Higher dietary intake and circulating levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been related to a reduced risk for dementia, but the pathways underlying this ...association remain unclear. We examined the cross-sectional relation of red blood cell (RBC) fatty acid levels to subclinical imaging and cognitive markers of dementia risk in a middle-aged to elderly community-based cohort.
We related RBC DHA and EPA levels in dementia-free Framingham Study participants (n = 1575; 854 women, age 67 ± 9 years) to performance on cognitive tests and to volumetric brain MRI, with serial adjustments for age, sex, and education (model A, primary model), additionally for APOE ε4 and plasma homocysteine (model B), and also for physical activity and body mass index (model C), or for traditional vascular risk factors (model D).
Participants with RBC DHA levels in the lowest quartile (Q1) when compared to others (Q2-4) had lower total brain and greater white matter hyperintensity volumes (for model A: β ± SE = -0.49 ± 0.19; p = 0.009, and 0.12 ± 0.06; p = 0.049, respectively) with persistence of the association with total brain volume in multivariable analyses. Participants with lower DHA and ω-3 index (RBC DHA+EPA) levels (Q1 vs. Q2-4) also had lower scores on tests of visual memory (β ± SE = -0.47 ± 0.18; p = 0.008), executive function (β ± SE = -0.07 ± 0.03; p = 0.004), and abstract thinking (β ± SE = -0.52 ± 0.18; p = 0.004) in model A, the results remaining significant in all models.
Lower RBC DHA levels are associated with smaller brain volumes and a "vascular" pattern of cognitive impairment even in persons free of clinical dementia.
Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. ...However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the eighth decade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1376 MRI scans. Volumetric changes among cortical regions of interest (ROIs) were more strongly correlated (average r = 0.805, SD = 0.252) than were cross-sectional volumes of the same ROIs (average r = 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r = 0.431, p < 0.001) and in the domains of visuospatial ability (r = 0.415, p = 0.002), processing speed (r = 0.383, p < 0.001) and memory (r = 0.372, p < 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.
The MAGENTA pragmatic parallel groups randomized controlled trial compared graded exercise therapy (GET) with activity management (AM) in treating paediatric myalgic encephalomyelitis or chronic ...fatigue syndrome (ME/CFS). Children aged 8-17 years with mild/moderate ME/CFS and presenting to NHS specialist paediatric services were allocated at random to either individualised flexible treatment focussing on physical activity (GET, 123 participants) or on managing cognitive, school and social activity (AM, 118 participants) delivered by NHS therapists. The primary outcome was the self-reported short-form 36 physical function subscale (SF-36-PFS) after 6 months, with higher scores indicating better functioning. After 6 months, data were available for 201 (83%) participants who received a mean of 3.9 (GET) or 4.6 (AM) treatment sessions. Comparing participants with measured outcomes in their allocated groups, the mean SF-36-PFS score changed from 54.8 (standard deviation 23.7) to 55.7 (23.3) for GET and from 55.5 (23.1) to 57.7 (26.0) for AM giving an adjusted difference in means of −2.02 (95% confidence interval −7.75, 2.70). One hundred thirty-five participants completed the mean SF-36-PFS at 12 months, and whilst further improvement was observed, the difference between the study groups remained consistent with chance. The two study groups showed similar changes on most of the secondary outcome measures: Chalder Fatigue, Hospital Anxiety and Depression Scale: Depression, proportion of full-time school attended, a visual analogue pain scale, participant-rated change and accelerometer measured physical activity, whether at the 6-month or 12-month assessment. There was an isolated finding of some evidence of an improvement in anxiety in those allocated to GET, as measured by the Hospital Anxiety and Depression Scale at 6 months, with the 12-month assessment, and the Spence Children’s Anxiety scale being aligned with that finding. There was weak evidence of a greater risk of deterioration with GET (27%) than with AM (17%;
p
= 0.069). At conventional UK cost per QALY thresholds, the probability that GET is more cost-effective than AM ranged from 18 to 21%. Whilst completion of the SF-36-PFS, Chalder Fatigue Scale and EQ-5D-Y was good at the 6-month assessment point, it was less satisfactory for other measures, and for all measures at the 12-month assessment.
Conclusion
: There was no evidence that GET was more effective or cost-effective than AM in this setting, with very limited improvement in either study group evident by the 6-month or 12-month assessment points.
