UTR genotype displayed a distinct dose-response curve from that of the other genotype groups, with an absence of typical linear improvement when the dose was increased from 18 mg to 36 and 54 mg. Further research is needed to determine the mechanisms related to poor response in patients with the 9/9-repeat genotype, and to determine if this group responds differentially to alternative treatments. [ABSTRACT FROM AUTHOR]

Objective. OROS methylphenidate HCL (MPH) is a recently developed long-acting stimulant medication used to treat attention-deficit/hyperactivity disorder (ADHD). This study was conducted to examine dosage effects on ADHD symptoms and stimulant side effects and to explore potential moderating effects of ADHD subtype. Methods. Children with ADHD combined type (ADHD-CT) or predominantly inattentive type (ADHD-PI; n = 47), ages 5 to 16 years, underwent a placebo-controlled, crossover trial using forced titration with weekly switches at 3 dosage levels. Parent and teacher ratings of ADHD symptoms were used to evaluate efficacy. In addition, vital signs and standardized measures of stimulant side effects were obtained weekly. Results. Parent ratings were more sensitive to treatment effects than teacher ratings. ADHD symptoms and Clinical Global Impressions Severity Index ratings at each dose condition differed significantly from placebo and baseline ratings, which did not differ from one another. For those with ADHD-CT, there was a clear linear dose-response relationship, with clinically significant reductions in ADHD Rating Scale-IV scores occurring in two thirds to three fourths of the subjects during either 36- or 54-mg dose conditions. Children with ADHD-PI, conversely, were more likely to respond optimally to lower doses and derived less benefit from higher doses, with 60% displaying significant improvement on the ADHD Rating Scale-IV at 36 mg or lower. Mild stimulant side effects were reported during placebo and at all dosage levels. With the exception of insomnia and decreased appetite, which were more common at higher... [ABSTRACT FROM AUTHOR]

Airway hyperresponsiveness is among the defining phenomena in asthma. In this article, 3 mechanisms are reviewed to explain how gastroesophageal reflux (GER) may influence airway hyperresponsiveness. First, microaspiration may cause not only direct tissue injury, but may also trigger vagal reflexes. Second, acid infusion of the esophagus in a dog model and in humans has been shown to result in vagally mediated reflexes leading to bronchoconstriction. These reflexes have been studied using immunohistochemical techniques. Third, neuroinflammatory reflexes have been found to play a role in airway responses through the release of tachykinins, including substance P and neurokinin A. Combined, these 3 mechanisms may lead to an increase in vagal efferent impulses that can cause or augment airway hyperresponsiveness. Studies indicate that there is an increase in airway responsiveness in asthma patients who have documented GER. Further, based on the reported number of reflux episodes occurring during 24-hour pH monitoring, airway hyperresponsiveness to methacholine challenge tends to increase as GER worsens. [Copyright &y& Elsevier]

Considers whether the conflation of many people into one can serve as a satisfactory theory of distributive justice. Argument that conflation is the way to treat people with equal respect; Comparison between conflation and utilitarianism; Implications on political science.

Background: Thyroid abnormalities have been associated with attention deficit/hyperactivity disorder (ADHD) and with other childhood psychiatric disorders. The goal of this study was to determine the relationships between thyroid hormone concentrations, neurocognitive functioning, and psychiatric diagnosis in children. Methods: Free thyroxine index (FT4I) and thyroid stimulating hormone (TSH) were obtained, along with diagnostic and descriptive information for 338 children referred to a clinic specializing in learning and behavior problems. Results: Thyroid abnormalities were uncommon in children referred for ADHD. After excluding children with thyroid disease, there was a greater proportion with low concentrations of normal FT4I for ADHD–Predominantly Inattentive type (ratio=7.0), but not for ADHD–Combined Type. High concentrations of normal FT4I were associated with mood lability, preoccupations, and lower ratings of attention problems. Thyroxine concentrations within the normal range were differentially associated with ADHD–Combined Type compared to ADHD–Predominantly Inattentive, mood disorders, and pervasive developmental disorders. Conclusion: Thyroxine concentrations were associated with mood symptoms and unusual behaviors, and were less strongly related to attentional functioning. Thyroxine concentrations were not related to hyperactivity. [Copyright &y& Elsevier]

Discusses the pharmacological action of stimulant dexmethylphenidate in the treatment of attention deficit hyperactivity disorder. Ability to increase dopamine levels in the striatum; Adverse effects of stimulant; Duration of action of stimulants.

