Persistent identifiers (PIDs) - for people (researchers), places (their organizations) and things (their research outputs and other contributions) - are foundational elements in the overall research ...information infrastructure. They enable these entities to be uniquely identified and connected, to create reliable links between them. In this paper we describe what PIDs are and how they work. We demonstrate how, if widely adopted, the connections they enable will result in improved access to information, opportunities for collaboration, reduced administrative overhead and, ultimately, increased trust in scholarship and research. To ensure they are fit for purpose, we propose that PID metadata should meet FAIR principles, and that the source of information they contain should be clear and transparent. We also recognize existing usage of persistent identifiers, and invite community support for wider adoption of PIDs in future.
Legionella pneumophila is an opportunistic human pathogen and causative agent of the acute pneumonia known as Legionnaire's disease. Upon inhalation, the bacteria replicate in alveolar macrophages ...(AM), within an intracellular vacuole termed the Legionella‐containing vacuole. We recently found that, in vivo, IFNγ was required for optimal clearance of intracellular L. pneumophila by monocyte‐derived cells (MC), but the cytokine did not appear to influence clearance by AM. Here, we report that during L. pneumophila lung infection, expression of the IFNγ receptor subunit 1 (IFNGR1) is down‐regulated in AM and neutrophils, but not MC, offering a possible explanation for why AM are unable to effectively restrict L. pneumophila replication in vivo. To test this, we used mice that constitutively express IFNGR1 in AM and found that prevention of IFNGR1 down‐regulation enhanced the ability of AM to restrict L. pneumophila intracellular replication. IFNGR1 down‐regulation was independent of the type IV Dot/Icm secretion system of L. pneumophila indicating that bacterial effector proteins were not involved. In contrast to previous work, we found that signaling via type I IFN receptors was not required for IFNGR1 down‐regulation in macrophages but rather that MyD88‐ or Trif‐ mediated NF‐κB activation was required. This work has uncovered an alternative signaling pathway responsible for IFNGR1 down‐regulation in macrophages during bacterial infection.
NF‐κB activation following Legionella lung infection resulted in downregulation of IFNGR1 expression in alveolar macrophages contributing to intracellular bacterial survival.
Abstract
Post-traumatic stress and other problems often occur after combat, deployment, and other military operations. Because techniques such as mindfulness meditation show efficacy in improving ...mental health, our team developed a mobile application (app) for individuals in the armed forces with subclinical psychological problems as secondary prevention of more significant disease. Based on the Personal Health Intervention Toolkit (PHIT), a mobile app framework for personalized health intervention studies, PHIT for Duty integrates mindfulness-based relaxation, behavioral education in sleep quality and alcohol use, and psychometric and psychophysiological data capture. We evaluated PHIT for Duty in usability and health assessment studies to establish app quality for use in health research. Participants (N = 31) rated usability on a 1 (very hard) to 5 (very easy) scale and also completed the System Usability Scale (SUS) questionnaire (N = 9). Results were (mean ± SD) overall (4.5 ± 0.6), self-report instruments (4.5 ± 0.7), pulse sensor (3.7 ± 1.2), sleep monitor (4.4 ± 0.7), sleep monitor comfort (3.7 ± 1.1), and wrist actigraphy comfort (2.7 ± 0.9). The average SUS score was 85 ± 12, indicating a rank of 95%. A comparison of PHIT-based assessments to traditional paper forms demonstrated a high overall correlation (r = 0.87). These evaluations of usability, health assessment accuracy, physiological sensing, system acceptability, and overall functionality have shown positive results and affirmation for using the PHIT framework and PHIT for Duty application in mobile health research.
