To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Introduction: Measures of satisfaction are essential to understanding patient experience, and pain management. Currently, there are no validated tools to quantify children’s satisfaction. To develop such a tool, we must first understand which words children use to communicate satisfaction. Our objectives were to (A) to identify the words commonly used by children of different ages to communicate satisfaction, in general, and in the context of pain management, and (B) to determine if this vocabulary is similar to that used by their caregiver. Methods: A qualitative study of 105 children-parent pairs, aged 3-16 years, who were evaluated at a pediatric emergency department (PED) from July-November 2014 was conducted. Children were interviewed using a semi-structured format of ten open-ended questions. They were asked to describe their feelings when 1) they received something they wanted/needed, 2) their expectations were met or not met in the ED, and 3) their pain was or was not relieved. A written survey was also completed by the caregiver. Interviews were transcribed and grounded theory was employed for data coding and analysis. Results: 105 child interviews were completed (n=53 female, mean age 9.91 SD 3.71, age range 4-16). 105 caregiver surveys were completed (n=80 female). “Good”, “better,” and “happy” were most commonly used by all children (n=99) to express satisfaction with pain management (27%, 21% and 22%, respectively), with PED care (31%, 14% and 33%) and in general (13%, 5% and 49%). Children (n=99) used the words “sad”, “bad,” and “not good” to communicate dissatisfaction with pain management (21%, 7% and 11% respectively), and with PED care (21%, 13% and 12%, respectively). Only 55% of children understood the meaning of the word ‘satisfaction’. Children used words that were similar to their caregiver 14% of the time. Conclusion: The word “satisfaction” should not be used to communicate with children in the emergency department, as many lack understanding of the term. The vocabulary that children use to describe satisfaction does not largely vary with context and involves simpler words than their parents. Caregiver vocabulary should not be used as a surrogate for pediatric patients. This study will inform the development of a validated tool to measure children’s satisfaction with pain management.
The reported incidence of the metastrongylid nematode Angiostrongylus vasorum, that infects dogs and other canids, is increasing worldwide outside recognized endemic foci. This apparent expansion of the parasite's range is causing concern to veterinary clinicians as the disease caused in dogs can be life threatening and its treatment is not straightforward. The red fox is thought to be a reservoir host for dogs. To investigate the spatial distribution of infection in foxes in Ireland, the hearts and lungs of 542 foxes from all over Ireland were examined. The incidence of infection was found to be 39·9% [95% confidence interval (CI) 35·7–44·1] with positive samples occurring in each of the country's 26 counties. This report confirms that the parasite is endemic in Ireland and the overall prevalence is the second highest in Europe. This is the first survey of A. vasorum infection in Irish foxes and highlights the potential exposure of the Irish dog population to high risk of cross-infection. Additionally, Crenosoma vulpis was found in seven of the foxes, a parasite not previously reported in the Irish fox.
To cope with phosphorus (P) deficiency, plants adapt root morphology to enhance inorganic P (Pi) acquisition from soil by allocating more biomass to roots, but whether the responses can be modified across gradients of P supply is not fully understood. The present study examined changes in root-length density (RLD), root-hair density (RHD) and root-hair length (RHL) of wheat (Triticum aestivum L.) in two contrasting soils, the Rough and Barnfield soils. Wheat plants were grown for 3 weeks in thin-plate rhizotrons in two soils with additions of 0, 10, 25, 50, 100 and 200 mg P/kg soil. Contrary to published literature, as P additions increased it was observed that a concomitant increase in RHL (250 to 1054 µm in the Rough soil and 303–1075 µm in the Barnfield soil) and RHD (57 to 122/mm in the Rough soil and 56–120/mm in the Barnfield soil), while RLD generally decreased (2480–1130 cm/cm3 in the Rough soil and 1716–865 cm/cm3 in the Barnfield soil). The levels of added P that resulted in critical P concentrations in the soils enabling maximum shoot biomass production were 50 mg/kg P in the Rough soil and 100 mg/kg P in the Barnfield soil, and these additions influenced root morphological changes. Under severe P deficiency, P supply increased RHL and RHD, but RLD was decreased. Improvement in lateral root and root-hair responses in wheat at extreme P deficiency may be a worthy target for breeding more sustainable genotypes for future agroecosystems.
