Transformational Leadership: An Urban Leaders\u27 Autoethnography

My story of lived experiences is told through a transformational leadership lens whereby the leader is charged with identifying the need for change, creating the vision to guide the change through inspiration and executing the change in tandem with committed members of the group. An autoethnography is a style of autobiographical writing that explores an individual\u27s unique life experiences in a natural setting. The researchers\u27 lived experiences are scholarly and justifiable interpretations supported by multiple sources of evidence and artifacts

Macrostrain measurement using radial collimators at LANSCE

A series of `short` radial collimators have been implemented in the 90{degrees} scattering geometries on the neutron powder diffractometer at Los Alamos. The capability to perform macrostrain measurements has been improved by the commensurate ability to rapidly select a sampling volume appropriate to the specimen. The compact design of the collimators was dictated by the need to fit them in a cylindrical vacuum chamber as well as providing space in which to manipulate a specimen in three dimensions. Collimators of different vane lengths were fabricated to give 4 different resolutions for which 2/3 of the diffracted intensity comes form distances of 0.75, 1. 25, 2.5, and 4.0 mm along the incident beam. Qualifying scans and a demonstration of a cracked ring, containing a steep stress gradient, are included

Design and Implementation of an X-Ray Strain Measurement Capability Using a Rotating Anode Machine

This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). Residual stresses close to the surface can improve the reliability and lifetime of parts for technological applications. X-ray diffraction plays a significant role in gaining an exact knowledge of the stresses at the surface and their depth distribution. An x-ray capability at Los Alamos is key to developing and maintaining industrial collaborations in strain effects. To achieve this goal, the authors implemented a residual strain measuring station on the rotating anode x-ray instrument at the Lujan Center. This capability has been used to investigate residual strains in heat treated automotive components, machining effects on titanium alloys, resistance welded steel joints, titanium matrix fiber reinforced composites, ceramic matrix composites, thin films, and ceramic coatings. The overall objective is to combine both x-ray and neutron diffraction measurements with numerical models (e.g., finite element calculations)

Mechanical properties of NiTi-TiC shape-memory composites

This paper reviews recent work on the mechanical behavior of martensitic NiTi composites reinforced with 10--20 vol.% TiC particulates. The behavior of the composites is compared to that of unreinforced NiTi, so as to elucidate the effect of mismatch due to matrix transformation, thermal expansion, twinning or slip, in the presence of purely elastic particles. The twinning and subsequent thermal recovery of deformed composites, measured both macroscopically (by compressive testing and by dilatometry) and microscopically (by neutron diffraction), are summarized

UV Circular Polarisation in Star Formation Regions : The Origin of Homochirality?

Ultraviolet circularly polarised light has been suggested as the initial cause of the homochirality of organic molecules in terrestrial organisms, via enantiomeric selection of prebiotic molecules by asymmetric photolysis. We present a theoretical investigation of mechanisms by which ultraviolet circular polarisation may be produced in star formation regions. In the scenarios considered here, light scattering produces only a small percentage of net circular polarisation at any point in space, due to the forward throwing nature of the phase function in the ultraviolet. By contrast, dichroic extinction can produce a fairly high percentage of net circular polarisation (∼10%) and may therefore play a key role in producing an enantiomeric excessPeer reviewe

Network analysis of inflammation and symptoms in recent onset schizophrenia and the influence of minocycline during a clinical trial

Abstract Attempts to delineate an immune subtype of schizophrenia have not yet led to the clear identification of potential treatment targets. An unbiased informatic approach at the level of individual immune cytokines and symptoms may reveal organisational structures underlying heterogeneity in schizophrenia, and potential for future therapies. The aim was to determine the network and relative influence of pro- and anti-inflammatory cytokines on depressive, positive, and negative symptoms. We further aimed to determine the effect of exposure to minocycline or placebo for 6 months on cytokine-symptom network connectivity and structure. Network analysis was applied to baseline and 6-month data from the large multi-center BeneMin trial of minocycline (N = 207) in schizophrenia. Pro-inflammatory cytokines IL-6, TNF-α, and IFN-γ had the greatest influence in the inflammatory network and were associated with depressive symptoms and suspiciousness at baseline. At 6 months, the placebo group network connectivity was 57% stronger than the minocycline group, due to significantly greater influence of TNF-α, early wakening, and pathological guilt. IL-6 and its downstream impact on TNF-α, and IFN-γ, could offer novel targets for treatment if offered at the relevant phenotypic profile including those with depression. Future targeted experimental studies of immune-based therapies are now needed

