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Suitable for both senior-level and first-year graduate courses, this fully revised edition provides a unique and systematic treatment of engineering dynamics that covers Newton–Euler and Lagrangian approaches. New to this edition are: two completely revised chapters on the constraints on, and potential energies for, rigid bodies, and the dynamics of systems of particles and rigid bodies; clearer discussion on coordinate singularities and their relation to mass matrices and configuration manifolds; additional discussion of contravariant basis vectors and dual Euler basis vectors, as well as related works in robotics; improved coverage of navigation equations; inclusion of a 350-page solutions manual for instructors, available online; a fully updated reference list. Numerous structured examples, discussion of various applications, and exercises covering a wide range of topics are included throughout, and source code for exercises, and simulations of systems are available online.
We compared antibiotic prescribing to older people in different settings to inform antibiotic stewardship interventions. We used data linkage to stratify individuals aged 65 years and over in Northern Ireland, 1st January 2012–31st December 2013, by residence: community dwelling, care home dwelling or ‘transitioned’ if admitted to a care home. The odds of being prescribed an antibiotic by residence were analysed using logistic regression, adjusting for patient demographics and selected medication use (proxy for co-morbidities). Trends in monthly antibiotic prescribing were examined in the 6 months pre- and post-admission to the care home. The odds of being prescribed at least one antibiotic were twofold higher in care homes compared with community dwellers (adjusted odds ratio 2.05, 95% CI 1.93–2.17). There was a proportionate increase of 51.5% in the percentage prescribed an antibiotic on admission, with a monthly average of 23% receiving an antibiotic in the 6 months post admission. While clinical need likely accounts for some of the observed antibiotic prescribing in care homes we cannot rule out more liberal prescribing, given the twofold difference between care home residents and their community dwelling peers having accounted for co-morbidities. The appropriateness of antibiotic prescribing in the care home setting should be examined.
Given the challenges in accurately identifying unexposed controls in case–control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within ‘control’ children (0–59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea (‘MSD pathogens’) in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and ‘any’ (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case–control studies examining diarrhoea.
Research shows that childhood dysregulation is associated with later psychiatric disorders. It does not yet resolve discrepancies in the operationalization of dysregulation. It is also far from settled on the origins and implications of individual differences in dysregulation. This study tested several operational definitions of dysregulation using Achenbach attention, anxious/depressed, and aggression subscales. Individual growth curves of dysregulation were computed, and predictors of growth differences were considered. The study also compared the predictive utility of the dysregulation indexes to standard externalizing and internalizing indexes. Dysregulation was indexed annually for 24 years in a community sample (n = 585). Hierarchical linear models considered changes in dysregulation in relation to possible influences from parenting, family stress, child temperament, language, and peer relations. In a test of the meaning of dysregulation, it was related to functional and psychiatric outcomes in adulthood. Dysregulation predictions were further compared to those of the more standard internalizing and externalizing indexes. Growth curve analyses showed strong stability of dysregulation. Initial levels of dysregulation were predicted by temperamental resistance to control, and change in dysregulation was predicted by poor language ability and peer relations. Dysregulation and externalizing problems were associated with negative adult outcomes to a similar extent.
Childhood trauma is a risk factor for psychosis. Deficits in response inhibition are common to psychosis and trauma-exposed populations, and associated brain functions may be affected by trauma exposure in psychotic disorders. We aimed to identify the influence of trauma-exposure on brain activation and functional connectivity during a response inhibition task.
We used functional magnetic resonance imaging to examine brain function within regions-of-interest [left and right inferior frontal gyrus (IFG), right dorsolateral prefrontal cortex, right supplementary motor area, right inferior parietal lobule and dorsal anterior cingulate cortex], during the performance of a Go/No-Go Flanker task, in 112 clinical cases with psychotic disorders and 53 healthy controls (HCs). Among the participants, 71 clinical cases and 21 HCs reported significant levels of childhood trauma exposure, while 41 clinical cases and 32 HCs did not.
In the absence of effects on response inhibition performance, childhood trauma exposure was associated with increased activation in the left IFG, and increased connectivity between the left IFG seed region and the cerebellum and calcarine sulcus, in both cases and healthy individuals. There was no main effect of psychosis, and no trauma-by-psychosis interaction for any other region-of-interest. Within the clinical sample, the effects of trauma-exposure on the left IFG activation were mediated by symptom severity.
Trauma-related increases in activation of the left IFG were not associated with performance differences, or dependent on clinical diagnostic status; increased IFG functionality may represent a compensatory (overactivation) mechanism required to exert adequate inhibitory control of the motor response.
Untreated maternal depression during the postpartum period can have a profound impact on the short- and long-term psychological and physical well-being of children. There is, therefore, an imperative for increased understanding of the determinants of depression and depression-related healthcare access during this period.
Respondents were 11 089 mothers of 9-month-old infants recruited to the Growing Up in Ireland study. Of this sample, 10 827 had complete data on all relevant variables. Respondents provided sociodemographic, socioeconomic and household information, and completed the Center for Epidemiologic Studies Depression Scale (CESD).
11.1% of mothers scored above the CESD threshold for depression. 10.0% of depressed mothers and 25.4% of depressed fathers had depressed partners. Among depressed mothers, 73.1% had not attended a healthcare professional for a mental health problem since the birth of the cohort infant. In the adjusted model, the likelihood of depression was highest in mothers who: had lower educational levels (odds ratio (OR) 1.26; 95% confidence intervals (CIs) 1.08, 1.46); were unemployed (OR 1.27; 95% CIs 1.10, 1.47); reported previous mental health problems (OR 6.55; 95% CIs 5.68, 7.56); reported that the cohort child was the result of an unintended pregnancy (OR 1.43; 95% CIs 1.22, 1.68), was preterm (OR 1.35; 95% CIs 1.07, 1.70), or had health/developmental problems (OR 1.20; 95% CIs 1.04, 1.39); had no partner in the household (OR 1.33; 95% CIs 1.04, 1.70) or were living with a depressed partner (OR 2.66; 95% CIs 1.97, 3.60); reported no family living nearby (OR 1.33; 95% CIs 1.16, 1.54); were in the lowest income group (OR 1.60; 95% CIs 1.21, 2.12). The primary determinant of not seeking treatment for depression was being of non-white ethnicity (OR 2.21; 95% CIs 1.18, 4.13).
Results highlight the prevalence of maternal depression in the later postpartum period, particularly for lower socioeconomic groups, those with previous mental health problems, and those with limited social support. The large proportion of unmet need in depressed mothers, particularly among ethnic minority groups, emphasises the need for a greater awareness of postpartum mental health problems and increased efforts by healthcare professionals to ensure that mothers can access the required services.
To determine whether living in a food swamp (≥4 corner stores within 0·40 km (0·25 miles) of home) or a food desert (generally, no supermarket or access to healthy foods) is associated with consumption of snacks/desserts or fruits/vegetables, and if neighbourhood-level socio-economic status (SES) confounds relationships.
Cross-sectional. Assessments included diet (Youth/Adolescent FFQ, skewed dietary variables normalized) and measured height/weight (BMI-for-age percentiles/Z-scores calculated). A geographic information system geocoded home addresses and mapped food deserts/food swamps. Associations examined using multiple linear regression (MLR) models adjusting for age and BMI-for-age Z-score.
Baltimore City, MD, USA.
Early adolescent girls (6th/7th grade, n 634; mean age 12·1 years; 90·7 % African American; 52·4 % overweight/obese), recruited from twenty-two urban, low-income schools.
