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Purpose: The efficacy of the 1-h bundle for emergency department (ED) patients with suspected sepsis, which includes lactate measurement, blood culture, broad-spectrum antibiotics administration, administration of 30 mL/kg crystalloid fluid for hypotension or lactate ≥ 4 mmol/L, remains controversial. Methods: We carried out a pragmatic stepped-wedge cluster-randomized trial in 23 EDs in France and Spain. Adult patients with Sepsis-3 criteria or a quick sequential organ failure assessment (SOFA) score ≥ 2 or a lactate > 2 mmol/L were eligible. The intervention was the implementation of the 1-h sepsis bundle. The primary outcome was in-hospital mortality truncated at 28 days. Secondary outcomes included volume of fluid resuscitation at 24 h, acute heart failure at 24 h, SOFA score at 72 h, intensive care unit (ICU) length of stay, number of days on mechanical ventilation or renal replacement therapy, vasopressor free days, unnecessary antibiotic administration, and mortality at 28 days. 1148 patients were planned to be analysed; the study period ended after 873 patients were included. Results: 872 patients (mean age 66, 42% female) were analyzed: 387 (44.4%) in the intervention group and 485 (55.6%) in the control group. Median SOFA score was 3 [1–5]. Median time to antibiotic administration was 40 min in the intervention group vs 113 min in the control group (difference − 73 [95% confidence interval (CI) − 93 to − 53]). There was a significantly higher rate, volume, and shorter time to fluid resuscitation within 3 h in the intervention group. There were 47 (12.1%) in-hospital deaths in the intervention group compared to 61 (12.6%) in the control group (difference in percentage − 0.4 [95% CI − 5.1 to 4.2], adjusted relative risk (aRR) 0.81 [95% CI 0.48 to 1.39]). There were no differences between groups for other secondary endpoints. Conclusions: Among patients with suspected sepsis in the ED, the implementation of the 1-h sepsis bundle was not associated with significant difference in in-hospital mortality. However, this study may be underpowered to report a statistically significant difference between groups. [ABSTRACT FROM AUTHOR]

The NICO (non-invasive airway management in comatose patients) randomized controlled trial found that withholding intubation in acute poisoned comatose patients with a Glasgow Coma Scale < 9 led to significant clinical improvement in terms of in-hospital death, length of stay in the intensive care unit (ICU), and length of hospital stay compared to routine practice. The trial also conducted an economic evaluation, which showed that withholding intubation was both cost-saving and event-reducing. The study suggests that policymakers should consider utilizing these monetary benefits in critical care. [Extracted from the article]

Variational quantum eigensolvers (VQEs) are leading candidates to demonstrate near-term quantum advantage. Here, we conduct density-matrix simulations of leading gate-based VQEs for a range of molecules. We numerically quantify their level of tolerable depolarizing gate-errors. We find that: (i) The best-performing VQEs require gate-error probabilities between 10−6 and 10−4 (10−4 and 10−2 with error mitigation) to predict, within chemical accuracy, ground-state energies of small molecules with 4 − 14 orbitals. (ii) ADAPT-VQEs that construct ansatz circuits iteratively outperform fixed-circuit VQEs. (iii) ADAPT-VQEs perform better with circuits constructed from gate-efficient rather than physically-motivated elements. (iv) The maximally-allowed gate-error probability, pc, for any VQE to achieve chemical accuracy decreases with the number NII of noisy two-qubit gates as p c ∝ ~ N II − 1 . Additionally, pc decreases with system size, even with error mitigation, implying that larger molecules require even lower gate-errors. Thus, quantum advantage via gate-based VQEs is unlikely unless gate-error probabilities are decreased by orders of magnitude. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chain-related MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chain-related MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC. Materials and methods: In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 63 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx). Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2. Results: The HLA disease association tests revealed a statistically significant predisposing association of HLA-F*01:01:02 (Pc = 0.0103, OR = 24.0194) with LSCC, while HLA-F*01:01:01 (Pc = 8.21e-04, OR = 0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically significant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P = 0.0054, haplotype score=-2.7801). Conclusion: Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of LSCC. [ABSTRACT FROM AUTHOR]

Background: Due to risks of texturization, the use of textured breast implants has been diminishing worldwide and is expected to continue to decline. The crisis with textured devices raises the need to revisit the use of smooth round silicone gel (SRSG) implants and to discuss the results that can be achieved with this alternative. The article aims to exclusively analyze SRSG devices: the changes associated with implant profile and degrees of filling, how these changes correlate to certain aesthetic outcomes, and the predictability and stability of these results over time. Methods: The experimental component of this study investigated the effect of gravity on various profiles of SRSG implants when their position was changed. The study's clinical component was a retrospective analysis of primary retropectoral breast augmentation patients with a minimum 1-year follow-up after the procedure. Results: In the experimental setting upon changing position, the anatomic conformation in higher profile devices was more visible compared with their lower profile counterparts. Clinical results of 92 augmented breasts (46 patients) with various types of SRSG implants revealed a full scope of aesthetic outcomes. Desired results were achieved even in challenging scenarios. Breast shape and upper pole contour were predictable with reliable and stable control over time. The overall complication rate was comparable to other breast implant studies. Conclusions: With proper device selection and good surgical technique, any aesthetic outcome can be achieved in retropectoral placement while keeping also prioritizing patient safety. Moderate and moderate plus profile underfilled implants are recommended when anatomical results are intended. Level of evidence: Level IV, Therapeutic. [ABSTRACT FROM AUTHOR]

