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Research is increasingly conducted through multi-institutional consortia, and best practices for establishing multi-site research collaborations must be employed to ensure efficient, effective, and productive translational research teams. In this manuscript, we describe how the Population-based Research to Optimize the Screening Process Lung Research Center (PROSPR-Lung) utilized evidence-based Science of Team Science (SciTS) best practices to establish the consortium’s infrastructure and processes to promote translational research in lung cancer screening. We provide specific, actionable examples of how we: (1) developed and reinforced a shared mission, vision, and goals; (2) maintained a transparent and representative leadership structure; (3) employed strong research support systems; (4) provided efficient and effective data management; (5) promoted interdisciplinary conversations; and (6) built a culture of trust. We offer guidance for managing a multi-site research center and data repository that may be applied to a variety of settings. Finally, we detail specific project management tools and processes used to drive collaboration, efficiency, and scientific productivity.
From November 2019 to April 2020, the prototypical red supergiant Betelgeuse experienced an unexpected and historic dimming. This event was observed worldwide by astrophysicists, and also by the general public with the naked eye. We present here the results of our observing campaign with ESO’s VLT and VLTI in the visible and infrared domains. The observations with VLT/SPHERE-ZIMPOL, VLT/SPHERE-IRDIS, VLTI/GRAVITY and VLTI/MATISSE provide spatially resolved diagnostics of this event. Using PHOENIX atmosphere models and RADMC3D dust radiative transfer simulations, we built a consistent model reproducing the images and the photometry.
The post-main sequence evolutionary path of massive stars comprises various transition phases, in which the stars shed large amounts of material into their environments. Our studies focus on two of them: B[e] supergiants and yellow hypergiants, for which we investigate the structure and dynamics within their environments. We find that each B[e] supergiant is surrounded by a unique set of rings or arc-like structures. These structures are either stable over time or they display high variability, including expansion and dilution. In contrast, yellow hypergiants are embedded in multiple shells of gas and dust. These objects are famous for their outburst activity. Moreover, the dynamics in their extended atmospheres imply an enhanced pulsation activity prior to outburst. The physical mechanism(s) leading to episodic mass ejections in these two types of stars is still uncertain. We propose that strange-mode instabilities, excited in the inflated envelopes of these objects, play a significant role.
Clinical studies point toward a potential role of the serotonin transporter (SERT) binding as a predictor of clinical outcome in the treatment of depression. After long-term treatment with clinical doses of SSRIs the expected SERT occupancy is about 80%. Here, we were interested to investigate the relationship of SERT occupancy values between short- and longterm treatment.
To test if the SERT occupancy at steady-state can be predicted based on the single dose occupancy by escitalopram (S-citalopram) or citalopram (racemate of S-citalopram and R-citalopram).
18 patients with major depressive disorder received either escitalpram (10 mg/d) or citalopram (20 mg/d) in a double-blind, randomized, longitudinal study. They underwent three PET scans using the radioligand [11C]DASB: PET1 baseline, PET2 6 hours after first drug intake and PET3 after three weeks of daily oral treatment. Occupancy of SERT was quantified in six subcortical regions: thalamus, N. caudatus, putamen, mibrain, dorsal raphe and median raphe nuclei. Data was analyzed by means of multiple linear regression models corrected for baseline SERT availability values using SPSS 15.0.
Single dose occupancy of the SERT significantly predicted steady-state occupancy after three weeks in three regions: thalamus (r2 = 0.45, p = 0.009), N. caudatus (r2 = 0.4, p = 0.006) and putamen (r2 = 0.43, p = 0.005). Other regions did not show significant relationships.
In this study we demonstrated that single-dose occupancy in SERT rich regions such as thalamus, N. caudatus and the putamen could serve as reliable predictors for steady-state occupancy. However, a linear model failed to explain the relationship in regions known for serotonergic cell origin.
