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It seems a truism of American politics that second presidential terms are destined to be less successful than the period of office which they follow and yet there is very little academic analysis as to why this is the case. Whether there are inherent or structural features of the US political system that unduly affects second-term presidencies and what impact these features might have on the remainder of the Bush administration is the subject of this article. While the impact of this phenomenon is analysed in general, particular attention is focused on the effect of American foreign policy since the Bush presidency, because of Iraq, this subject will ultimately determine the success or failure of the second term. This focus also reflects the fact that second-term administrations tend to be dominated by a focus on foreign policy. The article argues that despite being returned to power with a considerable number of political advantages compared with previous presidents at this stage of their tenure, the Bush administration is already displaying many of the characteristics of an underachieving second term. The article consists of three sections: part one examines the presidential record and analyses the contention that second terms are somehow different; part two sets out the reasons that might account for this factor; and part three applies these factors to the Bush administration to see which of these features apply to the present incumbent and thus what can be expected for the remainder of his second term in office until January 2009.

Children with epilepsy have a significant risk for problems with attention and/or attention deficit hyperactivity disorder. Clinical studies suggest a prevalence of 30% to 40%. Inattention is more common than hyperactivity and impulsivity. Additional central nervous system dysfunction and intractable seizures are major risk factors. Treatment should include psychoeducational interventions and medication. Stimulant drugs are safe and effective in children with epilepsy and currently are first-line agents for treatment of attention problems in this population.

We present Jupiter synchrotron radiation data obtained over a period of 18 yr (1.5 Jovian yr) taken at the VLA at ~20 cm. We look at intensity, polarization, Jovicentric distance, and magnetic latitude and compare the data to a model to distinguish variations over time from variations caused by viewing geometry, i.e., changing DE. No obvious changes in the nature of Jupiter's intrinsic synchrotron radiation were detected other than variations in intensity from year to year. Additionally, a comparison between the data and model at all DE indicate that Jupiter's magnetic field is much more complex than Connerney's O6 magnetic field model we used. Specifically, the intensity and polarization of the main radiation peaks of the model at λCML ~ 275°-360° show the largest deviations from the data in the main radiation peaks. Moreover, the radiation peaks in the model Jovian distances are overall farther away than in the data, which is an effect of various parameters such as the radial diffusion coefficient, the generic loss term in the diffusion coefficient, and the energy spectrum of electrons. Despite the differences between the data and model in intensity, polarization, and Jovian distance, the modeled magnetic latitude provides an excellent fit to the data.

Adolescents with disruptive behavior disorder (DBD) and controls were investigated using an optimized MR diffusion tensor imaging (DTI) protocol in order to assess any possible structural abnormalities associated with DBD. Thirty-six patients and 40 normal subjects were examined. The extracted diffusion fractional anisotropy (FA) results demonstrate that for the DBD patients there is significantly reduced FA in both the frontal and left temporal regions. The largest brain area with significantly reduced FA is located within the arcuate fasciculus, which has projections extending from the temporal lobe to the frontal lobe along the lateral ventricle, lateral to the tapetum. The reduced FA reflects directly a lower extent of myelination and less coherent fiber track structures in the fasciculus, which in turn may indicate communication weakness among the associated cortical areas. The detected white matter microstructural abnormality, therefore, may be related to the developmental deficits observed in the patient group.

We compared three maintenance immunosuppressive regimens in a rapid discontinuation of prednisone protocol. From March 1, 2001, through December 31, 2003, 239 first and second kidney transplant recipients (166 LD; 73 DD) were randomized. All recipients were treated with Thymoglobulin; all received steroids intraoperatively and for 5 days postoperatively. Randomization was to cyclosporine–mycophenolate mofetil (n = 85); high-level tacrolimus (TAC) (8–12 ng/mL)–low-level sirolimus (SRL) (3–7 ng/mL) (n = 72); or low-level TAC (3–7 ng/mL)–high-level SRL (8–12 ng/mL) (n = 82). We found no difference at 24 months between groups in patient, graft, death-censored graft, or acute rejection-free graft survival, or in kidney function. Wound complications were more common in SRL-treated recipients (p = 0.02); we found no other differences between groups in complication rates. Our data suggest that excellent patient and graft survival and low rejection rates can be obtained using a variety of maintenance protocols without prednisone.

‘Isolationism’ is a much used and abused term in the contemporary American foreign policy debate. This article seeks to illuminate some of the misunderstandings that surround the use of this term by challenging seven persistent myths about isolationism. In so doing it sheds light on the often unarticulated role that this and other ideas play in the US foreign policy debate. It also seeks to demonstrate the nature of the main ideational cleavages within this debate which the isolationist name-calling obscures, and to show the way in which language is used in the political discourse and how its meaning in this debate changes over time.

Summary Polymorphic Alu insertions (POALINs) are known to contribute to the strong polymorphic nature of the Major Histocompatibility Complex (MHC). Previous population studies on MHC POALINs were limited to only Australian Caucasians and Japanese. Here, we report on the individual insertion frequency of the five POALINs within the MHC class I region, their HLA-A and -B associations, and the three and four locus alpha block POALIN haplotype frequencies in the Northeastern (NE) Thai population. Of the five POALINs, the lowest frequency was 0.018 for AluyHF and the highest frequency was 0.292 for AluyHJ and AluyHG. The strongest positive associations between the POALINs and HLA class I alleles was between AluyMICB and HLA-B ∗ 57, AluyHJ and HLA-A ∗ 24 and HLA-A ∗ 01, and AluyHG and HLA-A ∗ 02, supporting previous findings in Caucasians and Japanese. Single POALIN haplotypes were found more frequently than multiple POALIN haplotypes. However, of the seven different POALIN haplotypes within the MHC alpha block, there were only two significant differences between the NE Thais, Caucasians and Japanese. This study confirms that the MHC POALINs are in linkage disequilibrium with HLA-A and ‐B alleles and that there are significant frequency differences for some of the POALINs when compared between NE Thai, Caucasians and Japanese.