Abstract Bidirectional intercellular signaling is an essential feature of multicellular organisms, and the engineering of complex biological systems will require multiple pathways for intercellular signaling with minimal crosstalk. Natural quorum‐sensing systems provide components for cell communication, but their use is often constrained by signal crosstalk. We have established new orthogonal systems for cell–cell communication using acyl homoserine lactone signaling systems. Quantitative measurements in contexts of differing receiver protein expression allowed us to separate different types of crosstalk between 3‐oxo‐C6‐ and 3‐oxo‐C12‐homoserine lactones, cognate receiver proteins, and DNA promoters. Mutating promoter sequences minimized interactions with heterologous receiver proteins. We used experimental data to parameterize a computational model for signal crosstalk and to estimate the effect of receiver protein levels on signal crosstalk. We used this model to predict optimal expression levels for receiver proteins, to create an effective two‐channel cell communication device. Establishment of a novel spatial assay allowed measurement of interactions between geometrically constrained cell populations via these diffusible signals. We built relay devices capable of long‐range signal propagation mediated by cycles of signal induction, communication and response by discrete cell populations. This work demonstrates the ability to systematically reduce crosstalk within intercellular signaling systems and to use these systems to engineer complex spatiotemporal patterning in cell populations.

This article presents the preparation and characterization of various calcium-magnesium phosphate suspensions with particular focus on nanostructured magnesium whitlockite as potential protein adsorbent. The phosphates were synthesized by precipitation from mixed Ca(II)/Mg(II) solutions with disodium hydrogen phosphate followed by thermal treatment at 95 or 115 °C for 1 or 3 h. Structural characterization was performed by means of transmission electron microscopy with elemental and electron diffraction analysis, X-ray powder diffraction and infrared spectroscopy. It was found that nanocrystalline magnesium whitlockite was obtained at initial Ca/Mg molar ratio from 65/35 up to 85/15. The crystallite sizes of magnesium whitlockite were estimated from X-ray diffraction and were found to vary from 5 to 45 nm depending on the heating temperature and time at constant Ca/Mg initial molar ratio of 75/25. The nanocrystalline magnesium whitlockite samples exhibited a relatively high protein adsorption capacity, which is an important prerequisite for applications in protein delivery. [ABSTRACT FROM AUTHOR]

Background: Little is known about the impact of hospital trajectory on survival and functional decline of older critically ill patients. We evaluate 6-month outcomes after admission to: intensive care units (ICU), intermediate care units (IMCU) or acute medical wards (AMW). Methods: Data from the randomised prospective multicentre clinical trial ICE-CUB2 was secondarily analysed. Inclusion criteria were: presenting at emergency departments in critical condition; age ≥ 75 years; activity of daily living (ADL) ≥ 4; preserved nutritional status; and no active cancer. A Cox model was fitted to compare survival according to admission destination adjusting for patient characteristics. Sensitivity analysis using multiple imputation for missing data and propensity score matching were performed. Results: Among 3036 patients, 1675 (55%) were women; median age was 85 [81–99] years; simplified acute physiology score (SAPS-3) 62 [55–69]; 1448 (47%) were hospitalised in an ICU, 504 in IMCU (17%), and 1084 (36%) in AMW. Six-month mortality was 629 (44%), 155 (31%) and 489 (45%) after admission in an ICU, IMCU and AMW (p < 0.001), respectively. In multivariate analysis, AMW admission was associated with worse 6-month survival (HR 1.31, 95% CI 1.04–1.63) in comparison with IMCU admission, after adjusting for age, gender, comorbidities, ADL, SAPS-3 and diagnosis. Survival was not significantly different between patients admitted in an ICU and an IMCU (HR 1.17, 95% CI 0.95–1.46). Sensitivity analysis using multiple imputation for missing data and propensity score matching found similar results. Hospital destination was not significantly associated with the composite criterion loss of 1-point ADL or mortality. Physical and mental components of the 12-Item Short-Form Health Survey were significantly lower in the acute medical ward group (34.3 [27.5–41.7], p = 0.037 and 44.3 [38.6–48.6], p = 0.028, respectively) than in the ICU group (34.7 [28.4–45.3] and 45.5 [40.0–50.0], respectively) and IMCU group (35.7 [29.7–43.8] and 44.5 [39.7–48.4], respectively). Conclusions: Admission in an AMW was associated with worse 6-month survival in older critically ill patients in comparison with IMCU admission, with no difference of survival between ICU and IMCU admission. There were no clinically relevant differences in quality of life in each group. These results should be confirmed in specific studies and raise the question of dedicated geriatric IMCUs. [ABSTRACT FROM AUTHOR]

