Clonal expansion and rapid characterization of Klebsiella pneumoniae ST1788, an otherwise uncommon strain spreading in Wales, UK.

A multidrug-resistant strain of Klebsiella pneumoniae (Kp) sequence type (ST) 1788, an otherwise uncommon ST worldwide, was isolated from 65 patients at 11 hospitals and 11 general practices across South and West Wales, UK, between February 2019 and November 2021. A collection of 97 Kp ST1788 isolates (including 94 from Wales) was analysed to investigate the diversity and spread across Wales and to identify molecular marker(s) to aid development of a strain-specific real-time PCR. Whole genome sequencing (WGS) was performed with Illumina technology and the data were used to perform phylogenetic analyses. Pan-genome analysis of further Kp genome collections was used to identify an ST1788-specific gene target; a real-time PCR was then validated against a panel of 314 strains and 218 broth-enriched screening samples. Low genomic diversity was demonstrated amongst the 94 isolates from Wales. Evidence of spread within and across healthcare facilities was found. A yersiniabactin locus and the KL2 capsular locus were identified in 85/94 (90.4 %) and 94/94 (100 %) genomes respectively; bla SHV-232, bla TEM-1, bla CTX-M-15 and bla OXA-1 were simultaneously carried by 86/94 (91.5 %) isolates; 4/94 (4.3 %) isolates also carried bla OXA-48 carbapenemase. Aminoglycoside and fluoroquinolone resistance markers were found in 94/94 (100 %) and 86/94 (91.5 %) isolates respectively. The ST1788-specific real-time PCR was 100 % sensitive and specific. Our analyses demonstrated recent clonal expansion and spread of Kp ST1788 in the community and across healthcare facilities in South and West Wales with isolates carrying well-defined antimicrobial resistance and virulence markers. An ST1788-specific marker was also identified, enabling rapid and reliable preliminary characterization of isolates by real-time PCR. This study confirms the utility of WGS in investigating novel strains and in aiding proactive implementation of molecular tools to assist infection control specialists.

Wearing different hats enriches "outside the box" thinking: Examining the relationship between personal life activity breadth and creativity at work.

People wear many salient hats across the different parts of their lives and recent advances in the work-life literature have called attention to the necessary addition of personal life activities to be studied as a unique facet of nonwork to better understand interrole relationships. We therefore draw on enrichment theory to examine why and when employees' participation in personal life activities can positively influence creativity at work through nonwork cognitive developmental resources. Moreover, by integrating insights from construal level theory, this research sheds new light on the ways people think about their personal life activities as playing a discernible role in how people can generate and/or apply resources from their activities. Results of two multiwave studies revealed that people who tend to engage in a greater breadth of personal life activities can gain nonwork cognitive developmental resources (i.e., skills, knowledge, and perspectives) that, in turn, enhance their creativity at work. Personal life construal level also moderated the resource generation stage of enrichment, but not resource application to work; people who adopted lower construal level (i.e., more concretely: how they do activities) were more likely to generate cognitive developmental resources from their participation in personal life activities versus those with higher construal level (i.e., more abstractly: why they do activities). This research meets at the convergence of real-world trends on parallel "work" and "nonwork" sides of the interface as well as offers novel and nuanced theoretical insights into instrumental personal life-to-work enrichment processes which can benefit employees and organizations alike. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Prognostic and Predictive Role of PD-L1 Expression in Stage III Non-small Cell Lung Cancer Treated With Definitive Chemoradiation and Adjuvant Durvalumab.

PURPOSE: It is unclear whether programmed death ligand 1 (PD-L1) expression is prognostic or predictive of immunotherapy benefit among patients with stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation and adjuvant durvalumab. METHODS AND MATERIALS: We determined pretreatment tumor PD-L1 expression for 312 patients with stage III NSCLC treated with definitive chemoradiation and at least 1 dose of adjuvant durvalumab between November 2017 and April 2021 across the national Veterans Health Administration. Progression-free survival (PFS) and overall survival (OS) in PD-L1 expression subgroups (<1%, 1%-49%, and 50%-100%) were compared with 994 patients with stage III NSCLC treated without adjuvant durvalumab from 2015 to 2016. RESULTS: PD-L1 expression was <1%, 1% to 49%, and 50% to 100% in 109 (34.9%), 96 (30.7%), and 107 (34.3%) patients, respectively. Increasing PD-L1 expression was associated with longer PFS (adjusted hazard ratio [aHR], 0.84 per 25% absolute increase in expression; 95% confidence interval [CI], 0.75-0.94; P = .003) and OS (aHR, 0.86 per 25% absolute increase in expression; 95% CI, 0.74-0.99; P = .036). Compared with the no-durvalumab group, PFS was longer for PD-L1 50% to 100% (aHR, 0.44; 95% CI, 0.32-0.60; P < .001) and PD-L1 1% to 49% (aHR, 0.64; 95% CI, 0.47-0.86; P = .003) but not PD-L1 <1% (aHR, 0.84; 95% CI, 0.64-1.10; P = .19). Similar results were found for OS, with no significant difference between the no-durvalumab group and PD-L1 <1% (aHR, 0.81; 95% CI, 0.58-1.13; P = .22). CONCLUSIONS: Increasing tumor PD-L1 expression is prognostic for PFS and OS among patients with stage III NSCLC treated with adjuvant durvalumab, and patients with PD-L1 expression <1% may have limited benefit from adjuvant durvalumab.

Timing of Adjuvant Durvalumab Initiation Is Not Associated With Outcomes in Stage III Non-small Cell Lung Cancer.

PURPOSE: It is unclear whether time from radiation therapy (RT) completion to durvalumab initiation influences the outcomes of stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation and adjuvant durvalumab. METHODS AND MATERIALS: Using the US Veterans Health Administration database, we retrospectively identified 728 patients with stage III NSCLC treated with definitive chemoradiation who started durvalumab within 120 days of radiation completion. Time between the last radiation treatment and first durvalumab infusion was analyzed in multivariable Cox regression models for the primary outcomes of progression-free survival (PFS) and overall survival (OS), adjusting for baseline patient and disease characteristics. The primary analysis used a 120-day landmark, measuring OS and PFS from 120 days after radiation completion. RESULTS: Among 728 patients, the median time from RT completion to durvalumab start was 41 days (interquartile range 30-58). In multivariable Cox regression, time from RT completion to durvalumab start showed no association with PFS (adjusted hazard ratio [aHR] 1.01 per week, 95% confidence interval [CI] 0.98-1.04, P = .4) or OS (aHR 1.02 per week, 95% CI 0.98-1.06, P = .3). Starting durvalumab ≤14 days after RT was also not associated with improved PFS or OS. Results were robust in sensitivity analyses varying analytical technique. CONCLUSIONS: Timing of durvalumab initiation up to 120 days after RT completion is not associated with PFS or OS in this real-world patient cohort.

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning.

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.