This study examined the degree to which neurophysiological activity on routine clinical EEG is associated with neuropsychological deficiencies in children with epilepsy.Ninety-five children with epilepsy (58 chronic, 37 recent-onset; mean age = 10.41 years, S.D. = 2.87 years; mean age at onset = 5.86 years, S.D. = 3.46 years) completed a neuropsychological battery. Neurophysiological data were collected from the most recent EEG.In the recent-onset sample, no neuropsychological scores were related to any EEG variable. In the chronic sample, however, presence of slow-wave activity was related to memory impairment (p0.01). Post-hoc analyses on other neuropsychological measures showed localization of epileptiform activity (EA) might be related to verbal learning.Children with slow-wave activity on EEG might be at increased risk for developing neuropsychological deficits. When these abnormalities are observed on a child's EEG, closer monitoring of cognitive and academic functioning seems warranted. Differences between these findings and past research suggest that conclusions drawn from adult surgical studies cannot be generalized to pediatric patients, especially recent-onset samples, without qualification. Differences between the recent-onset and chronic samples in this cross-sectional study raise the possibility that neurophysiological abnormalities have a cumulative effect on cognitive development.

We present high-quality data of Saturn and its ring system from the Berkeley-Illinois-Maryland Association and Owens Valley Radio Observatory arrays. We observed at wavelengths of 1.3 and 3.0 mm in 2002 October and 2003 March, respectively. At that time Saturn's rings were near their maximum ring opening angle (|B| ~ 26°), which allowed us to map the brightness distribution on Saturn's disk, as well as from its rings, despite the moderate resolution achieved (~25–4''). Clear latitudinal structure is seen on Saturn's disk, indicative of an overall upwelling of gas on the southern hemisphere and subsidence of dry air in the north. The rings are brighter at 1.3 mm than at 3.0 mm, as expected from the increase in ring particles' thermal emission at shorter wavelengths. We use our radiative transfer code to model the relative contributions of the scattered and thermal radiation emanating from the rings. Unlike previous (centimetric) observations, the present (millimetric) data serve as an adequate test of the model's ability to account for the thermal contribution from the rings. A comparison between the model and data shows that Saturn's light transmitted and scattered through the B ring, as well as the radiation reflected from the A ring behind and just off the planet's south pole, is much brighter than predicted by our model. Hence, the ring particles appear to scatter more efficiently both in the forward and backward directions than implied by an isotropic phase function.

This paper demonstrates the remarkably dynamic nature of America's 'War on Terrorism'. It shows the Bush administration's propensity to re-evaluate the terrorist threat and the responses required to deal with that threat. It identifies three distinct and sequential strategies that have been adopted in order to prosecute the War on Terrorism. The 'Counter-terrorism' strategy focused on the terrorists themselves, involved traditional counter-terrorism techniques and lead logically to war in Afghanistan. The second strategy, 'Pre-emption and pre-eminence', represented a step-change in Washington's conceptualisation of the terrorist threat and how to deal with it. The third approach, the 'Forward strategy for the democratisation of the Middle East', seeks to identify both the root causes of and the long term solutions to the War on Terrorism. The article shows how and why American thinking on this subject has evolved in period since 11 September 2001 through these three approaches, and how the tensions between these different strategies have complicated America's task of dealing with the terrorist threat.

The purpose of present study was to investigate differences in media violence exposure between groups of adolescents with and without Disruptive Behavior Disorders with Aggressive Features, using a case-controlled design and multimethod assessment. Samples of 27 adolescents aged 13-17 with Disruptive Behavior Disorder with Aggressive Features and 27 age-gender-IQ matched controls completed a semistructured interview about exposure to violence on television and video games; parents completed a corresponding questionnaire measure. Moderate intercorrelations were found between most self- and parent-report television and video game violence exposure measures. Compared to control adolescents, adolescents with Disruptive Behavior Disorder with Aggressive Features had higher aggregate media violence exposure, higher exposure to video game violence, and higher parent-reported exposure to television violence. Results show that adolescents and parents agree about the adolescent's level of media violence exposure, that exposure to violence on television tends to be accompanied by exposure to violence in video games, and that the association between media violence exposure and Disruptive Behavior Disorder with Aggressive Features is not due to a spurious effect of gender or IQ.

Adverse weather and soil conditions may prevent grain sorghum (Sorghum bicolor L. Moench) growers from achieving an evenly spaced, optimum plant density. In these situations, growers must decide whether to replant or manage a grain sorghum crop with uneven and/or lower stands. Research indicated that grain sorghum grain yield response to row spacing was variable and dependent upon environment. In uniform stands, grain sorghum was able to partially compensate for densities below 60,000 plants per acre by producing additional grain heads per plant. Results also indicated that in uniform grain sorghum stands, N at 100 to 150 lb/acre produced the highest grain yield under both high and low plant density conditions. In non-uniform stands with frequent 6- to 9-ft skips, sorghum had significantly reduced grain yield when compared to a uniform stand or 3-ft skips. These results do not support reduced N rates in either uniform or uneven grain sorghum stands with less than optimal plant densities.

Steatotic mice are particularly susceptible to hepatic ischemia/reperfusion injury compared with their lean littermates. We have previously demonstrated that livers of mice having a spontaneous mutation in the leptin gene (ob/ob), resulting in global obesity and liver steatosis, are ATP depleted, are endotoxin sensitive, and do not survive (I/R) injury. We hypothesize that administration of an anti-LPS monoclonal antibody (mAb) prior to initiation of I/R would be protective from that insult. Steatotic mice (ob/ob) were subjected to 15 min of ischemia via complete porta-hepatis occlusion and varying lengths of reperfusion with or without pre-treatment with an anti-LPS mAb. There was 14-31% survival of isotype matched control mAb treated ob/ob mice after 15 min of ischemia and 24 h of reperfusion. In contrast, 75-83% of ob/ob mice pre-treated with an anti-LPS mAb prior to initiation of I/R survived both ischemia and 24 h of reperfusion. Furthermore, there was a decrease in ALT and circulating endotoxin levels when treated with an anti-LPS mAb compared with control antibodies. Attenuation of the endotoxin load with anti-LPS mAb, prior to initiation of I/R, was cytoprotective and improved survival. Consequently, these studies might offer a solution to the problems associated with using steatotic livers in clinical transplantation.

