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Background: In modern Hybrid ORs, the synergies of navigation and robotics are assumed to contribute to the optimisation of the treatment in trauma, orthopaedic and spine surgery. Despite promising evidence in the area of navigation and robotics, previous publications have not definitively proven the potential benefits. Therefore, the aim of this retrospective study was to evaluate the potential benefit and clinical outcome of patients treated in a fully equipped 3D-Navigation Hybrid OR. Methods: Prospective data was collected (March 2022- March 2024) after implementation of a fully equipped 3D-Navigation Hybrid OR ("Robotic Suite") in the authors level 1 trauma centre. The OR includes a navigation unit, a cone beam CT (CBCT), a robotic arm and mixed reality glasses. Surgeries with different indications of the spine, the pelvis (pelvic ring and acetabulum) and the extremities were performed. Spinal and non-spinal screws were inserted. The collected data was analysed retrospectively. Pedicle screw accuracy was graded according to the Gertzbein and Robbins (GR) classification. Results: A total of n = 210 patients (118 m:92f) were treated in our 3D-Navigation Hybrid OR, with 1171 screws inserted. Among these patients, 23 patients (11.0%) arrived at the hospital via the trauma room with an average Injury Severity Score (ISS) of 25.7. There were 1035 (88.4%) spinal screws inserted at an accuracy rate of 98.7% (CI95%: 98.1-99.4%; 911 GR-A & 111 GR-B screws). The number of non-spinal screws were 136 (11.6%) with an accuracy rate of 99.3% (CI95%: 97.8-100.0%; 135 correctly placed screws). This resulted in an overall accuracy rate of 98.8% (CI95%: 98.2-99.4%). The robotic arm was used in 152 cases (72.4%), minimally invasive surgery (MIS) was performed in 139 cases (66.2%) and wound infection occurred in 4 cases (1,9%). Overall, no revisions were needed. Conclusion: By extending the scope of application, this study showed that interventions in a fully equipped 3D-Navigation Hybrid OR can be successfully performed not only on the spine, but also on the pelvis and extremities. In trauma, orthopaedics and spinal surgery, navigation and robotics can be used to perform operations with a high degree of precision, increased safety, reduced radiation exposure for the OR-team and a very low complication rate. [ABSTRACT FROM AUTHOR]

The present review studies total reaction cross sections from elastic scattering angular distributions of light stable and exotic projectiles ( 2 ≤ Z P ≤ 10 , 4 ≤ A P ≤ 24 ) on 208Pb at energies around the Coulomb barrier. From the overall about 200 data it is found that the widely accepted simple grouping of the derived reduced cross sections into three categories—tightly bound, weakly bound, and exotic halo projectiles—is too simplistic and does not fully reflect the range of the experimental data. Furthermore, the energy dependence of the reduced cross sections shows unexpected properties which were hitherto only sparsely considered. [ABSTRACT FROM AUTHOR]

Melanomas frequently harbour somatic mutations in BRAF (40%) or NRAS (20%). Impact of NRAS mutations on the therapeutic outcome of immune checkpoint inhibitors (ICI) remains controversial. Potential correlation of the NRAS mutational status and programmed cell death ligand-1 (PD-L1) expression in melanoma is unknown. Advanced, non-resectable melanoma patients with known NRAS mutation status treated with first-line ICI between 06/2014 and 05/2020 in the prospective multicenter skin cancer registry ADOREG were included. Overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) according to NRAS status were analysed. A multivariate Cox model was used to analyse factors associated with PFS and OS; survival was analysed using the Kaplan–Meier approach. Among 637 BRAF wild-type patients, 310 (49%) had an NRAS mutation with Q61R (41%) and Q61K (32%). NRAS -mutated (NRAS mut) melanomas were significantly more often located on the lower extremities and trunk (p = 0.001); nodular melanoma was the most common subtype (p < 0.0001). No significant differences were found for PFS and OS for anti-PD1 monotherapy (2-year PFS 39%, [95% confidence interval (CI), 33–47] in NRAS mut patients and 41% [95% CI, 35–48] in NRAS -wild type (NRAS wt) patients; 2-year OS was 54% [95% CI, 48–61] in NRAS mut patients and 57% [95% CI, 50–64] in NRAS wt patients) and anti-PD1 plus anti-CTLA4 therapy between both cohorts (2-year PFS was 54% [95% CI, 44–66] in NRAS mut patients and 53% [95% CI, 41–67] in NRAS wt patients; 2-year OS was 58% [95% CI, 49–70] in NRAS mut patients and 62% [95% CI, 51–75] in NRA Swt patients). The ORR to anti-PD1 was 35% for NRAS wt patients and 26% for NRAS mut patients and 34% compared to 32% for combinational therapy. Data on PD-L1 expression was available in 82 patients (13%). PD-L1 expression (> 5%) was not correlated to NRAS mutational status. In multivariate analysis, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group performance status ≥ 1, and brain metastases were significantly associated with a higher risk of death in all patients. The PFS and OS were not affected by NRAS mutational status in patients treated with anti-PD1-based ICI. Similar ORR was seen in NRAS wt and NRAS mut patients. Tumour PD-L1 expression did not correlate with NRAS mutational status. • PFS and OS were not affected by NRAS mutational status in patients treated with anti-PD1-based ICI. • Similar response rates to anti-PD1-based ICI were seen for NRAS mut and NRAS wt patients. • There was no correlation between NRAS mutation status and programmed cell death ligand-1 expression. [ABSTRACT FROM AUTHOR]

