CD 10 expression intensity in various grades and stages of urothelial carcinoma of urinary bladder.

PubMed

Atique, Muhammad; Abbasi, Muhammad Sajjad; Jamal, Shahid; Khadim, Muhammad Tahir; Akhtar, Farhan; Jamal, Nighat

2014-05-01

To evaluate CD10 expression in urothelial carcinoma of the urinary bladder and the association of immunohistochemical (IHC) CD10 expression intensity with grade and stage. Descriptive cross-sectional analytical study. Armed Forces Institute of Pathology, Rawalpindi, from January to December 2011. Fifty consecutive cases of urothelial bladder carcinomas, obtained through transurethral resections, were included in this study. Hematoxylin-eosin (HE) stained sections from each case were re-evaluated histopathologically according to WHO 2004 grading system. The TNM system was used for pathologic staging. On selected slides IHC CD10 marker was applied and a semiquantitative scoring for its expression based on the percentage of positive cells and intensity was performed. Data was entered and analysed on SPSS version 17. Fisher's exact test was used to compare grades, stages of urothelial carcinoma with CD 10 expression and age groups. P < 0.05 was taken as level of significance. Urothelial carcinoma was more common in males. The male to female ratio was 9:1. The older patients > 50 years had higher grade and stage as compared to the younger patients. All cases of high grade urothelial carcinoma showed higher positivity for CD 10. Twenty cases (86.95%) of high grade urothelial carcinoma were positive with +2 immunostaining while 3 cases (13.04 %) were positive with +1 staining. None of the tumors of stage pTa was positive for CD 10 expression. Of all patients with stage pT 1 tumor, 1 case (5.3%) was CD 10 negative and 17 cases (89.9%) were CD 10 positive having +1 staining with 5 - 50% staining and 1 case (5.3%) had +2 staining with more then 50% expression. Out of all patients with stage pT 2, no tumor was CD 10 negative, 3 (13.6%) patients were CD 10 positive with +1 staining and 19 (86.4%) with stage pT 2 tumor had stained positive with +2 staining. CD 10 expression was greater in high grade and invasive urothelial carcinomas; it may be associated with tumor progression

Four cycles of paclitaxel and carboplatin as adjuvant treatment in early-stage ovarian cancer: a six-year experience of the Hellenic Cooperative Oncology Group

PubMed Central

Bamias, Aristotle; Papadimitriou, Christos; Efstathiou, Eleni; Rodolakis, Alexandros; Vlahos, Georgios; Voulgaris, Zannis; Bozas, Georgios; Fountzilas, Georgios; Aravantinos, Gerassimos; Razis, Evagelia; Gika, Dimitra; Dimopoulos, Meletios A

2006-01-01

Background Surgery can cure a significant percentage of ovarian carcinoma confined to the pelvis. Nevertheless, there is still a 10–50% recurrence rate. We administered paclitaxel/carboplatin as adjuvant treatment in early-stage ovarian carcinoma. Methods Patients with stages Ia or Ib, Grade 2 or 3 and Ic to IIb (any grade) were included. Patients were treated with 4 cycles of Paclitaxel 175 mg/m2 and Carboplatin [area under the curve (AUC) 6 (Calvert Formula)] every 3 weeks. Results Sixty-nine patients with no residual disease following cytoreductive surgery and minimal or modified surgical staging were included in this analysis. Grade 3 or 4 neutropenia occured in 29.9% of patients, while neutropenic fever was reported in 4.5%. Neurotoxicity (all Grade 1 or 2) was reported in 50% of cases. Median follow-up was 62 months. 5-year overall survival (OS) and relapse-free survival (RFS) were: 87% (95% confidence intervals [CI]: 78–96) and 79% (95% CI: 69–89), respectively. Significantly fewer patients with stages Ic-IIb and tumor grade 2 or 3 achieved a 5-year RFS than patients with only one of these two factors (73% vs 92%, p = 0.03). Conclusion Paclitaxel/Carboplatin chemotherapy is a safe and effective adjuvant treatment in early-stage ovarian carcinoma. Patients with stages Ic-IIb and tumor grade 2 or 3 may benefit from more extensive treatment. PMID:16999858

Tier 1 and Tier 2 Early Intervention for Handwriting and Composing

ERIC Educational Resources Information Center

Berninger, Virginia W.; Rutberg, Judith E.; Abbott, Robert D.; Garcia, Noelia; Anderson-Youngstrom, Marci; Brooks, Allison; Fulton, Cynthia

2006-01-01

Three studies evaluated Tier 1 early intervention for handwriting at a critical period for literacy development in first grade and one study evaluated Tier 2 early intervention in the critical period between third and fourth grades for composing on high stakes tests. The results contribute to knowledge of research-supported handwriting and…

Gene Expression Analysis of Early Stage Endometrial Cancers Reveals Unique Transcripts Associated with Grade and Histology but Not Depth of Invasion

PubMed Central

Risinger, John I.; Allard, Jay; Chandran, Uma; Day, Roger; Chandramouli, Gadisetti V. R.; Miller, Caela; Zahn, Christopher; Oliver, Julie; Litzi, Tracy; Marcus, Charlotte; Dubil, Elizabeth; Byrd, Kevin; Cassablanca, Yovanni; Becich, Michael; Berchuck, Andrew; Darcy, Kathleen M.; Hamilton, Chad A.; Conrads, Thomas P.; Maxwell, G. Larry

2013-01-01

Endometrial cancer is the most common gynecologic malignancy in the United States but it remains poorly understood at the molecular level. This investigation was conducted to specifically assess whether gene expression changes underlie the clinical and pathologic factors traditionally used for determining treatment regimens in women with stage I endometrial cancer. These include the effect of tumor grade, depth of myometrial invasion and histotype. We utilized oligonucleotide microarrays to assess the transcript expression profile in epithelial glandular cells laser microdissected from 79 endometrioid and 12 serous stage I endometrial cancers with a heterogeneous distribution of grade and depth of myometrial invasion, along with 12 normal post-menopausal endometrial samples. Unsupervised multidimensional scaling analyses revealed that serous and endometrioid stage I cancers have similar transcript expression patterns when compared to normal controls where 900 transcripts were identified to be differentially expressed by at least fourfold (univariate t-test, p < 0.001) between the cancers and normal endometrium. This analysis also identified transcript expression differences between serous and endometrioid cancers and tumor grade, but no apparent differences were identified as a function of depth of myometrial invasion. Four genes were validated by quantitative PCR on an independent set of cancer and normal endometrium samples. These findings indicate that unique gene expression profiles are associated with histologic type and grade, but not myometrial invasion among early stage endometrial cancers. These data provide a comprehensive perspective on the molecular alterations associated with stage I endometrial cancer, particularly those subtypes that have the worst prognosis. PMID:23785665

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

PubMed Central

Winter-Roach, Brett A; Kitchener, Henry C; Lawrie, Theresa A

2014-01-01

trials were included in the meta-analyses and we considered them to be at a low risk of bias. Meta-analysis of five-year data from three trials indicated that women who received adjuvant platinum-based chemotherapy had better overall survival (OS) than those who did not (1008 women; hazard ratio (HR) 0.71; 95% confidence interval (CI) 0.53 to 0.93). Likewise, meta-analysis of five-year data from four trials indicated that women who received adjuvant chemotherapy had better progression-free survival (PFS) than those who did not (1170 women; HR 0.67; 95% CI 0.53 to 0.84). The trials included in these meta-analyses gave consistent estimates of the effects of chemotherapy. In addition, these findings were robust over time (10-year PFS: two trials, 925 women; HR 0.67; 95% CI 0.54 to 0.84). Subgroup analysis suggested that women who had optimal surgical staging of their disease were unlikely to benefit from adjuvant chemotherapy (HR for OS 1.22; 95% CI 0.63 to 2.37; two trials, 234 women) whereas those who had sub-optimal staging did (HR for OS 0.63; 95% CI 0.46 to 0.85; two trials, 772 women). One trial showed a benefit from adjuvant chemotherapy among women at high risk (HR for OS 0.48; 95% CI 0.32 to 0.72) but not among those at low/medium risk (HR for OS 0.95; 95% CI 0.54 to 1.66). However, these subgroup findings could be due to chance and should be interpreted with caution. Authors’ conclusions Adjuvant platinum-based chemotherapy is effective in prolonging the survival of the majority of patients who are assessed as having early (FIGO stage I/IIa) epithelial ovarian cancer. However, it may be withheld from women in whom there is well-differentiated encapsulated unilateral disease (stage 1a grade 1) or those with comprehensively staged Ib, well or moderately differentiated (grade 1/2) disease. Others with unstaged early disease or those with poorly differentiated tumours should be offered chemotherapy. A pragmatic approach may be necessary in clinical settings where

Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: A predictors- and nomogram-based analyses.

