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BACKGROUND: Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.METHODS: We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.RESULTS: Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = -0.16-0.79).CONCLUSIONS: This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.

Attention Deficit Hyperactivity Disorder (ADHD) is a common comorbid condition in children with epilepsy and migraine. Treatment of ADHD in children with epilepsy or migraine is essential but clinicians may overlook symptoms of ADHD and avoid appropriate use of medications that may reduce symptoms of ADHD without compromising treatment of epilepsy or migraine. Areas covered: PubMed was searched for articles on ADHD and epilepsy or migraine. Key papers were reviewed for additional articles. Areas of interest were: epidemiology, etiological factors, and treatment with emphasis on therapy. Expert commentary: Stimulant medication, especially methylphenidate, appears to be safe and effective in the treatment of ADHD in children with epilepsy or migraine. Unfortunately, data is limited with very few controlled trials of methylphenidate and very limited information on the use of amphetamines or non-stimulant drugs.

Background Minimisation of the delay to diagnosis is critical to achieving optimal outcomes for HIV patients and to limiting the potential for further onward infections. However, investigation of diagnosis delay is hampered by the fact that in most newly diagnosed patients the exact timing of infection cannot be determined and so inferences must be drawn from biomarker data. Methods We develop a Bayesian statistical model to evaluate delay-to-diagnosis distributions in HIV patients without known infection date, based on viral sequence genetic diversity and longitudinal viral load and CD4 count data. The delay to diagnosis is treated as a random variable for each patient and their biomarker data are modelled relative to the true time elapsed since infection, with this dependence used to obtain a posterior distribution for the delay to diagnosis. Data from a national seroconverter cohort with infection date known to within ± 6 months, linked to a database of viral sequences, are used to calibrate the model parameters. An exponential survival model is implemented that allows general inferences regarding diagnosis delay and pooling of information across groups of patients. If diagnoses are only observed within a given window period, then it is necessary to also model incidence as a function of time; we suggest a pragmatic approach to this problem when dealing with data from an established epidemic. The model developed is used to investigate delay-to-diagnosis distributions in men who have sex with men diagnosed with HIV in London in the period 2009–2013 with unknown date of infection. Results Cross-validation and simulation analyses indicate that the models developed provide more accurate information regarding the timing of infection than does CD4 count-based estimation. Delay-to-diagnosis distributions were estimated in the London cohort, and substantial differences were observed according to ethnicity. Conclusion The combination of all available biomarker data with pooled estimation of the distribution of diagnosis-delays allows for more precise prediction of the true timing of infection in individual patients, and the models developed also provide useful population-level information. Electronic supplementary material The online version of this article (10.1186/s12874-018-0522-x) contains supplementary material, which is available to authorized users.

Sea lamprey (Petromyzon marinus) is a species of invasive parasitic fish in the Great Lakes region of North America. Accurate estimates of larval lamprey populations in lake tributaries are necessary for making control decisions regarding treatment of lake tributaries with 3-trifluoromethyl-4-nitrophenol (TFM), a piscicide toxic to lamprey larvae. Analysis of environmental DNA (eDNA) isolated from water samples is a recent innovation under consideration for sea lamprey biomonitoring. eDNA analysis was performed before and at three time points after TFM treatment in a tributary of Lake Ontario (Ninemile Creek) to assess presence of invasive sea lamprey. Lamprey DNA was detected in four out of four sample locations before TFM treatment and three of four locations 72 hours following treatment. No lamprey DNA was detected in any of the locations 4 months or 12 months after TFM treatment of the creek. These results are consistent with known effectiveness of TFM treatment and provide evidence for the potential of eDNA analysis as a tool for monitoring decline of larval sea lamprey abundance due to TFM treatments.

There are several potential Nitrogen (N) loss mechanisms in a dry seeded and delayed flood system rice (Oryza Satvia L.) production system including urea volatilization and denitrification. The scope and magnitude of these potential losses are largely weather dependent. Two additives (stabilizers), Agrotain and Nutrisphere-N, have been offered to rice producers for controlling these potential losses. This study compared these two products in their ability to maintain rice grain yields, where cultural management maximizes these loss mechanisms. Response of rice to urea-N stabilizers varied in 2007 and 2008 depending on soil and environmental conditions. In 2007, dry soil surface at time of urea-N application and lack of rainfall resulted in a low loss due to N volatilization. However, urea-N volatilization or denitrification were higher in 2008 and using Agrotain stabilizer resulted in higher yields of rice at 78 kg N ha-1. Across years, Agrotain and Nutrisphere-N were similar in terms of slightly improving rice grain yields compared to untreated urea at the rate of 78 kg N ha-1. Therefore, urea stabilizers may offer a good solution in years with high potential for urea-N losses.

