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.
Previous research in clinical, community, and school settings has demonstrated positive outcomes for the Secret Agent Society (SAS) social skills training program. This is designed to help children on the autism spectrum become more aware of emotions in themselves and others and to ‘problem-solve’ complex social scenarios. Parents play a key role in the implementation of the SAS program, attending information and support sessions with other parents and providing supervision, rewards, and feedback as their children complete weekly ‘home mission’ assignments. Drawing on data from a school-based evaluation of the SAS program, we examined whether parents’ engagement with these elements of the intervention was linked to the quality of their children’s participation and performance. Sixty-eight 8–14-year-olds (M age = 10.7) with a diagnosis of autism participated in the program. The findings indicated that ratings of parental engagement were positively correlated with children’s competence in completing home missions and with the quality of their contribution during group teaching sessions. However, there was a less consistent relationship between parental engagement and measures of children’s social and emotional skill gains over the course of the program.
The climate crisis requires nations to achieve human well-being with low national levels of carbon emissions. Countries vary from one another dramatically in how effectively they convert resources into well-being, and some nations with low levels of emissions have relatively high objective and subjective well-being. We identify urgent research and policy agendas for four groups of countries with either low or high emissions and well-being indicators. Least studied are those with low well-being and high emissions. Understanding social and political barriers to switching from high-carbon to lower-carbon modes of production and consumption, and ways to overcome them, will be fundamental.
A key element of the right to self-determination is territorial integrity. This has usually been considered solely in relation to the territorial integrity of an existing State seeking to resist claims by peoples for the right to self-determination. Yet the Chagos Opinion by the International Court of Justice examines a different type of territorial integrity—that of the colonial territory itself. This article explores the consequence of the Court's view that the territorial integrity of the colonial territory is a matter of customary international law, and that any division, integration or other disruption of that colonial territory after December 1960 is unlawful, without the free and genuine consent of the people of the colonial territory. In particular this article seeks to explore what the Chagos Opinion means in terms of the territorial integrity of a colonial territory. It also examines the required conditions for ascertaining a free and genuine consent of the people of that territory, and the legal effects of not complying with them. There is also consideration of the implications for other situations from the clarification of customary international law in the Chagos Opinion, with a special focus on West Papua.
Individuals with posttraumatic stress disorder (PTSD) are at increased risk of various chronic diseases. One hypothesized pathway is via changes in diet quality. This study evaluated whether PTSD was associated with deterioration in diet quality over time.
Data were from 51 965 women in the Nurses' Health Study II PTSD sub-study followed over 20 years. Diet, assessed at 4-year intervals, was characterized via the Alternative Healthy Eating Index-2010 (AHEI). Based on information from the Brief Trauma Questionnaire and Short Screening Scale for DSM-IV PTSD, trauma/PTSD status was classified as no trauma exposure, prevalent exposure (trauma/PTSD onset before study entry), or new-onset (trauma/PTSD onset during follow-up). We further categorized women with prevalent exposure as having trauma with no PTSD symptoms, trauma with low PTSD symptoms, and trauma with high PTSD symptoms, and created similar categories for women with new-onset exposure, resulting in seven comparison groups. Multivariable linear mixed-effects spline models tested differences in diet quality changes by trauma/PTSD status over follow-up.
Overall, diet quality improved over time regardless of PTSD status. In age-adjusted models, compared to those with no trauma, women with prevalent high PTSD and women with new-onset high PTSD symptoms had 3.3% and 3.6% lower improvement in diet quality, respectively, during follow-up. Associations remained consistent after adjusting for health conditions, sociodemographics, and behavioral characteristics.
PTSD is associated with less healthy changes in overall diet quality over time. Poor diet quality may be one pathway linking PTSD with a higher risk of chronic disease development.