PubMed

Bogani, Giorgio; Tagliabue, Elena; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Casarin, Jvan; Chiappa, Valentina; Dondi, Giulia; Leone Roberti Maggiore, Umberto; Scaffa, Cono; Borghi, Chiara; Montanelli, Luca; Lorusso, Domenica; Raspagliesi, Francesco

2017-10-01

To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively (p=0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement (p<0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. Copyright © 2017 Elsevier Inc. All rights reserved.

Serum TIMP1 and TIMP2 concentration in patients with different grades of meningioma.

PubMed

Mashayekhi, Farhad; Saberi, Alia; Mashayekhi, Sohail

2018-07-01

Meningiomas are common primary brain tumors that constitute about 13% of all intracranial tumors. Matrix metalloproteinase-9 (MMP-9) is able to degrade the extracellular matrix and basement membrane leading to cancer cell invasion and metastasis. MMPs are specifically inhibited by a family of small extracellular proteins known as the tissue inhibitors of metalloproteinases (TIMPs). The objective of this project was to evaluate serum concentration of TIMP-1 and TIMP-2 in patients with different grades of meningioma. Ninety samples from different stages of patients with meningitis (42 cases of grade I, 28 grade II, 20 grade III) and 51 samples from normal healthy were included in this study. Total protein concentration (TPC) and the level TIMP-1 and TIMP-2 serum were determined by Bio-Rad protein assay based on the Bradford dye procedure and enzyme-linked immunosorbent assay (ELISA), respectively. No significant change in the TPC was seen in the serum of patients with meningioma when compared with normal controls. Results obtained demonstrated that all serum samples presented TIMP-1 and TIMP-2 expression, whereas, starting from grade I to III meningiomas, a significant decrease of TIMP-1 and TIMP-2 expression was observed as compared to controls. The results of this study show that a low expression of TIMP1 and TIMP2 is correlated with advanced stages of meningioma. It is also concluded that the detection of serum TIMP1 and TIMP2 may be useful in classifying different grades of meningioma. Copyright © 2018 Elsevier B.V. All rights reserved.

The relation between Ring Box-1 protein overexpression and tumor grade and stage in bladder urothelial cell carcinoma.

PubMed

Celik, Zeliha Esin; Kaynar, Mehmet; Karabagli, Pinar; Gergerlioglu, Nursadan; Goktas, Serdar

2017-12-06

Ring Box Protein-1 (RBX-1), a component of SCF E3 ubiquitin ligases, has a crucial role in bladder urothelial cell carcinoma (UCC) carcinogenesis and progression. In the present study, it is aimed to determine the expression of RBX-1 protein in bladder UCC and the association between tumor grade, stage and RBX-1 expression. Ninety UCC samples and 20 samples containing foci of normal bladder urothelium were recruited and analyzed immunohistochemically in terms of RBX-1 expression. Immuno-reactivity scoring system (IRS) was used to determine RBX-1 expression levels. RBX-1 overexpression was associated with high tumor grade (p= 0.001) and advanced stage (p= 0.001). pT1 tumors showed higher RBX-1 expression than pTa tumors. pT2 tumors showed not only higher expression than pTa tumors but also higher expression than the total of pTa and pT1 groups combined. There was no statistically significant relation between RBX-1 expression and patient gender (p= 0.116) or age (p= 0.191). In bladder UCC, RBX-1 overexpression is associated with high tumor grade and advanced stage and represents biological potential of invasiveness and aggressive disease. Results of the present study have to be supported with further studies to reveal clinical and therapeutic implications of RBX-1 overexpression in bladder UCC.

Prognosis of women with stage I endometrioid endometrial cancer and synchronous stage I endometrioid ovarian cancer.

PubMed

Matsuo, Koji; Machida, Hiroko; Frimer, Marina; Marcus, Jenna Z; Pejovic, Tanja; Roman, Lynda D; Wright, Jason D

2017-12-01

Synchronous endometrial and ovarian cancer with endometrioid histology at two cancer sites typically presents with early-stage disease and is thought to have a good prognosis. We examined the survival of women with early-stage endometrioid endometrial cancer who had synchronous early-stage endometrioid ovarian cancer. This is a retrospective case-control study examining the Surveillance, Epidemiology, and End Result Program between 1973 and 2013. Survival of women with stage I endometrioid endometrial cancer with stage I endometrioid ovarian cancer (n=839) were compared to women with stage I endometrioid endometrial cancer without synchronous ovarian cancer (n=123,692) after propensity score matching. Women with synchronous stage I endometrioid ovarian cancer were more likely to be diagnosed recently, be younger, have stage IA disease, grade 1 tumors, to have undergone lymphadenectomy, and were less likely to receive radiotherapy compared to those without synchronous ovarian cancer (all, P<0.001). In a propensity score matched model, the presence of synchronous ovarian cancer was not associated with endometrial cancer-specific survival (10-year rates 96.0% versus 95.3%, P=0.97) or overall survival (85.6% versus 87.2%, P=0.10). Among tumors with concordant grades at the two cancer sites, survival was similar regardless of presence of synchronous ovarian tumors (grade 1 tumors, 10-year rate for overall survival, 88.2% versus 89.1%, P=0.40; and grade 2 tumors, 84.0% versus 85.8%, P=0.78). Women with stage I endometrioid endometrial cancer with synchronous stage I endometrioid ovarian cancer have a survival outcome similar to those with stage I endometrioid endometrial cancer without synchronous ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior

PubMed Central

Morin, Emilie; Cheng, Sonia; Mete, Ozgur; Serra, Stefano; Araujo, Paula B; Temple, Sara; Cleary, Sean; Gallinger, Steven; Greig, Paul D; McGilvray, Ian; Wei, Alice; Asa, Sylvia L; Ezzat, Shereen

2013-01-01

Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel–Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not

How is anxiety related to math performance in young students? A longitudinal study of Grade 2 to Grade 3 children.

PubMed

Cargnelutti, Elisa; Tomasetto, Carlo; Passolunghi, Maria Chiara

2017-06-01

Both general and math-specific anxiety are related to proficiency in mathematics. However, it is not clear when math anxiety arises in young children, nor how it relates to early math performance. This study therefore investigated the early association between math anxiety and math performance in Grades 2 and 3, by accounting for general anxiety and by further inspecting the prevalent directionality of the anxiety-performance link. Results revealed that this link was significant in Grade 3, with a prevalent direction from math anxiety to performance, rather than the reverse. Longitudinal analyses also showed an indirect effect of math anxiety in Grade 2 on subsequent math performance in Grade 3. Overall, these findings highlight the importance of monitoring anxiety from the early stages of schooling in order to promote proficient academic performance.

Failing to progress or progressing to fail? Age-for-grade heterogeneity and grade repetition in primary schools in Karonga district, northern Malawi

PubMed Central

Sunny, Bindu S.; Elze, Markus; Chihana, Menard; Gondwe, Levie; Crampin, Amelia C.; Munkhondya, Masoyaona; Kondowe, Scotch; Glynn, Judith R.

2018-01-01

Timely progression through school is an important measure for school performance, completion and the onset of other life transitions for adolescents. This study examines the risk factors for grade repetition and establishes the extent to which age-for-grade heterogeneity contributes to subsequent grade repetition at early and later stages of school. Using data from a demographic surveillance site in Karonga district, northern Malawi, a cohort of 8174 respondents (ages 5–24 years) in primary school was followed in 2010 and subsequent grade repetition observed in 2011. Grade repetition was more common among those at early (grades 1–3) and later (grades 7–8) stages of school, with little variation by sex. Being under-age or over-age in school has different implications on schooling outcomes, depending on the stage of schooling. After adjusting for other risk factors, boys and girls who were under-age at early stages were at least twice as likely to repeat a grade as those at the official age-for-grade (girls: adjusted OR 2.06 p < 0.01; boys: adjusted OR 2.37 p < 0.01); while those over-age at early stages were about 30% less likely to repeat (girls: adjusted OR 0.65 p < 0.01; boys: adjusted OR 0.72 p < 0.01). Being under/over-age at later grades (4–8) was not associated with subsequent repetition but being over-age was associated with dropout. Other risk factors identified that were associated with repetition included both family-level factors (living away from their mother, having young children in the household, lower paternal education) and school-level factors (higher student-teacher ratio, proportion of female teachers and schools without access to water). Reducing direct and indirect costs of schooling for households; and improving school quality and resources at early stages of school may enable timely progression at early stages for greater retention at later stages. PMID:29391662

Failing to progress or progressing to fail? Age-for-grade heterogeneity and grade repetition in primary schools in Karonga district, northern Malawi.

PubMed

Sunny, Bindu S; Elze, Markus; Chihana, Menard; Gondwe, Levie; Crampin, Amelia C; Munkhondya, Masoyaona; Kondowe, Scotch; Glynn, Judith R

2017-01-01

Timely progression through school is an important measure for school performance, completion and the onset of other life transitions for adolescents. This study examines the risk factors for grade repetition and establishes the extent to which age-for-grade heterogeneity contributes to subsequent grade repetition at early and later stages of school. Using data from a demographic surveillance site in Karonga district, northern Malawi, a cohort of 8174 respondents (ages 5-24 years) in primary school was followed in 2010 and subsequent grade repetition observed in 2011. Grade repetition was more common among those at early (grades 1-3) and later (grades 7-8) stages of school, with little variation by sex. Being under-age or over-age in school has different implications on schooling outcomes, depending on the stage of schooling. After adjusting for other risk factors, boys and girls who were under-age at early stages were at least twice as likely to repeat a grade as those at the official age-for-grade (girls: adjusted OR 2.06 p < 0.01; boys: adjusted OR 2.37 p < 0.01); while those over-age at early stages were about 30% less likely to repeat (girls: adjusted OR 0.65 p < 0.01; boys: adjusted OR 0.72 p < 0.01). Being under/over-age at later grades (4-8) was not associated with subsequent repetition but being over-age was associated with dropout. Other risk factors identified that were associated with repetition included both family-level factors (living away from their mother, having young children in the household, lower paternal education) and school-level factors (higher student-teacher ratio, proportion of female teachers and schools without access to water). Reducing direct and indirect costs of schooling for households; and improving school quality and resources at early stages of school may enable timely progression at early stages for greater retention at later stages.

Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells

PubMed Central

2013-01-01

Background The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells. Methods To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0–2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway. Results Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin. Conclusions These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway

Shikonin suppresses ERK 1/2 phosphorylation during the early stages of adipocyte differentiation in 3T3-L1 cells.

PubMed

Gwon, So Young; Ahn, Ji Yun; Jung, Chang Hwa; Moon, Bo Kyung; Ha, Tae Youl

2013-08-06

The naphthoquinone pigment, shikonin, is a major component of Lithospermum erythrorhizon and has been shown to have various biological functions, including antimicrobial, anti-inflammatory, and antitumor effects. In this study, we investigated the effect of shikonin on adipocyte differentiation and its mechanism of action in 3T3-L1 cells. To investigate the effects of shikonin on adipocyte differentiation, 3T3-L1 cells were induced to differentiate using 3-isobutyl-1-methylzanthine, dexamethasone, and insulin (MDI) for 8 days in the presence of 0-2 μM shikonin. Oil Red O staining was performed to determine the lipid accumulation in 3T3-L1 cells. To elucidate the anti-adipogenic mechanism of shikonin, adipogenic transcription factors, the phosphorylation levels of ERK, and adipogenic gene expression were analyzed by Western blotting and quantitative real-time PCR. To further confirm that shikonin inhibits adipogenic differentiation through downregulation of ERK 1/2 activity, 3T3-L1 cells were treated with shikonin in the presence of FGF-2, an activator, or PD98059, an inhibitor, of the ERK1/2 signaling pathway. Shikonin effectively suppressed adipogenesis and downregulated the protein levels of 2 major transcription factors, PPARγ and C/EBPα, as well as the adipocyte specific gene aP2 in a dose-dependent manner. qRT-PCR analysis revealed that shikonin inhibited mRNA expression of adipogenesis-related genes, such as PPARγ, C/EBPα, and aP2. Adipocyte differentiation was mediated by ERK 1/2 phosphorylation, which was confirmed by pretreatment with PD98059 (an ERK 1/2 inhibitor) or FGF-2 (an ERK 1/2 activator). The phosphorylation of ERK1/2 during the early stages of adipogenesis in 3T3-L1 cells was inhibited by shikonin. We also confirmed that FGF-2-stimulated ERK 1/2 activity was attenuated by shikonin. These results demonstrate that shikonin inhibits adipogenic differentiation via suppression of the ERK signaling pathway during the early stages of adipogenesis.

Rituximab and Oblimersen in Treating Patients With Stage II, Stage III, or Stage IV Follicular Non-Hodgkin's Lymphoma

ClinicalTrials.gov

2013-01-04

Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma

Quantitative T2 Magnetic Resonance Imaging Compared to Morphological Grading of the Early Cervical Intervertebral Disc Degeneration: An Evaluation Approach in Asymptomatic Young Adults

PubMed Central

Han, Zhihua; Shao, Lixin; Xie, Yan; Wu, Jianhong; Zhang, Yan; Xin, Hongkui; Ren, Aijun; Guo, Yong; Wang, Deli; He, Qing; Ruan, Dike

2014-01-01

Objective The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI) for quantifying early cervical intervertebral disc (IVD) degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. Methods Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18–25 years) underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE) and three-plane T2-FSE, used to assign a Pfirrmann grade (I–V)) and for T2 mapping (multi-echo spin echo). T2 values in the nucleus pulposus (NP, n = 350) and anulus fibrosus (AF, n = 700) were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. Findings Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P<0.000). The NP, anterior AF and posterior AF values did not differ significantly between genders at the same anatomic level (P>0.05). T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000) but not the T2 values of the AF (P = 0.854). However, non-degenerated discs (Pfirrmann grades I and II) showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms), grade II (54.60–62.03 ms), grade III (<54.60 ms). Conclusions T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults. PMID:24498384

Quantitative T2 magnetic resonance imaging compared to morphological grading of the early cervical intervertebral disc degeneration: an evaluation approach in asymptomatic young adults.