The purpose of this study was to evaluate atomoxetine treatment effects in attention-deficit/hyperactivity disorder (ADHD-only), attention-deficit/hyperactivity disorder with comorbid dyslexia (ADHD+D), or dyslexia only on ADHD core symptoms and on sluggish cognitive tempo (SCT), working memory, life performance, and self-concept.Children and adolescents (10-16 years of age) with ADHD+D (n=124), dyslexia-only (n=58), or ADHD-only (n=27) received atomoxetine (1.0-1.4 mg/kg/day) or placebo (ADHD-only subjects received atomoxetine) in a 16 week, acute, randomized, double-blind trial with a 16 week, open-label extension phase (atomoxetine treatment only). Changes from baseline were assessed to weeks 16 and 32 in ADHD Rating Scale-IV-Parent-Version:Investigator-Administered and Scored (ADHDRS-IV-Parent:Inv); ADHD Rating Scale-IV-Teacher-Version (ADHDRS-IV-Teacher-Version); Life Participation Scale-Child- or Parent-Rated Version (LPS); Kiddie-Sluggish Cognitive Tempo (K-SCT) Interview; Multidimensional Self Concept Scale (MSCS); and Working Memory Test Battery for Children (WMTB-C).At week 16, atomoxetine treatment resulted in significant (p0.05) improvement from baseline in subjects with ADHD+D versus placebo on ADHDRS-IV-Parent:Inv Total (primary outcome) and subscales, ADHDRS-IV-Teacher-Version Inattentive subscale, K-SCT Interview Parent and Teacher subscales, and WMTB-C Central Executive component scores; in subjects with Dyslexia-only, atomoxetine versus placebo significantly improved K-SCT Youth subscale scores from baseline. At Week 32, atomoxetine-treated ADHD+D subjects significantly improved from baseline on all measures except MSCS Family subscale and WMTB-C Central Executive and Visuo-spatial Sketchpad component scores. The atomoxetine-treated dyslexia-only subjects significantly improved from baseline to week 32 on ADHDRS-IV-Parent:Inv Inattentive subscale, K-SCT Parent and Teacher subscales, and WMTB-C Phonological Loop and Central Executive component scores. The atomoxetine-treated ADHD-only subjects significantly improved from baseline to Week 32 on ADHDRS-Parent:Inv Total and subscales, ADHDRS-IV-Teacher-Version Hyperactive/Impulsive subscale, LPS Self-Control and Total, all K-SCT subscales, and MSCS Academic and Competence subscale scores.Atomoxetine treatment improved ADHD symptoms in subjects with ADHD+D and ADHD-only, but not in subjects with dyslexia-only without ADHD. This is the first study to report significant effects of any medication on SCT.This study was registered at: http://clinicaltrials.gov/ct2/home, NCT00607919.

The spectre of American decline is once again animating both observers and practitioners of US foreign policy. The global financial crisis, a faltering American economy and continued costly and controversial military engagements overseas have been presented as conclusive proof that American foreign policy will soon lack the resources needed to sustain its previous international hegemony. Arguments of domestic weakness have been linked to analyses of the economic vitality of America's competitors to demonstrate a seemingly watertight case for relative decline. The inexorable rise of China has been presented from various quarters as evidence that the American era will soon be drawing to a close. Yet, such declinist arguments continue to suffer from fundamental weaknesses, overestimating the likely future strength of America's rivals while concurrently downplaying the capacity of the US to rejuvenate its economy and thus revivify its liberal universalist creed. The most interesting development in this regard has been the sudden resurgence of the US energy sector. Written off less than a decade ago as being in terminal decline, the American oil and gas industry has staged a remarkable recovery. Vast reserves of shale gas and accompanying tight oil offer the potential to aid the revival of the American economy, with some forecasts pointing to US energy self-sufficiency within two decades. Notions of US relative decline may yet prove premature. The geopolitical impact of American energy self-sufficiency is likely to be very significant, making an important contribution to a reversal of the US trade deficit, a revival of America's industrial base, and the possibility of a corresponding relative decline in power for conventional fossil fuel exporters.

BACKGROUND Acoustic signals play a critical role in mate choice, species recognition, communication, territoriality, predator escape and prey selection. Bark beetles, which are significant disturbance agents of forests, produce a variety of acoustic signals. RESULTS A bioacoustic approach to reducing bark beetle reproduction within wood tissues was explored. Playback of modified biological sounds reduced beetle reproductive output, tunneling distance and adult survival. CONCLUSION The targeted use of biologically relevant sounds disrupts insect behaviors and could be a species-specific, environmentally friendly method of insect management. © 2013 Society of Chemical Industry

Cardiovascular disease is the leading cause of death worldwide. In the absence of sufficient numbers of organs for heart transplant, alternate approaches for healing or replacing diseased heart tissue are under investigation. Designing biomimetic materials to support these approaches will be essential to their overall success. Strategies for cardiac tissue engineering include injection of cells, implantation of three-dimensional tissue constructs or patches, injection of acellular materials, and replacement of valves. To replicate physiological function and facilitate engraftment into native tissue, materials used in these approaches should have properties that mimic those of the natural cardiac environment. Multiple aspects of the cardiac microenvironment have been emulated using biomimetic materials including delivery of bioactive factors, presentation of cell-specific adhesion sites, design of surface topography to guide tissue alignment and dictate cell shape, modulation of mechanical stiffness and electrical conductivity, and fabrication of three-dimensional structures to guide tissue formation and function. Biomaterials can be engineered to assist in stem cell expansion and differentiation, to protect cells during injection and facilitate their retention and survival in vivo, and to provide mechanical support and guidance for engineered tissue formation. Numerous studies have investigated the use of biomimetic materials for cardiac regeneration. Biomimetic material design will continue to exploit advances in nanotechnology to better recreate the cellular environment and advance cardiac regeneration. Overall, biomimetic materials are moving the field of cardiac regenerative medicine forward and promise to deliver new therapies in combating heart disease.

The Obama administration's controversial use of drones in Afghanistan, Pakistan and Yemen has made the subject a hot topic of political and academic discourse. While most of this debate has focused so far on the legal, ethical and prudential use of large armed aerial vehicles, this article seeks to address the potential wider impact of this new technological innovation. The article argues that drones constitute a new and disruptive technology not just in the way that they have been used to enable a new form of counterterrorism. Instead, it argues that drones pose a new form of terrorist threat against the West which is at present under-analysed, unarticulated and underestimated. Part of the reason for this underestimation is the failure to appreciate the scale and scope of drone use for commercial purposes which is about to unfold. Technological innovation now means that drones will be capable of many jobs currently performed by small planes and helicopters, but more cheaply and easily-in addition to many other new applications. The proliferation of this cheap and easily available technology will make its application for terrorist use easy to achieve and difficult to counter. The ability of drones to penetrate traditional defences and established conceptions of what constitutes a plausible threat is a challenge which so far has gone unheeded. This article seeks to challenge that complacency. [ABSTRACT FROM AUTHOR]

Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Results: Subtype B patients (n = 3410) were mostly MSM (78%) and those with subtype C (n = 810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55–2.62, P