Background: Endoscopic third ventriculostomy success score (ETVss) is widely utilised to predict outcomes for ETV. Accurate prediction of success for a procedure is of vital importance both for selecting the optimal management plan and for obtaining informed consent. Existing literature demonstrates a variety of opinions on the accuracy of the currently utilised ETVss and recommends a range of techniques to reduce the number of subsequent ventriculo-peritoneal (VP)-shunt insertions, prompting the present study. Methods: We retrospectively analysed data for ETV cases since 2007 to review success rate in our regional paediatric neurosurgical centre and if the currently utilised ETVss successfully predicted outcomes. Failed ETV cases were defined as any patient who received a VP-shunt at any time following ETV. Data was analysed with MS ExcelR and RStudioR. Results: 44 ETVs were performed over 13 years with approximately equal distribution between male and female patients; median age 7 years (IQR 4–13 years). Overall, mean ETVss for these 44 procedures was 78%; actual success rate was 70% with no statistically significant difference between them (p = 0.286; Welch two sample t-test). Accuracy of ETVss varied with pathology: tectal gliomas (mean ETVss 75% and actual success 78%); cerebellar tumours (mean ETVss 85% and actual success 81%); other tumours (mean ETVss 75% and actual success 81%); aqueduct stenosis (mean ETVss 71% and actual success 69%); and other pathologies (mean ETVss 70% and actual success 60%). < 1 month and 1–6 months and 1–10 years and > 10 years contributed equally to the accuracy of ETVss. Conclusion: Non-telencephalon tumours and obstruction at the level of the mid-brain are most strongly associated with successful ETV outcome. These findings can be used to modify the currently utilised ETVss to further improve accuracy of outcome prediction. We recommend a modified-ETVss (m-ETVss) and a future larger adequately powered prospective study to validate this. [ABSTRACT FROM AUTHOR]

Purpose: Degenerative cervical myelopathy (DCM) is the most common cause of adult spinal cord dysfunction worldwide. However, the current incidence of DCM is poorly understood. The Hospital Episode Statistics (HES) database contains details of all secondary care admissions across NHS hospitals in England. This study aimed to use HES data to characterise surgical activity for DCM in England. Methods: The HES database was interrogated for all cases of DCM between 2012 and 2019. DCM cases were identified from 5 ICD-10 codes. Age-stratified values were collected for 'Finished Consultant Episodes' (FCEs), which correspond to a patient's hospital admission under a lead clinician. Data was analysed to explore current annual activity and longitudinal change. Results: 34,903 FCEs with one or more of the five ICD-10 codes were identified, of which 18,733 (53.6%) were of working age (18–64 years). Mean incidence of DCM was 7.44 per 100,000 (SD ± 0.32). Overall incidence of DCM rose from 6.94 per 100,000 in 2012–2013 to 7.54 per 100,000 in 2018–2019. The highest incidence was seen in 2016–2017 (7.94 per 100,000). The median male number of FCEs per year (2919, IQR: 228) was consistently higher than the median female number of FCEs per year (2216, IQR: 326). The rates of both emergency admissions and planned admissions are rising. Conclusions: The incidence of hospitalisation for DCM in England is rising. Health care policymakers and providers must recognise the increasing burden of DCM and act to address both early diagnoses and access to treatment in future service provision plans. [ABSTRACT FROM AUTHOR]

The furin cleavage site (FCS) in SARS-CoV-2 is unique within the Severe acute respiratory syndrome–related coronavirus (SrC) species. We re-assessed diverse SrC from European horseshoe bats and analyzed the spike-encoding genomic region harboring the FCS in SARS-CoV-2. We reveal molecular features in SrC such as purine richness and RNA secondary structures that resemble those required for FCS acquisition in avian influenza viruses. We discuss the potential acquisition of FCS through molecular mechanisms such as nucleotide substitution, insertion, or recombination, and show that a single nucleotide exchange in two European bat-associated SrC may suffice to enable furin cleavage. Furthermore, we show that FCS occurrence is variable in bat- and rodent-borne counterparts of human coronaviruses. Our results suggest that furin cleavage sites can be acquired in SrC via conserved molecular mechanisms known in other reservoir-bound RNA viruses and thus support a natural origin of SARS-CoV-2. Genomic analyses of spike glycoprotein genes of European bat SARS-related coronaviruses suggest that furin cleavage sites can be acquired in the bat reservoir via conserved molecular mechanisms, supporting a natural origin of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Reverse transcriptase polymerase chain reaction (RT-PCR) is a key tool to diagnose Covid-19. Yet it may not be the most efficient test in all patients. In this paper, we develop a clinical strategy for prescribing RT-PCR to patients based on data from COVIDOM, a French cohort of 54,000 patients with clinically suspected Covid-19, including 12,810 patients tested by RT-PCR. We use a machine-learning algorithm (decision tree) in order to predict RT-PCR results based on the clinical presentation. We show that symptoms alone are sufficient to predict RT-PCR outcome with a mean average precision of 86%. We identify combinations of symptoms that are predictive of RT-PCR positivity (90% for anosmia/ageusia) or negativity (only 30% of RT-PCR+ for a subgroup with cardiopulmonary symptoms): in both cases, RT-PCR provides little added diagnostic value. We propose a prescribing strategy based on clinical presentation that can improve the global efficiency of RT-PCR testing. [ABSTRACT FROM AUTHOR]

