Use of logit transformation within statistical analyses of experimental results obtained as proportions: example of method validation experiments and EQA in flow cytometry.

In laboratory medicine, measurement results are often expressed as proportions of concentrations or counts. These proportions have distinct mathematical properties that can lead to unexpected results when conventional parametric statistical methods are naively applied without due consideration in the analysis of method validation experiments, quality assessments, or clinical studies. In particular, data points near 0% or 100% can lead to misleading analytical conclusions. To avoid these problems, the logit transformation-defined as the natural logarithm of the proportion/(1-proportion)-is used. This transformation produces symmetric distributions centered at zero that extend infinitely in both directions without upper or lower bounds. As a result, parametric statistical methods can be used without introducing bias. Furthermore, homogeneity of variances (HoV) is given. The benefits of this technique are illustrated by two applications: (i) flow cytometry measurement results expressed as proportions and (ii) probabilities derived from multivariable models. In the first case, naive analyses within external quality assessment (EQA) evaluations that lead to inconsistent results are effectively corrected. Second, the transformation eliminates bias and variance heterogeneity, allowing for more effective precision estimation. In summary, the logit transformation ensures unbiased results in statistical analyses. Given the resulting homogeneity of variances, common parametric statistical methods can be implemented, potentially increasing the efficiency of the analysis.

Annual variation of source contributions to PM10 and oxidative potential in a mountainous area with traffic, biomass burning, cement-plant and biogenic influences.

Toxicity of particulate matter (PM) depends on its sources, size and composition. We identified PM10 sources and determined their contribution to oxidative potential (OP) as a health proxy for PM exposure in an Alpine valley influenced by cement industry. PM10 filter sample chemical analysis and equivalent black carbon (eBC) were measured at an urban background site from November 2020 to November 2021. Using an optimized Positive Matrix Factorization (PMF) model, the source chemical fingerprints and contributions to PM10 were determined. The OP assessed through two assays, ascorbic acid (AA) and dithiothreitol (DTT), was attributed to the PM sources from the PMF model with a multiple linear regression (MLR) model. Ten factors were found at the site, including biomass burning (34, 40 and 38% contribution to annual PM10, OPAA and OPDDT, respectively), traffic (14, 19 and 7%), nitrate- and sulphate-rich (together: 16, 5 and 8%), aged sea salt (2, 2 and 0%) and mineral dust (10, 12 and 17%). The introduction of innovative organic tracers allowed the quantification of the PM primary and secondary biogenic fractions (together: 13, 8 and 21%). In addition, two unusual factors due to local features, a chloride-rich factor and a second mineral dust-rich factor (named the cement dust factor) were found, contributing together 10, 14 and 8%. We associate these two factors to different processes in the cement plant. Despite their rather low contribution to PM10 mass, these sources have one of the highest OPs per µg of source. The results of the study provide vital information about the influence of particular sources on PM10 and OP in complex environments and are thus useful for PM control strategies and actions.

High repetition-rate foam targetry for laser-plasma interaction experiments: Concept and preliminary results.

Foam targets have gained considerable importance over the last decade in laser-matter interaction. They find widespread applications such as in inertial confinement fusion and secondary sources for particles and radiation. At the same time, the advent of high repetition-rate laser systems, be they short-pulse in the tens of femtosecond regime or in the kilo-Joule nanosecond regime, calls for equally high repetition rate targetry systems. A well-established repetition-rate targetry system is the tape target. In this article, we present the successful marriage of a tape target delivery system with 3D-printed foam targets produced by two photon polymerization.

Coherent Control of the Fine-Structure Qubit in a Single Alkaline-Earth Atom.