Background: Lack of viral load monitoring of ART is known to be associated with slower switch from a failing regimen and thereby higher prevalence of MDR HIV-1. Many countries have continued to use thymidine analogue drugs despite recommendations to use tenofovir in combination with a cytosine analogue and NNRTI as first-line ART. The effect of accumulated thymidine analogue mutations (TAMs) on phenotypic resistance over time has been poorly characterized in the African setting. Patients and methods: A retrospective analysis of individuals with ongoing viral failure between weeks 48 and 96 in the NORA (Nevirapine OR Abacavir) study was conducted. We analysed 36 genotype pairs from weeks 48 and 96 of first-line ART (14 treated with zidovudine/lamivudine/nevirapine and 22 treated with zidovudine/lamivudine/abacavir). Phenotypic drug resistance was assessed using the Antivirogram assay (v. 2.5.01, Janssen Diagnostics). Results: At 96 weeks, extensive TAMs (≥3 mutations) were present in 50% and 73% of nevirapine- and abacavir-treated patients, respectively. The mean (SE) number of TAMs accumulating between week 48 and week 96 was 1.50 (0.37) in nevirapine-treated participants and 1.82 (0.26) in abacavir-treated participants. Overall, zidovudine susceptibility of viruses was reduced between week 48 [geometric mean fold change (FC) 1.3] and week 96 (3.4, P = 0.01). There was a small reduction in tenofovir susceptibility (FC 0.7 and 1.0, respectively, P = 0.18). Conclusions: Ongoing viral failure with zidovudine-containing first-line ART is associated with rapidly increasing drug resistance that could be mitigated with effective viral load monitoring.

BACKGROUND: Colorectal resection through a midline laparotomy is a commonly performed surgical procedure to treat various bowel conditions. The typical postoperative hospital stay after this operation is 6 to 10 days. The main factors hindering early recovery and discharge are thought to include postoperative pain and delayed return of bowel function. Continuous infusion of a local anaesthetic into tissues surrounding the surgical incision via a multi‐lumen indwelling wound catheter placed by the surgeon prior to wound closure may reduce postoperative pain, opioid consumption, the time to return of bowel function, and the length of hospital stay. OBJECTIVES: To evaluate the efficacy and adverse events of continuous local anaesthetic wound infusion for postoperative pain after midline laparotomy for colorectal resection in adults. SEARCH METHODS: We searched the CENTRAL, MEDLINE and Embase databases to January 2019 to identify trials relevant to this review. We also searched reference lists of relevant trials and reviews for eligible trials. Additionally, we searched two clinical trials registers for ongoing trials. SELECTION CRITERIA: We considered randomised controlled trials (including non‐standard designs) or quasi‐randomised controlled trials comparing continuous wound infusion of a local anaesthetic versus a placebo or a sham after midline laparotomy for colorectal resection in adults. We did not compare continuous local anaesthetic wound infusion to other techniques, such as transverse abdominis plane block or thoracic epidural analgesia. We allowed non‐randomised analgesic co‐interventions carried out equally in the intervention and control groups. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials for inclusion and assessed their quality using the Cochrane 'Risk of bias' tool. We extracted data using standardised forms, including pain at rest and on movement (10‐point scale), opioid consumption via a patient‐controlled analgesia (PCA) system (mg morphine equivalent), postoperative opioid‐related adverse events, the time to rescue analgesia, the time to first flatus and to first bowel movement, the time to ambulation, the length of hospital stay, serious postoperative adverse events, and patient satisfaction. We quantitatively synthesised the data by meta‐analysis. We summarised and graded the certainty of the evidence for critical outcomes using the GRADEpro tool and created a 'Summary of findings' table. MAIN RESULTS: This review included six randomised controlled trials that enrolled a total of 564 adults undergoing elective midline laparotomy for colorectal resection comparing continuous wound infusion of a local anaesthetic to a normal saline placebo. Due to 23 post‐randomisation exclusions, a total of 541 participants contributed data to the analysis of at least one outcome (local anaesthetic 268; control 273). Most participants were aged 55 to 65 years, with normal body mass index and low to moderate anaesthetic risk (American Society of Anesthesiologists class I‐III). Random sequence generation, allocation concealment, and blinding were appropriately carried out in most trials. However, we had to downgrade the certainty of the evidence for most outcomes due to serious study limitations (risk of bias), inconsistency, indirectness, imprecision and reporting bias. Primary outcomes On postoperative day 1, pain at rest (mean difference (MD) −0.59 (from 3.1), 95% confidence interval (CI) −1.12 to −0.07; 5 studies, 511 participants; high‐certainty evidence), pain on movement (MD −1.1 (from 6.1), 95% CI −2.3 to −0.01; 3 studies, 407 participants; low‐certainty evidence) and opioid consumption via PCA (MD −12 mg (from 41 mg), 95% CI −20 to −4; 6 studies, 528 participants; moderate‐certainty evidence) were reduced in the local anaesthetic group compared to the control group. Secondary outcomes There was a reduction in the time to first bowel movement (MD −0.67 from 4.4 days, 95% CI −1.17 to −0.17; 4 studies, 197 participants; moderate‐certainty evidence) and the length of hospital stay (MD −1.2 from 7.4 days, 95% CI −2.0 to −0.3; 4 studies, 456 participants; high‐certainty evidence) in the local anaesthetic group compared to the control group. There was no evidence of a difference in any serious postoperative adverse events until hospital discharge (RR 1.04, 95% CI 0.68 to 1.58; 6 studies, 541 participants; low‐certainty evidence) between the two study groups. AUTHORS' CONCLUSIONS: After elective midline laparotomy for colorectal resection, continuous wound infusion of a local anaesthetic compared to a normal saline placebo reduces postoperative pain at rest and the length of hospital stay, on the basis of high‐certainty evidence. This means we are very confident that the effect estimates for these outcomes lie close to the true effects. There is moderate‐certainty evidence to indicate that the intervention probably reduces opioid consumption via PCA and the time to first bowel movement. This means we are moderately confident that effect estimates for these outcomes are likely to be close to the true effects, but there is a possibility that they are substantially different. The intervention may reduce postoperative pain on movement, however, this conclusion is based on low‐certainty evidence. This means our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. There is low‐certainty evidence to indicate that the intervention may have little or no effect on the rates of any serious postoperative adverse events until hospital discharge. High‐quality randomised controlled trials to evaluate the intervention with a focus on important clinical and patient‐centred outcomes are needed.