Structural neural networks subserving oculomotor function in first-episode schizophrenia

BACKGROUND: Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. METHODS: In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. RESULTS: We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. CONCLUSIONS: These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia

STING agonism overcomes STAT3-mediated immunosuppression and adaptive resistance to PARP inhibition in ovarian cancer

BackgroundPoly (ADP-ribose) polymerase (PARP) inhibition (PARPi) has demonstrated potent therapeutic efficacy in patients with BRCA-mutant ovarian cancer. However, acquired resistance to PARPi remains a major challenge in the clinic.MethodsPARPi-resistant ovarian cancer mouse models were generated by long-term treatment of olaparib in syngeneic Brca1-deficient ovarian tumors. Signal transducer and activator of transcription 3 (STAT3)-mediated immunosuppression was investigated in vitro by co-culture experiments and in vivo by analysis of immune cells in the tumor microenvironment (TME) of human and mouse PARPi-resistant tumors. Whole genome transcriptome analysis was performed to assess the antitumor immunomodulatory effect of STING (stimulator of interferon genes) agonists on myeloid cells in the TME of PARPi-resistant ovarian tumors. A STING agonist was used to overcome STAT3-mediated immunosuppression and acquired PARPi resistance in syngeneic and patient-derived xenografts models of ovarian cancer.ResultsIn this study, we uncover an adaptive resistance mechanism to PARP inhibition mediated by tumor-associated macrophages (TAMs) in the TME. Markedly increased populations of protumor macrophages are found in BRCA-deficient ovarian tumors that rendered resistance to PARPi in both murine models and patients. Mechanistically, PARP inhibition elevates the STAT3 signaling pathway in tumor cells, which in turn promotes protumor polarization of TAMs. STAT3 ablation in tumor cells mitigates polarization of protumor macrophages and increases tumor-infiltrating T cells on PARP inhibition. These findings are corroborated in patient-derived, PARPi-resistant BRCA1-mutant ovarian tumors. Importantly, STING agonists reshape the immunosuppressive TME by reprogramming myeloid cells and overcome the TME-dependent adaptive resistance to PARPi in ovarian cancer. This effect is further enhanced by addition of the programmed cell death protein-1 blockade.ConclusionsWe elucidate an adaptive immunosuppression mechanism rendering resistance to PARPi in BRCA1-mutant ovarian tumors. This is mediated by enrichment of protumor TAMs propelled by PARPi-induced STAT3 activation in tumor cells. We also provide a new strategy to reshape the immunosuppressive TME with STING agonists and overcome PARPi resistance in ovarian cancer.Peer reviewe

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians?

What factors in rural and remote extended clinical placements may contribute to preparedness for practice, from the perspective of students and clinicians? Michele Daly, David Perkins, Koshila Kumar, Chris Roberts and Malcolm Moore Background: Community based rural education opportunities have expanded in Australia, attracting more medical students to placements in rural and remote settings. Aim: To identify the factors in an integrated, community engaged rural placement that may contribute to preparedness for practice (P4P), from the perspective of students and clinicians Methods: Forty two semi-structured interviews with medical students, supervisors and clinicians analysed thematically. Results: Opportunities for clinical learning, personal and professional development and cultural awareness were reported by students and clinicians as key factors that contribute to preparedness for practice. Potential barriers in rural and remote settings included geographical and academic isolation, perceived educational risk and differing degrees of program engagement. Conclusions: A longitudinal clinical placement in a rural setting may enable development of enhanced competencies leading to P4P. A rural setting can help provide a unique experience through hands-on learning, enhanced personal and professional development opportunities and observation of the cultural and contextual impact on health