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Access to cutting-edge technologies is essential for investigators to advance translational research. The Indiana Clinical and Translational Sciences Institute (CTSI) spans three major and preeminent universities, four large academic campuses across the state of Indiana, and is mandate to provide best practices to a whole state.
To address the need to facilitate the availability of innovative technologies to its investigators, the Indiana CTSI implemented the Access Technology Program (ATP). The activities of the ATP, or any program of the Indiana CTSI, are challenged to connect technologies and investigators on the multiple Indiana CTSI campuses by the geographical distances between campuses (1–4 hr driving time).
Herein, we describe the initiatives developed by the ATP to increase the availability of state-of-the-art technologies to its investigators on all Indiana CTSI campuses, and the methods developed by the ATP to bridge the distance between campuses, technologies, and investigators for the advancement of clinical translational research.
The methods and practices described in this publication may inform other approaches to enhance translational research, dissemination, and usage of innovative technologies by translational investigators, especially when distance or multi-campus cultural differences are factors to efficient application.
The emphasis on team science in clinical and translational research increases the importance of collaborative biostatisticians (CBs) in healthcare. Adequate training and development of CBs ensure appropriate conduct of robust and meaningful research and, therefore, should be considered as a high-priority focus for biostatistics groups. Comprehensive training enhances clinical and translational research by facilitating more productive and efficient collaborations. While many graduate programs in Biostatistics and Epidemiology include training in research collaboration, it is often limited in scope and duration. Therefore, additional training is often required once a CB is hired into a full-time position. This article presents a comprehensive CB training strategy that can be adapted to any collaborative biostatistics group. This strategy follows a roadmap of the biostatistics collaboration process, which is also presented. A TIE approach (Teach the necessary skills, monitor the Implementation of these skills, and Evaluate the proficiency of these skills) was developed to support the adoption of key principles. The training strategy also incorporates a “train the trainer” approach to enable CBs who have successfully completed training to train new staff or faculty.
Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Partial or non-adherence to medication is high amongst patients with schizophrenia. Rates of non-adherence of up to 72% have being reported depending on the method used and the patient population. Adherence is essential for optimal long-term patient outcomes in schizophrenia and failure to adhere to medication can have a major impact on the course of illness and treatment outcomes.
The objective of the EMEA (Europe, Middle east and Africa) ADHES survey was to collect psychiatrist's perceptions of the assessment, reasons and management of partial and non-adherence to medication.
The aim of this poster is to present psychiatrist's perceptions collected in the EMEA ADHES survey.
The survey was devised to ascertain psychiatrists’ preferred methods of assessing adherence, their perceptions of the level of adherence, reasons for non-adherence and on strategies to improve adherence.
Psychiatrists estimated that during the previous month more than half of their patients (53%) were partially or non-adherent. They estimated that as few as a third of patients who deteriorated after stopping medication was able to attribute this to their non-adherence. 76% of psychiatrists assessed adherence most frequently by asking their patient explicitly. Use of long-acting treatment was the preferred choice to address adherence problems for 62% of respondents.
This EMEA-wide survey illustrates that while respondents recognised the relevance and importance of partial and non-adherence to medication, there remains a need for more proactive management of treatment adherence of patients with schizophrenia to reduce the frequency and consequences of relapse.
Partial or non-adherence to medication is high amongst patients with schizophrenia. Many and often overlapping factors are considered to impact on treatment adherence, including: patient-related (lack of insight, psychotic, negative or cognitive symptoms), treatment-related (adverse effects, insufficient efficacy), environmental (living situation, negative attitudes of relatives/friends), and physician-related (patient-healthcare professionals relationship) factors.
The objective of the ADHES EMEA (Europe, Middle East and Africa) survey was to collect psychiatrist's perceptions of the assessment, reasons and management of partial and non-adherence to medication.
To present psychiatrist's opinion through EMEA of potential reasons for partial or non-adherence
The ADHES survey comprised 20 questions and was conducted in 36 countries across EMEA (over 4500 psychiatrists treating patients with schizophrenia).
