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Advanced imaging techniques are enhancing research capacity focussed on the developmental origins of adult health and disease (DOHaD) hypothesis, and consequently increasing awareness of future health risks across various subareas of DOHaD research themes. Understanding how these advanced imaging techniques in animal models and human population studies can be both additively and synergistically used alongside traditional techniques in DOHaD-focussed laboratories is therefore of great interest. Global experts in advanced imaging techniques congregated at the advanced imaging workshop at the 2019 DOHaD World Congress in Melbourne, Australia. This review summarizes the presentations of new imaging modalities and novel applications to DOHaD research and discussions had by DOHaD researchers that are currently utilizing advanced imaging techniques including MRI, hyperpolarized MRI, ultrasound, and synchrotron-based techniques to aid their DOHaD research focus.
An electrostatic and air driven (EStAD) electrospinning device was used to achieve deposition of polymer fiber mats that carry electrical charge. The EStAD device does not require the polymer stream to contact a deposition electrode, thereby allowing enhanced control and processing versatility over production of conductive polymer materials. Direct current (DC) conductivity in the fiber mats was enabled through the use of a composite multi-walled carbon nanotube-polyethylene oxide (MWCNT-PEO) blend for electrospinning (ES). The electrospun fiber mats contained three different concentrations of MWCNTs. Conductivity and resistance were measured for each concentration as an electrospun fiber mat and compared to that of a drop-cast thin film. Results showed that at 7.51 wt% MWCNTs, conductivity in the electrospun fiber mats began to approach that of the drop-cast thin films at 1.76E-01 S/cm. At the lowest weight percent tested (3.37 wt%), conductivity was still measurable at approximately 8.48E-05 S/cm and was comparable to results reported previously using traditional ES methods.
Rey’s Auditory Verbal Learning Test (AVLT) is a widely used word list memory test. We update normative data to include adjustment for verbal memory performance differences between men and women and illustrate the effect of this sex adjustment and the importance of excluding participants with mild cognitive impairment (MCI) from normative samples.
This study advances the Mayo’s Older Americans Normative Studies (MOANS) by using a new population-based sample through the Mayo Clinic Study of Aging, which randomly samples residents of Olmsted County, Minnesota, from age- and sex-stratified groups. Regression-based normative T-score formulas were derived from 4428 cognitively unimpaired adults aged 30–91 years. Fully adjusted T-scores correct for age, sex, and education. We also derived T-scores that correct for (1) age or (2) age and sex. Test-retest reliability data are provided.
From raw score analyses, sex explained a significant amount of variance in performance above and beyond age (8–10%). Applying original age-adjusted MOANS norms to the current sample resulted in significantly fewer-than-expected participants with low delayed recall performance, particularly in women. After application of new T-scores adjusted only for age, even in normative data derived from this sample, these age-adjusted T-scores showed scores <40 T occurred more frequently among men and less frequently among women relative to T-scores that also adjusted for sex.
Our findings highlight the importance of using normative data that adjust for sex with measures of verbal memory and provide new normative data that allow for this adjustment for the AVLT.
This paper proposes a new framework for thinking about hope, with certain unexpected consequences. Specifically, I argue that a shift in focus from locutions like “x hopes that” and “x is hoping that” to “x is hopeful that” and “x has hope that” can improve our understanding of hope. This approach, which emphasizes hopefulness as the central concept, turns out to be more revealing and fruitful in tackling some of the issues that philosophers have raised about hope, such as the question of how hope can be distinguished from despair or how people can have differing strengths in hope. It also allows us to see that many current accounts of hope, far from being rivals, are actually compatible with one another.
The Fontan Outcomes Network was created to improve outcomes for children and adults with single ventricle CHD living with Fontan circulation. The network mission is to optimise longevity and quality of life by improving physical health, neurodevelopmental outcomes, resilience, and emotional health for these individuals and their families. This manuscript describes the systematic design of this new learning health network, including the initial steps in development of a national, lifespan registry, and pilot testing of data collection forms at 10 congenital heart centres.
Two types of mentalization-based treatment (MBT), day hospital MBT (MBT-DH) and intensive outpatient MBT (MBT-IOP), have been shown to be effective in treating patients with borderline personality disorder (BPD). This study evaluated trajectories of change in a multi-site trial of MBT-DH and MBT-IOP at 36 months after the start of treatment.
All 114 patients (MBT-DH n = 70, MBT-IOP n = 44) from the original multicentre trial were assessed at 24, 30 and 36 months after the start of treatment. The primary outcome was symptom severity measured with the Brief Symptom Inventory. Secondary outcome measures included borderline symptomatology, personality and interpersonal functioning, quality of life and self-harm. Data were analysed using multilevel modelling and the intention-to-treat principle.