We report on the first realization of a novel neutral atom qubit encoded in the spin-orbit coupled metastable states ^{3}P_{0} and ^{3}P_{2} of a single ^{88}Sr atom trapped in an optical tweezer. Raman coupling of the qubit states promises rapid single-qubit rotations on par with the fast Rydberg-mediated two-body gates. We demonstrate preparation, readout, and coherent control of the qubit. In addition to driving Rabi oscillations bridging an energy gap of more than 17 THz using a pair of phase-locked clock lasers, we also carry out Ramsey spectroscopy to extract the transverse qubit coherence time T_{2}. When the tweezer is tuned into magic trapping conditions, which is achieved in our setup by tuning the tensor polarizability of the ^{3}P_{2} state via an external control magnetic field, we measure T_{2}=1.2 ms. A microscopic quantum mechanical model is used to simulate our experiments including dominant noise sources. We identify the main constraints limiting the observed coherence time and project improvements to our system in the immediate future. Our Letter opens the door for a so-far-unexplored qubit encoding concept for neutral atom-based quantum computing.

Coherent Subcycle Optical Shock from a Superluminal Plasma Wake.

We propose exploiting the superluminal plasma wake for coherent Cherenkov radiation by injecting a relativistic electron beam (REB) into a plasma with a slowly varying density up-ramp. Using three-dimensional particle-in-cell and far-field time-domain radiation simulations, we show that an isolated subcycle pulse is coherently emitted towards the Cherenkov angle by bubble-sheath electrons successively at the rear of the REB-induced superluminal plasma wake. A theoretical model based on a superluminal current dipole has been developed to interpret such coherent radiation, and agrees well with the simulation results. This radiation has ultrashort attosecond-scale duration and high intensity, and exhibits excellent directionality with ultralow angular divergence and stable carrier envelope phase. Its intensity increases with the square of the propagation length and its central frequency can be easily tuned over a wide range, from the far infrared to the ultraviolet.

Full aperture backscatter diagnostics for characterization of laser plasma instabilities at the extreme light infrastructure (ELI) beamlines.

We report on the commissioning of a full aperture backscatter diagnostics station for the kilojoule, nanosecond high repetition rate L4n laser operating at a wavelength of 527 nm at the Extreme Light Infrastructure (ELI) - Beamlines, Dolni Brezany, Czech Republic. Light scattered back from laser-plasma interaction into the cone of the final focusing lens is captured and split into different channels to measure the signatures of laser plasma instabilities from stimulated Brillouin scattering, stimulated Raman scattering, and two plasmon decay with respect to back scattered energy, its spectrum, and its temporal profile. The performance was confirmed in a commissioning experiment with more than 800 shots at laser intensities ranging from 0.5 × 1013 to 1.1 × 1015 W cm-2. These diagnostics are permanently installed at ELI Beamlines, and can be used to understand the details of laser-plasma interactions in experiments with kJ and 527 nm light. The large number of shots that can be collected in an experimental campaign will allow us to study the details of the laser-plasma interaction with a high level of confidence.

Smoked drug use in patients with TB is associated with higher bacterial burden.

BACKGROUND: Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association between smoked drug use and bacterial burden among patients newly initiated on drug-susceptible TB (DS-TB) therapy.METHODS: Data from 303 participants initiating DS-TB treatment in the Western Cape Province, South Africa, were analyzed. Smoked drug use was defined as self-reported or biologically verified methamphetamine, methaqualone and/or cannabis use. Proportional hazard and logistic regression models (adjusted for age, sex, HIV status and tobacco use) examined associations between smoked drug use and mycobacterial time to culture positivity (TTP), acid-fast bacilli sputum smear positivity and lung cavitation.RESULTS: People who smoked drugs (PWSD) comprised 54.8% (n = 166) of the cohort. TTP was faster for PWSD (hazard ratio 1.48, 95% CI 1.10-1.97; P = 0.008). Smear positivity was higher among PWSD (OR 2.28, 95% CI 1.22-4.34; P = 0.011). Smoked drug use (OR 1.08, 95% CI 0.62-1.87; P = 0.799) was not associated with increased cavitation.CONCLUSIONS: PWSD had a higher bacterial burden at diagnosis than those who do not smoke drugs. Screening for TB among PWSD in the community may facilitate earlier linkage to TB treatment and reduce community transmission.

