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Schizophrenia affects 1% of the population. Clozapine is the only medication licensed for treatment-resistant schizophrenia and is intensively monitored to prevent harm from neutropenia. Clozapine is also associated with increased risk of pneumonia although the mechanism is poorly understood.
To investigate the potential association between clozapine and antibody deficiency.
Patients taking clozapine and patients who were clozapine-naive and receiving alternative antipsychotics were recruited and completed a lifestyle, medication and infection-burden questionnaire. Serum total immunoglobulins (immunoglobulin (Ig)G, IgA, IgM) and specific IgG antibodies to haemophilus influenzae type B, tetanus and IgG, IgA and IgM to pneumococcus were measured.
Immunoglobulins were all significantly reduced in the clozapine-treated group (n = 123) compared with the clozapine-naive group (n = 111). Odds ratios (ORs) for a reduction in clozapine:control immunoglobulin values below the fifth percentile were IgG, OR = 6.00 (95% CI 1.31–27.44); IgA, OR = 16.75 (95% CI 2.18–128.60); and IgM, OR = 3.26 (95% CI 1.75–6.08). These findings remained significant despite exclusion of other potential causes of hypogammaglobulinaemia. In addition, duration on clozapine was associated with decline in IgG. A higher proportion of the clozapine-treated group reported taking more than five courses of antibiotics in the preceding year (5.3% (n = 5) versus 1% (n = 1).
Clozapine use was associated with significantly reduced immunoglobulin levels and an increased proportion of patients using more than five antibiotic courses in a year. Antibody testing is not included in existing clozapine monitoring programmes but may represent a mechanistic explanation and modifiable risk factor for the increased rates of pneumonia and sepsis-related mortality previously reported in this vulnerable cohort.
Declaration of interest
S.J. has received support from CSL Behring, Shire, LFB, Biotest, Binding Site, Sanofi, GSK, UCB Pharma, Grifols, BPL SOBI, Weatherden, Zarodex and Octapharma for projects, advisory boards, meetings, studies, speaker and clinical trials.
While the neuroanatomic substrates of symptoms of attention deficit hyperactivity disorder (ADHD) have been investigated, less is known about the neuroanatomic correlates of cognitive abilities pertinent to the disorder, particularly in adults. Here we define the neuroanatomic correlates of key cognitive abilities and determine if there are associations with histories of psychostimulant medication.
We acquired neuroanatomic magnetic resonance imaging data from 264 members of 60 families (mean age 29.5; s.d. 18.4, 116 with ADHD). Using linear mixed model regression, we tested for associations between cognitive abilities (working memory, information processing, intelligence, and attention), symptoms and both cortical and subcortical volumes.
Symptom severity was associated with spatial working memory (t = −3.77, p = 0.0002), processing speed (t = −2.95, p = 0.004) and a measure of impulsive responding (t = 2.19, p = 0.03); these associations did not vary with age (all p > 0.1). Neuroanatomic associations of cognition varied by task but centered on prefrontal, lateral parietal and temporal cortical regions, the thalamus and putamen. The neuroanatomic correlates of ADHD symptoms overlapped significantly with those of working memory (Dice's overlap coefficient: spatial, p = 0.003; verbal, p = 0.001) and information processing (p = 0.02). Psychostimulant medication history was associated with neither cognitive skills nor with a brain–cognition relationships.
Diagnostic differences in the cognitive profile of ADHD does not vary significantly with age; nor were cognitive differences associated with psychostimulant medication history. The neuroanatomic substrates of working memory and information overlapped with those for symptoms within these extended families, consistent with a pathophysiological role for these cognitive skills in familial ADHD.
Adolescents’ snacking habits are driven by both explicit reflective and implicit hedonic processes. Hedonic pathways and differences in sensitivity to food rewards in addition to reflective determinants should be considered. The present study evaluated the feasibility and impact of a mobile phone-delivered intervention, incorporating explicit reflective and implicit rewarding strategies, on adolescents’ snack intake.
Adolescents (n 988; mean age 14·9 (sd 0·70) years, 59·4 % boys) completed a non-randomized clustered controlled trial. Adolescents (n 416) in the intervention schools (n 3) were provided with the intervention application for four weeks, while adolescents (n 572) in the control schools (n 3) followed the regular curriculum. Outcomes were differences in healthy snacking ratio and key determinants (awareness, intention, attitude, self-efficacy, habits and knowledge). Process evaluation data were collected via questionnaires and through log data of the app.
No significant positive intervention effects on the healthy snack ratio (b=−3·52 (se 1·82), P>0·05) or targeted determinants were observed. Only 268 adolescents started using the app, of whom only fifty-five (20·5 %) still logged in after four weeks. Within the group of users, higher exposure to the app was not significantly associated with positive intervention effects. App satisfaction ratings were low in both high and low user groups. Moderation analyses revealed small positive intervention effects on the healthy snack ratio in high compared with low reward-sensitive boys (b=1·38 (se 0·59), P<0·05).
The intervention was not able to improve adolescents’ snack choices, due to low reach and exposure. Future interventions should consider multicomponent interventions, teacher engagement, exhaustive participatory app content development and tailoring.