Trial registration
: The study protocol was registered at
www.isrctn.com
(3rd September 2015; ISRCTN 23962803) before the start of enrolment to the initial feasibility phase.
What is Known:
• Paediatric ME/CFS is disabling with negative effects on physical and cognitive function, mood and quality of life. Although CBT improves fatigue, disability and school attendance, at least 37% of children and young people with ME/CFS have not recovered 6 months after beginning treatment.
• Graded exercise therapy (delivered flexibly) and activity management are acceptable to children and adolescents with ME/CFS; however, there is no evidence on effectiveness or cost-effectiveness.
What is New:
• Graded exercise therapy delivered in an out-patient setting is neither more effective nor more cost-effective than activity management for paediatric ME/CFS.
•Physical function did not improve greatly in either group over the 12 months in this pragmatic study conducted in the UK NHS
Summary
Circulating nucleic acids have been shown to have potential as non‐invasive diagnostic markers in cancer. We therefore investigated whether microRNAs also have diagnostic utility by comparing ...levels of tumour‐associated MIRN155 (miR‐155), MIRN210 (miR‐210) and MIRN21 (miR‐21) in serum from diffuse large B‐cell lymphoma (DLBCL) patients (n = 60) with healthy controls (n = 43). Levels were higher in patient than control sera (P = 0·009, 0·02 and 0·04 respectively). Moreover, high MIRN21 expression was associated with relapse‐free survival (P = 0·05). This is the first description of circulating microRNAs and suggests that microRNAs have potential as non‐invasive diagnostic markers for DLBCL and possibly other cancers.
One of the most intensely studied scenarios of high-temperature superconductivity (HTS) postulates pairing by exchange of magnetic excitations1. Indeed, such excitations have been observed up to ...optimal doping in the cuprates2, 3, 4, 5, 6, 7. In the heavily overdoped regime, neutron scattering measurements indicate that magnetic excitations have effectively disappeared8, 9, 10, and this has been argued to cause the demise of HTS with overdoping1, 8, 10. Here we use resonant inelastic X-ray scattering, which is sensitive to complementary parts of reciprocal space, to measure the evolution of the magnetic excitations in La2-xSrxCuO4 across the entire phase diagram, from a strongly correlated insulator (x = 0) to a non-superconducting metal (x = 0.40). For x = 0, well-defined magnon excitations are observed11. These magnons broaden with doping, but they persist with a similar dispersion and comparable intensity all the way to the non-superconducting, heavily overdoped metallic phase. The destruction of HTS with overdoping is therefore caused neither by the general disappearance nor by the overall softening of magnetic excitations. Other factors, such as the redistribution of spectral weight, must be considered. PUBLICATION ABSTRACT
Changes in diurnal temperature range (DTR) over global land areas are compared from a broad range of independent data sets. All data sets agree that global‐mean DTR has decreased significantly since ...1950, with most of that decrease occurring over 1960–1980. The since‐1979 trends are not significant, with inter‐data set disagreement even over the sign of global changes. Inter‐data set spread becomes greater regionally and in particular at the grid box level. Despite this, there is general agreement that DTR decreased in North America, Europe, and Australia since 1951, with this decrease being partially reversed over Australia and Europe since the early 1980s. There is substantive disagreement between data sets prior to the middle of the twentieth century, particularly over Europe, which precludes making any meaningful conclusions about DTR changes prior to 1950, either globally or regionally. Several variants that undertake a broad range of approaches to postprocessing steps of gridding and interpolation were analyzed for two of the data sets. These choices have a substantial influence in data sparse regions or periods. The potential of further insights is therefore inextricably linked with the efficacy of data rescue and digitization for maximum and minimum temperature series prior to 1950 everywhere and in data sparse regions throughout the period of record. Over North America, station selection and homogeneity assessment is the primary determinant. Over Europe, where the basic station data are similar, the postprocessing choices are dominant. We assess that globally averaged DTR has decreased since the middle twentieth century but that this decrease has not been linear.