PubMed

Chen, Chun; Huang, Minghua; Han, Zhihua; Shao, Lixin; Xie, Yan; Wu, Jianhong; Zhang, Yan; Xin, Hongkui; Ren, Aijun; Guo, Yong; Wang, Deli; He, Qing; Ruan, Dike

2014-01-01

The objective of this study was to evaluate the efficacy of quantitative T2 magnetic resonance imaging (MRI) for quantifying early cervical intervertebral disc (IVD) degeneration in asymptomatic young adults by correlating the T2 value with Pfirrmann grade, sex, and anatomic level. Seventy asymptomatic young subjects (34 men and 36 women; mean age, 22.80±2.11 yr; range, 18-25 years) underwent 3.0-T MRI to obtain morphological data (one T1-fast spin echo (FSE) and three-plane T2-FSE, used to assign a Pfirrmann grade (I-V)) and for T2 mapping (multi-echo spin echo). T2 values in the nucleus pulposus (NP, n = 350) and anulus fibrosus (AF, n = 700) were obtained. Differences in T2 values between sexes and anatomic level were evaluated, and linear correlation analysis of T2 values versus degenerative grade was conducted. Cervical IVDs of healthy young adults were commonly determined to be at Pfirrmann grades I and II. T2 values of NPs were significantly higher than those of AF at all anatomic levels (P<0.000). The NP, anterior AF and posterior AF values did not differ significantly between genders at the same anatomic level (P>0.05). T2 values decreased linearly with degenerative grade. Linear correlation analysis revealed a strong negative association between the Pfirrmann grade and the T2 values of the NP (P = 0.000) but not the T2 values of the AF (P = 0.854). However, non-degenerated discs (Pfirrmann grades I and II) showed a wide range of T2 relaxation time. T2 values according to disc degeneration level classification were as follows: grade I (>62.03 ms), grade II (54.60-62.03 ms), grade III (<54.60 ms). T2 quantitation provides a more sensitive and robust approach for detecting and characterizing the early stage of cervical IVD degeneration and to create a reliable quantitative in healthy young adults.

Massachusetts Early Warning Indicator System (EWIS). "Technical Descriptions of Risk Model Development": Early and Late Elementary Age Groupings (Grades 1-6)

ERIC Educational Resources Information Center

Massachusetts Department of Elementary and Secondary Education, 2013

2013-01-01

The Massachusetts Department of Elementary and Secondary Education (Department) created the grades 1-12 Early Warning Indicator System (EWIS) in response to district interest in the Early Warning Indicator Index (EWII) that the Department previously created for rising grade 9 students. Districts shared that the EWII data were helpful, but also…

Immersion francaise precoce: Sciences de la nature 1-7 (Early French Immersion: Natural Sciences for Grades 1-7).

ERIC Educational Resources Information Center

Burt, Andy; And Others

This curriculum guide for the natural sciences is intended for use in grades 1-7 in the early French immersion program. The guide presents the following topics: (1) a list of general objectives; (2) a list of simple skills for children aged 5-8 and for children aged 8-12; (3) activities dealing with matter and its properties, space-time, and human…

Treatment Strategies in Octogenarians with Early-Stage, High-Risk Breast Cancer

PubMed Central

Mamtani, Anita; Gonzalez, Julie J.; Neo, Dayna T.; Friedman, Robb S.; Recht, Abram; Hacker, Michele R.; Sharma, Ranjna

2018-01-01

Background Octogenarians with early-stage breast cancer often have low-risk tumor biology. However, optimal treatment strategies for those with high-risk biology remain unclear. Methods We reviewed the records of women ages 80–89 years with biopsy-proven, Stage I–II invasive breast cancer who were referred for surgical evaluation from January 2001 through December 2010. High-risk was defined as human epidermal growth factor receptor-positive (HER2+), triple-negative (TN), or histologic grade 3 disease. Results Among 178 patients, 40 (22%) were high-risk: 12 were grade 1–2 (10 HER2 +, 2 TN); 28 were grade 3 (7 HER2+, 6 TN, 15 estrogen receptor-positive (ER+)/HER2−). The high-risk group had larger tumors and more often had ductal histology and lymphovascular invasion than the low-risk group and was more likely to undergo mastectomy (18 vs. 5%, p = 0.02), radiotherapy (55 vs. 36%, p = 0.03), and chemotherapy (10 vs. 0%, p = 0.002). Endocrine therapy use was similar among ER+ patients in both groups. The four patients in the high-risk group given chemotherapy were HER2+ and received trastuzumab-based regimens, without any reported toxicities. At median follow-up of 67 months, 10% of the high-risk group had a recurrence (3 distant-only, 1 simultaneous locoregional and distant in a patient treated with mastectomy without radiotherapy). Conclusions Tailored locoregional and systemic therapy resulted in low incidence of failure in these octogenarians with high-risk cancers with low morbidity. Modern adjuvant therapies should be considered for elderly women with high-risk cancers in the absence of significant comorbidities. PMID:29427213

Involved-Field, Low-Dose Chemoradiotherapy for Early-Stage Anal Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatfield, Paul; Cooper, Rachel; Sebag-Montefiore, David

2008-02-01

Purpose: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. Methods and Materials: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m{sup 2} on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m{sup 2}/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that weremore » excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. Results: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. Conclusion: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.« less

Management of Early Stage, High-Risk Endometrial Carcinoma: Preoperative and Surgical Considerations

PubMed Central

Pettigrew, Gaetan

2013-01-01

Endometrial cancer is the most common gynecologic malignancy in the developed world. Most cases are diagnosed at an early stage and have low-grade histology, portending an overall excellent prognosis. There exists a subgroup of patients with early, high-risk disease, whose management remains controversial, as current data is clouded by inclusion of early stage tumors with different high-risk features for recurrence, unstandardized protocols for surgical staging, and an evolving staging system by which we are grouping these patients. Here, we present preoperative and intraoperative considerations that should be taken into account when planning surgical management for this population of patients. PMID:23878545

Early low-grade gastric MALToma rarely transforms into diffuse large cell lymphoma or progresses beyond the stomach and regional lymph nodes.

PubMed

Liu, Ting-Yun; Dei, Pei-Han; Kuo, Sung-Hsin; Lin, Chung-Wu

2010-06-01

Gastric mucosa-associated lymphoid tissue lymphoma (MALToma) usually presents at an early stage involving only the stomach and/or regional lymph nodes. Although a sequential transformation from low-grade gastric MALToma (GM) to high-grade GM to secondary diffuse large B-cell lymphoma (DLBCL) is commonly assumed, documented cases of transformation are rare. We aim to determine the frequency of transformation. We identified 55 early low-grade GMs, 18 early high-grade GMs, and 13 advanced GMs at the National Taiwan University Hospital from 1995 to 2005. The median follow-up time was 59 months. We found that only one early low-grade GM and two early high-grade GMs transformed into secondary DLBCLs and progressed outside the stomach and regional lymph nodes. Significantly, we identified 13 low-grade GMs that were refractory to Helicobacter eradication therapy or relapsed after initial response. All 13 cases had been followed-up for at least 3 years without development of secondary DLBCLs. The frequency of transformation for early low-grade GM was less than 2% (1/55). Although two lymphoma-unrelated mortalities were identified, none of the 55 patients with early-low grade GMs died of the disease. Compared with chronic lymphocytic leukemia, which has a 16% transformation rate and a median transformation time of 24 months, we conclude that early low-grade GM rarely transforms into secondary DLBCL or progresses beyond the stomach. Without transformation or progression, patients with early low-grade GM rarely die of the disease and should be treated conservatively. Copyright (c) 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.

Stereotactic ablative radiotherapy: a potentially curable approach to early stage multiple primary lung cancer.

