Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

A standardized method for evaluating test soils used to demonstrate cleaning efficacy.

BACKGROUND: Cleaning and associated validation requirements are essential for the safe use of reusable devices. In the past, test methods and associated endpoints for cleaning validations have varied worldwide. Recent international standards have updated the requirements to include cleaning endpoints and requirements for the use of test soils for demonstrating cleaning efficacy of washer-disinfectors. METHODS: A quantitative comparison of test soils used in cleaning efficacy studies was conducted using a new standardized test method as published in Annexe B ISO 15883-5:2021. Test soils included Artificial Test Soil (ATS 2015), Blood Test Soil (BTS), Coagulated Blood, Defibrinated Blood Soil (DBLSO), Modified Coagulated Blood Soil, Two Component Blood Test Soil and the UK Test Soil (Edinburgh Soil). CONCLUSION: All the test soils demonstrated acceptable performance in accordance with the standard.

Competition between Allowed and First-Forbidden ß Decay: The Case of

The ß decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Q_{ß} window, only three negative parity states are populated directly in the ß decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden ß decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0^{+}→0^{-}ß decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.

Correlation between extent of sinus surgery, radiographic disease, and postoperative outcomes.

BACKGROUND: The extent of endoscopic sinus surgery (ESS) required for optimal outcomes in chronic rhinosinusitis (CRS) is undefined. We evaluated whether concordance between the extent of surgery and degree of radiographic disease influences postoperative outcomes. METHODS: 247 CRS patients who underwent ESS were retrospectively assigned a concordance score reflecting the similarity between the extent of surgery and degree of radiographic disease. 0 points were assigned when sinusotomy was performed on a diseased sinus, or no sinusotomy was performed on a nondiseased sinus; plus 1 for sinusotomy on a nondiseased sinus; and -1 for a diseased sinus left unopened. The total possible score ranged from minus 10 to plus 10. Patients were divided into 5 subgroups according to variance from complete concordance. SNOT-22 scores and revision rates were compared at 6 and 24 months. RESULTS: All five subgroups had similar preoperative SNOT-22 scores and improved at 6 months postoperatively. At 6 months postoperatively, the most conservatively operated and most extensively operated subgroups each achieved equivalent improvements in SNOT-22 as the completely concordant subgroup. At 24 months, the most extensively operated subgroup had a 12.5-point smaller improvement in SNOT-22 scores compared to the completely concordant subgroup. Multivariate analysis showed no association between concordance score and revision rate. CONCLUSIONS: Symptom improvement and revision rates after ESS do not appear to correlate with the degree of concordance between extent of surgery and radiographic disease. More extensive surgery than indicated by CT confers neither greater symptomatic improvement nor long-term detriment.

Improved Value for the Gamow-Teller Strength of the

A record number of ^{100}Sn nuclei was detected and new isotopic species toward the proton dripline were discovered at the RIKEN Nishina Center. Decay spectroscopy was performed with the high-efficiency detector arrays WAS3ABi and EURICA. Both the half-life and the ß-decay end point energy of ^{100}Sn were measured more precisely than the literature values. The value and the uncertainty of the resulting strength for the pure 0^{+}→1^{+} Gamow-Teller decay was improved to B_{GT}=4.4_{-0.7}^{+0.9}. A discrimination between different model calculations was possible for the first time, and the level scheme of ^{100}In is investigated further.

Proton Shell Evolution below

The ß-delayed γ-ray spectroscopy of neutron-rich ^{123,125}Ag isotopes is investigated at the Radioactive Isotope Beam Factory of RIKEN, and the long-predicted 1/2^{-} ß-emitting isomers in ^{123,125}Ag are identified for the first time. With the new experimental results, the systematic trend of energy spacing between the lowest 9/2^{+} and 1/2^{-} levels is extended in Ag isotopes up to N=78, providing a clear signal for the reduction of the Z=40 subshell gap in Ag towards N=82. Shell-model calculations with the state-of-the-art V_{MU} plus M3Y spin-orbit interaction give a satisfactory description of the low-lying states in ^{123,125}Ag. The tensor force is found to play a crucial role in the evolution of the size of the Z=40 subshell gap. The observed inversion of the single-particle levels around ^{123}Ag can be well interpreted in terms of the monopole shift of the π1g_{9/2} orbitals mainly caused by the increasing occupation of ν1h_{11/2} orbitals.