Children with epilepsy are at great risk for academic difficulties (1–7) and for underemployment as adults (6,8). Fastenau et al. (9) described a model to explain how various risk factors might contribute to academic problems. In that model, neuropsychological functioning appears to play an integral role, possibly mediating the effects of structural and electrophysiologic abnormalities (10–14). Other risk factors in the model include seizure, demographic, and psychosocial variables (9). Studies to date have not been consistent in identifying seizure variables (e.g., seizure type, age at onset, seizure severity) that might influence the relation between neuropsychological functioning and academic achievement in children with epilepsy. For example, some studies have shown academic underachievement to be associated with absence epilepsy more so than with juvenile rheumatoid arthritis (15), and children with generalized seizures demonstrated worse outcomes than did those with partial seizures (5,16,17). Still, others found no association between seizure type and academic achievement (4,18,19), and no studies of academic achievement examined the interaction between seizure type and neuropsychological functioning. An early age at onset for seizures was associated with worse cognitive function in many studies (e.g., 5,20–22); yet others failed to find a relation (18,23). Persistent seizures and greater seizure severity also have been associated with greater academic underachievement in children (1,15), but others have failed to find a relation between seizure severity and achievement (e.g., 4). The lack of consistency in this literature suggests a need for further evaluation of seizure variables in academic functioning, particularly as they might interact with other variables (i.e., moderate other relations). In addition to seizure variables, demographic and psychosocial variables might serve as moderators in the relation between neuropsychological functioning and academic achievement. Past studies suggest that gender, family environment, and children’s perceptions influence academic achievement in children with epilepsy. With regard to gender, a study of children with epilepsy found males to be more at risk for academic underachievement than females (1). In contrast, Howe et al. (24) found male adolescents, including those with neurologic conditions, had higher achievement scores than did adolescent females. In addition, low stimulation and support in the family environment were related to poorer academic achievement in children with seizures (4). Negative child attitudes and perceptions have been associated with poorer academic performance in children with epilepsy (1). Negative attributions have been observed in epilepsy for both adults (25) and teens (26), and such attributions have been associated with poor academic achievement in school-age children (27). Despite the support for the roles of these psychosocial factors on classroom success, no studies have examined the extent to which psychosocial variables might interact with neuropsychological functioning to influence academic achievement in this population. Past studies focusing on seizure and psychosocial predictors of achievement in childhood epilepsy have been limited in several ways. They tended to rely on group tests of achievement or parent report or both, rather than using well-validated individual achievement tests (e.g., 1). In addition, neuropsychological functioning in many of those studies was assessed with limited measures, or a large battery of tests was used with no attempt to reduce the data into fewer and more relevant constructs (e.g., 28). We identified only one study of neuropsychology and academic achievement with this population that included a factor analysis to reduce the test battery into fewer, more salient neuropsychological constructs (29). Most important, no study to date has modeled the complex moderating roles of demographic, seizure, and psychosocial variables on the relation between neuropsychological functioning and academic achievement. The present study builds on past studies by (1) recruiting a large sample of school-age children with diverse seizure types, (2) using a more comprehensive battery of neuropsychological and achievement tests, (3) exploring the factor structure of that battery, (4) modeling the relative contributions of each of these cognitive deficits to specific outcomes in each major academic domain, and (5) testing whether demographic, seizure, and psychosocial variables serve as moderators of the relation between neuropsychological functioning and academic achievement.

We present a new Very Large Array (VLA) image of Saturn, made from data taken in October 1998 at a wavelength of λ 3.6 cm. The moderate ring opening angle ( B ≈15°) allows us to explore direct transmission of microwave photons through the A and C rings. We find a strong asymmetry of photons transmitted through the A ring, but not in the C ring, a new diagnostic of wake structure in the ring particles. We also find a weak asymmetry between east and west for the far side of the ansae. To facilitate quantitative comparison between dynamic models of the A ring and radio observations, we extend our Monte Carlo radiative transfer code (described in Dunn et al., 2002, Icarus 160, 132–160) to include idealized wakes. We show the idealized model can reproduce the properties of dynamic simulations in directly transmitted light. We examine the model behavior in directly transmitted and scattered light over a range of physical and geometric wake parameters. Finally, we present a wake model with a plausible set of physical parameters that quantitatively reproduces the observed intensity and asymmetry of the A ring both across the planet and in the ansae.

Successful clinical allotransplants only became possible with the development of immunosuppression. Initially, 6-mercaptopurine, or its derivative azathioprine (AZA), was used.1–3 Shortly thereafter, Starzl et al4 reported improved graft survival when AZA was combined with prednisone. Since that time, transplant clinical research has focused on improving short- and long-term graft survival while simultaneously minimizing immunosuppression-related complications. Prednisone has a well-defined side effect profile, which includes hypertension, osteoporosis (and fractures), avascular necrosis, cataracts, mood alterations, posttransplant diabetes, easy bruisability, and skin changes. Some of these side effects are related to the cumulative steroid dose.5 Others develop rapidly posttransplant6 and can occur early, even with use of relatively low-dose steroids.7–9 Consequently, even early in the history of transplantation, attempts were made to minimize the daily prednisone dose.10 In general, however, kidney transplant recipients who began prednisone at the time of their transplant tended to have better long-term graft survival than those who did not take prednisone. Throughout the 1980s and 1990s, many transplant centers studied whether selected, clinically well, immunologically low-risk kidney transplant recipients, without a previous acute rejection episode, could undergo prednisone withdrawal. Those studies showed that, even in carefully selected recipients, prednisone withdrawal was associated with an increased risk of acute rejection11,12 and of graft loss.12 Of particular concern was a Canadian multicenter, prospective, randomized study in which recipients on cyclosporine (CSA) and prednisone, without active rejection, were randomized at 90 days posttransplant to continue on CSA and either low-dose prednisone or placebo. The Canadian study found no difference in graft survival for the first 3 years posttransplant, but thereafter the steroid-free group had significantly worse graft survival (P = 0.03 versus the low-dose prednisone group).13 More recently, with the introduction of new, more potent immunosuppressive agents, interest in steroid-sparing protocols has resurged. Two prospective randomized studies of steroid withdrawal in recipients on CSA, mycophenolate mofetil (MMF), and prednisone showed an increased incidence of acute rejection episodes in the steroid withdrawal arm.14,15 In contrast, numerous other studies have now shown a low acute rejection rate when steroids are completely avoided or discontinued in the first week after kidney or simultaneous kidney-pancreas transplants.16–24 Outcome at 1 year posttransplant has been excellent with protocols incorporating prednisone avoidance or rapid discontinuation. Yet concern remains, fueled by the results of the Canadian study, that long-term outcome will be worse in prednisone-free recipients. We herein report 4-year outcome in a cohort of kidney transplant recipients who discontinued their prednisone in the first posttransplant week.

