Manipulating structure, defects and composition of a material at the atomic scale for enhancing its physical or mechanical properties is referred to as nanostructuring. Here, by combining advanced ...microscopy techniques, we unveil how formation of highly regular nano-arrays of nanoparticles doubles the strength of an Fe-based alloy, doped with Ti, Mo, and V, from 500 MPa to 1 GPa, upon prolonged heat treatment. The nanoparticles form at moving heterophase interfaces during cooling from the high-temperature face-centered cubic austenite to the body-centered cubic ferrite phase. We observe MoC and TiC nanoparticles at early precipitation stages as well as core-shell nanoparticles with a Ti-C rich core and a Mo-V rich shell at later precipitation stages. The core-shell structure hampers particle coarsening, enhancing the material's strength. Designing such highly organized metallic core-shell nanoparticle arrays provides a new pathway for developing a wide range of stable nano-architectured engineering metallic alloys with drastically enhanced properties.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective
Congenital heart disease (CHD) is the most common congenital malformation and causes major morbidity and mortality. Prenatal detection improves the neonatal condition before surgery, ...resulting in less morbidity and mortality. In the Netherlands a national prenatal screening programme was introduced in 2007. This study evaluates the effects of this screening programme.
Design
Geographical cohort study.
Setting
Large referral region of three tertiary care centres.
Population
Fetuses and infants diagnosed with severe CHD born between 1 January 2002 and 1 January 2012.
Methods
Cases were divided into two groups: before and after the introduction of screening.
Main outcome measures
Detection rates were calculated.
Results
The prenatal detection rate (n = 1912) increased with 23.9% (95% confidence interval 95% CI 19.5–28.3) from 35.8 to 59.7% after the introduction of screening and of isolated CHD with 21.4% (95% CI 16.0–26.8) from 22.8 to 44.2%. The highest detection rates were found in the hypoplastic left heart syndrome, other univentricular defects and complex defects with atrial isomerism (>93%). Since the introduction of screening, the ‘late’ referrals (after 24 weeks of gestation) decreased by 24.3% (95% CI 19.3–29.3).
Conclusions
This is the largest cohort study to investigate the prenatal detection rate of severe CHD in an unselected population. A nationally organised screening has resulted in a remarkably high detection rate of CHD (59.7%) compared with earlier literature.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Context.
Teegarden’s Star is the brightest and one of the nearest ultra-cool dwarfs in the solar neighbourhood. For its late spectral type (M7.0 V), the star shows relatively little activity and is a ...prime target for near-infrared radial velocity surveys such as CARMENES.
Aims.
As part of the CARMENES search for exoplanets around M dwarfs, we obtained more than 200 radial-velocity measurements of Teegarden’s Star and analysed them for planetary signals.
Methods.
We find periodic variability in the radial velocities of Teegarden’s Star. We also studied photometric measurements to rule out stellar brightness variations mimicking planetary signals.
Results.
We find evidence for two planet candidates, each with 1.1
M
⊕
minimum mass, orbiting at periods of 4.91 and 11.4 d, respectively. No evidence for planetary transits could be found in archival and follow-up photometry. Small photometric variability is suggestive of slow rotation and old age.
Conclusions.
The two planets are among the lowest-mass planets discovered so far, and they are the first Earth-mass planets around an ultra-cool dwarf for which the masses have been determined using radial velocities.
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FMFMET, NUK, UL, UM, UPUK
Lung alveoli, which are unique to air-breathing organisms, have been challenging to generate from pluripotent stem cells (PSCs) in part because there are limited model systems available to provide ...the necessary developmental roadmaps for in vitro differentiation. Here we report the generation of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, from human PSCs. Using multicolored fluorescent reporter lines, we track and purify human SFTPC+ alveolar progenitors as they emerge from endodermal precursors in response to stimulation of Wnt and FGF signaling. Purified PSC-derived SFTPC+ cells form monolayered epithelial “alveolospheres” in 3D cultures without the need for mesenchymal support, exhibit self-renewal capacity, and display additional AEC2 functional capacities. Footprint-free CRISPR-based gene correction of PSCs derived from patients carrying a homozygous surfactant mutation (SFTPB121ins2) restores surfactant processing in AEC2s. Thus, PSC-derived AEC2s provide a platform for disease modeling and future functional regeneration of the distal lung.
