Testing quantum electrodynamics in extreme fields using helium-like uranium.

Quantum electrodynamics (QED), the quantum field theory that describes the interaction between light and matter, is commonly regarded as the best-tested quantum theory in modern physics. However, this claim is mostly based on extremely precise studies performed in the domain of relatively low field strengths and light atoms and ions1-6. In the realm of very strong electromagnetic fields such as in the heaviest highly charged ions (with nuclear charge Z ≫ 1), QED calculations enter a qualitatively different, non-perturbative regime. Yet, the corresponding experimental studies are very challenging, and theoretical predictions are only partially tested. Here we present an experiment sensitive to higher-order QED effects and electron-electron interactions in the high-Z regime. This is achieved by using a multi-reference method based on Doppler-tuned X-ray emission from stored relativistic uranium ions with different charge states. The energy of the 1s1/22p3/2 J = 2 → 1s1/22s1/2 J = 1 intrashell transition in the heaviest two-electron ion (U90+) is obtained with an accuracy of 37 ppm. Furthermore, a comparison of uranium ions with different numbers of bound electrons enables us to disentangle and to test separately the one-electron higher-order QED effects and the bound electron-electron interaction terms without the uncertainty related to the nuclear radius. Moreover, our experimental result can discriminate between several state-of-the-art theoretical approaches and provides an important benchmark for calculations in the strong-field domain.

Evaluation of Skindex-16 construct validity in routinely collected psoriasis data: a retrospective analysis of the relationship between overall physician global assessment scores and Skindex-16 and measure discordance.

Patient-reported outcome measures (PROMs) capture disease severity metrics from the patient's perspective, including health-related quality of life (HRQL). Disease-specific validation of PROMs improves their clinical utility. We evaluated construct validity (HRQL) for Skindex-16 in routinely seen psoriasis patients and characterized instances of discordance between Skindex-16 scores and clinician-reported outcome measure of disease severity. We retrospectively studied psoriasis patients seen by University of Utah Dermatology from 2016 to 2020. Cross-sectional construct validity was assessed using quantile regression and Spearman correlation between overall physician global assessment (OPGA) score and Skindex-16 scores. Longitudinal within-subject correlation was performed using linear mixed models. Discordance (10th percentile or lower OPGA and 90th percentile or higher Skindex-16 score [clear skin, poor HRQL; cspHRQL] or the reverse [severe skin, good HRQL; ssgHRQL]) was characterized descriptively. 681 first-visit patients with psoriasis were included. Median overall Skindex-16 score varied by ≥ 10 points across all levels of OPGA scores. OPGA and Skindex-16 domain scores were moderately correlated (emotions ρ = 0.54, functioning ρ = 0.47, and symptoms ρ = 53). Longitudinal correlations were similar (emotion ρxy = 0.54, functioning ρxy = 0.65, symptoms ρxy = 0.47). Visits with cspHRQL discordance occurred for each Skindex-16 domain (emotions = 7, functioning = 13, symptoms = 12). The ssgHRQL group was observed within the emotions (n = 1) and functioning (n = 23) domains. Median Skindex-16 scores are different between different levels of OPGA and show moderate cross-sectional and longitudinal correlation. This supports construct validity in patients with psoriasis. Severe discordance was rare and most often for those with clear skin but poor HRQL. These discordances can prompt further patient-clinician conversation.

A 410 MHz resonant cavity pickup for heavy ion storage rings.

An improved design of a longitudinally sensitive resonant Schottky cavity pickup for the heavy ion storage rings of the Facility for Antiproton and Ion Research in Europe (FAIR) project is reported. The new detector has a higher measured Q value of ∼3000 and a higher simulated shunt impedance of 473.3 kΩ. It is possible to vary the sensitivity of the cavity with a motorized mechanism by inserting a dissipative blade during the operation based on experimental needs. Apart from a lower price tag, the new design features a more robust and production-friendly mechanical structure suitable for a series production in the future FAIR project. The manufactured cavity was built temporarily into the experimental storage ring and had delivered its first results using stored heavy ion beams. The structure, simulation results, and performance of this cavity are presented in this work.