Xenomitochondrial mice harboring trans-species mitochondria on a Mus musculus domesticus (MD) nuclear background were produced. We created xenomitochondrial ES cell cybrids by fusing Mus spretus (MS), Mus caroli (MC), Mus dunni (Mdu), or Mus pahari (MP) mitochondrial donor cytoplasts and rhodamine 6-G treated CC9.3.1 or PC4 ES cells. The selected donor backgrounds reflected increasing evolutionary divergence from MD mice and the resultant mitochondrial-nuclear mismatch targeted a graded respiratory chain defect. Homoplasmic (MS, MC, Mdu, and MP) and heteroplasmic (MC) cell lines were injected into MD ova, and liveborn chimeric mice were obtained (MS/MD 18 of 87, MC/MD 6 of 46, Mdu/MD 31 of 140, and MP/MD l of 9 founder chimeras, respectively). Seven MS/MD, 1 MC/MD, and 11 Mdu/MD chimeric founder females were mated with wild-type MD males, and 18 of 19 (95%) were fertile. Of fertile females, only one chimeric MS/MD (1% coat color chimerism) and four chimeric Mdu/MD females (80-90% coat color chimerism) produced homoplasmic offspring with low efficiency (7 of 135; 5%). Four male and three female offspring were homoplasmic for the introduced mitochondrial backgrounds. Three male and one female offspring proved viable. Generation of mouse lines using additional female ES cell lineages is underway. We hypothesize that these mice, when crossbred with neurodegenerative-disease mouse models, will show accelerated age-related neuronal loss, because of their suboptimal capacity for oxidative phosphorylation and putatively increased oxidative stress.

Purpose. The goal of this work is to describe psychometric properties of two scales measuring perceived stigma in children with epilepsy and their parents. Methods. Data were collected for the parent scale in two samples: parents of 173 children with epilepsy and of 224 children with new-onset seizures. The child scale was tested in the chronic sample. Content validity, internal consistency reliability, and construct validity were tested. Results. Both scales had strong internal consistency reliability and construct validity. Higher scores were associated with greater seizure severity scores. In the parent scale, lower scores were associated with more positive mood, less worry, and more family leisure activities. In the child scale, higher scores were correlated with more negative attitude, greater worry, poorer self-concept, and more depression symptoms. Conclusions. Both scales were found to have strong psychometric properties. They are short, and items are easy to understand. These scales have potential for use in research and in the clinical setting to measure stigma. 2004 Elsevier Inc. All rights reserved.

Mothers of children with epilepsy are at risk for problems in adapting to their child's condition; however, factors associated with maternal adaptation to a child's epilepsy have not been well articulated. The purpose of this study was to investigate the associations among maternal and child characteristics, maternal beliefs, and maternal adaptation outcomes. A conceptual model was formulated based on the literature. Maternal beliefs were proposed to mediate the relationships between maternal and child characteristics and maternal adaptation outcomes. A sample of 156 maternal-child dyads provided data via structured telephone interviews. Multiple regression analysis was used to test for additive and mediated relationships. Mediation was not supported statistically. Child behavior problems, maternal satisfaction with family, and maternal learned helplessness had the strongest associations with maternal outcomes, suggesting that maternal adaptation to a child's epilepsy is complex and includes multiple factors in addition to the child's seizure condition.

Historically, late steroid withdrawal after kidney transplants has been associated with an increased rejection rate. Recently, low rejection rates have been reported for recipients treated with complete avoidance or rapid elimination of steroids. However, follow-up has been short. We herein report on 3-year outcome in recipients whose prednisone was rapidly eliminated and who were maintained on a steroid-free regimen. From 10/1/1999 through 5/1/2003, 349 recipients (254 LD, 95 CAD; 319 in first 30 s) were immunosuppressed with polyclonal antibody (Thymoglobulin), a calcineurin inhibitor, either mycophenolate mofetil or sirolimus, and rapid discontinuation of prednisone. Actuarial 3-year patient survival was 95%; graft survival, 93%. Acute rejection-free graft survival at 1 year was 94%; at 3 years, 92%. There was no difference between LD and CAD. At 2 years, the mean (± SE) serum creatinine level for LDs was 1.6 ± 0.5 mg/dL; for CAD, 1.6 ± 0.4 mg/dL. We have no new cases of PTLD or avascular necrosis; 22 recipients (6%) developed CMV. Currently, 84% of recipients remain prednisone-free. We conclude that excellent 3-year patient and graft survival can be achieved without maintenance prednisone. With such a protocol, steroid-related side-effects are minimal.

