Primary Foci Research Articles

Sero-epidemiology of foot-and-mouth disease in Darfur area, Western Sudan.

A total of 367 bovine sera positive to antibodies against non-structural proteins (NSPs) of foot-and-mouth disease (FMD) virus were screened for serotype O, A and SAT2 antibodies using the virus neutralization test (VNT). Sera had been collected in 2016 from North (228) and South (139) Darfur States in Western Sudan, where high and low circulation of FMD virus, respectively, prevailed. Tested sera represented the positive-NSPs portion in a random sample of 669 sera collected from both States. According to standard statistical methods, calculations for serial testing (NSPs ELISA and VNT) were applied to estimate prevalence rates of serotype-specific antibodies in the two States. In each State, approximately 20% of NSPs positive sera failed typing. Prevalence's detected were 49% ± 5% (O), 27% ± 5% (A) and 14% ± 4% (SAT2) in North Darfur State and 27% ± 5% (O), 17% ± 4% (A) and 8.0% ± 3% (SAT2) in South Darfur State. In both States, prevalence rates were significantly higher for serotype O, followed by A then SAT2; the same order that was known in most parts of Sudan. Consistently, estimated prevalence's were statistically significantly higher (P < 0.05) in North Darfur than in South Darfur State. Apart from serotype SAT2, detected prevalence rates were lower or similar to those inside the country in previous occasions. Frequency and pattern of distribution of serotype O prevalence were consistent with its suggested pattern of circulation from the Nile valley to other parts in Sudan and significant within the country's circulation. Alternatively, serotype SAT2 prevalence and distribution in Darfur area were suggestive of sporadic occurrence. However, slightly higher prevalence rates of SAT2 antibodies in Darfur than in neighbouring Kordofan areas in 2013 reflected the wide dissemination of SAT2 ( http://www.wrlfmd.org ) in Sudan in early 2014. Risk of FMD in Darfur seemed to be associated with the movement of animals to the North in the wet season as part of the pastoral system, and with movement related to trade into urban centers more than with pastoralism across the Western borders. Generally, the result presented little evidence to suggest presence of FMD primary endemic foci in Darfur area.

On the time lag between human activity and biodiversity in Europe at the national scale

• We studied statistically the human activity/biodiversity relationship in Europe. • We used 5 biodiversity indicators (2 pressures, 2 states and 1 response). • Spatial density of human activity explained best variations of biodiversity. • There was a time lag of around one century for the two state indicators. • There was no such time-lag for the two pressure indicators. The relation between the environment and human activity has been the subject of many empirical studies. Complexities such as which indicators related to human activity best represent biodiversity, or time lags between socio-economic activities and biodiversity, remain unclear. This paper tackles these issues based on statistical analysis of the relationship between human activity and biodiversity at the country level in Europe. We used well-adapted statistical models to explain variations in two state indicators, two pressure indicators, and one response indicator representing biodiversity. We focused on (i) the relative efficiency of the various indicators of human activity (notably human population density, human appropriation of net primary productivity, and gross domestic product per area) in predicting the biodiversity indicators, and (ii) possible time lags between metrics representing human activity and biodiversity. Results indicate that gross domestic product per area and human population density best predict the indicators for the biodiversity state, whereas human population density best predicts the indicators of biodiversity pressure. Although the indicators for biodiversity pressure best related to present-day human activity metrics, biodiversity state reveals a time lag of approximately one century. Results suggest that drivers (human population density, density of economic activity) and pressures (land sealing) should serve as primary foci for biodiversity policies. Because of the long time lags (∼ one century) between these drivers and the state of biodiversity, policies regarding biodiversity should integrate a long-term view.

Prognostic features of gastro-entero-pancreatic neuroendocrine neoplasms in primary and metastatic sites: Grade, mesenteric tumour deposits and emerging novelties.

