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BACKGROUND: Pneumonia is a common cause of morbidity and mortality, yet a causative pathogen is identified in a minority of cases. Plasma microbial cell-free DNA sequencing may improve diagnostic yield in immunocompromised patients with pneumonia. METHODS: In this prospective, multicenter, observational study of immunocompromised adults undergoing bronchoscopy to establish a pneumonia etiology, plasma microbial cell-free DNA sequencing was compared to standardized usual care testing. Pneumonia etiology was adjudicated by a blinded independent committee. The primary outcome, additive diagnostic value, was assessed in the Per Protocol population (patients with complete testing results and no major protocol deviations) and defined as the percent of patients with an etiology of pneumonia exclusively identified by plasma microbial cell-free DNA sequencing. Clinical additive diagnostic value was assessed in the Per Protocol subgroup with negative usual care testing. RESULTS: Of 257 patients, 173 met Per Protocol criteria. A pneumonia etiology was identified by usual care in 52/173 (30.1%), plasma microbial cell-free DNA sequencing in 49/173 (28.3%) and the combination of both in 73/173 (42.2%) patients. Plasma microbial cell-free DNA sequencing exclusively identified an etiology of pneumonia in 21/173 patients (additive diagnostic value 12.1%, 95% confidence interval [CI], 7.7% to 18.0%, P < .001). In the Per Protocol subgroup with negative usual care testing, plasma microbial cell-free DNA sequencing identified a pneumonia etiology in 21/121 patients (clinical additive diagnostic value 17.4%, 95% CI, 11.1% to 25.3%). CONCLUSIONS: Non-invasive plasma microbial cell-free DNA sequencing significantly increased diagnostic yield in immunocompromised patients with pneumonia undergoing bronchoscopy and extensive microbiologic and molecular testing. CLINICAL TRIALS REGISTRATION: NCT04047719.

Coastal Antarctic marine ecosystems are significant in carbon cycling because of their intense seasonal phytoplankton blooms. Southern Ocean algae are primarily limited by light and iron (Fe) and can be co-limited by cobalamin (vitamin B12). Micronutrient limitation controls productivity and shapes the composition of blooms which are typically dominated by either diatoms or the haptophyte Phaeocystis antarctica. However, the vitamin requirements and ecophysiology of the keystone species P. antarctica remain poorly characterized. Using cultures, physiological analysis, and comparative omics, we examined the response of P. antarctica to a matrix of Fe-B12 conditions. We show that P. antarctica is not auxotrophic for B12, as previously suggested, and identify mechanisms underlying its B12 response in cultures of predominantly solitary and colonial cells. A combination of proteomics and proteogenomics reveals a B12-independent methionine synthase fusion protein (MetE-fusion) that is expressed under vitamin limitation and interreplaced with the B12-dependent isoform under replete conditions. Database searches return homologues of the MetE-fusion protein in multiple Phaeocystis species and in a wide range of marine microbes, including other photosynthetic eukaryotes with polymorphic life cycles as well as bacterioplankton. Furthermore, we find MetE-fusion homologues expressed in metaproteomic and metatranscriptomic field samples in polar and more geographically widespread regions. As climate change impacts micronutrient availability in the coastal Southern Ocean, our finding that P. antarctica has a flexible B12 metabolism has implications for its relative fitness compared to B12-auxotrophic diatoms and for the detection of B12-stress in a more diverse set of marine microbes.

BackgroundNon-sputum-based triage tests for tuberculosis are a priority for ending tuberculosis. We aimed to evaluate the diagnostic accuracy of the late-prototype Xpert MTB Host Response (Xpert HR) blood-based assay.MethodsWe conducted a prospective diagnostic accuracy study among outpatients with presumed tuberculosis in outpatient clinics in Viet Nam, India, the Philippines, Uganda, and South Africa. Eligible participants were aged 18 years or older and reported cough lasting at least 2 weeks. We excluded those receiving tuberculosis treatment in the preceding 12 months and those who were unwilling to consent. Xpert HR was performed on capillary or venous blood. Reference standard testing included sputum Xpert MTB/RIF Ultra and mycobacterial culture. We performed receiver operating characteristic (ROC) analysis to identify the optimal cutoff value for the Xpert HR to achieve the target sensitivity of 90% or more while maximising specificity, then calculated diagnostic accuracy using this cutoff value. This study was prospectively registered with ClinicalTrials.gov, NCT04923958.FindingsBetween July 13, 2021, and Aug 15, 2022, 2046 adults with at least 2 weeks of cough were identified, of whom 1499 adults (686 [45·8%] females and 813 [54·2%] males) had valid Xpert HR and reference standard results. 329 (21·9%) had microbiologically confirmed tuberculosis. Xpert HR had an area under the ROC curve of 0·89 (95% CI 0·86-0·91). The optimal cutoff value was less than or equal to -1·25, giving a sensitivity of 90·3% (95% CI 86·5-93·3; 297 of 329) and a specificity of 62·6% (95% CI 59·7-65·3; 732 of 1170). Sensitivity was similar across countries, by sex, and by subgroups, although specificity was lower in people living with HIV (45·1%, 95% CI 37·8-52·6) than in those not living with HIV (65·9%, 62·8-68·8; difference of 20·8%, 95% CI 13·0-28·6; p

