Awareness, Solidarity, and Action: An Educational Model

How Extension fosters social change and innovation can be improved through the use of theory-based educational models. Educational models can serve as foundations for the conceptual designs of educational interventions. I describe, using examples from my own work, one such model: the awareness, solidarity, and action model. This three-part model involves the participant\u27s (a) becoming aware of a need for change, (b) developing solidarity with other participants around the actions to be taken, and (c) learning skills to enable action

Using Evaluations to Identify and Eliminate a Barrier to Invasive Weed Control

Evaluation is an important component of educational programming. An example of how evaluation is used to assess need, identify barriers, and guide program development is presented. Impact evaluations from a yearlong project to teach landowners about invasive weed identification and control indicated one of the barriers to implementing knowledge was a lack of access to invasive species control tools. Knowledge of this barrier enabled community organizers to guide the development of a community herbicide shed (CHS). Evaluations of landowners who used the CHS show that the CHS effectively changed the knowledge, attitudes, and practices of all participants

Rorc restrains the potency of ST2+ regulatory T cells in ameliorating intestinal graft-versus-host disease

Soluble stimulation-2 (ST2) is increased during graft-versus-host disease (GVHD), while Tregs that express ST2 prevent GVHD through unknown mechanisms. Transplantation of Foxp3- T cells and Tregs that were collected and sorted from different Foxp3 reporter mice indicated that in mice that developed GVHD, ST2+ Tregs were thymus derived and predominantly localized to the intestine. ST2-/- Treg transplantation was associated with reduced total intestinal Treg frequency and activation. ST2-/- versus WT intestinal Treg transcriptomes showed decreased Treg functional markers and, reciprocally, increased Rorc expression. Rorc-/- T cells transplantation enhanced the frequency and function of intestinal ST2+ Tregs and reduced GVHD through decreased gut-infiltrating soluble ST2-producing type 1 and increased IL-4/IL-10-producing type 2 T cells. Cotransfer of ST2+ Tregs sorted from Rorc-/- mice with WT CD25-depleted T cells decreased GVHD severity and mortality, increased intestinal ST2+KLRG1+ Tregs, and decreased type 1 T cells after transplantation, indicating an intrinsic mechanism. Ex vivo IL-33-stimulated Tregs (TregIL-33) expressed higher amphiregulin and displayed better immunosuppression, and adoptive transfer prevented GVHD better than control Tregs or TregIL-33 cultured with IL-23/IL-17. Amphiregulin blockade by neutralizing antibody in vivo abolished the protective effect of TregIL-33. Our data show that inverse expression of ST2 and RORγt in intestinal Tregs determines GVHD and that TregIL-33 has potential as a cellular therapy avenue for preventing GVHD

Moderators, Mediators, and Prognostic Indicators of Treatment With Hip Arthroscopy or Physical Therapy for Femoroacetabular Impingement Syndrome: Secondary Analyses From the Australian FASHIoN Trial.

BACKGROUND Although randomized controlled trials comparing hip arthroscopy with physical therapy for the treatment of femoroacetabular impingement (FAI) syndrome have emerged, no studies have investigated potential moderators or mediators of change in hip-related quality of life. PURPOSE To explore potential moderators, mediators, and prognostic indicators of the effect of hip arthroscopy and physical therapy on change in 33-item international Hip Outcome Tool (iHOT-33) score for FAI syndrome. STUDY DESIGN Cohort study; Level of evidence, 2. METHODS Overall, 99 participants were recruited from the clinics of orthopaedic surgeons and randomly allocated to treatment with hip arthroscopy or physical therapy. Change in iHOT-33 score from baseline to 12 months was the dependent outcome for analyses of moderators, mediators, and prognostic indicators. Variables investigated as potential moderators/prognostic indicators were demographic variables, symptom duration, alpha angle, lateral center-edge angle (LCEA), Hip Osteoarthritis MRI Scoring System (HOAMS) for selected magnetic resonance imaging (MRI) features, and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) score. Potential mediators investigated were change in chosen bony morphology measures, HOAMS, and dGEMRIC score from baseline to 12 months. For hip arthroscopy, intraoperative procedures performed (femoral ostectomy ± acetabular ostectomy ± labral repair ± ligamentum teres debridement) and quality of surgery graded by a blinded surgical review panel were investigated for potential association with iHOT-33 change. For physical therapy, fidelity to the physical therapy program was investigated for potential association with iHOT-33 change. RESULTS A total of 81 participants were included in the final moderator/prognostic indicator analysis and 85 participants in the final mediator analysis after exclusion of those with missing data. No significant moderators or mediators of change in iHOT-33 score from baseline to 12 months were identified. Patients with smaller baseline LCEA (β = -0.82; P = .034), access to private health care (β = 12.91; P = .013), and worse baseline iHOT-33 score (β = -0.48; P < .001) had greater iHOT-33 improvement from baseline to 12 months, irrespective of treatment allocation, and thus were prognostic indicators of treatment response. Unsatisfactory treatment fidelity was associated with worse treatment response (β = -24.27; P = .013) for physical therapy. The quality of surgery and procedures performed were not associated with iHOT-33 change for hip arthroscopy (P = .460-.665 and P = .096-.824, respectively). CONCLUSION No moderators or mediators of change in hip-related quality of life were identified for treatment of FAI syndrome with hip arthroscopy or physical therapy in these exploratory analyses. Patients who accessed the Australian private health care system, had smaller LCEAs, and had worse baseline iHOT-33 scores, experienced greater iHOT-33 improvement, irrespective of treatment allocation