Diagnostic contribution of individual components of adrenal function tests to diagnose canine hyperadrenocorticism.

There is limited information regarding the value of constitutive components of the ACTH stimulation test (ACTHST) and low-dose dexamethasone suppression test (LDDST) including serum baseline cortisol (BC), difference between post-ACTH stimulation cortisol (PC) and BC (ΔACTHC), cortisol concentration 4h after dexamethasone administration (4HC), difference between 4HC and BC (Δ4C), and the difference between cortisol concentration 8h after dexamethasone administration and 4HC (Δ8C). Therefore, the objective of this study was to determine if these components can predict hyperadrenocorticism, pituitary-dependent hyperadrenocorticism (PDH), or functional adrenocortical tumor (FAT) in dogs. Cortisol concentrations were normalized, as fold change (FC), to the PC reference interval upper limit. A total of 1267 dogs were included, with hyperadrenocorticism diagnosed in 537 (PDH, n=356; FAT, n=28; undetermined, n=153) and excluded in 730. The area under the receiver operating curves for BC, ΔACTHC, 4HC, Δ4C, and Δ8C to predict hyperadrenocorticism were 0.76 (95% confidence interval (CI), 0.73-0.79), 0.91 (95% CI, 0.89-0.93), 0.83 (95% CI, 0.80-0.87), 0.55 (95% CI, 0.50-0.60), and 0.67 (95% CI, 0.62-0.72), respectively. A diagnostic limit of ≥0.78 FC for ΔACTHC had excellent sensitivity (1.00; 95% CI, 0.74-1.00), but poor specificity (0.67; 95% CI, 0.64-0.71), to predict FAT in dogs with a positive ACTHST. A diagnostic limit of ≥-0.26 FC for Δ4C had excellent sensitivity (1.00; 95% CI, 0.79-1.00), but poor specificity (0.21; 95% CI, 0.18-0.26), to predict FAT in dogs with a positive LDDST. In hyperadrenocorticoid dogs that have positive ACTHST or LDDST results, ΔACTHC or Δ4C, respectively, could be used to exclude FAT.

Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements.

For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 µg cm- 2 of copper and 56.6 ± 0.4 µg cm- 2 of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 µg ml-1 was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties.

Approaching the Gamow Window with Stored Ions: Direct Measurement of

We report the first measurement of low-energy proton-capture cross sections of ^{124}Xe in a heavy-ion storage ring. ^{124}Xe^{54+} ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The ^{125}Cs reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.

IL-1ß as mucosal vaccine adjuvant: the specific induction of tissue-resident memory T cells improves the heterosubtypic immunity against influenza A viruses.

A universal influenza vaccine must provide protection against antigenically divergent influenza viruses either through broadly neutralizing antibodies or cross-reactive T cells. Here, intranasal immunizations with recombinant adenoviral vectors (rAd) encoding hemagglutinin (HA) and nucleoprotein (NP) in combination with rAd-Interleukin-(IL)-1ß or rAd-IL-18 were evaluated for their efficacy in BALB/c mice. Mucosal delivery of rAd-IL-1ß enhanced HA-specific antibody responses including strain-specific neutralizing antibodies. Nevertheless, the beneficial effects on the local T cell responses were much more impressive reflected by increased numbers of CD103+CD69+ tissue-resident memory T cells (TRM). This increased immunogenicity translated into superior protection against infections with homologous and heterologous strains including H1N1, pH1N1, H3N2, and H7N7. Inhibition of the egress of circulating T cells out of the lymph nodes during the heterologous infection had no impact on the degree of protection underscoring the unique potential of TRM for the local containment of mucosal infections. The local co-expression of IL-1ß and antigen lead to the activation of critical checkpoints in the formation of TRM including activation of epithelial cells, expression of chemokines and adhesion molecules, recruitment of lung-derived CD103+ DCs, and finally local TRM imprinting. Given the importance of TRM-mediated protection at mucosal barriers, this study has major implications for vaccine development.

Spectrophotometry and Ultracentrifugation for Measurement of Plasma Lipids in Dogs with Diabetes Mellitus.