Case report: Rhabdomyolysis in children in acute and chronic disease-a challenging condition in pediatric emergency medicine.

Rhabdomyolysis is a challenging condition in pediatric emergency departments (PED): It ranges from asymptomatic illness with isolated elevation of creatine kinase (CK) levels to a life-threatening condition associated with extreme elevations in CK, electrolyte imbalances, circulatory failure (CF), acute kidney injury (AKI), and multi-organ disease. Most common causes of rhabdomyolysis are viral myositis and trauma, hereditary metabolic myopathies must be considered when facing rhabdomyolysis in early childhood. We report two cases of severe rhabdomyolysis with CF in our PED, thereby summarizing first-line management of rhabdomyolysis.

A rare case of Immunoglobulin A dominant post-infectious glomerulonephritis (IgA PIGN) in a young patient.

BACKGROUND: Immunoglobulin A dominant postinfectious glomerulonephritis (IgA PIGN) is a unique medical entity that is rare in the paediatric population. It usually presents with severe renal failure, heavy proteinuria, hypertension, and hypocomplementemia and frequently has an unfavourable prognosis. IgA PIGN generally occurs in association with staphylococcal infections and diabetes mellitus in adult patients. Other pathogens include Escherichia coli and Streptococcus sp. Immunofluorescence studies of kidney biopsy samples show IgA as dominant or codominant antibody. CASE PRESENTATION: We encountered a 3-year-old girl with IgA PIGN presenting with acute renal failure, oedema, hypertension, and heavy proteinuria of 7955 mg/g creatinine. Renal biopsy specimens showed diffuse glomerular endocapillary hypercellularity with prominent neutrophil and monocyte infiltration on light microscopy. Strong deposits of IgA and C3 were observed along the glomerular basement membranes and the mesangium by immunofluorescence microscopy, and electron microscopy revealed the presence of subepithelial humps. The patient was managed with steroid (and probatory antibiotic) therapy and is now undergoing follow-up, with a significant improvement 6 months after the initial presentation (glomerular filtration rate (GFR) and cystatin C clearance rate of 165 ml/min/1.73m2 and 106 ml/min/1.73m2, respectively). No signs of bacterial infection were detectable. CONCLUSION: This variant of IgA PIGN must be distinguished from other clinical entities, especially IgA nephropathy (mesangial IgA deposits) and postinfectious glomerulonephritis (C3, IgG and occasional IgM capillary loop deposits with or without mesangial distribution), since patients with IgA PIGN may require steroid treatment in addition to antibiotic therapy. Differential diagnosis should also include C3 glomerulopathy. IgA PIGN is a recently identified disease entity that generally manifests in adult patients with both IgA and C3 mesangial and glomerular capillary wall deposits. We present a biopsy-proven case of IgA PIGN that manifested in a patient at an exceptionally young age and that has had a good clinical outcome. To the best of our knowledge, this is the youngest IgA PIGN patient reported thus far.

TB disease patterns by HIV and diabetes status.

BACKGROUND: TB is commonly categorised as pulmonary (PTB) or extrapulmonary TB (EPTB). Knowledge of TB disease patterns (PTB and/or EPTB) and determining risk factors remains limited.METHODS: This was a prospective cohort study using point-of-care ultrasound (POCUS) in Indian patients with presumed TB. Clinical and imaging data were used to develop refined case definitions for PTB, concurrent PTB and EPTB (PTB + EPTB) and EPTB without PTB (EPTB). These groups were analysed by HIV (HIV+/-) and diabetes mellitus (DM+/-) status.RESULTS: Of 172 HIV-/DM- patients with TB, 48% had PTB, 23% PTB + EPTB and 29% had EPTB, totalling 52% with any EPTB (PTB + EPTB or EPTB). In HIV+/DM- patients with TB (n = 35), 6% had PTB, 40% had PTB + EPTB and 54% had EPTB, accounting for 94% with EPTB. In HIV-/DM+ patients with TB (n = 61), 61% had PTB, 28% had PTB + EPTB and 11% had EPTB, representing 39% with EPTB.CONCLUSION: Refined case definitions revealed high proportions of EPTB even without HIV or DM. HIV further altered the TB disease pattern towards EPTB and DM towards PTB. Therefore, the dichotomy between PTB or EPTB does not represent the actual spectrum of TB disease. EPTB should receive higher priority in research and clinical practice.