There is evidence that psychiatric diseases are accompanied by structural alterations in the human brain, partly reversible by pharmacological treatments. Several studies including Tost et al. (Nat.Neurosci.2010;13(8):920-2) investigated the effect of psychotropic drugs on neuronal plasticity pointing towards rapid pharmacologically induced brain grey matter variations, apart from already presumed slow structural changes within weeks. Here, we investigated the short-term (days) structural effects of SSRIs.
To identify structural changes of grey and white matter following 10d of oral administration (citalopram/escitalopram vs. placebo) in 18 healthy subjects investigated by magnetic resonance imaging (MRI) using voxel-based morphometry (VBM).
Study design: Randomized, cross-over, placebo-controlled, double-blind study.
ANOVA (grey matter: F(2,48) = 18.85, p < 0.05; white matter: F(2,48) = 17.79, p < 0.05) did not reveal suprathreshold clusters in grey or white matter.
This VBM-study does not support previous short-time (days) MR findings of pharmacologically-induced structural alterations in the brain, considering the lack of significant changes in grey and white matter volumes following 10d of SSRI administration. This divergence may be caused by dissent pharmacological effects of SSRIs compared to other psychotropic drugs.
The subgenual part of the anterior cingulate cortex (sgACC) has been frequently reported to be structurally and cytoarchitectually changed in major depressive disorder (MDD) and is also a promising target in deep brain stimulation in treatment-resistant MDD. Furthermore, substantial evidence demonstrates a high density of serotonin-1A (5-HT1A) receptors in the sgACC, a key area involved in emotional processing.
Here, we investigated the relationship between the 5-HT1A receptor in the sgACC and changes in regional grey matter volume with voxel-based morphometry.
PET ([carbonyl-11C]WAY-100635) was used to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance images from 32 healthy subjects (mean 26.68 ± 5.1 years; 17 women). Regression analysis was performed in SPM8 (p < .001 uncorr.) using sgACC 5-HT1A BPND as regressor, controlling for sex, age and total grey matter volume (GMV).
5-HT1A BPND in the sgACC was positively associated with regional GMV in the medial temporal gyri (T=4.37) and nucleus accumbens bilaterally (T = 4.19). Furthermore, sgACC 5-HT1A binding was negatively correlated with GMV within the inferior temporal gyri (T = 5.22) and putamen bilaterally (T = 5.12).
Our findings demonstrate structural relationships between sgACC 5-HT1A receptor binding and grey matter volume in the ventral striatum as well as in temporal regions, which both exhibit close neuronal connections with the sgACC. Moreover, the GMV of the ventral striatum has been reported to be decreased in patients with MDD. Conclusively, our results underpin the role of serotonergic neuronal transmission in cytoarchitectural processes within regions involved in the modulation of mood.
Dysfunctional neuroplasticity contributes to the pathogenesis of Alzheimer's disease, schizophrenia and depression. However, the underlying molecular mechanisms are not fully understood. Previous studies report neuromodulatory properties of the serotonin-1A (5-HT1A) receptor, which is also altered in these disorders. This suggests 5-HT1A mediated neuroplasticity as potential pathogenic factor.
The aim of this study was to demonstrate 5-HT1A mediated neuroplasticity in vivo.
We used positron emission tomography to quantify 5-HT1A receptor binding (BPND) together with structural magnetic resonance imaging in 35 healthy subjects (mean 26.6 ±6.8 years; 17 women). Voxel-wise regression analysis was performed with gray matter volume (GMV) as dependent and 5-HT1A BPND as independent variable. Additionally, regression analysis was calculated with whole brain GMV as dependent variable and 5-HT1A BPND of the dorsal raphe nucleus (DRN) as independent variable. Control variables were age, sex and total GMV, respectively.