Simple Summary: Knowledge on the real-world outcomes of patients with advanced melanoma and the value of different endpoints for evaluating survival benefits is limited. We investigated the outcomes and different surrogate endpoints for overall survival (OS) in 664 pembrolizumab-treated patients with advanced melanoma in Germany. Our findings support the effectiveness of pembrolizumab in real-world clinical practice. The real-world time to next treatment was most strongly correlated with OS, suggesting it as a valuable surrogate endpoint to assess treatment effectiveness. Real-world studies assessing time to next treatment could support clinical and payer decision making. Knowledge on the real-world characteristics and outcomes of pembrolizumab-treated advanced melanoma patients in Germany and on the value of different real-world endpoints as surrogates for overall survival (OS) is limited. A sample of 664 pembrolizumab-treated patients with advanced melanoma from the German registry ADOReg was used. We examined OS, real-world progression-free survival (rwPFS), real-world time to next treatment (rwTtNT), and real-world time on treatment (rwToT). Spearman's rank and iterative multiple imputation (IMI)-based correlation coefficients were computed between the OS and the rwPFS, rwTtNT, and rwToT and reported for the first line of therapy and the overall sample. The median OS was 30.5 (95%CI 25.0–35.4) months, the rwPFS was 3.9 months (95%CI 3.5–4.9), the rwTtNT was 10.7 months (95%CI 9.0–12.9), and the rwToT was 6.2 months (95%CI 5.1–6.8). The rwTtNT showed the highest correlation with the OS based on the IMI (rIMI = 0.83), Spearman rank correlations (rs = 0.74), followed by the rwToT (rIMI = 0.74 and rs = 0.65) and rwPFS (rIMI = 0.69 and rs = 0.56). The estimates for the outcomes and correlations were similar for the overall sample and those in first-line therapy. The median OS was higher compared to recent real-world studies, supporting the effectiveness of pembrolizumab in regular clinical practice. The rwTtNT may be a valuable OS surrogate, considering the highest correlation was observed with the OS among the investigated real-world endpoints. [ABSTRACT FROM AUTHOR]

Most patients with advanced basal cell carcinomas (BCCs) may not benefit sufficiently from standard treatment comprising surgery and radiation. Vismodegib, an oral selective hedgehog pathway inhibitor, is approved for treatment of patients with locally advanced BCC inappropriate for surgery or radiotherapy, or for patients with symptomatic metastatic BCC. In order to enhance understanding of the effectiveness, safety and utilization of vismodegib in clinical practice in Germany, a non-interventional study, JONAS, was conducted. A total of 53 patients with locally advanced BCC who initiated treatment with vismodegib between 2016 and 2018 were included in the study, which was embedded in the German ADOReg skin cancer registry. Duration of response, the primary endpoint, was 12.4 months, progression-free survival 32.2 months and overall response rate 77.4%. Most adverse events were mild to moderate. Overall, results confirmed previous findings, demonstrating favourable responses and manageable safety of vismodegib in patients with locally advanced BCC in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Following the pivotal phase II trial BOLT, the Hedgehog (Hh) inhibitor sonidegib was approved in the EU to treat locally advanced basal cell carcinoma (laBCC) in patients not amenable to surgery or radiotherapy. We report safety data from the interim analysis of the real-world NISSO study. Methods: NISSO is an ongoing non-interventional, multinational, post-authorization safety study (NCT04066504). Patients with laBCC are treated with sonidegib 200 mg orally once daily and followed for 3 years. Dose modifications were allowed according to the local prescribing information. Results: Between May 6, 2019, and March 15, 2022, 321 patients with laBCC were enrolled at 46 European sites (data cut-off: June 22, 2023). Treatment was discontinued in 241 (75.1%) patients, with the main reasons being the patient/guardian decision (n = 69, 28.6%), treatment success (n = 40, 16.6%) and the physician decision (n = 35, 14.5%). The median duration of sonidegib exposure was 8.8 months (4.4–13.7 months). Overall, 284 (88.5%) patients had ≥ one treatment-emergent adverse event (TEAE). Most TEAEs were ≤ grade 2 and the most common were muscle spasms (n = 141; 43.9%), dysgeusia (n = 119; 37.1%), and alopecia (n = 97; 30.2%). After 3 months of treatment, the cumulative rates of muscle spasms, dysgeusia, and alopecia were 21.8%, 16.2%, and 3.7%, respectively. TEAEs led to treatment discontinuation in 59 (18.4%) patients, while 149 (46.4%) patients had at least one TEAE leading to dose reduction or interruption. Serious drug-related TEAEs were reported in 13 (4.1%) patients. Conclusions: These results confirm the safety profile previously observed. Most patients experienced the onset of common TEAEs after 3 months of treatment, and the cumulative incidence of most common TEAEs was 10–20% lower compared to the BOLT study, except for dysgeusia and fatigue that had a similar incidence. The percentage of patients experiencing TEAEs requiring interruption or dose reduction was similar to the BOLT study, while the proportion of patients with TEAE leading to discontinuation of sonidegib was lower. This study demonstrates that the tolerability of sonidegib is manageable in routine clinical practice. Trial registration. NCT04066504. [ABSTRACT FROM AUTHOR]

