Age and schooling effects on early literacy and phoneme awareness

Previous research on age and schooling effects is largely restricted to studies of children who begin formal schooling from the age of 6 and the measures of phoneme awareness used have typically lacked sensitivity for beginning readers. Our study addresses these issues by testing children aged 4-6 (first two years of formal schooling in the UK) on a sensitive dynamic measure of phoneme awareness and tests of early literacy. There were significant effects of both age and schooling on dynamic and static measures of phoneme awareness, word reading, spelling and letter-name knowledge but no significant age × time interactions. This indicates that older children within this age group generally outperform their younger classmates (although they do not make faster progress), and that this advantage is developed prior to the start of school

Altered Human Neutrophil Function in Response to Acute Psychological Stress

Objective: To examine the effects of an acute laboratory psychological stress task on neutrophil function, specifically phagocytosis of Escherichia coli and stimulated superoxide production in human neutrophils. There is mounting evidence that acute stress is associated with short-term increases in a number of immune indices. \ud \ud Methods: Participants were 40 (n = 20 females) university students (mean age, 25.9 ± 4.56 years). Blood samples to determine neutrophil function by flow cytometry were taken at the end of resting baseline, during an acute stress task, and during recovery. The stress task was a 10-minute time-pressured mental arithmetic challenge with social evaluation. \ud \ud Results: There was an acute increase in phagocytic ability, $\rho$ = .047, η2p = 0.076, and a reduction of superoxide production, p = .026, η2p = 0.101, associated with the stress task relative to baseline. \ud \ud Conclusion: These findings suggest that neutrophil bactericidal function may be sensitive to mental challenge tasks that provoke acute psychological stress. Further research is needed to replicate the observed psychological stress-induced changes in neutrophil function. \ud \u

Early predictors of phonological and morphological awareness and the link with reading : evidence from children with different patterns of early deficit

This study examines the contribution of early phonological processing (PP) and language skills on later phonological awareness (PA) and morphological awareness (MA), as well as the links among PA, MA, and reading. Children 4–6 years of age with poor PP at the start of school showed weaker PA and MA 3 years later (age 7–9), regardless of their language skills. PA and phonological and morphological strategies predict reading accuracy, whereas MA predicts reading comprehension. Our findings suggest that children with poor early PP are more at risk of developing deficits in MA and PA than children with poor language. They also suggest that there is a direct link between PA and reading accuracy and between MA and reading comprehension that cannot be accounted for by strategy use at the word level

Metabolically exaggerated cardiac reactions to acute psychological stress: The effects of resting blood pressure status and possible underlying mechanisms

The study aimed to: confirm that acute stress elicits metabolically exaggerated increases in cardiac activity; test whether individuals with elevated resting blood pressure show more exaggerated cardiac reactions to stress than those who are clearly normotensive; and explore the underlying mechanisms. Cardiovascular activity and oxygen consumption were measured pre-, during, and post- mental stress, and during graded submaximal cycling exercise in 11 young men with moderately elevated resting blood pressure and 11 normotensives. Stress provoked increases in cardiac output that were much greater than would be expected from contemporary levels of oxygen consumption. Exaggerated cardiac reactions were larger in the relatively elevated blood pressure group. They also had greater reductions in total peripheral resistance, but not heart rate variability, implying that their more exaggerated cardiac reactions reflected greater β-adrenergic activation

Bereavement reduces neutrophil oxidative burst only in older adults: role of the HPA axis and immunesenescence

Background The effect of the chronic stress of bereavement on immunity is poorly understood. Previous studies have demonstrated negative effects on immunity in older adults, and those who report higher depressive symptoms. The aim of the present study was to compare the effect of bereavement on neutrophil function in healthy young and old adults, also assessing serum levels of the stress hormones, cortisol and dehydroepiandrosterone sulphate (DHEAS). 41 young (mean age 32 years) and 52 older adults (mean age 72 years), bereaved and non-bereaved, took part in the study. They completed questionnaires on socio-demographic and health behaviour characteristics, as well as psychosocial variables, and provided a blood sample for analysis of neutrophil function (phagocytosis and reactive oxygen species (ROS) production) and stress hormone analysis. Results Bereaved participants in both age groups reported more symptoms of depression and anxiety than controls and scored moderately highly on bereavement-specific questionnaires for these symptoms. Despite this, young bereaved participants showed robust neutrophil function when compared to age-matched non-bereaved controls, and comparable stress hormone levels, while reduced neutrophil ROS production and raised stress hormone levels (cortisol:DHEAS ratio) were seen in the older bereaved group compared to their age-matched controls. Conclusions Reduced neutrophil function among older bereaved participants may be the result of the inability to maintain stress hormone balance, specifically the cortisol:DHEAS ratio

New-Onset Depression Following Hip Fracture Is Associated With Increased Length of Stay in Hospital and Rehabilitation Centers

This article examines the coincident effects of new-onset depression post hip fracture on length of hospital stay, readmission rates, and incidence of infections in older adults. Participants were 101 hip fracture patients aged 60+ years; 38 developed depressive symptoms following their fracture. Infection rates, readmissions to hospital and rehabilitation units, and length of hospital stay were assessed over the 6 months post hip fracture from hospital and general practitioner notes. Patients who developed depression by Week 6 post fracture were likely to spend more time in hospital/rehabilitation wards (p = .02) and more likely to be discharged to a rehabilitation unit (p < .05). There were no group differences in readmissions or infection rates. New-onset depression coincident with hip fracture in older adults is associated with longer hospital ward stays and greater need for rehabilitation

Performance of PCA3 and TMPRSS2:ERG urinary biomarkers in prediction of biopsy outcome in the Canary Prostate Active Surveillance Study (PASS).