Patients in both MBT-DH and MBT-IOP maintained the substantial improvements made during the intensive treatment phase and showed further gains during follow-up. Across both conditions, 83% of patients improved in terms of symptom severity, and 97% improved on borderline symptomatology. No significant differences were found between MBT-DH and MBT-IOP at 36 months after the start of treatment. However, trajectories of change were different. Whereas patients in MBT-DH showed greater improvement during the intensive treatment phase, patients in MBT-IOP showed greater continuing improvement during follow-up.
Patients in both conditions showed similar large improvements over the course of 36 months, despite large differences in treatment intensity. MBT-DH and MBT-IOP were associated with different trajectories of change. Cost-effectiveness considerations and predictors of differential treatment outcome may further inform optimal treatment selection.
Less is known about the relationship between conduct disorder (CD), callous–unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9–18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- and parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD. However, only positive parenting differed between the CD/HCU and CD/LCU groups. In classification analyses, performance was best when distinguishing CD/HCU from TD groups and poorest when distinguishing CD/HCU from CD/LCU groups. Positive and negative parenting were both relevant when distinguishing CD/HCU from TD, negative parenting was most relevant when distinguishing between CD/LCU and TD, and positive parenting was most relevant when distinguishing CD/HCU from CD/LCU groups. These findings suggest that while positive parenting distinguishes between CD/HCU and CD/LCU, negative parenting is associated with both CD subtypes. These results highlight the importance of considering multiple parenting behaviors in CD with varying levels of CU traits in late childhood/adolescence.
Impairments in social cognition contribute significantly to disability in schizophrenia patients (SzP). Perception of facial expressions is critical for social cognition. Intact perception requires an individual to visually scan a complex dynamic social scene for transiently moving facial expressions that may be relevant for understanding the scene. The relationship of visual scanning for these facial expressions and social cognition remains unknown.
In 39 SzP and 27 healthy controls (HC), we used eye-tracking to examine the relationship between performance on The Awareness of Social Inference Test (TASIT), which tests social cognition using naturalistic video clips of social situations, and visual scanning, measuring each individual's relative to the mean of HC. We then examined the relationship of visual scanning to the specific visual features (motion, contrast, luminance, faces) within the video clips.
TASIT performance was significantly impaired in SzP for trials involving sarcasm (p < 10−5). Visual scanning was significantly more variable in SzP than HC (p < 10−6), and predicted TASIT performance in HC (p = 0.02) but not SzP (p = 0.91), differing significantly between groups (p = 0.04). During the visual scanning, SzP were less likely to be viewing faces (p = 0.0001) and less likely to saccade to facial motion in peripheral vision (p = 0.008).
SzP show highly significant deficits in the use of visual scanning of naturalistic social scenes to inform social cognition. Alterations in visual scanning patterns may originate from impaired processing of facial motion within peripheral vision. Overall, these results highlight the utility of naturalistic stimuli in the study of social cognition deficits in schizophrenia.
OBJECTIVES/GOALS: Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of death in epilepsy patients. This study aims to determine whether cardiac mechanisms contribute to SUDEP in epilepsy patients with variants in DEPDC5, a gene encoding a member of the mTOR GATOR complex, to identify SUDEP biomarkers. METHODS/STUDY POPULATION: SUDEP has been reported in 10% of epilepsy patients with DEPDC5 loss-of-function variants. We used human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to measure changes in cellular excitability that are known to be substrates for cardiac arrhythmias. CRISPR-derived isogenic DEPDC5 iPSC-CMs and DEPDC5 patient-derived iPSC-CMs were used in this study. Whole-cell patch-clamp was used to measure voltage-gated sodium current (INa) and calcium current (I>Ca) in single iPSC-CMs in voltage-clamp mode; and to measure action potentials (APs) in 3-dimentional iPSC-CM-derived micro-tissues in current-clamp mode. RESULTS/ANTICIPATED RESULTS: CRISPR generated heterozygous deletion of 1 base-pair in the first coding exon of DEPDC5 gene, resulting in a premature stop codon, simulated the variants identified in DEPDC5 epilepsy patients. In CRISPR generated heterozygousDEPDC5 iPSC-CMs, whole-cell voltage-clamp recordings revealed that INa was increased and ICa was reduced compared with isogenic control iPSC-CMs. Whole-cell current-clamp recordings revealed that AP duration at 80% and 90% of repolarization, APD80 and APD90, respectively, were prolonged compared to isogenic control iPSC-CMs. Similar measurements will be performed for iPSC-CMs derived from DEPDC5 patients. DISCUSSION/SIGNIFICANCE OF IMPACT: This study shows that epilepsy patients with non-ion channel gene variants in DEPDC5 have altered CM excitability, which may serve as a substrate for cardiac arrhythmias in DEPDC5 patients. Importantly, this work may allow us to identify biomarkers for SUDEP risk in these patients in the future. CONFLICT OF INTEREST DESCRIPTION: L.L.I. is the recipient of a collaborative research grant from Stoke Therapeutics.