Background Total pancreatectomy to treat chronic pancreatitis is associated with severe diabetic control problems in 15% to 75% of patients, causing up to 50% of deaths late postoperatively. We report our experience with islet autotransplants at the time of, or with pancreas allotransplants after, total pancreatectomy. Study design Between February 1, 1977, and June 30, 2003, we performed 112 islet autotransplants at the time of total pancreatectomy; we also performed 20 pancreas allotransplants in 13 patients who had already undergone total pancreatectomy months to years earlier. Results Islet autotransplants at the time of total pancreatectomy in patients who had not had previous operations on the body and tail of the pancreas were associated with a high islet yield (>2,500 islet equivalents/kg body weight), and >70% of the recipients achieved complete insulin independence. In contrast, a previous distal pancreatectomy or a Puestow drainage procedure was associated with a low islet yield in 75% of them and with complete insulin independence in A pancreas allotransplant after total pancreatectomy was not associated with any transplant-related mortality at 1 and 3 years posttransplant. The pancreas graft survival rate at 1 year posttransplant was 77% with tacrolimus-based immunosuppression (versus 67% with cyclosporine). Enteric (over bladder) drainage was preferred to manage exocrine graft secretions, to cure pancreatectomy-induced endocrine and exocrine insufficiency. Conclusions Our series shows that pancreas allotransplants can be performed without transplant-related mortality and, when tacrolimus-based immunosuppression is used, with 1-year pancreas graft survival rates >75%. In contrast to a simultaneous islet autotransplant, a pancreas allotransplant has the disadvantage of requiring lifelong immunosuppression, but the advantage of not only curing endocrine but also exocrine insufficiency. Both transplant options, if successful, improve the recipient's quality of life.

Assay miniaturization and the implementation of high-density 1,536-microwell screening increase the speed and efficiency of screening and lead discovery. To serve this need, a platform of miniaturizable assay technologies has been assembled for specific biological targets. This platform will enable initiation and completion of uHTS screens in a straightforward and expeditious manner. Although faster primary screening does contribute to a reduction in timelines, the process of assay development can become a bottleneck. Assay technologies that do not require the use of target-specific reagents can reduce the time necessary for assay development. Assays that measure inhibition of tyrosine kinases can be configured in a competitive format where only the enzyme itself is specific to the assay. In this context, several technologies, including time-resolved fluorometry (also known as DELFIA), time-resolved fluorescence resonance energy transfer (also known as LANCE( trade mark )), fluorescence polarization, enzyme fragmentation complementation assay, and confocal laser scanning imaging, were examined. Quality parameters such as assay reproducibility, signal:background ratio, Z factor, and assay sensitivity were compared. Additionally, the relative merits of each of these technologies are assessed in terms of assay miniaturization, ease of development, ultimate screening capability, efficiency, and cost.

ADHD is a common developmental disorder frequently associated with additional neurologic and psychiatric disorders. Stimulant medication is an effective first-line therapy for most children with ADHD. Current research is defining the genetic and neurobiologic basis for this disorder.

We present a summary of Jupiter data taken over an eighteen year span (1981–1998) by the Very Large Array at ∼21.0 cm. At this wavelength the emission is dominated by synchrotron radiation, which is roughly proportional to the product of the electron number density and magnetic field strength ( N e B ). At each epoch 8–12 hours of data were taken, which allowed us to examine Jupiter during an entire rotation period. We mapped the longitudinal structure of the synchrotron radiation by using a 3D reconstruction technique developed by Sault et al. [Astron. Astrophys. 324 (1997) 1190] which enabled us to produce plots of the latitude, radial distance, and peak intensity vs. jovian longitude (System III). The results show the shape of the synchrotron radiation has remained stable (except, of course, during the period of comet Shoemaker–Levy 9 impacts). Specifically, the latitudinal structure has remained nearly constant. Furthermore, the general dependence of the radial intensity profile has remained the same throughout the years, though radial distance has slightly, though significantly, changed. This constancy implies that the spatial structure of both the particle distribution and magnetic field have varied little over the eighteen year span. The primary changes in the synchrotron radiation have been seen in the intensity of emission as a function of time. There are certain epochs (e.g., 1987) which show more emissivity than others (e.g., 1981, 1995) at all longitudes. When each epoch is longitudinally averaged, there may be an anti-correlation between the radial distance and corresponding peak intensities of the synchrotron radiation, as one might expect if radial diffusion is important. We examine these trends by comparing the data to plots of the total intensity at 13 cm (by Klein et al., in: Rucker, H.O., et al., Planetary Radio Emissions V. Austrian Acad. Sci. Press, Vienna, p. 221). Overall, variations in our 21-cm data are similar to those measured at 13 cm, but there appears to be a change in spectral index and perhaps in the spatial brightness distribution in 1992. We attribute this to a change in both the spatial and energy distribution of the relativistic electrons.

A large proportion of Japanese with the HLA-B48 allele have a MICA gene deletion associated with a MICB null allele within the class I region of the Major Histocompatibility Complex (MHC). Here, we report for the first time a novel positive association between the presence of a polymorphic Alu insertion, AluyMICB, within the first intron of the MICB gene and the MICAdel/MICBnull/HLA-B48 haplotype for five of six well-characterized Japanese cell-lines. The AluyMICB insertion was found to be present at a frequency of 0.242 in 86 Japanese tissue donors and in four of the five individuals with the HLA-B48 allele. The AluyMICB insertion was also associated with at least three different MICB alleles, *0102, *0107N and *0105, and three different HLA-B alleles, B13, B48 and B57, respectively, in the seven Workshop cell-lines (the 4th Asia-Oceania Histocompatibility Workshop, and the 10th International Histocompatibility Workshop) and the six Japanese cell-lines that were selected for this study. Based on the analysis of associations between different polymorphic markers within the beta block, the MICB*0102 allele was inferred to be the ancestral form of the MICB*0105 and MICB*0107N alleles. The AluyMICB polymorphism can now be used to further investigate its relationship with other MICB alleles and consequently their origins. In addition, we have examined the absence and presence of three other polymorphic Alu markers distributed within the alpha block of the class I region of the HLA-B48/AluyMICB haplotype. We conclude that the extended HLA-B haplotypes are best defined by considering multiple genomic sites including the four polymorphic Alu insertions described in this study.