BackgroundFor men on active surveillance for prostate cancer, biomarkers may improve prediction of reclassification to higher grade or volume cancer. This study examined the association of urinary PCA3 and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.MethodsUrine was collected at baseline, 6, 12, and 24 months in the multi-institutional Canary Prostate Active Surveillance Study (PASS), and PCA3 and T2:ERG levels were quantitated. Reclassification was an increase in Gleason score or ratio of biopsy cores with cancer to ≥34%. The association of biomarker scores, adjusted for common clinical variables, with short- and long-term reclassification was evaluated. Discriminatory capacity of models with clinical variables alone or with biomarkers was assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA).ResultsSeven hundred and eighty-two men contributed 2069 urine specimens. After adjusting for PSA, prostate size, and ratio of biopsy cores with cancer, PCA3 but not T2:ERG was associated with short-term reclassification at the first surveillance biopsy (OR = 1.3; 95% CI 1.0-1.7, p = 0.02). The addition of PCA3 to a model with clinical variables improved area under the curve from 0.743 to 0.753 and increased net benefit minimally. After adjusting for clinical variables, neither marker nor marker kinetics was associated with time to reclassification in subsequent biopsies.ConclusionsPCA3 but not T2:ERG was associated with cancer reclassification in the first surveillance biopsy but has negligible improvement over clinical variables alone in ROC or DCA analyses. Neither marker was associated with reclassification in subsequent biopsies

Cognitive ability in early adulthood is associated with systemic inflammation in middle age: The Vietnam experience study

We examined the prospective association between cognitive ability in early adulthood and erythrocyte sedimentation rate, a marker of inflammation, in middle age. Participants were 4256 male Vietnam era US veterans. Data on cognitive ability, assessed by the Army General Technical Test, ethnicity, and place of service were extracted from enlistment files. Smoking behaviour, alcohol consumption, basic socio-demographics, and whether participants suffered from a physician diagnosed chronic disease were determined by telephone interview in middle-age in 1985. Erythrocyte sedimentation rate, cholesterol, blood pressure, height, and weight were measured at a 3-day medical examination in 1986. In linear regression models that adjusted for age and then additionally for circumstantial, socio-demographic, lifestyle, and health factors, poor cognitive ability in early adulthood was associated with greater erythrocyte sedimentation rate in middle age, β = -.09. Thus, it would appear that not only does systemic inflammation affect cognition, but also that poor cognitive ability earlier in life increases the risk of developing inflammation

Dephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastoma.

Pediatric cancers often resemble trapped developmental intermediate states that fail to engage the normal differentiation program, typified by high-risk neuroblastoma arising from the developing sympathetic nervous system. Neuroblastoma cells resemble arrested neuroblasts trapped by a stable but aberrant epigenetic program controlled by sustained expression of a core transcriptional circuit of developmental regulators in conjunction with elevated MYCN or MYC (MYC). The transcription factor ASCL1 is a key master regulator in neuroblastoma and has oncogenic and tumor-suppressive activities in several other tumor types. Using functional mutational approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells drives coordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating an enduring gene program driving mitotic exit and neuronal differentiation. IMPLICATIONS: These findings indicate that targeting phosphorylation of ASCL1 may offer a new approach to development of differentiation therapies in neuroblastoma. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/12/1759/F1.large.jpg.Work was supported by Cancer Research UK Programme Grant RG91505 (AP), Wellcome Trust Investigator Award 212253/Z/18/Z (AP), MRC Research Grant MR/L021129/1 (F.A, A.P); Neuroblastoma UK (D.M, T.P, A.P), CRUK Cambridge Centre Paediatric Programme (L.P), The Terry Fox Foundation (FA), MBRU College of Medicine Internal grant award MBRU-CM-RG2019-14 (FA), MBRU-ALMAHMEED Collaborative Research Award ALM1909 (FA) and core support from the Wellcome Trust and the MRC Cambridge Stem Cell Institute (F.A, D.M, J.D., A.P.) and Cancer Research UK Cambridge Insititute (I.C, J.C)

Depression following hip fracture is associated with increased physical frailty in older adults: the role of the cortisol: dehydroepiandrosterone sulphate ratio

Background: Hip fracture in older adults is associated with depression and frailty. This study examined the synergistic effects of depression and hip fracture on physical frailty, and the mediating role of the cortisol: dehydroepiandrosterone sulphate (DHEAS) ratio. Methods This was an observational longitudinal study of patients with a hip fracture carried out in a hospital setting and with follow up in the community. Participants were 101 patients aged 60+ years (81 female) with a fractured neck of femur. Measurements of the ability to carry out activities of daily living (ADL), cognitive function, physical frailty and assays for serum cortisol and DHEAS were performed six weeks and six months post-hip fracture. Depressed and non-depressed groups were compared by ANOVA at each time point. Results Hip fracture patients who developed depression by week six (n = 38) had significantly poorer scores on ADL and walking indices of frailty at both week six and month six, and poorer balance at week six. The association with slower walking speed was mediated by a higher cortisol:DHEAS ratio in the depressed group. Conclusion Depression following hip fracture is associated with greater physical frailty and poorer long term recovery post-injury. Our data indicate that the underlying mechanisms may include an increased cortisol:DHEAS ratio and suggest that correcting this ratio for example with DHEA supplementation could benefit this patient population