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The spatial distribution of basal water critically impacts the evolution of ice sheets. Current estimates of basal water distribution beneath the Greenland Ice Sheet (GrIS) contain large uncertainties due to poorly constrained boundary conditions, primarily from geothermal heat flux (GHF). The existing GHF models often contradict each other and implementing them in numerical ice-sheet models cannot reproduce the measured temperatures at ice core locations. Here we utilize two datasets of radar-detected basal water in Greenland to constrain the GHF at regions with a thawed bed. Using the three-dimensional ice-sheet model SICOPOLIS, we iteratively adjust the GHF to find the minimum GHF required to reach the bed to the pressure melting point, GHFpmp, at locations of radar-detected basal water. We identify parts of the central-east, south and northwest Greenland with significantly high GHFpmp. Conversely, we find that the majority of low-elevation regions of west Greenland and parts of northeast have very low GHFpmp. We compare the estimated constraints with the available GHF models for Greenland and show that GHF models often do not honor the estimated constraints. Our results highlight the need for community effort to reconcile the discrepancies between radar data, GHF models, and ice core information.
OBJECTIVES/SPECIFIC AIMS: The Johns Hopkins University Clinicaltrials.gov (CT.gov) Program has previously reported on a study showing reduction of “Late Results – per FDAAA” from 111 to 0. What we hope to do here is to focus on non-late results records. Over the years, some institutions spend their efforts solely on late results in order to avoid any penalties from the Food and Drug Administration (FDA). However, there are a number of variables that labels “problem records” within the Protocol and Registration System (PRS). These records are also subject to penalties. Our goal has been to minimize problem records and establish processes to improve and maintain our institutional compliance in regards to regulations governing clinical trials registration and results reporting. METHODS/STUDY POPULATION: The Johns Hopkins University implemented a Clinicaltrials.gov program solely mandated to assist Principal Investigators (PIs) and other study team members with clinical trial registration and results reporting. The program has developed processes in its duty towards reducing problem records in the PRS. Full-time staff have been assigned to assist research teams with registration and results reporting, while ensuring compliance with all relevant regulations. Several methods have been utilized to track metrics, such as monthly reports and internal databases. Features within the PRS have also been used to draw attention to newly-identified problem records on a daily basis in order to rectify these issues with the study team promptly. In order to ensure compliance, our office communicates with study teams regarding the problems within their CT.gov record that requires attention. In challenging cases, our program will also collaborate with the CT.gov PRS Team at the NIH to facilitate the process and avoid multiple review cycles, which can delay registration or the posting of results. Our Program has also formed internal collaborations with the Institutional Review Board (IRB) which allows us to verify study status and view active study team members. This is especially useful in cases where the study team members who are listed on the CT.gov record cannot be reached or the contact information is outdated (a common occurrence with older studies). With access in the IRB, we can contact the current study team members who may not be listed in CT.gov and assist them to resolve any outstanding issues of non-compliance within their CT.gov record. RESULTS/ANTICIPATED RESULTS: From September 2015 (before our program was established) to September 2016 (three months after the institution of our program), the total amount of problem records increased from 44% (339/774) to 45% (383/852). Since then, the processes we have developed resulted in a decline in problem records to 30% (282/955) in September 2017, and a further decline to 8% (83/1075) as of September 2018. The short rise that was observed in 2016, was a potential indicator that if our program was not instituted, it would have been more difficult to maintain compliance. DISCUSSION/SIGNIFICANCE OF IMPACT: According to the FDA Draft Guidance released in September 2018 referring to the Civil Money Penalties Relating to the ClinicalTrials.gov Data Bank, there are a number of ways to violate the FDA regulations, resulting in potential monetary penalties, which include “failing to submit required clinical trial information or submitting clinical trial information that is false or misleading”. These regulations apply to results as well as registration and study status updates. By paying attention to all problems that are identified by the PRS, institutions can rectify errors and remain complaint with all regulations that govern clinical trial registration and results reporting.
22q11.2 deletion syndrome (22q11DS), one of the most common recurrent copy number variant disorders, is associated with dopaminergic abnormalities and increased risk for psychotic disorders.
Given the elevated prevalence of substance use and dopaminergic abnormalities in non-deleted patients with psychosis, we investigated the prevalence of substance use in 22q11DS, compared with that in non-deleted patients with psychosis and matched healthy controls.
This cross-sectional study involved 434 patients with 22q11DS, 265 non-deleted patients with psychosis and 134 healthy controls. Psychiatric diagnosis, full-scale IQ and COMT Val158Met genotype were determined in the 22q11DS group. Substance use data were collected according to the Composite International Diagnostic Interview.
