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Numerical Analysis is a broad field, and coming to grips with all of it may seem like a daunting task. This text provides a thorough and comprehensive exposition of all the topics contained in a classical graduate sequence in numerical analysis. With an emphasis on theory and connections with linear algebra and analysis, the book shows all the rigor of numerical analysis. Its high level and exhaustive coverage will prepare students for research in the field and become a valuable reference as they continue their career. Students will appreciate the simple notation, clear assumptions and arguments, as well as the many examples and classroom-tested exercises ranging from simple verification to qualifying exam-level problems. In addition to the many examples with hand calculations, readers will also be able to translate theory into practical computational codes by running sample MATLAB codes as they try out new concepts.
Data-driven discovery is revolutionizing how we model, predict, and control complex systems. Now with Python and MATLAB®, this textbook trains mathematical scientists and engineers for the next generation of scientific discovery by offering a broad overview of the growing intersection of data-driven methods, machine learning, applied optimization, and classical fields of engineering mathematics and mathematical physics. With a focus on integrating dynamical systems modeling and control with modern methods in applied machine learning, this text includes methods that were chosen for their relevance, simplicity, and generality. Topics range from introductory to research-level material, making it accessible to advanced undergraduate and beginning graduate students from the engineering and physical sciences. The second edition features new chapters on reinforcement learning and physics-informed machine learning, significant new sections throughout, and chapter exercises. Online supplementary material – including lecture videos per section, homeworks, data, and code in MATLAB®, Python, Julia, and R – available on databookuw.com.
Neonatal enteroviral myocarditis is a rare but potentially fatal illness. We sought to identify echocardiographic markers at diagnosis that could help risk-stratify infants for poor outcome and to characterise late sequelae.
We reviewed data for infants <30 days of age diagnosed with enteroviral myocarditis between 1999 and 2019 at Children’s Wisconsin. Echo measures were collected retrospectively from the initial neonatal study including left ventricular ejection fraction, shortening fraction, diastolic and systolic dimensions, and peak global circumferential and longitudinal strain.
Fourteen neonates were diagnosed at an average age of 11 days. All had abnormal left ventricular ejection fraction (mean 38%; range 22–53%) at diagnosis. Three infants died, and one required transplantation during initial hospital. The 10 transplant-free survivors had significantly better global circumferential strain and global longitudinal strain at the initial echo compared to the 4 who died or needed transplant (global circumferential strain −13.2% versus −6.8%, p = 0.005; global longitudinal strain −8.8% versus −4.7%, p = 0.016). All other measures of left ventricular systolic function/dimensions were similar between the two groups. Follow-up data were available for 8/10 survivors; 5/8 had a persistently abnormal echo at an average interval of 8.3 years. 4/8 developed a left ventricular aneurysm that was consistently localised to the posterior basal wall.
Neonatal enteroviral myocarditis carries a high risk of early mortality and late morbidity. Echo-derived left ventricular strain measures have utility in risk stratifying infants with enteroviral myocarditis. Most survivors continue to have late dysfunction necessitating cardiology surveillance and medical therapy.
Second language (L2) teachers may shy away from self-assessments because of warnings that students are not accurate self-assessors. This information stems from meta-analyses in which self-assessment scores on average did not correlate highly with proficiency test results. However, researchers mostly used Pearson correlations, when polyserial could be used. Furthermore, self-assessments today can be computer adaptive. With them, nonlinear statistics are needed to investigate their relationship with other measurements. We wondered, if we explored the relationship between self-assessment and proficiency test scores using more robust measurements (polyserial correlation, continuation-ratio modeling), would we find different results? We had 807 L2-Spanish learners take a computer-adaptive, L2-speaking self-assessment and the ACTFL Oral Proficiency Interview – computer (OPIc). The scores correlated at .61 (polyserial). Using continuation-ratio modeling, we found each unit of increase on the OPIc scale was associated with a 131% increase in the odds of passing the self-assessment thresholds. In other words, a student was more likely to move on to higher self-assessment subsections if they had a higher OPIc rating. We found computer-adaptive self-assessments appropriate for low-stakes L2-proficiency measurements, especially because they are cost-effective, make intuitive sense to learners, and promote learner agency.
Patients with single ventricle CHD have significant morbidity and healthcare utilisation throughout their lifetime, including non-cardiac hospital admissions. Respiratory viral infections are the main cause of hospitalisation in children, but few data exist for single ventricle patients. We sought to identify how respiratory viral infections impact patients with single ventricle CHD and potential differences between Glenn and Fontan circulation.
We conducted a retrospective study of patients seen from 01/01/2011–12/31/2020. We identified patients with a history of single ventricle CHD and Glenn palliation, and a normoxic control group with isolated atrial septal defect requiring surgical closure. We compared viral-related clinical presentations, admissions, and admission characteristics.
