Search

—The paper provides the results of experiments with sediment traps in the deep-water part of the South Basin of Lake Baikal (depth of 1366 m), installed from March 2015 to March 2016 in order to study recent sedimentation within the lake. We present new data on total fluxes of particulate matter and fluxes of biogenic components (SiO2biog, Сorg, and Ntot) at different depths of the water column both for the whole year and for individual periods of the year. Diatom analyses were carried out for all obtained samples. The total flux of sedimentary material averaged 94.9 g/m2/y; the average fluxes of SiO2biog, Сorg, and Ntot were 23.9, 11.6, and 0.94 g/m2/y, respectively. The molar C/N ratio varies from 11 to 21 and indicates a predominance of allochthonous material in almost all samples. Maximum fluxes of sedimentary matter were recorded from 20 June to 20 July 2015. This period corresponds to the bloom of diatoms of the species Synedra acus. This species amounts to >94% of the total diatom content in all samples taken during this year. The recent predominance of Synedra acus in the water column, as well as in the surface bottom sediments of South Baikal, is probably due to the climate warming.

We performed the experimental and theoretical study of the heating and damaging of ruthenium thin films induced by femtosecond laser irradiation. Results of an optical pump-probe thermoreflectance experiment with rotating sample allowing to significantly reduce heat accumulation in irradiated spot are presented. We show the evolution of surface morphology from growth of a heat-induced oxide layer at low and intermediate laser fluences to cracking and grooving at high fluences. Theoretical analysis of pump-probe signal allows us to relate behavior of hot electrons in ruthenium to the Fermi smearing mechanism. The analysis of heating is performed with the two-temperature modeling and molecular dynamics simulation, results of which demonstrate that the calculated melting threshold is higher than experimental damage threshold. We attribute it to heat-induced surface stresses leading to cracking which accumulates to more severe damage morphology. Our results provide an upper limit for operational conditions for ruthenium optics and also direct to further studies of the Fermi smearing mechanism in other transition metals., 23 pages, 11 figures, 1 table, 7 data files in supplementary material

We investigate the use of Low Energy Ion Scattering (LEIS) to characterize buried interfaces of ultra-thin films. LEIS spectra contain depth-resolved information in the so-called sub-surface signal. However, the exact correlation between the sub-surface signal and the depth composition is still unknown. For this reason, LEIS spectra so far only provided qualitative information about buried interfaces. In this study, we investigate nm-thin films of Si-on-W and Si-on-Mo, where we compare simulated data to LEIS spectra. We present a method to extract depth-sensitive compositional changes -- resolving buried interfaces -- from LEIS spectra for the first few nanometers of a thin film sample. In the case of Si-on-Mo, the simulation of the LEIS sub-surface signal allows obtaining a quantitative measurement of the interface profile that matches the value determined using the LEIS layer growth profile method with an accuracy of 0.1 nm. These results pave the way to further extend the use of LEIS for the characterization of features buried inside the first few nanometers of a sample., 25 pages, 11 figures

Semi-empirical formulae like the Yamamura model provide a quick reference of sputter yields for applications such as sputter depth profiling and secondary ion mass spectrometry. Fit parameters in such models are prone to errors which can propagate into the prediction of sputter yields. We compare experimental sputter yields to predictions of the Yamamura model using a Bayesian Markov Chain Monte Carlo (MCMC) algorithm. The model parameters Q (linear scaling) and s (power-law scaling) are explored. The results from MCMC are then compared to propositions of Seah (Surface and Interface Analysis, 2005) and extended to a collection of target materials by fitting simulated yields for argon and neon using TRIDYN. Q was found to be proportional to the threshold energy and a simple relation is proposed. The simplicity notwithstanding, Q is speculated to be dependent on a multitude of parameters such as density, energy transfer and orbital filling.

Characterization of Peyronie’s disease (PD) involves manual goniometry and penile length measurement. These techniques neglect volume loss or hourglass deformities. Inter-provider variability complicates accuracy. Using 3D-printed models, we aimed to evaluate measurement accuracy and variability and establish computational assessment workflows. Five digital phantoms were created: 13.0 cm cylinder, 13.0 cm hourglass cylinder, 15.0 cm cylinder with 40° angulation, 12.0 cm straight penis, and 12.9 cm PD penis with 68° angulation and hourglass. Lengths, volumes, and angles were determined computationally. Each phantom was 3D-printed. Ten urology providers determined lengths, angles, and volumes with measuring tape, goniometer, and volume calculator. Provider versus computational measurements were compared to determine accuracy using t-tests or Wilcoxon rank-sum tests. No significant differences were observed between manual assessment of length of penile models and designed length in penile models. Average curvature angles from providers for bent cylinder and PD phantoms were 38.3° ± 3.9° (p = 0.25) and 57.5° ± 7.2° (p = 0.006), respectively. When assessing for volume, hourglass cylinder and bent cylinder showed significant differences between designed volume and provider averages. All assessments of length, angle, and volume showed significant provider variability. Our results suggest manual measurements suffer from inaccuracy and variability. Computational workflows are useful for improved accuracy and volume assessment.

In recent decades, reproductive science has revolutionized the options for biological parenthood for the 20–50% of infertility cases affected by male factors. However, current solutions exclude those who are infertile due to absent testicular tissue. This includes anorchic 46, XY individuals due to trauma or congenital factors and transgender men with a 46, XX genotype. There is a clinical need for methods to restore testicular function independent of pre-existing testicular tissue. This mini-review analyzes studies that have applied non-testicular cell lines to generate germline and non-germline testicular parenchymal components. While only 46, XY cell lines have been evaluated in this context to date, the potential for future application of cell lines from 46, XX individuals is also included. Additionally, the role of varied culture methods, media supplementation, and biologic and synthetic scaffolds to further support testicular parenchyma generation are critiqued. De novo testicular tissue generation in this manner will require a focus on both cellular and environmental aspects of tissue engineering. Put together, these studies highlight the future potential for expanded clinical, reproductive, and endocrine management options for individuals who are currently excluded from aspects of biologic reproduction most consistent with their gender identity and reproductive preferences.

Background and purpose Miltefosine is an alkylphosphocholine drug with proven effectiveness against various types of parasites and cancer cells. Miltefosine is not only able to induce direct parasite killing but also modulates host immunity, for example by reducing the severity of allergies in patients. To date, there are no reports on the effect of miltefosine on eosinophils, central effector cells involved in allergic inflammation. Experimental approach We tested the effect of miltefosine on the activation of human eosinophils and their effector responses in vitro and in mouse models of eosinophilic migration and ovalbumin-induced allergic lung inflammation. Key results The addition of miltefosine suppressed several eosinophilic effector reactions such as CD11b up-regulation, degranulation, chemotaxis and downstream signalling. Miltefosine significantly reduced the infiltration of immune cells into the respiratory tract of mice in an allergic cell recruitment model. Finally, in a model of allergic inflammation, treatment with miltefosine resulted in an improvement of lung function parameters. Conclusion and implications Our observations suggest a strong modulatory activity of miltefosine in the regulation of eosinophilic inflammation in vitro and in vivo. Our data underline the potential efficacy of miltefosine in the treatment of allergic diseases and other eosinophil-associated disorders and may raise important questions regarding the immunomodulatory effect of miltefosine in patients treated for leishmania infections.

IntroductionBiodesign innovation processes provide a needs-driven approach to medical innovation, empowering both medical trainees and health care providers to take action in addressing the shortcomings of health care encountered in daily clinical practice. Our objective was to uncover the most pressing unmet clinical needs within a specific clinical setting, pediatric urology at UCLA.MethodsThe biodesign process involves a sequential process of identifying, validating, and prioritizing unmet needs, followed by solution landscaping and prototyping for the most promising needs. Opportunities for medical innovation were first identified through six weeks of clinical immersion, which involved both clinical observation and interview-based insight extraction. Interviews were conducted with 35 stakeholders, including patients, patient families, and health care staff by a medical student participant in Sling Health LA, a program which provides innovation training and incubation for ideas. Follow-up interviews with key stakeholders were performed to validate needs. Priority scores were then assigned to each validated need using a series of pre-determined and weighted criteria. Finally, genealogy maps were constructed and used to guide subsequent solution landscaping for the top three needs.Results33 unmet clinical needs were identified throughout the clinical immersion phase, 27 of which were validated. Following coarse needs prioritization, five needs emerged as top contenders. After fine needs prioritization, three top needs were selected. The first top need arising from this ethnographic study was that “parents and children need a faster (ConclusionBiodesign processes offer a standardized method for identifying pressing unmet clinical needs and informing solution development. The top three needs discovered within pediatric urology through this ethnographic investigation represent promising innovation targets for further solution prototyping and design.

Objectives To evaluate an alternative to clean intermittent catheterization (CIC) for individuals with neurogenic bladder for its effects on independence, privacy, and convenience. This prospective cohort study provides an initial assessment of quality of life, safety, and efficacy of closed diurnal indwelling catheterization (CDIC). Materials and Methods Individuals with spinal cord disorders using CIC were prospectively screened at multidisciplinary clinic appointments. During the 24-week intervention, a foley was placed each morning and capped between scheduled bladder drainage each 3-4 hours. After a maximum of 8 hours of CDIC use, CIC was resumed. Quality of life outcome measures (the Short Form Health Survey, King's Health Questionnaire, and Pediatric Quality of Life InventoryTM (PedsQL) questionnaires), clinic evaluations, labs, imaging, and urodynamics were obtained at specified interval visits planned after 4-, 12-, and 24 weeks of study participation and compared to baseline. Results A total of 11 subjects enrolled; 8 completed the 24-week intervention. No significant difference with CDIC was observed in the Short Form Health Survey or PedsQL summary scores as compared to baseline. For the King's Health Questionnaire, physical limitations secondary to bladder function decreased significantly from baseline to the 4-week and 12-week (P = .02) but not 24-week visits. All 8 subjects who completed the 24-week intervention requested continued use. Early discontinuation occurred in 3 male participants due to urethral trauma (1) and incontinence (2). No increase in bacteriuria, urinary tract infections, or renal anatomic changes was observed. Conclusion This prospective study demonstrates that CDIC may be safe and effective for short-term use. This alternative to CIC for scheduled daytime bladder drainage for neurogenic bladder warrants further consideration.

Using newly constructed spatially disaggregated data for London from 1801 to 1921, we show that the invention of the steam railway led to the first large-scale separation of workplace and residence. We show that a class of quantitative urban models is remarkably successful in explaining this reorganization of economic activity. We structurally estimate one of the models in this class and find substantial agglomeration forces in both production and residence. In counterfactuals, we find that removing the whole railway network reduces the population and the value of land and buildings in London by up to 51.5% and 53.3% respectively, and decreases net commuting into the historical center of London by more than 300,000 workers.

The COVID-19 (coronavirus disease 2019) pandemic has highlighted the potential role that wastewater-based epidemiology can play in assessing aggregate community health. However, efforts to translate SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) gene copy numbers obtained from wastewater samples into meaningful community health indicators are nascent. In this study, SARS-CoV-2 nucleocapsid (N) genes (N1 and N2) were quantified weekly using reverse transcriptase droplet digital PCR from two municipal wastewater treatment plants for 6 months. Four biomarkers [ammonium, biological oxygen demand (BOD), creatinine and human mitochondrial gene NADH dehydrogenase subunit 5] were quantified and used to normalize SARS-CoV-2 gene copy numbers. These were correlated to daily new case data and 1-, 2- and 3-week cumulative case data. Over the course of the study, the strongest correlations were observed with a 1-day case data lag. However, early measurements were strongly correlated with a 5-day case data lag. This indicates that in the early stages of the pandemic, the wastewater samples may have indicated active COVID-19 cases before clinical indications. Mitochondrial and creatinine normalization methods showed the strongest correlations throughout the study, indicating that human-specific biomarkers were better at normalizing wastewater data than ammonium or BOD. Granger causality tests supported this observation and showed that gene copies in wastewater could be predictive of new cases in a sewershed.

We report the design and performance of a non-magnetic drift stable optically pumped cesium magnetometer with a measured sensitivity of 35 fT at 200 s integration time and stability below 50 fT between 70 s and 600 s. To our knowledge this is the most stable magnetic field measurement to date. The sensor is based on the nonlinear magneto-optical rotation effect: in a Bell-Bloom configuration a higher order polarization moment (alignment) of Cs atoms is created with a pump laser beam in an anti-relaxation coated Pyrex cell under vacuum, filled with Cs vapor at room temperature. The polarization plane of light passing through the cell is modulated due the precession of the atoms in an external magnetic field of 2.1 muT, used to optically determine the Larmor precession frequency. Operation is based on a sequence of optical pumping and observation of freely precessing spins at a repetition rate of 8 Hz. This free precession decay readout scheme separates optical pumping and probing and thus ensures a systematically highly clean measurement. Due to the residual offset of the sensor of < 15 pT together with the cross-talk free operation of adjacent sensors, this device is uniquely suitable for a variety of experiments in low-energy particle physics with extreme precision, here as highly stable and systematically clean reference probe in search for time-reversal symmetry violating electric dipole moments., Submitted in AIP Applied Physics Letter

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals. © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

The KArlsruhe TRItium Neutrino (KATRIN) experiment aims to determine the effective anti-electron neutrino mass with a sensitivity of 0.2 eV/c$^2$ by using the kinematics of tritium $\beta$-decay. It is crucial to have a high signal rate which is achieved by a windowless gaseous tritium source producing 10$^{11}$ $\beta$-electrons per second. These are guided adiabatically to the spectrometer section where their energy is analyzed. In order to maintain a low background rate below 0.01 cps, one essential criteria is to permanently reduce the flow of neutral tritium molecules between the source and the spectrometer section by at least 14 orders of magnitude. A differential pumping section downstream from the source reduces the tritium flow by seven orders of magnitude, while at least another factor of 10$^7$ is achieved by the cryogenic pumping section where tritium molecules are adsorbed on an approximately 3 K cold argon frost layer. In this paper, the results of the cryogenic pumping section commissioning measurements using deuterium are discussed. The cryogenic pumping section surpasses the requirement for the flow reduction of 10$^7$ by more than one order of magnitude. These results verify the predictions of previously published simulations.