To detect modest associations of dietary intake with disease risk, observational studies need to be large and control for moderate measurement errors. The reproducibility of dietary intakes of macronutrients, food groups and dietary patterns (vegetarian and Mediterranean) was assessed in adults in the UK Biobank study on up to five occasions using a web-based 24-h dietary assessment (n 211 050), and using short FFQ recorded at baseline (n 502 655) and after 4 years (n 20 346). When the means of two 24-h assessments were used, the intra-class correlation coefficients (ICC) for macronutrients varied from 0·63 for alcohol to 0·36 for polyunsaturated fat. The ICC for food groups also varied from 0·68 for fruit to 0·18 for fish. The ICC for the FFQ varied from 0·66 for meat and fruit to 0·48 for bread and cereals. The reproducibility was higher for vegetarian status (κ > 0·80) than for the Mediterranean dietary pattern (ICC = 0·45). Overall, the reproducibility of pairs of 24-h dietary assessments and single FFQ used in the UK Biobank were comparable with results of previous prospective studies using conventional methods. Analyses of diet–disease relationships need to correct for both measurement error and within-person variability in dietary intake in order to reliably assess any such associations with disease in the UK Biobank.
Project management expertise is employed across many professional sectors, including clinical research organizations, to ensure that efforts undertaken by the organization are completed on time and according to specifications and are capable of achieving the needed impact. Increasingly, project leaders (PLs) who possess this expertise are being employed in academic settings to support clinical and preclinical translational research team science. Duke University’s clinical and translational science enterprise has been an early adopter of project management to support clinical and preclinical programs. We review the history and evolution of project management and the PL role at Duke, examine case studies that illustrate their growing value to our academic research environment, and address challenges and solutions to employing project management in academia. Furthermore, we describe the critical role project leadership plays in accelerating and increasing the success of translational team science and team approaches frequently required for systems biology and “big data” scientific studies. Finally, we discuss perspectives from Duke project leadership professionals regarding the training needs and requirements for PLs working in academic clinical and translational science research settings.
An oriented Woodford Shale core from the eastern Ardmore Basin was sampled to test if the shale was an open or closed system to hydrothermal fluids, and to determine the timing of alteration. Mineralized fractures are ubiquitous in the core, and the shale exhibits a complex paragenesis with multiple hydrothermal minerals, including biotite, magnesite, norsethite, gorceixite and potassium feldspar present in and around the fractures. These minerals suggest that the Woodford Shale was an open system during part of its diagenetic history. Vitrinite reflectance (Ro) measurements indicate values of ∼1.81 % (∼230 °C). Palaeomagnetic analysis reveals a characteristic remanent magnetization (ChRM) with south-southeasterly declinations and shallow inclinations that resides in magnetite. This ChRM is interpreted to be either a chemical remanent magnetization (CRM) or a thermochemical remanent magnetization (TCRM) that was acquired at 245 ± 10 Ma during Late Permian time based on the pole position (51.0° N, 115.6° E). Because the palaeomagnetic specimens show evidence of extensive hydrothermal alteration, the CRM/TCRM is interpreted to date the migration of hydrothermal fluids through the shale. The agreement in timing with other studies that report hydrothermal alteration in southern Oklahoma and the Ouachita Mountains in Late Permian time, suggest that there were post-collisional fluid-flow events which accessed reservoirs of warm fluids.
Maternal mental health during pregnancy and postpartum predicts later emotional and behavioural problems in children. Even though most perinatal mental health problems begin before pregnancy, the consequences of preconception maternal mental health for children's early emotional development have not been prospectively studied.
We used data from two prospective Australian intergenerational cohorts, with 756 women assessed repeatedly for mental health problems before pregnancy between age 13 and 29 years, and during pregnancy and at 1 year postpartum for 1231 subsequent pregnancies. Offspring infant emotional reactivity, an early indicator of differential sensitivity denoting increased risk of emotional problems under adversity, was assessed at 1 year postpartum.
Thirty-seven percent of infants born to mothers with persistent preconception mental health problems were categorised as high in emotional reactivity, compared to 23% born to mothers without preconception history (adjusted OR 2.1, 95% CI 1.4–3.1). Ante- and postnatal maternal depressive symptoms were similarly associated with infant emotional reactivity, but these perinatal associations reduced somewhat after adjustment for prior exposure. Causal mediation analysis further showed that 88% of the preconception risk was a direct effect, not mediated by perinatal exposure.