CONTENTS S1 PrefaceFrank Besag, Albert Aldenkamp, Rochelle Caplan, David W. Dunn, Giuseppe Gobbi, Matti Sillanpaa S2 Epidemiology of psychiatric/behavioural disorder in children with epilepsyMatti Sillanpaa, Frank Besag, Albert Aldenkamp, Rochelle Caplan, David W. Dunn, Giuseppe Gobbi S8 Epilepsy and ADHDFrank Besag, Giuseppe Gobbi, Rochelle Caplan, Matti Sillanpaa, Albert Aldenkamp, David W. Dunn S16 Epilepsy and AutismFrank Besag, Albert Aldenkamp, Rochelle Caplan, David W. Dunn, Giuseppe Gobbi, Matti Sillanpaa S24 Anxiety, depression and childhood epilepsyDavid W. Dunn, Frank Besag, Rochelle Caplan, Albert Aldenkamp, Giuseppe Gobbi, Matti Sillanpaa S31 Epilepsy and psychosis in children and teenagersFrank Besag, Rochelle Caplan, Albert Aldenkamp, David W. Dunn, Giuseppe Gobbi, Matti Sillanpaa S37 Behavioural and psychiatric disorders associated with epilepsy syndromesFrank Besag, Giuseppe Gobbi, Albert Aldenkamp, Rochelle Caplan, David W. Dunn, Matti Sillanpaa S49 Subtle behavioural and cognitive manifestations of epilepsyFrank Besag, Giuseppe Gobbi, Albert Aldenkamp, Rochelle Caplan, David W. Dunn, Matti Sillanpaa S55 Adverse cognitive and behavioural effects of antiepileptic drugsAlbert Aldenkamp, Frank Besag, Giuseppe Gobbi, Rochelle Caplan, David W. Dunn, Matti Sillanpaa S68 Behavioural effects of epilepsy surgeryFrank Besag, Rochelle Caplan, Albert Aldenkamp, David W. Dunn, Giuseppe Gobbi, Matti Sillanpaa S77 When should pharmacotherapy for psychiatric/behavioural disorders in children with epilepsy be prescribed?Frank Besag, Albert Aldenkamp, Rochelle Caplan, David W. Dunn, Giuseppe Gobbi, Matti Sillanpaa PREFACE Psychiatric/behavioural problems are common in children with epilepsy, typically occurring in around 35-50% in epidemiological studies. They can affect the quality of life of the children and their families to a major degree. In many cases these problems create more of a challenge than the epilepsy itself. However, there are relatively few high-quality studies in this area. This collection of papers is intended to represent one step in a long journey towards addressing the lack of information by drawing together the available data on a number of key topics including epidemiology, the relationships between epilepsy and several psychiatric disorders, the role of the epilepsy itself, the effects of antiepileptic drugs and surgery and the place of pharmacotherapy. Although there is relatively good information on epidemiology there is very little information on the causes of and risk factors for psychiatric disorders in childhood epilepsy that might give insight into early diagnosis and prevention. Despite the growing amount of research in genetics, the impact on management has been minimal so far. There is also very sparse high-quality randomised controlled trial data on treatment of psychiatric disorders in childhood epilepsy. Furthermore, with a few exceptions, there is a striking lack of neuroimaging studies in this field. These are areas that would benefit from further attention and research. The information in this report has been put together by the members of the immediate past Child Neuropsychiatry Taskforce of the Neuropsychology Commission of the International League Against Epilepsy, guided by the then chairpersons of the commission: Andres Kanner and Marco Mula. The immediate past Task Force was officially in place from July 2009 to June 2013, although their work has continued since then, in relation to this publication and updating all the papers.

Psychiatric/behavioural problems can have a major effect on quality of life. Epidemiological studies in Europe, Scandinavia and the USA have confirmed a high rate of psychiatric disorder in children with epilepsy, typically around 35 to 50%. In children with additional impairment, particularly those with intellectual disability, the rates are even higher, over 50%. Determining the causes of these high rates and deciding on the best strategies, either for prevention or for optimal management, remain major challenges.

ADHD occurs in about 30% of children with epilepsy. The causes of ADHD features include some antiepileptic drugs, the epilepsy itself and underlying brain dysfunction. Management of the ADHD will depend on the cause. Treatment with methylphenidate is effective in about 70% of cases; standard treatments with methylphenidate, dexamfetamine and atomoxetine are very unlikely to exacerbate seizures.

Psychosis related to epilepsy or antiepileptic treatment can occur in teenagers and very rarely in children. Postictal, interictal and antiepileptic-drug-induced psychosis have all been reported in young people. Whether ictal psychosis occurs in this age group remains open to debate. Neuronal antibody encephalitis such as anti-NMDA receptor encephalitis can present with seizures and psychosis, both of which can resolve with prompt, appropriate immunotherapy. In addition, there have been several reports in which the terms psychosis or psychotic features have been used loosely to describe behavioural disturbance in children with epilepsy; in these cases there have apparently been no diagnostic features of psychosis, implying that these terms should not have been used. The management of epilepsy-related psychosis in young people is similar to that in adults. Antipsychotic medication should not be withheld if it is needed on clinical grounds. If the psychosis has been induced by antiepileptic medication then a medication review is necessary.

