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Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses.We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis.We conducted a double-blind parallel design trial in patients with cat allergy. A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks, followed by 52 weeks of observation. Nasal allergen challenge (NAC), skin testing, and blood and nasal samples were obtained throughout the study.At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as area under the curve [AUCInhibition of TSLP augments the efficacy of SCIT during therapy and may promote tolerance after a 1-year course of treatment. (ClinicalTrials.gov NCT02237196).

Reliable spatially resolved compositional analysis through atom probe tomography requires an accurate placement of the detected ions within the three-dimensional reconstruction. Unfortunately, for heterogeneous systems, traditional reconstruction protocols are prone to position some ions incorrectly. This stems from the use of simplified projection laws which treat the emitter apex as a spherical cap, although the actual shape may be far more complex. For instance, sampled materials with compositional heterogeneities are known to develop local variations in curvature across the emitter due to their material phase specific evaporation fields. This work provides three pivotal precursors to improve the spatial accuracy of the reconstructed volume in such cases. First, we show scanning probe microscopy enables the determination of the local curvature of heterogeneous emitters, thus providing the essential information for a more advanced reconstruction considering the actual shape. Second, we demonstrate the cyclability between scanning probe characterization and atom probe analysis. This is a key ingredient of more advanced reconstruction protocols whereby the characterization of the emitter topography is executed at multiple stages of the atom probe analysis. Third, we show advances in the development of an electrostatically driven reconstruction protocol which are expected to enable reconstruction based on experimental tip shapes.

Background: Instruments to assess surgical skills have been validated for several key indicator procedures in otolaryngology. Selective neck dissection is a core procedure for which trainees must integrate knowledge of complex head and neck anatomy with technical surgical skills. An instrument for assessment of surgical performance in selective neck dissection has not been previously developed. The objective of the current study is to develop and validate an instrument for assessing surgical competency for level II-IV selective neck dissection. Design: A Delphi working group comprised of 23 fellowship trained head and neck surgeons from 17 institutions was assembled. The modified Delphi method encompassed a 3-step process, including 2 anonymous voting rounds to successively refine individual items and establish levels of consensus. Thresholds for achieving strong consensus, at >80% agreement, were determined a priori. The resulting instrument was subsequently validated in a prospective cohort of 17 resident surgeons, spanning postgraduate year 1 to 5 training experience. Participants were asked to perform a level II-IV selective neck dissection on fresh-frozen cadaveric specimens. Performance was scored by 2 independent, blinded observers using the devised instrument and construct validity was assessed. Results: Through the modified Delphi process a final list of 30 items, considered to be the most essential items for achieving the goals of a level II-IV selective neck dissection, was developed. Construct validity was supported by a positive association between instrument scores compared to both resident postgraduate year level and number of head and neck rotations completed. Conclusion: The development and validation of a novel instrument for assessment of surgical competency in level II-IV selective neck dissection, a key indicator case in otolaryngology, is described. This new instrument may be used to provide objective feedback on overall and task-specific competency to identify surgical deficiencies and offer granular feedback to enhance surgical training.

Health care delivery organizations are positioned to have a tremendous impact on addressing the variables in the practice environment that contribute to occupational distress and that, when optimized, can promote clinician well-being. Many organizations are committed to this work and have clarity on how to address general, system-wide issues and provide resources for individual clinicians. While such top of the organization elements are essential for success, many of the specific improvement efforts that are necessary must address local challenges at the work unit level (department, division, hospital ward, clinic). Uncertainty of how to address variability and the unique needs of different work units is a barrier to effective action for many health care delivery systems. Overcoming this challenge requires organizations to recognize that unit-specific improvement efforts require a system-level approach. In this manuscript, we outline 7 steps for organizations to consider as they establish the infrastructure to improve professional well-being and provide a description of application and evidence of efficacy from a large academic medical center. Such unit-level efforts to address the unique needs of each specialty and occupation at the work unit level have the ability to address many of the day-to-day issues that drive clinician well-being. An enterprise approach is necessary to systematically advance such unit-level action.

Antigen-specific immunoglobulin responses have yet to be studied at the oral mucosal surface during peanut oral immunotherapy (PnOIT).We aimed to quantify salivary peanut-specific IgG4 (PNsIgG4) and IgA (PNsIgA) and total IgG4 and IgA in participants from the Immune Tolerance Network's IMPACT study, a phase 2 PnOIT trial.Peanut-allergic children, aged 12 months to younger than 48 months at screening, were enrolled and randomized to PnOIT or placebo oral immunotherapy (OIT) for 134 weeks. Per-protocol analysis included 69 PnOIT and 23 placebo participants. Double-blind, placebo-controlled food challenges were conducted at weeks 134 and 160 to assess desensitization and remission, respectively. Saliva samples were collected at baseline and 30, 82, 134, and 160 weeks to quantify PNsIgG4, PNsIgA, and total IgG4 and IgA.Participants who received PnOIT experienced significant increases in PNsIgG4 in saliva, whereas participants on placebo did not (P.01 at all time points). The PNsIgA/total IgA ratio was also significantly increased in participants treated with PnOIT when compared with those receiving placebo at 30 and 82 weeks (P.05). During PnOIT, desensitized participants had increased PNsIgA that plateaued, whereas the not desensitized/no remission group did not change over time. Interestingly, when the PnOIT group was evaluated by clinical outcome, PNsIgA was higher at baseline in the not desensitized/no remission group than in the desensitized/remission group (P.05).PnOIT induces substantial increases in allergen-specific IgG4 and IgA in saliva. These data provide insight into OIT-induced mucosal responses and suggest the utility of these easily obtained samples for biomarker development.

In the spring of 2021, the ACR approved a proposal to improve the consistency, transparency, and administrative oversight of the ACR Reporting and Data Systems (RADS). A working group of experts and stakeholders was convened to draft this governance document. Major advances include (1) forming a RADS Steering Committee, (2) establishing minimum requirements and evidence standards for new and existing RADS, and (3) outlining a governance structure and communication strategy for RADS.