The prevalence of total substance use (36.9%) and substance use disorders (1.2%), and weekly amounts of alcohol and nicotine use, in patients with 22q11DS was significantly lower than in non-deleted patients with psychosis or controls. Compared with patients with 22q11DS, healthy controls were 20 times more likely to use substances in general (P < 0.001); results were also significant for alcohol and nicotine use separately. Within the 22q11DS group, there was no relationship between the prevalence of substance use and psychosis or COMT genotype. Male patients with 22q11DS were more likely to use substances than female patients with 22q11DS.
The results suggest that patients with 22q11DS are at decreased risk for substance use and substance use disorders despite the increased risk of psychotic disorders. Further research into neurobiological and environmental factors involved in substance use in 22q11DS is necessary to elucidate the mechanisms involved.
Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness.
Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated.
Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated?
Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD.
The thermal state at the bed of a large ice sheet is a critical boundary condition governing its future evolution. Radar surveys provide an opportunity for direct but remote observation of the ice-sheet bed, and therefore offer a means of constraining numerical ice-sheet models at the ice–bed interface. Here we have processed results of radar surveys of the Greenland Ice Sheet undertaken by the Program for Arctic Regional Climate Assessment (PARCA) between 1999 and 2003, to explore this opportunity. We consider the robustness of the measurements in the context of uncertain dielectric losses in the ice sheet, concluding that the observed radar signal characteristics reflect the character of the bed itself rather than that of uncertain englacial absorption. However, the identification of thaw is restricted to areas where subglacial water has sufficient depth to influence the radar reflection. We derive a map of inferred areas of subglacial thaw, and compare our results with other studies predicting regions with temperate bed. We show that in many areas the radar inferences of ponded water lie within areas predicted to be thawed by modelling and radiostratigraphy. There is clear disagreement in certain areas, suggesting the presence of high geothermal flux anomalies.
In this Article I focus on the use of force in self-defense by United Nations peacekeepers that are members of military contingents. This is an important matter because the use of force in self-defense remains the foundation for the use of force in all United Nations peace operations—including aggressive or robust peacekeeping.
This study explored the subjective experiences of rehabilitation services undergraduate students in a short-term job shadowing experience. Experiential reflections of 61 undergraduate rehabilitation services students (females = 91 per cent, age range 18–22 for 77.5 per cent of sample) from a midsized state university in the USA with a brief job shadowing assignment were gathered utilising reflection journals and analysed through Interpretative Phenomenological Analysis. Four interrelated themes emerged: encouragement to enter case management professions, field experience based definition of case management, appreciation of time management in case manager role, and application of related course material learned in the classroom. Results from the study suggest a brief job shadowing experience does improve students’ career exploration, understanding of aspects of a typical career for undergraduate rehabilitation graduates, and how to connect course material to the field.
Second language (L2) research relies heavily and increasingly on ANOVA (analysis of variance)-based results as a means to advance theory and practice. This fact alone should merit some reflection on the utility and value of ANOVA. It is possible that we could use this procedure more appropriately and, as argued here, other analyses such as multiple regression may prove to be more illuminating in certain research contexts. We begin this article with an overview of problems associated with ANOVA; some of them are inherent to the procedure, and others are tied to the way it is applied in L2 research. We then present three rationales for when researchers might turn to multiple regression in place of ANOVA. Output from ANOVA and multiple regression analyses based on published and mock-up studies are used to illustrate major points.
The use of assessment tools has been shown to improve the inter-rater reliability of capacity assessments. However, instrument-based capacity assessments of people with dementia face challenges. In dementia research, measuring capacity with instruments like the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) mostly employ hypothetical treatment vignettes that can overwhelm the abstraction capabilities of people with dementia and are thus not always suitable for this target group. The primary aim of this study was to provide a standardized real informed consent paradigm that enables the dementia-specific properties of capacity to consent to treatment in people with dementia to be identified in a real informed consent process that is both externally valid and ethically justifiable.
The sample consisted of 53 people with mild to moderate dementia and a group of 133 people without cognitive impairment. Rather than using a hypothetical treatment vignette, we used a standardized version of the MacCAT-T to assess capacity to consent to treatment with cholinesterase inhibitors in people with dementia. Inter-rater reliability, item statistics, and psychometric properties were also investigated.
Intraclass correlations (ICCs) (0.951–0.990) indicated high inter-rater reliability of the standardized real informed consent paradigm. In the dementia group, performance on different items of the MacCAT-T varied. Most people with dementia were able to express a treatment choice, and were aware of the need to take a tablet. Further information on the course of the disorder and the benefits and risks of the treatment were less understood, as was comparative reasoning regarding treatment alternatives.
The standardized real informed consent paradigm enabled us to detect dementia-specific characteristics of patients’ capacity to consent to treatment with cholinesterase inhibitors. In order to determine suitable enhanced consent procedures for this treatment, we recommend the consideration of MacCAT-T results on an item level. People with dementia seem to understand only basic information. Our data indicate that one useful strategy to enhance capacity to consent is to reduce attention and memory demands as far as possible.
Limiting the post-weaning intake of the young rabbit is known to improve its resistance to digestive disorders, whereas a degradation of its housing hygiene is assumed to have a negative impact on its health. This study aims at providing insights into the mechanism of digestive health preservation regarding both host (growth and immune response) and its symbiotic digestive microbiota. A 2×2 factorial design from weaning (day 28) to day 64 was set up: ad libitum intake or restricted intake at 70% of ad libitum, and high v. low hygiene of housing (n=105 per group). At day 36 and day 45, 15 animals/group were subcutaneously immunized with ovalbumin (OVA) to assess their specific immune response. Blood was sampled at 36, 45, 57 and 64 days of age to determine total and anti-OVA immunoglobulin type G (IgG) and haptoglobin levels. The cecal bacterial community was explored (18 per group) by 454 pyrosequencing of genes coding for the 16S ribosomal RNA, whereas cecal pH, NH3 and volatile fatty acid (VFA) concentrations were measured to characterize fermentative activity. A 30% reduction in feed intake reduced the growth by only 17% (P<0.001), and improved the feed conversion ratio by 15% (P<0.001), whereas the degradation of hygiene conditions slightly decreased the feed intake in ad libitum fed rabbits (−3.5%, P<0.02). As poor hygiene conditions did not affect weight gain, feed conversion was improved from day 42 (P<0.05). Restricted feeding led to a lower mortality between day 28 and day 40 (P=0.047), whereas degraded hygiene conditions decreased overall morbidity (7.8% v. 16.6%; P<0.01). Both a reduced intake and low hygiene conditions of housing affected microbiota composition and especially dominant genera belonging to the Ruminococcaceae family (P<0.01). Moreover, low hygiene was associated with a higher Ruminococcaceae/Lachnospiraceae ratio (3.7 v. 2.4; P<0.05). Cecal total VFA and pH were increased (+19%; P<0.001) and decreased (−0.1 pH unit; P<0.05), respectively, in feed-restricted rabbits. Neither specific anti-OVA IgG nor haptoglobin was affected by treatments. Total IgG concentrations were the highest in animals raised in poor hygiene conditions after 8 days of restriction, but decreased after 19 days of restriction in high hygiene conditions (−2.15%; P<0.05). In conclusion, the degradation of hygiene conditions failed to induce a systematic specific and inflammatory response in rabbit, but reduced morbidity instead. Our results suggest that the microbiota composition would be a helpful source of biomarkers of digestive health.
The glass-forming Ti75Zr10Si15 and Ti60Zr10Nb15Si15 alloys composed of nontoxic elements may represent new materials for biomedical applications. For this study, melt-spun alloy samples exhibiting glass–matrix nanocomposite structures were subjected to thermal oxidation treatments in synthetic air to improve their surface characteristics. 550 °C was identified as the most appropriate temperature to carry out oxidative surface modifications while preserving the initial metastable microstructure. The modified surfaces were evaluated considering morphological and structural aspects, and it was found that the oxide films formed at 550 °C are amorphous and consist mainly of TiO2; their thicknesses were estimated to be ∼560 nm for Ti75Zr10Si15 and ∼460 nm for Ti60Zr10Nb15Si15. The thermally treated sample surfaces exhibit not only higher roughnesses and higher hardnesses but also improved wettability compared to the as-spun materials. By immersion of oxidized samples in simulated body fluid Ca- and P-containing coatings exhibiting typical morphologies of apatite are formed.
Electrochemical micromachining (ECMM) with microtool electrodes is a promising method for microshaping bulk metallic glasses (BMGs) at room temperature. A key challenge is the control of the electrode reactions to impede the disturbing passive layer formation on machined surface regions. In the example case of a Fe-based glassy Fe65.5Cr4Mo4Ga4P12C5B5.5 alloy, it will be demonstrated that by using an aqueous electrolyte based on 0.1 M H2SO4 solution with up to 0.1 M Fe2(SO4)3 addition and by applying ultrashort voltage pulses, complex microstructures can be machined with high precision. Potentiodynamic polarization measurements reveal that the salt addition reduces the charge transfer resistance of the microtool and therefore, the negative bias potential effect. The free corrosion and passive state of the BMG workpiece are affected, but not the transpassive regime. Systematic ECMM studies were conducted to obtain optimum parameters for shaping complex lateral structures with very smooth and well-defined machining areas.
We evaluated the usefulness of lissamine green B (LB) staining of cumulus–oocyte complexes (COC) as a non-invasive method of predicting maturational and developmental competence of slaughterhouse-derived porcine oocytes cultured in vitro. Cumulus cells of freshly aspirated COCs were evaluated either morphologically on the basis of thickness of cumulus cell layers, or stained with LB, which penetrates only non-viable cells. The extent of cumulus cell staining was taken as an inverse indicator of membrane integrity. The two methods of COC grading were then examined as predictors of nuclear maturation and development after parthenogenetic activation. In both cases LB staining proved a more reliable indicator than morphological assessment (P < 0.05). The relationship between LB staining and cumulus cell apoptosis was also examined. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay for DNA fragmentation revealed that oocytes within COCs graded as low quality by either LB staining or visual morphology showed significantly greater DNA fragmentation (P < 0.05) than higher grades, and that LB and visual grading were of similar predictive value. Expression of the stress response gene TP53 showed significantly higher expression in COCs graded as low quality by LB staining. However expression of the apoptosis-associated genes BAK and CASP3 was not significantly different between high or low grade COCs, suggesting that mRNA expression of BAK and CASP3 is not a reliable method of detecting apoptosis in porcine COCs. Evaluation of cumulus cell membrane integrity by lissamine green B staining thus provides a useful new tool to gain information about the maturational and developmental competence of porcine oocytes.
In Industrial and Organizational Psychology volume 7, issue 4, a commentary to the focal article Oswald et al.1 was unfortunately omitted. This commentary, “Imperfect Corrections or Correct Imperfections? Psychometric Corrections in Meta-Analysis,” by Frederick L. Oswald, Seydahmet Ercan, Samuel T. McAbee, Jisoo Ock, and Amy Shaw,2 is reproduced in the following pages.
There is understandable concern by LeBreton, Scherer, and James (2014) that psychometric corrections in organizational research are nothing more than a form of statistical hydraulics. Statistical corrections for measurement error variance and range restriction might inappropriately ratchet observed effects upward into regions of practical significance and publication glory—at the expense of highly questionable results.
Ecological systems are extraordinarily complex. Thus classical approaches to resolve ecosystem functioning have simplified analyses by conceptualizing ecosystems as being organized into trophic level compartments that contain organisms with similar feeding dependencies (e.g., producers, herbivores, carnivores) (Elton, 1927; Lindeman, 1942). Two competing worldviews on the regulation of ecosystem productivity emanated from such a conceptualization of ecosystem structure. The bottom-up view posits that the productivity of each trophic level is essentially limited by the one immediately below it (Lindeman, 1942; Feeny, 1968), while the top-down view recognizes that resource levels influence production, but contends that herbivore populations are mostly limited by predators rather than producer biomass (Hairston et al., 1960). Accordingly, predators can indirectly increase the productivity of a given system by reducing the negative effects of herbivores on plant biomass, resulting in a world that is green with plant material, rather than denuded by herbivory (Paine, 1969; Oksanen et al., 1981). Bottom-up theory countered that the world is green not because of predators, but instead due to variation in plant quality as a result of anti-herbivore defenses or weather patterns (Murdoch, 1966; Ehrlich and Birch, 1967; Scriber and Feeny, 1975; White, 1978; Feeny, 1991; Polis and Strong, 1996). This variation causes much of the “green” world to be inedible to herbivores; thus herbivores are still resource-limited.
The recognition of context-dependence in the degree of top-down or bottom-up control of ecosystems has resulted in gradual changes in how ecosystem functioning is envisioned. For instance, the “exploitation ecosystems” hypothesis (EEH) addresses context-dependence by combining elements of top-down and bottom-up concepts (Oksanen et al., 1981; Oksanen and Oksanen, 2000). At low levels of soil resource availability, plants are not productive enough to support herbivore populations and are thus bottom-up controlled (see Fig. 5.3). At medium levels of soil resources, an ecosystem can support herbivore populations, which in turn control plant productivity, while carnivores enter the ecosystem and control the herbivore population at the highest resource availability, thus releasing plant productivity from herbivore control.