Key Points
It is virtually certain globally diurnal temperature range declined since 1950
Large differences/method sensitivities preclude assessment of DTR before 1950
In some regions DTR has very likely increased in the last two to three decades
The hydrogenation disproportionation desorption recombination (HDDR) process has been investigated as a possible means of producing bonded magnets from used NdFeB-type sintered magnets with ...compositions, Nd13.4Dy0.8Al0.7Nb0.3Fe78.5B6.3 and Nd12.5Dy1.8Al0.9Nb0.6Co5.0Fe72.8B6.4 (atomic%). It has been shown that by increasing the processing temperature, an increase in the equilibrium pressure for disproportionation and in the overall reaction time was observed. The magnetic properties of the lower Dy content magnet were affected significantly by the change in processing temperature with a peak in properties observed at 880°C producing magnetic powder with a remanence of 1.08 (±0.02)T, a coercivity of 840 (±17)kAm−1, and a maximum energy product of 175 (±2.5)kJm−3. Further work on magnets with a significantly higher Dy content has shown that simultaneous processing of sintered magnets with varying compositions can be achieved by increasing the hydrogen pressure, however a range of magnetic properties are produced depending on the initial compositions of the samples in the input feed.
•Reduced oxidation during the HDDR processing in this work compared to the previous paper resulted in a powder with a higher coercivity.•Increasing the hydrogen pressure for disproportionation allowed for Dy, Co rich NdFeB compositions to be processed.•Mixed compositions (which will be typical from “real scrap”) can be processed simultaneously in the same equipment.•Mixed feeds produced lower magnetic properties due to overprocessing of the low Dy content compositions.
The quality of life (QOL) of children with developmental coordination disorder (DCD) is largely unknown, but evidence suggests that multiple QOL domains are affected by the disorder. While DCD is ...primarily considered a motor disorder, multiple studies have reported psychological and social concerns in children with this condition. Our primary aim was to present the current state of the evidence regarding the physical, psychological, and social QOL domains that can be affected in children with DCD. Systematic review of articles from seven databases through November 2010 (MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, CDSR, DARE) was conducted. Search terms included developmental coordination disorder, dyspraxia, quality of life, life satisfaction, well‐being, activities of daily living, and participation. Two independent reviewers screened titles, s, and full‐text articles. Studies meeting the following criteria were selected: (1) sample comprised solely of individuals with coordination difficulties consistent with DCD; (2) outcome measures related to physical, psychological, or socials domains of QOL; and (3) articles published in English. Data were extracted by one author and verified by a second. Outcomes were categorized according to physical, psychological and social domains of QOL and study quality was rated by case definitions of DCD based on diagnostic criteria as per the Diagnostic and Statistical Manual – 4th edition. Forty‐one articles were included. Most studies reported significantly poorer results in physical, psychological and social functioning in children with DCD compared with peers. Despite the impact of DCD on multiple domains, only one study used a QOL measure as an outcome. Although DCD impacts several QOL domains, the QOL of children with this disorder remains largely unknown. The next critical step is for clinicians and researchers to use QOL measures to gather information on how DCD may affect the QOL of children with this disorder.
The National Cancer Institute—Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients ...to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors.
Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed.
Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0–9; unknown in one patient). Median HER2 CN was 17 (range 7–139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% 90% confidence interval 14.2% to 39.2%. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay.
T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.
Obesity and shorter telomeres are commonly associated with elevated risk for age-related diseases and mortality. Whether telomere length (TL) may be associated with obesity or variations in adiposity ...is not well established. Therefore, we set out to test the hypothesis that TL may be a risk factor for increased adiposity using data from a large population-based cohort study.
Levels of adiposity were assessed in six ways (obesity status, body mass index (BMI), the percentage of body fat or % body fat, leptin, visceral and subcutaneous fat mass) in 2721 elderly subjects (42% black and 58% white). Associations between TL measured in leukocytes at baseline and adiposity traits measured at baseline, and three of these traits after 7 years of follow-up were tested using regression models adjusting for important covariates. Additionally, we look at weight changes and relative changes in BMI and % body fat between baseline and follow-up.
At baseline, TL was negatively associated with % body fat (ß=-0.35±0.09, P=0.001) and subcutaneous fat (ß=-2.66±1.07, P=0.01), and positively associated with leptin after adjusting for % body fat (ß=0.32±0.14, P=0.001), but not with obesity, BMI or visceral fat. Prospective analyses showed that longer TL was associated with positive percent change between baseline and 7-year follow-up for both BMI (ß=0.48±0.20, P=0.01) and % body fat (ß=0.42±0.23, P=0.05).
Our study suggests that shorter TL may be a risk factor for increased adiposity. Coupling with previous reports on their reversed roles, the relationship between adiposity and TL may be complicated and may warrant more prospective studies.
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