Electrostatic Trapping of N_{2} Molecules in High Rydberg States.

N_{2} molecules traveling in pulsed supersonic beams have been excited from their X ^{1}Σ_{g}^{+} ground electronic state to long-lived Rydberg states with principal quantum numbers between 39 and 48 using a resonance-enhanced two-color three-photon excitation scheme. The Rydberg states populated had static electric dipole moments exceeding 5000 D which allowed deceleration of the molecules to rest in the laboratory-fixed frame of reference and three-dimensional trapping using inhomogeneous electric fields. The trapped molecules were confined for up to 10 ms, with effective trap decay time constants increasing with principal quantum number, and ranging from 450 to 700 µs. These observations, and comparison with the results of similar measurements with He atoms, indicate that the decay dynamics of the trapped Rydberg N_{2} molecules are dominated by spontaneous emission and do not exhibit significant contributions from effects of intramolecular interactions that lead to non-radiative decay.

Co-design of an intervention to optimize mammographic screening participation in women with obesity and/or physical disabilities.

BACKGROUND: Mammographic breast screening/rescreening rates are suboptimal for women with obesity and/or physical disabilities. This study describes development of an intervention framework targeting obesity- and disability-related barriers to improve participation. METHODS: Mixed methods combined a systematic review with first-person perspectives to optimise screening engagement among women with obesity and/or physical disabilities. Phase 1 (systematic review) was conducted following the PRISMA framework. Phase 2 involved in-depth interviews with n = 8 women with lived experience of obesity and/or physical disabilities. An inductive coding approach was applied to the data which was then combined with Phase 1 results to develop the intervention framework. RESULTS: Six studies were included in the systematic review. Tailored education based on individual risk increased willingness to undergo mammographic screening. Recommendations to improve the screening experience included partnerships with consumers, targeted messaging, and enhanced professional development for breast screening staff. Participants also identified strategies to improve the uptake of screening and the experience itself. CONCLUSION: Development and evaluation of interventions informed by frameworks like the one developed in this study are needed to improve engagement in screening to promote regular participation among women with physical disabilities and/or obesity. IMPLICATIONS FOR PRACTICE: Successful implementation of practice interventions co-designed by women with obesity and/or physical disabilities are likely to improve their breast screening participation. Enhanced training of radiographers aimed at upskilling in empathetic communication around required manoeuvring and potentially longer screening times for clients with obesity and/or physical disabilities may encourage more positive client practitioner interactions. Client information aimed at women with obesity should include information on how to prepare for the appointment and explain there may be equipment limitations compromising imaging which may not be completed at an initial appointment.

Effects of rotational excitation on decay rates of long-lived Rydberg states in NO.

Nitric oxide (NO) molecules in pulsed supersonic beams have been excited to long-lived Rydberg-Stark states in series converging to the lowest vibrational level in the ground electronic state of NO+ with rotational quantum numbers N+ = 2, 4, and 6. The molecules in these excited states were then guided, or decelerated and trapped in a chip-based Rydberg-Stark decelerator, and detected in situ by pulsed electric field ionization. Time constants, reflecting the decay of molecules in N+ = 2 Rydberg-Stark states, with principal quantum numbers n between 38 and 44, from the electrostatic traps were measured to be ∼300µs. Molecules in Rydberg-Stark states with N+ = 4 and 6, and the same range of values of n were too short-lived to be trapped, but their decay time constants could be determined from complementary sets of delayed pulsed electric field ionization measurements to be ∼100 and ∼25 µs, respectively.

Precision Microwave Spectroscopy of the Positronium 2

We report the results of a new measurement of the positronium 2 ^{3}S_{1}→2 ^{3}P_{2} (ν_{2}) interval. Using a modified experimental arrangement we have significantly reduced the effects of microwave reflections, which in previous experiments resulted in shifts and asymmetric line shapes. With the improved apparatus we obtain an experimental value of ν_{2}=8627.94±0.95 MHz, which is within 1.3σ of the theoretical value 8626.71±0.08 MHz.