Girls’ consumption of fruit, vegetables and snacks/desserts: 1·2, 1·7 and 3·4 servings/d, respectively. Girls’ food environment: 10·4 % food desert only, 19·1 % food swamp only, 16·1 % both food desert/swamp and 54·4 % neither food desert/swamp. Average median neighbourhood-level household income: $US 35 298. In MLR models, girls living in both food deserts/swamps consumed additional servings of snacks/desserts v. girls living in neither (β=0·13, P=0·029; 3·8 v. 3·2 servings/d). Specifically, girls living in food swamps consumed more snacks/desserts than girls who did not (β=0·16, P=0·003; 3·7 v. 3·1 servings/d), with no confounding effect of neighbourhood-level SES. No associations were identified with food deserts or consumption of fruits/vegetables.
Early adolescent girls living in food swamps consumed more snacks/desserts than girls not living in food swamps. Dietary interventions should consider the built environment/food access when addressing adolescent dietary behaviours.
Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown.
Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS).
Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by −0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for.
Anticholinergic burden has a significant impact on patients’ ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.
We examined the use of functional analysis methodologies to identify the environmental determinants of challenging behaviour for two students with severe disabilities. With one student the functional analysis was conducted in an outpatient clinic which was removed from the school setting. The functional analysis was conducted in the classroom setting with the other student. These assessments produced clear hypotheses regarding the controlling contingencies for challenging behaviour with both students. Individualised support plans were then developed and were successfully implemented by classroom personnel. The results of this study are discussed in terms of using a flexible approach to functional assessment in schools based on the individual characteristics of the student and the classroom context.
Glucocorticoids and serotonin may mediate the link between maternal environment, fetal brain development and ‘programming’ of offspring behaviors. The placenta regulates fetal exposure to maternal hormonal signals in animal studies, but few data address this in humans. We measured prospectively maternal depressive symptoms during pregnancy and mRNAs encoding key gene products determining glucocorticoid and serotonin function in term human placenta and explored associations with infant regulatory behaviors.
Bi-weekly self-ratings of the Center for Epidemiologic Studies Depression Scale from 12th to 13th gestational week onwards and term placental mRNAs of 11beta-hydroxysteroid dehydrogenase type 2 (HSD2B11), type 1 (HSD1B11), glucocorticoid (NR3C1), mineralocorticoid receptors (NR3C2) and serotonin transporter (SLC6A4) were obtained from 54 healthy mothers aged 32.2 ± 5.3 years with singleton pregnancies and without pregnancy complications. Infant regulatory behaviors (crying, feeding, spitting, elimination, sleeping and predictability) were mother-rated at 15.6 ± 4.2 days.
Higher placental mRNA levels of HSD2B11 [0.41 standard deviation (s.d.) unit increase per s.d. unit increase; 95% confidence interval (CI) 0.13–0.69, p = 0.005], HSD1B11 (0.30, 0.03–0.57, p = 0.03), NR3C1 (0.44, 0.19–0.68, p = 0.001) and SLC6A4 (0.26, 0.00–0.53, p = 0.05) were associated with more regulatory behavioral challenges of the infant. Higher placental NR3C1 mRNA partly mediated the association between maternal depressive symptoms during pregnancy and infant regulatory behaviors (p < 0.05).
Higher placental expression of genes regulating feto-placental glucocorticoid and serotonin exposure is characteristic of infants with more regulatory behavioral challenges. Maternal depression acts, at least partly, via altering glucocorticoid action in the placenta to impact on offspring regulatory behaviors.
Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus.
We studied women participating in a prospective pregnancy cohort: the Prediction and Prevention of Preeclampsia (PREDO) Study, Helsinki, Finland. Maternal depressive symptoms were assessed at 2-week intervals throughout pregnancy in 56 healthy women with singleton, term pregnancies. Messenger ribonucleic acid (mRNA) levels of glucocorticoid (GR) and mineralocorticoid (MR) receptors and serotonin transporter (SLC6A4), 11β-hydroxysteroid dehydrogenase type 1 (HSD1) and 2 (HSD2) were quantified in placental biopsies.
