Routes to the top : the developmental journeys of medical, clinical and managerial NHS Chief Executives

Introduction Leadership, and the role of a Chief Executive in healthcare organisations, has never been more important. This review provides one of the first retrospective cross-sectional analyses of the developmental journeys of chief executives within the National Health Service (NHS). Methods Twenty-eight semi-structured qualitative interviews were conducted with medical, clinical and non-clinical NHS chief executives from the Health Service Journal’s list of ‘Top Chief Executives’ 2014–2018. Through a thematic analysis of their narratives, lessons for the development of aspiring NHS chief executives emerge. Results Few proactively sought leadership opportunities and there was a lack of an active leadership development strategy. Yet the ‘seeds of leadership development’ took root early. Combined with a blended approach of formal leadership development and ‘on-the-job’ informal leadership development, emerging NHS chief executives were exposed to multiple ‘crucible moments’ that helped them develop into and excel at the top of their field. Discussion Top NHS chief executives possess inherent values and a strong sense of social responsibility that underpin their developmental journeys, guide their behaviour, and strengthen their resilience. Capable, high quality leaders are needed from all professional backgrounds to support high quality care and much more needs to be done, particularly for medical and clinical professionals but for non-clinicians too, to maximise leadership potential within the NHS and develop a pipeline of aspiring NHS chief executives

Search for long lived charged massive particles in pp collisions at s-hat = 1.8TeV

We report a search for the production of long-lived charged massive particles in a data sample of 90   pb-1 of √s=1.8   TeV pp̅ collisions recorded by the Collider Detector at Fermilab. The search uses the muonlike penetration and anomalously high ionization energy loss signature expected for such a particle to discriminate it from backgrounds. The data are found to agree with background expectations, and cross section limits of O(1) pb are derived using two reference models, a stable quark and a stable scalar lepton

The Fair Labor Standards Act: A Tool for Those Who Represent Employees, Claimants, and Plaintiffs

The Fair Labor Standards Act (FLSA) of 1938 is a comprehensive federal statute that regulates minimum wages, maximum hours, and child labor. This article is intended to provide background for the general practitioner in an effort to help advance the interests of Kansas Association for Justice clients and workers. The FLSA was created to hold disreputable employers to account for chiseling their workers. The tangle of rules and regulations that followed may have complicated the operation of a basically straightforward law. But as long as lawyers understand and can navigate these highly technical provisions, FDR’s grand vision for fair and safe employment is within reach

Private Enforcement of the Kansas Wage Payment Act

This is the published version

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

SRC tyrosine kinase is frequently overexpressed and activated in late-stage, poor prognosis ovarian tumours, and preclinical studies have supported the use of targeted SRC inhibitors in the treatment of this disease. The SAPPROC trial investigated the addition of the SRC inhibitor saracatinib (AZD0530) to weekly paclitaxel for the treatment of platinum resistant ovarian cancer; however, this drug combination did not provide any benefit to progression free survival (PFS) of women with platinum resistant disease. In this study we aimed to identify mechanisms of resistance to SRC inhibitors in ovarian cancer cells. Using two complementary strategies; a targeted tumour suppressor gene siRNA screen, and a phospho-receptor tyrosine kinase array, we demonstrate that activation of MAPK signalling, via a reduction in NF1 (neurofibromin) expression or overexpression of HER2 and the insulin receptor, can drive resistance to AZD0530. Knockdown of NF1 in two ovarian cancer cell lines resulted in resistance to AZD0530, and was accompanied with activated MEK and ERK signalling. We also show that silencing of HER2 and the insulin receptor can partially resensitize AZD0530 resistant cells, which was associated with decreased phosphorylation of MEK and ERK. Furthermore, we demonstrate a synergistic effect of combining SRC and MEK inhibitors in both AZD0530 sensitive and resistant cells, and that MEK inhibition is sufficient to completely resensitize AZD0530 resistant cells. This work provides a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials

Cross sections for nu(mu) and (nu)over-bar(mu) induced pion production on hydrocarbon in the few-GeV region using MINERvA

Separate samples of charged-current pion production events representing two semi-inclusive channels nu(mu)-CC(pi(+)) and (nu) over bar (mu) -CC(pi(0)) have been obtained using neutrino and antineutrino exposures of the MINERvA detector. Distributions in kinematic variables based upon mu(+/-)-track reconstructions are analyzed and compared for the two samples. The differential cross sections for muon production angle, muon momentum, and four-momentum transfer Q(2) are reported, and cross sections versus neutrino energy are obtained. Comparisons with predictions of current neutrino event generators are used to clarify the role of the Delta(1232) and higher-mass baryon resonances in CC pion production and to show the importance of pion final-state interactions. For the nu(mu)-CC(pi(+)) [(nu) over bar (mu)-(pi(0))] sample, the absolute data rate is observed to lie below (above) the predictions of some of the event generators by amounts that are typically 1-to- 2 sigma. However the generators are able to reproduce the shapes of the differential cross sections for all kinematic variables of either data set