Adolescents’ snack choices could be altered by increasing the reinforcing value (RV) of healthy snacks compared with unhealthy snacks. This study assessed whether the RV of fruit increased by linking it to a reward and if this increased RV was comparable with the RV of unhealthy snacks alone. Moderation effects of sex, hunger, BMI z-scores and sensitivity to reward were also explored. The RV of snacks was assessed in a sample of 165 adolescents (15·1 (sd 1·5) years, 39·4 % boys and 17·4 % overweight) using a computerised food reinforcement task. Adolescents obtained points for snacks through mouse clicks (responses) following progressive ratio schedules of increasing response requirements. Participants were (computer) randomised to three experimental groups (1:1:1): fruit (n 53), fruit+reward (n 60) or unhealthy snacks (n 69). The RV was evaluated as total number of responses and breakpoint (schedule of terminating food reinforcement task). Multilevel regression analyses (total number of responses) and Cox’s proportional hazard regression models (breakpoint) were used. The total number of responses made were not different between fruit+reward and fruit (b −473; 95 % CI −1152, 205, P=0·17) or unhealthy snacks (b410; 95 % CI −222, 1043, P=0·20). The breakpoint was slightly higher for fruit than fruit+reward (HR 1·34; 95 % CI 1·00, 1·79, P=0·050), whereas no difference between unhealthy snacks and fruit+reward (HR 0·86; 95 % CI 0·62, 1·18, P=0·34) was observed. No indication of moderation was found. Offering rewards slightly increases the RV of fruit and may be a promising strategy to increase healthy food choices. Future studies should however, explore if other rewards, could reach larger effect sizes.
This study assessed the use and clinical yield of diagnostic imaging (radiography, computed tomography, and medical resonance imaging) ordered to assist in the diagnosis of acute neck injuries presenting to emergency departments (EDs) in Kingston, Ontario, from 2002–2003 to 2009–2010.
Acute neck injury cases were identified using records from the Kingston sites of the Canadian National Ambulatory Care Reporting System. Use of radiography was analyzed over time and related to proportions of cases diagnosed with clinically significant cervical spine injuries.
A total of 4,712 neck injury cases were identified. Proportions of cases referred for diagnostic imaging to the neck varied significantly over time, from 30.4% in 2002–2003 to 37.6% in 2009–2010 (ptrend = 0.02). The percentage of total cases that were positive for clinically significant cervical spine injury (“clinical yield”) also varied from a low of 5.8% in 2005–2006 to 9.2% in 2008–2009 (ptrend = 0.04), although the clinical yield of neck-imaged cases did not increase across the study years (ptrend = 0.23). Increased clinical yield was not observed in association with higher neck imaging rates whether that yield was expressed as a percentage of total cases positive for clinically significant injury (p = 0.29) or as a percentage of neck-imaged cases that were positive (p = 0.77).
We observed increases in the use of diagnostic images over time, reflecting a need to reinforce an existing clinical decision rule for cervical spine radiography. Temporal increases in the clinical yield for total cases may suggest a changing case mix or more judicious use of advanced types of diagnostic imaging.
This article describes three challenging yet accessible mathematics courses designed for middle school teachers and offered by the Department of Mathematics at the University of Nebraska-Lincoln (UNL). Their descriptions are based on the courses as we have taught them as part of the Math in the Middle (M2) Institute Partnership, a National Science Foundation Math Science Partnership (MSP) program that works with practicing teachers. As a grant funded MSP, we take seriously the responsibility to share information about our program and the courses we have created. Readers are directed to our website  for information about our program and specifically to our course materials  for a link to additional information about the courses described in this article as well as other courses that we offer.
The aim of the M2 Institute, and the university—public-school partnership that created it, is to develop intellectual leaders in middle level mathematics (grades 5–8). A core strategy that guides Math in the Middle is to offer teachers content rich mathematics courses that are accessible and useful. Practicing teachers who are admitted to the M2 Institute earn 36 graduate credit hours over several years, resulting in a Master's Degree. More information on the M2 Institute is in the companion article  in this volume.
We describe three Math in the Middle courses: Mathematics as a Second Language (MSL), Experimentation, Conjecture and Reasoning (ECR), and Number Theory and Cryptology for Middle Level Teachers (NT&C).
The proposition that declarative memory deficits are systematically related to smaller hippocampal volume was tested in a relatively large sample (n = 95) of U.S. military veterans with and without combat-related posttraumatic stress disorder. This correlative analysis was extended by including multiple measures of verbal and visual declarative memory and multiple memory-relevant regional brain volumes that had been shown to exhibit main effects of PTSD in prior work. Small-to-moderate effects were observed on verbal declarative memory in line with a recent meta-analysis; nevertheless, little or no evidence of systematic linear covariation between memory measures and brain volumes was observed. (JINS, 2009, 15, 830–839.)
One of the most notable political developments of the last thirty years has been increasing public and governmental demand for the quantification of social phenomena, yet sociologists generally have paid little attention to the spread of quantification or the significance of new regimes of measurement. Our article addresses this oversight by analyzing quantification – the production and communication of numbers – as a general sociological phenomenon. Drawing on scholarship across the social sciences in Europe and North America as well as humanistic inquiry, we articulate five sociological dimensions of quantification and call for an ethics of numbers.