The categorisation of the childhood epilepsies into a number of different syndromes has allowed greater insight into the prognosis, not only with regard to seizure control but also in relation to cognitive and behavioural outcome. The role of genetics in determining both the syndrome and the behavioural outcome remains promising, although the promise is still largely unfulfilled. The behavioural/psychiatric outcome of a selection of the large number of childhood epilepsy syndromes is presented. The rate of autism in West syndrome, particularly in children who have tuberous sclerosis with temporal tubers, is high. In Dravet syndrome there is a loss of skills, with an associated increase in behavioural problems. The frequency of both subtle and overt seizures in the Lennox-Gastaut syndrome almost certainly accounts for the apparent poor motivation; however, a marked improvement in seizure control with treatment can also result in behavioural problems, probably as a result of the "release phenomenon". A number of cognitive problems can arise in the so-called "benign" syndrome of epilepsy with centrotemporal spikes (BECTS) and the rate of ADHD is high. Autistic features and ADHD have been described in the Landau-Kleffner syndrome and other syndromes associated with electrical status epilepticus of slow-wave sleep (ESES). Early effective treatment may reverse some of these features. There is clear evidence for a behavioural syndrome in relation to juvenile myoclonic epilepsy (JME), in which both clinical descriptions and functional neuroimaging indicate frontal lobe deficits.

The literature was evaluated for cognitive and more general behavioural effects. We distinguished the older antiepileptic drugs (AEDs), from the newer and newest AEDs. The striking finding was the lack of information on children. From the available evidence it would appear that there may be negative cognitive effects with phenobarbital, phenytoin, topiramate and zonisamide, and adverse behavioural effects with phenobarbital, valproate, gabapentin, topiramate, levetiracetam and zonisamide. There is inconclusive data on ethosuximide, clobazam, vigabatrin, felbamate, pregabalin, stiripentol, rufinamide, lacosamide and retigabine. The following drugs appear to be neutral with regard to cognitive effects: valproate, carbamazepine, gabapentin and oxcarbazepine. Carbamazepine appears to be neutral with regard to behavioural effects. Positive cognitive effects have been reported with lamotrigine and levetiracetam. Positive behavioural effects have been reported with lamotrigine. Recommendations are provided.

There are relatively few studies of the behavioural outcome of epilepsy surgery in children that have used standardised behavioural measures before and after the procedure. Those investigations that have used such measures are often on mixed groups with mixed pathology, implying that the numbers, when stratified, are very small. They are also often retrospective. Furthermore, because placebo surgery is generally not an option, the studies have been open and they are usually uncontrolled. The few available data suggest that, although individual children may benefit or deteriorate, there is little overall group effect of temporal or extratemporal surgery on behavioural/psychiatric outcome. Hemispherectomy has traditionally been associated with the expectation of marked behavioural improvement but firm data are lacking. Multiple subpial transection performed for electrical status epilepticus of slow-wave sleep in the Landau-Kleffner syndrome can result in marked improvements in cognition and behaviour. Vagus nerve stimulation appears to improve quality of life and mood/behaviour but again the quality of the data has been questioned. There is a need for large, prospective, multicentre, collaborative studies using standardised cognitive and behavioural measures before and after surgery to provide an adequate database on the outcome of various categories of procedures, pathologies and patients.

Anxiety and depression are relatively common in children with epilepsy: anxiety has been reported in 15-36% and depression in 8-35% of patients. In some cases these conditions may be related specifically to the epilepsy or its treatment. For example, some antiepileptic drugs are known to be associated with depression in adults and are likely to have a similar effect in young people. Emotional reactions to the epilepsy, for example anxieties and social phobia related specifically to the seizures, might be expected and require appropriate management. However, there is a growing recognition of the bidirectional relationship between epilepsy and psychiatric disorders, including depression, largely based on adult data. Cognitive behavioural therapy and serotonin reuptake inhibitors are used for treatment of both anxiety and depression in children with epilepsy. There is a need for greater understanding of the causes of these conditions in young people and there is also a need for better evidence for optimal treatment.

A subtle behavioural or cognitive manifestation of epilepsy can be defined in two ways. First, epileptiform discharges not presenting as obvious seizures may nevertheless affect cognition and/or behaviour. Second, the actual seizures may be obvious but the way they affect cognition or behaviour may not be. There is a growing body of evidence indicating that the epileptiform discharges in benign epilepsy with centrotemporal spikes can affect behaviour and cognition. The focal discharges in other forms of epilepsy can also be associated with behavioural change. The Landau-Kleffner syndrome, the CSWS syndrome, transitory cognitive impairment and transient epileptic amnesia provide further examples of cognitive and behavioural manifestations resulting from subtle manifestations of the epilepsy. Prompt, effective antiepileptic treatment with medication or surgery can improve behaviour and cognition in at least some cases.

Background Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. Objectives We examined darunavir DRMs emerging in clinical practice in the UK. Patients and methods Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PI-naive controls. Results Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Conclusions Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility.

Looking at John Milbank’s recent turn to Fr. Sergej Bulgakov, this paper argues that the theological and philosophical commitments they share are overshadowed by a deeper difference concerning the role each assigns the church in secular culture. It turns to Milbank’s roots in Augustine’s philosophy of history, which he argues could have allowed the church to overtake the pagan (which founds the secular) were it not for his distinction between the “visible” church and its deferred (eschatological) perfection. Bulgakov also criticizes Augustine’s doctrine of the church, or so he thinks. He actually misreads Augustine, accusing the bishop of holding a doctrine of the church that Milbank would have liked him to have held. This suggests that Bulgakov would not agree with Milbank’s view that the church should “enact” God’s judgment in history by opposing itself to the secular.

In the study we describe adaptive functioning in children with epilepsy whose primary caregivers identified them as having learning problems. This was a cross-sectional study of 50 children with epilepsy and learning problems. Caregivers supplied information regarding the child’s adaptive functioning and behavior problems. Children rated their self-concept and completed a battery of neuropsychological tests. Mean estimated IQ (PPVT-III) in the participant children was 72.8 (SD = 18.3). On average, children scored 2 standard deviations below the norm on the Vineland Adaptive Behavior Scale–II and this was true even for children with epilepsy who had estimated IQ in the normal range. In conclusion, children with epilepsy and learning problems had relatively low adaptive functioning scores and substantial neuropsychological and mental health problems. In epilepsy, adaptive behavior screening can be very informative and guide further evaluation and intervention, even in those children whose IQ is in the normal range.

