Psychometric reliability, validity, and generalizability of 3MSE scores among American Indian adults: the Strong Heart Study.

OBJECTIVE: Modified Mini-Mental State Examination (3MSE) is often used to screen for dementia, but little is known about psychometric validity in American Indians. METHODS: We recruited 818 American Indians aged 65-95 for 3MSE examinations in 2010-2013; 403 returned for a repeat examination in 2017-2019. Analyses included standard psychometrics inferences for interpretation, generalizability, and extrapolation: factor analysis; internal consistency-reliability; test-retest score stability; multiple indicator multiple cause structural equation models. RESULTS: This cohort was mean age 73, majority female, mean 12 years education, and majority bilingual. The 4-factor and 2nd-order models fit best, with subfactors for orientation and visuo-construction (OVC), language and executive functioning (LEF), psychomotor and working memory (PMWM), verbal and episodic memory (VEM). Factor structure was supported for both research and clinical interpretation, and factor loadings were moderate to high. Scores were generally consistent over mean 7 years. Younger participants performed better in overall scores, but not in individual factors. Males performed better on OVC and LEF, females better on PMWM. Those with more education performed better on LEF and worse on OVC; the converse was true for bilinguals. All differences were significant, but small. CONCLUSION: These findings support use of 3MSE for individual interpretation in clinic and research among American Indians, with moderate consistency, stability, reliability over time. Observed extrapolations across age, sex, education, and bilingual groups suggest some important contextual differences may exist.

The Comparison of Newly Diagnosed Invasive Breast Patient Cohorts in Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative (GENIE-BPC) and Other Real-World Databases.

BACKGROUND: Oncology databases that integrate genomic and clinical data have become valuable resources for precision medicine. However, the generalizability of these databases has not been comprehensively assessed. OBJECTIVES: To describe the demographics, clinical characteristics, treatments, and overall survival of breast cancer cohorts in GENIE-BPC and three other databases. METHODS: This study utilized GENIE-BPC, SEER, SEER-Medicare, and Merative MarketScan Research Databases. Women with invasive breast cancer were identified through EHR, cancer registries or ICD-9/10-CM codes. The ages were 18+ years or per database requirement. Treatments were based on EHR or HCPCS/NDC codes in claims. Overall survival was estimated as time from diagnosis to death. RESULTS: Of female breast cancer patients in GENIE-BPC (n = 775), SEER (n = 548 336), SEER-Medicare (n = 68 914), and Marketscan (n = 109 499) databases, the median ages at initial diagnosis were 44, 62, 74, and 57 years, respectively. A greater proportion of patients in GENIE-BPC, compared to SEER/SEER-Medicare, had higher nuclear grades (%III-%IV: 57% vs. 26%/24%), advanced disease stage (%IV: 25.3% vs. 5%/3.6%), percent of triple negative breast cancer (19.7% vs. 10.2%/8.5%), and receipt of chemotherapy (85.0% vs. NA/22.3%). The 1-, 3-, and 5-year overall survival rates were lower in GENIE-BPC (78.5%, 60.5%, 55.5%) than in SEER (95.8%, 89.5%, 85.5%) and SEER-Medicare (91.6%, 81.4%, 75.0%). CONCLUSION: Breast cancer patients in GENIE-BPC were younger, had more advanced disease, had a higher proportion of triple negative breast cancer and recipients of chemotherapy, and had poorer overall survival. Researchers must use statistical adjustment when extrapolating results (e.g., biomarker prevalence) from GENIE-BPC to the larger breast cancer population.

Postnatal Ozone Exposure Disrupts Alveolar Development, Exaggerates Mucoinflammatory Responses, and Suppresses Bacterial Clearance in Developing Scnn1b-Tg+ Mice Lungs.

Increased levels of ambient ozone, one of the six criteria air pollutants, result in respiratory tract injury and worsening of ongoing lung diseases. However, the effect of ozone exposure on the respiratory tract undergoing active lung development and simultaneously experiencing mucoinflammatory lung diseases, such as cystic fibrosis, remains unclear. To address these questions, we exposed Scnn1b transgenic (Scnn1b-Tg+) mice, a mouse model of cystic fibrosis-like lung disease, and littermate wild-type (WT) mice to ozone from postnatal days (PND) 3-20 and examined the lung phenotypes at PND21. As compared with filtered air (FA)-exposed WT mice, the ozone-exposed WT mice exhibited marked alveolar space enlargement, in addition to significant eosinophilic infiltration, type 2 inflammation, and mucous cell metaplasia. Ozone-exposed Scnn1b-Tg+ mice also exhibited significantly increased alveolar space enlargement, which was also accompanied by exaggerated granulocytic infiltration, type 2 inflammation, and a greater degree of mucus obstruction. The alveolar space enlargement in ozone-exposed WT, FA-exposed Scnn1b-Tg+, and ozone-exposed Scnn1b-Tg+ mice was accompanied by elevated levels of MMP12 protein in macrophages and Mmp12 mRNA in the lung homogenates. Finally, although bacterial burden was largely resolved by PND21 in FA-exposed Scnn1b-Tg+ mice, ozone-exposed Scnn1b-Tg+ mice exhibited compromised bacterial clearance, which was also associated with increased levels of IL-10, an immunosuppressive cytokine, and marked mucus obstruction. Taken together, our data show that ozone exposure results in alveolar space remodeling during active phases of lung development and markedly exaggerates the mucoinflammatory outcomes of pediatric-onset lung disease, including bacterial infections, granulocytic inflammation, mucus obstruction, and alveolar space enlargement.

Ablation of IL-33 Suppresses Th2 Responses but Is Accompanied by Sustained Mucus Obstruction in the Scnn1b Transgenic Mouse Model.

Cystic fibrosis is characterized by dehydration of the airway surface liquid layer with persistent mucus obstruction. Th2 immune responses are often manifested as increased mucous cell density (mucous cell metaplasia) associated with mucus obstruction. IL-33 is a known inducer of Th2 immune responses, but its roles in mucus obstruction and related phenotypes in a cystic fibrosis-like lung disease model (i.e., Scnn1b-Tg-positive [Tg+]) mouse, remain unclear. Accordingly, IL-33 knockout (IL-33KO) Tg+ mice were examined and compared with IL-33 heterozygous (IL-33HET) Tg+ mice. As compared with IL-33HET/Tg+ mice, IL-33KO/Tg+ mice had complete absence of bronchoalveolar lavage fluid eosinophilia, accompanied with significant reduction in bronchoalveolar lavage fluid concentration of IL-5, a cytokine associated with eosinophil differentiation and recruitment, and IL-4, a major Th2 cytokine. As compared with IL-33HET/Tg+ mice, IL-33KO/Tg+ mice had significantly reduced levels of Th2-associated gene signatures (Slc26a4, Clca1, Retnla, and Chi3l4), along with complete loss of intracellular mucopolysaccharide staining in the airway epithelium. As compared with IL-33HET/Tg+ mice, although the IL-33KO/Tg+ mice had significantly reduced levels of MUC5AC protein expression, they showed no reduction in the degree of mucus obstruction, MUC5B protein expression, bacterial burden, and neonatal mortality. Interestingly, the histological features, including subepithelial airway inflammation and alveolar space enlargement, were somewhat exaggerated in IL-33KO/Tg+ mice compared with IL-33HET/Tg+ mice. Taken together, our data indicate that although IL-33 modulates Th2 inflammatory responses and MUC5AC protein production, mucus obstruction is not dependent on IL-33.

Real-world outcomes of systemic therapy in locally advanced, recurrent or metastatic cutaneous squamous cell carcinoma.

