A Pilot Study of Ketotifen in Patients Aged 8-17 Years with Functional Dyspepsia Associated with Mucosal Eosinophilia.

BACKGROUND AND OBJECTIVE: Mast cells have been implicated in abdominal pain-associated disorders of gut-brain interaction, such as functional dyspepsia. As such, ketotifen, a second-generation antihistamine and mast cell stabilizer, could represent a viable treatment option in these conditions. The primary aim of the current pilot study was to assess clinical response to ketotifen and assess pharmacokinetics in youth with functional dyspepsia. METHODS: We conducted a pilot randomized, double-blind, placebo-controlled, cross-over trial of ketotifen in 11 youth with functional dyspepsia and duodenal mucosal eosinophilia with 4 weeks of active treatment at a dose of 1 mg twice daily. Global clinical response was graded on a 5-point Likert Scale. A single plasma sample was obtained at steady state for pharmacokinetic analysis. RESULTS: Ketotifen was not superior to placebo with regard to global clinical response. Only 18% of patients demonstrated a complete or near-complete clinical response. The estimated half-life was 3.3 h. CONCLUSIONS: While ketotifen was not superior to placebo, this study highlights several important challenges for developing drug trials for youth with chronic abdominal pain. Recommendations are made for designing a larger treatment trial for ketotifen in this patient group. CLINICAL TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov: NCT02484248.

Health related quality of life during dialysis modality transitions: a qualitative study.

BACKGROUND: Modality transitions represent a period of significant change that can impact health related quality of life (HRQoL). We explored the HRQoL of adults transitioning to new or different dialysis modalities. METHODS: We recruited eligible adults (≥ 18) transitioning to dialysis from pre-dialysis or undertaking a dialysis modality change between July and September 2017. Nineteen participants (9 incident and 10 prevalent dialysis patients) completed the KDQOL-36 survey at time of transition and three months later. Fifteen participants undertook a semi-structured interview at three months. Qualitative data were thematically analyzed. RESULTS: Four themes and five sub-themes were identified: adapting to new circumstances (tackling change, accepting change), adjusting together, trading off, and challenges of chronicity (the impact of dialysis, living with a complex disease, planning with uncertainty). From the first day of dialysis treatment to the third month on a new dialysis therapy, all five HRQoL domains from the KDQOL-36 (symptoms, effects, burden, overall PCS, and overall MCS) improved in our sample (i.e., those who remained on the modality). CONCLUSIONS: Dialysis transitions negatively impact the HRQoL of people with kidney disease in various ways. Future work should focus on how to best support people during this time.

In Vivo Detection of Changes Related to Cortical Columnar Organization and Neuroinflammation Across the AD Continuum.

BACKGROUND: Alzheimer's disease (AD) neuropathology reveals progressive microstructural alterations of cortical architecture. Recent studies reported intriguing biphasic trajectories of cortical structural changes in the early stages of Alzheimer's disease (AD), comprising decreased mean diffusivity (MD) and increased cortical thickness in cognitively normal amyloid-positive individuals, ahead of increases and decreases, respectively, in subsequent disease stages. OBJECTIVE: To better understand the cytoarchitectural correlates of these observations, we assessed novel cortical diffusion tensor imaging (DTI) metrics that are correlated with disruption of cortical minicolumns and protein deposition. DESIGN: Cross-sectional and longitudinal analysis of whole brain and temporal lobe cortical diffusivity measures. Investigation of associations between baseline cortical diffusivity values and 24-month longitudinal structural-MRI changes. Investigations of the relationships between cortical diffusivity measures and biomarkers of neuroinflammation. SETTING: Alzheimer's Disease Neuroimaging Initiative (ADNI). PARTICIPANTS: Twenty-four amyloid-negative controls (CN-), 28 amyloid-positive controls (CN+), 46 amyloid-positive subjects with mild cognitive impairment (MCI+) and 22 amyloid-positive subjects with AD were included. MEASUREMENTS: 3DT1 and DTI scans at baseline and approximately 24-month follow-up were used to calculate cortical MD and three novel cortical diffusivity measures: the angle between the radial minicolumnar axis and the principal diffusion direction (AngleR); the diffusion components perpendicular to the minicolumns (PerpPD+), and the principal diffusion component parallel with the minicolumns (ParlPD). Cortical macrostructural measurements (cortical volume fraction and cortical thickness), were used to test the hypothesis that baseline cortical diffusivity values can predict change in structural MRI outcomes over approximately 24 months. CSF soluble TREM2 and progranulin (PGRN) concentrations were used to investigate associations with microglial activity and potentially other aspects of neuroinflammation. RESULTS: Cortical diffusivity metrics revealed a dependence on disease stage, with AngleR and PerpPD+ displaying biphasic relationships and ParlPD a monotonic relationship with clinical severity. The novel metrics were able to differentiate between Amyloid+ and Amyloid- controls (AngleR) and to differentiate among disease stages along the AD continuum (PerpPD+). Linear regression revealed significant associations between baseline cortical diffusivity values and subsequent 24-month longitudinal structural-MRI changes. AngleR values were significantly associated with CSF sTREM2 and PGRN concentrations. CONCLUSIONS: Cortical diffusivity parameters reflecting minicolumnar organization and neuroinflammation may provide a sensitive and biologically interpretable measurement of cortex quality and microstructure across the AD continuum.

In-center nocturnal hemodialysis improves health-related quality of life for patients with end-stage renal disease.

BACKGROUND: Conventional in-center hemodialysis (HD) is associated with significant symptom burden and reduced health-related quality of life (HRQOL). The HRQOL effects of conversion to in-center nocturnal hemodialysis (INHD) remain unclear, especially amongst those with poor HRQOL. METHODS: Prospective cohort study of HD patients converting to INHD. Linear regression models summarized the mean score at baseline and at 12 months for the cohort. To assess whether patients with low baseline HRQOL derive greater benefit, we compared values before and after by levels of baseline score for each domain (below vs equal to or above the median) using a formal interaction test (t test). RESULTS: 36 patients started INHD, 7 withdrew (5 transplanted, 1 death, 1 moved) and 5 declined follow-up. After 12 months the mental component score (MCS) increased by 7.1 points to a value of 51.0 (95% CI + 1.5 to 10.9, p = 0.01). Amongst patients with baseline scores below the median, improvements were seen in: Symptoms/Problems of Kidney Disease (+ 15.2, 95% CI + 5.5 to + 24.9, p = 0.003), Effects of Kidney Disease (+ 16.9, 95% CI + 2.2 to + 31.7, p = 0.026), Physical Component Score (+ 9.4, 95% CI + 1.69 to + 17.2, p = 0.018), MCS (+ 10.7, 95% CI + 2.4 to + 19.1, p = 0.013). Burden of Kidney Disease domain change was not significant (+ 15.1, 95% CI - 2.1 to + 32.3, p = 0.083). DISCUSSION: INHD is a potential intervention for HD patients who struggle with reduced HRQOL, especially for those who struggle with poor mental health. Medical benefits of reduced pill burden and improved phosphate control occur with transition to INHD.

Are body surface area based estimates of liver volume applicable to children with overweight or obesity? An in vivo validation study.

The liver is the primary organ responsible for clearing most drugs from the body and thus determines systemic drug concentrations over time. Drug clearance by the liver appears to be directly related to organ size. In children, organ size changes as children age and grow. Liver volume has been correlated with body surface area (BSA) in healthy children and adults and has been estimated by functions of BSA. However, these relationships were derived from "typical" populations and it is unknown whether they extend to estimations of liver volumes for population "outliers," such as children with overweight or obesity, who today represent one-third of the pediatric population. Using computerized tomography or magnetic resonance imaging, this study measured liver volumes in 99 children (2-21 years) with normal weight, overweight, or obesity and compared organ measurements with estimates calculated using an established liver volume equation. A previously developed equation relating BSA to liver volume adequately estimates liver volumes in children, regardless of weight status.