The omnipresence of smartphones among adolescents and adults gives rise to the questions about excessive use and personality factors which are associated with heavier engagement with these devices. Previous studies have found behavioral similarities between smartphone use and maladaptive behaviors (e.g. drinking, gambling, drug abuse) in the context of intertemporal choice but mostly relied on participants' self-reports regarding engagement with their phone. In this study, we collected actual usage data by smartphone application from 101 participants and assessed their tendency to discount future rewards, their reward responsiveness, self-control and consideration of future consequences. We found that smartphone screen time was correlated with choosing smaller immediate over larger delayed rewards and that usage of social media and gaming apps predicted delay discounting. Additionally, smartphone use was negatively correlated with self-control but not correlated with consideration of future consequences. Neither psychological variable could mediate the relationship between smartphone usage and delay discounting. Our findings provide further evidence that smartphone use and impulsive decision-making go hand in hand and that engagement with these devices needs to be critically examined by researchers to guide prudent behavior. [ABSTRACT FROM AUTHOR]

The yrast band in the heavy N = Z nucleus 88 Ru is studied in the framework of the α -cluster model in combination with double-folding potentials. It is found that the excitation energies of the yrast band in 88 Ru can be nicely described within the α -cluster approach using a smooth and mildly L-dependent adjustment of the potential strength. This result is similar to well-established α -cluster states in nuclei with a (magic core ⊗ α ) structure. Contrary, the yrast bands in neighboring N ≠ Z nuclei deviate from such a typical α -cluster behavior. Finally, the α -cluster model predicts reduced transition strengths of about 10 Weisskopf units for intraband transitions between low-lying states in the yrast band of 88 Ru. [ABSTRACT FROM AUTHOR]

Emotion regulation impacts the expected emotional responses to the outcomes of risky decisions via activation of cognitive control strategies. However, whether the regulation of emotional responses to preceding, incidental stimuli also impacts risk-taking in subsequent decisions is still poorly understood. In this study, we investigated the interplay between the regulation of incidentally induced emotional responses and subsequent choice behavior using a risky decision-making task in two independent samples (behavioral and functional magnetic resonance imaging experiment). We found that overall, emotion regulation was followed by less risky decisions, which was further reflected in an increase in activation in brain regions in dorsolateral and ventrolateral prefrontal cortex and cingulate cortex. These findings suggest that altering incidental emotions using reappraisal strategies impacts on subsequent risk-taking in decision-making. [ABSTRACT FROM AUTHOR]

Cross-sections for 4 0 Ca + α at low energies have been calculated from two different models and three different α -nucleus potentials. The first model determines the cross-sections from the barrier transmission in a real nuclear potential. Second, cross-sections are derived within the optical model (OM) using a complex nuclear potential. The excitation functions from barrier transmission are smooth, whereas the excitation functions from the OM show a significant sensitivity to the chosen imaginary potential. Cross-sections far below the Coulomb barrier are lower from barrier transmission than from the OM. This difference is explained by additional absorption in the tail of the imaginary part of the potential in the OM. At higher energies, the calculations from the two models and all α -nucleus potentials converge. Finally, in contradiction to another recent study where a double-folding potential failed in a WKB calculation, the applicability of double-folding potentials for 4 0 Ca + α at low energies is clearly confirmed in the present analysis for the simple barrier transmission model and for the full OM calculation. [ABSTRACT FROM AUTHOR]

$ \alpha$ -cluster states in Cr and Cr are investigated in the double-folding model. This study complements a recent similar work by Souza and Miyake, Eur. Phys. J. A 53, 146 (2017), which was based on a specially shaped potential. Excitation energies, reduced widths, intercluster separations, and intra-band transition strengths are calculated and compared to experimental values for the ground state bands in Cr and Cr . The $ \alpha$ -cluster potential is also applied to elastic scattering at low and intermediate energies. Here, as a byproduct, a larger radial extent of the neutron density in Ti is found. [ABSTRACT FROM AUTHOR]

The article discusses the new International System of Units (SI) to explore the values of certain physical constants for high school teachers and students. Topics discussed include description of physical science; information on the 1875 Treaty of the Meter defined International Bureau of Weights and Measures; and explaining other constants such as frequency and time, speed and length, and voltage and resistance.