Charged pion production in nu(mu) interactions on hydrocarbon at \u3c E-nu \u3e=4.0 GeV

Charged pion production via charged-current nu(mu) interactions on plastic scintillator (CH) is studied using the MINERvA detector exposed to the NuMI wideband neutrino beam at Fermilab. Events with hadronic invariant massW \u3c 1.4 GeV and W \u3c 1.8 GeV are selected in separate analyses: the lower W cut isolates single pion production, which is expected to occur primarily through the Delta(1232) resonance, while results from the higher cut include the effects of higher resonances. Cross sections as functions of pion angle and kinetic energy are compared to predictions from theoretical calculations and generator-based models for neutrinos ranging in energy from 1.5-10 GeV. The data are best described by calculations which include significant contributions from pion intranuclear rescattering. These measurements constrain the primary interaction rate and the role of final state interactions in pion production, both of which need to be well understood by neutrino oscillation experiments

Activation of MAPK signalling results in resistance to saracatinib (AZD0530) in ovarian cancer

SRC tyrosine kinase is frequently overexpressed and activated in late-stage, poor prognosis ovarian tumours, and preclinical studies have supported the use of targeted SRC inhibitors in the treatment of this disease. The SAPPROC trial investigated the addition of the SRC inhibitor saracatinib (AZD0530) to weekly paclitaxel for the treatment of platinum resistant ovarian cancer; however, this drug combination did not provide any benefit to progression free survival (PFS) of women with platinum resistant disease. In this study we aimed to identify mechanisms of resistance to SRC inhibitors in ovarian cancer cells. Using two complementary strategies; a targeted tumour suppressor gene siRNA screen, and a phospho-receptor tyrosine kinase array, we demonstrate that activation of MAPK signalling, via a reduction in NF1 (neurofibromin) expression or overexpression of HER2 and the insulin receptor, can drive resistance to AZD0530. Knockdown of NF1 in two ovarian cancer cell lines resulted in resistance to AZD0530, and was accompanied with activated MEK and ERK signalling. We also show that silencing of HER2 and the insulin receptor can partially resensitize AZD0530 resistant cells, which was associated with decreased phosphorylation of MEK and ERK. Furthermore, we demonstrate a synergistic effect of combining SRC and MEK inhibitors in both AZD0530 sensitive and resistant cells, and that MEK inhibition is sufficient to completely resensitize AZD0530 resistant cells. This work provides a preclinical rationale for the combination of SRC and MEK inhibitors in the treatment of ovarian cancer, and also highlights the need for biomarker driven patient selection for clinical trials

A case of limbic encephalitis presenting as a paraneoplastic manifestation of limited stage small cell lung cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>The differential diagnosis of altered mental status and behavioral change is very extensive. Paraneoplastic limbic encephalitis is a rare cause of cognitive impairment, which should be considered in the differential diagnosis.</p> <p>Case presentation</p> <p>A 64-year-old British Caucasian woman presented to our hospital with a 12-week history of confusion and short-term memory loss. She was hyponatremic with a serum sodium level of 128mmol/L. Moreover, there was evidence of left hilar prominence on the chest radiograph. A thoracic computed tomography scan showed left hilar opacity with confluent lymphadenopathy. A percutaneous biopsy confirmed a diagnosis of small cell lung cancer. There was no radiological evidence of brain metastasis on the computed tomography scan. In view of continued cognitive impairment, which was felt to be disproportionate to hyponatremia, a magnetic resonance imaging scan of the brain was undertaken. It showed hyperintense signals from both hippocampi, highly suggestive of limbic encephalitis presenting as a paraneoplastic manifestation of small cell lung cancer. She had a significant radiological and clinical response following chemotherapy and radiotherapy.</p> <p>Conclusion</p> <p>This case highlights the importance of considering paraneoplastic syndromes in patients with neurological symptoms in the context of lung malignancy. If initial investigations fail to reveal the cause of cognitive impairment in a patient with malignancy, magnetic resonance imaging may be invaluable in the diagnosis of limbic encephalitis. The clinical presentation, diagnostic techniques and management of paraneoplastic limbic encephalitis are discussed in this case report.</p