In adjusted analyses women who reported higher depressive symptoms across the whole pregnancy had higher mRNA levels of GR [effect size 0.31 s.d. units, 95% confidence interval (CI) 0.01–0.60, p = 0.042] and MR (effect size 0.34 s.d. units, 95% CI 0.01–0.68, p = 0.047). These effects were significant for symptoms experienced in the third trimester of pregnancy for GR; findings for MR were also significant for symptoms experienced in the second trimester. GR and MR mRNA levels increased linearly by having the trimester-specific depressive symptoms scores 0, 1 or 2–3 times above the clinical cut-off for depression (p = 0.003, p = 0.049, respectively, and p = 0.004, p = 0.15 in adjusted analyses).
Our findings offer potential gestational-age-specific mechanisms linking maternal depressive symptoms during pregnancy via placental biology. Future studies will test whether these also link with adverse offspring outcomes.
We couple a node-centered finite volume method to a high order finite difference method to simulate dynamic earthquake ruptures along nonplanar faults in two dimensions. The finite volume method is implemented on an unstructured mesh, providing the ability to handle complex geometries. The geometric complexities are limited to a small portion of the overall domain and elsewhere the high order finite difference method is used, enhancing efficiency. Both the finite volume and finite difference methods are in summation-by-parts form. Interface conditions coupling the numerical solution across physical interfaces like faults, and computational ones between structured and unstructured meshes, are enforced weakly using the simultaneous-approximation-term technique. The fault interface condition, or friction law, provides a nonlinear relation between fields on the two sides of the fault, and allows for the particle velocity field to be discontinuous across it. Stability is proved by deriving energy estimates; stability, accuracy, and efficiency of the hybrid method are confirmed with several computational experiments. The capabilities of the method are demonstrated by simulating an earthquake rupture propagating along the margins of a volcanic plug.
The intake of the mainly plant-derived n-3 PUFA α-linolenic acid (ALA) has been reported to be associated with a lower risk of CHD. However, the results have been inconsistent. Therefore, the objective of the present study was to examine the association between the intake of ALA and the risk of CHD. Potential effect modification by the intake of long-chain n-3 PUFA (n-3 LCPUFA) was also investigated. Data from eight American and European prospective cohort studies including 148 675 women and 80 368 men were used. The outcome measure was incident CHD (CHD event and death). During 4–10 years of follow-up, 4493 CHD events and 1751 CHD deaths occurred. Among men, an inverse association (not significant) between the intake of ALA and the risk of CHD events and deaths was observed. For each additional gram of ALA consumed, a 15 % lower risk of CHD events (hazard ratios (HR) 0·85, 95 % CI 0·72, 1·01) and a 23 % lower risk of CHD deaths (HR 0·77, 95 % CI 0·58, 1·01) were observed. No consistent association was observed among women. No effect modification by the intake of n-3 LCPUFA was observed.
To date, no study has directly and simultaneously measured the discrepancy between what people actually eat and what they report eating under observation in the context of energy balance (EB). The present study aimed to objectively measure the ‘extent’ and ‘nature’ of misreporting of dietary intakes under conditions in which EB and feeding behaviour were continuously monitored. For this purpose, a total of fifty-nine adults were recruited for 12 d, involving two 3 d overt phases and two 3 d covert phases of food intake measurement in a randomised cross-over design. Subjects had ad libitum access to a variety of familiar foods. Food intake was covertly measured using a feeding behaviour suite to establish actual energy and nutrient intakes. During the overt phases, subjects were instructed to self-report food intake using widely accepted methods. Misreporting comprised two separate and synchronous phenomena. Subjects decreased energy intake (EI) when asked to record their food intake (observation effect). The effect was significant in women ( − 8 %, P< 0·001) but not in men ( − 3 %, P< 0·277). The reported EI was 5 to 21 % lower (reporting effect) than the actual intake, depending on the reporting method used. Semi-quantitative techniques gave larger discrepancies. These discrepancies were identical in men and women and non-macronutrient specific. The ‘observation’ and ‘reporting’ effects combined to constitute total misreporting, which ranged from 10 to 25 %, depending on the intake measurement assessed. When studied in a laboratory environment and EB was closely monitored, subjects under-reported their food intake and decreased the actual intake when they were aware that their intake was being monitored.
