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 email@example.com
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.
We present the current status of a scalable computing framework to address the need of the multidisciplinary effort to study chemical dynamics. Specifically, we are enabling scientists to process and store experimental data, run large-scale computationally expensive high-fidelity physical simulations, and analyze these results using state-of-the-art data analytics, machine learning, and uncertainty quantification methods using heterogeneous computing resources. We present the results of this framework on a single metadata-driven workflow to accelerate an additive manufacturing use-case.
We present the case of a 17-year-old boy with a cardiac venous malformation. This case highlights the diagnostic challenges of such tumours and demonstrates the potential efficacy of a watch-and-wait management approach.
Current techniques for measuring the dry matter intake (DMI) of grazing lactating beef cows are invasive, time consuming and expensive making them impractical for use on commercial farms. This study was undertaken to explore the potential to develop and validate a model to predict DMI of grazing lactating beef cows, which could be applied in a commercial farm setting, using non-invasive animal measurements. The calibration dataset used to develop the model was comprised of 94 measurements recorded on 106 beef or beef–dairy crossbred cows (maternal origin). The potential of body measurements, linear type scoring, grazing behaviour and thermal imaging to predict DMI in combination with known biologically plausible adjustment variables and energy sinks was investigated. Multivariable regression models were constructed for each independent variable using SAS PROC REG and contained milk yield, BW, parity, calving day and maternal origin (dairy or beef). Of the 94 variables tested, 32 showed an association with DMI (P < 0.25) upon multivariable analysis. These variables were incorporated into a backwards linear regression model using SAS PROC REG. Variables were retained in this model if P < 0.05. Five variables; width at pins, full body depth, ruminating mastications, central ligament and rump width score, were retained in the model in addition to milk yield, BW, parity, calving day and maternal origin. The inclusion of these variables in the model increased the predictability of DMI by 0.23 (R2 = 0.68) when compared to a model containing milk yield, BW, parity, calving day and maternal origin only. This model was applied to data recorded on an independent dataset; a herd of 60 lactating beef cows two years after the calibration study. The R2 for the validation was 0.59. Estimates of DMI are required for measuring feed efficiency. While acknowledging challenges in applicability, the findings suggest a model such as that developed in this study may be used as a tool to more easily and less invasively estimate DMI on large populations of commercial beef cows, and therefore measure feed efficiency.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Culturally linked family influences during adolescence are important predictors of health and well-being for Latino youth, yet few studies have examined whether these familial influences are associated with indicators of typical physiological stress processes. Following a cultural neurobiology framework, we examined the role of family in the everyday lives of Latino adolescents (N = 209; Mage = 18.10; 85.1% Mexican descent; 64.4% female) by investigating familism values and perceptions of parent support as well as daily family assistance behaviors in relation to hypothalamic–pituitary–adrenal axis diurnal patterns, indexed by salivary cortisol five times a day for 3 weekdays. Three-level growth curve analyses revealed that perceptions of parental support were associated with greater cortisol awakening responses, whereas familism values were not associated with diurnal cortisol patterns. In day-to-day analyses, assisting family during the day (compared to not assisting family) was associated with lower waking cortisol levels and flatter diurnal slopes the next day. Our findings highlight the dynamic associations and multiple time courses between cultural values and behaviors, daily experiences, and physiological stress processes for Latino adolescents. Further, we identified important cultural risk and promotive factors associated with physiological regulation in daily life and potential pathways toward health outcomes in adulthood.
Prenatal adversity shapes child neurodevelopment and risk for later mental health problems. The quality of the early care environment can buffer some of the negative effects of prenatal adversity on child development. Retrospective studies, in adult samples, highlight epigenetic modifications as sentinel markers of the quality of the early care environment; however, comparable data from pediatric cohorts are lacking. Participants were drawn from the Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) study, a longitudinal cohort with measures of infant attachment, infant development, and child mental health. Children provided buccal epithelial samples (mean age = 6.99, SD = 1.33 years, n = 226), which were used for analyses of genome-wide DNA methylation and genetic variation. We used a series of linear models to describe the association between infant attachment and (a) measures of child outcome and (b) DNA methylation across the genome. Paired genetic data was used to determine the genetic contribution to DNA methylation at attachment-associated sites. Infant attachment style was associated with infant cognitive development (Mental Development Index) and behavior (Behavior Rating Scale) assessed with the Bayley Scales of Infant Development at 36 months. Infant attachment style moderated the effects of prenatal adversity on Behavior Rating Scale scores at 36 months. Infant attachment was also significantly associated with a principal component that accounted for 11.9% of the variation in genome-wide DNA methylation. These effects were most apparent when comparing children with a secure versus a disorganized attachment style and most pronounced in females. The availability of paired genetic data revealed that DNA methylation at approximately half of all infant attachment-associated sites was best explained by considering both infant attachment and child genetic variation. This study provides further evidence that infant attachment can buffer some of the negative effects of early adversity on measures of infant behavior. We also highlight the interplay between infant attachment and child genotype in shaping variation in DNA methylation. Such findings provide preliminary evidence for a molecular signature of infant attachment and may help inform attachment-focused early intervention programs.