5-HT1A receptor density predicted GMV of the hippocampus, medial temporal cortex, inferior temporal cortex, medial occipital cortex and the pericalcarine region in each hemisphere (p < 0.05 false discovery rate corrected, R2: 0.308–0.503). These associations were independent from local numbers of neurons. Furthermore, 5−HT1A receptor levels in the DRN predicted GMV of the anterior cingulate cortex (p = 0.001, R2=0.656, uncorrected).
These results demonstrate 5-HT1A receptor mediated morphogenetic mechanisms in healthy human subjects' brains, which occur not only locally but also at the macro-network level. Finally, morphogenetic signaling investigated with multimodal neuroimaging could contribute to better understanding and diagnostic identification of gray matter loss in neuropsychiatric disorders.
This chapter reviews the most researched psychotherapeutic interventions for individuals with cognitive impairment (CI) and common symptoms targeted by these interventions. Elements of assessment and psychotherapy modifications to consider when working with individuals with dementia are also discussed. Assessment components might include clarification of medical symptom overlap, collateral information, assessment instruments developed for individuals with cognitive difficulties, and incorporating consultation with other specialties. In general, clinicians should consider using simplified skills, increasing the number and frequency of sessions, shortening sessions, reducing group size, and providing more guidance during skill instruction and practice when working with individuals with cognitive impairments. Despite their promise and recommendations for their use, nonpharmacological therapies for individuals with dementia have a small research base and warrant continued development and evaluation.
Necrotising otitis externa is a severe inflammatory process affecting soft tissue and bone, mostly in diabetic patients. Diabetic patients are also at risk of diabetic foot osteomyelitis, another inflammatory condition involving soft tissue and bone. This review aimed to describe the similarities and differences of these entities in an attempt to further advance the management of necrotising otitis externa.
A PubMed search was conducted using the key words ‘otitis externa’, ‘necrotising otitis externa’, ‘malignant otitis externa’, ‘osteomyelitis’ and ‘diabetic foot’.
Results and conclusion
The similarities regarding patient population and pathophysiology between necrotising otitis externa and diabetic foot osteomyelitis raise basic questions concerning the effects of long-standing diabetes on the external ear. The concordance between local swabs and bone cultures in diabetic foot osteomyelitis is less than 50 per cent. If this holds true also to necrotising otitis externa, the role of deep tissue cultures should be strongly considered. Similar to diabetic foot osteomyelitis, magnetic resonance imaging should be considered in selected necrotising otitis externa subgroups.
We present the results from an ongoing long-term monitoring of the 22 GHz H2O maser in W49N with the 100-m Effelsberg radio telescope from February 2014 to September 2017. The unique Effelsbergs spectral line observation capability provides a broad velocity range coverage from −500 to +500 km s−1 with a spectral resolution better than 0.1 km/s. Following the strong major outburst in W49N in late 2013, we have started a long-term monitoring programme at Effelsberg. The major outburst feature (up to 80,000 Jy at VLSR − 98 km s−1) faded away by June 2014. However, we found that the site is still active with several high velocity outbursts (both blue and redshifted). Some features appear at extremely high velocities (up to ±280 km s−1) and show rapid flux variations within a 1-2 month period. This sub-year scale variability implies that the water masers could be excited by episodic shock propagation caused by a high-velocity protostellar jet.
A number of laser facilities coming online all over the world promise the capability of high-power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating, and laser-driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.