Efficacy of Weight Reduction on Pediatric Nonalcoholic Fatty Liver Disease: Opportunities to Improve Treatment Outcomes Through Pharmacotherapy.

Obesity is the single greatest risk factor for nonalcoholic fatty liver disease (NAFLD). Without intervention, most pediatric patients with NAFLD continue to gain excessive weight, making early, effective weight loss intervention key for disease treatment and prevention of NAFLD progression. Unfortunately, outside of a closely monitored research setting, which is not representative of the real world, lifestyle modification success for weight loss in children is low. Bariatric surgery, though effective, is invasive and can worsen NAFLD postoperatively. Thus, there is an evolving and underutilized role for pharmacotherapy in children, both for weight reduction and NAFLD management. In this perspective article, we provide an overview of the efficacy of weight reduction on pediatric NAFLD treatment, discuss the pros and cons of currently approved pharmacotherapy options, as well as drugs commonly used off-label for weight reduction in children and adolescents. We also highlight gaps in, and opportunities for, streamlining obesity trials to include NAFLD assessment as a valuable, secondary, therapeutic outcome measure, which may aid drug repurposing. Finally, we describe the already available, and emerging, minimally-invasive biomarkers of NAFLD that could offer a safe and convenient alternative to liver biopsy in pediatric obesity and NAFLD trials.

Relationships between disaccharidase deficiencies, duodenal inflammation and symptom profile in children with abdominal pain.

Abdominal pain has been associated with disaccharidase deficiencies. While relationships with individual symptoms have been assessed, relationships between disaccharidase deficiencies and symptom complexes or inflammation have not been evaluated in this group. The primary aims of the current study were to assess relationships between disaccharidase deficiency and symptoms or symptom complexes and duodenal inflammation, respectively. Patients with abdominal pain who underwent endoscopy with evaluation of disaccharidase activity levels were identified. After excluding all patients with inflammatory bowel disease, celiac disease, H. pylori, or gross endoscopic lesions, patients were evaluated for disaccharidase deficiency frequency. Disaccharidase were compared between patients with and without histologic duodenitis. Lastly, relationships between individual gastrointestinal symptoms or symptom complexes were evaluated. Lactase deficiency was found in 34.3% of patients and disaccharidase pan-deficiency in 7.6%. No individual symptoms or symptom complexes predicted disaccharidase deficiency. While duodenitis was not associated with disaccharidase deficiency, it was only present in 5.9% of patients. Disaccharidase deficiency, particularly lactase deficiency, is common in youth with abdominal pain and multiple deficiencies are not uncommon. Disaccharidase deficiency cannot be predicted by symptoms in this population. Further studies are needed to assess the clinical significance of disaccharidase deficiency.

Meckel's diverticulum in adults: seldom suspected and frequently found.

Meckel's diverticulum (MD) is a well-defined diagnosis in children presenting with either bleeding or obstruction. Although anecdotally adult patients may present with complications from MD, their presentation seems to be different, with a reported predominance of non-bleed-related presentations. Reports in this population, however, are limited, and little is known of the epidemiology of MD in older patients. We performed a retrospective analysis of the Agency of Healthcare Research and Quality National Inpatient Sample of all US hospital discharges from 2012 to 2016. We identified patients with a primary discharge diagnosis of MD. Data were abstracted as raw numbers and population weighted rates of discharge with age group, income level, length of stay (LOS) and hospital charges as additional information. On average, 2030 individuals were discharged annually; most (71.1%) were adults (>18 years). Although MD was predominant in males in all age groups, the gender ratio decreased with older age categories from 3.5:1.0 (1-17 years) to 1.6:1.0 (65-84 years). LOS averaged 5.3 days with no clear relationship to other parameters. Median income category, however, closely correlated (R2=0.9996) with diagnosis in older age categories. MD may be significantly more prevalent in adult patients than was previously understood. Differences in gender preponderance suggest that gender may influence the pattern of presentation. Diagnosis in older individuals is closely associated with income or socioeconomic status but not hospital charges or LOS.