Updates in classification of gastro-entero-pancreatic neuroendocrine neoplasms better reflect the biological characteristics of these tumours. In the present study, we analysed the characteristics of neuroendocrine tumours that could aid in a more precise stratification of risk groups. In addition, we have highlighted the importance of grade (re)assessment based on investigation of secondary tumour lesions. Two hundred and sixty-four cases of neuroendocrine tumours of gastro-entero-pancreatic origin from three centres were included in the study. Tumour morphology, mitotic count and Ki67 labelling index were evaluated in specimens of primary tumours, lymph node metastases and distant metastases. These variables were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour stage, number of affected lymph nodes, presence of tumour deposits and synchronous/metachronous metastases were tested as possible prognostic features. Mitotic count, Ki-67 labelling index, primary tumour site, tumour stage, presence of tumour deposits and two or more affected lymph nodes were significant predictors of OS and RFS. At the same time, mitotic count and Ki-67 labelling index can be addressed as continuous variables determining prognosis. We observed a very high correlation between the measures of proliferative activity in primary and secondary tumour foci. The presence of isolated tumour deposits was identified as an important determinant of both RFS and OS for pancreatic (hazard ratio [HR]=7.61, 95% confidence interval [CI]=3.96-14.6, P<0.0001 for RFS; HR=3.28, 95% CI=1.56-6.87, P=0.0017 for OS) and ileal/jejunal neuroendocrine tumours (HR=1.98, 95% CI=1.25-3.13, P=0.0036 for RFS and HR 2.59, 95% CI=1.27-5.26, P=0.009 for OS). The present study identifies the presence of mesenterial tumour deposits as an important prognostic factor for gastro-entero-pancreatic neuroendocrine tumours, provides evidence that proliferative parameters need to be treated as continuous variables and further supports the importance of grade determination in all available tumour foci.

The Immune Microenvironment in Brain Metastases of Non-Small Cell Lung Cancer.

Brain metastasis of non-small cell lung cancer is associated with poor survival outcomes and poses rough clinical challenges. At the era of immunotherapy, it is urgent to perform a comprehensive study uncovering the specific immune microenvironment of brain metastases of NSCLC. The immune microenvironment of brain is distinctly different from microenvironments of extracranial lesions. In this review, we summarized the process of brain metastases across the barrier and revealed that brain is not completely immune-privileged. We comprehensively described the specific components of immune microenvironment for brain metastases such as central nervous system-derived antigen-presenting cells, microglia and astrocytes. Besides, the difference of immune microenvironment between brain metastases and primary foci of lung was particularly demonstrated.

Neoadjuvant chemotherapy combined with radical surgery for stage IB2/IIA2 cervical squamous cell carcinoma: a prospective, randomized controlled study of 35 patients

ObjectiveThis study aimed to evaluate the clinical outcomes for patients with stage IB2/IIA2 cervical squamous cell carcinoma treated with neoadjuvant chemotherapy combined with radical surgery.MethodsA total of 68 patients with cervical squamous cell carcinoma were randomly divided into the experimental group (n = 35) and the control group (n = 33). The patients in the experimental group received paclitaxel plus cisplatin neoadjuvant chemotherapy for two cycles, then underwent radical hysterectomy and bilateral adnexectomy at 2 weeks post-chemotherapy. The control group only underwent radical hysterectomy and bilateral adnexectomy after the diagnosis of cervical squamous cell carcinoma. The toxic and side effects of chemotherapy in the experimental group were observed. Also, the operation method, operation time, blood loss, grade of wound healing, complications, and postoperative pathology were noted in the two groups. Primary foci and pelvic lymph node recurrence and distant metastasis were observed, and 3-year and 5-year survival rates were calculated.ResultsOnly one patient in the experiment had grade III bone marrow suppression; no other grade III and IV chemotherapy toxic reactions were observed. The operation was successfully completed in all patients. The operation time, intraoperative blood loss, placement of the ureteral catheter, bladder injury, ureteric injury, postoperative urinary tub, pelvic drainage tube indwelling time, anal exhaust time, postoperative complications, and metastatic ratio of lymph nodes were not significantly different between the two groups (P > 0.05). The number of dissected lymph nodes, deep myometrial invasion, and vascular tumor emboli showed a significant difference in the experimental group compared with the control group (P < 0.05). The 3-year disease-free survival (82.9% vs 81.9%), 5-year disease-free survival (71.4% vs 60.6%), 3-year overall survival (91.4% vs 87.8%), and 5-year overall survival (82.9% vs 75.6%) were not statistically significantly different between the experimental group and the control group (P > 0.05).ConclusionsNeoadjuvant chemotherapy in IB2/IIA2 stage cervical squamous cell carcinoma showed low toxic side effects. Radical surgery after chemotherapy is safe and feasible. It plays a coordinating role in reducing the tumor infiltration depth of the deep muscle layer and the incidence of vascular tumor emboli, reducing the use of postoperative adjuvant therapy, and improving the quality of life of patients, but does not improve the 3-year/5-year survival rate.