A Multilayer Monte Carlo Model for the Investigation of Optical Path and Penetration Depth at Different Perfusion States of the Colon.

There is a great interest in monitoring the oxygen supply delivered to the colon. Insufficient oxygen delivery may lead to hypoxia, sepsis, multiorgan dysfunction and death. For assessing colonic perfusion, more information and understanding is required relating to the light-interaction within the colonic tissue. A multilayer Monte Carlo model of a healthy human colon has been developed to investigate the light-tissue behavior during different perfusion states within the mucosal layer of the colon. Results from a static multilayer model of optical path and reflectance at two wavelengths, 660 nm and 880 nm, through colon tissue, containing different volume fractions of blood with a fixed oxygen saturation are presented. The effect on the optical path and penetration depth with varying blood volumes within the mucosa for each wavelength has been demonstrated. The simulation indicated both wavelengths of photons penetrated similar depths, entering the muscularis layer.

Discovery of

In this Letter, the observation of two previously unknown isotopes is presented for the first time: ^{72}Rb with 14 observed events and ^{77}Zr with one observed event. From the nonobservation of the less proton-rich nucleus ^{73}Rb, we derive an upper limit for the ground-state half-life of 81 ns, consistent with the previous upper limit of 30 ns. For ^{72}Rb, we have measured a half-life of 103(22) ns. This observation of a relatively long-lived odd-odd nucleus, ^{72}Rb, with a less exotic odd-even neighbor, ^{73}Rb, being unbound shows the diffuseness of the proton drip line and the possibility of sandbanks to exist beyond it. The ^{72}Rb half-life is consistent with a 5^{+}→5/2^{-} proton decay with an energy of 800-900 keV, in agreement with the atomic mass evaluation proton-separation energy as well as results from the finite-range droplet model and shell model calculations using the GXPF1A interaction. However, we cannot explicitly exclude the possibility of a proton transition between 9^{+}(^{72}Rb)→9/2^{+}(^{71}Kr) isomeric states with a broken mirror symmetry. These results imply that ^{72}Kr is a strong waiting point in x-ray burst rp-process scenarios.

94 ß-Decay Half-Lives of Neutron-Rich _{55}Cs to _{67}Ho: Experimental Feedback and Evaluation of the r-Process Rare-Earth Peak Formation.

The ß-decay half-lives of 94 neutron-rich nuclei ^{144-151}Cs, ^{146-154}Ba, ^{148-156}La, ^{150-158}Ce, ^{153-160}Pr, ^{156-162}Nd, ^{159-163}Pm, ^{160-166}Sm, ^{161-168}Eu, ^{165-170}Gd, ^{166-172}Tb, ^{169-173}Dy, ^{172-175}Ho, and two isomeric states ^{174m}Er, ^{172m}Dy were measured at the Radioactive Isotope Beam Factory, providing a new experimental basis to test theoretical models. Strikingly large drops of ß-decay half-lives are observed at neutron-number N=97 for _{58}Ce, _{59}Pr, _{60}Nd, and _{62}Sm, and N=105 for _{63}Eu, _{64}Gd, _{65}Tb, and _{66}Dy. Features in the data mirror the interplay between pairing effects and microscopic structure. r-process network calculations performed for a range of mass models and astrophysical conditions show that the 57 half-lives measured for the first time play an important role in shaping the abundance pattern of rare-earth elements in the solar system.

Dual targeting of the cancer antioxidant network with 1,4-naphthoquinone fused Gold(i) N-heterocyclic carbene complexes.