Molecular simulations with the variational quantum eigensolver (VQE) are a promising application for emerging noisy intermediate-scale quantum computers. Constructing accurate molecular ansätze that are easy to optimize and implemented by shallow quantum circuits is crucial for the successful implementation of such simulations. Ansätze are, generally, constructed as series of fermionic-excitation evolutions. Instead, we demonstrate the usefulness of constructing ansätze with "qubit-excitation evolutions", which, contrary to fermionic excitation evolutions, obey "qubit commutation relations". We show that qubit excitation evolutions, despite the lack of some of the physical features of fermionic excitation evolutions, accurately construct ansätze, while requiring asymptotically fewer gates. Utilizing qubit excitation evolutions, we introduce the qubit-excitation-based adaptive (QEB-ADAPT)-VQE protocol. The QEB-ADAPT-VQE is a modification of the ADAPT-VQE that performs molecular simulations using a problem-tailored ansatz, grown iteratively by appending evolutions of qubit excitation operators. By performing classical numerical simulations for small molecules, we benchmark the QEB-ADAPT-VQE, and compare it against the original fermionic-ADAPT-VQE and the qubit-ADAPT-VQE. In terms of circuit efficiency and convergence speed, we demonstrate that the QEB-ADAPT-VQE outperforms the qubit-ADAPT-VQE, which to our knowledge was the previous most circuit-efficient scalable VQE protocol for molecular simulations. Existing methods for molecular simulations with quantum computers use ansatz constructed as series of fermionic excitation evolution. Here, qubit excitation evolutions are employed instead, in combination with the ADAPT-VQE protocol, to construct short and accurate ansatz suitable for noisy and imperfect quantum computers. [ABSTRACT FROM AUTHOR]

In a large regional observational cohort study of adult (≥ 18 years), outpatients with COVID-19, prevalence, characteristics, and outcome of patients with rash and/or chilblain-like lesions (CLL), compared with population without cutaneous features, were studied. In total, 28,957 outpatients were included; the prevalence of rash and CCL were 9.5% and 3.7%, respectively. Presence of rash was significantly associated with presence of asthenia, shivers or myalgia, respiratory and gastro-intestinal symptoms, and anosmia/ageusia. The presence of CCL was associated with chest pain, chest oppression, nausea/vomiting, and anosmia/ageusia. Patients with CCL were significantly less prone to an unfavourable outcome (hospitalization or death). [ABSTRACT FROM AUTHOR]

Landslide susceptibility mapping is a crucial initial step in risk mitigation strategies. Landslide hazards are widely spread all over the world and, as such, mapping the relevant susceptibility levels is in constant research and development. As a result, numerous modelling techniques and approaches have been adopted by scholars, implementing these models at different scales and with different terrains, in search of the best-performing strategy. Nevertheless, a direct comparison is not possible unless the strategies are implemented under the same environmental conditions and scenarios. The aim of this work is to implement three statistical-based models (Statistical Index, Logistic Regression, and Random Forest) at the basin scale, using various scenarios for the input datasets (terrain variables), training samples and ratios, and validation metrics. A reassessment of the original input data was carried out to improve the model performance. In total, 79 maps were obtained using different combinations with some highly satisfactory outcomes and others that are barely acceptable. Random Forest achieved the highest scores in most of the cases, proving to be a reliable modelling approach. While Statistical Index passes the evaluation tests, most of the resulting maps were considered unreliable. This research highlighted the importance of a complete and up-to-date landslide inventory, the knowledge of local conditions, as well as the pre- and post-analysis evaluation of the input and output combinations. [ABSTRACT FROM AUTHOR]

Targeted high-throughput DNA sequencing is a primary approach for genomics and molecular diagnostics, and more recently as a readout for DNA information storage. Oligonucleotide probes used to enrich gene loci of interest have different hybridization kinetics, resulting in non-uniform coverage that increases sequencing costs and decreases sequencing sensitivities. Here, we present a deep learning model (DLM) for predicting Next-Generation Sequencing (NGS) depth from DNA probe sequences. Our DLM includes a bidirectional recurrent neural network that takes as input both DNA nucleotide identities as well as the calculated probability of the nucleotide being unpaired. We apply our DLM to three different NGS panels: a 39,145-plex panel for human single nucleotide polymorphisms (SNP), a 2000-plex panel for human long non-coding RNA (lncRNA), and a 7373-plex panel targeting non-human sequences for DNA information storage. In cross-validation, our DLM predicts sequencing depth to within a factor of 3 with 93% accuracy for the SNP panel, and 99% accuracy for the non-human panel. In independent testing, the DLM predicts the lncRNA panel with 89% accuracy when trained on the SNP panel. The same model is also effective at predicting the measured single-plex kinetic rate constants of DNA hybridization and strand displacement. DNA probes used in next generation sequencing (NGS) have variable hybridisation kinetics, resulting in non-uniform coverage. Here, the authors develop a deep learning model to predict NGS depth using DNA probe sequences and apply to human and non-human sequencing panels. [ABSTRACT FROM AUTHOR]