Maternal preconception mental health problems predict infant emotional reactivity, independently of maternal perinatal mental health; while associations between perinatal depressive symptoms and infant reactivity are partially explained by prior exposure. Findings suggest that processes shaping early vulnerability for later mental disorders arise well before conception. There is an emerging case for expanding developmental theories and trialling preventive interventions in the years before pregnancy.
We assessed the impact of personal protective equipment (PPE) doffing errors on healthcare worker (HCW) contamination with multidrug-resistant organisms (MDROs).
Prospective, observational study.
The study was conducted at 4 adult ICUs at 1 tertiary-care teaching hospital.
HCWs who cared for patients on contact precautions for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci, or multidrug-resistant gram-negative bacilli were enrolled. Samples were collected from standardized areas of patient body, garb sites, and high-touch environmental surfaces in patient rooms. HCW hands, gloves, PPE, and equipment were sampled before and after patient interaction. Research personnel observed PPE doffing and coded errors based on CDC guidelines.
We enrolled 125 HCWs; most were nurses (66.4%) or physicians (19.2%). During the study, 95 patients were on contact precautions for MRSA. Among 5,093 cultured sites (HCW, patient, environment), 652 (14.7%) yielded the target MDRO. Moreover, 45 HCWs (36%) were contaminated with the target MDRO after patient interactions, including 4 (3.2%) on hands and 38 (30.4%) on PPE. Overall, 49 HCWs (39.2%) made multiple doffing errors and were more likely to have contaminated clothes following a patient interaction (risk ratio [RR], 4.69; P = .04). All 4 HCWs with hand contamination made doffing errors. The risk of hand contamination was higher when gloves were removed before gowns during PPE doffing (RR, 11.76; P = .025).
When caring for patients on CP for MDROs, HCWs appear to have differential risk for hand contamination based on their method of doffing PPE. An intervention as simple as reinforcing the preferred order of doffing may reduce HCW contamination with MDROs.
OBJECTIVES/SPECIFIC AIMS: Previously, we showed decreased development of endometriotic lesions in CD44 knockout mice compared to control.(1) CD44 has 10 different variants and a standard form. Menstrual endometrial cells (MECs) from women with endometriosis have increased adhesion and also express higher levels of CD44 variant 6 (v6) than v3, compared to MECs from women without endometriosis. (2) Here, we assessed the effects of CD44 standard (CD44s), CD44v3 and CD44v6 overexpression (OE) on immortalized human endometrial epithelial (iEECs) and stroma cells (hESCs) in vivo attachment in a nude mouse xenograft model. 1. Knudtson JF, Tekmal RR, Santos MT, et al. Impaired Development of Early Endometriotic Lesions in CD44 Knockout Mice. Reproductive sciences (Thousand Oaks, Calif.). 2016;23(1):87-91. 2. Griffith JS, Liu YG, Tekmal RR, Binkley PA, Holden AE, Schenken RS. Menstrual endometrial cells from women with endometriosis demonstrate increased adherence to peritoneal cells and increased expression of CD44 splice variants. Fertility and sterility. 2010;93(6):1745-1749. METHODS/STUDY POPULATION: Overexpression of CD44s, CD44v3 and CD44v6 was carried out using lipofectamine and their expression verified with qRT-PCR in iEEC and hESCs. Nude mice, 8-10 week old, were injected with estrogen 1 week prior to injection of iEECs and hESCs (n=7 per group). The cells were counted after transfection and at least 300,000 iEECs and 300,000 hESCs were injected per mouse. The transfected cells were tagged with cell tracker red (iEECs) and green (hESCs). Forty-eight hours after injection into the xenograft, the mice were sacrificed. The cells were counted using fluorescent stereo microscopy (FSM). Percent attachment was calculated based on the number of cells visualized by FSM divided by the number of transfected cells injected. Unpaired student t-test was performed to analyze differences in the percent attachment of the cells. RESULTS/ANTICIPATED RESULTS: The majority of cells were attached to the peritoneum. There was increased attachment of hESCs with OE of CD44v6 compared to control (p=0.03). CD44v6 OE did not change attachment of iEECs. There was no difference in attachment in iEECs or hESCs with OE of CD44s or CD44v3. DISCUSSION/SIGNIFICANCE OF IMPACT: Overexpression of CD44v6 increases attachment of ESCs to PMCs in an in vivo xenograft model. Menstrual endometrial cell type and CD44 variants play a complex role in the development of the early endometriotic lesion.