Cutaneous manifestations induced by check point inhibitors in 120 melanoma patients-The European MelSkinTox study.

BACKGROUND: Checkpoint inhibitors provide an effective approach for the melanoma treatment. They prolong lymphocyte effects, which explains the cytotoxicity underlying immune-related adverse events (IrAEs). Cutaneous IrAEs affect nearly 40% of PD-1i and 50% of CTLA4i-treated patients. Severe cutaneous irAE do not often occur but could be life-threatening and may persist despite treatment discontinuation. METHODS: We aimed to investigate cutaneous IrAEs in a cohort of patients treated with ICI across Europe in an effort to characterize the reactions in a real-world, phase IV, post-marketing study using a follow-up questionnaire. Data since November 2016 until March 2021 were obtained from the Melskintox database, a European multicentric biobank dedicated to the follow-up of melanoma and cutaneous adverse events, supported by EADO. The dermatoses reported were pooled into four categories: inflammatory dermatosis, bullous diseases, drug-related eruptions and pigmentary diseases. RESULTS: Inflammatory benign dermatoses (n = 63) represented the most common group of reactions (52.5%), followed by drug-related eruptions (n = 24, 20%), pigmentary diseases (n = 23, 19.2%) and bullous diseases (n = 10, 8.3%). Grade II (n = 41, 34.2%) are represented by bullous pemphigoid, eczema, hypodermitis, lichenoid eruption, maculopapular rash, pruritus, psoriasis-like rash, urticarial eruption and vitiligo. Grade III (n = 18, 15.0%) are represented by bullous pemphigoid, lichenoid eruption and rashes. Grade IV (n = 2, 1.7%) is only represented by bullous disease. Most cutaneous IrAEs led to immunotherapy continuation (n = 95, 88.0%). CR is associated with more severe the cutaneous irAEs. We report an average time-to-onset of 208 days and some late-onset events. CONCLUSION: Our study has characterized the clinical spectrum of cutaneous irAEs, their timing and severity and their relationship with tumour response. Grade I-II cutaneous IrAE are easily managed allowing ongoing anticancer treatment. Severe late-onset cutaneous irAE are not uncommon. A dermatological follow-up helps mitigate the risk of life-threatening adverse events. These findings highlight the importance of oncodermatological involvement in management of patients with melanoma receiving immunotherapy.

PET/CT radiomics for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibitors.

Purpose: This study evaluated pretreatment 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET/CT-based radiomic signatures for prediction of hyperprogression in metastatic melanoma patients treated with immune checkpoint inhibition (ICI). Material and method: Fifty-six consecutive metastatic melanoma patients treated with ICI and available imaging were included in the study and 330 metastatic lesions were individually, fully segmented on pre-treatment CT and FDG-PET imaging. Lesion hyperprogression (HPL) was defined as lesion progression according to RECIST 1.1 and doubling of tumor growth rate. Patient hyperprogression (PD-HPD) was defined as progressive disease (PD) according to RECIST 1.1 and presence of at least one HPL. Patient survival was evaluated with Kaplan-Meier curves. Mortality risk of PD-HPD status was assessed by estimation of hazard ratio (HR). Furthermore, we assessed with Fisher test and Mann-Whitney U test if demographic or treatment parameters were different between PD-HPD and the remaining patients. Pre-treatment PET/CT-based radiomic signatures were used to build models predicting HPL at three months after start of treatment. The models were internally validated with nested cross-validation. The performance metric was the area under receiver operating characteristic curve (AUC). Results: PD-HPD patients constituted 57.1% of all PD patients. PD-HPD was negatively related to patient overall survival with HR=8.52 (95%CI 3.47-20.94). Sixty-nine lesions (20.9%) were identified as progressing at 3 months. Twenty-nine of these lesions were classified as hyperprogressive, thereby showing a HPL rate of 8.8%. CT-based, PET-based, and PET/CT-based models predicting HPL at three months after the start of treatment achieved testing AUC of 0.703 +/- 0.054, 0.516 +/- 0.061, and 0.704 +/- 0.070, respectively. The best performing models relied mostly on CT-based histogram features. Conclusions: FDG-PET/CT-based radiomic signatures yield potential for pretreatment prediction of lesion hyperprogression, which may contribute to reducing the risk of delayed treatment adaptation in metastatic melanoma patients treated with ICI.