Most Alu members of the large SINE family are fixed within the human genome but some younger mobile members are dimorphic, that is, they are either present or absent in the genome. Four different dimorphic Alu insertions have been identified and characterized previously within the class I region of the major histocompatibility complex (MHC). Here we report on (i) the identification and characterization of a new dimorphic Alu insertion, AluyTF, located between the transcription factor II H (TFIIH) and corneodesmosin (CDSN) genes within a region of the MHC that is telomeric of the human leukocyte antigen type B (HLA-B) locus and centromeric of the HLA-A locus, (ii) the haplotypic relationships between the AluyTF dimorphism and the HLA-A and -B loci within a panel of 48 IHW cell-lines representing at least 36 different HLA class I haplotypes, (iii) the AluyTF genotype, allele and haplotype frequencies present in the Australian caucasian and Japanese populations, and (iv) the frequency of association between the AluTF dimorphisms and HLA-A and -B alleles in 108 Australian caucasians and 99 Japanese. The AluyTF insertion was present at 27% in the IHW cell lines, and the gene frequency was 0.107 and 0.083 in the Australian caucasian and Japanese population, respectively. The Alu haplotype frequencies constructed from four different dimorphic Alu loci including AluyTF within the MHC were not significantly different (p > 0.05) between the two populations. There were no significant associations between the Alu insertion and either the HLA-A or -B alleles except for a moderately strong association with HLA-A29 in the Australians (71.7%). This polymorphic AluyTF element, along with the four other previously described polymorphic Alu elements within the class I region of the MHC, will be useful lineage and linkage markers in human population studies and for elucidating the evolution of HLA class I haplotypes.

We observed Jupiter’s synchrotron radiation at frequencies of 15 and 22 GHz using the VLA (Very Large Array) in its most compact configuration (D-array) in March 1991. The spatial brightness distribution of the emission at these high frequencies appears to be very similar to that seen at lower frequencies (5 GHz down to 330 MHz). We measured a total nonthermal flux density at 15 and 22 GHz of 1.5 ± 0.15 Jy and 1.5 ± 0.4 Jy, respectively (both normalized to a geocentric distance of 4.04 AU). These numbers agree well with model spectra of Jupiter’s synchrotron radiation that were obtained by fitting the planet’s nonthermal radio emission between 74 MHz and 8 GHz and suggest a maximum cutoff in electron energies at ∼100 MeV. The degree of linear polarization observed with the VLA is 21.5 ± 1.9% at 15 GHz.

IMAP is a non-separation-based, antibody-independent, FP assay that can be applied to many types of protein kinases and phosphatases. This technology is currently being used in many high-throughput screening campaigns throughout the industry. In this technology, a fluorescently labeled peptide substrate is phosphorylated and then captured on immobilized metal (M(III)) nanoparticles, an interaction that is enhanced at low pH (pH 5.5). The binding of the phosphorylated peptide to the nanoparticles is detected using FP. IMAP differs from other FP formats in that the polarization signal is antibody-independent and involves metal coordination complexes detected at low pH. Here, this technology is evaluated against a 4000000-member compound collection using a 1536-well assay design that is devoid of enzymes so that only interference of the compounds with the detection system is measured. Miniaturization of the assay to 1536-well plates is discussed. Compound interference due to inhibition of phosphopeptide binding to the M(III) nanoparticles is not observed. Additionally, it is concluded that the level of fluorescence compound interference is similar to typical FP formats for the majority of the compound collection.

Background. As short-term transplant results improve, it has become difficult to use patient or graft survival or acute rejection as clinical trial endpoints, except in large, multicenter studies. Despite better outcomes, graft failure continues over time.Methods. We studied 6- and 12-month creatini

This study is a retrospective review of patients with pediatric laminoplasty. The objective was to determine the incidence of postlaminoplasty deformity. Long-term follow-up of patients with pediatric laminoplasty is lacking. Previous studies have shown spine deformity to be as high as 100% following laminectomy procedures. From 1986 until present, 31 superiorly based laminoplasties were performed on pediatric patients, ranging from two to 12 levels. Twenty-one of the 31 were available for complete review. A retrospective review of the radiographic deformity of these patients was conducted. Preoperative and postoperative scoliotic and kyphotic deformities were measured, and the correlating diagnoses were recorded. The average follow-up period was 6.8 years, and average age at follow-up was 11.9 years. Sixteen of 21 showed no increase in spinal deformity. Five of 21 showed nonunion at one or more levels. Five patients showed an increased deformity, of which two required surgical intervention to correct deformity. Although the technique of laminoplasty has very low morbidity (essentially no different from laminectomy), this review has not shown that this procedure eliminates postsurgical deformity. However, we recommend the use of laminoplasty in the pediatric patient because it may reduce the incidence of deformity, allow future segmental instrumentation if necessary, and has a low morbidity.

This article explores the myths and motivations behind US foreign policy towards Iraq in America's ‘war on terrorism’. It argues that the foreign policy of the Bush administration is widely misunderstood and that much of the debate about Iraq policy that has taken place has been conducted at an unhelpful level of analysis. It addresses arguments that the Bush administration is motivated by oil, revenge or hubris as well as the more mainstream arguments that an attack on Iraq would provoke instability through the entire Middle East, as well as encouraging further acts of and support for murderous terrorism; that there is no urgency to act against Iraq as containment and deterrence remain adequate means to manage this threat; and that Iraq should be a lower priority than dealing with North Korea. It does this by analysing the development of American foreign policy thinking on the war on terrorism, what motivates it, and why it rejects the arguments of its critics. The article explains the intellectual process by which the US decided upon this course of action and how Europe's failure to understand this process added to its incomprehension of American policy. It does not argue that European's opposition would have been swept aside had they better understood the Bush administration, the central disagreement about the necessity and prudence of military action versus containment remains, but that such an understanding would have allowed for a better and more focused level of debate than the one which has got us to this point. Nor does it argue that the Bush administration approach is necessarily persuasive or justified, merely that its case is reasoned and explicable in terms of America's foreign policy traditions.