We have evaluated copy number variants (CNVs) in six monozygotic twin pairs discordant for schizophrenia. The data from Affymetrix® Human SNP 6.0 arrays™ were analyzed using Affymetrix® Genotyping Console™, Partek® Genomics Suite™, PennCNV, and Golden Helix SVS™. This yielded both program-specific and overlapping results. Only CNVs called by Affymetrix Genotyping Console, Partek Genomics Suite, and PennCNV were used in further analysis. This analysis included an assessment of calls in each of the six twin pairs towards identification of unique CNVs in affected and unaffected co-twins. Real time polymerase chain reaction (PCR) experiments confirmed one CNV loss at 7q11.21 that was found in the affected patient but not in the unaffected twin. The results identified CNVs and genes that were previously implicated in mental abnormalities in four of the six twin pairs. It included PYY (twin pairs 1 and 5), EPHA3 (twin pair 3), KIAA1211L (twin pair 4), and GPR139 (twin pair 5). They represent likely candidate genes and CNVs for the discordance of four of the six monozygotic twin pairs for this heterogeneous neurodevelopmental disorder. An explanation for these differences is ontogenetic de novo events that differentiate in the monozygotic twins during development.
Accumulative evidence demonstrates the crucial role of evolutionary conserved Toll-like receptors (TLRs) in identifying microbial or viral compounds. TLRs are also able to recognise endogenous molecules which are released upon cell damage or stress and have been shown to play a key role in numerous autoimmune diseases including systemic sclerosis (SSc). A classic feature of SSc, is vascular injury manifested as Raynaud's phenomenon and ischaemia of the skin, resulting in the release of endogenous TLR ligands during inflammation and local tissue damage. These locally released TLR ligands bind TLRs possibly complexed to autoantibodies, and initiate intracellular signalling pathways and may be one of the mechanisms that initiate and drive autoimmunity and subsequent fibrosis. Activation of the immune system results in interferon (IFN) sensitive gene transcription. There is also an IFN gene signature in SSc peripheral blood. TLRs may represent the link between immune activation, common in SSc, and tissue fibrosis. Therefore, a better understanding of the mechanisms of TLR-mediated pathogenesis and therapies targeting individual TLRs, may provide a more specific approach of treating multi-systemic autoimmune diseases. This review aims to integrate the current knowledge of TLR function in the autoimmune disorders with particular emphasis on SSc. We suggest the TLR system as a new therapeutic target.
Objectives: Approximately 10–15 percent of individuals with diabetes mellitus develop foot ulcers, which precede 85 percent of amputations. Increased oxygen, through the use of hyperbaric oxygen therapy (HBOT), has been suggested to encourage ulcer healing thus reducing the risk of amputation. The objective of this systematic review is to evaluate the efficacy of systemic HBOT for nonhealing ulcers of the lower limb in diabetes patients.
Methods: A systematic search, using controlled and keyword terms focusing on “HBOT” and “lower limb diabetic ulcers,” was conducted. Databases searched included Medline, EMBASE, CINAHL, PubMed, Wiley's Cochrane Library, and Biosis. Randomized controlled trials (RCTs) and observational studies were included. Pooled estimates of outcomes were determined when appropriate.
Results: Of the 654 citations identified, 157 articles underwent full-text review. Data were abstracted from twelve publications (six RCTs and six comparative observational studies). Pooled analysis of the RCT and observational data showed that treatment with HBOT reduced the risk of major amputation by 60 percent (p = .29) and 61 percent (p = .003) compared with standard wound care, respectively. The RCT data revealed that the relative risk of having an unhealed wound following HBOT was 0.54 (p = .10) and 0.24 (p < .0001) based on observational data.
Conclusions: Due to the limited RCT evidence, it is not possible to conclusively establish the benefits and harms of treating diabetic lower limb ulcers with HBOT. No significant effects on amputation rates were found in the RCT evidence and in the high quality studies, no difference was found.