BACKGROUND There is substantial evidence that antidepressant medications treat moderate to severe depression effectively, but there is less data on cognitive therapy’s effects in this population. ...OBJECTIVE To compare the efficacy in moderate to severe depression of antidepressant medications with cognitive therapy in a placebo-controlled trial. DESIGN Random assignment to one of the following: 16 weeks of medications (n = 120), 16 weeks of cognitive therapy (n = 60), or 8 weeks of pill placebo (n = 60). SETTING Research clinics at the University of Pennsylvania, Philadelphia, and Vanderbilt University, Nashville, Tenn. PATIENTS Two hundred forty outpatients, aged 18 to 70 years, with moderate to severe major depressive disorder. INTERVENTIONS Some study subjects received paroxetine, up to 50 mg daily, augmented by lithium carbonate or desipramine hydrochloride if necessary; others received individual cognitive therapy. MAIN OUTCOME MEASURE The Hamilton Depression Rating Scale provided continuous severity scores and allowed for designations of response and remission. RESULTS At 8 weeks, response rates in medications (50%) and cognitive therapy (43%) groups were both superior to the placebo (25%) group. Analyses based on continuous scores at 8 weeks indicated an advantage for each of the active treatments over placebo, each with a medium effect size. The advantage was significant for medication relative to placebo, and at the level of a nonsignificant trend for cognitive therapy relative to placebo. At 16 weeks, response rates were 58% in each of the active conditions; remission rates were 46% for medication, 40% for cognitive therapy. Follow-up tests of a site × treatment interaction indicated a significant difference only at Vanderbilt University, where medications were superior to cognitive therapy. Site differences in patient characteristics and in the relative experience levels of the cognitive therapists each appear to have contributed to this interaction. CONCLUSION Cognitive therapy can be as effective as medications for the initial treatment of moderate to severe major depression, but this degree of effectiveness may depend on a high level of therapist experience or expertise.Arch Gen Psychiatry. 2005;62:409-416-->
Prior studies assessing the relation between negative affective traits and cortisol have yielded inconsistent results. Two studies assessed the relation between individual differences in ...repressive-defensiveness and basal salivary cortisol levels. Experiment 1 assessed midafternoon salivary cortisol levels in men classified as repressors, high-anxious, or low-anxious. In Experiment 2, more rigorous controls were applied as salivary cortisol levels in women and men were assessed at 3 times of day on 3 separate days. In both studies, as hypothesized, repressors and high-anxious participants demonstrated higher basal cortisol levels than low-anxious participants. These findings suggest that both heightened distress and the inhibition of distress may be independently linked to relative elevations in cortisol. Also discussed is the possible mediational role of individual differences in responsivity to, or mobilization for, uncertainty or change.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Anxiety and depressive disorders share many features, suggesting a common set of physiologic substrates. Recent research has indicated that mood can be categorized into 3 components by factor ...analysis: (1) somatic anxiety (a factor relatively specific to panic disorder), (2) anhedonic depression (which includes symptoms related to motivation and enjoyment and found to be specific to depression), and (3) general distress (a factor that cuts across all depressive and anxiety disorders studied). Antidepressant drugs, particularly serotonin reuptake inhibitors and serotonin receptor modulators, are effective for a wide variety of anxiety and depressive disorders. The impact on both anxiety and depression may be a result of an effect on a common set of physiologic targets relevant to the general distress dimension. At a cellular level, the antidepressants target components of the stress-adaptation system in brain, which may explain these common effects. On the other hand, there appear to be differences in the relative impact of serotonergic and noradrenergic drugs on the spectrum of distress and motivational symptoms. Basic research and clinical research suggest that serotonergic agents may be preferentially effective for symptoms of general distress, whereas catecholaminergic agents may target anhedonic depression symptoms.
Isolated cryopreserved human liver cells, attached to collagen-coated microcarriers, were injected intraperitoneally into mutant rat recipients genetically deficient in either bilirubin uridine ...diphosphoglucuronosyltransferase activity (Gunn rats) or albumin synthesis (Nagase analbuminemic rats). One group of the recipient Gunn and analbuminemic rats were made genetically immunodeficient by interbreeding with athymic rats with inherited T-cell deficiency. Injected microcarriers and cells formed aggregates on the surface of the pancreas. There was no morphologic evidence of rejection in athymic recipients, whereas immunocompetent recipients demonstrated rejection within 5 days of transplantation. Athymic-Gunn rat recipients demonstrated excretion of bilirubin glucuronides in bile for 30 days and reduction in their serum bilirubin levels. In recipient athymic-analbuminemic rats, plasma albumin levels increased from pretransplantation levels of 0.025-0.05 mg/ml to 3.9-4.8 mg/ml 8 days posttransplantation and remained nearly at that level throughout the 30 days of the study. A method of harvesting, attaching to microcarriers, cryopreserving, and in vivo testing of human hepatocytes with prolonged survival and function in athymic-Gunn and athymic-analbuminemic hybrid rats is reported. These rats are excellent animal models for testing xenograft function.
To be an effective urban educator requires teachers to understand the contextual factors of students, the school, and the community, and their cumulative effects on learning. Urban teacher academies ...support a better understanding of urban classrooms and challenge stereotypes of the urban context. The focus of this study was to compare participants' perceptions of urban settings before and after 2 weeks spent at an urban teacher academy for high school students.
Mycobacterium simiae is found primarily in the southwestern United States, Israel, and Cuba, with tap water as its suspected reservoir. Our institution saw an increase in M. simiae isolates in 2001. ...An investigation into possible contaminated water sources was undertaken.
Environmental cultures were performed from water taps in the microbiology laboratory, patient rooms, points in the flow of water to the hospital, and patients' homes. Patient and environmental M. simiae were compared by PFGE.
Military treatment facility in San Antonio, Texas.
All patients with cultures positive for M. simiae between January 2001 and April 2002. Medical records were reviewed.
M. simiae was recovered from water samples from the hospital, patients' home showers, and a well supplying the hospital. A single PFGE clone was predominant among water isolates (9 of 10) and available patient isolates (14 of 19). There was an association between exposure to hospital water and pulmonary samples positive for the clonal M. simiae strain (P = .0018). Only 3 of 22 culture-positive patients met criteria for M. simiae pulmonary disease. Of them, two had indistinguishable M. simiae strains from tap water to which they were routinely exposed.
This represents an outbreak of M. simiae colonization with one nosocomial infection. It is only the second time that M. simiae has been recovered from hospital tap water and its first presentation in municipal water. This study raises issues about the need and feasibility of eliminating or avoiding exposure to M. simiae from tap water.
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