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The impact of age on survival and excess mortality after autologous hematopoietic cell transplantation in newly diagnosed multiple myeloma patients
Get PDFDespite the availability of novel agents, autologous hematopoietic cell transplantation (auto-HCT) remains the standard of care in newly diagnosed multiple myeloma (MM) patients. The impact of age on overall survival (OS), progression-free survival (PFS), relapse incidence, non-relapse mortality (NRM), and excess mortality (taking account of general population mortality) was investigated using information on 61,797 MM patients transplanted between 2013 and 2017. The median age at auto-HCT was 60.8 (range: 18.1–83.2) years of whom 2.0% were 18–39 years, 68.9% 40–64 years, 21.8% 65–69 years, 6.5% 70–74 years, and 0.8% ≥75 years of age, respectively. The corresponding OS probabilities at three years were 85.9%, 82.8%, 81.1%, 78.4%, and 74.8%, respectively (p<0.001). Excess mortality cumulative incidences were 13.1%, 15.0%, 14.6%, 15.0%, and 14.1% at three years, respectively (p=0.67). In multivariable analyses, older age was a significant risk factor for OS, PFS, and NRM but not for excess mortality or relapse risk. Our results indicate that advanced age alone should not preclude the use of auto-HCT in patients with MM
Observing differential spin currents by resonant inelastic X-ray scattering
Get PDFControlling spin currents, i.e., the flow of spin angular momentum, in small magnetic devices is the principal objective of spin electronics, a main contender for future
energy efficient information technologies. Surprisingly, a pure spin current has never
been measured directly since the associated electric stray fields and/or shifts in the
non-equilibrium spin-dependent distribution functions are too small for conventional
experimental detection methods optimized for charge transport. Here we report that
resonant inelastic x-ray scattering (RIXS) can bridge this gap by measuring the spin
current carried by magnons – the quanta of the spin wave excitations of the magnetic
order – in the presence of temperature gradients across a magnetic insulator. This is
possible due to the sensitivity of the momentum- and energy-resolved RIXS intensity
to minute changes in the magnon distribution under non-equilibrium conditions. We
use the Boltzmann equation in the relaxation time approximation to extract transport parameters, such as the magnon lifetime at finite momentum, essential for the
realization of magnon spintronics
Stated preferences for the colours, smells, and sounds of biodiversity
Get PDFForest creation and restoration are embedded in global policy. Both result in landscape changes that have far-reaching socioeconomic consequences. However, there is limited evidence on public preferences for the biodiversity these forests contain. Here we used a choice experiment to explore the British public's willingness to pay (WTP) for different forest biodiversity attributes. We began with a multiple-step deliberative participatory process. This revealed that participants conceptualised forest biodiversity through visual, aural and olfactory senses. We subsequently developed and pre-tested sensory attributes based on colours, smells and sounds. Depending on the size of the proposed change, participants (N = 1711) were willing-to-pay for a greater variety of sensory attributes and for an indicator of improved ecological functioning (deadwood for decomposition). WTP for sensory attributes was influenced by participants' having related sensory impairments or visiting forests frequently. Our wider contribution highlights the importance of participatory methods to unearth novel and uncommon attributes that can then be used in stated preference studies. Ensuring that we evaluate stated preferences in a manner that reflects how the public conceives biodiversity is important if we are to improve the alignment between forest creation/restoration and public views, which could thus help bolster public support for the planning and implementation of landscape changes
Digital transformation and the AI imperative in public and private sector projects: Methods and skills for project management
No full textBalancing rigour and practicality when conducting large-scale, longitudinal audio diary studies: guidance for business and management research
Get PDFPurpose
This paper aims to expand the methodological toolkit by detailing an approach for conducting large-scale audio diary studies in business and management education research. The authors address two research questions: (1) How can large-scale, longitudinal audio diary studies be conducted in a way that balances rigour and practicality? (2) What methodological challenges arise when implementing a longitudinal audio diary study at scale, and how might these be addressed?
Design/methodology/approach
They draw on insights from a study with 128 international students in a UK business school who provided a combined 602 reflective audio diary contributions to inform a ten-step process for conducting large-scale audio diary studies.
Findings
They present a flexible ten-step process, discussing challenges and recommendations regarding participant engagement and retention, technology, data quality and resource demands.