PubMed

Chang, Joe Y; Liu, Yung-Hsien; Zhu, Zhengfei; Welsh, James W; Gomez, Daniel R; Komaki, Ritsuko; Roth, Jack A; Swisher, Stephen G

2013-09-15

Surgical resection has been the standard treatment for early stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. For this report, the authors explored the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC. Patients with MPLC who received SABR (50 grays [Gy] in 4 fractions or 70 Gy in 10 fractions) for the second tumor were reviewed. Four-dimensional, computed tomography-based, planning/volumetric image-guided treatment was used for all patients. Treatment outcomes/toxicities were analyzed. For the 101 patients who received SABR, at a median follow-up of 36 months and with a median overall survival (OS) of 46 months, the 2-year and 4-year in-field local control rates were 97.4% and 95.7%, respectively. The 2-year and 4-year OS rates were 73.2% and 47.5%, respectively; and the progression-free survival (PFS) rates were 67% and 58%, respectively. Patients who had metachronous tumors had better OS and PFS than patients who had synchronous tumors (2-year OS: 80.6% metachronous vs 61.5% synchronous; 4-year OS: 52.7% vs 39.7%, respectively; P = .047; 2-year PFS: 84.7% vs 49.4%, respectively; 4-year PFS: 75.6% vs 30.4%, respectively; P = .0001). For patients who either underwent surgery or received SABR for an index tumor, the incidence of grade ≥ 3 radiation pneumonitis was 3% (2 of 71 patients); however, this increased to 17% (5 of 30 patients) for those who received conventional radiotherapy for an index tumor. Other grade ≥ 3 toxicities included grade 3 chest wall pain (3 of 101 patients; 3%) and grade 3 skin toxicity (1 of 101 patients; 1%). SABR achieves promising long-term tumor control and survival and may be a potential curative treatment for early stage MPLC. © 2013 American Cancer Society.

HMGCR inhibits the early stage of PCV2 infection, while PKC enhances the infection at the late stage.

PubMed

Ma, Teng; Chen, Xinrong; Ouyang, Hongsheng; Liu, Xiaohui; Ouyang, Ting; Peng, Zhiyuan; Yang, Xin; Chen, Fuwang; Pang, Daxin; Bai, Jieying; Ren, Linzhu

2017-02-02

Porcine circovirus type 2 (PCV2) is the smallest DNA virus, which causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD). Due the small size of viral genomic DNA, PCV2 replication predominantly relies on the host factors. In this study, effects of PKC and HMGCR on PCV2 infection were evaluated using real time PCR and western blot. We found that PKC and HMGCR participated in different stages of PCV2 infection. HMGCR works on the early stage of the infection to inhibit the virus infection, while PKC enhances the infection at the late stage. Furthermore, PKC enhances PCV2 replication by activating JNK1/2 and inactivating HMGCR via regulating phosphorylation of these two proteins, while HMGCR can suppress phosphorylation of JNK1/2. The results in the present study will provide new sights in the pathogenesis of PCV2 infection, as well as interactions between host factors during PCV2 infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Elective Inguinal Node Irradiation in Early-Stage T2N0 Anal Cancer: Prognostic Impact on Locoregional Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zilli, Thomas, E-mail: Thomas.Zilli@hcuge.ch; Betz, Michael; Radiation Oncology Institute, Hirslanden Lausanne, Lausanne

2013-09-01

Purpose: To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. Methods and Materials: Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. Results: Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC,more » cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). Conclusions: In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.« less

Mucin-1 and its relation to grade, stage and survival in ovarian carcinoma patients

PubMed Central

2012-01-01

Background Mucin-1 is known to be over-expressed by various human carcinomas and is shed into the circulation where it can be detected in patient’s serum by specific anti-Mucin-1 antibodies, such as the tumour marker assays CA 15–3 and CA 27.29. The prognostic value of Mucin-1 expression in ovarian carcinoma remains uncertain. One aim of this study was to compare the concentrations of Mucin-1 in a cohort of patients with either benign or malignant ovarian tumours detected by CA 15–3 and CA 27.29. Another aim of this study was to evaluate Mucin-1 expression by immunohistochemistry in a different cohort of ovarian carcinoma patients with respect to grade, stage and survival. Methods Patients diagnosed with and treated for ovarian tumours were included in the study. Patient characteristics, histology including histological subtype, tumour stage, grading and follow-up data were available from patient records. Serum Mucin-1 concentrations were measured with ELISA technology detecting CA 15–3 and CA 27.29, Mucin-1 tissue expression was determined by immunohistochemistry using the VU4H5 and VU3C6 anti-Mucin-1 antibodies. Statistical analysis was performed by using SPSS 18.0. Results Serum samples of 118 patients with ovarian tumours were obtained to determine levels of Mucin-1. Median CA 15–3 and CA 27.29 concentrations were significantly higher in patients with malignant disease (p< 0.001) than in patients with benign disease. Paraffin-embedded tissue of 154 patients with ovarian carcinoma was available to determine Mucin-1 expression. The majority of patients presented with advanced stage disease at primary diagnosis. Median follow-up time was 11.39 years. Immunohistochemistry results for VU4H5 showed significant differences with respect to tumour grade, FIGO stage and overall survival. Patients with negative expression had a mean overall survival of 9.33 years compared to 6.27 years for patients with positive Mucin-1 expression. Conclusions This study found

Prognostic Factors, Treatment, and Outcomes in Early Stage, Invasive Papillary Breast Cancer: A SEER Investigation of Less Aggressive Treatment in a Favorable Histology.

PubMed

Fakhreddine, Mohamad H; Haque, Waqar; Ahmed, Awad; Schwartz, Mary R; Farach, Andrew M; Paulino, Arnold C; Bonefas, Elizabeth; Miltenburg, Darlene; Niravath, Polly; Butler, E Brian; Teh, Bin S

2018-06-01

Invasive papillary breast cancer (IPBCA) represents 0.5% of invasive BCA, and is thought to carry a favorable prognosis. This population-based study reports on prognostic factors, treatment, and outcomes of early-stage IPBCA to explore whether there is any evidence to support less aggressive treatment. IPBCA cases from 1990 to 2009 of the recent Surveillance, Epidemiology, and End Results were analyzed. Inclusion criteria included patients with stage T1-2, N0 IPBCA. Univariate and multivariate analyses were performed using the variables of treatment, stage, race, hormone receptor status, grade (G1-3), and age. Treatment modalities included lumpectomy alone (LA), lumpectomy with radiation treatment (LRT), and mastectomy alone (MA). Among 10,485 patients, median follow-up was 56 months. Five and 10-year overall survival (OS) were 93.1% and 76.8%, respectively. Patients treated with LRT had superior mean OS 16.8 versus 14.9 years for MA (P=0.0004) and 14.2 years for LA (P=0.0003). Improved OS also correlated with lower histologic grade (P<0.0001), lower T-stage (P<0.0001), and younger age (P<0.0001). Black patients had the worst OS (12.7 y, P<0.0001). LRT is associated with superior OS for early-stage invasive papillary BCA patients, when compared with LA or MA in this population-based study. The findings support the standard of care breast conservation approach for patients with invasive papillary BCA. Other prognostic factors associated with worse OS include increased age, higher T-stage, higher histologic grade, and black race.

Early childhood precursors and adolescent sequelae of grade school peer rejection and victimization.

PubMed

Bierman, Karen L; Kalvin, Carla B; Heinrichs, Brenda S

2015-01-01

This study examined the early childhood precursors and adolescent outcomes associated with grade school peer rejection and victimization among children oversampled for aggressive-disruptive behaviors. A central goal was to better understand the common and unique developmental correlates associated with these two types of peer adversity. There were 754 participants (46% African American, 50% European American, 4% other; 58% male; average age=5.65 at kindergarten entry) followed into seventh grade. Six waves of data were included in structural models focused on three developmental periods. Parents and teachers rated aggressive behavior, emotion dysregulation, and internalizing problems in kindergarten and Grade 1 (Waves 1-2); peer sociometric nominations tracked "least liked" and victimization in Grades 2, 3, and 4 (Waves 3-5); and youth reported on social problems, depressed mood, school adjustment difficulties, and delinquent activities in early adolescence (Grade 7, Wave 6). Structural models revealed that early aggression and emotion dysregulation (but not internalizing behavior) made unique contributions to grade school peer rejection; only emotion dysregulation made unique contributions to grade school victimization. Early internalizing problems and grade school victimization uniquely predicted adolescent social problems and depressed mood. Early aggression and grade school peer rejection uniquely predicted adolescent school adjustment difficulties and delinquent activities. Aggression and emotion dysregulation at school entry increased risk for peer rejection and victimization, and these two types of peer adversity had distinct as well as shared risk and adjustment correlates. Results suggest that the emotional functioning and peer experiences of aggressive-disruptive children deserve further attention in developmental and clinical research.