Objectives: The objective of this study was to evaluate clinical outcomes and patency rates using the Viabahn endoprosthesis in complex (TASC-II C and D) femoropopliteal lesions.Background: Traditional treatment of symptomatic TASC-II C and D femoropopliteal lesions has mainly centered on open surgical options in patients deemed appropriate candidates. Endovascular treatment of these lesions with balloon angioplasty has been historically hampered by aggressive restenosis and relatively early clinical failure. The Viabahn endoprosthesis was developed with the intent of reducing restenosis while improving overall flexibility in the femoropopliteal segment.Methods: Between March 2009 and July 2011 a total of 51 limbs in 41 patients underwent implantation of one or more Viabahn endovascular stent grafts for the treatment of symptomatic TASC-II C or D lesions. Patients were followed clinically at regular intervals and also underwent routine surveillance duplex ultrasound at 1, 3, 6, and 12 months post-procedure. The average follow-up from the index procedure was 14.6 months (range 13-35.2 months).Results: A total of 22 TASC-II C and 29 TASC-II D lesions were treated (51 limbs in 41 patients). The mean lesion length was 22.4 cm. The overall 1-year primary patency rate was 74.8% (95% CI: 61.2%-88.4%), assisted primary patency rate was 87.4% (95% CI: 70.9%-95.9%), and the secondary patency rate was 94.9% (95% CI: 88.0%-100.0%).Conclusions: The Viabahn endoprosthesis is a safe and effective option for the treatment of TASC-II C and D femoropopliteal lesions. Patency rates are favorable despite the complexity of these lesions, although multiple endovascular re-interventions may be necessary to achieve an acceptable long-term result. [ABSTRACT FROM AUTHOR]

The determination of absolute widths of two observed levels above the proton threshold in 15N has been improved by a combined analysis of our recent 15N(γ, γ) 15N* photon scattering data, resonance strengths ωγ of the l4C(p, γ) 15N reaction, and γ-ray branchings bγ, i in 15N. The revised data are compared to the adopted values, and some inconsistencies in the adopted values are illustrated. [ABSTRACT FROM AUTHOR]

Background: The neuraminidases (NAs) of MDCK passaged human influenza A(H3N2) strains isolated since 2005 are reported to have dual functions of cleavage of sialic acid and receptor binding. NA agglutination of red blood cells (RBCs) can be inhibited by neuraminidase inhibitors (NAIs), thus distinguishing it from haemagglutinin (HA) binding. We wanted to know if viruses prior to 2005 can demonstrate this property. Methods: Pairs of influenza A(H3N2) isolates ranging from 1993-2008 passaged in parallel only in eggs or in MDCK cells were tested for inhibition of haemagglutination by various NAIs. Results: Only viruses isolated since 1994 and cultured in MDCK cells bound chicken RBCs solely through their NA. NAI inhibition of agglutination of turkey RBCs was seen for some, but not all of these same MDCK grown viruses. Efficacy of inhibition of enzyme activity and haemagglutination differed between NAIs. For many viruses lower concentrations of oseltamivir could inhibit agglutination compared to zanamivir, although they could both inhibit enzyme activity at comparable concentrations. An E119V mutation reduced sensitivity to oseltamivir and 4-aminoDANA for both the enzyme assay and inhibition of agglutination. Sequence analysis of the NAs and HAs of some paired viruses revealed mutations in the haemagglutinin of all egg passaged viruses. For many of the paired egg and MDCK cultured viruses we found no differences in their NA sequences by Sanger sequencing. However, deep sequencing of MDCK grown isolates revealed low levels of variant populations with mutations at either D151 or T148 in the NA, suggesting mutations at either site may be able to confer this property. Conclusions: The NA active site of MDCK cultured human influenza A(H3N2) viruses isolated since 1994 can express dual enzyme and receptor binding functions. Binding correlated with either D151 or T148 mutations. The catalytic and receptor binding sites do not appear to be structurally identical since relative concentrations of the NAIs to inhibit enzyme activity and agglutination differ. [ABSTRACT FROM AUTHOR]

New experimental data for the 33S(α,p)36CI reaction show a very unusual energy dependence. Contrary to common findings for many other «-induced reactions, statistical model calculations underestimate the measured cross sections at very low energies. The relatively huge cross sections at these low energies require a significant amount of single-particle strength in the measured energy range which exceeds, by far, 100% as soon as the additional strength from the competing 33S(α,p)36CI reaction is taken into account. In addition, the new data deviate from a general trend for the energy dependence of a-induced reaction cross sections. [ABSTRACT FROM AUTHOR]

Background Previous studies have shown statistically significant differences in electrical impedance between various cutaneous lesions. Electrical impedance spectroscopy (EIS) may therefore be able to aid clinicians in differentiating between benign and malignant skin lesions. Objectives The aim of the study was to develop a classification algorithm to distinguish between melanoma and benign lesions of the skin with a sensitivity of at least 98% and a specificity approximately 20 per cent higher than the diagnostic accuracy of dermatologists. Patients/Methods A total of 1300 lesions were collected in a multicentre, prospective, non-randomized clinical trial from 19 centres around Europe. All lesions were excised and subsequently evaluated independently by a panel of three expert dermatopathologists. From the data two classification algorithms were developed and verified. Results For the first classification algorithm, approximately 40% of the data were used for calibration and 60% for testing. The observed sensitivity for melanoma was 98.1% (101/103), non-melanoma skin cancer 100% (25/25) and dysplastic nevus with severe atypia 84.2% (32/38). The overall observed specificity was 23.6% (66/280). For the second classification algorithm, approximately 55% of the data were used for calibration. The observed sensitivity for melanoma was 99.4% (161/162), for non-melanoma skin cancer was 98.0% (49/50) and dysplastic nevus with severe atypia was 93.8% (60/64). The overall observed specificity was 24.5% (116/474). Conclusion EIS has the potential to be an adjunct diagnostic tool to help clinicians differentiate between benign and malignant (melanocytic and non-melanocytic) skin lesions. Further studies are needed to confirm the validity of the automatic assessment algorithm. [ABSTRACT FROM AUTHOR]

Angular distributions of elastic 140Ce(α,α)140Ce scattering are analyzed in the framework of the optical model from low energies around the Coulomb barrier up to about 40 MeV. From the local fits the total reaction cross section σreac is extracted. This procedure requires experimental scattering data with small uncertainties. The results for σreac are compared to predictions of different systematic global potentials. It is found that the total reaction cross section σreac is well predicted from all global potentials under study although the reproduction of the angular distributions is not perfect in all cases. In addition, the lower energy limit for the extraction of σreac from elastic scattering angular distributions is analyzed. Finally, the potentials under study are used to calculate the 143Nd(n,α)140Ce cross section, and the predictions are compared to experimental data. [ABSTRACT FROM AUTHOR]

The cross sections of the 130Sn(n,?)131Sn and 132Sn(n,?)/)133Sn reactions are calculated in the direct capture model at low energies below 1.5 MeV. Using recent data from (d,p) transfer experiments on 130Sn and 132Sn, it is possible to avoid global input parameters with their inherent uncertainties and to determine all inputs to the direct capture model by local adjustments. The calculated direct capture cross sections of 130Sn and 132Sn are almost identical and have uncertainties of less than a factor of 2. The stellar reaction rates NA (sv) show a slight increase with temperature. Finally, an estimate for the influence of low-lying resonances to the stellar reaction rates is given. [ABSTRACT FROM AUTHOR]

Introduction: Fibrillary glomerulonephritis (FibGN) is characterized by extracellular deposition of Congo red-negative microfibrils within the glomerular mesangium and leads to gross proteinuria or nephrotic syndrome. After diagnosis of FibGN, end-stage renal disease occurs within four years in 50% of patients.Case Presentation: A 36-year-old Caucasian woman with proteinuria and intermittent nephrotic syndrome due to FibGN intermittently received immunosuppressive therapies, including glucocorticoids, mycophenolate mofetil, and rituximab, for 10 years. However, disease remission was not achieved and progressive kidney injury developed. Ultimately, in stage IV of chronic kidney disease (Kidney Disease: Improving Global Outcomes), three cycles of plasmapheresis of five to seven sessions each were performed every three to four months, reducing steady-state proteinuria from 7 to less than 1 g/day. Here, plasmapheresis led to a remission of nephrotic syndrome associated with FibGN.Conclusions: Plasmapheresis therapy is proposed as a further option for immunosuppressant-refractory FibGN. [ABSTRACT FROM AUTHOR]

Elastic scattering data for 141Pr(α, α)141Pr have been analyzed to derive a new energy-dependent local potential for the 141Pr-α System. This potential is used successfully to predict the cross section of the 141Pr(α, n)144Pm reaction at low energies where new experimental data have become available very recently. In contrast to various global potentials, this new potential is able to reproduce simultaneously elastic scattering data around and above the Coulomb barrier and reaction data below the Coulomb barrier for the 141Pr-α System. Reasons for the partial failure of the global potentials are explained by intrinsic properties of the scattering matrix and their Variation with energy. The new local potential may become the basis for the construction of a new global α-nucleus potential. [ABSTRACT FROM AUTHOR]

The influenza neuraminidase (NA) inhibitors zanamivir, oseltamivir and peramivir were all designed based on the knowledge that the transition state analogue of the cleaved sialic acid, 2-deoxy,2,3-dehydro N-acetyl neuraminic acid (DANA) was a weak inhibitor of NA. While DANA bound rapidly to the NA, modifications leading to the improved potency of these new inhibitors also conferred a time dependent or slow binding phenotype. Many mutations in the NA leading to decreased susceptibility result in loss of slow binding, hence this is a phenotypic marker of many but not all resistant NAs. We present here a simplified approach to determine whether an inhibitor is fast or slow binding by extending the endpoint fluorescent enzyme inhibition assay to a real time assay and monitoring the changes in IC50s with time. We carried out two reactions, one with a 30 min preincubation with inhibitor and the second without. The enzymatic reaction was started via addition of substrate and IC50s were calculated after each 10 min interval up to 60 min. Results showed that without preincubation IC50s for the wild type viruses started high and although they decreased continuously over the 60 min reaction time the final IC50s remained higher than for pre-incubated samples. These results indicate a slow equilibrium of association and dissociation and are consistent with slow binding of the inhibitors. In contrast, for viruses with decreased susceptibility, preincubation had minimal effect on the IC50s, consistent with fast binding. Therefore this modified assay provides additional phenotypic information about the rate of inhibitor binding in addition to the IC50, and critically demonstrates the differential effect of incubation times on the IC50 and Ki values of wild type and mutant viruses for each of the inhibitors. [ABSTRACT FROM AUTHOR]

In our everyday life, we often have to make decisions with risky consequences, such as choosing a restaurant for dinner or choosing a form of retirement saving. To date, however, little is known about how the brain processes risk. Recent conceptualizations of risky decision making highlight that it is generally associated with emotions but do not specify how emotions are implicated in risk processing. Moreover, little is known about risk processing in non-choice situations and how potential losses influence risk processing. Here we used quantitative meta-analyses of functional magnetic resonance imaging experiments on risk processing in the brain to investigate (1) how risk processing is influenced by emotions, (2) how it differs between choice and non-choice situations, and (3) how it changes when losses are possible. By showing that, over a range of experiments and paradigms, risk is consistently represented in the anterior insula, a brain region known to process aversive emotions such as anxiety, disappointment, or regret, we provide evidence that risk processing is influenced by emotions. Furthermore, our results show risk-related activity in the dorsolateral prefrontal cortex and the parietal cortex in choice situations but not in situations in which no choice is involved or a choice has already been made. The anterior insula was predominantly active in the presence of potential losses, indicating that potential losses modulate risk processing. [ABSTRACT FROM AUTHOR]

Abstract: Economic decision making is a complex process of integrating and comparing various aspects of economically relevant choice options. Neuroeconomics has made important progress in grounding these aspects of decision making in neural systems and the neurotransmitters therein. The dopaminergic and serotoninergic brain systems have been identified as key neurotransmitter systems involved in economic behavior. Both are known to be prone to significant changes during the adult lifespan. Similarly, economic behavior undergoes significant age-related changes over the course of the adult lifespan. Here we propose a triadic relationship between (a) economic decision making, (b) dopaminergic and serotonergic neuromodulation, and (c) aging. In this review, we describe the different relationships around this triad in detail and summarize current evidence that supports them. Based on the reviewed evidence, we propose new research agendas that take the entire triad into account. [Copyright &y& Elsevier]

This Resource Letter provides a guide to the literature on the physics of fundamental constants and their values as determined within the International System of Units (SI). Journal articles, books, and websites that provide relevant information are surveyed. Literature on redefining the SI in terms of exact values of fundamental constants is also included. [ABSTRACT FROM AUTHOR]

Abstract: Properties of six-component electromagnetic field solutions of a matrix form of the Maxwell equations, analogous to the four-component solutions of the Dirac equation, are described. It is shown that the six-component equation, including sources, is invariant under Lorentz transformations. Complete sets of eigenfunctions of the Hamiltonian for the electromagnetic fields, which may be interpreted as photon wave functions, are given both for plane waves and for angular-momentum eigenstates. Rotationally invariant projection operators are used to identify transverse or longitudinal electric and magnetic fields. For plane waves, the velocity transformed transverse wave functions are also transverse, and the velocity transformed longitudinal wave functions include both longitudinal and transverse components. A suitable sum over these eigenfunctions provides a Green function for the matrix Maxwell equation, which can be expressed in the same covariant form as the Green function for the Dirac equation. Radiation from a dipole source and from a Dirac atomic transition current are calculated to illustrate applications of the Maxwell Green function. [Copyright &y& Elsevier]

Abstract: Many decisions people make can be described as decisions under risk. Understanding the mechanisms that drive these decisions is an important goal in decision neuroscience. Two competing classes of risky decision making models have been proposed to describe human behavior, namely utility-based models and risk–return models. Here we used a novel investment decision task that uses streams of (past) returns as stimuli to investigate how consistent the two classes of models are with the neurobiological processes underlying investment decisions (where outcomes usually follow continuous distributions). By showing (a) that risk–return models can explain choices behaviorally and (b) that the components of risk–return models (value, risk, and risk attitude) are represented in the brain during choices, we provide evidence that risk–return models describe the neural processes underlying investment decisions well. Most importantly, the observed correlation between risk and brain activity in the anterior insula during choices supports risk–return models more than utility-based models because risk is an explicit component of risk–return models but not of the utility-based models. [Copyright &y& Elsevier]