The purpose of this study was to explore the association between seizures and behavior problems in children with new-onset seizures using teachers' ratings of behavior. Subjects were 209 children with new-onset seizures and 93 children with asthma. Teacher ratings of behavior were collected prospectively over 24 months to determine differences between children with recurrent seizures, children without recurrent seizures, and children with asthma. During the 2-year period, 155 (74%) children had at least one recurring seizure. Data were analyzed using repeated-measures analysis of variance both with and without covariates. Controlling for covariates, children experiencing recurrent seizures had higher Total (P=0.002) and Internalizing (P=0.018) Behavior Problems scores across all times than those not experiencing recurrent seizures. Children with asthma were similar to children not experiencing recurrent seizures. The association between seizures and behavioral problems was supported using behavioral ratings from teachers.

Progress in animal modeling of polymorphisms and mutations in mitochondrial DNA (mtDNA) is not as developed as nuclear transgenesis due to a host of cellular and physiological distinctions. mtDNA mutation modeling is of critical importance as mutations in the mitochondrial genome give rise to a variety of pathological conditions and play a contributing role in many others. Nuclear localization and transcription of mtDNA genes followed by cytoplasmic translation and transport into mitochondria (allotopic expression, AE) provide an opportunity to create in vivo modeling of a targeted mutation in mitochondrial genes and has been suggested as a strategy for gene replacement therapy in patients harboring mitochondrial DNA mutations. Here, we use our AE approach to transgenic mouse modeling of the pathogenic human T8993G mutation in mtATP6 as a case study for designing AE animal models.

Mitochondrial dynamics play an important role in numerous physiological and pathophysiological phenomena in the developing and adult human heart. Alterations in structural aspects of cellular mitochondrial composition as a function of changes in physiology can easily be visualized using fluorescence microscopy. Commonly, mitochondrial location, number, and morphology are reported qualitatively due to the lack of automated and user-friendly computer-based analysis tools. Mitochondrial Quantification using MATLAB (MQM) is a computer-based tool to quantitatively assess these parameters by analyzing fluorescently labeled mitochondria within the cell; in particular, MQM provides numerical information on the number, area, and location of mitochondria within a cell in a time-efficient, automated, and unbiased way. This chapter describes the use of MQM's capabilities to quantify mitochondrial changes during human pluripotent stem cell (hPSC) differentiation into spontaneously contracting cardiomyocytes (SC-CMs), which follows physiological pathways of human heart development.

Progress in animal modeling of polymorphisms and mutations in mitochondrial DNA (mtDNA) is not as developed as nuclear transgenesis due to a host of cellular and physiological distinctions. mtDNA mutation modeling is of critical importance as mutations in the mitochondrial genome give rise to a variety of pathological conditions and play a contributing role in many others. Nuclear localization and transcription of mtDNA genes followed by cytoplasmic translation and transport into mitochondria (allotopic expression, AE) provide an opportunity to create in vivo modeling of a targeted mutation in mitochondrial genes and has been suggested as a strategy for gene replacement therapy in patients harboring mitochondrial DNA mutations. Here, we use our AE approach to transgenic mouse modeling of the pathogenic human T8993G mutation in mtATP6 as a case study for designing AE animal models.

Background Tuberous sclerosis complex is a multisystem genetic disorder with a range of physical manifestations that require evaluation, surveillance, and management. Individuals with tuberous sclerosis complex also have a range of behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial difficulties. These may represent the greatest burden of the disease. Around 90% of individuals with tuberous sclerosis complex will have some of these difficulties during their lifetime, yet only about 20% ever receive evaluation and treatment. The Neuropsychiatry Panel at the 2012 Tuberous Sclerosis Complex International Consensus Conference expressed concern about the significant "treatment gap" and about confusion regarding terminology relating to the biopsychosocial difficulties associated with tuberous sclerosis complex. Methods The Tuberous Sclerosis Complex Neuropsychiatry Panel coined the term TAND—tuberous sclerosis complex-associated neuropsychiatric disorders—to bring together these multidimensional manifestations of the disorder, and recommended annual screening for TAND. In addition, the Panel agreed to develop a TAND Checklist as a guide for screening. Results Here, we present an outline of the conceptualization of TAND, rationale for the structure of the TAND Checklist, and include the full US English version of the TAND Checklist. Conclusion We hope that the unified term TAND and the TAND Checklist will raise awareness of the importance of tuberous sclerosis complex-associated neuropsychiatric disorders and of the major burden of disease associated with it, provide a shared language and a simple tool to describe and evaluate the different levels of TAND, alert clinical teams and families or individuals of the importance of screening, assessment, and treatment of TAND, and provide a shared framework for future studies of tuberous sclerosis complex-associated neuropsychiatric disorders.

Mitochondrial dynamics play an important role in numerous physiological and pathophysiological phenomena in the developing and adult human heart. Alterations in structural aspects of cellular mitochondrial composition as a function of changes in physiology can easily be visualized using fluorescence microscopy. Commonly, mitochondrial location, number, and morphology are reported qualitatively due to the lack of automated and user-friendly computer-based analysis tools. Mitochondrial Quantification using MATLAB (MQM) is a computer-based tool to quantitatively assess these parameters by analyzing fluorescently labeled mitochondria within the cell; in particular, MQM provides numerical information on the number, area, and location of mitochondria within a cell in a time-efficient, automated, and unbiased way. This chapter describes the use of MQM's capabilities to quantify mitochondrial changes during human pluripotent stem cell (hPSC) differentiation into spontaneously contracting cardiomyocytes (SC-CMs), which follows physiological pathways of human heart development.