Medical procedures and patient care activities may facilitate environmental dissemination of healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus (MRSA).
Observational cohort study of MRSA-colonized patients to determine the frequency of and risk factors for environmental shedding of MRSA during procedures and care activities in carriers with positive nares and/or wound cultures. Bivariate analyses were performed to identify factors associated with environmental shedding.
A Veterans Affairs hospital.
This study included 75 patients in contact precautions for MRSA colonization or infection.
Of 75 patients in contact precautions for MRSA, 55 (73%) had MRSA in nares and/or wounds and 25 (33%) had positive skin cultures. For the 52 patients with MRSA in nares and/or wounds and at least 1 observed procedure, environmental shedding of MRSA occurred more frequently during procedures and care activities than in the absence of a procedure (59 of 138, 43% vs 8 of 83, 10%; P < .001). During procedures, increased shedding occurred ≤0.9 m versus >0.9 m from the patient (52 of 138, 38% vs 25 of 138, 18%; P = .0004). Contamination occurred frequently on surfaces touched by personnel (12 of 38, 32%) and on portable equipment used for procedures (25 of 101, 25%). By bivariate analysis, the presence of a wound with MRSA was associated with shedding (17 of 29, 59% versus 6 of 23, 26%; P = .04).
Environmental shedding of MRSA occurs frequently during medical procedures and patient care activities. There is a need for effective strategies to disinfect surfaces and equipment after procedures.
Posttraumatic stress disorder (PTSD) is associated with higher risk of incident hypertension, but it is unclear whether specific aspects of PTSD are particularly cardiotoxic. PTSD is a heterogeneous disorder, comprising dimensions of fear and dysphoria. Because elevated fear after trauma may promote autonomic nervous system dysregulation, we hypothesized fear would predict hypertension onset, and associations with hypertension would be stronger with fear than dysphoria.
We examined fear and dysphoria symptom dimensions in relation to incident hypertension over 24 years in 2709 trauma-exposed women in the Nurses’ Health Study II. Posttraumatic fear and dysphoria symptom scores were derived from a PTSD diagnostic interview. We used proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for each symptom dimension (quintiles) with new-onset hypertension events (N = 925), using separate models. We also considered lower-order symptom dimensions of fear and dysphoria.
Higher levels of fear (P-trend = 0.02), but not dysphoria (P-trend = 0.22), symptoms were significantly associated with increased hypertension risk after adjusting for socio-demographics and family history of hypertension. Women in the highest v. lowest fear quintile had a 26% higher rate of developing hypertension [HR = 1.26 (95% CI 1.02–1.57)]; the increased incidence associated with greater fear was similar when further adjusted for biomedical and health behavior covariates (P-trend = 0.04) and dysphoria symptoms (P-trend = 0.04). Lower-order symptom dimension analyses provided preliminary evidence that the re-experiencing and avoidance components of fear were particularly associated with hypertension.
Fear symptoms associated with PTSD may be a critical driver of elevated cardiovascular risk in trauma-exposed individuals.