Spatiotemporal development of Ascochyta blight in chickpea from primary infection foci: insights from plant, pathogen and the environment interactions to inform an epidemic risk

Ascochyta blight epidemics have been observed in many countries since the early 1900s but studies on an interaction between the amount of inoculum, environmental factors and the spatiotemporal development of Ascochyta blight are rare due to the historic emphasis on developing resistant cultivars and chemical control of the disease. I used generalised linear mixed models to investigate key environmental factors affecting the spatiotemporal development of Ascochyta blight from primary infection foci. Briefly, four replicate plots (20 m × 20 m) of a susceptible chickpea cultivar were planted at two different locations (Billa Billa and Tosari) in Queensland, Australia. Four naturally infested stubble pieces were placed at the centre of each newly emerged chickpea plot 14 days after sowing. The number of infected plants was counted in 1 m2 observation quadrats at the distances of 3, 6 and 9 m in a concentric arrangement. The number of infected plants increased with each assessment date, approaching 100% plant infections at the time of final assessment. The rate of disease progress was significantly faster at Tosari. The rate of disease progress significantly decreased as the distance from the primary infection foci increased. There was a significant positive effect of an optimum temperature, increasing rainfall and omni-directional wind. The influence of wind speed was not significant. The finding that single infection foci were enough to spread disease across whole plots indicate that limited inoculum is not a barrier in the development of an epiphytotic under conducive conditions.

Comprehensive Analysis of Peritoneal Metastasis Sequencing Data to Identify LINC00924 as a Prognostic Biomarker in Gastric Cancer.

BackgroundGastric cancer peritoneal metastasis has high mortality. At present, there is no effective way to cure the patients diagnosed with gastric cancer peritoneal metastasis due to its indistinct molecular mechanism. Therefore, to understand the pathogenesis and help for further target therapy, we conduct comprehensive analysis of peritoneal metastasis by bioinformatics in gastric cancer.MethodsMicroarray sequencing was used to find differential mRNAs and long non-coding RNAs (lncRNAs) expression between primary foci and peritoneal metastases lesion in gastric cancer. RT-qPCR was used to verify the expression levels of lncRNAs in gastric cancer cells after co-culture with adipocytes. TCGA, Cytoscape, lnCAR, cBioPoratal and R packages (ggrisk, survival, survminer, timeROC, forestplot, immunedeconv, ggplot2, pheatmap and ggpubr) were applied in this work.ResultsAdipocytes co-culture model was used to mimic the peritoneal microenvironment and found that LINC01151 (NR_126348), FAM27B (NR_027422) and LINC00924 (NR_027133) were up-regulated in co-culture group. Increased LINC00924 expression was significantly associated with reduced overall survival and up-regulated percentage abundance of tumor-infiltrating CD8+ T, B, macrophage and NK immune cells; moreover, immune checkpoint blockers (ICBs) had a worse effect on the LINC00924 high expression group. Furthermore, through univariate and multivariate Cox regression analysis, we found that LINC00924-related PEX5L in CNC network was an independent prognostic factor in gastric cancer progression.ConclusionLINC00924 expression was associated with poor survival, immune infiltrations and worse response to ICBs. LINC00924 might be immunotherapeutic targets of advanced gastric cancer.

Brain-based learning research for adult education and human resource development

PurposeThe purpose of this study is to reveal how research on brain-based learning (BBL) addressing adult learners’ education and training issues has contributed to the overall knowledge base linking neuroscience, adult education and human resource development (HRD) research and practices. Through this comprehensive review of the BBL studies, this paper aims to expand the landscape of understanding educational phenomenon in adult education and organizational settings using the lens of neuroscience.Design/methodology/approachUsing the content analysis method, this study extracts key research themes and methodological choices from the body of BBL studies. In addition, this paper explores the relationships and proximity among key concepts of BBL research using keyword network analysis. For data analysis, this study reviews the current literature on BBL addressing both adult education and HRD topics from 1985 to 2019.FindingsThe findings of this study provide a clearer picture of the potential mechanisms of BBL approaches observed in the literature of adult education and HRD. What has been found from the thematic analysis is that addressing misconceptions about the neuroscience of learning is regarded as an important topic. In terms of the methodological approaches, the literature review was a dominantly used method, whereas experimental or quantitative research has yet to be fully performed. Influential keywords and topics obtained from the keyword network analysis reveal the primary foci and structural patterns of current BBL research.Originality/valueThis study makes a significant contribution to theories and research in adult education and HRD scholarship as it provides an integrative view of key research themes and major issues about BBL. Additionally, our findings offer practical insights for adult educators and HR professionals to successfully apply neuroscientific approaches.

Elemental composition of indoor and outdoor coarse particulate matter at an inner-city high school

Paired PM10 and fine particulate matter (PM2.5) samples were collected indoor and outdoor at a fully mechanically ventilated high school in the ultraindustrialized ship channel region of Houston, Texas over a two-month period. The primary foci of this research are to measure the elemental composition of ambient outdoor and indoor coarse particulate matter (PM10-2.5), characterize aerosol infiltration/ventilation, and obtain clues to their origins. Several metallic hazardous air pollutants were detected inside the school but at concentrations lower than even the most rigorous indoor air quality benchmarks. Only chromium may have potentially posed a hazard based on indoor air quality standards set by the California Environmental Protection Agency. Indoor-to-outdoor (I/O) mass abundance ratios for some metals (Li, Be, Si, Ti, Cr, Co, Ni, Zn, As, Se, Zr, Cd, Sn, Sb, Hf, and Pb) were significantly greater than 1 in PM10-2.5, suggesting corresponding indoor sources in the PM10-2.5 size range. Some other metals (Al, K, Ca, V, Mn, Fe, Cu, Ga, Rb, Sr, Y, Mo, Ce, Pr, Nd, Sm, Gd, Dy, Yb, and U) in PM10-2.5 had I/O ratios close to one suggesting they had predominantly outdoor origins. Enrichment factors of several metals including light rare earths (e.g. Cu, Sb, Pb, Mo, Cd, La, Ce, Pr, Nd, and Sm) with respect to local soil were overall the highest both indoors and outdoors, illustrating their anthropogenic origins. Several lines of evidence including light lanthanoid ratios, simultaneous La–Ce-Sm variations (ternary diagrams), and correlations with cracking catalysts indicated that petroleum refineries are principally responsible for the elevated lanthanoid concentrations. Rare earth element analysis revealed shifts between transient catalyst releases from petroleum refining operations and windblown soil resuspension as their dominant sources.

Clinical information and management status of de novo stage IV breast cancer patients: a Chinese multicenter investigation (CSBrS-002).

Background:Although de novo stage IV breast cancer is so far incurable, it has entered an era of individualized treatment and chronic disease management. Based on systemic treatment, whether the surgical resection of primary or metastatic foci of de novo stage IV breast cancer can bring survival benefits is currently controversial. We aimed to explore the clinicopathological factors and current status of the management of de novo stage IV breast cancer in China to provide a reference for clinical decisions.Methods:Based on the assistance of Chinese Society of Breast Surgery, a retrospective study was conducted to analyze the clinical data of patients with de novo stage IV breast cancer in 33 centers from January 2017 to December 2018. The relationship between basic characteristic (age, menstrual status, family history, reproductive history, pathological type, estrogen receptor [ER] status, progesterone receptor [PR] status, human epidermal growth factor receptor 2 [HER2] status, Ki-67 percentage, and molecular subtype), and metastasis sites (lung metastasis, liver metastasis, and bone metastasis) was examined by Pearson Chi-square tests.Results:A total of 468 patients with de novo stage IV breast cancer were enrolled. The median age of the enrolled patients was 51.5 years. The most common pathological type of primary lesion was invasive carcinoma (97.1%). Luminal A, luminal B, HER2 overexpressing, and triple-negative subtypes accounted for 14.3%, 51.8%, 22.1%, and 11.8% of all cases, respectively. Age, PR status, and HER2 status were correlated with lung metastasis (χ2 = 6.576, 4.117, and 8.643 and P = 0.037, 0.043, and 0.003, respectively). Pathological type, ER status, PR status, and molecular subtype were correlated with bone metastasis (χ2 = 5.117, 37.511, 5.224, and 11.603 and P = 0.024, <0.001, 0.022, and 0.009, respectively). Age, PR status, HER2 status, Ki-67 percentage, and molecular subtype were correlated with liver metastasis (χ2 = 11.153, 13.378, 10.692, 21.206, and 17.684 and P = 0.004, <0.001, 0.001, <0.001, and 0.001, respectively). Combined treatment with paclitaxel and anthracycline was the most common first-line chemotherapy regimen for patients with de novo stage IV breast cancer (51.7%). Overall, 91.5% of patients used paclitaxel-containing regimens. Moreover, 59.3% of hormone receptor-positive patients underwent endocrine therapy.Conclusions:In 2018, 1.07% of patients from all studied centers were diagnosed with de novo stage IV breast cancer. This study indicated that 95.1% of patients received systemic therapy and 54.2% of patients underwent surgical removal of the primary lesion in China.

Platelet Membrane-Coated and VAR2CSA Malaria Protein-Functionalized Nanoparticles for Targeted Treatment of Primary and Metastatic Cancer.