Adolescents born prematurely with isolated grade 2 haemorrhage in the early 1990s face increased risks of learning challenges.

PubMed

Vohr, Betty R; Allan, Walter; Katz, Karol H; Schneider, Karen; Tucker, Richard; Ment, Laura R

2014-10-01

To compare the impact of low-grade haemorrhage on neurocognitive function in 16-year-old adolescents born preterm, by grade of intraventricular haemorrhage, and term controls. We evaluated 338 preterm adolescents (birth weight 600-1250 g) for intelligence, executive function and memory tasks. Eleven had grade 3-4 haemorrhage, 44 had grade 2, 31 had grade 1, and 251 had no haemorrhage. Group comparisons were made with 102 term age-matched controls, and regression models used to identify the risk that low-grade haemorrhage posed for cognitive, executive function and memory deficits. Preterm adolescents with grade 2 haemorrhage had higher deficit rates of verbal intelligence, receptive vocabulary, phonemic fluency, cognitive flexibility and phonological fluency than preterm adolescents with grade 1 or no haemorrhage, compared with term controls. After excluding preterm adolescents with both grade 2 haemorrhage and cystic periventricular leukomalacia, those with isolated grade 2 haemorrhage remained at greater risk of cognitive and executive function deficits than term controls and of cognitive deficits than preterm adolescents with no haemorrhage. Our findings suggest that preterm adolescents born in the early 1990s with isolated grade 2 haemorrhage are at increased risk of learning challenges, including cognitive and executive function deficits. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Heparanase 2 expression inversely correlates with bladder carcinoma grade and stage

PubMed Central

Gross-Cohen, Miriam; Feld, Sari; Naroditsky, Inna; Nativ, Ofer; Ilan, Neta; Vlodavsky, Israel

2016-01-01

While the pro-tumorigenic function of heparanase is well taken, the role of its close homolog, heparanase 2 (Hpa2) in cancer is by far less investigated. Utilizing immunohistochemical analysis we found that Hpa2 is expressed by normal bladder transitional epithelium and its levels are decreased substantially in bladder cancer. Notably, tumors that retain high levels of Hpa2 were diagnosed as low grade (p=0.001) and low stage (p=0.002), suggesting that Hpa2 is required to preserve cell differentiation and halt cell motility. Indeed, migration of 5637 bladder carcinoma cells was attenuated significantly by exogenous addition of purified Hpa2, and over expression of Hpa2 in 5637 cells resulted in smaller tumors that were diagnosed as low grade. We also noted that tumors produced by Hpa2 over expressing cells are abundantly decorated with stromal cells and collagen deposition evident by Masson's/Trichrome staining, correlating with a marked increase in lysyl oxidase (LOX) staining. The association between Hpa2 and LOX was further confirmed clinically, because of the 16 cases that exhibited strong staining of Hpa2, 14 (87.5%) were also stained strongly for LOX (p=0.05). Collectively, our results suggest that Hpa2 functions as a tumor suppressor in bladder cancer, maintaining cellular differentiation and decreasing cell motility in a manner that appears to be independent of regulating heparanase activity. PMID:26968815

Identification of early B cell precursors (stage 1 and 2 hematogones) in the peripheral blood.

PubMed

Kurzer, Jason H; Weinberg, Olga K

2018-05-25

Differentiating malignant B-lymphoblasts from early benign B cell precursors (hematogones) is a vital component of the diagnosis of B-lymphoblastic leukaemia. It has been previously reported that only late-stage B cell precursors circulate in the peripheral blood. Consequently, flow cytometric detection of cells with immunophenotypic findings similar to earlier stage precursors in the peripheral blood justifiably raises concern for involvement by B-lymphoblastic leukaemia. We report here, however, that benign early B cell precursors can indeed be detected in the peripheral blood, thus complicating the interpretation of flow cytometric findings derived from these sample types. A retrospective search of our collective databases identified 13 cases containing circulating early stage B cell precursors. The patients ranged in age from 15 days to 85 years old. All positive cases demonstrated that the earlier B cell precursors were associated with later stage precursors, a finding that could help differentiate these cells from B-lymphoblastic leukaemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

STIM1 and TRPV4 regulate fluid flow-induced calcium oscillation at early and late stages of osteoclast differentiation.

PubMed

Li, Ping; Bian, Xueyan; Liu, Chenglin; Wang, Shurong; Guo, Mengmeng; Tao, Yingjie; Huo, Bo

2018-05-01

Bone resorption is mainly mediated by osteoclasts (OCs), whose formation and function are regulated by intracellular Ca 2+ oscillation. Our previous studies demonstrated that fluid shear stress (FSS) lead to Ca 2+ oscillation through mechanosensitive cation-selective channels. However, the specific channels responsible for this FSS-induced Ca 2+ oscillation remain unknown. In the present study, we examined the expression of several Ca 2+ channels in OCs, including STIM1, ORAI1, TRPV1, TRPV4, TRPV5, and TRPV6, by western blotting and reverse transcription-polymerase chain reaction. The results showed that STIM1 was highly expressed in early stage OCs, while TRPV4 was highly expressed in late stage OCs. We observed intracellular Ca 2+ responses in OCs that were mechanically stimulated by FSS. When we blocked STIM1-dependent store-operated Ca 2+ entry or inhibited TRPV4 using siRNA or drug inhibition, FSS-induced Ca 2+ oscillations were almost undetectable in early and late stage OCs, respectively. These results indicate that STIM1 and TRPV4 act as mechanical transduction channels for OCs during the early and late differentiation stages, respectively, suggesting that these calcium channel could serve as markers of osteoclastogenesis or bone resorption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nuclear grade and DNA ploidy in stage IV breast cancer with only visceral metastases at initial diagnosis.

PubMed

De Lena, M; Barletta, A; Marzullo, F; Rabinovich, M; Leone, B; Vallejo, C; Machiavelli, M; Romero, A; Perez, J; Lacava, J; Cuevas, M A; Rodriguez, R; Schittulli, F; Paradisco, A

1996-01-01

The presence of early metastases to distant sites in breast cancer patients is an infrequent event whose mechanisms are still not clear. The aim of this study was to evaluate the biologic and clinical role of DNA ploidy and cell nuclear grade of primary tumors in the metastatic process of a series of stage IV previously untreated breast cancer patients with only visceral metastases. DNA flow cytometry analysis on paraffin-embedded material and cell nuclear grading of primary tumors was performed on a series of 50 breast cancer patients with only visceral metastases at the time of initial diagnosis. Aneuploidy was found in 28/46 (61%) of evaluable cases and was independent of site of involvement, clinical response, time of progression and overall survival of patients. Of the 46 cases evaluable for nuclear grade, 5 (11%), 16 (35%) and 25 (54%) were classified as G1 (well-differentiated) G2 and G3, respectively. Nuclear grade also was unrelated to response to therapy and overall survival, whereas time to progression was significantly longer in G1-2 than G3 tumors with the logrank test (P < 0.03) and multivariate analysis. Our results seem to stress the difficulty to individualize different prognostic subsets from a series of breast cancer patients with only visceral metastases at initial diagnosis according to DNA flow cytometry and nuclear grade.