Introduction: The Institute of Medicine (IOM) has recommended that high-quality, evidence-based guidelines be developed for emergency medical services (EMS). The National Association of EMS Physicians (NAEMSP) has outlined a strategy that will see this task fulfilled, consisting of multiple working groups focused on all aspects of guideline development and implementation. A first step, and our objective, was a cataloguing and appraisal of the current guidelines targeting EMS providers. Methods: A systematic search of the literature was conducted in MEDLINE (1175), EMBASE (519), PubMed (14), Trip (416), and guidelines.gov (64) through May 1, 2016. Two independent reviewers screened titles for relevance to prehospital care, and then abstracts for essential guideline features, including a systematic review, a grading system, and an association between level of evidence and strength of recommendation. All disagreements were moderated by a third party. Citations meeting inclusion criteria were appraised with the AGREE II tool, which looks at six different domains of guideline quality, containing a total of 23 items rated from 1 to 7. Each guideline was appraised by three separate reviewers, and composite scores were calculated by averaging the scaled domain totals. Results: After primary (kappa 97%) and secondary (kappa 93%) screening, 49 guidelines were retained for full review. Only three guidelines obtained a score of >90%, the topics of which included aeromedical transport, analgesia in trauma, and resuscitation of avalanche victims. Only two guidelines scored between 80% and 90%, the topics of which included stroke and pediatric seizure management. One guideline, splinting in an austere environment, scored between 70% and 80%. Nine guidelines scored between 60% and 70%, the topics of which included ischemic stroke, cardiovascular life support, hemorrhage control, intubation, triage, hypothermia, and fibrinolytic use. Of the remaining guidelines, 14 scored between 50% and 60%, and 20 obtained a score of <50%. Conclusion: There are few high-quality, evidence-based guidelines in EMS. Of those that are published, the majority fail to meet established quality measures. Although a lack of randomized controlled trials (RCTs) conducted in the prehospital field continues to limit guideline development, suboptimal methodology is also commonplace within the existing literature.
Dansgaard–Oeschger (D–O) cycles had far-reaching effects on Northern Hemisphere and tropical climate systems during the last glacial period, yet the climatic response to D–O cycles in western North America is controversial, especially prior to 55 ka. We document changes in precipitation along the western slope of the central Sierra Nevada during early Marine Oxygen Isotope Stages (MIS) 3 and 4 (55–67 ka) from a U-series dated speleothem record from McLean's Cave. The timing of our multi-proxy geochemical dataset is coeval with D–O interstadials (15–18) and stadials, including Heinrich Event 6. The McLean's Cave stalagmite indicates warmer and drier conditions during Greenland interstadials (GISs 15–18), signified by elevated δ18O, δ13C, reflectance, and trace element concentrations, and less radiogenic 87Sr/86Sr. Our record extends evidence of a strong linkage between high-latitude warming and reduced precipitation in western North America to early MIS 3 and MIS 4. This record shows that the linkage persists in diverse global climate states, and documents the nature of the climatic response in central California to Heinrich Event 6.
The evolution of massive stars encompasses short-lived transition phases in which mass-loss is more enhanced and usually eruptive. A complex environment, combining atomic, molecular and dust regions, is formed around these stars. In particular, the circumstellar environment of B[e] Supergiants is not well understood. To address that, we have initiated a campaign to investigate their environments for a sample of Galactic and Magellanic Cloud sources. Using high-resolution optical and near-infrared spectra (MPG-ESO/FEROS, GEMINI/Phoenix and VLT/CRIRES, respectively), we examine a set of emission features ([OI], [CaII], CO bandheads) to trace the physical conditions and kinematics in their formation regions. We find that the B[e] Supergiants are surrounded by a series of rings of different temperatures and densities, a probable result of previous mass-loss events. In many cases the CO forms very close to the star, while we notice also an alternate mixing of densities and temperatures (which give rise to the different emission features) along the equatorial plane.
Negative symptoms and cognitive deficits in schizophrenia are partially overlapping. However, the nature of the relationship between negative symptoms and cognition remains equivocal. Recent reviews have demonstrated the presence of two negative symptom subdomains, diminished emotional expression (DEE) and avolition. In view of this, we sought to clarify the relationship between negative symptoms and cognitive domains.
A total of 687 participants with schizophrenia were assessed on measures of psychopathology and cognition. Three cognitive factors, namely executive function, fluency/memory and speed/vigilance were computed from the cognitive tests. Confirmatory factor analysis was utilized to examine if a one-factor or two-factor negative model was applicable to our sample. Subsequently, the relationships between negative symptoms and cognition were examined using structural equation modeling.