Critical need for pharmacologic treatment options in NAFLD: A pediatric perspective.

Nonalcoholic fatty liver disease (NAFLD) affects up to 70% of children with obesity and has become the number one etiology for liver transplant in the United States. Early, effective intervention is critical to prevent disease progression into adulthood. Yet, it is seldom achieved through lifestyle modification alone. Thus, children must be included in NAFLD pharmacology trials, which, to date, continue to focus primarily on adult populations. This commentary serves as a call to action.

Using diffusion tensor imaging to detect cortical changes in fronto-temporal dementia subtypes.

Fronto-temporal dementia (FTD) is a common type of presenile dementia, characterized by a heterogeneous clinical presentation that includes three main subtypes: behavioural-variant FTD, non-fluent/agrammatic variant primary progressive aphasia and semantic variant PPA. To better understand the FTD subtypes and develop more specific treatments, correct diagnosis is essential. This study aimed to test the discrimination power of a novel set of cortical Diffusion Tensor Imaging measures (DTI), on FTD subtypes. A total of 96 subjects with FTD and 84 healthy subjects (HS) were included in the study. A "selection cohort" was used to determine the set of features (measurements) and to use them to select the "best" machine learning classifier from a range of seven main models. The selected classifier was trained on a "training cohort" and tested on a third cohort ("test cohort"). The classifier was used to assess the classification power for binary (HS vs. FTD), and multiclass (HS and FTD subtypes) classification problems. In the binary classification, one of the new DTI features obtained the highest accuracy (85%) as a single feature, and when it was combined with other DTI features and two other common clinical measures (grey matter fraction and MMSE), obtained an accuracy of 88%. The new DTI features can distinguish between HS and FTD subgroups with an accuracy of 76%. These results suggest that DTI measures could support differential diagnosis in a clinical setting, potentially improve efficacy of new innovative drug treatments through effective patient selection, stratification and measurement of outcomes.

Central venous catheters for chronic hemodialysis: Is "last choice" never the "right choice"?

Since the publication of the first vascular access clinical practice guidelines in 1997, the global nephrology community has dedicated significant time and resources toward increasing the prevalence of arteriovenous fistulas and decreasing the prevalence of central venous catheters for hemodialysis. These efforts have been bolstered by observational studies showing an association between catheter use and increased patient morbidity and mortality. To date, however, no randomized comparisons of the outcomes of different forms of vascular access have been conducted. There is mounting evidence that much of the difference in patient outcomes may be explained by patient factors, rather than choice of vascular access. Some have called into question the appropriateness of fistula creation for certain patient populations, such as those with limited life expectancy and those at high risk of fistula-related complications. In this review, we explore the extent to which catheters and fistulas exhibit the characteristics of the "ideal" vascular access and highlight the significant knowledge gaps that exist in the current literature. Further studies, ideally randomized comparisons of different forms of vascular access, are required to better inform shared decision making.

Development of the embryonic heat shock response and the impact of repeated thermal stress in early stage lake whitefish (Coregonus clupeaformis) embryos.