Metastasis is the main cause of death in cancer patients. The efficacy of pharmacological therapy for cancer is limited by the heterogeneous nature of cancer cells and the lack of knowledge of microenvironments in metastasis. Evidence has shown that activated platelets possess both tumor-homing and metastasis-targeting properties via intrinsic cell adhesion molecules on platelets, and malaria protein VAR2CSA is able to specifically bind to oncofetal chondroitin sulfate, which is overexpressed on cancer cells with both epithelial and mesenchymal phenotypes. Inspired by these mechanisms, we developed a recombinant VAR2CSA peptide (rVAR2)-modified activated platelet-mimicking nanoparticles (rVAR2-PM/PLGA-ss-HA) by coating the surface of disulfide-containing biodegradable PLGA conjugate nanoparticles (PLGA-ss-HA) with an activated platelet membrane. The results demonstrated that the engineered 122 nm rVAR2-PM/PLGA-ss-HA inherited the innate properties of the activated platelet membrane and achieved enhanced homing to both primary and metastatic foci. The nanoparticles were endocytosed and responded to a high intracellular concentration of reduced glutathione, resulting in nanoparticle disintegration and the release of chemotherapeutic drugs to kill tumor cells. Thus, rVAR2-decorated activated platelet-targeting nanoparticles with controlled drug release provide a promising drug delivery strategy for efficient treatment of primary and metastatic cancer.

Hyaluronan heterogeneity in pancreatic ductal adenocarcinoma, primary tumors, and sites of metastasis.

e16231 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers with an estimated five-year survival rate of 10%. The dense desmoplastic stroma in PDAC contributes to its aggressive nature and treatment resistance. Among the components comprising the stroma, hyaluronan (HA) has been demonstrated to play a critical role in tumor progression and survival. Previous preliminary studies have suggested differences in HA expression in primary and metastatic foci in PDAC. However, the effects of treatment and location of HA expression as well as the role of CD44, a known receptor for HA, on HA as a biomarker signature remain unknown. Thus, we investigated the potential of HA as a biomarker in primary PDAC and metastases. Methods: PDAC tissue from primary (n = 43) and metastatic (n = 66) sites were obtained from Cedars-Sinai Medical Center along with associated clinical data. Tissue slides were stained with H&amp;E, HA using a histochemical assay, and CD44 by immunohistochemistry. HA staining was scored according to the proportion of stromal staining at an intensity greater than the background stroma. HA status was defined as ≥ 50% staining being HA high and &lt; 50% as being HA low. CD44 staining was recorded as an H-score (percentage of tumor cells staining multiplied by intensity of staining on a scale from 0 to 3). Associations between HA levels and the requested variables were examined with t-test, Wilcoxon rank-sum test, Chi-squared test, Fisher’s exact test, or Cox regression model where appropriate. Kaplan-Meier curves were created to assess progression free survival and overall survival. Analyses were performed using SAS 9.4 with two-sided tests and a significance level of 0.05. Results: HA score was significantly higher in primary PDAC tissue compared to sites of metastases (p = 0.0148). Within the metastases, HA score was significantly higher in liver metastasis compared to other sites of metastasis (p = 0.0478). In the liver metastasis tissue, HA score trended lower in patients with previously treated tissue compared to treatment naïve tissue (p = 0.0622). In the treatment naive liver metastasis cohort, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status (p = 0.0032 and p = 0.0478, respectively). Using HA score and CD44 in a Cox regression model demonstrated that for every one unit increase in HA score, the risk for recurrence/progression increased by 4.4% at any fixed point in time, adjusting for CD44 score (p = 0.0049). Conclusions: HA score is variable between primary PDAC, PDAC metastatic to the liver, and PDAC metastatic to other sites. Within liver metastases, patients with HA high status had decreased progression free survival and overall survival compared to patients with HA low status. HA levels can serve as a potential biomarker to guide pancreatic cancer treatments and trial design for agents targeting the stroma.

Clinical Observation of Three Dimensional Conformal Intensity-modulated Radiotherapy Combined with Cisplatin Chemotherapy and Nituzumab in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Objective . To observe the clinical effect of three-dimensional conformal intensity-modulated radiotherapy combined with cisplatin chemotherapy and nituzumab in the treatment of locally advanced nasopharyngeal carcinoma. Selection method. From January 2016 - January 2019 in fujian province third hospital treated 62 cases of patients with locally advanced nasopharyngeal carcinoma were selected as the research objects, which randomly divided into observation group (31 cases) and control group (31 cases). Control group were treated by three-dimensional conformal intensity modulated radiation therapy synchronous paclitaxel and cisplatin chemotherapy, observers group on the basis of control group, this bead sheet were given, and the treatment. Clinical efficacy and adverse reactions of 2 groups were compared. Results . The CR rate of nasopharyngeal primary foci 2 months after radiotherapy, the CR rate of cervical lymph node, the control rate of primary foci 1 year after radiotherapy . The rate of no distant metastasis in observation group were all higher than those in control group (P 0.05). Conclusion. Three-dimensional conformal intensity-modulated radiotherapy combined with cisplatin chemotherapy and nituzumab in the treatment of advanced nasopharyngeal carcinoma can improve the short-term efficacy, but in terms of improving the long-term efficacy and survival rate of patients, further follow-up investigation is needed.

