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The thickness of glaciers in High-Mountain Asia (HMA) is critical in determining when the ice reserve will be lost as these glaciers thin but is remarkably poorly known because very few measurements have been made. Through a series of ground-based and airborne field tests, we have adapted a low-frequency ice-penetrating radar developed originally for Antarctic over-snow surveys, for deployment as a helicopter-borne system to increase the number of measurements. The manoeuvrability provided by helicopters and the ability of our system to detect glacier beds through thick, dirty, temperate ice makes it well suited to increase greatly the sample of measurements available for calibrating ice thickness models on the regional and global scale. The Bedmap Himalayas radar-survey system can reduce the uncertainty in present-day ice volumes and therefore in projections of when HMA's river catchments will lose this hydrological buffer against drought.
Transition from child-centred to adult mental health services has been reported as challenging for young people. It can be especially difficult for young people with autism spectrum disorder (ASD) as they manage the challenges of adolescence and navigate leaving child and adolescent mental health services (CAMHS).
This study examines the predictors of transfer to adult mental health services, and using a qualitative analysis, explores the young people’s experiences of transition.
A UK sample of 118 young people aged 14–21 years, with ASD and additional mental health problems, recruited from four National Health Service trusts were followed up every 12 months over 3 years, as they were discharged from CAMHS. Measures of mental health and rich additional contextual information (clinical, family, social, educational) were used to capture their experiences. Regression and framework analyses were used.
Regression analysis showed having an attention-deficit hyperactivity disorder diagnosis and taking medication were predictors of transfer from child to adult mental health services. Several features of young people's transition experience were found to be associated with positive outcomes and ongoing problems, including family factors, education transitions and levels of engagement with services.
The findings show the importance of monitoring and identifying those young people that might be particularly at risk of negative outcomes and crisis presentations. Although some young people were able to successfully manage their mental health following discharge from CAMHS, others reported levels of unmet need and negative experiences of transition.
Abnormal body mass index (BMI) has been associated with development of psychopathology. This association in children is well documented, for both overweight and underweight children. However, the association between change in BMI and the development of psychopathology has been less investigated.
To investigate the association between change in BMI between childhood and adolescence and psychopathology in adolescence.
Data from the Growing Up in Ireland cohort were used. We investigated the ’98 cohort (also known as the child cohort) at age 9/13. BMI, defined using internationally recognised definitions as underweight, healthy or overweight, was used as the exposure, and abnormal Strength and Difficulties Questionnaire scores were used as the outcome. Logistic regression was undertaken for the analysis. All analyses were adjusted for confounders.
A change to overweight from healthy BMI was significantly associated with increased risk of psychopathology (adjusted OR 1.66; 95% CI 1.19–2.32). Both change from underweight to healthy (adjusted OR 0.12; 95% CI 0.03–0.43) or from overweight to healthy (adjusted OR 0.47; 95% CI 0.79–0.8) was associated with a significantly reduced risk of developing psychopathology.
As a child’s BMI returns to within the healthy range, their risk of adolescent psychopathology is reduced. Interventions to restore healthy BMI, in both underweight and overweight, children may reduce their risk of adolescent psychopathology.
Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts.
To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes.
Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders.
In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being.
Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.
Introduction: Distal radial fractures (DRF) remain the most commonly encountered fracture in the Emergency Department (ED). The initial management of displaced DRFs by Emergency Physicians (EP) poses considerable resource allocation. We wished to determine the adequacy of reduction, both initially and at follow up. This data updates previously presented high level findings. Methods: We performed a mixed-methods study including patients who underwent procedural sedation and manipulation by an EP for a DRF. Radiological images performed at initial assessment, post-reduction, and clinic follow up were reviewed by a panel of orthopedic surgeons and radiologists blinded to outcomes, and assessed for evidence of displacement. Demographic data were pooled from patient records and included in statistical analysis. Results: Seventy patients were included and had follow-up completed. Initial reduction was deemed to be adequate in 37 patients (53%; 95% CI 41.32 to 64.10%). At clinic follow-up assessment, 26 reductions remained adequate; a slippage rate of 30% (95% CI of 17.37 to 45.90). Overall 7 patients (10%; 95% CI 4.65 to 19.51%) required revision of the initial reduction in the operating room. Agreement on adequacy of reduction on post-reduction radiographs between radiologists and orthopedic surgeons was 38.6% (95% CI -38.3 to -7.4, Kappa -0.229). The statistical strength of this agreement is worse than what would be expected by chance alone. There was no association found between age, sex, or of time of initial presentation and final outcomes. Conclusion: Although blinded review by specialists determined only half of initial EP DRF reductions to be radiographically adequate, only 10 percent actually required further intervention. Agreement between specialists on adequacy was poor. The majority of DRFs reduced by EPs do not require further surgical intervention.