Reviews of the relative efficacy of psychotherapy and combined therapy (psychotherapy with pharmacotherapy) for depression have yielded contradicting conclusions. This may be explained by the clinical heterogeneity of the studies reviewed.
To conduct a meta-analysis with an acceptable level of homogeneity in order to investigate the relative efficacy of psychotherapy and combined therapy in the acute treatment of depression.
A systematic search was performed for RCTs published between 1980 and 2005 comparing psychotherapy and combined therapy in adult psychiatric outpatients with non-psychotic unipolar major depressive disorder. The studies were classified according to the chronicity and severity of the depression. Data were pooled by means of meta-analysis and statistical tests were conducted to measure heterogeneity.
The meta-analysis included seven studies looking at a total of 903 patients. None of the heterogeneity tests established significance. This indicates a lack of evidence for the heterogeneity of the results. The dropout rates did not differ significantly between the two treatment modalities (25% in combined therapy and 24% in psychotherapy, p = 0.77). At treatment termination, the intention-to-treat remission rate for combined therapy (46%) was better than for psychotherapy (34%) (p = 0.0007); Relative Risk 1.32 (95% CI: 1.12–1.56), Odds Ratio 1.59 (95% CI: 1.22–2.09). In moderate depression, the difference between the remission rate for combined therapy and psychotherapy was statistically significant (47% compared to 34% respectively, p = 0.001). This was not the case in mild major depression (42% compared to 37% respectively, p = 0.29). The difference was also statistically significant in chronic major depression (48% compared to 32%, p < 0.001), but not in non-chronic major depression (43% compared to 37%, p = 0.22). On a more specific level, no differences were found in the remission rates for the treatment modalities in mild or moderate non-chronic depression. Combined therapy led to significantly better results than psychotherapy in moderate chronic depression only (48% compared to 32%, p < 0.001).
In the acute treatment of adult psychiatric outpatients with major depressive disorder, patient compliance with combined therapy matches compliance with psychotherapy alone. Combined therapy is more efficacious than psychotherapy alone. However, these results depend on severity and chronicity. Combined therapy outperformed psychotherapy in moderate chronic depression only. No differences were found in mild and moderate non-chronic depression. No data were found for mild chronic depression and for severe depression.
The elimination of unwanted catch in mixed species fisheries is technically challenging given the complexity of fish behaviour within nets. Most approaches to date have employed technologies that modify the nets themselves or use physical sorting grids within the gear. There is currently increasing interest in the use of artificial light to either deter fish from entering the net, or to enhance their escapement from within the net. Here, we evaluated the differences in catch retained in a standard otter trawl, relative to the same gear fitted with a square mesh panel, or a square mesh panel fitted with LEDs. We found that the selectivity of the gear differed depending on water depth. When using a square mesh panel in shallow depths of 29–40 m the unwanted bycatch of whiting and haddock was reduced by 86% and 58% respectively. In deep, darker water (45–95 m), no change in catch was observed in the square-mesh panel treatment, however when LEDs were added to the square-mesh panel, haddock and flatfish catches were reduced by 47% and 25% respectively. These findings demonstrate the potential to improve the performance of bycatch reduction devices through the addition of light devices to enhance selectivity. The results also highlight species-specific and site-specific differences in the performance of bycatch reduction devices, and hence a more adaptive approach to reduce bycatch is probably required to maximize performance.
Lifespan outcomes of simultaneous versus sequential myelomeningocele repair and shunt placement or effects of repeated shunt revisions on specific domains of IQ or fine motor dexterity are largely unknown. The current study addressed these gaps in a large cohort of children and adults with spina bifida myelomeningocele (SBM).
Participants between 7 and 44 years of age with SBM and shunted hydrocephalus were recruited from international clinics at two time points. Each participant completed a standardized neuropsychological evaluation that included estimates of IQ and fine motor dexterity. Simultaneous versus sequential surgical repair and number of shunt revisions were examined in relation to long-term IQ and fine motor scores.
Simultaneous myelomeningocele repair and shunting were associated with more frequent shunt revisions, as well as to lower Full Scale and verbal IQ scores, controlling for number of shunt revisions. More shunt revisions across study time points were associated with higher nonverbal IQ (NVIQ) scores. No effects were observed on fine motor dexterity.
Findings indicate generally greater influence of surgery type over shunt revision history on outcomes in well-managed hydrocephalus. Findings supported apparent, domain-specific benefits of sequential compared to simultaneous surgery across the lifespan in SBM. Higher NVIQ scores with greater number of additional shunt revisions across surgery type supported positive outcomes with effective surgical management for hydrocephalus.