A total of 312 patients were included (182 single ventricle, 130 atrial septal defect). Single ventricle patients were more likely than children with isolated atrial septal defect to be admitted with a respiratory virus (odds ratio 4.15 [2.30–7.46]), but there was no difference in mechanical ventilation or hospital length of stay (p = 0.4709). Single ventricle patients with Glenn circulation were more likely than those with Fontan circulation to present and be admitted (odds ratio 3.25 [1.62–6.52]), but there was no difference in ICU admission, mechanical ventilation, or hospital length of stay (p = 0.1516).
Respiratory viral infections are prevalent but uncomplicated in patients with single ventricle CHD. Viral-related presentations and admissions are more prevalent during the period of Glenn circulation compared to Fontan circulation; however, rate of mechanical ventilation and hospital length of stay are similar.
Artifacts, including ceramics, ground stone, and soil samples, as well as dental calculus, recovered from sites in the eastern North American central Plains were submitted to multiple laboratories for analysis of microbotanical remains. Direct accelerator mass spectrometer (AMS) dates of 361–197 cal BC provide evidence for the earliest use of maize (Zea mays ssp. mays) in this region. Squash (Cucurbita sp.), wild rice (cf. Zizania spp.), and palm (Arecaceae sp.) microremains were also found. This research adds to the growing evidence of the importance of microbotanical analysis in documenting plant use and in the identification of early maize. The combined data on early maize from the eastern Plains adds to our understanding of the timing and dispersal of this crop out of the American Southwest. Alternative explanations for the adoption and early use of maize by eastern central Plains communities include its value as a secondary resource, as an addition to an existing farming strategy, or as a component of Middle Woodland rituals.
OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.
Post-operative nausea and vomiting is frequent after congenital cardiac surgery.
We sought to determine factors associated to severe post-operative vomiting after congenital cardiac surgery and the effect on post-operative outcomes.
Patients > 30 days of age who underwent elective cardiac surgical repair as part of an enhanced recovery after congenital cardiac surgery programme were retrospectively reviewed. Patient characteristics and perioperative factors were compared by univariate analysis for patients with severe post-operative vomiting, defined as three events or more, and for patients with no-or-mild post-operative vomiting. All variables with a p-value < 0.1 were included in a multivariable model, and major post-operative outcomes were compared using regression analysis.
From 1 October, 2018 to 30 September, 2019, 430 consecutive patients were included. The median age was 4.8 years (interquartile range 1.2–12.6). Twenty-one per cent of patients (91/430) experienced severe post-operative vomiting. Total intraoperative opioids > 5.0 mg/kg of oral morphine equivalent (adjusted odds ratio 1.72) and post-operative inotropes infusion(s) (adjusted odds ratio 1.64) were identified as independent predictors of severe post-operative vomiting after surgery. Patients suffering from severe post-operative vomiting had increased pulmonary complications (adjusted odds ratio 5.18) and longer post-operative hospitalisation (adjusted coefficient, 0.89).
Greater cumulative intraoperative opioids are associated with severe post-operative vomiting after congenital cardiac surgery. Multimodal pain strategies targeting the reduction of intraoperative opioids should be considered during congenital cardiac surgery to enhance recovery after surgery.
Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied.
58 pre-adolescent children (aged 9–10-years) with BED (mBMI = 25.05; s.d. = 5.40) and 66 age, BMI and developmentally matched control children (mBMI = 25.78; s.d. = 0.33) were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward [orbitofrontal cortex (OFC), nucleus accumbens, amygdala] and inhibitory control [dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)] networks via hypothesis-driven seed-to-seed analyses, and secondary seed-to-voxel analyses.
Findings revealed reduced FC between the dlPFC and amygdala, and between the ACC and OFC in pre-adolescent children with BED, relative to controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses.
Early-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.
This paper is the fourth in a series of low-frequency searches for technosignatures. Using the Murchison Widefield Array over two nights, we integrate 7 h of data toward the Galactic Centre (centred on the position of Sagittarius
) with a total field-of-view of
. We present a targeted search toward 144 exoplanetary systems, at our best yet angular resolution (75 arcsec). This is the first technosignature search at a central frequency of 155 MHz toward the Galactic Centre (our previous central frequencies have been lower). A blind search toward in excess of 3 million stars toward the Galactic Centre and Galactic bulge is also completed, placing an equivalent isotropic power limit
at the distance to the Galactic Centre. No plausible technosignatures are detected.
Schizophrenia endophenotypes may help elucidate functional effects of genetic risk variants in multiply affected consanguineous families that segregate recessive risk alleles of large effect size. We studied the association between a schizophrenia risk locus involving a 6.1Mb homozygous region on chromosome 13q22–31 in a consanguineous multiplex family and cognitive functioning, haemodynamic response and white matter integrity using neuroimaging.
We performed CANTAB neuropsychological testing on four affected family members (all homozygous for the risk locus), ten unaffected family members (seven homozygous and three heterozygous) and ten healthy volunteers, and tested neuronal responses on fMRI during an n-back working memory task, and white matter integrity on diffusion tensor imaging (DTI) on four affected and six unaffected family members (four homozygous and two heterozygous) and three healthy volunteers. For cognitive comparisons we used a linear mixed model (Kruskal–Wallis) test, followed by posthoc Dunn's pairwise tests with a Bonferroni adjustment. For fMRI analysis, we counted voxels exceeding the p < 0.05 corrected threshold. DTI analysis was observational.