Second-mode wave growth within the hypersonic boundary layer of a slender cone is investigated experimentally using high-speed schlieren visualizations. Experiments were performed in AEDC Tunnel 9 over a range of unit Reynolds number conditions at a Mach number of approximately 14. A thin lens with a known density profile placed within the field of view enables calibration of the schlieren set-up, and the relatively high camera frame rates employed allow for the reconstruction of time-resolved pixel intensities at discrete streamwise locations. The calibration in conjunction with the reconstructed signals enables integrated spatial amplification rates (
factors) to be calculated for each unit Reynolds number condition and compared to
factors computed from both pressure transducer measurements and linear parabolized stability equation (PSE) solutions. Good agreement is observed between
factors computed from the schlieren measurements and those computed from the PSE solutions for the most-amplified second-mode frequencies. The streamwise development of
factors calculated from the schlieren measurements compares favourably to that calculated from the pressure measurements with slight variations in the
factor magnitudes calculated for harmonic frequencies. Finally, a bispectral analysis is carried out to identify nonlinear phase-coupled quadratic interactions present within the boundary layer. Multiple interactions are identified and revealed to be associated with the growth of disturbances at higher harmonic frequencies.
Early detection of karyotype abnormalities, including aneuploidy, could aid producers in identifying animals which, for example, would not be suitable candidate parents. Genome-wide genetic marker data in the form of single nucleotide polymorphisms (SNPs) are now being routinely generated on animals. The objective of the present study was to describe the statistics that could be generated from the allele intensity values from such SNP data to diagnose karyotype abnormalities; of particular interest was whether detection of aneuploidy was possible with both commonly used genotyping platforms in agricultural species, namely the Applied BiosystemsTM AxiomTM and the Illumina platform. The hypothesis was tested using a case study of a set of dizygotic X-chromosome monosomy 53,X sheep twins. Genome-wide SNP data were available from the Illumina platform (11 082 autosomal and 191 X-chromosome SNPs) on 1848 male and 8954 female sheep and available from the AxiomTM platform (11 128 autosomal and 68 X-chromosome SNPs) on 383 female sheep. Genotype allele intensity values, either as their original raw values or transformed to logarithm intensity ratio (LRR), were used to accurately diagnose two dizygotic (i.e. fraternal) twin 53,X sheep, both of which received their single X chromosome from their sire. This is the first reported case of 53,X dizygotic twins in any species. Relative to the X-chromosome SNP genotype mean allele intensity values of normal females, the mean allele intensity value of SNP genotypes on the X chromosome of the two females monosomic for the X chromosome was 7.45 to 12.4 standard deviations less, and were easily detectable using either the AxiomTM or Illumina genotype platform; the next lowest mean allele intensity value of a female was 4.71 or 3.3 standard deviations less than the population mean depending on the platform used. Both 53,X females could also be detected based on the genotype LRR although this was more easily detectable when comparing the mean LRR of the X chromosome of each female to the mean LRR of their respective autosomes. On autopsy, the ovaries of the two sheep were small for their age and evidence of prior ovulation was not appreciated. In both sheep, the density of primordial follicles in the ovarian cortex was lower than normally found in ovine ovaries and primary follicle development was not observed. Mammary gland development was very limited. Results substantiate previous studies in other species that aneuploidy can be readily detected using SNP genotype allele intensity values generally already available, and the approach proposed in the present study was agnostic to genotype platform.
To investigate the effectiveness and usability of automated procedural guidance during virtual temporal bone surgery.
Two randomised controlled trials were performed to evaluate the effectiveness, for medical students, of two presentation modalities of automated real-time procedural guidance in virtual reality simulation: full and step-by-step visual presentation of drillable areas. Presentation modality effectiveness was determined through a comparison of participants’ dissection quality, evaluated by a blinded otologist, using a validated assessment scale.
While the provision of automated guidance on procedure improved performance (full presentation, p = 0.03; step-by-step presentation, p < 0.001), usage of the two different presentation modalities was vastly different (full presentation, 3.73 per cent; step-by-step presentation, 60.40 per cent).
Automated procedural guidance in virtual temporal bone surgery is effective in improving trainee performance. Step-by-step presentation of procedural guidance was engaging, and therefore more likely to be used by the participants.
