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OBJECTIVES/SPECIFIC AIMS: Despite the high prevalence of individuals diagnosed with sickle cell disease (SCD) in Tennessee, comprehensive care and education for patients with SCD is not as widely available as healthcare services for individuals managing other chronic illnesses. We aimed to engage SCD stakeholders in patient-centered outcomes research (PCOR) as a mechanism for advancing care and translational research for this rare disease population. METHODS/STUDY POPULATION: Through a partnership with the Sickle Cell Foundation of Tennessee, we implemented Community Health Ambassadors to systematically engage patient partners with SCD and their caregivers, aged 18–50 from rural and urban communities throughout Tennessee, in PCOR to establish a sustainable infrastructure, focused on connecting the SCD community through a service providing community-based organization to offer (1) information on how to connect with other families; and be informed about SCD community activities, or educational offerings; (2) training in basic research principals; and (3) opportunities to contribute to PCOR, including feedback on effective and practical ways for providing input on research efforts through patient centered input, comparing urban and rural area preferences. Community ambassadors utilized health fairs, clinic days at various hospitals and community centers, and social media to spread awareness of the project, in addition to boosting the recruitment process. RESULTS/ANTICIPATED RESULTS: A statewide SCD network was developed to offer social support and increase access to education, medical care, and engagement in research activities. Findings include: recruitment of 150 patients and 35 executive committee members (local physicians, community leaders, adults with SCD and parents of children with SCD). DISCUSSION/SIGNIFICANCE OF IMPACT: Most rural and urban families affected by SCD have no systematic way to engage in, or lend their expertise to, PCOR. A statewide network of patient partners, community stakeholders, researchers, and medical professionals will ultimately increase the standard of care for patients, and provide valuable insight for SCD research. The opportunity to create the underpinnings for coordinated patient-centered education for patients with SCD and their caregivers holds promise for developing a scalable PCOR process model for replication and implementation in other states and emulate this model with other rare disease populations.
Parents are a major supplier of alcohol to adolescents, yet there is limited research examining the impact of this on adolescent alcohol use. This study investigates associations between parental supply of alcohol, supply from other sources, and adolescent drinking, adjusting for child, parent, family and peer variables.
A cohort of 1927 adolescents was surveyed annually from 2010 to 2014. Measures include: consumption of whole drinks; binge drinking (>4 standard drinks on any occasion); parental supply of alcohol; supply from other sources; child, parent, family and peer covariates.
After adjustment, adolescents supplied alcohol by parents had higher odds of drinking whole beverages [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.33–2.45] than those not supplied by parents. However, parental supply was not associated with bingeing, and those supplied alcohol by parents typically consumed fewer drinks per occasion (incidence rate ratio 0.86, 95% CI 0.77–0.96) than adolescents supplied only from other sources. Adolescents obtaining alcohol from non-parental sources had increased odds of drinking whole beverages (OR 2.53, 95% CI 1.86–3.45) and bingeing (OR 3.51, 95% CI 2.53–4.87).
Parental supply of alcohol to adolescents was associated with increased risk of drinking, but not bingeing. These parentally-supplied children also consumed fewer drinks on a typical drinking occasion. Adolescents supplied alcohol from non-parental sources had greater odds of drinking and bingeing. Further follow-up is necessary to determine whether these patterns continue, and to examine alcohol-related harm trajectories. Parents should be advised that supply of alcohol may increase children's drinking.
We examine the game theoretic properties of a model of crime first introduced by Short et al. (2010 Phys. Rev. E82, 066114) as the SBD Adversarial Game. We identify the rationalizable strategies and one-shot equilibria under multiple equilibrium refinements. We further show that SBD's main result about the effectiveness of defecting-punishers (“Informants”) in driving the system to evolve to the cooperative equilibrium under an imitation dynamic generalizes to a best response dynamic, though only under certain parameter regimes. The nature of this strategy's role, however, differs significantly between the two dynamics: in the SBD imitation dynamic, Informants are sufficient but not necessary to achieve the cooperative equilibrium, while under the best response dynamic, Informants are necessary but not sufficient for convergence to cooperation. Since a policy of simply converting citizens to Informants will not guarantee success under best response dynamics, we identify alternative strategies that may help the system reach cooperation in this case, e.g., the use of moderate but not too severe punishments on criminals.
Adverse uterine environments caused by maternal stress (such as bacterial endotoxin) can alter programming of the fetal hypothalamic–pituitary–adrenal axis (HPAA) rendering offspring susceptible to various adulthood diseases. Thus, protection against this type of stress may be critical for ensuring offspring health. The present study was designed to determine if maternal supplementation with omega-3 polyunsaturated fatty acids (n-3 PUFAs) during pregnancy helps to protect against stress-induced fetal programming. Briefly, 53 ewes were fed a diet supplemented with fishmeal (FM) or soybean meal (SM) from day 100 of gestation (gd100) through lactation. On gd135, half the ewes from each dietary group were challenged with either 1.2 μg/kg Escherichia coli lipopolysaccharide (LPS) endotoxin, or saline as the control. The offspring’s cortisol response to weaning stress was assessed 50 days postpartum by measuring serum cortisol concentrations 0, 6 and 24 h post weaning. Twenty-four hours post-weaning, lambs were subjected to an adrenocorticotropic hormone (ACTH) challenge (0.5 μg/kg) and serum cortisol concentrations were measured 0, 0.25, 0.5, 1 and 2 h post injection. At 5.5 months of age, offspring were also challenged with 400 ng/kg of LPS, and serum cortisol concentrations were measured 0, 2, 4 and 6 h post challenge. Interestingly, female offspring born to FM+LPS mothers had a greater cortisol response to weaning and endotoxin challenge compared with the other treatments, while female offspring born to SM+LPS mothers had a faster cortisol response to the ACTH stressor. Additionally, males born to FM+LPS mothers had a greater cortisol response to the ACTH challenge than the other treatments. Overall, FM supplementation during gestation combined with LPS challenge alters HPAA responsiveness of the offspring into adulthood.
The Australian Imaging, Biomarkers and Lifestyle (AIBL) Flagship Study of Ageing is a prospective study of 1,112 individuals (211 with Alzheimer's disease (AD), 133 with mild cognitive impairment (MCI), and 768 healthy controls (HCs)). Here we report diagnostic and cognitive findings at the first (18-month) follow-up of the cohort. The first aim was to compute rates of transition from HC to MCI, and MCI to AD. The second aim was to characterize the cognitive profiles of individuals who transitioned to a more severe disease stage compared with those who did not.
Eighteen months after baseline, participants underwent comprehensive cognitive testing and diagnostic review, provided an 80 ml blood sample, and completed health and lifestyle questionnaires. A subgroup also underwent amyloid PET and MRI neuroimaging.
The diagnostic status of 89.9% of the cohorts was determined (972 were reassessed, 28 had died, and 112 did not return for reassessment). The 18-month cohort comprised 692 HCs, 82 MCI cases, 197 AD patients, and one Parkinson's disease dementia case. The transition rate from HC to MCI was 2.5%, and cognitive decline in HCs who transitioned to MCI was greatest in memory and naming domains compared to HCs who remained stable. The transition rate from MCI to AD was 30.5%.
There was a high retention rate after 18 months. Rates of transition from healthy aging to MCI, and MCI to AD, were consistent with established estimates. Follow-up of this cohort over longer periods will elucidate robust predictors of future cognitive decline.
In recent years, livestock producers have been supplementing animal diets with fish meal (FM) to produce value-added products for health conscious consumers. As components of FM have unique neuroendocrine–immunomodulatory properties, we hypothesize that livestock producers may be influencing the overall health of their animals by supplementing diets with FM. In this study, 40 pregnant ewes were supplemented with rumen protected (RP) soybean meal (SBM: control diet) or RP FM, commencing gestation day 100 (gd100), in order to evaluate the impact of FM supplementation on the innate and acquired immune response and neuroendocrine response of sheep during pregnancy and lactation. On gd135, half the ewes from each diet (n = 10 FM, n = 10 SBM) were challenged iv with lipopolysaccharide (LPS) to simulate a systemic bacterial infection and the febrile, respiratory and neuroendocrine responses were monitored over time; the other half (n = 10 FM, n = 10 SBM) of the ewes received a saline injection as control. On lactation day 20 (ld20), all ewes (n = 20 FM, n = 20 SBM) were sensitized with hen egg white lysozyme (HEWL) and the serum haptoglobin (Hp) response was measured over time. The cutaneous hypersensitivity response (CHR) to HEWL challenge was measured on ld30 (n = 20 FM, n = 20 SBM), and blood samples were collected over time to measure the primary and secondary immunoglobulin G (IgG) response to HEWL. There was an attenuated trend in the LPS-induced febrile response by the FM treatment when compared with the SBM treatment (P = 0.06), as was also true for the respiratory response (P = 0.07), but significant differences in neuroendocrine function (serum cortisol and plasma ACTH) were not observed between treatments. Basal Hp levels were significantly lower in the FM supplemented ewes when compared with the SBM supplemented ewes (P < 0.01), and the Hp response to HEWL sensitization differed significantly over time between treatments (P < 0.01). The CHR to HEWL was also significantly attenuated in the FM treatment compared with the SBM (P < 0.01); however, treatment differences in the primary and secondary IgG responses to HEWL were not observed. These results indicate that FM supplementation differentially affects the innate and acquired immune responses in pregnant and lactating sheep compared with a typical SBM diet of commercial flocks. The long-term implications of this immunomodulation warrant further investigation.