Great Crossings: Indians, Settlers, and Slaves in the Age of Jackson

In Great Crossings, Christina Snyder documents the creation, development, and eventual closure of the Choctaw Academy located in Great Crossings, Kentucky. US expansion, racist rhetoric, and a Jacksonian ideology of white American identity during the era of forced Indian removal are all common themes as Snyder uses the Choctaw Academy and its locale to chart an “intimate view of the ambitions and struggles of Indians, settlers and slaves” in the antebellum period (16). Great Crossings itself illustrated the transformation of American identity, from one that the Indian students at the Choctaw Academy could personally join in constructing, to one of racial exclusion and forced removal. With a compelling narrative and an intertwined history located at the heart of the continent, Snyder defines a changing America through the eyes of Choctaw Academy students.The residents, enslaved peoples, instructors, and Native students of the school and community illustrate the complexities and contradictions inherent in the tri-racial antebellum South. Choctaw Academy founder Richard Johnson illustrates this dichotomy, as he championed the education and so-called civilization of Native communities, publicly displayed his relationship with enslaved Black woman Julia Chinn, and even covertly used the Choctaw Academy to educate their two daughters while he actively participated in the slave market and plantation economy. Native students also complicated the racial and social characteristics in Great Crossings, as they were often connected to elite families in their nation and refused to be treated as a racial underclass. Snyder deftly illustrates the agency of Indigenous and Black actors as they “asserted that they were not savages or wenches, but rather gentlemen and ladies” (123).The primary foci of Snyder’s work are the Choctaw and other Native students at Great Crossings. Choctaws themselves were at the “vanguard of the education movement,” but many other Indian communities from throughout the eastern Plains and Trans-Appalachia sent young men to the Choctaw Academy (13). Hundreds of students attended the Choctaw Academy, and Snyder painstakingly details the lived experiences of these students as they “became a different type of warrior,” one that used their education at the Choctaw Academy to advance themselves and defend their nations from American predation (40). Students learned skills such as Italian bookkeeping and surveying, while a select few learned advanced degrees in law and medicine. By the 1830s, however, forced removal and the hardening of racial identities in the United States had repercussions at the Choctaw Academy, as education now included manual labor as well as poorer food and lodging. Snyder catalogs how the students responded to these shifts and their agency as they fought to change the Choctaw Academy, shutter it, or go home. As Snyder notes, these battles over the curriculum of the school illustrate the influence and agency of students like Potawatomi Joseph Bourassa and Choctaw William Trahern. As Johnson fell into debt, he “increasingly relied on them to act as spokesmen, monitors, and teachers” to maintain school funding, and these students demanded he provide them access to advanced studies in return (183).The dissolution of the Choctaw Academy in 1848, and the forced removal of Choctaws to Indian Territory, was not the death knell of Choctaw educational programs. Instead, Snyder’s final chapters describe the considerable educational advances in Choctaw country, the foundation of public-school systems, elite academies, and women’s education that preceded the educational revolutions in most of the United States. Leaders of the new school systems, led by Peter Pitchlynn and other Choctaw Academy graduates, changed American conceptions of educational pageantry, such as the annual examinations of students at Choctaw Academy, from a “showcase for a white audience” to a festive event for students’ families (276).Snyder’s concluding chapter reads more as an epilogue, detailing the lives of Choctaw Academy graduates after the Civil War, and it connects the history of Indian country to that of the development of the United States. Through her history of the Choctaw Academy, Snyder uncovers a multicultural and intertwined American South, in which Indian students, white settlers, and enslaved Blacks navigated the “thousand anxieties over race, citizenship, and America’s destiny” that consumed the antebellum era (17). Aptly named, Snyder’s book illustrates the necessary inclusion of Native voices, agency, and dispossession in the creation of an American identity.