Quantum-state-dependent decay rates of electrostatically trapped Rydberg NO molecules.

Nitric oxide (NO) molecules travelling in pulsed supersonic beams have been prepared in long-lived Rydberg-Stark states by resonance-enhanced two-colour two-photon excitation from the X 2Π1/2 (v'' = 0, J'' = 3/2) ground state, through the A 2Σ+ (v' = 0, N' = 0, J' = 1/2) intermediate state. These excited molecules were decelerated from 795 ms-1 to rest in the laboratory-fixed frame of reference, in the travelling electric traps of a transmission-line Rydberg-Stark decelerator. The decelerator was operated at 30 K to minimise effects of blackbody radiation on the molecules during deceleration and trapping. The molecules were electrostatically trapped for times of up to 1 ms, and detected in situ by pulsed electric field ionisation. Measurements of the rate of decay from the trap were performed for states with principal quantum numbers between n = 32 and 50, in Rydberg series converging to the N+= 0, 1, and 2 rotational states of NO+. For the range of Rydberg states studied, the measured decay times of between 200 µs and 400 µs were generally observed to reduce as the value of n was increased. For some particular values of n deviations from this trend were seen. These observations are interpreted, with the aid of numerical calculations, to arise as a result of contributions to the decay rates, on the order of 1 kHz, from rotational and vibrational channel interactions. These results shed new light on the role of weak intramolecular interactions on the slow decay of long-lived Rydberg states in NO.

Assessment of the response of indigenous microflora and inoculated Bacillus licheniformis endospores in reconstituted skim milk to microwave and conventional heating systems by flow cytometry.

Heat treatment is one of the most widely used processing technologies in the dairy industry. Its primary purpose is to destroy microorganisms, both pathogenic and spoilage, to ensure the product is safe and has a reasonable shelf life. In this study microwave volumetric heating (MVH) was compared with a conventional tubular heat exchanger (THE), in terms of the effects of each at a range of temperatures (75°C, 85°C, 95°C, 105°C, 115°C, and 125°C) on indigenous microflora viability and the germination of inoculated Bacillus licheniformis endospores in reconstituted skim milk. To assess the heat treatment-related effects on microbial viability, classical agar-based tests were applied to obtain the counts of 4 various microbiological groups including total bacterial, thermophilic bacterial, mesophilic aerobic bacterial endospore, and thermophilic aerobic bacterial endospore counts, and additional novel insights into cell permeability and spore germination profiles post-heat treatment were obtained using real-time flow cytometry (FC) methods. No significant differences in the plate counts of the indigenous microorganisms tested, the plate counts of the inoculated B. licheniformis, or the relative percentage of germinating endospores were observed between MVH- and THE-treated samples, at equal temperatures in the range specified above, indicating that both methods inactivated inoculated endospores to a similar degree (up to 70% as measured by FC and 5 log reduction as measured by plate counting for some treatments of inoculated endospores). Furthermore, increased cell permeability of indigenous microflora was observed by FC after MVH compared with THE treatment of uninoculated skim milk, which was reflected in lower total bacterial count at a treatment temperature of 105°C. This work demonstrates the utility of FC as a rapid method for assessing cell viability and spore inactivation for postthermal processing in dairy products and overall provides evidence that MVH is at least as effective at eliminating native microflora and inoculated B. licheniformis endospores as THE.

Two dimensionless parameters and a mechanical analogue for the HKB model of motor coordination.