Correlation of the cell surface antigens with stage and grade in cancer of the bladder.

PubMed

Emmott, R C; Javadpour, N; Bergman, S M; Soares, T

1979-01-01

We examined 76 bladder tumors of various stages and grades for the presence of the ABO (H) cell surface antigen, using the specific red cell adherence technique. Of the grade I lesions studied 70 per cent were positive for the cell surface antigen and none of the 26 grade III tumors retained the antigens. When correlated with clinical stage the tumors showed no antigens for those of stages B1 to D, while 12 of 16 stage A lesions were positive for the antigen. When stage A lesions were studied and the findings were correlated with recurrence and metastasis/invasion rates the cell surface antigen was present on the initial tumor in only 1 lesion that recurred at an invasive stage. The findings of this study show that the specific red cell adherence technique may be valuable for predicting malignant potential in low grade, low stage cancer of the bladder. If supported by further investigation this technique may offer the capability of selecting low grade, low stage bladder tumors that are destined to invade or metastasize while they are at curable stages.

AJAP1 is Dysregulated at an Early Stage of Gliomagenesis and Suppresses Invasion Through Cytoskeleton Reorganization

PubMed Central

Han, Lei; Zhang, Kai-Liang; Zhang, Jun-Xia; Zeng, Liang; Di, Chun-Hui; Fee, Brian E.; Rivas, Miriam; Bao, Zhao-Shi; Jiang, Tao; Bigner, Darrell; Kang, Chun-Sheng; Adamson, David Cory

2015-01-01

SUMMARY Aims Down-regulation of AJAP1 in glioblastoma multiforme (GBM) has been reported. However, the expression profiles of AJAP1 in gliomas and the underlying mechanisms of AJAP1 function on invasion are still poorly understood. Methods The gene profiles of AJAP1 in glioma patients were studied among four independent cohorts. Confocal imaging was used to analyze the AJAP1 localization. After AJAP1 overexpression in GBM cell lines, cellular polarity, cytoskeleton distribution, and antitumor effect were investigated in vitro and in vivo. Results AJAP1 expression was significantly decreased in gliomas compared with normal brain in REMBRANDT and CGCA cohorts. Additionally, low AJAP1 expression was associated with worse survival in GBMs in REMBRANDT and TCGA U133A cohorts and was significantly associated with classical and mesenchymal subtypes of GBMs among four cohorts. Confocal imaging indicated AJAP1 localized in cell membranes in low-grade gliomas and AJAP1-overexpressing GBM cells, but difficult to assess in high-grade gliomas due to its absence. AJAP1 overexpression altered the cytoskeleton and cellular polarity in vitro and inhibited the tumor growth in vivo. Conclusions AJAP1 is dysregulated at an early stage of gliomagenesis and may suppress glioma cell invasion and proliferation, which suggests that AJAP1 may be a potential diagnostic and prognostic marker for gliomas. PMID:24483339

Diffusion tensor imaging can detect the early stages of cartilage damage: a comparison study.

PubMed

Ukai, Taku; Sato, Masato; Yamashita, Tomohiro; Imai, Yutaka; Mitani, Genya; Takagaki, Tomonori; Serigano, Kenji; Mochida, Joji

2015-02-21

In the present study, we measured damaged areas of cartilage with diffusion tensor (DT) imaging and T2 mapping, and investigated the extent to which cartilage damage could be determined using these techniques. Forty-one patients underwent arthroscopic knee surgery for osteoarthritis of the knee, a meniscus injury, or an anterior cruciate ligament injury. Preoperative magnetic resonance imaging of the knee was performed, including T2 mapping and diffusion tensor imaging. The presence of cartilage injury involving the medial and lateral femoral condyles and tibia plateau was assessed during surgery using the Outerbridge scale. The ADC, T2 values and fractional anisotropy of areas of cartilage injury were then retrospectively analysed. The ADC results identified significant differences between Outerbridge grades 0 and 2 (P = 0.041); 0 and 3 (P < 0.001); 1 and 2 (P = 0.045); 1 and 3 (P < 0.001); and 2 and 3 (P = 0.028). The FA results identified significant differences between grades 0 and 1 (P < 0.001); 0 and 2 (P < 0.001); and 0 and 3 (P < 0.001). T2 mapping identified significant differences between Outerbridge grades 0 and 2 (P = 0.032); 0 and 3 (P < 0.001); 1 and 3 (P < 0.001); and 2 and 3 (P < 0.001). Both the T2 mapping (R(2) = 0.7883) and the ADC (R(2) = 0.9184) correlated significantly with the Outerbridge grade. The FA (R(2) = 0.6616) correlated slightly with the Outerbridge grade. T2 mapping can be useful for detecting moderate or severe cartilage damage, and the ADC can be used to detect early stage cartilage damage. The FA can also distinguish normal from damaged cartilage.

Examining Text Complexity in the Early Grades

ERIC Educational Resources Information Center

Fitzgerald, Jill; Elmore, Jeff; Hiebert, Elfrieda H.; Koons, Heather H.; Bowen, Kimberly; Sanford-Moore, Eleanor E.; Stenner, A. Jackson

2016-01-01

The Common Core raises the stature of texts to new heights, creating a hubbub. The fuss is especially messy at the early grades, where children are expected to read more complex texts than in the past. But early-grades teachers have been given little actionable guidance about text complexity. The authors recently examined early-grades texts to…

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, Elizabeth, E-mail: Enichols1@umm.edu; Kesmodel, Susan B.; Bellavance, Emily

Purpose: To assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy. Patients and Methods: This was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 (<3 cm), N0 tumors. Patients received 38.5 Gy in 3.85-Gy fractions delivered twice daily. Surgery was performed >21 days after radiation therapy. Adjuvant therapy was given as per standard of care. Results: Twenty-seven patients completed treatment. With a median follow-up of 3.6 years (range, 0.5-5 years), there have been no local or regional failures.more » A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment. Conclusions: Preoperative 3-dimensional conformal radiation therapy−APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm.« less

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

PubMed

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Ocriplasmin for treatment of stage 2 macular holes: early clinical results.

PubMed

Miller, John B; Kim, Leo A; Wu, David M; Vavvas, Demetrios G; Eliott, Dean; Husain, Deeba

2014-01-01

To review clinical and structural outcomes of ocriplasmin for treatment of stage 2 macular holes. A retrospective review of the first patients with stage 2 macular holes to be treated with ocriplasmin at Massachusetts Eye and Ear Infirmary. All patients were imaged with spectral-domain optical coherence tomography (SD-OCT). Eight patients with stage 2 macular holes received a single injection of 125 μg of ocriplasmin. One patient (12.5%) demonstrated macular hole closure. The posterior hyaloid separated from the macula in six eyes (75%). All seven holes that remained open showed enlargement in hole diameters (narrowest, apical, and basal) at 1 week and 1 month. All seven were successfully closed with surgery. Ellipsoid zone disruptions were observed by OCT in four eyes (50%) and persisted throughout follow-up (more than 6 months on average). In early clinical results, the authors found a lower macular hole closure rate with ocriplasmin than previously reported. Enlargement was observed in all holes that failed to close with ocriplasmin. The authors found ellipsoid zone disruptions that persisted through 6 months of follow-up after ocriplasmin injection. Further work is needed to investigate the cause for these ellipsoid zone changes. Copyright 2014, SLACK Incorporated.