PyMoDAQ: An open-source Python-based software for modular data acquisition.

Thanks to the recent multiplication of scientific Python packages in the open-source software landscape, Data Acquisition frameworks (DAQ-Fs) appear as versatile replacements of custom-made or costly commercial solutions. PyMoDAQ is a DAQ-F focusing on easy-to-use graphical user interfaces allowing a simple control and automation of a large variety of experimental setups. Its development included a highly modular structure allowing any experimental data acquisition as a function of multiple varying parameters. It offers numerous additional functionalities: instrument and setup configuration, plotting, saving, logging, etc. Live visual feedback is available at all times to monitor the ongoing experiment. Flexibility of its user interfaces is the key advantage of PyMoDAQ allowing also its integration as the core of more focused applications. Its hierarchical binary format data saving mechanism includes experimental metadata highly compatible with FAIR (Findable, Accessible,Interoperable, Reusable) data. Among the presented characteristics, seven criteria have been chosen to judge the pertinence of PyMoDAQ as a versatile DAQ-F. They are also the basis for a comparison with other existing frameworks highlighting the novelty of PyMoDAQ.

High-repetition rate solid target delivery system for PW-class laser-matter interaction at ELI Beamlines.

L3-HAPLS (High-repetition-rate Advanced Petawatt Laser System) at ELI (Extreme Light Infrastructure) Beamlines currently delivers 0.45 PW pulses (12 J in 27 fs) at 3.3 Hz repetition rate. A fresh target surface for every shot was placed at the laser focus using an in-house tape target system designed to withstand large laser intensities and energies. It has been tested for different material thicknesses (25 and 7.6 µm), while L3-HAPLS delivered laser shots for energies ranging from 1 to 12 J. A technical description of the tape target system is given. The device can be used in diverse geometries needed for laser-matter interaction studies by providing an ≈300° free angle of view on the target in the equatorial plane. We show experimental data demonstrating the shot-to-shot stability of the device. An x-ray crystal spherical spectrometer was set up to measure the Kα yield stability, while a GHz H-field probe was used to check the shot-to-shot electromagnetic pulse generation. Finally, we discuss short and mid-term future improvements of the tape target system for efficient user operation.

Transesophageal Echocardiography - Dysphagia Risk in Acute Stroke (TEDRAS): a prospective, blind, randomized and controlled clinical trial.

BACKGROUND AND PURPOSE: Dysphagia is common in acute stroke and leads to worse overall outcome. Transesophageal echocardiography (TEE) is used in the diagnostic evaluation of stroke with regard to its etiology and is a known cause of postoperative dysphagia in cardiac surgery. The prevalence of dysphagia in acute stroke patients undergoing TEE remains unknown. The aim of the Transesophageal Echocardiography - Dysphagia Risk in Acute Stroke (TEDRAS) study was to assess the influence of TEE on swallowing among patients who have experienced acute stroke. METHODS: The TEDRAS study was a prospective, blind, randomized, controlled trial that included two groups of patients with acute stroke. Simple unrestricted randomization was performed, and examiners were blinded to each other's results. Swallowing was tested using flexible endoscopic evaluation of swallowing (FEES) at three different time points in the intervention group (24 h before, immediately after and 24 h after TEE) and in the control group (FEES on three consecutive days and TEE earliest after the third FEES). Validated scales were used to assess dysphagia severity for all time points as primary outcome measures. RESULTS: A total of 34 patients were randomized: 19 to the intervention group and 15 to the control group. The key findings of the repeated-measures between-group comparisons were significant increases in the intervention group for the following dysphagia measures: (1) secretion severity score (immediately after TEE: P < 0.001; 24 h after TEE: P < 0.001) and (2) Penetration-Aspiration Scale score for saliva (immediately after TEE: P < 0.001; 24 h after TEE: P = 0.007), for small (immediately after TEE: P = 0.009) and large liquid boli (immediately after TEE: P = 0.009; 24 h after TEE: P = 0.025). CONCLUSION: The results indicate a negative influence of TEE on swallowing in acute stroke patients for at least 24 hours.