Across EMEA 37% of psychiatrists viewed lack of insight as the most important reason for their patients stopping medication. 23% of psychiatrists viewed patient's feeling better and thinking it unnecessary to take medication as the most important reason for their patients stopping medication. 7% or less of psychiatrists viewed undesirable side effects, insufficient efficacy, cognitive impairment or drug/alcohol abuse as the most important reasons for their patients stopping medication.
In this survey, psychiatrists estimated that patient’s lack of insight and subjective improvement could constitute the main factors explaining poor adherence. Other factors (i.e., side effects, substance abuse) were regarded as less important. Strategies aimed at raising awareness of maintaining treatment, are warranted within EMEA, with the aim of improving clinical outcomes.
Rates of non-adherence of up to 72% have being reported, in schizophrenia, depending on the method used and the patient population. Rates of approximately 59% over 1 year have been reported for individuals with a first episode. Patients who stop medication are almost five times more likely to experience relapse than adherent patients. Failure to adhere to medication can have a major impact on the course of illness and treatment outcomes.
The EMEA (Europe, Middle East and Africa) ADHES schizophrenia survey was a survey of psychiatrists across the region, treating patients with schizophrenia, designed to canvas their perceptions of assessment, potential reasons and management for partial or non-adherence to medication amongst their patients.
To present methodology and demographics of the EMEA ADHES survey in schizophrenia.
The EMEA ADHES survey comprised 20 questions and was conducted in 36 countries across EMEA. In addition to recording the gender, age and practice setting of the respondents, questions related directly to the issue of partial-/non-adherence in patients with schizophrenia.
The survey was conducted amongst psychiatrists (including neurologists with psychiatric background in Germany) from January - March 2010. Results were obtained from 4722 respondents. Psychiatrists perceived that during the previous month more than half of their patients (53%) were partially or non-adherent across all EMEA regions
The EMEA ADHES schizophrenia survey is a large and geographically broad survey providing insight on psychiatrists’ perceptions of the assessment, causes and management of partial and non-adherence to medication.
The prevalence, symptomatology and correlates of anger attacks were studied in 103 depressed French patients, using a French version of the Anger Attacks Questionnaire. The prevalence of anger attacks during the previous month was 46.7%, and the most frequently reported symptoms were feeling of panic (85.1%), tachycardia (83.7%), and feeling out of control (81.3%). The occurrence of anger attacks was significantly associated with intensity of loss of control, and history of panic attacks. There was no significant association with age, gender, severity of depression or anxiety, history of suicidal attempts or mood disorder. Three weeks of treatment with serotoninergic antidepressants induced a significant decrease in anger attack prevalence.
Partial/non-adherence to medication is common amongst patients with schizophrenia. Nurses play an important role in assessing and managing mental health problems and are often involved in helping patients manage and adhere to their medication. As such, the perception of nurses regarding the burden and potential causes of non-adherence is vital in addressing the adherence problem.
The ADHES nurses survey collected opinions of nurses across the EMEA (Europe, Middle East and Africa) region.
To ascertain nurses' perceptions of assessment, potential causes and management of partial/non-adherence to medication in patients with schizophrenia.
The survey was conducted from January-March 2010 in 29 countries across EMEA, comprising 14 questions addressing the issue of partial/non-adherence and the use of long-acting injectable (LAI) antipsychotic medication in patients with schizophrenia.
Results were obtained from 4120 respondents. Nurses estimated high levels of partial/non-adherence (mean 54%) amongst patients with schizophrenia and 85% believed improving medication adherence would have a huge/sizable impact on patient outcomes. 93% believed that continuous medication with an LAI would have long-term benefits for patients with schizophrenia, and that many patients (mean 40%) would prefer LAI medication.
Nurses recognize the issue of partial/non-adherence to medication in patients with schizophrenia. Most nurses believe patients are well informed about LAI antipsychotics, however, approximately a third of nurses believe patients to be poorly informed. There is a need to address the problem of partial/non-adherence in clinical practice with a multidisciplinary approach to avoid suboptimal treatment outcomes in patients with schizophrenia.
One in ten children and adolescents experience mental health difficulties at any given time, yet only one third of those suffering access treatment. Untreated mental illness predisposes to longstanding individual difficulties, and presents a great public health burden. Large scale initiatives to reduce stigmatization of mental illness in children and adolescents, identified as a key deterrent to treatment, have had limited success, and research is scarce.