To achieve a systems-based approach to targeting the antioxidant pathway, 1,4-naphthoquinone annulated N-heterocyclic carbene (NHC) [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] [silver(i) dichloride] (1), [bis(1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i)] chloride (2), and 1,3-dimesityl-4,5-naphthoquino-imidazol-2-ylidene)-gold(i) chloride (3)) were designed, synthesized, and tested for biological activity in a series of human cancer cell lines. The solution phase of complexes 1-3 were assigned using several spectroscopy techniques, including NMR spectroscopic analysis. Complexes 1 and 3 were further characterized by single crystal X-ray diffraction analysis. Electrochemical and spectroelectrochemical studies revealed that quinone reductions are reversible and that the electrochemically generated semiquinone and quinone dianions are stable under these conditions. Complex 1, containing two NHC-quinone moieties (to accentuate exogenous ROS via redox cycling) centered around a Au(i) center (to inactivate thioredoxin reductase (TrxR) irreversibly), was found to inhibit cancer cell proliferation to a much greater extent than the individual components (i.e., Au(i)-NHC alone or naphthoquinone alone). Treatment of A549 lung cancer cells with 1 produced a 27-fold increase in exogenous reactive oxygen species (ROS) which was found to localize to the mitochondria. The inhibition of TrxR, an essential mediator of ROS homeostasis, was achieved in the same cell line at low administrated concentrations of 1. TrxR inhibition by 1 was similar to that of auranofin, a gold(i) containing complex known to inhibit TrxR irreversibly. Complex 1 was found to induce cell death via an apoptotic mechanism as confirmed by annexin-V staining. Complex 1 was demonstrated to be efficacious in zebrafish bearing A549 xenografts. These results provide support for the suggestion that a dual targeting approach that involves reducing ROS tolerance while concurrently increasing ROS production can perturb antioxidant homeostasis, enhance cancer cell death in vitro, and reduce tumor burden in vivo, as inferred from preliminary zebra fish model studies.

Role of the Δ Resonance in the Population of a Four-Nucleon State in the

The ^{54}Fe nucleus was populated from a ^{56}Fe beam impinging on a Be target with an energy of E/A=500 MeV. The internal decay via γ-ray emission of the 10^{+} metastable state was observed. As the structure of this isomeric state has to involve at least four unpaired nucleons, it cannot be populated in a simple two-neutron removal reaction from the ^{56}Fe ground state. The isomeric state was produced in the low-momentum (-energy) tail of the parallel momentum (energy) distribution of ^{54}Fe, suggesting that it was populated via the decay of the Δ^{0} resonance into a proton. This process allows the population of four-nucleon states, such as the observed isomer. Therefore, it is concluded that the observation of this 10^{+} metastable state in ^{54}Fe is a consequence of the quark structure of the nucleons.

New Isotopes and Proton Emitters-Crossing the Drip Line in the Vicinity of

Several new isotopes, ^{96}In, ^{94}Cd, ^{92}Ag, and ^{90}Pd, have been identified at the RIKEN Nishina Center. The study of proton drip-line nuclei in the vicinity of ^{100}Sn led to the discovery of new proton emitters ^{93}Ag and ^{89}Rh with half-lives in the submicrosecond range. The systematics of the half-lives of odd-Z nuclei with T_{z}=-1/2 toward ^{99}Sn shows a stabilizing effect of the Z=50 shell closure. Production cross sections for nuclei in the vicinity of ^{100}Sn measured at different energies and target thicknesses were compared to the cross sections calculated by epax taking into account contributions of secondary reactions in the primary target.

A comparative reference study for the validation of HLA-matching algorithms in the search for allogeneic hematopoietic stem cell donors and cord blood units.

The accuracy of human leukocyte antigen (HLA)-matching algorithms is a prerequisite for the correct and efficient identification of optimal unrelated donors for patients requiring hematopoietic stem cell transplantation. The goal of this World Marrow Donor Association study was to validate established matching algorithms from different international donor registries by challenging them with simulated input data and subsequently comparing the output. This experiment addressed three specific aspects of HLA matching using different data sets for tasks of increasing complexity. The first two tasks targeted the traditional matching approach identifying discrepancies between patient and donor HLA genotypes by counting antigen and allele differences. Contemporary matching procedures predicting the probability for HLA identity using haplotype frequencies were addressed by the third task. In each task, the identified disparities between the results of the participating computer programs were analyzed, classified and quantified. This study led to a deep understanding of the algorithms participating and finally produced virtually identical results. The unresolved discrepancies total to less than 1%, 4% and 2% for the three tasks and are mostly because of individual decisions in the design of the programs. Based on these findings, reference results for the three input data sets were compiled that can be used to validate future matching algorithms and thus improve the quality of the global donor search process.

Higher Body Mass Index Is Associated with Subjective Olfactory Dysfunction.

