3,669 research outputs found
Advances in breast cancer treatment and prevention: preclinical studies on aromatase inhibitors and new selective estrogen receptor modulators (SERMs).
Intensive basic and clinical research over the past 20 years has yielded crucial molecular understanding into how estrogen and the estrogen receptor act to regulate breast cancer and has led to the development of more effective, less toxic, and safer hormonal therapy agents for breast cancer management and prevention. Selective potent aromatase inhibitors are now challenging the hitherto gold standard of hormonal therapy, the selective estrogen-receptor modulator tamoxifen. Furthermore, new selective estrogen-receptor modulators such as arzoxifene, currently under clinical development, offer the possibility of selecting one with a more ideal pharmacological profile for treatment and prevention of breast cancer. Two recent studies in preclinical model systems that evaluate mechanisms of action of these new drugs and suggestions about their optimal clinical use are discussed
Learning to ride the high growth “rollercoaster” : the role of publicly funded business accelerator programmes
Funding: Welsh Government.High growth firms (HGFs) are a vital determinant of regional economic competitiveness. This paper examines the effectiveness of a Welsh publicly funded business accelerator programme (BAP) designed to nurture HGFs via relational support measures. The paper teases out both the support requirements sought by high growth entrepreneurs, together with the perceived effectiveness of the programme’s offering. Hitherto, the literature has been silent in terms of the mental well-being and psychological resilience of founders of HGFs. This study discovered how mental well-being and psychological resilience of entrepreneurs was very acutely and detrimentally affected when experiencing periods of rapid firm growth. The research also uncovered a disconnect between the support needs of HGFs and those provided by BAPs. To help develop the capabilities and durability of entrepreneurs, “growth readiness” coaching together with psychological resilience training seem appropriate policy measures to help entrepreneurs successfully navigate turbulent episodes of high growth.Peer reviewe
Trigger points and high growth firms : the vital role of founder “sensing” and “seizing” capabilities
The authors wish to acknowledge the funding this research received from the Welsh Government through the Business Wales Accelerated Growth Programme (AGP).Purpose Research on high growth firms (HGFs) is booming yet a strong conceptual understanding of how these firms obtain (and sustain) rapid growth remains (at best) partial. The main purpose of this paper to explore the role founders play in enabling episodes of rapid growth and how they help navigate this process. Design/methodology/approach This paper reports the findings from a qualitative study involving in-depth interviews with entrepreneurs enlisted onto a publicly funded high growth business accelerator programme in Wales. These interviews explored the causes of the firms’ rapid growth, their key growth trigger points, and the organisational consequences of rapid growth. Findings The research reveals that periods of high growth are intrinsically and inextricably inter-linked with the entrepreneurial traits and capabilities of their founders coupled with their ability to “sense” and “seize” pivotal growth opportunities. It also demonstrates founder-level dynamic capabilities enable firms to capitalise on pivotal “trigger points” thereby enabling their progression to a new “dynamic state” in a firm’s temporal evolution. Originality/value The novel approach towards theory building deployed herein is the use of theoretical elaboration as means of extending important existing theoretical constructs such as growth “trigger points” and founder dynamic capabilities. To capitalise on these trigger points, founders have to undergo a process of “temporal transitioning” to effectively manage and execute the growth process in firms. The work also has important policy implications, underlining the need for more relational forms of support for entrepreneurial founders.Peer reviewe
Hydrogen Balmer Line Broadening in Solar and Stellar Flares
The broadening of the hydrogen lines during flares is thought to result from
increased charge (electron, proton) density in the flare chromosphere. However,
disagreements between theory and modeling prescriptions have precluded an
accurate diagnostic of the degree of ionization and compression resulting from
flare heating in the chromosphere. To resolve this issue, we have incorporated
the unified theory of electric pressure broadening of the hydrogen lines into
the non-LTE radiative transfer code RH. This broadening prescription produces a
much more realistic spectrum of the quiescent, A0 star Vega compared to the
analytic approximations used as a damping parameter in the Voigt profiles. We
test recent radiative-hydrodynamic (RHD) simulations of the atmospheric
response to high nonthermal electron beam fluxes with the new broadening
prescription and find that the Balmer lines are over-broadened at the densest
times in the simulations. Adding many simultaneously heated and cooling model
loops as a "multithread" model improves the agreement with the observations. We
revisit the three-component phenomenological flare model of the YZ CMi
Megaflare using recent and new RHD models. The evolution of the broadening,
line flux ratios, and continuum flux ratios are well-reproduced by a
multithread model with high-flux nonthermal electron beam heating, an extended
decay phase model, and a "hot spot" atmosphere heated by an ultrarelativistic
electron beam with reasonable filling factors: 0.1%, 1%, and 0.1% of the
visible stellar hemisphere, respectively. The new modeling motivates future
work to understand the origin of the extended gradual phase emission.Comment: 31 pages, 13 figures, 2 tables, accepted for publication in the
Astrophysical Journa
FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.
Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs. Independent genome-wide association analyses for skeletal dysplasia (short limbs) within a single breed (PBonferroni = 0.01) and intervertebral disc disease (IVDD) across breeds (PBonferroni = 4.0 Ă— 10-10) both identified a significant association to the same region on CFA12. Whole genome sequencing identified a highly expressed FGF4 retrogene within this shared region. The FGF4 retrogene segregated with limb length and had an odds ratio of 51.23 (95% CI = 46.69, 56.20) for IVDD. Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species. FGF signaling abnormalities have been associated with skeletal dysplasia in humans, and our findings present opportunities for both selective elimination of a medically and financially devastating disease in dogs and further understanding of the ever-growing complexity of retrogene biology
Outlier detection of vital sign trajectories from COVID-19 patients
There is growing interest in continuous wearable vital sign sensors for
monitoring patients remotely at home. These monitors are usually coupled to an
alerting system, which is triggered when vital sign measurements fall outside a
predefined normal range. Trends in vital signs, such as an increasing heart
rate, are often indicative of deteriorating health, but are rarely incorporated
into alerting systems. In this work, we present a novel outlier detection
algorithm to identify such abnormal vital sign trends. We introduce a
distance-based measure to compare vital sign trajectories. For each patient in
our dataset, we split vital sign time series into 180 minute, non-overlapping
epochs. We then calculated a distance between all pairs of epochs using the
dynamic time warp distance. Each epoch was characterized by its mean pairwise
distance (average link distance) to all other epochs, with large distances
considered as outliers. We applied this method to a pilot dataset collected
over 1561 patient-hours from 8 patients who had recently been discharged from
hospital after contracting COVID-19. We show that outlier epochs correspond
well with patients who were subsequently readmitted to hospital. We also show,
descriptively, how epochs transition from normal to abnormal for one such
patient.Comment: 4 pages, 4 figures, 1 table. Submitted to IEEE BHI 2022, decision
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