The widely cited Haken-Kelso-Bunz (HKB) model of motor coordination is used in an enormous range of applications. In this paper, we show analytically that the weakly damped, weakly coupled HKB model of two oscillators depends on only two dimensionless parameters; the ratio of the linear damping coefficient and the linear coupling coefficient and the ratio of the combined nonlinear damping coefficients and the combined nonlinear coupling coefficients. We illustrate our results with a mechanical analogue. We use our analytic results to predict behaviours in arbitrary parameter regimes and show how this led us to explain and extend recent numerical continuation results of the full HKB model. The key finding is that the HKB model contains a significant amount of behaviour in biologically relevant parameter regimes not yet observed in experiments or numerical simulations. This observation has implications for the development of virtual partner interaction and the human dynamic clamp, and potentially for the HKB model itself.

Interventions for basal cell carcinoma: abridged Cochrane systematic review and GRADE assessments.

BACKGROUND: Basal cell carcinoma (BCC) is the most common cancer affecting white-skinned individuals, and the worldwide incidence is increasing. Although rarely fatal, BCC is associated with significant morbidity and costs. OBJECTIVES: To assess the effects of interventions for primary BCC in immunocompetent adults. METHODS: We updated our searches of the following databases to November 2019: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and LILACS. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. We used standard methodological procedures expected by Cochrane. RESULTS: We included 52 randomized controlled trials with 6990 participants (median age 65 years; range 20-95). Mean study duration was 13 months (range 6 weeks-10 years). Ninety-two per cent (n = 48/52) of studies exclusively included histologically low-risk BCC (nodular and superficial subtypes). The certainty of evidence was predominantly low or moderate for the outcomes of interest. Overall, surgical interventions have the lowest recurrence rates, and there may be slightly fewer recurrences with Mohs micrographic surgery over surgical excision for primary, facial BCC (high-risk histological subtype or located in the 'H-zone' or both) (low-certainty evidence). Nonsurgical treatments, when used for low-risk BCC, are less effective than surgical treatments, but recurrence rates are acceptable and cosmetic outcomes are probably superior. CONCLUSIONS: Surgical interventions have lower recurrence rates and remain the gold standard for high-risk BCC. Of the nonsurgical treatments, topical imiquimod has the best evidence to support its efficacy for low-risk BCC. Priorities for future research include agreement on core outcome measures and studies with longer follow-up.

The role of a virtual telephone clinic in the follow-up management of lateral skull base tumours.

OBJECTIVE: The purpose of this article was to determine the impact of employing a telephone clinic for follow-up of patients with stable lateral skull-base tumours. METHOD: An analysis of 1515 patients in the national lateral skull-base service was performed, and 148 patients enrolled in the telephone clinic to date were identified. The length of time that patients waited for results of their follow-up scans and the travel distance saved by patients not having to attend the hospital for their results was determined. RESULTS: The mean time from scan to receiving results was 30.5 ± 32 days, 14 days sooner than in the face-to-face group (p = 0.0016). The average round-trip distance travelled by patients to the hospital for results of their scans was 256 ± 131 km. CONCLUSION: The telephone clinic led to a significant reduction in time until patients received their scan results and helped reduce travel distance and clinic numbers in traditional face-to-face clinics.

Developments allergy in 2019 through the eyes of Clinical and Experimental Allergy, Part II clinical allergy.

In the second of two linked articles, we describe the development in clinical as described by Clinical & Experimental Allergy and other journals in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered. In this article, we described the development in the field of allergy as described by Clinical and Experimental Allergy in 2019. Epidemiology, clinical allergy, asthma and rhinitis are all covered.

Developments allergy in 2019 through the eyes of clinical and experimental allergy, part I mechanisms.

In the first of two linked articles, we describe the development in the mechanisms underlying allergy as described by Clinical & Experimental Allergy and other journals in 2019. Experimental models of allergic disease, basic mechanisms, clinical mechanisms and allergens are all covered.

Precision Microwave Spectroscopy of the Positronium n=2 Fine Structure.

