Exploring Leadership Characteristics and Their Effects on Sustaining Federally Qualified Health Centers

An argument can be made for the continued existence of Federally Qualified Health Centers (FQHCs) because of the level of importance of the service they provide to society. The problem addressed in this research is that despite the millions of people in need of affordable health care, the leaders of many FQHCs are fighting to keep facilities open amidst financial struggles. The purpose of this research was to identify leadership characteristics that promote FQHCs’ success by assessing effective leadership styles. This study applied a quantitative, descriptive non-experimental approach. Probability sampling was used to select the sample size and the Multifactor Leadership Questionnaire Form 5X-Short survey instrument was used to gather the data from 17 participants. The results revealed that participants perceived transformational leadership as valuable. There was no significant association between leadership characteristics and organization financial success. It is recommended that FQHC leaders incorporate transformational leadership styles into their existing leadership development program. Further research is needed to validate the findings of this study, such as the application of transformational leadership and organizational success. Transformation leadership style, when incorporated into FQHCs’ organizational strategies, could provide positive social change implications whereby changes in staff engagement can lead to better accountability and result in sustainability of FQHCs to continue the service delivery of primary preventative medical and supportive services, at low cost. This effort could create additional access to medical care for more than 30 million underserved individuals and support the continued existence and survivability of these organizations

FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes.

Mutations in the transcription factor FOXA1 define a unique subset of prostate cancers but the functional consequences of these mutations and whether they confer gain or loss of function is unknown1-9. Here, by annotating the landscape of FOXA1 mutations from 3,086 human prostate cancers, we define two hotspots in the forkhead domain: Wing2 (around 50% of all mutations) and the highly conserved DNA-contact residue R219 (around 5% of all mutations). Wing2 mutations are detected in adenocarcinomas at all stages, whereas R219 mutations are enriched in metastatic tumours with neuroendocrine histology. Interrogation of the biological properties of wild-type FOXA1 and fourteen FOXA1 mutants reveals gain of function in mouse prostate organoid proliferation assays. Twelve of these mutants, as well as wild-type FOXA1, promoted an exaggerated pro-luminal differentiation program, whereas two different R219 mutants blocked luminal differentiation and activated a mesenchymal and neuroendocrine transcriptional program. Assay for transposase-accessible chromatin using sequencing (ATAC-seq) of wild-type FOXA1 and representative Wing2 and R219 mutants revealed marked, mutant-specific changes in open chromatin at thousands of genomic loci and exposed sites of FOXA1 binding and associated increases in gene expression. Of note, ATAC-seq peaks in cells expressing R219 mutants lacked the canonical core FOXA1-binding motifs (GTAAAC/T) but were enriched for a related, non-canonical motif (GTAAAG/A), which was preferentially activated by R219-mutant FOXA1 in reporter assays. Thus, FOXA1 mutations alter its pioneering function and perturb normal luminal epithelial differentiation programs, providing further support for the role of lineage plasticity in cancer progression

Cost–utility analysis of imatinib mesilate for the treatment of advanced stage chronic myeloid leukaemia

Imatinib mesilate (Glivec®, Novartis Pharmaceuticals) is a novel therapy for the treatment of chronic myeloid leukaemia (CML). We evaluated the cost-effectiveness of imatinib (600 mg daily) when used for the treatment of patients in advanced stages of CML (accelerated phase and blast crisis) against conventional therapies of combination chemotherapy (DAT) and palliative care in hospital or at home. A Markov model simulated the transitions of hypothetical patient cohorts and outcomes were modelled for 5 years from the start of treatment. Costs were estimated from the perspective of the UK National Health Service. Over 5 years, a patient in accelerated phase will, on average, accrue an additional 2.09 QALYs with imatinib compared to conventional therapies, while patients in blast crisis will accrue an additional 0.58 quality-adjusted life-years (QALYs) with imatinib compared to conventional therapies. The costs per additional QALY gained from treatment with imatinib compared with conventional therapies were £29 344 (accelerated phase) and £42 239 (blast crisis). The results were particularly sensitive to the price of imatinib, improvements in quality of life, and the duration of haematological responses. We conclude that treatment of CML with imatinib confers considerably greater survival and quality of life than conventional treatments but at a cost

Genetic network properties of the human cortex based on regional thickness and surface area measures