Depression is characterized by poor executive function, but – counterintuitively – in some studies, it has been associated with highly accurate performance on certain cognitively demanding tasks. The psychological mechanisms responsible for this paradoxical finding are unclear. To address this issue, we applied a drift diffusion model (DDM) to flanker task data from depressed and healthy adults participating in the multi-site Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression (EMBARC) study.
One hundred unmedicated, depressed adults and 40 healthy controls completed a flanker task. We investigated the effect of flanker interference on accuracy and response time, and used the DDM to examine group differences in three cognitive processes: prepotent response bias (tendency to respond to the distracting flankers), response inhibition (necessary to resist prepotency), and executive control (required for execution of correct response on incongruent trials).
Consistent with prior reports, depressed participants responded more slowly and accurately than controls on incongruent trials. The DDM indicated that although executive control was sluggish in depressed participants, this was more than offset by decreased prepotent response bias. Among the depressed participants, anhedonia was negatively correlated with a parameter indexing the speed of executive control (r = −0.28, p = 0.007).
Executive control was delayed in depression but this was counterbalanced by reduced prepotent response bias, demonstrating how participants with executive function deficits can nevertheless perform accurately in a cognitive control task. Drawing on data from neural network simulations, we speculate that these results may reflect tonically reduced striatal dopamine in depression.
Cytokines and vitamin D both have a role in modulating the immune system, and are also potentially useful biomarkers in mental illnesses such as major depressive disorder (MDD) and schizophrenia. Studying the variability of cytokines and vitamin D in a healthy population sample may add to understanding the association between these biomarkers and mental illness. To assess genetic and environmental contributions to variation in circulating levels of cytokines and vitamin D (25-hydroxy vitamin D: 25(OH)D3), we analyzed data from a healthy adolescent twin cohort (mean age 16.2 years; standard deviation 0.25). Plasma cytokine measures were available for 400 individuals (85 MZ, 115 DZ pairs), dried blood spot sample vitamin D measures were available for 378 individuals (70 MZ, 118 DZ pairs). Heritability estimates were moderate but significant for the cytokines transforming growth factor-β1 (TGF-β1), 0.57 (95% CI 0.26–0.80) and tumor necrosis factor-receptor type 1 (TNFR1), 0.50 (95% CI 0.11–0.63) respectively. Measures of 25(OH)D3 were within normal range and heritability was estimated to be high (0.86, 95% CI 0.61–0.94). Assays of other cytokines did not generate meaningful results. These potential biomarkers may be useful in mental illness, with further research warranted in larger sample sizes. They may be particularly important in adolescents with mental illness where diagnostic uncertainty poses a significant clinical challenge.
PILOT (the Pathfinder for an International Large Optical Telescope) is a proposed 2.5-m optical/infrared telescope to be located at Dome C on the Antarctic plateau. Conditions at Dome C are known to be exceptional for astronomy. The seeing (above ∼30 m height), coherence time, and isoplanatic angle are all twice as good as at typical mid-latitude sites, while the water-vapour column, and the atmosphere and telescope thermal emission are all an order of magnitude better. These conditions enable a unique scientific capability for PILOT, which is addressed in this series of papers. The current paper presents an overview of the optical and instrumentation suite for PILOT and its expected performance, a summary of the key science goals and observational approach for the facility, a discussion of the synergies between the science goals for PILOT and other telescopes, and a discussion of the future of Antarctic astronomy. Paper II and Paper III present details of the science projects divided, respectively, between the distant Universe (i.e. studies of first light, and the assembly and evolution of structure) and the nearby Universe (i.e. studies of Local Group galaxies, the Milky Way, and the Solar System).
We have used high-resolution, HST WFC3/IR, near-infrared imaging to conduct a detailed bulge-disk decomposition of the morphologies of ≃ 200 of the most massive (M* > 1011 M⊙) galaxies at 1 < z < 3 in the CANDELS-UDS field. We find that, while such massive galaxies at low redshift are generally bulge-dominated, at redshifts 1<z<2 they are predominantly mixed bulge+disk systems, and by z > 2 they are mostly disk-dominated. Interestingly, we find that while most of the quiescent galaxies are bulge-dominated, a significant fraction (25–40%) of the most quiescent galaxies, have disk-dominated morphologies. Thus, our results suggest that the physical mechanisms which quench star-formation activity are not simply connected to those responsible for the morphological transformation of massive galaxies.