Summary: Purpose: Children with epilepsy have high rates of behavior problems. The purpose was to describe prospectively the association of seizures and behavior problems in children with new-onset seizures. Methods: Subjects were 224 children with new-onset seizures (aged 4–14 years) and 159 siblings (4–18 years). Caregiver's ratings of the behavior were collected 4 times: at baseline, and at 6, 12, and 24 months. During the 2-year period, 163 (73%) children had at least one additional seizure, and 61 (27%) had none. Data were analyzed by using repeated measures analysis of variance both with and without covariates [site, age, gender, race, caregiver education (years), and seizure medications]. Results: On average, children had higher CBCL Total and Internalizing Behavior Problems scores across all times when experiencing recurrent seizures than when not experiencing recurrent seizures (Total Problems, p = 0.041, controlling for demographics and seizure medications). Siblings had significantly lower Total and Internalizing Problems scores than both children experiencing (Total Problems adjusting for covariates, p = 0.0001) and not experiencing recurrent seizures (p = 0.0004). Externalizing Problems scores were not significantly different among children with recurring seizures, children without recurring seizures, and siblings. Conclusions: Recurrent seizures significantly predicted behavior problems very early in the course of a seizure condition, even when key child, demographic, and seizure variables were controlled. Explanations for these findings include the possibilities that both seizures and behavior problems are caused by an underlying neurological disorder, that seizures per se disrupt behavior, or that children have negative psychological responses to seizure activity.

The purpose of this study was to develop and test the psychometric properties of a Seizure Self-Efficacy Scale for Children (SSES-C). An initial pool of test items was generated using a variety of resources, including literature reviews, child self-efficacy measures from other chronic diseases, and self-efficacy measures for adult patients with epilepsy. Experts in the field of self-efficacy, chronic illness self-management, and behavioral management of seizure disorders were asked to evaluate item content and readability. The scale was administered via computer-assisted telephone interviews to 175 children ages 9 through 14 years who had had epilepsy for 6 months or more. Content validity of the SSES-C was ensured by 80% agreement on test items by experts. The final version of the scale has 15 items. Construct validity was supported by factor analysis and correlation of the SSES-C to other constructs of influence on the health behavior of children with epilepsy. Specifically, the SSES-C was significantly...

OBJECTIVE: The authors assessed the efficacy of once-daily atomoxetine administration in the treatment of children and adolescents with attention deficit hyperactivity disorder (ADHD). METHOD: In a double-blind study, children and adolescents with ADHD (N=171, age range=6–16 years) were randomly assigned to receive 6 weeks of treatment with either atomoxetine (administered once daily) or placebo. RESULTS: Outcomes among atomoxetine-treated patients were superior to those of the placebo treatment group as assessed by investigator, parent, and teacher ratings. The treatment effect size (0.71) was similar to those observed in previous atomoxetine studies that used twice-daily dosing. Parent diary ratings suggested that drug-specific effects were sustained late in the day. Discontinuations due to adverse events were low (less than 3%) for both treatment groups, and no serious safety concerns were observed. CONCLUSIONS: Once-daily administration of atomoxetine is an effective treatment for children and adolesc...

We present a second epoch of Very Large Array Saturn observations taken in February 1997 spanning wavelengths 1.3–21 cm. These observations complement earlier observations at Saturn's autumnal equinox in November 1995. In this epoch, however, we generally have better signal-to-noise ratios and the ring inclination of the present observations was −5.0°, whereas the previous observations were made with ring inclination +2.7°. Our observations confirm the latitudinal structure on the saturnian disk as seen at 2.0, 3.6, and 6.1 cm. We also see some latitudinal structure at 1.3 cm for the first time. The details of this structure have changed dramatically from those reported by I. de Pater and J. R. Dickel (1991, Icarus 94 , 474–492) for the 1980s and are consistent with those seen in F. van der Tak et al. (1999, Icarus 142 , 125–147). The most prominent features are a pair of brightness enhancements just inside the edges of the Equatorial Zone. The rings do not show the east–west asymmetry seen in our previous epoch, perhaps indicative of a viewing angle effect on the scattering properties of the rings. The radial trend in brightness in the ansae is generally consistent with that expected from optical depth variations and increasing distance from the source of scattered light. In particular the increased optical depth towards the center of the C ring is evident. Azimuthal variation in brightness in the C ring shows the forward scattering expected of Mie scattering. By contrast, the A and B rings show little or no azimuthal variation. We present Monte Carlo simulations of the ring brightness under the assumptions of isotropic and Mie scattering. These are the first synthetic maps of Saturn which can be directly compared to the images we obtained. Neither model fits all the data well. However, a hybrid model combining isotropic and Mie scattering does fit well. We interpret the consistency with isotropic scattering in the outer rings as an indication that near-field effects may be important. This in turn implies geometrically thin rings, as predicted by dynamical simulations of these rings.

Five preventable causes of kidney graft loss in the 1990s: A single-center analysis. Background Despite improvements in immunosuppressive protocols and patient care, kidney allografts continue to fail. We studied causes of graft loss for primary kidney transplants in the 1990s to determine major causes and potential interventions. Methods Causes of graft loss were reviewed for 1467 primary kidney transplants done at our institution between January 1, 1990, and December 31, 1999. Graft loss for that entire population was studied and then the causes of loss selectively examined at 5 years post-transplant. Finally, causes of loss in the 1990s versus the 1980s were compared. Results Five major causes of graft loss were noted in the 1990s: thrombosis, acute rejection (either alone or combined with delayed graft function or infection), chronic rejection, death with function, and noncompliance. In the first year post-transplant, thrombosis (25%) and death with function (41%) were the major causes of graft loss. After the first year, chronic rejection and death with function predominated. For recipients dying with graft function, cardiovascular disease was the major cause of death. Conclusions This study identified the five major causes of kidney graft loss in the 1990s. Different interventions are required to decrease loss from each of these causes. Future research needs to be directed at such interventions.

(2002). Poland: America's new model ally. Defence Studies: Vol. 2, Poland ‐ A New Power in Transatlantic Security, pp. 63-86.

ISSUES AND PURPOSE. To investigate factors associated with depressive symptoms in mothers of children with chronic seizure disorders. DESIGN AND METHODS. A cross-sectional correlational design was used with a sample of 115 mother-child dyads in families where the child had chronic epilepsy. RESULTS. A three-factor model consisting of family income, satisfaction with family relationships, and presence of child behavior problems explained 32% of the variance in maternal depressive symptoms. PRACTICE IMPLICATIONS. Childhood epilepsy has a negative effect on the mother's mood in many families. Child behavior problems were found to be the strongest predictor of maternal depressive symptoms. Assessing for behavior problems and maternal depression should become a routine part of the family nursing assessment.