BACKGROUND: Morbidly obese patients demonstrate altered olfactory acuity. There has been no study directly assessing Body Mass Index (BMI) in patients with olfactory dysfunction. Our purpose was to compare BMI in a group of patients with subjective olfactory dysfunction to those without subjective olfactory complaints. METHODS: Retrospective matched case-control study. Sixty patients who presented to a tertiary care otolaryngology center with subjective smell dysfunction over one year were identified. Neoplastic and obstructive etiologies were excluded. Demographics, BMI, and smoking status were reviewed. Sixty age, gender, and race matched control patients were selected for comparison. Chi-square testing was used. RESULTS: 48 out of 60 patients (80%) in the olfactory dysfunction group fell into the overweight or obese categories, compared to 36 out of 60 patients (60%) in the control group. There was a statistically significant difference between the olfactory dysfunction and control groups for this stratified BMI (p = 0.0168). CONCLUSION: This study suggests high BMI is associated with olfactory dysfunction. Prospective clinical research should examine this further to determine if increasing BMI may be a risk factor in olfactory loss and to elucidate what role olfactory loss may play in diet and feeding habits of obese patients.

ß-Decay Half-Lives of 110 Neutron-Rich Nuclei across the N=82 Shell Gap: Implications for the Mechanism and Universality of the Astrophysical r Process.

The ß-decay half-lives of 110 neutron-rich isotopes of the elements from _{37}Rb to _{50}Sn were measured at the Radioactive Isotope Beam Factory. The 40 new half-lives follow robust systematics and highlight the persistence of shell effects. The new data have direct implications for r-process calculations and reinforce the notion that the second (A≈130) and the rare-earth-element (A≈160) abundance peaks may result from the freeze-out of an (n,γ)⇄(γ,n) equilibrium. In such an equilibrium, the new half-lives are important factors determining the abundance of rare-earth elements, and allow for a more reliable discussion of the r process universality. It is anticipated that universality may not extend to the elements Sn, Sb, I, and Cs, making the detection of these elements in metal-poor stars of the utmost importance to determine the exact conditions of individual r-process events.

Monopole-driven shell evolution below the doubly magic nucleus 132Sn explored with the long-lived isomer in 126Pd.

A new isomer with a half-life of 23.0(8) ms has been identified at 2406 keV in (126)Pd and is proposed to have a spin and parity of 10(+) with a maximally aligned configuration comprising two neutron holes in the 1h(11/2) orbit. In addition to an internal-decay branch through a hindered electric octupole transition, ß decay from the long-lived isomer was observed to populate excited states at high spins in (126)Ag. The smaller energy difference between the 10(+) and 7(-) isomers in (126)Pd than in the heavier N=80 isotones can be interpreted as being ascribed to the monopole shift of the 1h(11/2) neutron orbit. The effects of the monopole interaction on the evolution of single-neutron energies below (132)Sn are discussed in terms of the central and tensor forces.

Isomer decay spectroscopy of 164Sm and 166Gd: midshell collectivity around N=100.

Excited states in the N=102 isotones 166Gd and 164Sm have been observed following isomeric decay for the first time at RIBF, RIKEN. The half-lives of the isomeric states have been measured to be 950(60) and 600(140) ns for 166Gd and 164Sm, respectively. Based on the decay patterns and potential energy surface calculations, including ß6 deformation, a spin and parity of 6- has been assigned to the isomeric states in both nuclei. Collective observables are discussed in light of the systematics of the region, giving insight into nuclear shape evolution. The decrease in the ground-band energies of 166Gd and 164Sm (N=102) compared to 164Gd and 162Sm (N=100), respectively, presents evidence for the predicted deformed shell closure at N=100.

Isomers in 128Pd and 126Pd: evidence for a robust shell closure at the neutron magic number 82 in exotic palladium isotopes.

The level structures of the very neutron-rich nuclei 128Pd and 126Pd have been investigated for the first time. In the r-process waiting-point nucleus 128Pd, a new isomer with a half-life of 5.8(8) µs is proposed to have a spin and parity of 8(+) and is associated with a maximally aligned configuration arising from the g(9/2) proton subshell with seniority υ=2. For 126Pd, two new isomers have been identified with half-lives of 0.33(4) and 0.44(3) µs. The yrast 2(+) energy is much higher in 128Pd than in 126Pd, while the level sequence below the 8(+) isomer in 128Pd is similar to that in the N=82 isotone 130Cd. The electric quadrupole transition that depopulates the 8(+) isomer in 128Pd is more hindered than the corresponding transition in 130Cd, as expected in the seniority scheme for a semimagic, spherical nucleus. These experimental findings indicate that the shell closure at the neutron number N=82 is fairly robust in the neutron-rich Pd isotopes.