During foetal development, calcium requirements are met as a consequence of maternal adaptations independent of vitamin D status. In contrast, after birth, dependency on vitamin D appears necessary for calcium metabolism and skeletal health. We used a rodent model (Sprague-Dawley rats), to determine if maternal vitamin D deficiency during pregnancy had a deleterious effect on bone structure at birth. Vitamin D deplete females were maintained under deplete conditions until birth of the pups, whereupon all dams were fed a vitamin D replete diet. Offspring were harvested at birth, and 140 days of age. Bones were analyzed using micro-computed tomography and strength tested to study differences in bone structure, density and strength and subjected to elemental analysis using plasma mass spectrometry to determine strontium, barium and calcium contents. Offspring from deplete mothers displayed altered trabecular parameters in the femur at birth and 140 days of age. In addition, at 140 days of age there was evidence of premature mineralization of the secondary ossification centre of the femoral head. Elemental analysis showed increased strontium uptake in the femur of the developmentally vitamin D-deficient offspring. Vitamin D depletion during development in the offspring may have a long-lasting effect, despite repletion of vitamin D from birth. This may have consequences for human health given the low vitamin D levels seen during pregnancy and current lifestyle of sun avoidance due to the risk of skin cancer.
The microwave heatability of various thermoplastic polymers was investigated. The concept of microwave calorimetry was proposed to quantitatively illustrate how viscoelastic behavior controlled microwave heatability. Specifically, heating rate as a function of sample temperature revealed a distinct maximum which was identified as the Tg at 2.45 GHz. The critical temperature, Tc, necessary for rapid microwave heating was identified by drawing a tangent to the heating rate curve and extrapolating to a critical value at zero heating rate. In separate experiments, low frequency (100 kHz) dielectric measurements were made which show the frequency dependence of Tg by means of Arrhenius activation energy plots. In general, the larger the activation energy, the closer the critical heating temperature, TC, was to the Tg determined by DSC. The smaller the activation energy, the further dielectric loss shifted with increased frequency so that Tc was very far from Tg determined by DSC.
Microwave processing has been utilized to process thermosetting polymeric materials. Specifically, fundamental studies relating epoxy network generation to processing conditions have been investigated in a tunable cylindrical cavity operating at a frequency of 2.45 GHz. These studies demonstrate that fully cured networks can be generated in ten minutes with the retention of good mechanical properties. Furthermore, toughened epoxy systems which utilize carefully designed amine terminated poly(arylene ether sulfone) thermoplastics as reactive oligomers have resulted in novel phase separated morphologies. In fact, it has been demonstrated that the morphology in these multiphase systems can actually be controlled by utilizing microwave processing. Bismaleimide toughened systems, devised by similar strategies, have demonstrated a 10–20 fold reduction in the time required to achieve full cure.
Polyimides are attractive candidates for advanced electronic and space applications due to their high performance thermal and mechanical properties. However, the typical intractability and insolubility of polyimides has been a disadvantage. Utilization of the soluble intermediate amic acid can, to some extent, circumvent this problem. However, drawbacks to this approach include the hydrolytic instability of the amic acid and the liberation of water during its subsequent thermal cyclization. Residual stress build-up at the imide-substrate interface may occur due to swelling and drying cycles caused by the loss of water and solvent. In addition, the liberation of volatiles from a polyimide adhesive or coating can lead to the creation of voids which may significantly detract from mechanical properties. Polymeric adhesives must flow in order to provide good wetting of adherend surfaces and consolidation of the bond components. Thus, fully imidized, melt and solution processable, high Tg aromatic polyimides are of great interest.
Novel morphologies were produced in phase segmented, toughened epoxies via microwave processing. Novel and exciting chemistries have been demonstrated through the specificity of delivery of electromagnetic radiation in tuned cavities.
Foamed polyimides have been developed in order to obtain thin film dielectric layers with very low dielectric constants for use in microelectronic devices. In these systems the pore sizes are in the nanometer range, thus, the term “nanofoam”. The polyimide foams are prepared from block copolymers consisting of thermally stable and thermally labile blocks, the latter being the dispersed phase. Foam formation is effected by thermolysis of the thermally labile block leaving pores the size and shape corresponding to the initial copolymer morphology. Nanofoams prepared from a number of polyimides as matrix materials, were investigated as well as a number of thermally labile polymers. The foams were characterized by a variety of experiments including, TEM, SAXS, WAXD, DMTA, density measurements, refractive index measurements and dielectric constant measurements. Thin film foams, with high thermal stability and dielectric constants approaching 2.0, can be prepared using the copolymer/nanofoam approach.