Lake whitefish (Coregonus clupeaformis) embryos were exposed to thermal stress (TS) at different developmental stages to determine when the heat shock response (HSR) can be initiated and if it is altered by exposure to repeated TS. First, embryos were subject to one of three different TS temperatures (6, 9, or 12°C above control) at 4 points in development (21, 38, 60 and 70 days post-fertilisation (dpf)) for 2h followed by a 2h recovery to understand the ontogeny of the HSR. A second experiment explored the effects of repeated TS on the HSR in embryos from 15 to 75 dpf. Embryos were subjected to one of two TS regimes; +6°C TS for 1h every 6 days or +9°C TS for 1h every 6 days. Following a 2h recovery, a subset of embryos was sampled. Our results show that embryos could initiate a HSR via upregulation of heat shock protein 70 (hsp70) mRNA at all developmental ages studied, but that this response varied with age and was only observed with a TS of +9 or +12°C. In comparison, when embryos received multiple TS treatments, hsp70 was not induced in response to the 1h TS and 2h recovery, and a downregulation was observed at 39 dpf. Downregulation of hsp47 and hsp90α mRNA was also observed in early age embryos. Collectively, these data suggest that embryos are capable of initiating a HSR at early age and throughout embryogenesis, but that repeated TS can alter the HSR, and may result in either reduced responsiveness or a downregulation of inducible hsps. Our findings warrant further investigation into both the short- and long-term effects of repeated TS on lake whitefish development.

Advanced age is not a barrier to creating a functional arteriovenous fistula: a retrospective study.

INTRODUCTION: Arteriovenous fistulas (AVFs) are the recommended form of vascular access for hemodialysis. However, controversy exists regarding whether AVFs are suitable for elderly patients. METHODS: Single-center retrospective review to investigate the impact of age on AVF outcomes. Five hundred and twenty-five patients with AVF creation were stratified based on age <65, 65-75, and >75 years. AVF outcomes including primary failure, AVF patency (primary, secondary, and functional), and AVF complications were studied for 3 years following AVF creation. RESULTS: The cohort was 63% male, 44% Caucasian, and 55% had diabetes or cardiovascular disease. 39% were aged <65 years, 33% 65-75 years, and 28% were aged >75 years. No differences in rates of primary failure, loss of primary patency, complications, or need for intervention were observed between age groups. There was a significant association of age with secondary patency and functional patency, with age >75 being an independent risk factor for shortened lifespan of the fistula. For patients aged >75 years, secondary patency at 3 years was 64% compared to 75%-78% for younger patients. Functional patency at 2 years was 69% for those aged >75 years compared to 78%-81% for younger patients. CONCLUSIONS: We found no difference in AVF maturation, primary patency, complications, or interventions in those over the age of 75 compared to younger counterparts. While secondary and functional patency rates were significantly lower in those aged >75 years, the magnitude of difference is likely not clinically relevant. Therefore, we recommend that advanced age alone should not preclude patients from AVF creation.

Thermal stress and the heat shock response in embryonic and young of the year juvenile lake whitefish.

We investigated the effects of thermal stress on embryonic (fin flutter, vitelline circulation stage) and young of the year (YOY) juvenile lake whitefish by characterizing the kinetics of the heat shock response (HSR). Lake whitefish were subjected to one of three different heat shock (HS) temperatures (3, 6, or 9 °C above control) for six different lengths of time (0.25, 0.50, 1, 2, 3, or 4h) followed by a 2h recovery period at the control temperature of 2 °C or 14 °C for embryos and YOY juveniles, respectively. The duration of the HSR was examined by allowing the fish to recover for 1, 2, 4, 8, 12, 16, 24, 36, or 48 h following a 2h HS. In embryos, at the fin flutter stage, only hsp70 mRNA levels were upregulated in response to the various HS treatments. By comparison, all three typically inducible hsps, hsp90α, hsp70 and hsp47, were upregulated in the YOY juveniles. In both instances the HSR was long lasting, but much more so in embryos where hsp70 mRNA levels continued to increase for 48 h after a 2h HS and remained significantly higher than untreated controls. Collectively our data indicate that both embryo and YOY juvenile lake whitefish have a robust HSR which permits them to survive a 4h, 9 °C HS. Moreover, both life history stages are capable of triggering a HSR following a moderate 3 °C HS which is likely an important protective mechanism against environmental stressors during embryogenesis and early life history stages of lake whitefish.