BACKGROUND: There are conflicting reports of plasma lipoprotein lipid content in dogs with diabetes mellitus (DM). OBJECTIVES: To determine lipoprotein lipid content of plasma of dogs with DM by spectrophotometry and ultracentrifugation; to compare lipoprotein lipid content in diabetic and healthy dogs; and to quantify apolipoprotein B-100 (ApoB) in dogs with DM. ANIMALS: 22 dogs with DM and 9 healthy dogs. METHODS: Cross-sectional study. Triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) concentrations were measured by spectrophotometry. Very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) concentrations were calculated after ultracentrifugation. Non-HDL-C cholesterol was calculated by subtracting HDL-C from TC. ApoB was quantified by ELISA. The Mann-Whitney test was used for comparison of median lipoprotein concentrations, and Spearman's correlation was used to assess associations between ApoB and lipoprotein fractions. RESULTS: All values are reported in mg/dL. Median TG (122), TC (343.5), HDL-C, (200), VLDL-C, (27) LDL-C (68), non-HDL-C (114), and ApoB (320) were significantly higher in dogs with DM, compared to healthy dogs (57, 197, 168, 12, 16, 31, and 258, respectively, P-values 0.0079, <0.001, 0.029, 0.011, <0.001, <0.001, 0.025, respectively). A significant association was found between ApoB and LDL-C (Spearman's rho = 0.41, P = 0.022) and between ApoB and non-HDL-C (Spearman's rho = 0.40, P = 0.027). CONCLUSIONS AND CLINICAL IMPORTANCE: Dyslipidemia of dogs with DM is characterized by pronounced increases in LDL-C and non-HDL-C concentrations, although all lipoprotein fractions are significantly increased. Knowledge of specific lipoprotein fraction alterations in dogs with DM can enhance treatment options for diabetic dyslipidemia in dogs.

Interocular interaction of contrast and luminance signals in human primary visual cortex.

Interocular interaction in the visual system occurs under dichoptic conditions when contrast and luminance are imbalanced between the eyes. Human psychophysical investigations suggest that interocular interaction can be explained by a contrast normalization model. However, the neural processes that underlie such interactions are still unresolved. We set out to assess, for the first time, the proposed normalization model of interocular contrast interactions using magnetoencephalography (MEG) and to extend this model to incorporate interactions based on interocular luminance differences. We used MEG to record steady-state visual evoked responses (SSVER), and functional magnetic resonance imaging (fMRI) to obtain individual retinotopic maps that we used in combination with MEG source imaging in healthy participants. Binary noise stimuli were presented in monocular or dichoptic viewing and were frequency-tagged at 4 and 6 Hz. The contrast of the stimuli was modulated in a range between 0 and 32%. Monocularly, we reduced the luminance by placing a 1.5 ND filter over one eye in the maximal contrast condition. This ND filter reduces the mean light level by a factor of 30 without any alteration to the physical contrast. We observed in visual area V1 a monotonic increase in the magnitude of SSVERs with changes in contrast from 0 to 32%. For both eyes, dichoptic masking induced a decrease in SSVER signal power. This power decrease was well explained by the normalization model. Reducing mean luminance delayed monocular processing by approximately 38 ms in V1. The reduced luminance also decreased the masking ability of the eye under the filter. Predictions based on a temporal filtering model for the interocular luminance difference prior to the model's binocular combination stage were incorporated to update the normalization model. Our results demonstrate that the signals resulting from different contrast or luminance stimulation of the two eyes are combined in a way that can be explained by an interocular normalization model.

Sertoli cells are capable of proliferation into adulthood in the transition region between the seminiferous tubules and the rete testis in Wistar rats.

Sertoli cells (SCs) play a crucial role in testis differentiation, development and function, determining the magnitude of sperm production in sexually mature animals. For over 40 years, it has been considered that these key testis somatic cells stop dividing during early pre-pubertal phase, between around 10 to 20 days after birth respectively in mice and rats, being after that under physiological conditions a stable and terminally differentiated population. However, evidences from the literature are challenging this dogma. In the present study, using several important functional markers (Ki-67, BrdU, p27, GATA-4, Androgen Receptor), we investigated the SC differentiation status in 36 days old and adult Wistar rats, focusing mainly in the transition region (TR) between the seminiferous tubules (ST) and the rete testis. Our results showed that SCs in TR remain undifferentiated for a longer period and, although at a lesser degree, even in adult rats proliferating SCs were observed in this region. Therefore, these findings suggest that, different from the other ST regions investigated, SCs residing in the TR exhibit a distinct functional phenotype. These undifferentiated SCs may compose a subpopulation of SC progenitors that reside in a specific microenvironment capable of growing the ST length if needed from this particular testis region. Moreover, our findings demonstrate an important aspect of testis function in mammals and opens new venues for other experimental approaches to the investigation of SC physiology, spermatogenesis progression and testis growth. Besides that, the TR may represent an important site for pathophysiological investigations and cellular interactions in the testis.

Beta-hydroxybutyrate Concentrations in Dogs with Acute Pancreatitis and Without Diabetes Mellitus.

BACKGROUND: ß-hydroxybutyrate (BOHB) concentrations have not been quantified in dogs with acute pancreatitis (AP). OBJECTIVE: The aim of this study was to investigate BOHB concentrations in dogs with AP. ANIMALS: A total of 154 client-owned dogs without DM. METHODS: Prospective clinical study. Dogs were enrolled into 1 of 3 groups: AP, sick without an AP diagnosis, or fasted. Dogs were diagnosed with AP (44) if they had vomiting or anorexia, and either ultrasonographic findings consistent with AP or increased pancreatic lipase. Sick dogs without AP (68) had vomiting or anorexia but a diagnosis of AP was either not suspected or was excluded based on ultrasonographic findings or a normal pancreatic lipase. Dogs without anorexia or vomiting that were fasted for over 10 hours for a procedure were also enrolled (42). BOHB was measured on whole blood with a portable ketone meter. The Kruskal-Wallis test was performed to compare BOHB in the 3 groups. Pair-wise comparisons were performed using the Mann-Whitney test and Bonferroni corrected P-values are reported. RESULTS: Median BOHB concentration was significantly higher in dogs with AP (0.3 mmol/L, range 0-2.9 mmol/L) compared to sick dogs without AP (0.20 mmol/L, range 0-0.9 mmol/L, P = .007) and fasted dogs (0.1 mmol/L, range 0-0.4 mmol/L, P = .0001). Median BOHB concentration was significantly higher in sick dogs without AP compared to fasted dogs (P = .0002). CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs without DM, BOHB is significantly higher in dogs with AP compared to other dogs. The diagnostic utility of this finding remains to be investigated.

The Sertoli cell: one hundred fifty years of beauty and plasticity.

It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.

[Resection at symptomatic cam impingement. Use of a minimally invasive antero-lateral approach]. / Offene Offsetkorrektur bei symptomatischem Cam-Impingement. Therapie über einen minimalinvasiven anterolateralen Zugang.

BACKGROUND: Surgical treatment of femoroacetabular impingement (FAI) is nowadays achieved by either open surgical hip dislocation or hip arthroscopy. However, drawbacks of both procedures include the invasiveness of the open procedure and a high learning curve to successfully perform arthroscopic treatment. In our institution, we established a minimally invasive, arthroscopically assisted, antero-lateral approach for the correction of cam type FAI. OBJECTIVES: The goal of the study was to describe the surgical technique and highlight the short-term clinical outcome in a consecutive series of patients operated between 2011 and 2014 in our institution. MATERIALS AND METHODS: In total, 77 patients were included in this study. The patients were allocated to two groups (Toennis = 0: Group I; Toennis 1 and 2: Group II). Clinical and radiographic follow up was obtained at 6 and 12 weeks postoperatively. Clinical outcome was assessed using the Hip-Outcome-Score. RESULTS: The mean age of patients in Group I was 25 (16-48) years and in Group II 38 (17-50) years respectively. Internal rotation (IR) in 90° flexion increased by 11 degrees from pre- to postoperatively in Group I (p < 0.001) and by 14° in Group II (p < 0.001). The Hip Outcome Score revealed the ability to perform sports with reduced pain at three months follow up. Subjectively, all patients benefitted in terms of pain and hip function in both groups (p < 0.001). There were no complications with long-term morbidity during the perioperative course. CONCLUSION: Arthroscopically assisted cam resection using a minimally invasive anterolateral approach is a safe technique for the treatment of FAI. At short term follow up, nearly all operated patients seem to benefit in terms of pain and hip function. The influence of progression of osteoarthritis still has to be shown.