Disruptive behavior disorders (DBD) are among the most commonly diagnosed mental disorders in children and adolescents. Some important characteristics of DBD vary based on the presence or absence of comorbid attention-deficit/hyperactivity disorder (ADHD), which may affect the understanding of and treatment decision-making related to the disorders. Thus, identifying neurobiological characteristics of DBD with comorbid ADHD (DBD+ADHD) can provide a basis to establish a better understanding of the condition. This study aimed to assess abnormal white matter microstructural alterations in DBD+ADHD as compared to DBD alone and healthy controls using diffusion tensor imaging (DTI). Thirty-three DBD (19 with comorbid ADHD) and 46 age-matched healthy adolescents were studied using DTI. Fractional anisotropy (FA), and mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were analyzed using tract-based spatial statistics (TBSS). Significantly lower FA and higher MD, RD and AD in many white matter fibers were found in adolescents with DBD+ADHD compared to controls. Moreover, lower FA and higher RD were also found in the DBD+ADHD versus the DBD alone group. Alterations of white matter integrity found in DBD patients were primarily associated with ADHD, suggesting that ADHD comorbidity in DBD is reflected in greater abnormality of microstructural connections.

Mutations in mitochondrial DNA (mtDNA) cause a variety of pathologic states in human patients. Development of animal models harboring mtDNA mutations is crucial to elucidating pathways of disease and as models for preclinical assessment of therapeutic interventions.This review covers the knowledge gained through animal models of mtDNA mutations and the strategies used to produce them. Animals derived from spontaneous mtDNA mutations, somatic cell nuclear transfer (SCNT), nuclear translocation of mitochondrial genes followed by mitochondrial protein targeting (allotopic expression), mutations in mitochondrial DNA polymerase gamma, direct microinjection of exogenous mitochondria, and cytoplasmic hybrid (cybrid) embryonic stem cells (ES cells) containing exogenous mitochondria (transmitochondrial cells) are considered.A wide range of strategies have been developed and utilized in attempts to mimic human mtDNA mutation in animal models. Use of these animals in research studies has shed light on mechanisms of pathogenesis in mitochondrial disorders, yet methods for engineering specific mtDNA sequences are still in development.Research animals containing mtDNA mutations are important for studies of the mechanisms of mitochondrial disease and are useful for the development of clinical therapies. This article is part of a Special Issue entitled Biochemistry of Mitochondria.

OBJECTIVE To assess the efficacy of atomoxetine (ATX) and impact of treatment on family functioning in adults with ADHD. METHODS Adults with attention-deficit/hyperactivity disorder (ADHD) having both a spouse/partner and child were randomized to placebo (n = 234) or ATX (n = 268) for 24 weeks. Attention-deficit/hyperactivity disorder measures included the Conners Adult ADHD Rating Scale total ADHD Symptoms score and Clinical Global Impression-ADHD-Severity. Marital measures included the Dyadic Adjustment Scale and the Family Assessment Measure Dyadic Relationship Scale (FAM III). Parenting measures included the Parenting Stress Index, Alabama Parenting Questionnaire, and Parenting Sense of Competence Scale (PSCS). RESULTS Improvement was greater with ATX over placebo at 24 weeks on the Conners Adult ADHD Rating Scale (-16.43 vs -8.65; P < 0.001, repeated measures) and Clinical Global Impression (P < 0.001, last observation carried forward). Baseline-to-end point changes in marital and parenting measures were significant but not between treatment groups. Post hoc analyses showed significant interaction of treatment and impairment for the FAM III Task Accomplishment (patient) and Role Performance (patient and spouse) items and PSCS efficacy. Further stratification by sex or presence of a child with ADHD yielded significant interaction and treatment differences for the FAM III Task Accomplishment and the FAM III and Dyadic Adjustment Scale affective expression items, PSCS total score, Alabama Parenting Questionnaire Corporal Punishment, and Parenting Stress Index attachment items. CONCLUSIONS Atomoxetine demonstrated significant ADHD symptom reduction over 24 weeks. Although both groups demonstrated baseline-to-end point changes on many marital and parenting measure items, there were no treatment differences. Maladaptive behaviors of long-standing ADHD may benefit from both medication and behavioral-psychosocial intervention.

United States ports must be prepared for the threat of a small-vessel attack using weapons of mass destruction (WMD). To reduce the risk of such an attack, modeling was conducted at the Savannah River National Laboratory (SRNL) in Aiken, South Carolina, to develop options for redeployment of existing maritime law enforcement resources, deployment of new resources, and optimal use of geographic terrain. Agent-based modeling (ABM) implemented by the Automated Vulnerability Evaluation for Risks of Terrorism (AVERT®) software was used to conduct computer-based simulation modeling. The port-specific models provided estimates for the probability of encountering an adversary based on allocated resources under varying environmental conditions and traffic flow rates. Defensive resources include patrol and response platforms, some of which may be more appropriate in particular environmental conditions. A diverse range of potential adversary and attack scenarios was assessed for a large area port and also for a port with a narrow inlet, thereby identifying vulnerable pathways. For chokepoint operations, the probability of encountering an adversary was estimated for various configurations and operational tempos. As traffic flow increased, the probability of encountering an adversary decreased because the adversary could assimilate into traffic, while security forces were preoccupied inspecting pleasure craft. However, there was a significant increase in the probability of encountering an adversary ( P(Encounter)) when additional patrols were added. Noted was a decreasing marginal benefit of additional patrols at low traffic levels. In open water, use of helicopters on patrol substantially increased the P(Encounter) by directing on-water security to target vessels. This capability was due to the far-reaching vision and speed capabilities of helicopters. As a result of ABM, more effective countermeasures can be deployed with available resources to reduce the risk of a small-vessel attack using WMD. The models can be expanded to all ports in the United States using generic models similar to those presented herein that can be matched to any port based on its size and shape.