Results demonstrated that the two-factor model fitted the data well. While negative symptoms were mildly to moderately associated with cognition, we found that DEE had unique associations with cognition compared to social avolition, contributing to the validity of the constructs and suggesting the possibility of common underlying substrates in negative symptoms and cognition.
Our study highlighted the need to classify DEE and social avolition separately as both are necessary in refining the complex relationship between negative symptoms and cognition as well as potentially guiding treatment and management of schizophrenia.
This is a review of the total care of those acute spinal cord injury patients in Ontario during the years 1969 and 1970, from extrication and transportation following the accident to death, or the completion of primary definitive rehabilitation.
Information was extracted from the available ambulance records, the patients and many of the responsible physicians were interviewed personally. The study was detailed and intensive and included a review of each patient's hospital records in each hospital up to discharge from the rehabilitation programme into the community, or to a chronic care unit. The data was compiled in accordance with a detailed and lengthy questionnaire developed for this study.
The incidence of acute cord injuries in Ontario in 1969 and 1970 amounted to 244; in 1969, 15.9 per million population and in 1970, 13.6 per million. As in other studies road accidents took first place, followed by falls from a height; sports injuries ranked third and 65.7% of these were caused by diving into shallow water. Age incidence, and incidence by month, day of week and time of day were identified. Fridays and Saturday afternoons in July and August are particularly hazardous.
The study continued to the end of 1974 by which time 34 deaths had been recorded. Peak incidence of death occurred within fourteen days of injury. The most common cause of death was respiratory in origin.
Geographical distribution was identified and the type of hospital treating the acutely injured patient.
Fourteen percent of persons with spinal column injury suffered progressive or sequential spinal cord damage both prior to and following medical contact. The incidence of pressure sores and genitourinary sepsis and calculosis was high in all types of hospitals. The effect of operative treatment was noted in the cases of complete quadriplegia and paraplegia.
Of the 133 survivors who undertook a rehabilitation program, 84% returned to their homes and 59% achieved gainful employment or ongoing education.
The cost was determined of general hospital services and rehabilitation programmes.
A new model for the care of the spinal cord injury patients in Ontario was proposed.
We report a multi-wavelength study of a recent major flare (~ 80,000 Jy at VLSR ~ -98.1 km s−1) of the 22-GHz water maser in W49A. In February 2014, we started monthly monitoring with the Effelsberg 100-m radio telescope. In May 2014, we carried out the nearly simultaneous observations of the 22-GHz transition with selected submillimeter water transitions using the IRAM 30-m telescope (at 183 GHz) and the Atacama Pathfinder Experiment (APEX) 12-m telescope (from 321 to 475 GHz). We have also performed interferometric observations using the NRAO Very Long Baseline Array (VLBA) at 22 GHz and the Submillimeter Array (SMA) at 321 and 325 GHz. One remarkable result is the detection of very high velocity emission features in several transitions. Our data also represent its first detection of the 475-GHz water transition in a star-forming region. Studying these multiple masing transitions in conjunction with theoretical modeling of their excitation not only places strong constraints on the physical conditions of the masing gas but also allows us to study their association with the embedded massive stellar cluster in W49A.
Further to the publication by the London School of Economics and Political Science of the report Ending the Drug Wars, this editorial focuses on the mental health impact of the ‘war on drugs' and on the need to end such policies in favour of evidence-based interventions to manage drug dependence as a health condition.
We have been spectroscopically monitoring a number of blue supergiants, focusing on several strategic photospheric and wind lines. Our aim is to detect line profile variability, and to determine its origin. Here, we present preliminary results for ρ Leo and ε Ori. We conduct an asteroseismic analysis of Hei λ6678. We find in each star multiple periods raging from hours to several days. In addition, we observe strong, night to night variability in Hα.