Abstract: Sulfonylureido thiazoles were identified from a HTS campaign and optimized through a combination of structure–activity studies, X-ray crystallography and molecular modeling to yield potent inhibitors of fructose-1,6-bisphosphatase. Compound 12 showed favorable ADME properties, for example, F =70%, and a robust 32% glucose reduction in the acute db/db mouse model for Type-2 diabetes. [Copyright &y& Elsevier]

Abstract: Background: Somatostatin regulates numerous endocrine processes, including glucose homeostasis. The contribution and effects of the 5 somatostatin receptors are still unclear, in part due to the lack of suitable subtype specific receptor antagonists. We explored the effects of two novel, non-peptidic, orally bioavailable somatostatin receptor subtype 5 antagonists named Compound A and Compound B on glycemia in animal models of type 2 diabetes after an initial in vitro characterization. Methods and results: Compound A led to a dose-dependent decrease in glucose and insulin excursions during an OGTT in Zucker (fa/fa) rats after single treatment by up to 17% and 49%, respectively. Diet-induced obese mice showed after three weeks treatment with compounds A and B a dose-dependent decrease of the glucose excursion of up to 45% and 37%, respectively. In contrast to the acute effect observed in Zucker rats, Compound A showed a dose-dependent insulin increase by up to 72%, whereas body weight, liver triglycerides, ALT and AST were dose-dependently decreased. Conclusions: SSTR5 antagonists have the potential for short- and long-term improvements of the glucose homeostasis in rodent models of type 2 diabetes. Further work on the mechanism and the relevance for human disease is warranted. [Copyright &y& Elsevier]

Abstract: SAR studies of a recently described SST5R selective benzoxazole piperidine lead series are described with particular focus on the substitution pattern on the benzyl and benzoxazole side-chains. Introduction of a second meta substituent at the benzyl unit significantly lowers residual hH1 activity and insertion of substituents onto the benzoxazole periphery entirely removes remaining h5-HT2B activity. Compounds with single digit nM activity, functional antagonism and favorable physicochemical properties endowed with a good pharmacokinetic profile in rats are described which should become valuable tools for exploring the pharmacological role of the SST5 receptor in vivo. [Copyright &y& Elsevier]

A comparison of precision frequency measurements to quantum electrodynamic (QED) theoretical predictions can be used to test theory and to obtain information regarding fundamental constants. We find that for Rydberg states, theoretical uncertainties due to the problematic nuclear size correction are very small. With the help of QED calculations, the largest remaining source of uncertainty can be eliminated. Theoretical predictions, taking advantage of the latest theoretical results, in combination with planned experiments, can lead to an improved value for the Rydberg constant. [ABSTRACT FROM AUTHOR]

Abscisic acid (ABA) has been implicated in determining the outcome of interactions between many plants and their pathogens. We had previously shown that increased concentrations of ABA within leaves of Arabidopsis induced susceptibility towards an avirulent strain of Pseudomonas syringae pathovar (pv.) tomato. We now show that ABA induces susceptibility via suppression of the accumulation of components crucial for a resistance response. Lignin and salicylic acid concentrations in leaves were increased during a resistant interaction but reduced when plants were treated with ABA. The reduction in lignin and salicylic acid production was independent of the development of the hypersensitive response (HR), indicating that, in this host-pathogen system, HR is not required for resistance. Genome-wide gene expression analysis using microarrays showed that treatment with ABA suppressed the expression of many defence-related genes, including those important for phenylpropanoid biosynthesis and those encoding resistance-related proteins. Together, these results show that resistance induction in Arabidopsis to an avirulent strain of P. syringae pv. tomato is regulated by ABA. [ABSTRACT FROM AUTHOR]

This article reports that the Committee on Data for Science and Technology is preparing to issue a new set of recommended values for basic constants and conversion factors for physics and chemistry. The complete 2006 CODATA set of more than 300 recommended values, together with a detailed description of the data and their analysis, is in preparation and will be posted on arXiv.org and submitted for publication later this year.

Abstract: A new set of values of the fundamental constants, based on a recent least-squares adjustment, has been recommended by CODATA. An overview of the experiments and theory that influence the values of the new set of constants will be given. Quantum electrodynamic (QED) theory plays a significant role in determining these constants and the consistency of the values obtained from various sources of information provides an important test of the theory. [Copyright &y& Elsevier]

Reports on the completion of the 1998 Committee on Data for Science and Technology (CODATA) least-squares adjustment of a new set of recommended values of basic constants and conversion factors of physics and chemistry, as of August 2003. History of the committee; Comparison of the least-squares adjustments of 1986 and the 1998 CODATA; Analysis of input data using the new least-squares method.