INTRODUCTION AND OBJECTIVE:Despite randomized controlled trials (RCTs) demonstrating feasibility and short-term oncologic non-inferiority of robotic radical cystectomy and urinary diversion, its su...

Summary Background Testicular torsion is a surgical emergency, and time to detorsion is imperative for testicular salvage. During the COVID-19 pandemic, patients may delay emergency care due to stay-at-home orders and concern of COVID-19 exposure. Objective To assess whether emergency presentation for testicular torsion was delayed during the COVID-19 pandemic, and whether the rate of orchiectomy increased compared to a retrospective period. Study design Patients were prospectively enrolled in a multicenter study from seven institutions in the United States and Canada. Inclusion criteria were patients two months to 18 years of age with acute testicular torsion from March through July 2020. The retrospective group included patients from January 2019 through February 2020. Statistical analysis was performed using Kruskal–Wallis tests, Chi-square tests, and logistic regression. Results A total of 221 patients were included: 84 patients in the COVID-19 cohort and 137 in the retrospective cohort. Median times from symptom onset to emergency department presentation during COVID-19 compared to the retrospective period were 17.9 h (IQR 5.5–48.0) and 7.5 h (IQR 4.0–28.0) respectively (p = 0.04). In the COVID-19 cohort, 42% of patients underwent orchiectomy compared to 29% of pre-pandemic controls (p = 0.06). During COVID-19, 46% of patients endorsed delay in presentation compared to 33% in the retrospective group (p = 0.04). Discussion We found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a higher proportion of patients reported delaying care. Strengths of the study include the number of included patients and the multicenter prospective design during the pandemic. Limitations include a retrospective pre-pandemic comparison group. Conclusions In a large multicenter study we found a significantly longer time from testicular torsion symptom onset to presentation during the pandemic and a significantly higher proportion of patients reported delaying care. Based on the findings of this study, more patient education is needed on the management of testicular torsion during a pandemic.

Background The prostaglandin D2 receptor DP2 has been implicated in eosinophil infiltration and the development of eosinophilic esophagitis (EoE). Aims and Methods In this study, we investigated an involvement of PGE2 (EP1–EP4) and PGD2 (DP1) receptors in EoE by measuring their expression in peripheral blood eosinophils and esophageal mucosal biopsies of EoE patients and by performing migration and adhesion assays with eosinophils from healthy donors. Results Expression of EP2 and EP4, but not EP1 and EP3, was decreased in blood eosinophils of patients with EoE vs. control subjects. Adhesion of eosinophils to esophageal epithelial cells was decreased by EP2 receptor agonist butaprost and EP4 agonist ONO-AE1-329, whereas DP1 agonist BW245C increased adhesion. In chemotaxis assays with supernatant from human esophageal epithelial cells, only ONO-AE1-329 but not butaprost or BW245C inhibited the migration of eosinophils. Expression of EP and DP receptors in epithelial cells and eosinophils was detected in sections of esophageal biopsies from EoE patients by immunohistochemistry. qPCR of biopsies from EoE patients revealed that gene expression of EP4 and DP1 was the highest among PGE2 and PGD2 receptors. Esophageal epithelial cells in culture showed high gene expression for EP2 and EP4. Activation of EP2 and EP4 receptors decreased barrier integrity of esophageal epithelial cells in impedance assays. Conclusions Activation of EP2 and EP4 receptors may inhibit eosinophil recruitment to the esophageal mucosa. However, their activation could negatively affect esophageal barrier integrity suggesting that eosinophilic rather than epithelial EP2 and EP4 have a protective role in EoE.