The photoinduced birefringence of two 4-substituted phthalimide 2-hydroxy Schiff bases, containing salicylic (4) and 2-hydroxy-1-naphthyl (5) moieties has been investigated in PMMA matrix. Their optical behaviour as nanocomposite films was revealed by combined use of DFT quantum chemical calculations (in ground and excited state) and experimental optical spectroscopy (UV–Vis and fluorescence). The results have shown that solid-state reversible switching takes place by enol/keto tautomerization and Z/E isomerization. Birefringence study was performed in the PMMA nanocomposite films using pump lasers at λrec = 355 nm and λrec = 442 nm. Fast response time and high stability of anisotropy up to 58% for (4) and 95% for (5) after turning off the excitation laser, was observed, which makes these materials appropriate candidates for cutting-edge optical information technology materials. The possibility for multiple cycles of recording, reading and optical erasure of the photoinduced birefringence at λrec = 442 nm in 5 has been demonstrated. The obtained results have shown that the maximum value of the measured birefringence is close to the anisotropic characteristics of the most frequently used azo materials. [ABSTRACT FROM AUTHOR]

Bud-break is an economically and environmentally important process in trees and shrubs from boreal and temperate latitudes, but its molecular mechanisms are poorly understood. Here, we show that two previously reported transcription factors, EARLY BUD BREAK 1 (EBB1) and SHORT VEGETATIVE PHASE-Like (SVL) directly interact to control bud-break. EBB1 is a positive regulator of bud-break, whereas SVL is a negative regulator of bud-break. EBB1 directly and negatively regulates SVL expression. We further report the identification and characterization of the EBB3 gene. EBB3 is a temperature-responsive, epigenetically-regulated, positive regulator of bud-break that provides a direct link to activation of the cell cycle during bud-break. EBB3 is an AP2/ERF transcription factor that positively and directly regulates CYCLIND3.1 gene. Our results reveal the architecture of a putative regulatory module that links temperature-mediated control of bud-break with activation of cell cycle. An AP2/ERF family gene EBB1 and a MADS-box gene SVL encode two regulators of poplar bud break. Here, the authors report another AP2/ERF transcription factor EBB3, which functions together with EBB1, SVL, and cell cycle progression promoter CYCD3.1 to regulate poplar bud break. [ABSTRACT FROM AUTHOR]

Mixes of sucrose and various proportions of ascorbic acid were irradiated with γ-rays and studied by an electron paramagnetic resonance (EPR) spectroscopy. Before irradiation no EPR signals have been recorded. After irradiation an EPR spectrum of sucrose has been observed from all samples independently of the quantity of ascorbic acid. The influence of the microwave power and the modulation amplitude on the EPR intensity was reported. It has been found that the EPR signal intensity of sucrose decreased when the ascorbic acid is added to it. This result suggests that ascorbic acid play role of free radical scavenger because of its antiradical activity. [ABSTRACT FROM AUTHOR]

Tin is the chemical element with the largest number of stable isotopes. Its complete proton shell, comparable with the closed electron shells in the chemically inert noble gases, is not a mere precursor to extended stability; since the protons carry the nuclear charge, their spatial arrangement also drives the nuclear electromagnetism. We report high-precision measurements of the electromagnetic moments and isomeric differences in charge radii between the lowest 1/2+, 3/2+, and 11/2− states in 117–131Sn, obtained by collinear laser spectroscopy. Supported by state-of-the-art atomic-structure calculations, the data accurately show a considerable attenuation of the quadrupole moments in the closed-shell tin isotopes relative to those of cadmium, with two protons less. Linear and quadratic mass-dependent trends are observed. While microscopic density functional theory explains the global behaviour of the measured quantities, interpretation of the local patterns demands higher-fidelity modelling. Measurements of the hyperfine structure of chemical elements isotopes provide unique insight into the atomic nucleus in a nuclear model-independent way. The authors present collinear laser spectroscopy data obtained at the CERN ISOLDE and measure hyperfine splitting along a long chain of odd-mass tin isotopes. [ABSTRACT FROM AUTHOR]

Acquired resistance to chemotherapy is an important clinical problem and can also occur without detectable cytogenetic aberrations or gene mutations. Chronic lymphocytic leukemia (CLL) is molecularly well characterized and has been elemental for establishing central paradigms in oncology. This prompted us to check whether specific epigenetic changes at the level of DNA methylation might underlie development of treatment resistance. We used Illumina Infinium HumanMethylation450 BeadChips to obtain DNA methylation profiles of 71 CLL patients with differential responses. Thirty-six patients were categorized as relapsed/refractory after treatment with fludarabine or bendamustine and 21 of them had genetic aberrations of TP53. The other 35 patients were untreated at the time of sampling and 15 of them had genetic aberration of TP53. Although we could not correlate chemoresistance with epigenetic changes, the patients were comprehensively characterized regarding relevant prognostic and molecular markers (e.g. IGHV mutation status, chromosome aberrations, TP53 mutation status, clinical parameters), which makes our dataset a unique and valuable resource that can be used by researchers to test alternative hypotheses. Measurement(s) DNA methylation Technology Type(s) methylation profiling by array Factor Type(s) TP53 mutation status • response to fludarabine or bendamustine • chromosomal aberration • IGHV mutation status Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12006624 [ABSTRACT FROM AUTHOR]