To gain a better understanding of the stigma experienced by children and adolescents with mental health difficulties.
We conducted a systematic review of the literature examining stigma and self-stigma towards children and adolescents with mental health difficulties, in order to better understand the extent and type of discrimination directed towards this particularly vulnerable group.
Following PRISMA guidelines, the databases Pubmed, PsychINFO and Cochrane were searched for original research published between 1980 and 2014, assessing public stigma (i.e. the reaction of the general public) and self-stigma (i.e. internalized public stigma) towards children and adolescents with mental health difficulties.
Thirty-seven studies were identified, confirming that stigmatization towards children and young people suffering mental health difficulties is a universal and disabling problem. There was some variation by diagnosis and gender, and stigmatization was for the most part unaffected by labelling. Self-stigmatization led to more secrecy and avoidance of interventions.
The findings confirm that stigmatization of mental illness is poorly understood due to a lack of evidence and methodological discrepancies. Implications of the findings are discussed, and suggestions made for future research.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Acifluorfen is a nonsystemic PPO-inhibiting herbicide commonly used for POST Palmer amaranth control in soybean, peanut, and rice across the southern United States. Concerns have been raised regarding herbicide selection pressure and particle drift, increasing the need for application practices that optimize herbicide efficacy while mitigating spray drift. Field research was conducted in 2016, 2017, and 2018 in Mississippi and Nebraska to evaluate the influence of a range of spray droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)], using acifluorfen to create a novel Palmer amaranth management recommendation using pulse width modulation (PWM) technology. A pooled site-year generalized additive model (GAM) analysis suggested that 150-μm (Fine) droplets should be used to obtain the greatest Palmer amaranth control and dry biomass reduction. Nevertheless, GAM models indicated that only 7.2% of the variability observed in Palmer amaranth control was due to differences in spray droplet size. Therefore, location-specific GAM analyses were performed to account for geographical differences to increase the accuracy of prediction models. GAM models suggested that 250-μm (Medium) droplets optimize acifluorfen efficacy on Palmer amaranth in Dundee, MS, and 310-μm (Medium) droplets could sustain 90% of maximum weed control. Specific models for Beaver City, NE, indicated that 150-μm (Fine) droplets provide maximum Palmer amaranth control, and 340-μm (Medium) droplets could maintain 90% of greatest weed control. For Robinsonville, MS, optimal Palmer amaranth control could be obtained with 370-μm (Coarse) droplets, and 90% maximum control could be sustained with 680 μm (Ultra Coarse) droplets. Differences in optimal droplet size across location could be a result of convoluted interactions between droplet size, weather conditions, population density, plant morphology, and soil fertility levels. Future research should adopt a holistic approach to identify and investigate the influence of environmental and application parameters to optimize droplet size recommendations.
Brominated flame retardants (BFR) are primarily used as flame retardant additives in insulating materials. These lipophilic compounds can bioaccumulate in animal tissues, leading to human exposure via food ingestion. Although their concentration in food is not yet regulated, several of these products are recognised as persistent organic pollutants; they are thought to act as endocrine disruptors. The present study aimed to characterise the occurrence of two families of BFRs (hexabromocyclododecane (HBCDD) and polybrominated diphenyl ethers (PBDE)) in hen eggs and broiler or pig meat in relation to their rearing environments. Epidemiological studies were carried out on 60 hen egg farms (34 without an open-air range, 26 free-range), 57 broiler farms (27 without an open-air range, 30 free-range) and 42 pig farms without an open-air range in France from 2013 to 2015. For each farm, composite samples from either 12 eggs, five broiler pectoral muscles or three pig tenderloins were obtained. Eight PBDE congeners and three HBCDD stereoisomers were quantified in product fat using gas chromatography–high-resolution mass spectrometry, or high-performance liquid chromatography–tandem mass spectrometry, respectively. The frequencies of PBDE detection were 28% for eggs (median concentration 0.278 ng/g fat), 72% for broiler muscle (0.392 ng/g fat) and 49% for pig muscle (0.403 ng/g fat). At least one HBCDD stereoisomer was detected in 17% of eggs (0.526 ng/g fat), 46% of broiler muscle (0.799 ng/g fat) and 36% of pig muscle (0.616 ng/g fat). Results were similar in concentration to those obtained in French surveillance surveys from 2012 to 2016. Nevertheless, the contamination of free-range eggs and broilers was found to be more frequent than that of conventional ones, suggesting that access to an open-air range could be an additional source of exposure to BFRs for animals. However, the concentration of BFRs in all products remained generally very low. No direct relationship could be established between the occurrence of BFRs in eggs and meat and the characteristics of farm buildings (age, building materials). The potential presence of BFRs in insulating materials is not likely to constitute a significant source of animal exposure as long as the animals do not have direct access to these materials.