The appeal of ketamine – in promptly ameliorating depressive symptoms even in those with non-response – has led to a dramatic increase in its off-label use. Initial promising results await robust corroboration and key questions remain, particularly concerning its long-term administration. It is, therefore, timely to review the opinions of mood disorder experts worldwide pertaining to ketamine's potential as an option for treating depression and provide a synthesis of perspectives – derived from evidence and clinical experience – and to consider strategies for future investigations.
The proximity of minerals found in human hard tissues may influence cell phenotype. Since cells respond to a range of environmental cues, this study sought to identify the influence of two apatite-based microparticles, hydroxyapatite (HA) and fluoroapatite (FA), upon dental and bone cells. After bone marrow stromal cells (BMSCs), 7F2 osteoblasts and dental pulp stem cells (DPSCs) were plated into media with or without HA or FA particles, the cells were analyzed for alkaline phosphatase (ALP) production, collagen I production, osteocalcin production, and mineralization for two weeks. The BMSCs and DPSCs in media without any microparticles produced more ALP compared to those with microparticles from Day 5 forward. In addition, the collagen I and osteocalcin production in cultures without microparticles was higher than in cultures containing either HA or FA particles. While some studies have shown increased osteogeonic differentiation in the presence of mineral particles, those studies used nanoparticles that were able to be internalized by the cells and were smaller than the microparticles used in this study.
The goal of this study was to examine the mental health needs of children and youth who present to the emergency department (ED) for mental health care and to describe the type of, and satisfaction with, follow-up mental health services accessed.
A 6-month to 1.5-year prospective cohort study was conducted in three Canadian pediatric EDs and one general ED, with a 1-month follow-up post-ED discharge. Measures included 1) clinician rating of mental health needs, 2) patient and caregiver self-reports of follow-up services, and 3) interviews regarding follow-up satisfaction. Data analysis included descriptive statistics and the Fisher’s exact test to compare sites.
The cohort consisted of 373 children and youth (61.1% female; mean age 15.1 years, 1.5 standard deviation). The main reason for ED presentations was a mental health crisis. The three most frequent areas of need requiring action were mood (43.8%), suicide risk (37.4%), and parent-child relational problems (34.6%). During the ED visit, 21.6% of patients received medical clearance, 40.9% received a psychiatric consult, and 19.4% were admitted to inpatient psychiatric care. At the 1-month post-ED visit, 84.3% of patients/caregivers received mental health follow-up. Ratings of service recommendations were generally positive, as 60.9% of patients obtained the recommended follow-up care and 13.9% were wait-listed.
Children and youth and their families presenting to the ED with mental health needs had substantial clinical morbidity, were connected with services, were satisfied with their ED visit, and accessed follow-up care within 1-month with some variability.
You can continue to thoughtlessly pollute, Ruskin warns his readers, but in so doing you will destroy the earth and end your own existence. Six years earlier, in 1865, Ruskin coined the term “dis-ease” to denote a clear link between ill-being and environmental detachment. He yoked physical and mental health, elucidating “[h]ow literally that word Dis-Ease, the Negation and impossibility of Ease, expressed the entire moral state of our English Industry and its Amusements!” (“Of Kings’ Treasuries” 282). For Ruskin, nineteenth-century mills and factories, despite promising consumer satisfaction, made comfort impossible by endlessly producing frivolous, disposable goods, and thus waste. This needless consumption, a symptom of industry, produced an ignorance of true needs. Dis-ease, mental and bodily discomfort, resulted from alienation from the ecosystem, the networks of dependence between all species, and that estrangement blinded human beings to their actual role in the environment. While Ruskin focused on urban toxicity, the toxic ideological separation between humans and their environment impacted all spaces, a concern that several Victorian writers raised decades earlier than he did. This article traces the salutary cultural anxiety over improper sanitation and contaminants in two popular mid-nineteenth-century novels that demonstrate the effects of anthropogenic pollution in urban and rural environments, respectively. Published almost exactly one year apart, both Elizabeth Gaskell's Mary Barton (1848) and Charlotte Brontë’s Jane Eyre (1847) invoke what I call eco-consciousness in their description of urban and rural filth, portrayed as both visible and invisible toxins. Gaskell uncovers urban pollution in plain sight, going beyond smell to expose the causes of toxicity, while Brontë challenges the belief in the country as a safe haven from pollution, going beyond beauty to expose rural toxicity. Characters suffer physical disease and mental dis-ease resulting from a poor understanding of ecological relationships. Reading Jane Eyre alongside Mary Barton accentuates Brontë’s use of eco-consciousness to expose the hidden dangers of rural pollution that resulted from the very types of urban toxicity that Gaskell identifies.