Family members with schizophrenia and unaffected family members homozygous for the risk haplotype showed attention (p < 0.01) and working memory deficits (p < 0.01) compared with healthy controls; a neural activation laterality bias towards the right prefrontal cortex (voxels reaching p < 0.05, corrected) and observed lower fractional anisotropy in the anterior cingulate cortex and left dorsolateral prefrontal cortex.
In this family, homozygosity at the 13q risk locus was associated with impaired cognition, white matter integrity, and altered laterality of neural activation.
This essay considers the goodness of God and the psalmists’ gratitude toward God in connection with divine aseity and divine freedom. The plenitude of God's goodness entails that he is fully sufficient and actualised in himself. The psalmists’ gratitude toward God implies that he acts in freedom when he communicates his goodness to creatures. The essay then explores how contemplating this teaching in the Psalter can help us to articulate in a broader dogmatic scope the coherence of God's pure actuality, freedom and constancy.
Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time.
As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors.
Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants.
The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.
Cesario claims that all bias research tells us is that people “end up using the information they have come to learn as being probabilistically accurate in their daily lives” (sect. 5, para. 4). We expose Cesario's flawed assumptions about the relationship between accuracy and bias. Through statistical simulations and empirical work, we show that even probabilistically accurate responses are regularly accompanied by bias.
Theories of early cooperation in human society often draw from a small sample of ethnographic studies of surviving populations of hunter–gatherers, most of which are now sedentary. Borneo hunter–gatherers (Punan, Penan) have seldom figured in comparative research because of a decades-old controversy about whether they are the descendants of farmers who adopted a hunting and gathering way of life. In 2018 we began an ethnographic study of a group of still-nomadic hunter–gatherers who call themselves Punan Batu (Cave Punan). Our genetic analysis clearly indicates that they are very unlikely to be the descendants of neighbouring agriculturalists. They also preserve a song language that is unrelated to other languages of Borneo. Dispersed travelling groups of Punan Batu with fluid membership use message sticks to stay in contact, co-operate and share resources as they journey between rock shelters and forest camps. Message sticks were once widespread among nomadic Punan in Borneo, but have largely disappeared in sedentary Punan villages. Thus the small community of Punan Batu offers a rare glimpse of a hunting and gathering way of life that was once widespread in the forests of Borneo, where prosocial behaviour extended beyond the face-to-face community, facilitating successful collective adaptation to the diverse resources of Borneo's forests.
We expand upon prior work (Gibbons et al., 2012) relating childhood stressor effects, particularly harsh childhood environments, to risky behavior and ultimately physical health by adding longer-term outcomes – deoxyribonucleic acid (DNA) methylation-based measures of accelerated aging (DNAm-aging). Further, following work on the effects of early exposure to danger (McLaughlin et al., 2014), we also identify an additional pathway from harsh childhood environments to DNAm-aging that we label the danger/FKBP5 pathway, which includes early exposure to dangerous community conditions that are thought to impact glucocorticoid regulation and pro-inflammatory mechanisms. Because different DNAm-aging indices provide different windows on accelerated aging, we contrast effects on early indices of DNAm-aging based on chronological age with later indices that focused on predicting biological outcomes. We utilize data from Family and Community Health Study participants (N = 449) from age 10 to 29. We find that harshness influences parenting, which, in turn, influences accelerated DNAm-aging through the risky cognitions and substance use (i.e., behavioral) pathway outlined by Gibbons et al. (2012). Harshness is also associated with increased exposure to threat/danger, which, in turn, leads to accelerated DNAm-aging through effects on FKBP5 activity and enhanced pro-inflammatory tendencies (i.e., the danger/FKBP5 pathway).
The 90-km long Stuoragurra Fault Complex, part of the approximately 4–5-km wide Precambrian Mierojávri–Sværholt Shear Zone, constitutes the Norwegian part of the larger Lapland province of postglacial faults. It consists of three separate fault systems being 6–12 km apart. The faults dip 30–75° to the SE and can be traced to about 500 m depth. Deep seismic profiling shows that the shear zone dips at an angle of about 43° to the southeast and can be traced to about 3 km depth. A total of approximately 80 earthquakes were registered here between 1991 and 2019. Most of them occurred to the southeast of the fault scarps. The maximum moment magnitude was 4.0. The formation of postglacial faults in northern Fennoscandia has previously been associated with the deglaciation of the last inland ice. Dating of fault reactivation reveals, however, a late Holocene age (between around 700 and 4000 a BP). The reverse displacement of around 9 m and fault system lengths of 14 and 21 km of the two southernmost fault systems indicate a moment magnitude of about 7. The results from this study indicate that the expected maximum magnitude of future earthquakes in Fennoscandia is about 7.