Right cerebellar-left frontal (RC-LF) white matter integrity (WMI) has been associated with working memory. However, prior studies have employed measures of working memory that include processing speed and attention. We examined the relationships between the RC-LF WMI and processing speed, attention, and working memory to clarify the relationship of RC-LF WMI with a specific cognitive function. Right superior longitudinal fasciculus II (SLF II) WMI and visual attention were included as a negative control tract and task to demonstrate a double dissociation.
Adult survivors of childhood brain tumors [n = 29, age: M = 22 years (SD = 5), 45% female] and demographically matched controls were recruited (n = 29). Tests of auditory attention span, working memory, and visual attention served as cognitive measures. Participants completed a 3-T MRI diffusion-weighted imaging scan. Fractional anisotropy (FA) and radial diffusivity (RD) served as WMI measures. Partial correlations between WMI and cognitive scores included controlling for type of treatment.
A correlational double dissociation was found. RC-LF WMI was associated with auditory attention (FA: r = .42, p = .03; RD: r = −.50, p = .01) and was not associated with visual attention (FA: r = −.11, p = .59; RD: r = −.11, p = .57). SLF II FA WMI was associated with visual attention (FA: r = .44, p = .02; RD: r = −.17, p = .40) and was not associated with auditory attention (FA: r = .24, p = .22; RD: r = −.10, p = .62).
The results show that RC-LF WMI is associated with auditory attention span rather than working memory per se and provides evidence for a specificity based on the correlational double dissociation.
Determining best practices for managing free farrowing systems is crucial for uptake. Cross-fostering, the exchange of piglets between litters, is routinely performed amongst crate-housed sows. However, cross-fostering can increase fighting amongst the litter and may be more challenging within free farrowing systems as sows have more freedom to respond to cross-fostered piglets. This study compared the effect of either cross-fostering (FOS), or a control of sham-fostering (CON), of four focal piglets per litter on Day 6 postpartum in crates (CRATE) and free farrowing pens (PEN). The post-treatment behavioural responses of sows were recorded (Day 6 = 60 min; Day 7 = 300 min; n = 48), as were the average daily gain (ADG; g/day), total weight gain (TWG; kg) and body lesion scores of focal piglets and their littermates throughout lactation (Day 6, Day 8, Day 11 and Day 26; n = 539) and the post-weaning period (Day 29, Day 32 and Day 60; n = 108). On Day 6, though post-reunion latency to nursing did not differ, latency to successful nursing was longer amongst FOS than CON litters (P < 0.001), more so amongst CRATE FOS than PEN FOS (P < 0.01). On Day 7, PEN FOS sows had fewer successful nursing bouts (P < 0.05) and exhibited decreased lateral (P < 0.01) and increased ventral lying frequencies (P < 0.01) compared to all other housing and treatment combinations. Focal piglet ADG was lower for FOS than CON in the CRATE during Day 6 to Day 8 (P < 0.01) and lower in the PEN during Day 6 to Day 8 (P < 0.001), Day 8 to Day 11 (P < 0.01) and Day 11 to Day 26 (P < 0.05). The TWG of pre-weaned focal piglets (Day 6 to Day 26) was higher amongst CON than FOS litters (P = 0.01). Post-weaning, piglet ADG was higher for PEN than CRATE during Day 26 to Day 29 (P < 0.01) and higher for FOS than CON during Day 26 to Day 29 (P < 0.05), Day 29 to Day 32 (P < 0.001) and Day 32 to Day 60 (P < 0.01); thus, TWG was higher for FOS than CON during the weaner (P = 0.001) and the combined lactation and weaner periods (P = 0.09). In conclusion, sow behaviour was disrupted by cross-fostering in the crates and pens and continued to be disturbed on the following day amongst penned sows. FOS piglets exhibited reduced ADG after cross-fostering, which extended throughout lactation in the pens. However, the increased post-weaning weight gain of FOS piglets meant that their TWG was higher than CON piglets, irrespective of the farrowing system used.
In 2016, the US FDA issued an industry guidance document “Quality Attribute Considerations for Chewable Tablets” which describes the quality attributes to be considered when developing chewable tablets. It includes recommendations on selection of acceptance criteria for measuring palatability (having a taste acceptable to the patient or has adequate masking). These data are now recommended as part of ANDA submissions. Palatability is a known positive contributing factor to drug adherence and persistence. We summarize here palatability data for a new amphetamine extended-release tablet (Dyanavel XR® Extended Release Tablet; AMPH ER TAB).