Spousal Dementia Grief: A Research Report from the Two-Track Model of Dementia Grief Project

Caregiving for a loved one suffering from cognitive decline involves coping with many challenges and losses. This experience increases the risk of worsening the physical and mental health of the caregiver and has been the subject of a substantial number of studies focusing on the stress and burden of the primary caretaker. Theory and research on the grief reactions experienced by the family members, however, continues to lag in terms of the attention given to the behavioral and psychological burden of caregivers. This study aimed for a deeper understanding of the emotional processes in an individual involved in caring and caregiving for a spouse suffering from cognitive decline, through the prism of the Two-Track Model of Dementia Grief (TTM-DG). The TTM-DG emphasizes the continuous emotional attachment to the loved one suffering from cognitive decline (Track II), along with a medico-psychiatric perspective associated with stress, trauma, and changes in life (Track I). In this research project, we examined the degree to which spouses of cognitively impaired, deceased, and healthy partners showed differences and perceptible patterns considering the elements associated with the model and their interrelationship. These elements include behavioral characteristics of the clinical patients suffering from cognitive decline, objective circumstances of the caregiving situation, personality measures of attachment of the caring spouse, and a range of measures assessing psychological well-being and spousal relationship. The current study is a part of a larger ongoing project in Israel to address loss and grief among caregiving family members whose loved ones suffer from cognitive decline. The findings reported in the current paper are based on data derived from self-report questionnaires (i.e., socio-demographic variables, problematic behaviors in patients, objective burden, social support, physical health status, attachment patterns, depression, dementia grief, and relationship satisfaction). Participants in the sample size of 49 came from three groups: (a) spouses of patients suffering from cognitive decline, (b) widowers of deceased dementia sufferers, (c) and a control group of similarly aged participants whose spouses have no cognitive or functional impairment. Examination of the research hypotheses was done by running correlations and one/two-way analyses of variance (ANOVA). Behavioral disorders in the affected spouse correlated positively with the objective burden of the caring/caregiving spouse and with outcome variables. That is, biopsychosocial functioning (Track I) and the ongoing attachment bond with the ill spouse (Track II); objective burden correlated positively with depression and dementia grief, but not with relationship satisfaction; poor caregiver’s physical health was associated positively with depression and dementia grief, but not with relationship satisfaction; social support correlated positively with low levels of depression and dementia grief, as well as to the higher degree of relationship satisfaction; insecure attachment was found to correlate positively with depression and dementia grief, but not with relationship satisfaction. Spouses of cognitively impaired patients reported more difficulties in outcome variables compared to the control group; widowers of deceased dementia sufferers reported higher levels of dementia grief and depression than the control group. In terms of outcome measures, there was no difference between widowers and spouses of cognitively impaired patients. Among the control group participants, there was no difference between secure and insecure attachment on outcome variables. A significant difference between secure and insecure attachment on outcome variables was observed among spouses of cognitively impaired patients and widowers so that insecure participants reported higher levels of distress. The findings of the present study constitute the initial empirical evidence for the utility of the TTM-DG and support the transition of the field of loss and bereavement, which emphasizes the importance of the emotional attachment with the loved one as one of the primary foci of the process of coping with the loss. Furthermore, the findings highlight factors that contribute to the health and emotional resilience (secure attachment style, perceived social support, etc.) and provide a framework that can assist in the process of clinical assessment and intervention to improve the quality of life of caregivers whose loved one suffers from cognitive decline.

Mutational concordance analysis provides supportive information for double cancer diagnosis

BackgroundMutation analysis using next-generation sequencing highlights the features of tumors with somatic alterations. However, the mutation profile of double cancer remains unclear. Here, we analyzed tumors derived from the same patient using whole exome sequencing (WES) to investigate the coherence of somatic mutations in double cancer.MethodsFirst, the tumor mutational burden (TMB) was investigated using WES of 5521 tumor specimens from a Japanese pan-cancer cohort. The frequencies of mutation concordance were then compared in these cancers. Finally, we calculated the expected value of mutational concordance fitting a Poisson distribution to determine the relationship between double and metastatic cancers.ResultsIn all, 44, 58, and 121 paired samples were diagnosed as double cancer, multifocal lesions (derived from identical tissues), and metastasis, respectively. Our analysis revealed that common somatic mutations were almost entirely absent in double cancer, whereas primary tumors and metastatic foci harbored several identical alterations. Concordance of the mutation profile in the same patient reflects the tumor origin and development, suggesting the potential for identifying double cancer based on common somatic mutations. Furthermore, according to a Poisson distribution, double cancer could be discriminated based on paired samples from the same patient. The probability of double cancer with more than 10 mutations was ≤1 part-per-billion (ppb, 10− 9). In multifocal lesions, 74% of tumor pairs accumulated ≤10 common mutations, implying a difference in tumor origin within identical tissues.ConclusionsThese findings indicate that counting common somatic mutations can indicate the differences in origin between tumors derived from the same patient. Our mutation coherence analysis can thus provide beneficial information for diagnosing double cancer.