Childhood adversity can negatively impact development across various domains, including physical and mental health. Adverse childhood experiences have been linked to aggression and substance use; however, developmental pathways to explain these associations are not well characterized. Understanding early precursors to later problem behavior and substance use can inform preventive interventions. The aim of the current study was to examine neurobiological pathways through which childhood adversity may lead to early adolescent problem behavior and substance use in late adolescence by testing two prospective models. Our first model found that early adolescent externalizing behavior mediates the association between childhood adversity and alcohol, cigarette, and marijuana use in late adolescence. Our second model found that activation in the anterior cingulate cortex (ACC) during an inhibitory control task mediates the association between childhood adversity and early adolescent externalizing behavior, with lower ACC activation associated with higher levels of adversity and more externalizing behavior. Together these findings indicate that the path to substance use in late adolescence from childhood adversity may operate through lower functioning in the ACC related to inhibitory control and externalizing behavior. Early life stressors should be considered an integral component in the etiology and prevention of early and problematic substance use.
Alteplase is an effective treatment for ischaemic stroke patients, and it is widely available at all primary stroke centres. The effectiveness of alteplase is highly time-dependent. Large tertiary centres have reported significant improvements in their door-to-needle (DTN) times. However, these same improvements have not been reported at community hospitals.
Red Deer Regional Hospital Centre (RDRHC) is a community hospital of 370 beds that serves approximately 150,000 people in their acute stroke catchment area. The RDRHC participated in a provincial DTN improvement initiative, and implemented a streamlined algorithm for the treatment of stroke patients. During this intervention period, they implemented the following changes: early alert of an incoming acute stroke patient to the neurologist and care team, meeting the patient immediately upon arrival, parallel work processes, keeping the patient on the Emergency Medical Service stretcher to the CT scanner, and administering alteplase in the imaging area. Door-to-needle data were collected from July 2007 to December 2017.
A total of 289 patients were treated from July 2007 to December 2017. In the pre-intervention period, 165 patients received alteplase and the median DTN time was 77 minutes [interquartile range (IQR): 60–103 minutes]; in the post-intervention period, 104 patients received alteplase and the median DTN time was 30 minutes (IQR: 22–42 minutes) (p < 0.001). The annual number of patients that received alteplase increased from 9 to 29 in the pre-intervention period to annual numbers of 41 to 63 patients in the post-intervention period.
Community hospitals staffed with community neurologists can achieve median DTN times of 30 minutes or less.
Abnormal thyroid function is prevalent among women and has been linked to increased risk of chronic disease. Posttraumatic stress disorder (PTSD) has been linked to thyroid dysfunction in some studies; however, the results have been inconsistent. Thus, we evaluated trauma exposure and PTSD symptoms in relation to incident thyroid dysfunction in a large longitudinal cohort of civilian women.
We used data from 45 992 women from the ongoing Nurses’ Health Study II, a longitudinal US cohort study that began in 1989. In 2008, history of trauma and PTSD were assessed with the Short Screening Scale for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, PTSD, and incident thyroid dysfunction was determined by participants’ self-report in biennial questionnaires of physician-diagnosed hypothyroidism and Graves’ hyperthyroidism. The study period was from 1989 to 2013. Proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) for incident hypothyroidism and Graves’ hyperthyroidism.
In multivariable-adjusted models, we found significant associations for PTSD only with hypothyroidism [p-trend <0.001; trauma with no PTSD symptoms, 1.08 (95% CI 1.02–1.15); 1–3 PTSD symptoms, 1.12 (95% CI 1.04–1.21); 4–5 PTSD symptoms, 1.23 (95% CI 1.13–1.34); and 6–7 PTSD symptoms, 1.26 (95% CI 1.14–1.40)]. PTSD was not associated with risk of Graves’ hyperthyroidism (p-trend = 0.34). Associations were similar in sensitivity analyses restricted to outcomes with onset after 2008, when PTSD was assessed.
PTSD was associated with higher risk of hypothyroidism in a dose-dependent fashion. Highlighted awareness for thyroid dysfunction may be especially important in women with PTSD.
