To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Electron blocks are typically composed of a low melting point alloy (LMPA), which is poured into an insert frame containing a manually placed Styrofoam aperture negative used to define the desired field shape. Current implementations of the block fabrication process involve numerous steps which are subjective and prone to user error. Occasionally, bowing of the sides of the insert frame is observed, resulting in premature frame decommissioning. Recent works have investigated the feasibility of utilising 3D printing technology to replace the conventional electron block fabrication workflow; however, these approaches involved long print times, were not compatible with commonly used cadmium-free LMPAs, and did not address the problem of insert frame bowing. In this work, we sought to develop a new 3D printing technique that would remedy these issues.
Materials and Methods:
Electron cutout negatives and alignment jigs were printed using Acrylonitrile Butadiene Styrene, which does not warp at the high temperatures associated with molten cadmium-free alloys. The accuracy of the field shape produced by electron blocks fabricated using the 3D printed negatives was assessed using Gafchromic film and beam profiler measurements. As a proof-of-concept, electron blocks with off-axis apertures, as well as complex multi-aperture blocks to be used for passive electron beam intensity modulation, were also created.
Film and profiler measurements of field size were in excellent agreement with the values calculated using the Eclipse treatment planning system, showing less than a 1% difference in line profile full-width at half-maximum. The multi-aperture electron blocks produced fields with intensity modulation ≤3.2% of the theoretically predicted value. Use of the 3D printed alignment jig – which has contours designed to match those of the insert frame – was found to reduce the amount of frame bowing by factors of 1.8 and 2.1 in the lateral and superior–inferior directions, respectively.
The 3D printed ABS negatives generated with our technique maintain their spatial accuracy even at the higher temperatures associated with cadmium-free LMPA. The negatives typically take between 1 and 2 hours to print and have a material cost of approximately $2 per patient.
Adolescent diet, physical activity and nutritional status are generally known to be sub-optimal. This is an introduction to a special issue of papers devoted to exploring factors affecting diet and physical activity in adolescents, including food insecure and vulnerable groups.
Eight settings including urban, peri-urban and rural across sites from five different low- and middle-income countries.
Focus groups with adolescents and caregivers carried out by trained researchers.
Our results show that adolescents, even in poor settings, know about healthy diet and lifestyles. They want to have energy, feel happy, look good and live longer, but their desire for autonomy, a need to ‘belong’ in their peer group, plus vulnerability to marketing exploiting their aspirations, leads them to make unhealthy choices. They describe significant gender, culture and context-specific barriers. For example, urban adolescents had easy access to energy dense, unhealthy foods bought outside the home, whereas junk foods were only beginning to permeate rural sites. Among adolescents in Indian sites, pressure to excel in exams meant that academic studies were squeezing out physical activity time.
Interventions to improve adolescents’ diets and physical activity levels must therefore address structural and environmental issues and influences in their homes and schools, since it is clear that their food and activity choices are the product of an interacting complex of factors. In the next phase of work, the Transforming Adolescent Lives through Nutrition consortium will employ groups of adolescents, caregivers and local stakeholders in each site to develop interventions to improve adolescent nutritional status.
The COVID-19 pandemic has had a major impact on clinical practice. Safe standards of practice are essential to protect health care workers while still allowing them to provide good care. The Canadian Society of Clinical Neurophysiologists, the Canadian Association of Electroneurophysiology Technologists, the Association of Electromyography Technologists of Canada, the Board of Registration of Electromyography Technologists of Canada, and the Canadian Board of Registration of Electroencephalograph Technologists have combined to review current published literature about safe practices for neurophysiology laboratories. Herein, we present the results of our review and provide our expert opinion regarding the safe practice of neurophysiology during the COVID-19 pandemic in Canada.
Physiological regulation may interact with early experiences such as maltreatment to increase risk for behavior problems. In the current study, we investigate the role of parasympathetic nervous system regulation (respiratory sinus arrhythmia [RSA] at rest and in response to a frustration task) as a moderator of the association between early risk for maltreatment (i.e., involvement with Child Protective Services; CPS) and externalizing behavior problems in middle childhood. CPS involvement was associated with elevated externalizing problems, but only among children with average to high RSA at rest and average to high RSA withdrawal in response to frustration. Effects appeared to be specific to CPS involvement as the association between cumulative risk (i.e., nonmaltreatment experiences of early adversity) and externalizing problems was not significantly moderated by RSA activity. These findings are consistent with the theoretical idea that the consequences of early maltreatment for later externalizing behavior problems depend on children's biological regulation abilities.