Aim: Real-world treatment patterns and clinical outcomes in advanced cutaneous squamous cell carcinoma were evaluated. Methods: Adults receiving their first systemic therapy for unresectable, locally advanced or recurrent/metastatic cutaneous squamous cell carcinoma from 4 September 2014 to 30 June 2017, were evaluated. The primary end point was real-world overall response rate per Response Evaluation Criteria in Solid Tumors or physician assessment. Time-to-event outcomes were assessed using the Kaplan-Meier method. Results: Of 51 eligible patients, the median age was 76 years, 80% were male and 65% had an Eastern Cooperative Oncology Group score of 0-1. The most common regimens were cetuximab (51%) and carboplatin + paclitaxel (22%). Median real-world overall response rate ranged from 9.8% per Response Evaluation Criteria in Solid Tumors to 43.1% when supplemented by physician assessment. Median overall survival was 10.7 months, and median time to next treatment was 7.5 months. Conclusion: Survival in advanced cutaneous squamous cell carcinoma was short. Real-world overall response rate was lower with Response Evaluation Criteria in Solid Tumors than physician assessment.

This study looked at chemotherapy treatments and responses in patients receiving treatment for advanced cutaneous squamous cell carcinoma, a type of skin cancer. Patients had advanced and metastatic cancer that could not be cured by radiation or surgery. Most of the patients were white males, and their median age was 76 years. About two-thirds of the patients in the study had their original cancer in the head and neck, and in most patients (approximately 80%), the cancer had spread, mostly to the lungs or lymph nodes. Half of the patients in the study were treated with cetuximab, and about a quarter received platinum chemotherapy or other cetuximab-based treatment. The study examined how response to treatment may be measured in clinical care and clinical trials. Response to treatment and length of survival were short: patients responded to treatment for a median of 9 months and survived for a median of 10.7 months.

Compartment-specific transcriptomics of ozone-exposed murine lungs reveals sex- and cell type-associated perturbations relevant to mucoinflammatory lung diseases.

Ozone is known to cause lung injury, and resident cells of the respiratory tract (i.e., epithelial cells and macrophages) respond to inhaled ozone in a variety of ways that affect their survival, morphology, and functioning. However, a complete understanding of the sex-associated and the cell type-specific gene expression changes in response to ozone exposure is still limited. Through transcriptome profiling, we aimed to analyze gene expression alterations and associated enrichment of biological pathways in three distinct cell type-enriched compartments of ozone-exposed murine lungs. We subchronically exposed adult male and female mice to 0.8 ppm ozone or filtered air. RNA-Seq was performed on airway epithelium-enriched airways, parenchyma, and purified airspace macrophages. Differential gene expression and biological pathway analyses were performed and supported by cellular and immunohistochemical analyses. While a majority of differentially expressed genes (DEGs) in ozone-exposed versus air-exposed groups were common between both sexes, sex-specific DEGs were also identified in all of the three tissue compartments. As compared with ozone-exposed males, ozone-exposed females had significant alterations in gene expression in three compartments. Pathways relevant to cell division and DNA repair were enriched in the ozone-exposed airways, indicating ozone-induced airway injury and repair, which was further supported by immunohistochemical analyses. In addition to cell division and DNA repair pathways, inflammatory pathways were also enriched within the parenchyma, supporting contribution by both epithelial and immune cells. Further, immune response and cytokine-cytokine receptor interactions were enriched in macrophages, indicating ozone-induced macrophage activation. Finally, our analyses also revealed the overall upregulation of mucoinflammation- and mucous cell metaplasia-associated pathways following ozone exposure.

Prognostic impact of PD-L1 in oropharyngeal cancer after primary curative radiotherapy and relation to HPV and tobacco smoking.

Background: Incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rising rapidly in many western countries due to Human papillomavirus (HPV) and tobacco smoking, with a considerable overlap. Immunotherapy directed at the PD1/PD-L1 axis have shown promise in head and neck cancer and other cancer types. PD-L1 expression may indicate a poorer prognosis, and at the same time indicate a possible benefit of anti-PD-L1 immunotherapeutic agents. The primary aim of this study was to establish the prognostic effect of PD-L1 expression after primary curative radiotherapy alone.Material and methods: A cohort of 303 OPSCC patients treated with primary, curative intended radiotherapy was established. PD-L1 expression was evaluated by immunohistochemistry on formalin fixed, paraffin embedded tissue sections. PD-L1 positivity was defined as a Combined Positive Score (CPS) ≥1, indicating staining of either tumor cells, lymphocytes or macrophages.Results: Median follow-up was 5.3 years. With 199 deaths, there was no difference in overall survival between patients with PD-L1+ and PD-L1- tumors (adjusted hazard ratio [aHR] and 95% confidence interval [CI]: 1.0 [0.71-1.4]). Also, locoregional failure was similar between the two groups (aHR 1.1 [CI: 0.68 - 1.7]). Tumors were PD-L1+ in 76% of cases, significantly more among HPV p16+ tumors (82% vs. 70%, p = .01). Interestingly, higher prevalence of PD-L1+ expression was seen in HPV p16+ patients with <10 pack-years of tobacco-smoking (93%) compared to HPV p16+ smokers (76%) or HPV p16-negative patients (70%) (p = .003).Conclusion: PD-L1 expression had no prognostic significance in OPSCC patients treated with primary radiotherapy alone. A substantial proportion of OPSCC tumors show PD-L1 overexpression, especially in HPV p16+ tumors in patients with little or no smoking history.

Impact of PD-L1 and T-cell inflamed gene expression profile on survival in advanced ovarian cancer.

OBJECTIVE: Programmed death ligand 1 (PD-L1) expression affects tumor evasion of immune surveillance. The prognostic value and relationship of PD-L1 expression to T-cell-inflamed immune signatures in ovarian cancer are unclear. The purpose of this study is to evaluate the impact of PD-L1 on overall survival and its correlation with an immune-mediated gene expression profile in patients with advanced ovarian cancer. METHODS: PD-L1 expression in tumor and immune cells was assessed by immunohistochemistry, and PD-L1-positive expression was defined as a combined positive score ≥1; a T-cell-inflamed gene expression profile containing interferon γ response genes was evaluated using extracted RNA from surgical samples. Associations between PD-L1 expression, gene expression profile status, and overall survival were analyzed using the Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazards regression models. RESULTS: A total of 376 patients with advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer treated by cytoreductive surgery and platinum-based therapy were included. PD-L1-positive expression was observed in 50.5% of patients and associated with more advanced stage (p=0.047), more aggressive histologic subtype (p=0.001), and platinum sensitivity defined by increasing treatment-free interval from first platinum-based chemotherapy to next systemic treatment (p=0.027). PD-L1-positive expression was associated with longer overall survival in multivariate analyses (adjusted HR 0.72, 95% CI 0.56 to 0.93). In subgroup analyses, this association was most pronounced in patients with partially platinum-sensitive disease (treatment-free interval ≥6 to <12 months). T-cell-inflamed gene expression profile status correlated with PD-L1 expression (Spearman, ρ=0.712) but was not an independent predictor of overall survival. CONCLUSION: PD-L1 expression is associated with longer overall survival among advanced ovarian cancer patients. PD-L1 expression may be an independent prognostic biomarker.

Crafting study tasks among medical students: the role of authentic medical teachers.

BACKGROUND: Though leadership has been highlighted as a salient skill for medical teachers in the medical education literature, the role of authentic leadership style among medical teachers in activating medical students' learning behaviors has not been explored. Our study seeks to examine the effects of medical teachers' authentic leadership on study task crafting behaviors among medical students. METHODS: Our study adopted a mixed-methods research design comprising observations of 100 surgical operations and 100 ward conferences led by medical teachers, and surveys on authentic leadership, study task crafting, and promotion focus. Structural equation modelling was utilized in the data analysis. RESULTS: Medical teachers' authentic leadership demonstrated positive effects on the two study task crafting behaviors (seeking resources (B = 0.36, p < 0.001) and seeking challenges (B = 0.21, p < 0.05)) but not on reducing study task demands (B = 0.11, p > 0.10). Promotion focus was found to strengthen such positive effects of authentic leadership on seeking resources (B = 0.23, p < 0.05) and seeking challenges (B = 0.18, p < 0.05). Illustrative excerpts of intraoperative and conference conversations are presented. CONCLUSIONS: Our study provided empirical evidence that medical students guided by authentic teachers expressed increased levels of study task crafting, which were further increased if medical students were promotion-focused.

Development and psychometric properties of the Healthy Aging Activity Engagement Scale (HAAE).

OBJECTIVES: Accumulating research indicates that engaging in healthy lifestyle behaviors (e.g. exercise, cognitive and social engagement, stress reduction) can prevent illness and disability as people age and improve mental health. The Healthy Aging Activity Engagement (HAAE) scale was developed to holistically assess an individual's level of engagement in healthy aging behaviors across multiple health domains. METHODS: Participants were 275 healthy younger, midlife and older adults. Participants rated engagement in 38 healthy aging lifestyle behaviors over the past 7 days on a scale from 1 (strongly disagree) to 5 (strongly agree). RESULTS: Traditional measurement analysis and Rasch modelling techniques resulted in a 32-item scale with three subscales representing biologic health, social and cognitive strategies, and health safeguard behaviors. With the exception of the health safeguard subscale, the HAAE total score and subscales demonstrated good internal consistency, test-retest reliability, convergent and discriminant validity, and responsiveness to a program designed to promote engagement in healthy brain aging behaviors. DISCUSSION: With further validation, the HAAE may be useful for holistic clinical assessment of behaviors that promote healthy aging, support brain and mental health, and for treatment planning. Furthermore, the HAAE can be used to measure the outcome of multi-domain lifestyle interventions.

Energetic salts with π-stacking and hydrogen-bonding interactions lead the way to future energetic materials.

Among energetic materials, there are two significant challenges facing researchers: 1) to develop ionic CHNO explosives with higher densities than their parent nonionic molecules and (2) to achieve a fine balance between high detonation performance and low sensitivity. We report a surprising energetic salt, hydroxylammonium 3-dinitromethanide-1,2,4-triazolone, that exhibits exceptional properties, viz., higher density, superior detonation performance, and improved thermal, impact, and friction stabilities, then those of its precursor, 3-dinitromethyl-1,2,4-triazolone. The solid-state structure features of the new energetic salt were investigated with X-ray diffraction which showed π-stacking and hydrogen-bonding interactions that contribute to closer packing and higher density. According to the experimental results and theoretical analysis, the newly designed energetic salt also gives rise to a workable compromise in high detonation properties and desirable stabilities. These findings will enhance the future prospects for rational energetic materials design and commence a new chapter in this field.

Tetranitroacetimidic acid: a high oxygen oxidizer and potential replacement for ammonium perchlorate.

Considerable work has been focused on developing replacements for ammonium perchlorate (AP), a primary choice for solid rocket and missile propellants, due to environmental concerns resulting from the release of perchlorate into groundwater systems [corrected]. Additionally, the generation of hydrochloric acid contributes to high concentrations of acid rain and to ozone layer depletion. En route to synthesizing salts that contain cationic FOX-7, a novel, high oxygen-containing oxidizer, tetranitroacetimidic acid (TNAA), has been synthesized and fully characterized. The properties of TNAA were found to be exceptional, with a calculated specific impulse exceeding that of AP, leading to its high potential as a replacement for AP. TNAA can be synthesized easily in a one-step process by the nitration of FOX-7 in high yield (>93%). The synthesis, properties, and chemical reactivity of TNAA have been examined.

Selective Late-Stage Functionalization of Tryptophan-Containing Peptides To Facilitate Bioorthogonal Tetrazine Ligation.

Site-selective modification of complex peptides and the functionalization of their C-H bonds hold great promise for expanding their use in therapeutics and biomedical research. Herein, we leverage the power of late-stage chemoenzymatic catalysis using an indole prenyltransferase (IPT) enzyme and alkyl diphosphates to specifically modify the indole ring of tryptophan in clinically relevant peptides. Furthermore, the installed handle enables bioorthogonal click chemistry through an inverse electron-demand Diels-Alder (IEDDA) reaction with a biotin-conjugated tetrazine probe.

Psychometric Reliability, Validity, and Generalizability of MoCA in American Indian Adults: The Strong Heart Study.

Standardized neuropsychological instruments are used to evaluate cognitive impairment, but few have been psychometrically evaluated in American Indians. We collected Montreal Cognitive Assessment (MoCA) in 403 American Indians 70 to 95 years, as well as age, sex, education, bilingual status, depression symptoms, and other neuropsychological instruments. We evaluated inferences of psychometric validity, including scoring inference using confirmatory factor analysis and structural equation modeling, generalizability inference using reliability coefficient, and extrapolation inference by examining performance across different contexts and substrata. The unidimensional (total score) model had good fit criteria. Internal consistency reliability was high. MoCA scores were positively associated with crystallized cognition (ρ = 0.48, p < .001) and inversely with depression symptoms (ρ = -0.27, p < .001). Significant differences were found by education (d = 0.79, p < .05) depression (d = 0.484, p < .05), and adjudicated cognitive status (p = .0001) strata; however, MoCA was not sensitive or specific in discriminating cognitive impairment from normal cognition (area under the curve <0.5). MoCA scores had psychometric validity in older American Indians, but education and depression are important contextual features for score interpretability. Future research should evaluate cultural or community-specific adaptations, to improve test discriminability in this underserved population.

Psychometric Properties of Controlled Oral Word Association (COWA) Test and Associations With Education and Bilingualism in American Indian Adults: The Strong Heart Study.

The Controlled Oral Word Association (COWA) test is used to assess phonemic fluency and executive function. Formal validation of test scores is important for accurate cognitive evaluation. However, there is a dearth of psychometric validation among American Indian adults. Given high burden of dementia risk and key contextual factors associated with cognitive assessments, this represents a critical oversight. In a large, longitudinal population-based cohort study of adult American Indians, we examined several validity inferences for COWA, including scoring, generalization, and extrapolation inferences, by investigation of factor structure, internal consistency, test-retest reliability, and differential test functioning. We found adequate unidimensional model fit, with high factor loadings. Internal consistency reliability and test-retest reliability were 0.88 and 0.77, respectively, for the full group. COWA scores were lowest among the oldest, lowest education, bilingual speakers; group effects for sex and bilingual status were small; age effect was medium; and education effect was largest. However, Wide Range Achievement Test (WRAT) score effect was stronger than education effect, suggesting better contextualization may be needed. These results support interpretation of total COWA score, including across sex, age, or language use strata.

Telangiectatic osteosarcoma in four dogs: Cytologic, histopathologic, cytochemical, and immunohistochemical findings.

Telangiectatic osteosarcoma is a rare variant of osteosarcoma histologically and clinically similar to hemangiosarcoma (HSA). This case series describes the imaging and cytologic features of four histologically confirmed telangiectatic osteosarcomas, including the use of cytochemical stains. Alkaline phosphatase (ALP) was applied to Wright-Giemsa-stained cytology slides, and Factor VIII immunohistochemistry was evaluated. Cytologic characteristics included atypical mesenchymal cells with evidence of acute and chronic hemorrhage. Telangiectatic osteosarcoma cases had positive ALP cytochemical staining, while control HSA cases were negative. Factor VIII immunohistochemistry was negative in telangiectatic osteosarcoma and positive in HSA. Cytologic diagnosis of telangiectatic osteosarcoma with positive ALP cytochemical staining can help differentiate this neoplasm from HSA.

New roles for 1,1-diamino-2,2-dinitroethene (FOX-7): halogenated FOX-7 and azo-bis(diahaloFOX) as energetic materials and oxidizers.