INTRODUCTION The CD4 count and CD4 percentage (CD4%) are both strong predictors of clinical disease progression in human immunodeficiency virus (HIV). Although individuals may show discordancy between their CD4 count and CD4%, the clinical relevance of this is unclear. METHODS Discordancy was defined where the CD4% was ≤10th percentile for a selected CD4 count range (referred to as low discordancy), within the central 80% range (concordant), or ≥90th percentile (high discordancy). Regression methods identified factors associated with low and high discordancy in untreated individuals and assessed the impact of discordancy on treatment responses to highly active antiretroviral therapy (HAART). RESULTS High discordancy was associated with female sex, low viral load, and white ethnicity; low discordancy was associated with black or nonwhite ethnicity, older age, and injection drug use. Clinical event rates were higher in individuals with high discordancy starting HAART, but there was no association with subsequent HIV progression by 6 months after starting HAART. CD4 count increases remained lower, by 20 cells/mm(3), in individuals with low discordancy, and higher, by 27 cells/mm(3), in those with high discordancy. CONCLUSIONS Overall discrepancies between the CD4/CD4% are small, confirming the use of absolute CD4 counts as a monitoring tool.

Objectives The purposes of this 36-month study of children with first recognized seizures were: (1) to describe baseline differences in behavior problems between children with and without prior unrecognized seizures; (2) to identify differences over time in behavior problems between children with seizures and their healthy siblings; (3) to identify the proportions of children with seizures and healthy siblings who were consistently at risk for behavior problems for 36 months; and (4) to identify risk factors for behavior problems 36 months following the first recognized seizure. Risk factors explored included demographic (child age and gender, caregiver education), neuropsychological (IQ, processing speed), seizure (epileptic syndrome, use of antiepileptic drug, seizure recurrence), and family (family mastery, satisfaction with family relationships, parent response) variables. Methods Participants were 300 children aged 6 through 14 years with a first recognized seizure and 196 healthy siblings. Data were collected from medical records, structured interviews, self-report questionnaires, and neuropsychological testing. Behavior problems were measured using the Child Behavior Checklist and the Teacher's Report Form. Data analyses included descriptive statistics and linear mixed models. Results Children with prior unrecognized seizures were at higher risk for behavior problems at baseline. As a group, children with seizures showed a steady reduction in behavior problems over time. Children with seizures were found to have significantly more behavior problems than their siblings over time, and significantly more children with seizures (11.3%) than siblings (4.6%) had consistent behavior problems over time. Key risk factors for child behavior problems based on both caregivers and teachers were: less caregiver education, slower initial processing speed, slowing of processing speed over the first 36 months, and a number of family variables including lower levels of family mastery or child satisfaction with family relationships, lower parent support of the child's autonomy, and lower parent confidence in their ability to discipline their child. Conclusions Children with new-onset seizures who are otherwise developing normally have higher rates of behavior problems than their healthy siblings; however, behavior problems are not consistently in the at-risk range in most children during the first 3 years after seizure onset. When children show behavior problems, family variables that might be targeted include family mastery, parent support of child autonomy, and parents’ confidence in their ability to handle their children's behavior.

Only recently have investigations of the relationship between media violence exposure (MVE) and aggressive behavior focused on brain functioning. In this study, we examined the relationship between brain activation and history of media violence exposure in adolescents, using functional magnetic resonance imaging (fMRI). Samples of adolescents with no psychiatric diagnosis or with disruptive behavior disorder (DBD) with aggression were compared to investigate whether the association of MVE history and brain activation is moderated by aggressive behavior/personality. Twenty-two adolescents with a history of aggressive behavior and diagnosis of either conduct disorder or oppositional-defiant disorder (DBD sample) and 22 controls completed an emotional Stroop task during fMRI. Primary imaging results indicated that controls with a history of low MVE demonstrated greater activity in the right inferior frontal gyrus and rostral anterior cingulate during the violent word condition. In contrast, in adolescents with DBD, those with high MVE exhibited decreased activation in the right amygdala, compared with those with low MVE. These findings are consistent with research demonstrating the importance of fronto-limbic structures for processing emotional stimuli, and with research suggesting that media violence may affect individuals in different ways depending on the presence of aggressive traits.

Objectives Children with long-standing epilepsy have a significantly increased risk of academic underachievement compared with healthy controls. We prospectively followed children from seizure onset to assess the relationship between change in neuropsychological functioning and change in academic achievement and to explore the risk and protective moderating effects of demographic, seizure, and family variables. Methods As part of a larger study, neuropsychological and academic data were collected at both baseline and 36 months for 219 children 6–14 years of age with seizures. Prior factor analysis of results from a battery of well-standardized neuropsychological tests yielded four factors: language, processing speed, attention/executive/construction, and verbal memory/learning. Academic achievement was measured with the Woodcock–Johnson Revised Achievement Test Battery. Correlation coefficients and linear mixed models were used for analysis. Results The reading and math scores of children with seizures and siblings did not differ at baseline, but children with seizures had lower scores than siblings at 36 months. Writing scores were significantly lower for affected children than siblings at both times. Among children with seizures, there were positive correlations between neuropsychological functioning and academic achievement at baseline and 36 months. Changes in language and in verbal memory/learning were positively correlated with change in reading achievement ( r = 0.25 and r = 0.17, respectively). Age at onset moderated the association between change in neuropsychological functioning and change in reading and writing achievement ( P ≤ 0.006), with stronger relationships among younger children (β = 0.25–0.44). The association between change in language and change in writing achievement was moderated by caregiver anxiety ( P = 0.04; stronger for more anxious parents, β = 0.40), and the association between change in processing speed and change in math achievement was moderated by etiology ( P = 0.02; stronger for symptomatic/cryptogenic vs idiopathic, β = 0.29). Gender and other family variables did not have significant moderating effects. Conclusions Changes in neuropsychological function were associated with changes in academic achievement following onset of seizures, with risk factors being younger age at onset, lower caregiver education, high parental anxiety, and symptomatic/cryptogenic etiology. Academic performance should be closely monitored in children with early-onset seizures.