Cortisol Concentrations in Well-Regulated Dogs with Hyperadrenocorticism Treated with Trilostane.

BACKGROUND: There are no clear treatment guidelines for dogs with clinically well-regulated hyperadrenocorticism in which serum cortisol concentrations before and after an ACTH stimulation test performed 3-6 hours after trilostane administration are < 2.0 µg/dL. OBJECTIVE: To determine if serum cortisol concentrations measured before (Pre1) and after (Post1) ACTH stimulation at 3-6 hours after trilostane administration are significantly lower than cortisol concentrations measured before (Pre2) and after (Post2) ACTH stimulation 9-12 hours after trilostane administration, in a specific population of dogs with clinically well-regulated hyperadrenocorticism and Pre1 and Post1 <2 µg/dL. ANIMALS: Thirteen client-owned dogs with clinically well-regulated hyperadrenocorticism and Pre1 and Post1 serum cortisol concentrations <2.0 µg/dL 3-6 hours after trilostane administration. METHODS: Prospective study. Dogs had a second ACTH stimulation test performed 9-12 hours after trilostane administration, on the same day of the first ACTH stimulation test. Cortisol concentrations before and after ACTH stimulation were compared using a paired t-test. RESULTS: Cortisol concentrations before (1.4 ± 0.3 µg/dL) and after the first stimulation (1.5 ± 0.3 µg/dL, mean ± SD) were significantly lower than cortisol concentration before the second stimulation (3.3 ± 1.6 µg/dL, P = .0012 each). Cortisol concentration before the first stimulation was also significantly lower than cortisol concentration after the second stimulation (5.3 ± 2.4 µg/dL, P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with clinically well-regulated, trilostane-treated, hyperadrenocorticism, and cortisol concentrations <2 µg/dL before and after the first stimulation, a second ACTH stimulation test performed 9-12 hours after treatment can result in higher cortisol concentrations that could support continued trilostane treatment.

Small tubules, surprising discoveries: from efferent ductules in the turkey to the discovery that estrogen receptor alpha is essential for fertility in the male.

Efferent ductules are small, delicate tubules that connect rete testis with the head of the epididymis, first identified by de Graaf in 1668. Although difficult to find in routine dissection, the ductules are an essential component of the male reproductive tract and in larger mammals occupy up more than 50% of the caput epididymidis. My introduction to research began with the study of efferent ductules in the domestic turkey, and to my surprise these small structures with kidney-like function become the core for numerous discoveries throughout my scientific career. In this review, only two discoveries that I found interesting will be discussed: cilia that line the efferent ductule lumen and estrogen receptors that play an essential role in regulating fluid reabsorption. A potential link between these two discoveries was uncovered in the study of efferent ductule effects observed in the estrogen receptor knockout mouse and following toxic exposure to the fungicide benomyl.

[Securing transplantation medicine. Duties of the German Foundation for Organ Transplantation (DSO)]. / Sicherung der Transplantationsmedizin. Aufgaben der Deutschen Stiftung Organtransplantation.

Due to a lack of confidence, the organ transplantation system in Germany is currently in a crisis. This was triggered by waiting list manipulations at four transplant centers in 2012, which led to a public debate that continues to this day and a dramatic decline in the number of post-mortem organ donations. This problem affects the 11,000 critically ill patients on the waiting list who are in urgent need of a post-mortem organ donation for their own survival. Also affected are transplantation medicine physicians and facilities whose work in organ donations is severely influenced by the resurgent discussion of brain death diagnosis and the medical and ethical criteria for the allocation of organs. Despite extensive documentation of donor/organ data, receiver data, and functional data, the necessary transparency to assess and represent the quality of transplantation medicine in Germany is not available due to systematic segregation of the information by the databases. Therefore, the joint efforts of all stakeholders are required to restore confidence in a transparent high-quality organ donation and transplantation process based on a transplant registry.