Characterization of Peyronie's disease (PD) involves manual goniometry and penile length measurement. These techniques neglect volume loss or hourglass deformities. Inter-provider variability complicates accuracy. Using 3D-printed models, we aimed to evaluate measurement accuracy and variability and establish computational assessment workflows. Five digital phantoms were created: 13.0 cm cylinder, 13.0 cm hourglass cylinder, 15.0 cm cylinder with 40° angulation, 12.0 cm straight penis, and 12.9 cm PD penis with 68° angulation and hourglass. Lengths, volumes, and angles were determined computationally. Each phantom was 3D-printed. Ten urology providers determined lengths, angles, and volumes with measuring tape, goniometer, and volume calculator. Provider versus computational measurements were compared to determine accuracy using t-tests or Wilcoxon rank-sum tests. No significant differences were observed between manual assessment of length of penile models and designed length in penile models. Average curvature angles from providers for bent cylinder and PD phantoms were 38.3° ± 3.9° (p = 0.25) and 57.5° ± 7.2° (p = 0.006), respectively. When assessing for volume, hourglass cylinder and bent cylinder showed significant differences between designed volume and provider averages. All assessments of length, angle, and volume showed significant provider variability. Our results suggest manual measurements suffer from inaccuracy and variability. Computational workflows are useful for improved accuracy and volume assessment.

Background High-altitude therapy has been used as add-on treatment for allergic asthma with considerable success. However, the underlying mechanisms remain unclear. In order to investigate the possible therapeutic effects of high-altitude therapy on allergic asthma, we utilized a new in vivo mouse model. Methods Mice were treated with house dust mite (HDM) extract over 4 weeks and co-exposed to 10% oxygen (Hyp) or room air for the final 2 weeks. Experimental asthma was assessed by airway hyper-responsiveness, mucus hypersecretion and inflammatory cell recruitment. Isolated immune cells from mouse and allergic patients were stimulated in vitro with HDM under Hyp and normoxia in different co-culture systems to analyse the adaptive immune response. Results Compared to HDM-treated mice in room air, HDM-treated Hyp-mice displayed ameliorated mucosal hypersecretion and airway hyper-responsiveness. The attenuated asthma phenotype was associated with strongly reduced activation of antigen-presenting cells (APCs), effector cell infiltration and cytokine secretion. In vitro, hypoxia almost completely suppressed the HDM-induced adaptive immune response in both mouse and human immune cells. While hypoxia did not affect effector T-cell responses per-se, it interfered with antigen-presenting cell (APC) differentiation and APC/effector cell crosstalk. Conclusions Hypoxia-induced reduction in the Th2-response to HDM ameliorates allergic asthma in vivo. Hypoxia interferes with APC/T-cell crosstalk and confers an unresponsive phenotype to APCs.

We report the results of the second measurement campaign of the Karlsruhe Tritium Neutrino (KATRIN) experiment. KATRIN probes the effective electron anti-neutrino mass, mν, via a high-precision measurement of the tritium β-decay spectrum close to its endpoint at 18.6 keV. In the second physics run presented here, the source activity was increased by a factor of 3.8 and the background was reduced by 25% with respect to the first campaign. A sensitivity on mν of 0.7 eV/c2 at 90% confidence level (CL) was reached. This is the first sub-eV sensitivity from a direct neutrino-mass experiment. The best fit to the spectral data yields mν2=(0.26±0.34) eV2/c4, resulting in an upper limit of mν2 (90% CL). By combining this result with the first neutrino mass campaign, we find an upper limit of mν2 (90% CL).

To evaluate if ultrasound during urodynamics (uUS) will show that traditional ultrasound (tUS) routinely underestimates the potential magnitude of upper tract dilation (UTD).Prospective pilot study of 10 consecutive patients ≥ 5 years of age undergoing same day uUS and tUS. Using randomized images, the study pediatric radiologist determined anterior-posterior renal pelvic diameter (APD), bladder volume, vesicoureteral reflux (VUR) and UTD grades. A single pediatric urologist determined urodynamic bladder capacity and assigned either hostile, intermediate, abnormal but safe, or normal national spina bifida patient registry classification (NSBPR).Bladder volume on tUS was significantly smaller than final bladder volume on uUS (180 vs 363 ml: P.001). On average, patient reported maximum catheterized/voided volumes were also 82 ml greater than final bladder capacity on uUS. UTD was upgraded in 25% of kidneys and APD increased by 0.6 cm on uUS over that seen on tUS (P=.001). Units with VUR had greater increases in APD (1.2 P=.007 vs. 0.3 cm P=0.06). Changes in APD stratified by NSBPR revealed average increases of up to 1.3 cm.Despite instructions to the contrary, patients come for tUS with a relatively empty bladder as compared to either their urodynamic or patient-reported capacity. This translates to a significant underestimation of UTD with tUS, most notably in those with VUR. Alternatives to traditional protocols include insisting patients wait until their bladder is truly full for tUS, retrograde filling their bladder, or performing uUS. Accurate assessment of UTD severity may help guide long term management.