The syntheses and full characterization of two new halogenated 1,1-diamino-2,2-dinitroethene (FOX-7) compounds and three halogenated azo-bridged FOX-7 derivatives are described. Some of these new structures demonstrate properties that approach those of the commonly used secondary explosive RDX (cyclo-1,3,5-trimethylene-2,4,6-trinitramine). All the compounds display hypergolic properties with common hydrazine-based fuels and primary aliphatic amines (ignition delay times of 2-53 ms). This is a new role that has yet to be reported for FOX-7 and its derivatives. Their physical and energetic properties have been investigated. All compounds were characterized by single-crystal X-ray crystallography, elemental analysis, infrared spectra, and differential scanning calorimetry. These new molecules as energetic materials and hypergolic oxidizers contribute to the expansion of the chemistry of FOX-7.

Explant of a Chronic Atlantoaxial Implant Infection in a Dog.

An 11-year-old male neutered Yorkshire Terrier was presented with a cervical mass that developed a draining tract. Aside from the dysphagia reported by the owner, his neurologic exam was normal. Three years prior, the patient was diagnosed with an atlantoaxial subluxation that was ventrally stabilized with polymethylmethacrylate (PMMA) and self-tapping titanium screws. There were no postoperative complications until presenting with the cervical mass and dysphagia. Computerized tomography (CT) of the cervical spine confirmed caudal migration of the PMMA and screws with an abscess surrounding the implant. A surgical explant of the PMMA and screws was performed without complication. The atlantoaxial joint remained normally aligned on postoperative radiographs. Cultures of the implant grew Streptococcus bovis. He was treated with cephalexin (22 mg/kg PO BID) for 30 days. At the time of his one-month recheck, he was swallowing normally with no neurologic deficits. He remains normal at the time of this report (17 months later). This case reports a successful explant of a chronic atlantoaxial implant infection.

Elevated white blood cell counts in ischemic stroke patients are associated with increased mortality and new vascular events.

Background and purpose: High levels of white blood cells (WBC) in ischemic stroke have been shown to increase the risk of new vascular events and mortality in short and intermediate follow-up studies, but long-term effects remain unknown. We studied whether elevated levels of WBC in ischemic stroke patients are associated with new vascular events and mortality in a 10-year follow-up period. Methods: We included ischemic stroke patients hospitalized between 2011 and 2012, categorizing their WBC counts within 48 h of stroke onset as high or normal (3.5-8.8 × 109 mmol/L; >8.8 × 109 mmol/L). Using Aahlen Johansen and Cox proportional hazard models with competing risk, we analyzed the association between WBC levels and new vascular events. Kaplan-Meier and standard Cox proportional hazard models were used to assess the risk of all-cause mortality. Results: Among 395 patients (median age 69, [IQR: 63, 78], female patients 38,0%), 38.5% had elevated WBC at admission. During the 10-year follow-up, 113 vascular events occurred, with 46% in patients with elevated WBC and 54% in patients with normal WBC. After adjusting for relevant factors, elevated WBC levels were independently associated with increased risk of new vascular events (HR: 1.61, CI: 1.09-2.39 p < 0.05) and death (HR: 1.55, CI: 1.15-2.09, p < 0.05). Conclusion: Elevated WBC levels in ischemic stroke patients are linked to a higher risk of new vascular events and mortality. Thus, ischemic stroke patients with elevated WBC without clinical infection need special attention to investigate possible underlying conditions to prevent future vascular events and reduce mortality. The interpretation of our results is limited by the absence of adjustment to premorbid functional status, stroke severity, and stroke treatment.

Latent profile similarity of middle and high school youth risk and needs.

Research concerning school success and completion has grown increasingly complex with the number of proposed associated risk and needs domains. As the number of domains expands, various data analytical techniques have been employed to understand them, including the modeling of latent profiles, to better understand how risks and needs aggregate at the level of individual persons. Latent profile analysis helps identify individuals' subgroups based on salient combinations of characteristics. The present study used latent profile analysis and a systematic profile similarity approach to examine the profiles across middle and high school student cohorts. The study replicates the profiles of previous work with high school students and extends this to middle school students. We used two independent cohorts to replicate a 3-profile solution for middle and high school samples. Results supported a similar 3-profile solution for both samples, with minor discrepancies. Results are discussed with respect to the replication and extension of the 3-profile model and its application to efforts to improve outcomes for youth in both grade level cohorts.