Social outings can trigger influenza transmission, especially in children and elderly. In contrast, school closures are associated with reduced influenza incidence in school-aged children. While influenza surveillance modelling studies typically account for holidays and mass gatherings, age-specific effects of school breaks, sporting events and commonly celebrated observances are not fully explored. We examined the impact of school holidays, social events and religious observances for six age groups (all ages, ⩽4, 5–24, 25–44, 45–64, ⩾65 years) on four influenza outcomes (tests, positives, influenza A and influenza B) as reported by the City of Milwaukee Health Department Laboratory, Milwaukee, Wisconsin from 2004 to 2009. We characterised holiday effects by analysing average weekly counts in negative binomial regression models controlling for weather and seasonal incidence fluctuations. We estimated age-specific annual peak timing and compared influenza outcomes before, during and after school breaks. During the 118 university holiday weeks, average weekly tests were lower than in 140 school term weeks (5.93 vs. 11.99 cases/week, P < 0.005). The dampening of tests during Winter Break was evident in all ages and in those 5–24 years (RR = 0.31; 95% CI 0.22–0.41 vs. RR = 0.14; 95% CI 0.09–0.22, respectively). A significant increase in tests was observed during Spring Break in 45–64 years old adults (RR = 2.12; 95% CI 1.14–3.96). Milwaukee Public Schools holiday breaks showed similar amplification and dampening effects. Overall, calendar effects depend on the proximity and alignment of an individual holiday to age-specific and influenza outcome-specific peak timing. Better quantification of individual holiday effects, tailored to specific age groups, should improve influenza prevention measures.
Neighbourhood greenness or vegetative presence has been associated with indicators of health and well-being, but its relationship to depression in older adults has been less studied. Understanding the role of environmental factors in depression may inform and complement traditional depression interventions, including both prevention and treatment.
This study examines the relationship between neighbourhood greenness and depression diagnoses among older adults in Miami-Dade County, Florida, USA.
Analyses examined 249 405 beneficiaries enrolled in Medicare, a USA federal health insurance programme for older adults. Participants were 65 years and older, living in the same Miami location across 2 years (2010–2011). Multilevel analyses assessed the relationship between neighbourhood greenness, assessed by average block-level normalised difference vegetative index via satellite imagery, and depression diagnosis using USA Medicare claims data. Covariates were individual age, gender, race/ethnicity, number of comorbid health conditions and neighbourhood median household income.
Over 9% of beneficiaries had a depression diagnosis. Higher levels of greenness were associated with lower odds of depression, even after adjusting for demographics and health comorbidities. When compared with individuals residing in the lowest tertile of greenness, individuals from the middle tertile (medium greenness) had 8% lower odds of depression (odds ratio 0.92; 95% CI 0.88, 0.96; P = 0.0004) and those from the high tertile (high greenness) had 16% lower odds of depression (odds ratio 0.84; 95% CI 0.79, 0.88; P < 0.0001).
Higher levels of greenness may reduce depression odds among older adults. Increasing greenery – even to moderate levels – may enhance individual-level approaches to promoting wellness.
Objectives: Fluency is a major problem for individuals with neurodevelopmental disorders, including fluency deficits for academic skills. The aim of this study was to determine neurocognitive predictors of academic fluency within and across domains of reading, writing, and math, in children and adults, with and without spina bifida. In addition to group differences, we expected some neurocognitive predictors (reaction time, inattention) to have similar effects for each academic fluency outcome, and others (dexterity, vocabulary, nonverbal reasoning) to have differential effects across outcomes. Methods: Neurocognitive predictors were reaction time, inattention, dexterity, vocabulary, and nonverbal reasoning; other factors included group (individuals with spina bifida, n=180; and without, n=81), age, and demographic and untimed academic content skill covariates. Univariate and multivariate regressions evaluated hypotheses. Results: Univariate regressions were significant and robust (R2=.78, .70, .73, for reading, writing, and math fluency, respectively), with consistent effects of covariates, age, reaction time, and vocabulary; group and group moderation showed small effect sizes (<2%). Multivariate contrasts showed differential prediction across academic fluency outcomes for reaction time and vocabulary. Conclusions: The novelty of the present work is determining neurocognitive predictors for an important outcome (academic fluency), within and across fluency domains, across population (spina bifida versus typical), over a large developmental span, in the context of well-known covariates. Results offer insight into similarities and differences regarding prediction of different domains of academic fluency, with implications for addressing academic weakness in spina bifida, and for evaluating similar questions in other neurodevelopmental disorders. (JINS, 2019, 25, 249–265)