This was a 2-arm preplanned secondary analysis from a comparative bioavailability study: single-dose AMPH ER TAB 20 mg chewed under fasting (Treatment A) and fed (Treatment B) conditions. Subjects rated the palatability of AMPH ER TAB (Treatments A+B) through a 5-question palatability questionnaire. The questions included in the palatability questionnaire were as follows:
1. Oral sensation/mouth feel of the drug product
2. Taste of the drug product
3. How strong is the taste?
4. Aftertaste of the product
5. How strong is the aftertaste?
Subjects completed the questionnaire within 10 minutes from the time of drug administration, which was evaluated and scored according to the rubric below:
Q1, Q2, Q4: palatability- Very unpleasant (score of 1), Unpleasant (2), No sensation or mouthfeel (3), Pleasant (4), and Very pleasant (5)
Q3, Q5 (Taste/aftertaste strength): Very strong (score of 1), Strong (2), Moderate (3), Mild (4), No aftertaste (5).
Scores of 1-2 for both categories were Negative; score of 3 was Neutral, and 4-5 were Positive.
35 subjects comprised the palatability dataset (completed one question on the questionnaire). In the palatability analysis, for treatments A and B, most of the subjects rated the oral sensation/mouth feel of AMPH ER TAB (Question 1) and the taste of AMPH ER TAB (Question 2) as positive (pleasant to very pleasant) (70.1% and 83.6%, respectively).
When evaluating taste strength (Question 3): 43.3% rated the strength as positive (mild/no taste) and 43.3% of subjects rated the strength as neutral (moderate taste). Also, 82.1% rated the aftertaste of AMPH ER TAB (Question 4) as positive (pleasant/very pleasant) and 52.2% rated the strength of the aftertaste as positive (mild/no taste).
Most subjects rated the oral sensation and taste as pleasant or very pleasant, whether chewed under fasted conditions or after a meal. With respect to the taste strength, most subjects rated it as moderate (chewed under fasted conditions) or mild/no taste (chewed after a meal). Aftertaste was rated as pleasant or very pleasant in most subjects, with the strength as moderate (chewed under fasted conditions) or mild/no aftertaste (chewed after a meal). AMPH ER Tablets provided an overall pleasant taste and mouthfeel experience for patients.
Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.
To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.
A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.
The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.
The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5’-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r –0·33, Plinear < 0·0001), serum amyloid A (SAA) (r –0·23, Plinear = 0·003), IL-6 (r –0·39, Plinear < 0·0001), IL-8 (r –0·20, Plinear = 0·02) and TNFα (r –0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r –0·14), SAA (r –0·14) and TNFα (r –0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.
Evaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.
Healthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.
Thirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.
Single doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.
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.
This chapter, reviews the basics for children undergoing abdominal mass resections. Combined with the chapter on neuroblastoma, the authors discuss the incidence, diagnosis and perioperative considerations for patients undergoing resection of large abdominal tumors. The anesthetic evaluation and planning for these patients is presented with the relative tumor specific management principles.
This chapter, reviews the basics of monitoring in children. The author provides a discussion on the utility of a host of invasive and non-invasive monitoring techniques from non-invasive blood pressure measurements to placement of umbilical lines. Most importantly, the chapter highlight the limitations of these monitoring devices in small children.
This chapter, reviews the basics for children undergoing abdominal mass resections. Combined with the chapter on nephroblastoma, the authors discuss the incidence, diagnosis and perioperative considerations for patients undergoing resection of large abdominal tumors. The anesthetic evaluation and planning for these patients is presented with the relative tumor specific management principles.
Structural characterization and X-ray reference powder pattern determination have been conducted for the Co- and Zn-containing tridymite derivatives Ba(Co1−xZnx)SiO4 (x = 0.2, 0.4, 0.6, 0.8). The bright blue series of Ba(Co1−xZnx)SiO4 crystallized in the hexagonal P63 space group (No. 173), with Z = 6. While the lattice parameter “a” decreases from 9.126 (2) Å to 9.10374(6) Å from x = 0.2 to 0.8, the lattice parameter “c” increases from 8.69477(12) Å to 8.72200(10) Å, respectively. Apparently, despite the similarity of ionic sizes of Zn2+ and Co2+, these opposing trends are due to the framework tetrahedral tilting of (ZnCo)O4. The lattice volume, V, remains comparable between 626.27 Å3 and 626.017 (7) Å3 from x = 0 to x = 0.8. UV-visible absorption spectrum measurements indicate the band gap of these two materials to be ≈3.3 and ≈3.5 eV, respectively, therefore potential UV photocatalytic materials. Reference powder X-ray diffraction patterns of these compounds have been submitted to be included in the Powder Diffraction File (PDF).