National and international research has shown the association between depression and anxiety disorders with the risk of planned and impulsive suicidal behavior. Patients with depression may have severe anxiety or agitation associated with their depression with or without comorbid additional anxiety disorder diagnoses.
1. Evaluate differences between self rated overall suicide risk of inpatients on a treatment resistant depression unit based on presence or absence of comorbid anxiety disorder.
2. Evaluate association of pharmacogenetic testing results with self-ratings of suicide risk.
1. To determine if suicide risk of psychiatric inpatients is higher in patients with depression and comorbid anxiety disorder.
2. To determine utility of pharmacogenetic testing with suicide risk assessment and patterns of use in patients with treatment resistant depression at a large academic medical center.
This is a retrospective records review study of a sample of over 700 inpatients on a treatment resistant depression unit at the Mayo Clinic. Patients overall suicide risk self-assessments will be analyzed for differences in suicide risk assessment controlling for diagnoses, age, and sex. Pharmacogenetic testing results, including serotonin transporter and p450 2D6 testing results, will be analyzed for their association with suicide risk.
Statistical analyses results are pending at time of abstract submission.
At a population level, the interplay between anxiety disorders and depressive symptoms is felt to be key to understanding the progression from suicidal ideation to suicidal behavior. Factors complicating this at an individual patient level along with results of research study will be discussed.
Infant colic is a condition of unknown cause which can result in carer distress and attachment difficulties. Recent studies have implicated the gut microbiota in infant colic, and certain probiotics have demonstrated possible efficacy. We aim to investigate whether the intestinal microbiota composition in infants with colic is associated with cry/fuss time at baseline, persistence of cry/fuss at 4-week follow-up, or child behavior at 2 years of age. Fecal samples from infants with colic (n = 118, 53% male) were analyzed using 16S rRNA sequencing. After examining the alpha and beta diversity of the clinical samples, we performed a differential abundance analysis of the 16S data to look for taxa that associate with baseline and future behavior, while adjusting for potential confounding variables. In addition, we used random forest classifiers to evaluate how well baseline gut microbiota can predict future crying time. Alpha diversity of the fecal microbiota was strongly influenced by birth mode, feed type, and child gender, but did not significantly associate with crying or behavioral outcomes. Several taxa within the microbiota (including Bifidobacterium, Clostridium, Lactobacillus, and Klebsiella) associate with colic severity, and the baseline microbiota composition can predict further crying at 4 weeks with up to 65% accuracy. The combination of machine learning findings with associative relationships demonstrates the potential prognostic utility of the infant fecal microbiota in predicting subsequent infant crying problems.
The importance of timely identification and treatment of psychosis are increasingly the focus of early interventions, with research targeting the initial high-risk period in the months following first-episode hospitalization. However, ongoing psychiatric treatment and service utilization after the symptoms have been stabilized over the initial years following first-episode has received less research attention.
To model the variables predicting continued service utilization with psychiatrists for adolescents following their first-episode psychosis; examine associated temporal patterns in continued psychiatric service utilization.
This study utilized a cohort design to assess adolescents (age 14.4 ± 2.5 years) discharged following their index hospitalization for first-episode psychosis. Bivariate analyses were conducted on predictor variables associated with psychiatric service utilization. All significant predictor variables were included in a logistic regression model.
Variables that were significantly associated with psychiatric service utilization included: diagnosis with a schizophrenia spectrum disorder rather than major mood disorder with psychotic features (OR = 24.0; P = 0.02), a first degree relative with depression (OR = 0.12; P = 0.05), and months since last psychiatric inpatient discharge (OR = 0.92; P = 0.02). Further examination of time since last hospitalization found that all adolescents continued service utilization up to 18 months post-discharge.
Key findings highlight the importance of early diagnosis, that a first degree relative with depression may negatively influence the adolescent's ongoing service utilization, and that 18 months post-discharge may a critical time to review current treatment strategies and collaborate with youth and families to ensure that services continue to meet their needs.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The hepatic safety of agomelatine was assessed in 49 phase II and III studies. The aim was to analyze the characteristics of patients who developed an increase in transaminases whilst taking agomelatine.
A retrospective pooled analysis of changes in serum transaminase in 7605 patients treated with agomelatine (25 mg or 50 mg/day) from 49 completed studies was undertaken. A significant increase in serum transaminase was defined as > 3-fold the upper limit of normal (> 3 ULN). Final causality was determined in a case-by-case review by five academic experts.