We report a new measurement of the positronium (Ps) 2^{3}S_{1}→2^{3}P_{0} interval. Slow Ps atoms, optically excited to the radiatively metastable 2^{3}S_{1} level, flew through a microwave radiation field tuned to drive the transition to the short-lived 2^{3}P_{0} level, which was detected via the time spectrum of subsequent ground state Ps annihilation radiation. After accounting for Zeeman shifts we obtain a transition frequency ν_{0}=18501.02±0.61 MHz, which is not in agreement with the theoretical value of ν_{0}=18498.25±0.08 MHz.

Slow Decay Processes of Electrostatically Trapped Rydberg NO Molecules.

Nitric oxide (NO) molecules initially traveling at 795 m/s in pulsed supersonic beams have been photoexcited to long-lived hydrogenic Rydberg-Stark states, decelerated and electrostatically trapped in a cryogenically cooled, chip-based transmission-line Rydberg-Stark decelerator. The decelerated and trapped molecules were detected in situ by pulsed electric field ionization. The operation of the decelerator was validated by comparison of the experimental data with the results of numerical calculations of particle trajectories. Studies of the decay of the trapped molecules on timescales up to 1 ms provide new insights into the lifetimes of, and effects of blackbody radiation on, Rydberg states of NO.

Coupling Rydberg Atoms to Microwave Fields in a Superconducting Coplanar Waveguide Resonator.

Rydberg helium atoms traveling in pulsed supersonic beams have been coupled to microwave fields in a superconducting coplanar waveguide (CPW) resonator. The atoms were initially prepared in the 1s55s ^{3}S_{1} Rydberg level by two-color two-photon laser excitation from the metastable 1s2s ^{3}S_{1} level. Two-photon microwave transitions between the 1s55s ^{3}S_{1} and 1s56s ^{3}S_{1} levels were then driven by the 19.556 GHz third-harmonic microwave field in a quarter-wave CPW resonator. This superconducting microwave resonator was fabricated from niobium nitride on a silicon substrate and operated at temperatures between 3.65 and 4.30 K. The populations of the Rydberg levels in the experiments were determined by state-selective pulsed electric field ionization. The coherence of the atom-resonator coupling was studied by time-domain measurements of Rabi oscillations.

Excitation and characterization of long-lived hydrogenic Rydberg states of nitric oxide.

High Rydberg states of nitric oxide (NO) with principal quantum numbers between 40 and 100 and lifetimes in excess of 10 µs have been prepared by resonance enhanced two-color two-photon laser excitation from the X 2Π1/2 ground state through the A 2Σ+ intermediate state. Molecules in these long-lived Rydberg states were detected and characterized 126 µs after laser photoexcitation by state-selective pulsed electric field ionization. The laser excitation and electric field ionization data were combined to construct two-dimensional spectral maps. These maps were used to identify the rotational states of the NO+ ion core to which the observed series of long-lived hydrogenic Rydberg states converge. The results presented pave the way for Rydberg-Stark deceleration and electrostatic trapping experiments with NO, which are expected to shed further light on the decay dynamics of these long-lived excited states, and are of interest for studies of ion-molecule reactions at low temperatures.

Rydberg-State-Resolved Resonant Energy Transfer in Cold Electric-Field-Controlled Intrabeam Collisions of NH3 with Rydberg He Atoms.

The resonant transfer of energy from the inversion sublevels in NH3 to He atoms in triplet Rydberg states with principal quantum number n = 38 has been controlled using electric fields below 15 V/cm in intrabeam collisions at translational temperatures of ∼1 K. The experiments were performed in pulsed supersonic beams of NH3 seeded in He at a ratio of 1:19. The He atoms were prepared in the metastable 1s2s 3S1 level in a pulsed electric discharge in the trailing part of the beams. The velocity slip between the heavy NH3 and the lighter metastable He was exploited to perform collision studies at center-of-mass collision speeds of ∼70 m/s. Resonant energy transfer in the atom-molecule collisions was identified by Rydberg-state-selective electric-field ionization. The experimental data have been compared to a theoretical model of the resonant dipole-dipole interactions between the collision partners based on the impact parameter method.