Utilitarianism is more convincing than resource egalitarianism or welfare egalitarianism as a theory of how resources should be distributed between disabled people and nondisabled people. Unlike resource egalitarianism, utilitarianism can redistribute resources to the disabled when they would benefit more from those resources than nondisabled people. Unlike welfare egalitarianism, utilitarianism can halt redistribution when the disabled would no longer benefit more than the nondisabled from additional resources. The author considers one objection to this view: it has been argued, by Sen and others, that there are circumstances under which utilitarianism would unfairly distribute fewer resources to the physically disabled than to nondisabled people, on the ground that the disabled would derive less benefit from those resources. In response, the author claims that critics of utilitarianism have fallaciously exaggerated the circumstances under which the disabled would benefit less than the nondisabled from additional resources. In those limited circumstances in which the disabled really would benefit less from resources, the author argues, it does not seem unfair to distribute fewer resources to them. [ABSTRACT FROM AUTHOR]

The article discusses the distribution of life of people suffering from disabilities under the concept of utilitarianism. The distribution issues involving people with disabilities have been a long-time subject of discussion in the field of sociology. The utilitarian distributive policy has apparent implications on the distribution of life between the disabled and the not disabled. According to utilitarian, the key divide is the division between the distribution of life-saving resources and of the non-life saving facility.

The article discusses various opportunities and risks for business owners in America in relation to the expansion of generic top-level domains (gTLDs) as of 2015. The legal aspects of gTLDs and Internet domain names are mentioned, along with the Internet Corporation for Assigned Names and Numbers' (ICANN's) acceptance of additional gTLD applications in 2012. According to the article, corporations such as the Internet company Google Inc. have applied for gTLDs.

Evaluates the short-term efficacy and side effects associated with two methylphenidate hydrochloride (MPH) dosing patterns. Thrice a day dosing as the optimum treatment for must children with attention deficit hyperactivity disorder (ADHD); Severity and time course of ADHD symptoms as the basis of dosing schedule.

Examines the psychometric properties of the Children's Atypical Development Scale (CADS). Internal consistency and temporal stability; Assessment of pervasive developmental disorder and neurobehavioral disorders.

Adaptive functioning was examined in children with Attention Deficit Hyperactivity Disorder (ADHD) or Attention Deficit Disorder (ADD), and a psychiatric comparison group of children with pervasive developmental disorders or mild mental retardation (PDD/MR). As assessed with the Vineland Adaptive Behavior Scales, adaptive functioning was well below average for all three clinic groups. (The PDD/MR group had the lowest adaptive functioning scores, although not statistically different from the other groups.) However, the level of adaptive functioning relative to IQ in the areas of Socialization, Communication and Daily Living was significantly lower for the ADD and ADHD groups. These deficits in adaptive functioning that characterize children with ADHD and ADD may help explain the poor long-term prognosis of ADHD, suggesting that increased attention should be paid to the assessment and treatment of adaptive functioning in individuals with ADHD and ADD. [ABSTRACT FROM AUTHOR]

Persistent and early-onset externalizing behavior problems are associated with a wide range of impairments.1 Parent management training (PMT) is frequently recommended as either a prevention strategy in at-risk children, or as first -line treatment. Although several group-based and individually based models of PMT have demonstrated efficacy in reducing preschool behavior problems, there is a paucity of comparative effectiveness studies to help guide treatment selection. [ABSTRACT FROM AUTHOR]

The article discusses the impairments associated with attention-deficit/hyperactivity disorder (ADHD) in adults. A study by G. Weiss and L. Hectman found that ADHD adults have difficulties in sexual adjustment such as early sexual activity, promiscuousity and sexually transmitted diseases. Longitudinal studies showed that adults with ADHD tend to have more academic and vocational underachievement. They also tend to have difficulties at work, school and relationships, low self-esteem, antisocial behaviors and involve in subtance abuse and crimes.

Focuses on the international conference titled Representation and Reality which focused on author Olaudah Equiano. Significance of the debate on the authenticity of the book "The Interesting Narrative," by Equiano; Information on the book.

Explores the contributions of genetics, neurobiology and environment to the development and perpetuation of eating disorders. Genetics of anorexia nervosa; Biocultural influences on the development of eating disorders; Gender-based effects of serotonin.

Background: fSCIG can be administered at similar doses/volumes and dosing intervals as intravenous immunoglobulin G (IgG) (IVIG) but, similar to conventional subcutaneous IgG, is associated with a lower risk of systemic and higher risk of local adverse reactions (ARs). Objective: We report local AR rates over time in patients with PID aged ≥ 16 years treated with fSCIG for up to ~3.5 years in the fSCIG pivotal phase 3 study and its extension. Methods: Following a 3-month IVIG treatment period, patients initiated fSCIG on a dose ramp-up schedule and thereafter received fSCIG every 3 (Q3W) or 4 weeks (Q4W) for ~18 months, followed by up to an additional 21 months. Local AR (temporally associated and/or causally related adverse events) rates were evaluated over time. Results: Of the 63 enrolled patients aged ≥ 16 (16-78) years, 61 received fSCIG for up to ~3.5 years at the established dose. Overall, the local AR rate per infusion was 0.191; discomfort/pain was the most commonly reported local AR. Rates of ARs per infusion decreased over time: 0.28 (months 1-12), 0.15 (months 13-24), and 0.08 (months 25-33.6). The percentage of patients experiencing ≥ 1 local AR per infusion was highest during the dose ramp-up period (33.3-41.7 % [Q3W] and 29.2-37.5 % [QW4]), and rapidly declined over time. Conclusions: In adults treated with fSCIG for up to ~3.5 years, rates of local ARs per infusion and the percentage of patients experiencing ≥ 1 local AR markedly declined over time. [ABSTRACT FROM AUTHOR]