Transaminase increased to > 3 ULN in 1.3% and 2.5% of patients treated with 25 mg and 50 mg of agomelatine respectively, compared to 0.5% for placebo. The onset of increased transaminases occurred at < 12 weeks in 64% of patients. The median time to recovery (to ≤ 2ULN) was 14 days following treatment withdrawal. Liver function tests recovered in 36.1% patients despite the continuation of agomelatine, suggesting the presence of a liver adaptive mechanism. Patients with elevated transaminases at baseline, secondary to obesity and fatty liver disease (NAFLD), had an equally increased risk of developing further elevations of transaminases with agomelatine and placebo. This reflects the widespread fluctuations of serum transaminases in patients with NAFLD.
The overall incidence of abnormal transaminases was low and dose dependent. No specific population was identified regarding potential risk factors. Withdrawal of agomelatine led to rapid recovery, and some patients exhibited an adaptive phenomenon. The liver profile of agomelatine seems safe when serum transaminases are monitored.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Nearly half of care home residents with advanced dementia have clinically significant agitation. Little is known about costs associated with these symptoms toward the end of life. We calculated monetary costs associated with agitation from UK National Health Service, personal social services, and societal perspectives.
Prospective cohort study.
Thirteen nursing homes in London and the southeast of England.
Seventy-nine people with advanced dementia (Functional Assessment Staging Tool grade 6e and above) residing in nursing homes, and thirty-five of their informal carers.
Data collected at study entry and monthly for up to 9 months, extrapolated for expression per annum. Agitation was assessed using the Cohen-Mansfield Agitation Inventory (CMAI). Health and social care costs of residing in care homes, and costs of contacts with health and social care services were calculated from national unit costs; for a societal perspective, costs of providing informal care were estimated using the resource utilization in dementia (RUD)-Lite scale.
After adjustment, health and social care costs, and costs of providing informal care varied significantly by level of agitation as death approached, from £23,000 over a 1-year period with no agitation symptoms (CMAI agitation score 0–10) to £45,000 at the most severe level (CMAI agitation score >100). On average, agitation accounted for 30% of health and social care costs. Informal care costs were substantial, constituting 29% of total costs.
With the increasing prevalence of dementia, costs of care will impact on healthcare and social services systems, as well as informal carers. Agitation is a key driver of these costs in people with advanced dementia presenting complex challenges for symptom management, service planners, and providers.
The Wisconsin Twin Project comprises multiple longitudinal studies that span infancy to early adulthood. We summarize recent papers that show how twin designs with deep phenotyping, including biological measures, can inform questions about phenotypic structure, etiology, comorbidity, heterogeneity, and gene–environment interplay of temperamental constructs and mental and physical health conditions of children and adolescents. The general framework for investigations begins with rich characterization of early temperament and follows with study of experiences and exposures across childhood and adolescence. Many studies incorporate neuroimaging and hormone assays.
The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework’s major proposition is that it situates D&I sciences as targeted “sub-sciences” of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages.
Methamphetamine (MA) dependence contributes to neurotoxicity and neurocognitive deficits. Although combined alcohol and MA misuse is common, how alcohol consumption relates to neurocognitive performance among MA users remains unclear. We hypothesized that alcohol and MA use would synergistically diminish neurocognitive functioning, such that greater reported alcohol consumption would exert larger negative effects on neurocognition among MA-dependent individuals compared to MA-nonusing persons.
Eighty-seven MA-dependent (MA+) and 114 MA-nonusing (MA−) adults underwent neuropsychological and substance use assessments. Linear and logistic regressions examined the interaction between MA status and lifetime average drinks per drinking day on demographically corrected global neurocognitive T scores and impairment rates, controlling for recent alcohol use, lifetime cannabis use, WRAT reading performance, and lifetime depression.
MA+ displayed moderately higher rates of impairment and lower T scores compared to MA−. Lifetime alcohol use significantly interacted with MA status to predict global impairment (ORR = 0.70, p = .003) such that greater lifetime alcohol use increased likelihood of impairment in MA−, but decreased likelihood of impairment in MA+. Greater lifetime alcohol use predicted poorer global T scores among MA− (b = −0.44, p = .030) but not MA+ (b = 0.08, p = .586).
Contrary to expectations, greater lifetime alcohol use related to reduced risk of neurocognitive impairment among MA users. Findings are supported by prior research identifying neurobiological mechanisms by which alcohol may attenuate stimulant-driven vasoconstriction and brain thermotoxicity. Replication and examination of neurophysiologic mechanisms underlying alcohol use in the context of MA dependence are warranted to elucidate whether alcohol confers a degree of neuroprotection.