Objectives: To describe the resistance mutations selected by a first-line regimen of zidovudine/lamivudine/tenofovir in the absence of real-time viral load monitoring. Design: A substudy of 300 participants from the Development of Antiretroviral Therapy in Africa trial in Uganda and Zimbabwe, which compared managing antiretroviral therapy with and without laboratory monitoring. Methods: Stored plasma samples from selected time points were assayed retrospectively for HIV-1 RNA. The pol gene in all baseline samples and those with HIV RNA >1000 copies per milliliter at weeks 24 and 48 were sequenced. Results: The proportion with HIV RNA >1000 copies per milliliter increased from 15% at 24 weeks to 24% at 48 weeks. Eighteen of 31 (58%) genotyped samples at 24 weeks had ≥1 major nucleoside reverse transcriptase inhibitor-associated mutations compared with 41 of 47 (87%) at 48 weeks. Excluding 1 nonadherent patient, a mean of 2.0 (95% confidence interval: 1.3 to 2.8) thymidine analogue mutations (TAMs) developed between weeks 24 and 48 among 14 patients with HIV RNA >1000 copies per milliliter at both time points. K65R was detected in 8 of 63 (13%) patients and was negatively associated with number of TAMs (P = 0.01) but not viral subtype (P = 0.30). Conclusions: A high rate of acquisition of TAMs, but not of K65R, among patients with prolonged viraemia was observed. However, most patients were virologically suppressed at 48 weeks, and long-term clinical and immunological outcomes in the Development of Antiretroviral Therapy in Africa trial were favorable.

Background There is an increasing prevalence of non-B subtype HIV type-1 (HIV-1) infections in Europe, refecting patterns of migration. We examined the characteristics of HIV-1 drug resistance in antiretroviral treatment (ART)-naive individuals migrating to the UK. Methods Resistance tests reported to the UK HIV Drug Resistance Database between 2001 and 2006 were included. Demographic data were obtained via linkage to national databases. Resistance was defined as ≥1 drug resistance mutation. Non-B HIV-1 subtype was used as a surrogate marker of infection acquired outside the UK. Logistic regression was used to examine the association between demographics and the prevalence of resistance. Results Overall, 196/4,291 (4.6%) samples with non-B subtype showed resistance compared with 745/6,435 (11.6%) samples for subtype B. Among non-B subtypes, the prevalence of resistance decreased over time (6.0% in 2001–2003 to 3.2% in 2006) and was independently associated with later calendar year of sampling ( P=0.001). Resistance was confined mainly to one ART class (85%); non-nucleoside reverse transcriptase inhibitor resistance was more common in subtype C (47%) compared with non-B non-C subtypes (29%; P=0.02). M184V was more common in non-B subtypes (non-B 30% versus B 5%; PConclusions In ART-naive individuals living in the UK, but who are likely to have acquired HIV-1 abroad, we observed a downward trend in resistance over time, which is surprising in light of ART roll-out in resource-limited settings. Reassuringly, resistance was mainly confined to one drug class; however, patterns of resistance differed by subtype, with some evidence of possible undisclosed prior therapy in non-B subtypes.

The nature of executive dysfunction in youth with disruptive behavior disorders (DBD) remains unclear, despite extensive research in samples of children with attention-deficit hyperactivity disorder (ADHD). To determine the relationship between DBD, ADHD, and executive function deficits in aggressive teens, adolescents with DBD and comorbid ADHD (DBD + ADHD; n = 25), DBD without ADHD (DBD-ADHD; n = 23), and healthy controls (HC; n = 25) were compared on neurocognitive tests and questionnaires measuring executive functioning. Teens with DBD + ADHD performed worse on both neurocognitive and questionnaire measures of executive function than the DBD-ADHD and HC groups. Results suggest that subgroups of DBD may exist depending on the presence or absence of comorbid ADHD, which may have implications for the selection and efficacy of treatment strategies.

We present a Monte Carlo model of the uranian rings, and compare this model to images of the system obtained with the Keck adaptive optics system in July 2004, at a wavelength of 2.2 μm (from de Pater et al. (de Pater, I., Gibbard, S.G., Hammel, H.B. [2006a]. Icarus 180, 186–200)). We confirm the presence of the ζ ring, but show that this ring must extend inwards much further than previously thought, although with an optical depth much lower than that in the main ζ ring component. We further confirm dust rings between rings α–4 and β–α, as well as near the λ ring. In addition, we show that a broad sheet of faint material (τ0 ∼ 10−3) must be present through most of the ring region, from the α ring through the λ ring.

Data from 5 atomoxetine trials in pediatric outpatients with attention-deficit/hyperactivity disorder (ADHD) were divided into training and validation data sets to develop models predicting atomoxetine treatment response, using changes in individual ADHD Rating Scale (ADHD-RS) items early in treatment. Treatment response was predicted after 1 week by a ≥1-point score decrease in ADHD-RS item 15 (“easily distracted;” positive predictive values [PPVs]: 84.9%, 74.3%, and 73.3%; negative predictive values [NPVs]: 52.6%, 50.5%, and 46.3%; training and 2 validation data sets, respectively); after 2 to 3 weeks, by a ≥1-point score decrease in ADHD-RS item 1 (“fails to give close attention or makes careless mistakes;” PPV = 77.7% and 77.9%) and by the absence of a ≥1-point score decrease on ADHD-RS items 1 and 10 (“on the go;” NPV = 72.2% and 77.5%), or by the combination of items 1 and 10 (PPVs: 75.1% and 75.4%; NPVs: 72.2% and 77.5%; training and validation data sets, respectively).