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Within the Biostatistics, Epidemiology, and Research Design (BERD) component of the Northwestern University Clinical and Translational Sciences Institute, we created a mentoring program to complement training provided by the associated Multidisciplinary Career Development Program (KL2). Called Research design Analysis Methods Program (RAMP) Mentors, the program provides each KL2 scholar with individualized, hands-on mentoring in biostatistics, epidemiology, informatics, and related fields, with the goal of building multidisciplinary research teams. From 2015 to 2019, RAMP Mentors paired 8 KL2 scholars with 16 individually selected mentors. Mentors had funded/protected time to meet at least monthly with their scholar to provide advice and instruction on methods for ongoing research, including incorporating novel techniques. RAMP Mentors has been evaluated through focus groups and surveys. KL2 scholars reported high satisfaction with RAMP Mentors and confidence in their ability to establish and maintain methodologic collaborations. Compared with other Northwestern University K awardees, KL2 scholars reported higher confidence in obtaining research funding, including subsequent K or R awards, and selecting appropriate, up-to-date research methods. RAMP Mentors is a promising partnership between a BERD group and KL2 program, promoting methodologic education and building multidisciplinary research teams for junior investigators pursuing clinical and translational research.
To characterize the spectrum of BRCA1 and BRCA2 pathogenic germline variants in women from south-west Poland and west Ukraine affected with breast or ovarian cancer. Testing in women at high risk of breast and ovarian cancer in these regions is currently mainly limited to founder mutations.
Unrelated women affected with breast and/or ovarian cancer from Poland (n = 337) and Ukraine (n = 123) were screened by targeted sequencing. Excluded from targeted sequencing were 34 Polish women who had previously been identified as carrying a founder mutation in BRCA1. No prior testing had been conducted among the Ukrainian women. Thus, this study screened BRCA1 and BRCA2 in the germline DNA of 426 women in total.
We identified 31 and 18 women as carriers of pathogenic/likely pathogenic (P/LP) genetic variants in BRCA1 and BRCA2, respectively. We observed five BRCA1 and eight BRCA2 P/LP variants (13/337, 3.9%) in the Polish women. Combined with the 34/337 (10.1%) founder variants identified prior to this study, the overall P/LP variant frequency in the Polish women was thus 14% (47/337). Among the Ukrainian women, 16/123 (13%) women were identified as carrying a founder mutation and 20/123 (16.3%) were found to carry non-founder P/LP variants (10 in BRCA1 and 10 in BRCA2).
These results indicate that genetic testing in women at high risk of breast and ovarian cancer in Poland and Ukraine should not be limited to founder mutations. Extended testing will enhance risk stratification and management for these women and their families.
Irritability and anxiety frequently co-occur in pediatric populations. Studies separately looking at the neural correlates of these symptoms have identified engagement of similar neural systems – particularly those implicated in emotional processing. Both irritability and anxiety can be considered negative valence emotional states that might relate to emotion dysregulation. However, previous work has not examined the neural responding during the performance of an emotion regulation task as a function of interaction between irritability and anxiety simultaneously.
This fMRI study involved 155 participants (90 with significant psychopathologies and 92 male) who performed the Affective Stroop Task, designed to engage emotion regulation as a function of task demands. The Affective Reactivity Index (ARI) was used to index irritability and the Screen for Child Anxiety Related Emotional Disorders (SCARED) was used to index anxiety.
Levels of irritability, but not anxiety, was positively correlated with responses to visual images within the right rostro-medial prefrontal cortex and left anterior cingulate cortex during view trials. The second region of ventral anterior cingulate cortex showed a condition-by-emotion-by-ARI score-by-SCARED score interaction. Specifically, anxiety level was significantly correlated with a decreased differential BOLD response to negative relative to neutral view trials but only in the presence of relatively high irritability.
Atypical maintenance of emotional stimuli within the rostro-medial prefrontal cortex may exacerbate the difficulties faced by adolescents with irritability. Moreover, increased anxiety combined with significant irritability may disrupt an automatic emotional conflict-based form of emotion regulation that is particularly associated with the ventral anterior cingulate cortex.
Acute cannabis administration can produce transient psychotic-like effects in healthy individuals. However, the mechanisms through which this occurs and which factors predict vulnerability remain unclear. We investigate whether cannabis inhalation leads to psychotic-like symptoms and speech illusion; and whether cannabidiol (CBD) blunts such effects (study 1) and adolescence heightens such effects (study 2).
Two double-blind placebo-controlled studies, assessing speech illusion in a white noise task, and psychotic-like symptoms on the Psychotomimetic States Inventory (PSI). Study 1 compared effects of Cann-CBD (cannabis containing Δ-9-tetrahydrocannabinol (THC) and negligible levels of CBD) with Cann+CBD (cannabis containing THC and CBD) in 17 adults. Study 2 compared effects of Cann-CBD in 20 adolescents and 20 adults. All participants were healthy individuals who currently used cannabis.