Neurological diseases as primary gliopathies: a reassessment of neurocentrism

Diseases of the human brain are almost universally attributed to malfunction or loss of nerve cells. However, a considerable amount of work has, during the last decade, expanded our view on the role of astrocytes in CNS (central nervous system), and this analysis suggests that astrocytes contribute to both initiation and propagation of many (if not all) neurological diseases. Astrocytes provide metabolic and trophic support to neurons and oligodendrocytes. Here, we shall endeavour a broad overviewing of the progress in the field and forward the idea that loss of homoeostatic astroglial function leads to an acute loss of neurons in the setting of acute insults such as ischaemia, whereas more subtle dysfunction of astrocytes over periods of months to years contributes to epilepsy and to progressive loss of neurons in neurodegenerative diseases. The majority of therapeutic drugs currently in clinical use target neuronal receptors, channels or transporters. Future therapeutic efforts may benefit by a stronger focus on the supportive homoeostatic functions of astrocytes

Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency.

BACKGROUND: The potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI) and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS) patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) in patients with MS and in sex- and age-matched healthy controls (HC). METHODS: 59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV), venous intracranial fraction (VIF) and average distance-from-vein (DFV) were calculated for various vein mean diameter categories: .9 mm. RESULTS: CCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p < .0001). Patients with MS showed decreased overall ATVV, ATVV of veins with a diameter < .3 mm, and increased DFV compared to HC (all p < .0001). Subjects diagnosed with CCSVI had significantly increased DFV (p < .0001), decreased overall ATVV and ATVV of veins with a diameter < .3 mm (p < .003) compared to subjects without CCSVI. The severity of CCSVI was significantly related to decreased VVV in MS (p < .0001) on pre- and post-contrast SWI, but not in HC. CONCLUSIONS: MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS

matscipy : materials science at the atomic scale with Python

Behaviour of materials is governed by physical phenomena that occur at an extreme range of length and time scales. Computational modelling requires multiscale approaches. Simulation techniques operating on the atomic scale serve as a foundation for such approaches, providing necessary parameters for upper-scale models. The physical models employed for atomic simulations can vary from electronic structure calculations to empirical force fields. However, construction, manipulation and analysis of atomic systems are independent of the given physical model but dependent on the specific application. matscipy implements such tools for applications in materials science, including fracture, plasticity, tribology and electrochemistry

The fallacy of placing confidence in confidence intervals

Interval estimates – estimates of parameters that include an allowance for sampling uncertainty – have long been touted as a key component of statistical analyses. There are several kinds of interval estimates, but the most popular are confidence intervals (CIs): intervals that contain the true parameter value in some known proportion of repeated samples, on average. The width of confidence intervals is thought to index the precision of an estimate; CIs are thought to be a guide to which parameter values are plausible or reasonable; and the confidence coefficient of the interval (e.g., 95 %) is thought to index the plausibility that the true parameter is included in the interval. We show in a number of examples that CIs do not necessarily have any of these properties, and can lead to unjustified or arbitrary inferences. For this reason, we caution against relying upon confidence interval theory to justify interval estimates, and suggest that other theories of interval estimation should be used instead

Split-Cre Complementation Indicates Coincident Activity of Different Genes In Vivo

Cre/LoxP recombination is the gold standard for conditional gene regulation in mice in vivo. However, promoters driving the expression of Cre recombinase are often active in a wide range of cell types and therefore unsuited to target more specific subsets of cells. To overcome this limitation, we designed inactive “split-Cre” fragments that regain Cre activity when overlapping co-expression is controlled by two different promoters. Using transgenic mice and virus-mediated expression of split-Cre, we show that efficient reporter gene activation is achieved in vivo. In the brain of transgenic mice, we genetically defined a subgroup of glial progenitor cells in which the Plp1- and the Gfap-promoter are simultaneously active, giving rise to both astrocytes and NG2-positive glia. Similarly, a subset of interneurons was labelled after viral transfection using Gad67- and Cck1 promoters to express split-Cre. Thus, split-Cre mediated genomic recombination constitutes a powerful spatial and temporal coincidence detector for in vivo targeting

From insect to man: Photorhabdus sheds light on the emergence of human pathogenicity

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway