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The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
Identifying risk factors of individuals in a clinical-high-risk state for psychosis are vital to prevention and early intervention efforts. Among prodromal abnormalities, cognitive functioning has shown intermediate levels of impairment in CHR relative to first-episode psychosis and healthy controls, highlighting a potential role as a risk factor for transition to psychosis and other negative clinical outcomes. The current study used the AX-CPT, a brief 15-min computerized task, to determine whether cognitive control impairments in CHR at baseline could predict clinical status at 12-month follow-up.
Baseline AX-CPT data were obtained from 117 CHR individuals participating in two studies, the Early Detection, Intervention, and Prevention of Psychosis Program (EDIPPP) and the Understanding Early Psychosis Programs (EP) and used to predict clinical status at 12-month follow-up. At 12 months, 19 individuals converted to a first episode of psychosis (CHR-C), 52 remitted (CHR-R), and 46 had persistent sub-threshold symptoms (CHR-P). Binary logistic regression and multinomial logistic regression were used to test prediction models.
Baseline AX-CPT performance (d-prime context) was less impaired in CHR-R compared to CHR-P and CHR-C patient groups. AX-CPT predictive validity was robust (0.723) for discriminating converters v. non-converters, and even greater (0.771) when predicting CHR three subgroups.
These longitudinal outcome data indicate that cognitive control deficits as measured by AX-CPT d-prime context are a strong predictor of clinical outcome in CHR individuals. The AX-CPT is brief, easily implemented and cost-effective measure that may be valuable for large-scale prediction efforts.
As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
The efficient and effective movement of research into practice is acknowledged as crucial to improving population health and assuring return on investment in healthcare research. The National Center for Advancing Translational Science which sponsors Clinical and Translational Science Awards (CTSA) recognizes that dissemination and implementation (D&I) sciences have matured over the last 15 years and are central to its goals to shift academic health institutions to better align with this reality. In 2016, the CTSA Collaboration and Engagement Domain Task Force chartered a D&I Science Workgroup to explore the role of D&I sciences across the translational research spectrum. This special communication discusses the conceptual distinctions and purposes of dissemination, implementation, and translational sciences. We propose an integrated framework and provide real-world examples for articulating the role of D&I sciences within and across all of the translational research spectrum. The framework’s major proposition is that it situates D&I sciences as targeted “sub-sciences” of translational science to be used by CTSAs, and others, to identify and investigate coherent strategies for more routinely and proactively accelerating research translation. The framework highlights the importance of D&I thought leaders in extending D&I principles to all research stages.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
Cardiopulmonary exercise testing has been used to measure functional capacity in children who have undergone a heart transplant. Cardiopulmonary exercise testing results have not been compared between children transplanted for a primary diagnosis of CHD and those with a primary diagnosis of cardiomyopathy despite differences in outcomes. This study is aimed to compare cardiopulmonary exercise testing performance between these two groups.
Patients who underwent heart transplant with subsequent cardiopulmonary exercise testing at least 6 months after transplant at our institution were identified. They were then divided into two groups based on primary cardiac diagnosis: CHD or cardiomyopathy. Patient characteristics, echocardiograms, cardiac catheterisations, outcomes, and cardiopulmonary exercise test results were compared between the two groups.
From the total of 35 patients, 15 (43%) had CHD and 20 (57%) had cardiomyopathy. Age at transplant, kidney disease, lung disease, previous rejection, coronary vasculopathy, catheterisation, and echocardiographic data were similar between the groups. Mean time from transplant to cardiopulmonary exercise testing, exercise duration, and maximum oxygen consumption were similar in both groups. There was a difference in heart rate response with CHD heart rate response of 63 beats per minute compared to cardiomyopathy group of 78 (p = 0.028). Patients with CHD had more chronotropic incompetence than those with cardiomyopathy (p = 0.036).
Primary diagnosis of CHD is associated with abnormal heart rate response and more chronotropic incompetence compared to those transplanted for cardiomyopathy.
The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.
The Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI) are the most frequently used observer-rated and self-report scales of depression, respectively. It is important to know what a given total score or a change score from baseline on one scale means in relation to the other scale.
We obtained individual participant data from the randomised controlled trials of psychological and pharmacological treatments for major depressive disorders. We then identified corresponding scores of the HAMD and the BDI (369 patients from seven trials) or the BDI-II (683 patients from another seven trials) using the equipercentile linking method.
The HAMD total scores of 10, 20 and 30 corresponded approximately with the BDI scores of 10, 27 and 42 or with the BDI-II scores of 13, 32 and 50. The HAMD change scores of −20 and −10 with the BDI of −29 and −15 and with the BDI-II of −35 and −16.
The results can help clinicians interpret the HAMD or BDI scores of their patients in a more versatile manner and also help clinicians and researchers evaluate such scores reported in the literature or the database, when scores on only one of these scales are provided. We present a conversion table for future research.
We describe the motivation and design details of the ‘Phase II’ upgrade of the Murchison Widefield Array radio telescope. The expansion doubles to 256 the number of antenna tiles deployed in the array. The new antenna tiles enhance the capabilities of the Murchison Widefield Array in several key science areas. Seventy-two of the new tiles are deployed in a regular configuration near the existing array core. These new tiles enhance the surface brightness sensitivity of the array and will improve the ability of the Murchison Widefield Array to estimate the slope of the Epoch of Reionisation power spectrum by a factor of ∼3.5. The remaining 56 tiles are deployed on long baselines, doubling the maximum baseline of the array and improving the array u, v coverage. The improved imaging capabilities will provide an order of magnitude improvement in the noise floor of Murchison Widefield Array continuum images. The upgrade retains all of the features that have underpinned the Murchison Widefield Array’s success (large field of view, snapshot image quality, and pointing agility) and boosts the scientific potential with enhanced imaging capabilities and by enabling new calibration strategies.
Patient expectancy is an important source of placebo effects in antidepressant clinical trials, but all prior studies measured expectancy prior to the initiation of medication treatment. Little is known about how expectancy changes during the course of treatment and how such changes influence clinical outcome. Consequently, we undertook the first analysis to date of in-treatment expectancy during antidepressant treatment to identify its clinical and demographic correlates, typical trajectories, and associations with treatment outcome.
Data were combined from two randomized controlled trials of antidepressant medication for major depressive disorder in which baseline and in-treatment expectancy assessments were available. Machine learning methods were used to identify pre-treatment clinical and demographic predictors of expectancy. Multilevel models were implemented to test the effects of expectancy on subsequent treatment outcome, disentangling within- and between-patient effects.
Random forest analyses demonstrated that whereas more severe depressive symptoms predicted lower pre-treatment expectancy, in-treatment expectancy was unrelated to symptom severity. At each measurement point, increased in-treatment patient expectancy significantly predicted decreased depressive symptoms at the following measurement (B = −0.45, t = −3.04, p = 0.003). The greater the gap between expected treatment outcomes and actual depressive severity, the greater the subsequent symptom reductions were (B = 0.49, t = 2.33, p = 0.02).
Greater in-treatment patient expectancy is associated with greater subsequent depressive symptom reduction. These findings suggest that clinicians may benefit from monitoring and optimizing patient expectancy during antidepressant treatment. Expectancy may represent another treatment parameter, similar to medication compliance and side effects, to be regularly monitored during antidepressant clinical management.
Silvery-Thread Moss (Bryum argenteum Hedw.) is an undesirable invader of golf course putting greens across North America, establishing colonies and proliferating despite practices to suppress it. The goal was to grow genotypes of green (growing in putting greens) and native (growing in habitats outside of putting greens) B. argenteum in a common garden experiment, allowing an experimental test of life-history traits between genotypes from these two habitats. Seventeen collections of green and 17 collections of native B. argenteum were cloned to single genotypes and raised through a minimum of two asexual generations in the lab. A culture of each genotype was initiated using a single detached shoot apex and was allowed to grow for 6 mo under conditions of inorganic nutrients present and absent. Compared with genotypes from native habitats, genotypes of B. argenteum from putting greens exhibited earlier shoot regeneration and shoot induction, faster protonemal extension, longer (higher) shoots, lower production of gemmae and bulbils, and greater aerial rhizoid cover, and showed similar tendencies of chlorophyll fluorescence properties and chlorophyll content. Cultures receiving no inorganic nutrients produced less chlorophyll content, greatly reduced growth, and bleaching of shoots. Mosses from putting greens establish more quickly, grow faster, produce more abundant rhizoids, and yet do not produce as many specialized asexual propagules compared with mosses of the same species from native habitats. The highly managed putting green environment has either selected for a suite of traits that allow the moss to effectively compete with grasses, or genotypic diversity is very high in this species, allowing a set of specialized genotypes to colonize the putting green from native habitats. Successful golf course weeds have been able to adapt to this highly competitive environment by selection acting on traits or genotypes to produce plants more successful in competing with golf course grasses.
The Texas red beds represent one of the richest series of early Permian deposits in the world. In particular, the Clear Fork Group has produced a diverse assemblage of temnospondyls, early reptiles, and synapsids. However, most of this material has been sourced from the oldest member, the Arroyo Formation, and the understanding of the paleoecosystem of the younger Vale and Choza formations is less well resolved. Here we present a previously undescribed Vale locality, the first vertebrate-bearing locality from the formation to be described in detail in several decades, from near Abilene, Texas with juvenile diplocaulids, captorhinids, abundant material of rare taxa such as Varanops and diadectids, and the first report of a recumbirostran ‘microsaur’ from the formation. This assemblage is atypical of early Permian deposits in the taxonomic and size distribution of the vertebrate fauna in comparison to other localities from the Vale Formation that preserve a greater abundance of aquatic taxa (e.g., fishes, Trimerorhachis) and synapsids (e.g., Dimetrodon). Minimal abrasion of the elements, relative articulation and association of the specimen of Varanops, and the paucity of aquatic taxa suggest an ephemeral pond deposit in which organisms were preserved essentially in situ. Our characterization of the locality also permits a revision and discussion of the vertebrate faunal assemblage of the Vale Formation.
Germanium is a small-gap semiconductor that efficiently absorbs visible light, resulting in photoexcited electrons predicted to be sufficiently energetic to reduce H2O for H2 gas evolution. In order to protect the surface from corrosion and prevent surface charge recombination in contact with aqueous pH 7 electrolyte, we grew epitaxial SrTiO3 layers of different thicknesses on p-Ge (001) surfaces. Four-nanometer SrTiO3 allows photogenerated electrons to reach the surface and evolve H2 gas, while 13 nm SrTiO3 blocks these electrons. Ambient pressure x-ray photoelectron spectroscopy indicates that the surface readily dissociates H2O to form OH species, which may impact surface band bending.
Evening-dosed DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, was designed to provide efficacy upon awakening and through the evening. The objective was to evaluate whether treatment with DR/ER-MPH in children with attention-deficit/hyperactivity disorder (ADHD): (1) improves caregiver-rated ADHD symptoms, and (2) reduces caregiver strain, versus placebo.
Caregiver-rated ADHD symptoms (Conners’ Global Index–Parent [CGI-P]) and caregiver strain (Caregiver Strain Questionnaire [CGSQ]) were assessed as secondary endpoints following 3 weeks of treatment in a randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) with ADHD (NCT02520388). Using the 10-item CGI-P, parents rated their child’s ADHD symptoms on a 4-point scale (0=never/seldom; 3=very often/frequently). Caregivers also rated the impact of caring for a child with emotional and behavioral challenges on the 21-item CGSQ (5-point scale: 1=not at all; 5=very much). A reduction on individual item and total scores for both measures indicated an improvement.
Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose after 3 weeks of treatment was 68.1 mg. Mean CGI-P scores at baseline and CGSQ scores at screening (ie, before washout of prior ADHD therapy) were comparable for both DR/ER-MPH (CGI-P: 22.8, CGSQ: 54.5) and placebo (CGI-P: 21.8; CGSQ: 54.9) groups. After 3 weeks of treatment, caregivers of children onDR/ER-MPH reported significant reductions in CGI-P scores versus those on placebo (least-squares [LS] mean: 12.3 vs 17.4; P<0.001). Additionally, there was a significant reduction in CGSQ scores after 3 weeks of treatment with DR/ER-MPH versus placebo (LS mean: 41.2 vs 49.1; P<0.001). Post hoc analyses on the effect of DR/ER-MPHversus placebo on individual items of CGI-P and CGSQ, and the two subscales of CGI-P will be presented. No serious TEAEs were reported and all TEAEs were consistent with those of MPH.
Caregivers reported significant improvements in their child’s ADHD symptoms and these improvements coincided with reductions in caregiver strain after 3 weeks of treatment on evening-dosed DR/ER-MPH versus placebo.
In a phase 3 trial of children with ADHD, DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, improved ADHD symptoms and reduced at-home early morning and late afternoon/evening functional impairments versus placebo, as measured by the validated Parent Rating of Evening andMorning Behaviors-Revised, Morning (PREMB-R AM) and Evening (PREMB-R PM) subscales. This post hoc analysis evaluated the effect of DR/ER-MPH versus placebo onindividual PREMB-R AM/PM item scores.
Data were analyzed from a pivotal, randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) withADHD (NCT02520388). Using the 3-item PREMB-R AM and 8-item PREMB-R PM, both key secondary endpoints, investigators evaluated early morning and lateafternoon/evening functional impairment by scoring each item on a severity scale from 0 (none) to 3 (a lot). For post hoc analyses, treatment comparisons between DR/ER-MPH and placebo at endpoint were determined by using least squares mean changes from baseline on individual PREMB-R AM/PM items score derived from an analysis ofcovariance (ANCOVA) model with treatment as the main effect, and study center and baseline score as covariates.
Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose achieved after 3 weeks of treatment was 68.1 mg. Following 3 weeks of treatment, DR/ER-MPH significantly reduced mean individual item scores from baseline versus placebo on all PREMB-R AM items (all P≤0.002; “getting out of bed”, “getting ready”, and “arguing or struggling in the morning”). Additionally, DR/ER-MPH significantly reduced mean individual item scores from baseline on 5 out of 8 PREMB-R PM items (P<0.01 in 2 items [“sitting through dinner” and “playing quietly”] and P<0.05 in 3 items [“inattentive/distractible”, “transitioning between activities”, and “settling down/getting ready for bed”]). There was a trend towards a reduction on 2 other items of the PREMB-R PM (P<0.09). Distributions of the ratings for each item will be presented. No serious TEAEs were reported; TEAEs were consistent withmethylphenidate.
Post hoc analyses revealed that DR/ER-MPH significantly reduced all PREMB-R AM item scores, including “getting out of bed”, and many PREMB-R PM items, including “getting ready for bed” in children with ADHD. These findings are worth further exploration.
In a phase 3 trial of children with attention-deficit/hyperactivity disorder (ADHD), DR/ER-MPH (formerly HLD200), a delayed-release and extended-release methylphenidate, improved ADHD symptoms and reduced at-home early morning and late afternoon/evening functional impairment versus placebo. The validated Before School Functioning Questionnaire (BSFQ), a key secondary endpoint, was used to measure early morning functional (EMF) impairment. This post hoc analysis evaluated the effect of DR/ER-MPH versus placebo on individual BSFQ item scores from baseline.
Data were analyzed from a pivotal, randomized, double-blind, multicenter, placebo-controlled, parallel-group, phase 3 trial of DR/ER-MPH in children (6-12 years) withADHD (NCT02520388). Using the 20-item BSFQ, investigators evaluated EMF impairment by scoring each item on a severity scale of 0 to 3, with 0 denoting “no impairment” and 3 denoting “severe impairment”. For post hoc analyses, treatment comparisons between DR/ER-MPH and placebo at endpoint were determined by using least squares mean changes from baseline on individual BSFQ items score derived from an analysis of covariance (ANCOVA) model with treatment as the main effect, and study center and baseline score as covariates.
Of 163 children enrolled across 22 sites, 161 were included in the intent-to-treat population (DR/ER-MPH, n=81; placebo, n=80) and 138 completed the study. The mean DR/ER-MPH dose achieved after 3 weeks of treatment was 68.1 mg. Following 3 weeks of treatment, DR/ER-MPH significantly reduced mean BSFQ item scores frombaseline on 18 out of 20 items versus placebo (P<0.001 in 8 items [listening, following directions, attention, forgetfulness, talkativeness, silliness, time awareness, getting to school]; P<0.01 in 7 items [overall organization, being quiet, distraction, interrupt/blurt out, breakfast, hygiene, independence]; P<0.05 in 3 items [procrastination, hyperactivity, awaiting turn]). Only “dressing” and “misplacing/losing items” showed no significant between-group differences (P=0.171 and P=0.175, respectively). Distributions of the severity ratings for each item will be presented. No serious TEAEs were reported; TEAEs were consistent with methylphenidate.
Post hoc analyses revealed that DR/ER-MPH significantly reduced 18 out of 20 individual BSFQ item scores versus placebo in children with ADHD. These findings are worth further exploration.
Child maltreatment is a significant public health issue in the United States. Yet, fewer than half of pediatricians discuss behavioral, developmental, or parenting issues with parents.
This paper describes the testing of bundles of tools and processes, part of a larger intervention, Practicing Safety, targeted at changing physician and staff behavior to identify families at risk for child maltreatment, provide anticipatory guidance, refer to community resources, and follow-up and track at-risk families. The intervention was implemented with 14 pediatric primary care practices throughout the United States; the study was completed in 2011.
A within-subjects repeated measures pre-post follow-up design was used to evaluate the intervention. Baseline and repeated measurements of pediatric practices’ processes were collected using qualitative and quantitative methods. In total, 14 core improvement teams from across the country tested three bundles of tools (maternal, infant, toddler) within a quality improvement framework over seven months.
Quantitative results showed statistically significant adoption of tools and processes and enhancement of practice behaviors and office environmental supports. The increase in tool use was immediate and was sustained for six months after implementation. Qualitative data provided insight as to how meaningful the intervention was to the core improvement teams, especially with more complicated behaviors (eg, engaging social workers or community agencies for referrals). Barriers included lack of community resources. Findings showed unanticipated outcomes such as helping practices to become medical homes.
Lessons learned included that practices appreciate and can adopt brief interventions that have meaningful and useful tools and process to enhance psychosocial care for children 0–3 and that do not place a burden on pediatric practice. An innovative, quality improvement strategy, intuitive to pediatricians, with a brief intervention may help prevent child maltreatment.