The neuropathology of schizophrenia: A selective review of past studies and emerging themes in brain structure and cytoarchitecture.

Schizophrenia is a devastating mental illness. Although its etiology is still largely unknown, strides have been taken throughout the last several decades to elucidate the nature of the neuropathology behind this disorder. The advent of neuroimaging technologies such as computerized axial tomography and magnetic resonance imaging have progressed knowledge about the macroscopic brain changes that occur in schizophrenia, including the characteristic enlarged ventricle size and reductions in gray matter volume, whole-brain volume, and white matter anisotropy. Although this review presents a broad outline of current and historical neuropathological research, the focus is primarily on the quantitative neuropathology of the cerebral cortex in schizophrenia, which may underlie many of the larger scale changes observed. The reduced neuropil hypothesis has been suggested as a microanatomical explanation to account for these macroscopic changes, although the present review finds that evidence does not always support this. A quantitative meta-analytic summary of these studies, focused on neuron density, provides support for the finding of increased neuron density in schizophrenia, with variation dependent on age. This is consistent with neuroimaging data and implicates an altered aging trajectory as a factor in the pathogenesis of schizophrenia. Combined with evidence from other neuroanatomical studies reviewed here, as well as studies in childhood-onset schizophrenia, the evidence converges on a progressive neurodevelopmental model of schizophrenia related to altered neuroplasticity. The evidence also supports a particular vulnerability of inhibitory cortical circuits with markers of interneurons showing some of the more consistent reductions in schizophrenia.

Changing radiation dose from diagnostic computed tomography examinations in Saskatchewan.

PURPOSE: Follow-up study to observe if provincial mean effective radiation dose for head, chest, and abdomen-pelvis (AP) computed tomographies (CTs) remained stable or changed since the initial 2006 survey. METHODS: Data were collected in July 2008 from Saskatchewan's 13 diagnostic CT scanners of 3358 CT examinations. These data included the number of scan phases and projected dose length product (DLP). Technologists compared projected DLP with 2006 reference data before scanning. Projected DLP was converted to effective dose (ED) for each head, chest, and AP CT. The total dose that the patients received with scans of multiple body parts at the same visit also was determined. RESULTS: The mean (± SD) provincial ED was 3.4 ± 1.6 mSv for 1023 head scans (2.7 ± 1.6 mSv in 2006), 9.6 ± 4.8 mSv for 588 chest scans (11.3 ± 8.9 mSv in 2006), and 16.1 ± 9.9 mSv for 983 AP scans (15.5 ± 10.0 mSv in 2006). Single-phase multidetector row CT ED decreased by 31% for chest scans (9.5 ± 3.9 mSv vs 13.7 ± 9.7 mSv in 2006) and 17% for AP scans (13.9 ± 6.0 mSv vs 16.8 ± 10.6 mSv in 2006) and increased by 19% for head scans (3.2 ± 1.2 mSv vs 2.7 ± 1.5 mSv in 2006). The total patient dose was highest (33.8 ± 10.1 mSv) for the 20 patients who received head, neck, chest, and AP scans during a single visit. Because of increased utilisation and the increased CT head dose, Saskatchewan per capital radiation dose from CT increased by 21% between 2006 and 2008 (1.14 vs 1.38 mSv/person per year). CONCLUSION: Significant dose and variation reduction was seen for single-phase CT chest and AP examinations between 2006 and 2008, whereas CT head dose increased over the same interval. These changes, combined with increased utilisation, resulted in per capita increase in radiation dose from CT between the 2 studies.

The relationship between callosal axons and cortical neurons in the planum temporale: alterations in schizophrenia.