Although infants less than 18 months old are capable of engaging in self-regulatory behavior (e.g., avoidance, withdrawal, and orienting to other aspects of their environment), the use of self-regulatory strategies at this age (as opposed to relying on caregivers) is associated with elevated behavioral and physiological distress. This study investigated infant dopamine-related genotypes (dopamine receptor D2 [DRD2], dopamine transporter solute carrier family C6, member 4 [SLC6A3], and catechol-O-methyltransferase [COMT]) as they interact with maternal self-reported history of maltreatment to predict observed infant independent emotion regulation behavior. A community sample (N = 193) of mother–infant dyads participated in a toy frustration challenge at infant age 15 months, and infant emotion regulation behavior was coded. Buccal cells were collected for genotyping. Maternal maltreatment history significantly interacted with infant SLC6A3 and COMT genotypes, such that infants with more 10-repeat and valine alleles of SLC6A3 and COMT, respectively, relative to infants with fewer or no 10-repeat and valine alleles, utilized more independent (i.e., maladaptive) regulatory behavior if mother reported a more extensive maltreatment history, as opposed to less. The findings indicate that child genetic factors moderate the intergenerational impact of maternal maltreatment history. The results are discussed in terms of potential mechanism of Gene × Environment interaction.
Heightened reactivity to unpredictable threat (U-threat) is a core individual difference factor underlying fear-based psychopathology. Little is known, however, about whether reactivity to U-threat is a stable marker of fear-based psychopathology or if it is malleable to treatment. The aim of the current study was to address this question by examining differences in reactivity to U-threat within patients before and after 12-weeks of selective serotonin reuptake inhibitors (SSRIs) or cognitive-behavioral therapy (CBT).
Participants included patients with principal fear (n = 22) and distress/misery disorders (n = 29), and a group of healthy controls (n = 21) assessed 12-weeks apart. A well-validated threat-of-shock task was used to probe reactivity to predictable (P-) and U-threat and startle eyeblink magnitude was recorded as an index of defensive responding.
Across both assessments, individuals with fear-based disorders displayed greater startle magnitude to U-threat relative to healthy controls and distress/misery patients (who did not differ). From pre- to post-treatment, startle magnitude during U-threat decreased only within the fear patients who received CBT. Moreover, within fear patients, the magnitude of decline in startle to U-threat correlated with the magnitude of decline in fear symptoms. For the healthy controls, startle to U-threat across the two time points was highly reliable and stable.
Together, these results indicate that startle to U-threat characterizes fear disorder patients and is malleable to treatment with CBT but not SSRIs within fear patients. Startle to U-threat may therefore reflect an objective, psychophysiological indicator of fear disorder status and CBT treatment response.
Determining what external stimuli influence cell differentiation, morphology, and growth continues to be a focus on many research groups to meet the healthcare Grand Challenges. While prior work has shown the influence of stiffness, surface chemistry and topography, these parameters often change in tandem, making it difficult to delineate the role of an individual component. This study examined the possible incorporation of microelectronic processing to produce reusable substrates for cell guidance studies. Subsequent plating of substrates cleaned with methods common in a microelectronic fabrication process showed complex responses including migration. Optical characterization of surfaces after cleaning showed remaining cellular debris that could be removed through the incorporation of a piranha solution. The micro patterned substrates did allow controlled comparison between dental pulp stem cells and osteoblast cells. The dental pulp cells did not show any cell alignment or cell proliferation (as indicated by cell density) with the isotropic or anisotropic micropatterns on the initial plating. The osteoblast cells (control) only aligned with the lines and not any of the other patterns (dots, holes or hexagons).
Background: Sepsis is a systemic response to infection that can affect brain function by inducing resident cells (including astrocytes and microglia) to generate brain chemokines and cytokines. However, there are few studies on the human brain. Since this information may shed further light on pathogenesis, our study objective was to measure the expression of 36 chemokines and cytokines in autopsied brain from 3 cases of sepsis and 10 controls, and to relate this to astrocyte and microglial activation. Methods: The right frontal pole was removed at autopsy and chemokine and cytokine expression measured by multiplexed enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (qPCR). Immunohistochemistry and image analysis were carried out to determine the expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, and CD68 and CD45, markers of activated microglial cells. Results: Concentrations of the chemokines CXCL8, CXCL10, CXCL12, CCL13 and CCL22 were increased in pooled data from the three cases of sepsis (p<0.05); however, their messenger RNA (mRNA) expression was unaltered. CXCL13, CXCL1, CXCL2, CCL1, CCL2, CCL8, CCL20, (interleukin) IL-16, IL-1β and (tumour necrosis factor) TNF concentrations showed increases in two of three sepsis cases. Additionally, individual sepsis cases showed increases in mRNA expression for HDAC (histone deacetylase) 6 and EIF (eukaryotic translation initiation factor) 4A2. Brain GFAP expression was significantly increased (p<0.05) in pooled data from the three sepsis cases. Individual sepsis cases showed increases in CD68 or CD45 expression. Conclusions: These expression patterns add to our understanding of the pathogenesis of sepsis and its effects on the brain.