Sunflower (Helianthus annuus L.) is an important oilseed crop in the world and the sunflower oil is prized for its exceptional quality and flavor. The recent availability of the sunflower genome can allow genome-wide characterization of genes and gene families. With plant transformation usually being the rate-limiting step for gene functional studies of sunflower, composite plants can alleviate this bottleneck. Composite plants, produced using Agrobacterium rhizogenes, are plants with transgenic roots and wild type shoots. Composite plants offer benefits over creating fully transgenic plants, namely time and cost. Here we outlined the critical steps and parameters for a protocol for the production of sunflower composite plants. We tested more than a dozen genotypes and three constitutive promoters to validate the utility and efficiency of this protocol. Moreover, functional gene characterization by overexpression and RNAi silencing of a root-related transcription factor, HaLBD16, further emphasize the value of the system in the sunflower studies. With the protocol developed here an experiment can be carried efficiently and in only 2 months. This procedure adds to the arsenal of approaches for the functional genetics/genomics in sunflower for characterization candidate genes involved in root development and stress adaptation. Key message: Composite plants technique described here is fast and efficient approach for roots functional studies in sunflower. [ABSTRACT FROM AUTHOR]

Purpose: The majority of terrorist acts are carried out by explosion or shooting. The objective of this study was first, to describe the management implemented to treat a large number of casualties and their flow together with the injuries observed, and second, to compare these resources according to the mechanism of trauma.Methods: This retrospective cohort study collected medical data from all casualties of the attacks on November 13th 2015 in Paris, France, with physical injuries, who arrived alive at any hospital within the first 24 h after the events. Casualties were divided into two groups: explosion injuries and gunshot wounds.Results: 337 casualties were admitted to hospital, 286 (85%) from gunshot wounds and 51 (15%) from explosions. Gunshot casualties had more severe injuries and required more in-hospital resources than explosion casualties. Emergency surgery was required in 181 (54%) casualties and was more frequent for gunshot wounds than explosion injuries (57% vs. 35%, p < 0·01). The types of main surgery needed and their delay following hospital admission were as follows: orthopedic [n = 107 (57%); median 744 min]; general [n = 27 (15%); 90 min]; vascular [n = 19 (10%); median 53 min]; thoracic [n = 19 (10%); 646 min]; and neurosurgery [n = 4 (2%); 198 min].Conclusion: The resources required to deal with a terrorist attack vary according to the mechanism of trauma. Our study provides a template to estimate the proportion of various types of surgical resources needed overall, as well as their time frame in a terrorist multisite and multitype attack.Funding: Assistance Publique-Hôpitaux de Paris. [ABSTRACT FROM AUTHOR]

The aim of the study was to describe the thermal characteristics of poultry pates enriched with vegetable components in relation to their chemical composition and technological process. Two poultry pates from chicken liver, chicken or turkey meat with vegetables were developed. The thermal characteristics of the raw materials and the ready pates were examined by differential scanning calorimetry; fatty acid profiles were detected by gas chromatography analysis. The study investigated the effect of such factors as heating/cooling rate and matrix effect of other components (e.g., proteins) in the raw materials and in the pates. It was observed that the cooling rate has a considerable effect on melting/crystallization temperature, enthalpy, and height of peaks in the process of pates fat crystallization, as well as peak height and enthalpy in the melting process. The first peaks formed during the crystallization were characterized by high instability, demonstrated by various peak shapes. The rapid cooling led to lowering of the melting point, assigned to the presence of unstable α crystals. The slow cooling led to mainly stable β′ crystals. The fraction of unsaturated fatty acids present in the fat was important for both crystallization rate and melting points in the raw materials and in the products as well. This effect was stronger in the pate products because of the presence of diverse components such as proteins. The results obtained could be used for the evaluation of thermal stability of pate fatty acids and further optimization of the pate thermal treatment. [ABSTRACT FROM AUTHOR]