Originality/value
They conclude with examples of four themes for future research applications of audio diary studies: employability perceptions, mental health and well-being, ethical decision-making and corporate social responsibility awareness and innovation and entrepreneurial mindset development. These research avenues represent opportunities to promote a sustainable career trajectory for individuals and offer societal benefits via a sustainable career ecosystem
Search for a new pseudoscalar decaying into a pair of bottom and antibottom quarks in top-associated production in √s = 13 TeV proton–proton collisions with the ATLAS detector
Get PDFA search for a pseudoscalar a produced in association with a top-quark pair, or in association with a single
top quark plus a W boson, with the pseudoscalar decaying
into b-quarks (a → bb¯), is performed using the full Run 2
data sample using a dileptonic decay mode signature. The
search covers pseudoscalar boson masses between 12 and
100 GeV and involves both the kinematic regime where the
decay products of the pseudoscalar are reconstructed as two
standard b-tagged small-radius jets, or merged into a largeradius jet due to its Lorentz boost. No significant excess relative to expectations is observed. Assuming a branching ratio
BR(a → bb¯) = 100%, the range of pseudoscalar masses
between 50 and 80 GeV is excluded at 95% confidence level
for a coupling of the pseudoscalar to the top quark of 0.5,
while a coupling of 1.0 is excluded at 95% confidence level
for the masses considered, with the coupling defined as the
strength modifier of the Standard Model Yukawa coupling
Urinary P75: a promising biomarker for amyotrophic lateral sclerosis
Get PDFBackground
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease. The urinary neurotrophin receptor p75 extracellular domain (p75ECD) has previously been reported as a potential disease biomarker for diagnosis, severity assessment and monitoring therapeutic response.
Methods
This study measured urinary p75ECD using an enzyme-linked immunoassay and normalised the results against urinary creatinine. Participants were recruited via A Multicentre Biomarker Resource Strategy in ALS (AMBroSIA) programme. Study participants included 97 ALS patients, 24 of whom were studied longitudinally, and 27 healthy controls. The study focused on urinary p75ECD and its potential association with different subtypes of ALS, change over time, disease progression, severity of symptoms and survival from symptom onset.
Results
Confirming previous findings, urinary p75ECD levels were significantly higher in patients with ALS (median 6.78 ng/mg, 95% CI (5.12 to 9.23)) compared with controls (4.57 ng/mg, 95% CI (3.35 to 5.89)) at first study visit. There was a significant negative correlation between absolute change in the Revised ALS Functional Rating Scale score and p75ECD levels (Spearman’s rho=−0.371, p≤0.0004, 95% CI (−0.543 to –0.169)), indicating that an increase in the severity of motor neuron injury correlated with an increase in p75ECD levels. There was a significant increase in p75ECD between first and second samples in the same participants, indicating an increase in the level of this biomarker longitudinally during the disease course (moderate effect size of −0.3).
Conclusions
Urinary p75ECD is a promising candidate as a biomarker, which increases with disease progression and has the potential to serve as a pharmacodynamic biomarker
Channel Matters: Overcoming Diffusion Bottlenecks via Loop Engineering of LinD for Enhanced Isoprene Production
Get PDFThe selective chemical dehydration leading to C=C double bond formation is a challenging reaction that harbors great potential for industrial applications. The cofactor independent bifunctional linalool dehydratase isomerase (LinD) from Castellaniella defragrans catalyzes the reversible dehydration of (S)-linalool to myrcene, as well as its isomerization to geraniol. We previously reported that LinD is able to convert the small alkenol 2-methyl-3-buten-2-ol to the valuable product isoprene. To foster the LinD-catalyzed production of isoprene in a novel recombinant E. coli whole-cell two-phase system, we targeted the active site and a flexible α-helix near the putative substrate channel via enzyme engineering. Interestingly, none of the active site variants exhibited an increased product formation. In contrast, saturation mutagenesis of the 10 amino acids forming the α-helix, identified the variants K103N, R104G, G107T and D112T, which exhibited a 1.73 ± 0.05, 1.56 ± 0.12, 2.08 ± 0.12 and 1.93 ± 0.06-fold increase in product formation compared to the wild-type enzyme, respectively. Notably, a combinatorial approach targeting these four variants led to decreased activity in all cases, compared to the corresponding single-point variants, indicating negative epistatic interactions. Thus, employing the most catalytically efficient single point variant G107T, which exhibited a 28-fold higher kcat (app) compared to the wild-type, a total of 2.8 ± 0.2 mM isoprene was obtained utilizing the whole-cell two-phase system. Crystallographic analysis of G107T revealed only minor structural changes; however, molecular dynamic simulations uncovered striking conformational differences relative to the LinD wild-type, emphasizing the role of altered substrate channel in variant G107T
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