The energy levels of hydrogen and deuterium atoms are calculated to provide frequencies for transitions between highly excited states with principal quantum number n up to 200. All known quantum electrodynamics and relativistic corrections have been included in the calculation. In some cases, contributions originally calculated for a few states have been extrapolated to highly excited states. The fundamental constants necessary for the calculation are taken from the 1998 CODATA least-squares adjustment. Evaluated uncertainties take into account uncertainties in the theoretical calculations, uncertainties in the fundamental constants, and covariances between the various contributions and input parameters. PACS Nos.: 31.15Pf, 31.30Jv, 32.10HqNous calculons les niveaux d'énergie de l'hydrogène et du deutérium pour fournir les fréquences de transition entre des niveaux hautement excités dont le nombre quantique principal n peut aller jusqu'à 200. Nous incluons dans les calculs toutes les corrections QED et relativistes connues. Dans certains cas, nous avons extrapolé vers des niveaux hautement excités des contributions initialement calculées pour des niveaux de basse énergie. Les constantes fondamentales nécessaires à ces calculs sont tirées des valeurs de 1998 CODATA obtenues par moindre carré. Notre calcul d'erreur tient compte des incertitudes dans le calcul théorique, des incertitudes dans la valeur des constantes fondamentales et des covariances entre différentes contributions et les paramétres d'entrée.[Traduit par la Rédaction] [ABSTRACT FROM AUTHOR]

Presents a new set of recommended values of the basic constants and conversion factors of physics and chemistry issued by the Committee on Data for Science and Technology (CODATA) in 1998. Background of the CODATA; Explanation on the changes of the values of basic constants from the recommendation issued in 1986.

We investigate nonresonant contributions to resonant Rayleigh-scattering cross sections of atoms. The problematic nonresonant contributions set a limit to the accuracy t o which atomic spectra determine energy levels. We discuss the off-resonance effects in one-photon transitions. We also show that off-resonance contributions for the 1S-2S two-photon transition in atomic hydrogen are negligible at current and projected levels of experimental accuracy. The possibility of a differential measurement for the detection of off-resonance effects in one-photon transitions in atomic hydrogen is discussed. [ABSTRACT FROM AUTHOR]

Examines the role of fundamental physical constants in the International System of Units (SI). Role of constants in SI electric unit representations; Future role of constants in the SI.

Discusses the adjustments in the values of the fundamental constants in physics. Problems associated with the values of fundamental constants; Categories of information needed in the adjustment of constant values; Details on the constant value adjustments set by the Committee on Data for Science and Technology in 1998.

Simple Summary: We studied real-world patient trends and cancer survival in adult patients in a European registry, EUMelaReg. We included 200 patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. Patients initiated treatment with adjuvant pembrolizumab from 1 January 2019 to 17 April 2021 with a median follow-up of 16.5 months. Comparison with previously published real-world data showed that patients were older and more likely to have stage IIIC and IIID disease than those in the Keynote 054 clinical trial. Background: Although data on patients treated with pembrolizumab are available from clinical trials and single-country real-world reports, to our knowledge no multi-country real-world studies have investigated the use of pembrolizumab as an adjuvant treatment for stage III melanoma. Methods: We used the European Melanoma Registry (EUMelaReg), a disease entity-based registry specific for melanoma, to examine treatment and outcomes for adult patients with stage III melanoma with lymph node involvement who had complete resection and received adjuvant treatment with pembrolizumab. The primary objectives were to describe the demographic and clinical characteristics of the included patients as well as time on adjuvant pembrolizumab treatment (TOT), real-world recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) from adjuvant pembrolizumab initiation. Secondary objectives were time to next treatment (TTNT) after adjuvant use of pembrolizumab, next-line therapy for stage III and unresectable stage IV melanoma and overall survival (OS) from initiation of pembrolizumab. Results: Patients were stratified according to age, sex, BRAF status, number of positive lymph nodes and disease substage. Median TOT was 11.1 (9.2–11.5) months, median RFS was 29.6 [18.7–not reached (NR)] months and median DMFS was 32.4 (22.7–NR) months. TTNT was 29.9 (22.2–NR) months, while median OS was not reached. Conclusions: The results of this study offer insights into the real-world use of pembrolizumab as an adjuvant therapy for melanoma in Europe. [ABSTRACT FROM AUTHOR]

Presents a study which prepared A-ring phosphine oxide. Information on A-ring phosphine oxides; Details on the synthesis of phosphine oxides; Results of the study.

Obtains the asymptotic expansion of the Dirac-Coulomb radial Green's function G[sub kappa](x[sub 2], x[sub 1], z) when the magnitude of the angular momentum quantum number kappa is large. Whittaker function; Radial Green's function; Incorporation of the method into a computer algorithm to generate an arbitrary number of terms.