The number of trials assessing Simulation-Based Medical Education (SBME) interventions has rapidly expanded. Many studies show that potential flaws in design, conduct and reporting of randomized controlled trials (RCTs) can bias their results. We conducted a methodological review of RCTs assessing a SBME in Emergency Medicine (EM) and examined their methodological characteristics. We searched MEDLINE via PubMed for RCT that assessed a simulation intervention in EM, published in 6 general and internal medicine and in the top 10 EM journals. The Cochrane Collaboration risk of Bias tool was used to assess risk of bias, intervention reporting was evaluated based on the "template for intervention description and replication" checklist, and methodological quality was evaluated by the Medical Education Research Study Quality Instrument. Reports selection and data extraction was done by 2 independents researchers. From 1394 RCTs screened, 68 trials assessed a SBME intervention. They represent one quarter of our sample. Cardiopulmonary resuscitation (CPR) is the most frequent topic (81%). Random sequence generation and allocation concealment were performed correctly in 66 and 49% of trials. Blinding of participants and assessors was performed correctly in 19 and 68%. Risk of attrition bias was low in three-quarters of the studies (n = 51). Risk of selective reporting bias was unclear in nearly all studies. The mean MERQSI score was of 13.4/18.4% of the reports provided a description allowing the intervention replication. Trials assessing simulation represent one quarter of RCTs in EM. Their quality remains unclear, and reproducing the interventions appears challenging due to reporting issues. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the epidemiological characteristics of blood or fluid exposure (BFE) and occupational infection risk among emergency medicine (EM) residents and young physicians (<35 years old) in France. We led a cross-sectional, anonymous, online survey. 1779 participants were contacted with a response rate of 36 % (n = 633). Among the respondents, 459 (72 %) reported at least one BFE. Among participants with at least one BFE, 35 % (n = 163) never reported the exposure to the relevant medical authorities or support. Among participants who reported exposure, 63 % (n = 232) did it immediately. Among participants who never or not systematically reported their BFE, most of them (62 %, n = 181/289) did not do so because the procedure was too long, and 28 % (n = 82/289) estimated the risk as low even if only one-third (n = 166/458) checked their HIV status even though the BFE was at a transmission risk. Circumstances in which the participants had the most BFE were: suturing 57 % (n = 262/457) and when making precipitated gestures 24 % (n = 111/457). The latest exposures were caused by a solid needle in 42 % (n = 191/455) or hollow-bore needle in 27 % (n = 123/455). Post-exposure reporting rates were low. Reporting procedure itself and self-management were the main reasons for BFE underreporting. Simplifying procedures might increase BFE reporting, and allow appropriate post-exposure counseling and/or prophylaxis. [ABSTRACT FROM AUTHOR]

Transition frequencies of the $$2s\,^2{\text{S}}_{1/2} \rightarrow 2p\,^2 {\text{P}}_{1/2,\,3/2}$$ transitions in Be $$^+$$ were measured in stable and short-lived isotopes at ISOLDE (CERN) using collinear laser spectroscopy and frequency-comb-referenced dye lasers. Quasi-simultaneous measurements in copropagating and counterpropagating geometry were performed to become independent from acceleration voltage determinations for Doppler-shift corrections of the fast ion beam. Isotope shifts and fine-structure splittings were obtained from the transition frequencies measured with a frequency comb with accuracies better than 1 MHz and led to a precise determination of the nuclear charge radii of $$^{7,10-12}$$ Be relative to the stable isotope Be. Moreover, an accurate determination of the 2 p fine-structure splitting allowed a test of high-precision bound-state QED calculations in the three-electron system. Here, we describe the laser spectroscopic method in detail, including several tests that were carried out to determine or estimate systematic uncertainties. Final values from two experimental runs at ISOLDE are presented, and the results are discussed. [ABSTRACT FROM AUTHOR]

Gynecomastia is a benign enlargement of the male breast which can be a source of significant anxiety and embarrassment for the patients. A great variety of etiologic factors have been investigated and discussed. However, only few studies in the literature have accentuated on the possible role of the chronic tissue trauma for the de novo development of gynecomastia. Nevertheless, the exact mechanism of its onset in such cases remains unclear. The authors report on a case of posttraumatic unilateral progression of preexisting stable gynecomastia. The possible role of a single episode of acute trauma as a trigger mechanism for the new onset of the breast enlargement is discussed. Level of Evidence: Level V, risk/prognostic study. [ABSTRACT FROM AUTHOR]

Mondor's disease is the eponym used to describe a self-limited phlebitis or thrombophlebitis of the superficial veins localized mainly on the thoracoabdominal area of the human body. Its clinical manifestation includes painful superficial cords causing skin retraction. This medical condition could be idiopathic, iatrogenic or a manifestation of underlying pathology such as breast cancer and seems to be more common than has been previously thought. The vast majority of the clinical studies and case reports to date focus on Mondor's disease as a disorder which is more or less directly related to a previous surgical intervention. In this case report, the author discusses the possible role of breast surgery as a predisposing factor only and the trauma on the operated breast as a trigger for onset and earlier manifestation of Mondor's disease. A special emphasis is put on the importance of trauma prevention in breast augmentation surgery, especially when maneuvers like postoperative massages are considered. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