Treatment of intraoperative hypotension with cafedrine/theodrenaline versus ephedrine : A prospective, national, multicenter, non-interventional study-the HYPOTENS trial.

BACKGROUND: Sympathomimetic drugs are a therapeutic cornerstone for the management of hypotensive states like intraoperative hypotension (IOH). While cafedrine/theodrenaline (C/T) is widely used in Germany to restore blood pressure in patients with IOH, more research is required to compare its effectiveness with alternatives such as ephedrine (E) that are more commonly available internationally. METHODS: HYPOTENS (NCT02893241, DRKS00010740) was a prospective, national, multicenter, open-label, two-armed, non-interventional study that compared C/T with E for treatment of IOH. We describe a prospectively defined cohort of patients ≥50 years old with comorbidities undergoing general anesthesia induced with propofol and fentanyl. Primary objectives were to examine treatment precision, rapidity of onset and the ability to restore blood pressure without relevant increases in heart rate. Secondary endpoints were treatment satisfaction and the number of required additional boluses or other accompanying measures. RESULTS: A total of 1496 patients were included in the per protocol analysis. Overall, effective stabilization of blood pressure was achieved with both C/T and E. Post-hoc analysis showed that blood pressure increase from baseline was more pronounced with C/T. Fewer additional boluses or other accompanying measures were required in the C/T arm. The incidence of tachycardia was comparable between groups. Post-hoc analysis showed that E produced dose-dependent elevated heart rate values. By contrast, heart rate remained stable in patients treated with C/T. Physicians reported a higher level of treatment satisfaction with C/T, with a higher proportion of anesthetists rating treatment precision and rapidity of onset as good or very good when compared with E. CONCLUSION: Neither drug was superior in restoring blood pressure levels; however, post-hoc analyses suggested that treatment is more goal-orientated and easier to control with C/T. Heart rate was shown to be more stable with C/T and fewer additional interventions were required to restore blood pressure, which could have contributed to the increased treatment satisfaction reported by anesthetists using C/T.

[Lung ultrasound in COVID-19]. / Lungensonographie bei COVID­19.

Providing medical care to patients suffering from the coronavirus disease 2019 (COVID-19) pandemic is a major challenge for government healthcare systems around the world. The new coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shows a high organ specificity for the lower respiratory tract. Since there is so far no effective treatment or vaccination against the virus, early diagnostic recognition is of great importance. Due to the specific aspects of the infection, which mainly begins in the peripheral lung parenchyma, lung ultrasonography is suitable as a diagnostic imaging method to identify suspected cases as such in the early stages of the disease. Serial ultrasound examinations on patients with confirmed COVID-19 can promptly detect changes in the affected lung tissue at the bedside. This article summarizes the diagnostic potential of lung ultrasound with respect to screening and therapeutic decision-making in patients with suspected or confirmed SARS-CoV­2 pneumonia.

Capacity of solutions involving organic acids in the extraction of the anthocyanins present in jabuticaba skins (Myrciaria cauliflora) and red cabbage leaves (Brassica oleracea).

Anthocyanins make up the largest group of water-soluble pigments of the vegetable kingdom. These bio-compounds with antioxidant properties are attracting great interest in the food, pharmaceutical and cosmetic industry mainly because of their presence in many fruits and vegetables. The extraction of the pigment is still in need of further studies, especially concerning the extraction yield and the use of friendly solvents. The use of acidulants has shown an alternative to improve the extraction. This work presents the capability of pure solvents and binary mixtures associated with organic acids in the extraction of anthocyanins present in jabuticaba fruit skins and red cabbage leaves. The results suggest that the application of organic acids dissolved in binary mixtures formed by water and ethanol can provide an increase in the extraction of anthocyanins.

Genetic variant c.711A>T in the hepatobiliary phospholipid transporter ABCB4 is associated with significant liver fibrosis.

Liver fibrosis is the common consequence of chronic liver diseases (CLD). Recently liver stiffness measurements (LSM) ≥ 9.1 kPa, as determined by transient elastography (TE), were demonstrated to predict significant fibrosis (stages ≥ F2) in a population-based setting. The PNPLA3 (adiponutrin) p.I148M polymorphism enhances the risk of liver injury. The aim of our study was to investigate the association between the procholestatic ABCB4 polymorphism c.711A>T and LSM ≥ 9.1 kPa in humans as well as the interaction between ABCB4 and PNPLA3 in a mouse model of chronic cholestasis. Prospectively, we recruited 712 patients with CLD (278 women, age 50 ± 13 years) with available TE results; liver biopsy results were available in 165 individuals. The ABCB4 c.711 genotype was determined by PCR-based assays. PNPLA3 expression and liver injury were studied in Abcb4-/- mice and wild-type controls. Overall, median LSM in our cohort was 6.7 kPa, and 226 individuals had LSM ≥ 9.1 kPa. Carriers of the ABCB4 variant c.711A presented more frequently with LSM ≥ 9.1 kPa (OR = 1.33, P = 0.020) and FIB-4 score ≥ 2.67 (OR = 1.38, P = 0.040). The presence of the risk allele was associated (P = 0.002) with FIB-4. In a multivariate model, the ABCB4 variant (OR = 1.43, P = 0.047) as well as BMI (P = 0.043, OR = 1.04) and age (OR = 1.02, P < 0.010) were independent risk factors for fibrosis stage ≥ F2. Abcb4 deficiency in mice led to enhanced liver injury, coupled with a decrease (P = 0.020) of hepatic PNPLA3 expression. To conclude, the procholestatic variant ABCB4 c.711A>T might represent a new genetic risk factor for clinically significant liver fibrosis. Lower expression of PNPLA3 in fibrotic Abcb4-/- livers points to the interaction between phospholipid metabolism and PNPLA3 in progressive liver injury.

Reduced Neural Satiety Responses in Women Affected by Obesity.

Overweight and obesity are major risk factors for a number of chronic diseases, including diabetes, cardiovascular diseases, and cancer. Obesity rates are on the rise worldwide with women more frequently affected than men. Hedonic responses to food seem to play a key role in obesity, but the exact mechanisms and relationships are still poorly understood. In this study, we investigate the perceived pleasantness of food rewards in relation to satiety and calories consumed during an ad libitum meal in women. Using functional magnetic resonance imaging (fMRI) and a milkshake consumption task, we studied how experienced food values are encoded in women with healthy weight, overweight or obesity. Participants rated the pleasantness and intensity of high and low caloric milkshakes in the fMRI scanner during both the fasted and fed states. We found differences in the neural responses and experienced pleasantness of high and low caloric milkshakes depending on satiety and Body Mass Index (BMI). Women with both high ad libitum consumption levels and high BMI reported greater experienced pleasantness for milkshakes. In contrast, among women with low ad libitum consumption levels, greater BMI was associated with less experienced pleasantness. At the neural level, satiety affected women with obesity to a lesser degree than women with healthy weight. Thus, having obesity was associated with altered relationships between food consumption and the hedonic responses to food rewards as well as reduced satiety effects in women.