In 2017, dicamba-resistant (DR) soybean was commercially available to farmers in the United States. In August and September of 2017, a survey of 312 farmers from 60 Nebraska soybean-producing counties was conducted during extension field days or online. The objective of this survey was to understand farmers’ adoption and perceptions regarding DR soybean technology in Nebraska. The survey contained 16 questions and was divided in three parts: (1) demographics, (2) dicamba application in DR soybean, and (3) dicamba off-target injury to sensitive soybean cultivars. According to the results, 20% of soybean hectares represented by the survey were planted to DR soybean in 2017, and this number would probably double in 2018. Sixty-five percent of survey respondents own a sprayer and apply their own herbicide programs. More than 90% of respondents who adopted DR soybean technology reported significant improvement in weed control. Nearly 60% of respondents used dicamba alone or glyphosate plus dicamba for POST weed control in DR soybean; the remaining 40% added an additional herbicide with an alternative site of action (SOA) to the POST application. All survey respondents used one of the approved dicamba formulations for application in DR soybean. Survey results indicated that late POST dicamba applications (after late June) were more likely to result in injury to non-DR soybean compared to early POST applications (e.g., May and early June) in 2017. According to respondents, off-target dicamba movement resulted both from applications in DR soybean and dicamba-based herbicides applied in corn. Although 51% of respondents noted dicamba injury on non-DR soybean, 7% of those who noted injury filed an official complaint with the Nebraska Department of Agriculture. Although DR soybean technology allowed farmers to achieve better weed control during 2017 than previous growing seasons, it is apparent that off-target movement and resistance management must be addressed to maintain the viability and effectiveness of the technology in the future.
Objectives: To examine academic performance in dystrophinopathy as a function of dystrophin gene mutation position as well as intellectual function, executive skills, socioeconomic status (SES), behavior, and physical ability. Methods: In a cross-sectional study, boys with dystrophinopathy (ages 5–17; n=50) completed tests of academics (Woodcock-Johnson-III: spelling, reading, calculation and total scores), executive functioning (selective attention/inhibitory control, set shifting, working memory, and processing speed), single word comprehension and nonverbal reasoning. Motor skills were assessed and parents provided demographic information and child behavioral assessments. Dystrophin gene mutation positions were dichotomized into groups (upstream versus downstream of exon 43, location of isoforms previously linked to intellectual impairment). Genetic mutation groups were compared on measures of academic achievement, and multiple regression analyses examined unique and joint contributions of executive skills, intelligence quotient (IQ), SES, motor abilities, behavior, and mutation positions to academic outcomes. Results: Academic performance was slightly, yet significantly, lower than IQ and varied as a function of dystrophin gene position, wherein boys possessing the downstream mutation exhibited greater impairment than boys with the upstream mutation. Digit span forward (indexing verbal span), but no other measure of executive function, contributed significant variance to total academic achievement, spelling and calculation. Conclusions: Weak academic performance is associated with dystrophinopathy and is more common in downstream mutations. A specific deficit in verbal span may underlie inefficiencies observed in children with dystrophinopathy and may drive deficits impacting academic abilities. (JINS, 2018, 24, 928–938)
Children of alcoholics (COAs) are at risk for elevated internalizing and externalizing symptoms. Yet, little is known about the familial and behavioral adjustments of COAs following parental separation. Using an ecological–transactional framework, we examined how multiple risk factors contributed to the formation of different alcoholic family structures and how living in heterogeneous family structures affected COAs’ behavioral problems. The Michigan Longitudinal Study, a multiwave study on initially intact alcoholic and control families with preschool-age children (n = 503), was used to evaluate outcomes of offspring, when families either remained intact or were separated when the child was aged 12–14. Alcoholic families who later transitioned into stepfamilies were characterized with higher paternal antisociality, marital aggression, and serious family crises than alcoholic families that remained intact. COAs in stepfamilies (but not in single-parent families) exhibited higher levels of internalizing and externalizing symptoms in preadolescence compared with those in alcoholic intact families, in part because of elevated behavioral risk at age 3. Structural equation modeling indicated that the aggregated risk of stepfamily residence directly related to COAs’ internalizing and indirectly related to COAs’ externalizing problems, partially mediated by family stressors. Findings suggest targeting COAs in separated families for early intervention.