A better understanding of the factors regulating feed efficiency and their potential as predictors of feed efficiency in cattle is needed. Therefore, the potential of three classes of traits, namely, feeding behavior characteristics: daily time at feeder (TF; min/day), time per meal (TM; min), meal size (MS; g DM), eating rate (ER; g DM/min), number of daily meals (NM) and daily visits to the feeder (VF); infrared (IR) thermography traits (°C): eye (EY), cheek (CK), snout (SN), ribs (RB) and hind area (HA); and glucocorticoid levels: fecal cortisol metabolites (FCM; ng/g) and plasma cortisol (PC; ng/ml) as predictors of efficiency were evaluated in 91 steers (436 ± 37 kg) over 2 years (Y1 = 46; Y2 = 45). Additionally, the individual traits of each of these three classes were combined to define three single traits. Individual daily feed intake of a corn silage and high-moisture corn-based diet was measured using an automated feeding system. Body weight and thermographs were taken every 28 days over a period of 140 days. Four productive performance traits were calculated: daily dry matter intake (DMI), average daily gain (ADG), feed to gain ratio (F : G) and residual feed intake (RFI). Steers were also classified into three RFI categories (low-, medium- and high-RFI). Among the feeding behavior characteristics, MS and ER were correlated with all efficiency traits (range: 0.26 to 0.75). Low-RFI (more efficient steers) had smaller MS, lower ER and fewer VF in comparison to high-RFI steers. Less efficient steers (high-RFI) performed more VF during the nocturnal period than more efficient steers. More efficient steers had lower CK and SN temperatures than less efficient steers (28.1°C v. 29.2°C and 30.0°C v. 31.2°C), indicating greater energetic efficiency for low-RFI steers. In terms of glucocorticoids, PC was not correlated with efficiency traits. In contrast, more efficient steers had higher FCM in comparison to less efficient steers (51.1 v. 31.2 ng/g), indicating that a higher cortisol baseline is related to better feed efficiency. The overall evaluation of the three classes of traits revealed that feeding behavior, IR thermography and glucocorticoids accounted for 18%, 59% and 7% of the total variation associated with RFI, respectively. These classes of traits have usefulness in the indirect assessment of feed efficiency in cattle. Among them, IR thermography was the most promising alternative to screen cattle for this feed efficiency. These findings might have application in selection programs and in the better understanding of the biological basis associated with productive performance.
The SMC represents an exciting opportunity to observe the direct results of tidal interactions on star birth. One of the best indicators of recent star birth activity is the presence of significant numbers of High-Mass X-ray Binaries (HMXBs) — and the SMC has them in abundance! We present results from nearly 10 years of monitoring these systems plus a wealth of other ground-based optical data. Together they permit us to build a picture of a galaxy with a mass of only a few percent of the Milky Way but with a more extensive HMXB population. However, as often happens, new discoveries lead to some challenging puzzles — where are the other X-ray binaries (e.g., black hole systems) in the SMC? And why do virtually all the SMC HMXBs have Be star companions? The evidence arising from these extensive optical observations for this apparently unusual stellar evolution are discussed.
Although empirical support for the efficacy of cognitive behavioural therapy (CBT) as a treatment for major depressive disorder (MDD) is well established, its mechanism of action is uncertain. In this investigation, we examined evidence for the cognitive mediational model in a randomized control trial involving CBT, interpersonal therapy (IPT) and pharmacotherapy (PHT) in patients with MDD.
One hundred and thirty participants diagnosed with MDD were treated with CBT, IPT or PHT. Participants completed the Hamilton Depression Rating Scale, Beck Depression Inventory – II and Dysfunctional Attitudes Scale prior to and following treatment.
The cognitive mediational model, in which dysfunctional attitudes are proposed to mediate depressive symptom reduction in response to treatment, provided a good fit to the data when contrasting CBT v. IPT, with results supporting a mediational role for dysfunctional attitude change in depressive symptom reduction. The complication model, in which dysfunctional attitudes are proposed to be a consequence of depressive symptom reduction, provided a good fit to the data when contrasting CBT v. PHT, with results supporting a mediational role for depressive symptom reduction in dysfunctional attitude change.
There was no evidence for a mediational role for dysfunctional attitude change in IPT. Changes in dysfunctional attitudes accompanied both CBT and PHT; however, empirical evidence suggests that the role of attitudes in treatment outcome may differ between these two treatments.
The population of Saturn's outermost tenuous E-ring is dominated by tiny water ice particles, some of which contain organic or mineral impurities. Active cryo-volcanism on the moon Enceladus, embedded in the E-ring, has been known to be a major source of particles replenishing the ring since late 2005. Therefore, particles in the vicinity of Enceladus provide crucial information about the dynamic and chemical processes occurring far below the moon's icy surface.
We present a compositional analysis of thousands of impact ionisation mass spectra of Saturn's E-ring particles, with sizes predominantly below 1 μm, detected by the Cosmic Dust Analyser onboard the Cassini spacecraft. Our findings imply that organic compounds are a significant component of icy particles ejected by Enceladus plumes. Our in situ measurements are supported by detections of other Cassini instruments. They hint at a dynamic interaction of a hot rocky core with liquid water below the icy surface, where the organic molecules are generated. Further insights are expected from two close Enceladus flybys to be performed by Cassini in 2008. Then, for the first time, we will obtain spectra of freshly ejected particles at the traversals through the cryo-volcanic plumes.