Rapid On-Site Cytologic Evaluation: A Feasibility Study Using Ancillary Interventional Pulmonary Personnel

Background: Ancillary health professionals helping in a procedural service is a common practice everywhere. Objectives: This was a proof-of-concept study to assess feasibility of using ancillary personnel for rapid on-site cytologic evaluation (ROSE) at interventional pulmonary procedures. Methods: After a training interval, a respiratory therapist (RT) performed ROSE on consecutive interventional pulmonary specimens. Sample sites included lymph nodes, lung, liver, and the left adrenal gland. RT findings were subsequently correlated with blinded cytopathology-performed ROSE and with final histopathology results, with primary foci of adequacy and the presence or absence of malignancy. Results: Seventy consecutive cases involved 163 separate sites for ROSE analysis. Adequacy: There was a high level of concordance between RT-performed ROSE (RT-ROSE) and cytopathology ROSE (CYTO-ROSE). They agreed upon the adequacy of 159 specimens. The Cohen’s κ coefficient ± asymptotic standard error (ASE) was 0.74 ± 0.175, with p < 0.0001. Malignancy: RT-ROSE concurred highly with CYTO-ROSE, with agreement on 150 (92%) of the 163 specimens. Cohen’s κ coefficient ± ASE was 0.83 ± 0.045, with p < 0.0001. When the comparison was for malignancy by case rather than individual site, Cohen’s κ coefficient ± ASE was 0.68 ± 0.08, with p < 0.0001. Conclusion: This study demonstrates that ancillary personnel supporting an interventional pulmonary service can be trained to perform initial ROSE. Cytopathology can be called after sampling and staining have produced adequate samples. This setup streamlines ROSE evaluation with regard to time and cost.

Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer

Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.

Thermochemistry of Tungsten-3p Elements for Density Functional Theory, Caveat Lector!

There are two primary foci in this research on WE (E = Si, P, and S) bonds: prediction of their bond dissociation enthalpies (BDEs), including σ- and π-bond energy components, and assessing the uncertainty of these BDE predictions for levels of theory commonly used in the literature. The internal standards for computational accuracy include metal-element bond lengths (mean absolute error = 1.8 ± 1.2%), main group homolog BDEs versus higher levels of ab initio theory (W1U and G4 BDEs, R2 = 0.98), and DLPNO-CCSD(T)/def2-QZVPP calculations for metal-ligand BDEs (R2 = 0.88). The W═Si first π-bond is underreported for density functional theory (DFT)/MP2 methods versus DLPNO-CCSD(T), while the latter shows negligible strength for the W;Si second π-bond, consistent with the literature. This research highlights clear issues with the underlying assumptions required for the use of perturbation theory methods for the fragments derived from W-P homolysis. The difficulties associated with modeling the metal thermochemistry with DFT (and MP2) levels of theory are manifest in the broad standard deviations observed. However, the average BDEs found using 48 popular DFT and MP2 levels of theory are reliable, 10.8 ± 6.8% mean absolute error (with W-P removed) versus DLPNO-CCSD(T), with the caveat that the individual basis set/pseudopotential/valence basis set combination can vary wildly. Analysis of the absolute error percentages with respect to the level of theory indicates little benefit to going higher on Jacob's Ladder, as simpler methods have lower error versus high-level ab initio techniques such as G4 and DLPNO-CCSD(T).

Work Patterns and Financing College: A Descriptive Regional Report regarding Students at Hispanic-Serving Institutions in New Mexico and Texas

College students at 14 Hispanic-Serving Institutions (HSIs) in New Mexico and Texas were surveyed about their experiences in and perceptions of higher education. Three primary foci were students’ employment status, work commitments, and means of financing college. Most of the informants reported working while in college and, similar to previously reported national averages, 69.4% of the informants were actively employed. Twice as many of the actively employed informants worked off campus as on campus and over three-quarters of employed students reported working part-time. There were no significance differences in these areas by gender, ethnicity, or even when broken out as Latinas, Latinos, non-Hispanic females and non-Hispanic males but students of non-traditional age reported a work commitment at significantly higher levels. For hours of work per week, there were also no significant differences by gender, ethnicity, and for the four possible subsets (Latinas, Latinos, etc.) but being a non-traditional aged student and being married/cohabiting were associated with working more hours at statistically significant levels. Students at the HSIs in New Mexico also reported more hours of work at statistically significant levels. Differences by gender, ethnicity, age, relational status, and state were found for means of funding college.