In study 1, relative to placebo, both Cann-CBD and Cann+CBD increased PSI scores but not speech illusion. No differences between Cann-CBD and Cann+CBD emerged. In study 2, relative to placebo, Cann-CBD increased PSI scores and incidence of speech illusion, with the odds of experiencing speech illusion 3.1 (95% CIs 1.3–7.2) times higher after Cann-CBD. No age group differences were found for speech illusion, but adults showed heightened effects on the PSI.
Inhalation of cannabis reliably increases psychotic-like symptoms in healthy cannabis users and may increase the incidence of speech illusion. CBD did not influence psychotic-like effects of cannabis. Adolescents may be less vulnerable to acute psychotic-like effects of cannabis than adults.
Data from an ongoing family interview study suggest that schizoaffective probands - including even those with a very brief history of a major depressive or manic syndrome - display a high prevalence of major mood disorders in their first-degree relatives. In this respect, schizoaffective probands proved significantly different from ‘pure’ schizophrenic probands, but not significantly different from bipolar probands.
The aim of this study was to assess the effects of anxiety on attentional performance with neutral stimuli. It was set up as follows: a fourfold comparison was made of trait anxiety and state anxiety. Sixty-two undergraduate students were included in the study, and four groups of subjects were set up by a median split of the scores obtained on the Spielberger Trait and State Anxiety Inventory (STAI): high trait-high state (N = 18); high trait-low state (N = 11); low trait-low state (N = 23); low trait-high state (N = 10). A computerized battery of neuropsychological tests, the ACE battery, was administered to provide a multidimensional assessment of attention. The ACE battery comprises five tests which assess the following aspects of attention: ability to monitor a routine task; temporal preparation; visual detection; memory span; visual spatial attention and memory. High state anxious subjects displayed impairment in executive functions, manifested by a significantly higher level of motor preparation in a simple reaction time (RT) task and a speed accuracy trade-off in a divided attention task; high trait anxious subjects performed significantly better on the visual detection task. No trait × state interaction was found. It was concluded that high state anxiety is associated with psychomotor alertness and high trait anxiety with perceptual alertness. These two dimensions of psychometric anxiety seem to have effects on attention that are independent of one another and which should be analysed separately in the future.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
Selective laser sintering methods are workhorses for additively manufacturing polymer-based components. The ease of rapid prototyping also means it is easy to produce illicit components. It is necessary to have a data-calibrated in-situ physical model of the build process in order to predict expected and defective microstructure characteristics that inform component provenance. Toward this end, sintering models are calibrated and characteristics such as component defects are explored. This is accomplished by assimilating multiple data streams, imaging analysis, and computational model predictions in an adaptive Bayesian parameter estimation algorithm. From these data sources, along with a phase-field model, bulk porosity distributions are inferred. Model parameters are constrained to physically-relevant search directions by sensitivity analysis, and then matched to predictions using adaptive sampling. Using this feedback loop, data-constrained estimates of sintering model parameters along with uncertainty bounds are obtained.
Research in developmental psychology suggests that children are poor tool innovators. However, such research often overlooks the ways in which children's social and physical environments may lead to cross-cultural variation in their opportunities and proclivity to innovate. In this paper, we examine contemporary hunter–gatherer child and adolescent contributions to tool innovation. We posit that the cultural and subsistence context of many hunter–gatherer societies fosters behavioural flexibility, including innovative capabilities. Using the ethnographic and developmental literature, we suggest that socialisation practices emphasised in hunter–gatherer societies, including learning through autonomous exploration, adult and peer teaching, play and innovation seeking may bolster children's ability to innovate. We also discuss whether similar socialisation practices can be interpreted from the archaeological record. We end by pointing to areas of future study for understanding the role of children and adolescents in the development of tool innovations across cultures in the past and present.
What does the rise and election of Donald J. Trump as president mean for the future of conservatism? Republican elites continue to argue about whether Trump is changing the definition of conservatism for better or worse, although many Republicans seem content to let him shape the issues, direction, and brand of the traditional party of conservatism. We examine the ideological characteristics of different groups of Republican voters across three types of ideology: symbolic, operational, and conceptual. We find distinct differences between Republicans who consistently supported Trump and other groups that either supported him in the general election only and those who never supported him. The Never Trump camp stands out as a group that is less symbolically and operationally conservative but also better able to articulate what it means to be a conservative than do Trump’s core supporters, who look very much the opposite. These results suggest a contemporary Republican Party that is far from unified in what it means to be a conservative.
New radiocarbon (14C) dates suggest a simultaneous appearance of two technologically and geographically distinct axe production practices in Neolithic Britain; igneous open-air quarries in Great Langdale, Cumbria, and from flint mines in southern England at ~4000–3700 cal BC. In light of the recent evidence that farming was introduced at this time by large-scale immigration from northwest Europe, and that expansion within Britain was extremely rapid, we argue that this synchronicity supports this speed of colonization and reflects a knowledge of complex extraction processes and associated exchange networks already possessed by the immigrant groups; long-range connections developed as colonization rapidly expanded. Although we can model the start of these new extraction activities, it remains difficult to estimate how long significant production activity lasted at these key sites given the nature of the record from which samples could be obtained.