The relationship between "connectivity" measures such as DTI and the cellular alterations in the cortex that give rise to those connections remains unclear. Cytoarchitectural changes in the planum temporale (PT) suggest impaired layer III feedforward projection neurons in schizophrenia. Altered hemispheric asymmetry of the PT has been reported in patients, along with altered white matter density in the corpus callosum, and there is anomalous activation of the PT during auditory hallucinations. We measured layer III cell density and pyramidal neuron size in PT of both hemispheres of post-mortem brains from patients with schizophrenia (n=16) and control subjects (n=16). We found reduced cell density and the loss of a correlation between magnopyramidal neuron density and axon number in the isthmus of the corpus callosum in schizophrenia. The normal asymmetry indicated that magnopyramidal neurons tend towards being larger and denser in the left PT but this asymmetry is significantly reduced in schizophrenia. The findings offer cytoarchitectural insight into the relationship between PT cortex and callosal white matter abnormalities in schizophrenia.

Computed tomography radiation dose: a primer for administrators.

The use of computed tomography (CT) is growing, and, consequently, the associated radiation dose to patients is increasing as well. There is also increasing evidence linking the radiation dose within the range of diagnostic CT with a significantly increased risk of malignancy. These two factors combine to make radiation dose from diagnostic CT a public health concern. In order to practise to the best of our abilities and avoid harming patients, the radiation dose from CT must be minimized. Administrators, technologists, radiologists and other physicians are encouraged to work toward this goal through the use of education and a multi-faceted team approach. The objective of this paper is to educate healthcare professionals about the radiation dose from diagnostic CT, including utilization rates, typical examination doses and the risks of this radiation. Our experience in Saskatchewan is discussed. Suggestions regarding CT dose management and optimization are highlighted.

Radiation dose from diagnostic computed tomography in Saskatchewan.

OBJECTIVE: To calculate the effective dose from diagnostic computed tomography (CT) scans in Saskatchewan, Canada, and compare with other reported dose levels. METHODS: Data from CT scans were collected from 12 scanners in 7 cities across Saskatchewan. The patient age, scan type, and selected technique parameters including the dose length product and the volume computed tomography dose index were collected for a 2-week period. This information then was used to calculate effective doses patients are exposed to during CT examinations. Data from 2,061 clinically indicated CT examinations were collected, and of them 1,690 were eligible for analysis. Every examination during a 2-week period was recorded without selection. RESULTS: The average provincial estimated patient dose was as follows: head, 2.7 mSv (638 scans; standard deviation [SD], +/-1.6); chest, 11.3 mSv (376 scans; SD, +/-8.9); abdomen-pelvis, 15.5 mSv (578 scans; SD, +/-10.0); abdomen, 11.7 mSv (80 scans; SD, +/-11.48), and pelvis, 8.6 mSv (18 scans; SD, +/-6.04). Significant variation in dose between the CT scanners was observed (P = .049 for head, P = .001 for chest, and P = .034 for abdomen-pelvis). CONCLUSIONS: Overall, the estimated dose from diagnostic CT examinations was similar to other previously published Canadian data from British Columbia. This dose varied slightly from some other published standards, including being higher than those found in a review conducted in the United Kingdom in 2003.

Callosal misconnectivity and the sex difference in psychosis.

The sex difference in age of onset in schizophrenia is paradoxical in the sense that the brain is developing faster in females but onsets are earlier in males. Therefore if schizophrenia, as widely believed, is a disorder of development, the difference is in the wrong direction. Here we attempt to resolve the paradox with the hypothesis that psychosis is an anomaly of development of cerebral asymmetry and the following assumptions: (1) asymmetry (the torque) confers directionality on the 'language circuit'--failure to develop asymmetry leads to the risk of reverse transmission, a putative mechanism of psychotic symptoms; (2) the corpus callosum goes on developing in an antero-posterior direction into the third and fourth decades of life; (3) a sex difference in structure and development of the corpus callosum (with some anterior components greater in males and posterior components greater in females) reflects stronger, faster lateralization in females; (4) because of the inverse relationship between asymmetry and interhemispheric connections, females, by developing faster, avoid the misconnectivity phenomena in the frontal lobes that males, developing more slowly, may encounter at a younger age with particular risk of negative symptoms.