BACKGROUND: In India, the prevalence of Latent TB infection (LTBI) is estimated to be around 40%. Various formulations of PPD(Purified protein derivative) are available, for diagnosis of LTBI, which may give variable responses. The commercially available PPD in India is by Arkray Healthcare (TST-Arkray). It is unclear if this product may have a similar sensitivity compared to other internationally accepted tuberculins (TST-Tubersol). OBJECTIVES: To assess the performance of the two TSTs compared to Quantiferon-Gold Plus (QFT-Plus). METHODOLOGY: A blood sample was collected for the QFT-Plus test. Both the TSTs were placed in the right and the left volar aspect of the forearms and 48 hrs later, the subjects came back to the study site for reading. RESULTS: Among the 512 participants who were recruited, 326 subjects were healthcare professionals and 186 subjects were household contacts of patients with tuberculosis. They were tested with both TST-Tubersol and TST-Arkray, 139(27 %) participants tested positive for TST-Tubersol (≥10 mm), whereas 203 participants (40.1 %)tested positive for TST-Arkray. There was moderate agreement between the two tests with k = 0.58. Also, there was only poor agreement between both the TSTs with QFT Plus(kappa = 0.19 for Tubersol and 0.17 for Arkray). With QFT-Plus as gold standard, the sensitivity, specificity, PPV and NPV of TST-Tubersol, ast an induration cut-off of 10 mm was 46.8 %,76.3 %,31.8 % and 85.8 %. respectively and TST- Arkray; 60.6 %, 64 %, 28.5 % and 87.2 % respectively. CONCLUSION: The Indian TST (Arkray Diagnostics) has shown moderate agreement with the internationally accepted Tubersol. Additionally, there was poor agreement between the TSTs and QFT plus test.

Improvements in survival have been made over the past two decades for childhood acute myeloid leukemia (AML), but the approximately 40% of patients who relapse continue to have poor outcomes. A combination of checkpoint-inhibitor nivolumab and azacitidine has demonstrated improvements in median survival in adults with AML. This phase I/II study with nivolumab and azacitidine in children with relapsed/refractory AML (NCT03825367) was conducted through the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium. Thirteen patients, median age 13.7 years, were enrolled. Patients had refractory disease with multiple reinduction attempts. Twelve evaluable patients were treated at the recommended phase II dose (established at dose level 1, 3 mg/kg/dose). Four patients (33%) maintained stable disease. This combination was well tolerated, with no dose-limiting toxicities observed. Grade 3-4 adverse events (AEs) were primarily hematological. Febrile neutropenia was the most common AE ≥ grade 3. A trend to improved quality of life was noted. Increases in CD8+ T cells and reductions in CD4+/CD8+ T cells and demethylation were observed. The combination was well tolerated and had an acceptable safety profile in pediatric patients with relapsed/refractory AML. Future studies might explore this combination for the maintenance of remission in children with AML at high risk of relapse.

BACKGROUND: Multimodal lifestyle interventions, employing food as medicine, stand as the recommended first-line treatment for obesity. The Shared Medical Appointment (SMA) model, where a physician conducts educational sessions with a group of patients sharing a common diagnosis, offers an avenue for delivery of comprehensive obesity care within clinical settings. SMAs, however, are not without implementation challenges. We aim to detail our experience with three implementation models in launching a virtual integrative health SMA for weight management. METHODS: Eligible patients included individuals 18 years of age or older, having a body mass index (BMI) of 30 kg/m2 or 27 kg/m2 or greater with at least one weight related comorbidity. The Practical, Robust Implementation and Sustainability Model (PRISM), Plan, Do, Study, Act (PDSA), and the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME) models were applied to guide the implementation of the Supervised Lifestyle Integrative Medicine (SLIM) program, a virtually delivered, lifestyle medicine focused SMA program, in a weight management clinic within a major health system. We describe how these models, along with attendance for the initial cohorts, were used for decision-making in the process of optimizing the program. RESULTS: 172 patients completed the SLIM program over two years. Attendance was lowest for sessions held at 8:00 AM and 4:00 PM compared to sessions at 10:00 AM, 1:00 PM, and 3:00 PM, leading to only offering midday sessions (p = 0.032). Attendance data along with feedback from patients, facilitators, and administrative partners led to changes in the curriculum, session number and frequency, session reminder format, and intake visit number. CONCLUSION: The use of implementation and quality improvement models provided crucial insight for deployment and optimization of a virtual, lifestyle medicine focused SMA program for weight management within a large healthcare system.