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•SFTPC reporter PSC lines allow isolation of putative PSC-derived AEC2s (iAEC2s)•iAEC2s extensively self-renew, growing as proliferative alveolospheres•Lamellar bodies present in iAEC2s are able to functionally process surfactant•Temporal regulation of Wnt activity promotes PSC-derived AEC2 maturation
Jacob et al. differentiate human pluripotent stem cells (PSCs) into type II alveolar cells (iAEC2s). They find that iAEC2s display many of the functions, transcriptomic features, and surfactant-processing capacities that characterize primary cells. Finally, they derive AEC2s from gene-edited, patient-specific PSCs to model surfactant protein B deficiency in vitro.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Submergence limits plants' access to oxygen and light, causing massive changes in metabolism; after submergence, plants experience additional stresses, including reoxygenation, dehydration, ...photoinhibition and accelerated senescence. Plant responses to waterlogging and partial or complete submergence have been well studied, but our understanding of plant responses during post‐submergence recovery remains limited. During post‐submergence recovery, whether a plant can repair the damage caused by submergence and reoxygenation and re‐activate key processes to continue to grow, determines whether the plant survives. Here, we summarize the challenges plants face when recovering from submergence, primarily focusing on studies of Arabidopsis thaliana and rice (Oryza sativa). We also highlight recent progress in elucidating the interplay among various regulatory pathways, compare post‐hypoxia reoxygenation between plants and animals and provide new perspectives for future studies.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ ...hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The COVID-19 pandemic led to the closure of the IDEA syringe services program medical student-run free clinic in Miami, Florida. In an effort to continue to serve the community of people who inject ...drugs and practice compassionate and non-judgmental care, the students transitioned the clinic to a model of TeleMOUD (medications for opioid use disorder). We describe development and implementation of a medical student-run telemedicine clinic through an academic medical center-operated syringe services program.
Students advertised TeleMOUD services at the syringe service program on social media and created an online sign-up form. They coordinated appointments and interviewed patients by phone or videoconference where they assessed patients for opioid use disorder. Supervising attending physicians also interviewed patients and prescribed buprenorphine when appropriate. Students assisted patients in obtaining medication from the pharmacy and provided support and guidance during home buprenorphine induction.
Over the first 9 weeks in operation, 31 appointments were requested, and 22 initial telehealth appointments were completed by a team of students and attending physicians. Fifteen appointments were for MOUD and 7 for other health issues. All patients seeking MOUD were prescribed buprenorphine and 12/15 successfully picked up medications from the pharmacy. The mean time between appointment request and prescription pick-up was 9.5 days.
TeleMOUD is feasible and successful in providing people who inject drugs with low barrier access to life-saving MOUD during the COVID-19 pandemic. This model also provided medical students with experience treating addiction during a time when they were restricted from most clinical activities.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
For the August‐September 2008 Olympic and the Paralympic Games held in Beijing, China, strict controls on pollutant emissions and motor vehicle traffic were imposed on Beijing and neighboring ...provinces to the South to improve the air quality in and around the city. Satellite measurements over Beijing between July and September showed 43% reductions of tropospheric column nitrogen dioxide, compared to the past three years. When neighboring provinces to the south are included in our analyses, satellite measurements show boundary layer sulfur dioxide reductions of 13% and carbon monoxide reductions of 12% at 700 hPa. Thus, based on satellites observations alone, noticeable reductions in these pollutant tracers were measured during both games.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We aimed to determine whether frailty, a validated geriatric construct of increased vulnerability to physiologic stressors, predicts mortality in liver transplant candidates. Consecutive adult ...outpatients listed for liver transplant with laboratory Model for End‐Stage Liver Disease (MELD) ≥ 12 at a single center (97% recruitment rate) underwent four frailty assessments: Fried Frailty, Short Physical Performance Battery (SPPB), Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales. Competing risks models associated frailty with waitlist mortality (death/delisting for being too sick for liver transplant). Two hundred ninety‐four listed liver transplant patients with MELD ≥ 12, median age 60 years and MELD 15 were followed for 12 months. By Fried Frailty score ≥3, 17% were frail; 11/51 (22%) of the frail versus 25/243 (10%) of the not frail died/were delisted (p = 0.03). Each 1‐unit increase in the Fried Frailty score was associated with a 45% (95% confidence interval, 4–202) increased risk of waitlist mortality adjusted for MELD. Similarly, the adjusted risk of waitlist mortality associated with each 1‐unit decrease (i.e. increasing frailty) in the Short Physical Performance Battery (hazard ratio 1.19, 95% confidence interval 1.07–1.32). Frailty is prevalent in liver transplant candidates. It strongly predicts waitlist mortality, even after adjustment for liver disease severity demonstrating the applicability and importance of the frailty construct in this population.
In this study, the researchers report that frailty, a validated geriatric construct of increased vulnerability to physiologic stressors, is highly prevalent in patients with cirrhosis awaiting liver transplantation and strongly predicts waitlist mortality, demonstrating the applicability and importance of the frailty construct in this population.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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