We examined network properties of genetic covariance between average cortical thickness (CT) and surface area (SA) within genetically-identified cortical parcellations that we previously derived from human cortical genetic maps using vertex-wise fuzzy clustering analysis with high spatial resolution. There were 24 hierarchical parcellations based on vertex-wise CT and 24 based on vertex-wise SA expansion/contraction; in both cases the 12 parcellations per hemisphere were largely symmetrical. We utilized three techniques—biometrical genetic modeling, cluster analysis, and graph theory—to examine genetic relationships and network properties within and between the 48 parcellation measures. Biometrical modeling indicated significant shared genetic covariance between size of several of the genetic parcellations. Cluster analysis suggested small distinct groupings of genetic covariance; networks highlighted several significant negative and positive genetic correlations between bilateral parcellations. Graph theoretical analysis suggested that small world, but not rich club, network properties may characterize the genetic relationships between these regional size measures. These findings suggest that cortical genetic parcellations exhibit short characteristic path lengths across a broad network of connections. This property may be protective against network failure. In contrast, previous research with structural data has observed strong rich club properties with tightly interconnected hub networks. Future studies of these genetic networks might provide powerful phenotypes for genetic studies of normal and pathological brain development, aging, and function

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic

Is there a cloud in the silver lining for imatinib?

Imatinib mesylate (Gleevec® or Glivec®), a small molecule tyrosine kinase inhibitor for the treatment of chronic myeloid leukaemia, has been said to herald the dawn of a new er-a of rationally designed, molecularly targeted oncotherapy. Lurking on the same new horizon, however, is the age-old spectre of drug resistance. This review sets the intoxicating clinical perspective against the more sobering laboratory evidence of such divergent mechanisms of imatinib resistance as gene amplification and stem cell quiescence. Polychemotherapy has already been considered to combat resistance, but a more innovative, as yet unformulated, approach may be advocated

Raman-IR spectroscopic, and XRD analysis of selected samples from Fogo Island, Cabo Verde: Implications for ancient Martian volcanology

Several space missions from NASA, and ESA have visited and will land on Mars in the search for life. The last mission to arrive was the Mars 2020 Perseverance rover on 18 February 2021. The next mission to Mars will be ExoMars Rosalind Franklin rover, expected to touch down sometime after 2028. Both Mars2020 and ExoMars are equipped with Raman spectroscopic systems: SuperCam and SHERLOC on Perseverance, and Raman Laser Spectrometer (RLS) on Rosalind Franklin (RF). These instruments will be tasked with identifying rocks, minerals, and potential organic biosignatures on the Martian surface. There are many challenges associated with the qualitative and quantitative analysis of resulting data received from current missions on Mars. It is our belief that studies of new terrestrial Martian analogues can help to overcome these challenges. Here, we introduce Chã das Caldeiras Outcrop, Fogo Island, Cabo Verde as a new volcanic terrestrial analog for Mars. We sampled several areas of relevance in Chã das Caldeiras and conducted a complete band analysis of Raman spectra for targets from this site. Additional analyses included ATR-FTIR and XRD. We detected several pyroxene types (augite and diopside) and plagioclase feldspar species (orthoclase, bytownite, sanidine, albite, and anorthite), olivine (forsterite), oxides (magnetite), and leucite. The alteration and secondary minerals detected were carbonates (calcite and dolomite), oxides (goethite, anatase, and hematite), spinel (chromite), phosphate (apatite), various clays, and zeolites (chabazite and muscovite and analcime). We present the Chã das Caldeiras site as a possible new volcanic analogue for Mars given: 1) the similarities to other volcanic places in the Canary Islands; 2) the exclusive geological evolution that is only present in the volcanic emplacement from the Macaronecia-group; 3) the pristine quality of the samples from the outcrop as well as the alteration volcanic minerals.MGD at CRESS, York University, is especially thankful for the financial support provided by the Natural Sciences and Engineering Research Council of Canada (NSERC), the Ontario Centre of Excellence (OCE), and the Canadian Space Agency. GLR, MV, FR, and JAM would like to acknowledge the financial support provided for this project by the European Research Council in the H2020- COMPET-2015 Programme (grant 687302) and the Ministry of Economy and Competitiveness (MINECO, grant PID2019-107442RB-C31/AEI/10.13039/501100011033). EAC thanks the Canada Foundation for Innovation, Research Manitoba, NSERC, the Canadian Space Agency, and the University of Winnipeg for supporting this study. Finally, EAL and MK want to thank Pebbles for her logistical support.Peer reviewe