Herbicide applications performed with pulse width modulation (PWM) sprayers to deliver specific spray droplet sizes could maintain product efficacy, minimize potential off-target movement, and increase flexibility in field operations. Given the continuous expansion of herbicide-resistant Palmer amaranth populations across the southern and midwestern United States, efficacious and cost-effective means of application are needed to maximize Palmer amaranth control. Experiments were conducted in two locations in Mississippi (2016, 2017, and 2018) and one location in Nebraska (2016 and 2017) for a total of 7 site-years. The objective of this study was to evaluate the influence of a range of spray droplet sizes [150 (Fine) to 900 μm (Ultra Coarse)] on lactofen and acifluorfen efficacy for Palmer amaranth control. The results of this research indicated that spray droplet size did not influence lactofen efficacy on Palmer amaranth. Palmer amaranth control and percent dry-biomass reduction remained consistent with lactofen applied within the aforementioned droplet size range. Therefore, larger spray droplets should be used as part of a drift mitigation approach. In contrast, acifluorfen application with 300-μm (Medium) spray droplets provided the greatest Palmer amaranth control. Although percent biomass reduction was numerically greater with 300-μm (Medium) droplets, results did not differ with respect to spray droplet size, possibly as a result of initial plant injury, causing weight loss, followed by regrowth. Overall, 900-μm (Ultra Coarse) droplets could be used effectively without compromising lactofen efficacy on Palmer amaranth, and 300-μm (Medium) droplets should be used to achieve maximum Palmer amaranth control with acifluorfen.
Children from language minority (LM) environments speak a language at home that differs from that at school, are often from socioeconomically disadvantaged backgrounds, and are at risk for reading impairment. We evaluated the main effects and interaction of language status and phonological memory and awareness on reading disorder in 352 children from socioeconomically disadvantaged backgrounds. A significant phonological memory by language status interaction indicated that phonological memory problems were magnified in predicting reading impairment in children from LM versus English dominant (ED) homes. Among children without reading disorder, language minority status was unrelated to phonological processing.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Alternatives to skin preparation with conventional preoperative antiseptics are required because of adverse reactions and the potential emergence of resistance. Here, we present 2 phase 2 studies of ZuraGard (ZG), a novel formulation of isopropyl alcohol and functional excipients developed for preoperative skin antisepsis.
Microbial skin flora on abdominal and inguinal sites in healthy volunteers were quantitatively assessed following application of ZG versus a negative control (ZV) and a chlorhexidine/alcohol preparation, Chloraprep (CP). In trial 1, ZG administered for both recommended and abbreviated application times was compared with CP and ZV via bacterial reductions at 10 minutes, and 6 hours, 12 hours, and 24 hours following application. In trial 2, the 10-minute postapplication responder rates (RRs) for ZG, participants with abdominal ≥2 log10 per cm2, and inguinal ≥3 log10 per cm2 reductions in colony-forming units (CFU) were compared to RRs of participants treated with CP.
In trial 1, ZG at the recommended application time reduced mean bacterial counts by ~3.18 log10 CFU/cm2 and ~2.98 log10 CFU/cm2 at abdominal and inguinal sites, respectively. Qualitatively similar reductions were observed for the abbreviated ZG application time and all CP applications. Application of ZV was ineffective. In trial 2, 10-minute RRs for ZG and CP exceeded 90% at abdominal sites. At inguinal sites, RRs were 83.3% for ZG and 86.7% for CP. No skin irritation or other adverse events were observed.
ZG matched CP efficacy under these experimental conditions with immediate and persistent microbial reductions, including abbreviated application times. Further clinical studies of this novel preoperative antiseptic are merited.