Background: The benefit of ICU admission for elderly patients remains controversial. This report highlights the methodology, the feasibility of and the ethical and logistical constraints in designing and conducting a cluster-randomized trial of intensive care unit (ICU) admission for critically ill elderly patients. Methods: We designed an interventional open-label cluster-randomized controlled trial in 24 centres in France. Clusters were healthcare centres with at least one emergency department (ED) and one ICU. Healthcare centres were randomly assigned either to recommend a systematic ICU admission (intervention group) or to follow standard practices regarding ICU admission (control group). Clusters were stratified by the number of ED annual visits (<44,616 or >44,616 visits), the presence or absence of a geriatric ward and the geographical area (Paris area vs other regions in France). All elderly patients (≥75 years of age) who got to the ED were assessed for eligibility. Patients were included if they had one of the pre-established critical conditions, a preserved functional status as assessed by an ADL scale ≥4 (0 = very dependent, 6 = independent), a preserved nutritional status (subjectively assessed by physicians) and without active cancer. Exclusion criteria were an ED stay >24 h, a secondary referral to the ED and refusal to participate. The primary outcome was the mortality at 6 months calculated at the individual patient level. Secondary outcomes were ICU and hospital mortality, as well as ADL scale and quality of life (as assessed by the SF-12 Health Survey) at 6 months. Results: Between January 2012 and April 2015, 3036 patients were included in the trial, 1518 patients in 11 clusters allocated to intervention group and 1518 patients in 13 clusters allocated to standard care. There were 51 protocol violations. Conclusions: The ICE-CUB 2 trial was deemed feasible and ethically acceptable. The ICE-CUB 2 trial will be the first cluster-randomized trial to assess the benefits of ICU admission for selected elderly patients on long-term mortality. Trial registration Clinical trials.gov identifier: NCT01508819 [ABSTRACT FROM AUTHOR]

We report a case of an adult patient undergoing three unsuccessful Helicobacter pylori treatments, including proton pump inhibitor (PPI), bismuth subcitrate, metronidazole and tetracycline in 2012, PPI, amoxicillin and clarithromycin in 2013, and PPI, amoxicillin and rifampin in 2014. Following the first treatment, the isolate was metronidazole and ciprofloxacin/levofloxacin resistant. After the second treatment, the isolate was resistant to metronidazole, ciprofloxacin/levofloxacin and rifampin, developing secondary clarithromycin resistance by A2143G mutation and was susceptible only to tetracycline. After the third treatment, the patient still remained H. pylori positive. Patient's strain was highly virulent ( cagA, cagE and vacA s1a/m1/i1). The evolution of the patient's disease was from gastroesophageal reflux disease in 2012 to two duodenal ulcers in 2015. Briefly, the infecting strain showed quadruple antibiotic resistance and a transient amoxicillin resistance. Triple clarithromycin-based treatment induced secondary clarithromycin resistance by A2143G mutation, while rifampin resistance caused the third treatment failure. Several options for the next treatment regimens are discussed. [ABSTRACT FROM AUTHOR]

Wood formation is an economically and environmentally important process and has played a significant role in the evolution of terrestrial plants. Despite its significance, the molecular underpinnings of the process are still poorly understood. We have previously shown that four lateral organ boundaries (LBD) transcription factors have important roles in the regulation of secondary (woody) growth with two (LBD1 and LBD4) involved in secondary phloem and ray cell development and two (LBD15 and LBD18) in secondary xylem formation. We studied gene copy number and variation in DNA and amino acid sequences of the four LBDs in a wide range of woody and herbaceous plant taxa with fully sequenced and annotated genomes. LBD1 showed the highest gene copy number across species, and gene copy number was strongly and significantly correlated with tangential ray width. The climbing vines, cucumber and grape, with wide multiseriate rays (>10 cells wide) showed the highest gene copy number. Because the growth habit of woody lianas like grape requires significant twisting and bending, it was suggested that the unlignified ray parenchyma cells likely facilitate stem flexibility and maintenance of xylem conductivity. We further demonstrate conservation of amino acids in LBD18 protein sequences specific to woody taxa downstream of the LBD domain. Neutrality tests showed evidence for strong purifying selection on these regions across various orders, indicating important functional roles in woody taxa. Additionally, structural modeling demonstrates that these regions have a significant impact on tertiary protein structure and thus are likely of significant functional importance. [ABSTRACT FROM AUTHOR]

In this study, the preparation of poloxamer 188-coated poly(butyl cyanoacrylate) colloidal nanospheres of controlled size distribution and their physicochemical characterisation were investigated and their cytotoxic effects in cervical carcinoma (HeLa) cells evaluated. The nanoparticles were prepared by controlled emulsion polymerisation of butyl cyanoacrylate in an aqueous medium containing poloxamer 188 as an amphiphilic non-ionic colloidal stabiliser. The colloids thus obtained were characterised by scanning electron microscopy, dynamic and electrophoretic light-scattering, Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy. The average size of the particles could be finely controlled within an interval between 220 nm and 290 nm by varying the concentration of the precursor and citric acid in the polymerisation medium. The particle zeta-potentials in phosphate-buffered saline were approximately -4.5 mV. FTIR and NMR data confirmed the expected composition of nanoparticles and the complete precursor polymerisation. In-vitro studies with cervical carcinoma (HeLa) cells demonstrated the dose-dependent cytotoxicity of nanoparticles (IC50 ≈ 30 μg mL-1). Observations by phase contrast and fluorescence microscopy revealed that at cytotoxic concentrations (40 μg mL-1) nanoparticles induced changes in cell morphology and chromatin fragmentation. The colloidal stabiliser (poloxamer 188) alone was not cytotoxic at the applied concentrations. [ABSTRACT FROM AUTHOR]