Objective: To identify patient- and treatment-level factors that predict intervention engagement and outcome for adolescents with attention-deficit/hyperactivity disorder (ADHD), guiding efforts to enhance care.Method: Integrative data analysis was used to pool data from 4 randomized controlled trials of adolescent ADHD treatment with participants (N = 854) receiving various evidence-based behavioral therapy packages in 5 treatment arms (standard [STANDARD], comprehensive [COMP], engagement-focused [ENGAGE]), community-based usual care (UC), or no treatment (NOTX). Participants also displayed varying medication use patterns (negligible, inconsistent, consistent) during the trial. Regression and latent growth curve analyses examined treatment- and patient-level predictors of engagement and outcome.Results: Compared with COMP, ENGAGE was associated with higher parent engagement in behavioral therapy (d = 1.35-1.73) when delivered in university, but not community, clinics. Under some conditions, ENGAGE also predicted youth engagement in behavioral therapy (d = 1.21) and lower likelihood of negligible medication use (odds ratio = 0.49 compared with NOTX). UC was associated with poorer parent engagement compared with COMP (d = -0.59) and negligible medication use (odds ratio = 2.29) compared with NOTX. Compared with COMP, ENGAGE (in university settings) was consistently associated with larger ADHD symptom improvements (d = 0.41-0.83) at 6-month follow-up and sometimes associated with larger grade point average (d = 0.68) and parent-teen conflict (d = 0.41) improvements. Consistent medication use during behavioral therapy was associated with larger improvements in ADHD symptoms (d = 0.28) and parent-teen conflict (d = 0.25-0.36). An ADHD+internalizing clinical profile predicted larger improvements in grade point average (d = 0.45). Family adversity predicted poorer parent and youth engagement (rate ratio = 0.90-0.95), negligible medication use (odds ratio = 1.22), and smaller improvements in grade point average (d = -0.23). African American race predicted smaller improvements in parent-teen conflict (d = -0.49).Conclusion: Engagement-focused behavioral therapy and consistent medication use most frequently predicted stronger clinical engagement and outcomes for adolescents with ADHD. Youths who are African American or who experience family adversity may demonstrate treatment-related disparities for certain outcomes; youths with ADHD+internalizing symptoms may demonstrate excellent academic outcomes following behavioral therapy.Data Sharing: The full ADHD TIDAL dataset is publicly available through the National Data Archive (https://nda.nih.gov), including a data dictionary. The study protocol is also publicly available: https://doi.org/10.1186/s12888-020-02734-6. [ABSTRACT FROM AUTHOR]

Formal Thought Disorder (FTD) is a defining feature of schizophrenia, which is often assessed through patients' speech. Meanwhile, the written language is less studied. The aim of the present study is to establish and validate a comprehensive clinical screening scale, capturing the full variety of empirical characteristics of writing in patients with schizophrenia. The 16-item Screening Instrument for Schizophrenic Features in Writing (SISFiW) is derived from detailed literature review and a "brainstorming" discussion on 30 samples written by patients with schizophrenia. One hundred and fifty-seven participants (114 patients with an ICD-10 diagnoses of schizophrenia; 43 healthy control subjects) were interviewed and symptoms assessed with the Positive and Negative Syndrome Scale (PANSS) and the Scale for the Assessment of Thought, Language, and Communication (TLC). Article samples written by each participant were rated with the SISFiW. Results demonstrated significant difference of the SISFiW-total between the patient group and healthy controls [(3.61 ± 1.72) vs. (0.49 ± 0.63), t = 16.64, p <0.001]. The inter-rater reliability (weighted kappa = 0.72) and the internal consistency (Cronbach's alpha coefficient = 0.613) were acceptable, but correlations with the criterion (PANSS and TLC) were unremarkable. The ROC analysis indicated a cutoff point at 2 with the maximal sensitivity (93.0 %)/specificity (93.0 %). Discriminant analysis of the SISFiW items yielded 8 classifiers that discriminated between the diagnostic groups at a perfect overall performance (with 90.4 % of original and 88.5 % cross-validated grouped cases classified correctly). This instrument appears to be practicable and reliable, with relatively robust discriminatory power, and may serve as a complementary tool to existing FTD rating scales. • Developed a screening instrument to assess features within the writing of subjects. • Items cover full variety of empirical characteristics of written language, as well as traits in graphology and writing trace. • The inter-rater reliability and the internal consistency of this scale are acceptable. • A minimum of 2 items can differentiate patient with schizophrenia from healthy people with accuracy higher than 90 %. • The properties measured in this screening instrument may not equate to Formal Thought Disorder (FTD) in written language. [ABSTRACT FROM AUTHOR]