PURPOSE: Although maternal depression is associated with adverse outcomes in women and children, its relationship with lower urinary tract symptoms (LUTS) in offspring is less well-characterized. We examined the association between prenatal and postpartum maternal depression and LUTS in primary school-age daughters. DESIGN: Observational cohort study. SUBJECTS AND SETTING: The sample comprised 7148 mother-daughter dyads from the Avon Longitudinal Study of Parents and Children. METHOD: Mothers completed questionnaires about depressive symptoms at 18 and 32 weeks gestation and 21 months postpartum and their childrens LUTS (urinary urgency, nocturia, and daytime and nighttime wetting) at 6, 7, and 9 years of age. Multivariable logistic regression models were used to estimate the association between maternal depression and LUTS in daughters. RESULTS: Compared to daughters of mothers without depression, those born to mothers with prenatal and postpartum depression had higher odds of LUTS, including urinary urgency (adjusted odds ratio [aOR] range = 1.99-2.50) and nocturia (aOR range = 1.67-1.97) at 6, 7, and 9 years of age. Additionally, daughters born to mothers with prenatal and postpartum depression had higher odds of daytime wetting (aOR range = 1.81-1.99) and nighttime wetting (aOR range = 1.63-1.95) at 6 and 7 years of age. Less consistent associations were observed for depression limited to the prenatal or postpartum periods only. CONCLUSIONS: Exposure to maternal depression in the prenatal and postpartum periods was associated with an increased likelihood of LUTS in daughters. This association may be an important opportunity for childhood LUTS prevention. Prevention strategies should reflect an understanding of potential biological and environmental mechanisms through which maternal depression may influence childhood LUTS.

The intersection of childhood and sexuality is a relatively less researched topic in India. This paper presents teachers' narratives and explores cultural beliefs concerning childhood sexuality. The investigation attempts to understand ways in which the cross-cutting modalities of religion, caste, gender, and sexuality of the teacher and the student shape students' sexual subjectivities. The "Domains of Power" as outlined by Patricia. H. Collins is used to analyse teacher interviews to understand how dominant sexualities are privileged and attain their power within schools. Further, a descriptive analysis is provided for how power relations inform interactions between students and teachers and how such interactions shape teachers' expectations of students' sexual knowledge, experiences, and expressions.

Introduction: Pennsylvania's Student Assistance Program (SAP) began in the mid-1980s to address student barriers to academic success. SAP teams, groups of trained school and community professionals, review referrals, and connect students to services. State leadership conducts an annual SAP team survey, but capacity to evaluate data and affect change is limited. In 2020, leadership partnered with [institution name] to collaboratively review the survey data. Methods: Frequencies and percentages were calculated. Open responses were coded. Logistic regression models evaluated the association between SAP team size, team meeting frequency, and team maintenance. Results: The 2019 to 2020 survey had 1003 respondents. Median number of SAP team members was 8 (range 1-21). The majority (54%) indicated their SAP team met once per week/cycle for 30 to 90+ minutes. Larger teams met more often. Annual team maintenance occurred for 38% of teams, and was more common for larger teams. SAP team members identified mental health (68%), trauma (44%), and parent engagement (36%) as top training needs. Conclusions: An academic partnership successfully provided the capacity to review SAP survey responses, and informed evidenced-based discussion of best practice guidelines and realignment of staff professional development opportunities.

Background: The whole school, whole community, whole child (WSCC) model suggests wellness councils, ongoing review of wellness policy, and a plan for evaluating set objectives are some of the key features needed to support school wellness infrastructure. This study explored the relationship between implementation of these infrastructure features and overall school wellness environment assessment scores among a sampling of Pennsylvania schools. Methods: The Healthy Champions program provides Pennsylvania schools an opportunity to self-assess their wellness environments across several school wellness topics. Staff enrolled their school in the program by completing a self-report electronic assessment. Enrollment data from the 2020/2021 program year were analyzed using the Kruskal-Wallis test and linear fixed model to identify the impact of varied implementation levels across 3 wellness infrastructure activities. Interactions between these variables and overall assessment score were also analyzed. Results: Of the 645 Pennsylvania schools enrolled and analyzed, we observed higher mean wellness environment assessment scores ([delta] 0.74 95% CI 0.40-1.07; p < 0.001) among schools that reported some frequency of all 3 wellness infrastructure activities, compared to schools that reported no frequency for the activities. Implications: Schools with existing policies and practices related to the 3 wellness infrastructure activities should consider the degree of implementation to best support overall wellness in their school setting. Additional research to explore implementation barriers and supports is needed. Conclusions: Analyses indicated that overall wellness environment assessment scores are impacted by implementation thresholds for wellness council meeting frequency, revision of wellness policy, and review of student health promotion objectives.

Plurilingual pedagogies determine that the totality of the students' linguistic and cultural repertoires should be brought into the teaching and learning process. Despite the still prevailing monolingual norm in educational institutions of today, more and more reports on student and teacher recognition of plurilingual approaches as a valuable resource for learning start to emerge. As one of the most multicultural and multilingual countries in the world, the UAE offers a plethora of curricula where the languages of instruction vary, thus appearing as the ideal setting to explore affordances and challenges of plurilingual pedagogies. Therefore, the goal of this study was to understand UAE K-12 teachers' perceptions and potential uses of plurilingual instruction in their mostly bi- or multilingual classrooms. The results seem to indicate that the majority of the teachers surveyed acknowledged the value of other languages, apart from the language of instruction, as support for learning in diverse contexts, choosing to discretely challenge the monolingual stance preferred by their school policies by instinctively implementing plurilingual practices in their teaching.