Formation of Si{sup 1+} in the early stages of the oxidation of the Si[001] 2 × 1 surface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herrera-Gomez, Alberto, E-mail: aherrerag@cinvestav.mx; Aguirre-Tostado, Francisco-Servando; Pianetta, Piero

2016-03-15

The early stages of the oxidation of the Si[001] 2 × 1 surface were studied with synchrotron radiation photoelectron spectroscopy. The analysis was based on the block approach, which is a refinement of spectra-subtraction that accounts for changes on the background signal and for band-bending shifts. By this method, it was possible to robustly show that the formation of Si{sup 1+} is due to oxygen bonding to the upper dimer atoms. Our results contrast with ab initio calculation, which indicates that the most favorable bonding site is the back-bond of the down-dimer.

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian

Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating verymore » good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.« less

Trust During the Early Stages of the 2009 H1N1 Pandemic

PubMed Central

FREIMUTH, VICKI S.; MUSA, DON; HILYARD, KAREN; QUINN, SANDRA CROUSE; KIM, KEVIN

2013-01-01

Distrust of the government often stands in the way of cooperation with public health recommendations in a crisis. The purpose of this paper is to describe the public’s trust in government recommendations during the early stages of the H1N1 pandemic and identify factors that might account for these trust levels. We surveyed 1543 respondents about their experiences and attitudes related to H1N1 influenza between June 3, 2009 and July 6, 2009, during the first wave of the pandemic using the Knowledge Networks (KN) online panel. This panel is representative of the US population, and uses a combination of random-digit dial and address-based probability sampling frames covering 99% of the US household population to recruit participants. To ensure participation of low-income individuals and those without Internet access, KN provides hardware and access to the Internet if needed. Measures included standard demographics, a trust scale, trust ratings for individual spokespersons, involvement with H1N1, experience with H1N1, and past discrimination in health care. We found that trust of government was low (2.3 out of 4) and varied across demographic groups. Blacks and Hispanics reported higher trust in government than did Whites. Of the spokespersons included, personal health professionals received the highest trust ratings and religious leaders the lowest. Attitudinal and experience variables predicted trust better than demographic characteristics. Closely following the news about the flu virus, having some self-reported knowledge about H1N1, self-reporting of local cases and previously experiencing discrimination were the significant attitudinal and experience predictors of trust. Using a second longitudinal survey, trust in the early stages of the pandemic did predict vaccine acceptance later but only for white, non-Hispanic individuals. PMID:24117390

Correlation of serum intercellular adhesion molecule 1 and vascular endothelial growth factor with tumor grading and staging in breast cancer patients.

PubMed

Haghi, Alireza Rastgoo; Vahedi, Amir; Shekarchi, Ali Akbar; Kamran, Aziz

2017-01-01

Breast cancer is the most common cancer among women. There are several prognostic factors for this disease. The aim of this article is to explore the correlation of serum level of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM1) with tumor, node, metastasis staging and grading of breast cancer. Serum samples of 51 patients with breast cancer were assessed with enzyme-linked immunosorbent assay for the level of VEGF and ICAM1 preoperatively. After the operation, histopathologic specimens stained with hematoxylin and eosin were evaluated for tumor size, histopathologic subtype, grade, lymph node, vascular and lymphatic involvement. Then, the correlation of tumor stage and grade and serum level of markers was analyzed. There was no significant correlation between serum level of markers with vascular invasions, lymph node involvement, and menstruation. There was a weak correlation between tumor size and serum level of ICAM1 with Pearson score correlation, but there was no significant correlation with VEGF. There was no significant correlation between tumor grading and staging with the level of markers. There was a significant correlation between the level of VEGF and ICAM1 and histologic type of tumors in invasive through in situ tumors. Levels of VEGF and ICAM1 can be used as a predictor of tumor invasion and also for target therapy.

Immersion francaise precoce: Education physique 1-7 (Early French Immersion: Physical Education for Grades 1-7).

ERIC Educational Resources Information Center

Burt, Andy; And Others

This curriculum guide for physical education is intended for use in grades 1-7 in the early French immersion program. It is a translation of the regular physical education program and a compilation of references and supplementary teaching material. It is noted that because of the comparative lack of references in French, much of the reference…

Immersion francaise precoce: Arts plastiques 1-7 (Early French Immersion: Plastic Arts for Grades 1-7).

ERIC Educational Resources Information Center

Burt, Andy; And Others

This curriculum guide in art education is intended for use in grades 1-7 in the early French immersion program. An introductory chapter describes the educational objectives of the art program, the role of art education in child development, general and terminal objectives, methodology, the steps in graphic evolution, and an outline of the program.…

Rituximab and Dexamethasone in Treating Patients With Low-Grade Non-Hodgkin Lymphoma

ClinicalTrials.gov

2017-04-14

Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Grade 1 Follicular Lymphoma; Stage I Grade 2 Follicular Lymphoma; Stage I Marginal Zone Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Marginal Zone Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

PubMed

Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

2017-06-01

A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

DTIC Science & Technology

2012-03-01

patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy.

PubMed

Li, Changyou; Xu, Jing; Wang, Qi; Geng, Shaoqing; Yan, Zheng; You, Jin; Li, Zhenfeng; Zou, Xiao

2018-05-01

The present study was performed to explore the prognostic significance of periostin expression in a cohort of patients with early-stage breast cancer treated with breast conserving surgery following radiotherapy. A tissue microarray of tumor samples from 259 patients with early-stage breast cancer was assayed for periostin, estrogen receptor (ER), progesterone receptor (PR), ErbB2 receptor tyrosine kinase 2 and Ki-67 expression by immunohistochemistry. The association of periostin with other clinicopathological parameters and clinical outcomes, including local recurrence free survival (RFS), distant metastasis free survival (DFS) and overall survival (OS), were assessed through log-rank tests and univariate and multivariate analysis. Periostin expression was identified in 91 of the 259 tissue samples (35%). The periostin status was significantly associated with histological grade (P=0.001), nodal status (P=0.023), molecular subtype (P<0.01), ER status (P<0.01), PR status (P<0.01) and Ki-67 expression (P=0.011). Furthermore, periostin expression was associated with an increased risk of five-year local recurrence (95.8% vs. 89.0%; P=0.017) and distant metastasis (92.3% vs. 79.1%; P=0.001) in patients with early stage breast cancer. Multivariate analysis using Cox's proportional hazards model demonstrated that periostin expression was an independent predictor of all clinical outcomes in breast cancer (RFS, P=0.018; DFS, P=0.025; OS, P=0.047). Therefore, it was concluded that periostin is associated with an increased risk of local relapse and distant metastasis in early-stage breast cancer treated with conserving surgery and radiotherapy. This association should be further investigated in larger cohorts to validate the clinical significance of periostin expression.

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.

PubMed

Gómez-Aristizábal, A; Sharma, A; Bakooshli, M A; Kapoor, M; Gilbert, P M; Viswanathan, S; Gandhi, R

2017-05-01

Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium. Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF. Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

The performance of the new prognostic grade and stage groups in conservatively treated prostate cancer.

PubMed

Chen, Cheng; Chen, Ye; Hu, Lin-Kun; Jiang, Chang-Chuan; Xu, Ren-Fang; He, Xiao-Zhou

2018-02-27

We evaluated the prognosis of the new grade groups and American Joint Committee on Cancer (AJCC) stage groups in men with prostate cancer (PCa) who were treated conservatively. A total of 13 798 eligible men were chosen from the Surveillance Epidemiology and End Results database. The new grade and AJCC stage groups were investigated on prostate biopsy specimens. Kaplan-Meier survival analysis and multivariable hazards models were applied to estimate the association of new grade and stage groups with overall survival (OS) and PCa-specific survival (CSS). Mean follow-up was 42.65 months (95% confidence interval: 42.47-42.84) in the entire cohort. The 3-year OS and CSS rates stepped down for grade groups 1-5 and AJCC stage groups I-IVB, respectively. After adjusting for clinical and pathological characteristics, all grade groups and AJCC stage groups were associated with higher all-cause and PCa-specific mortality compared to the reference group (all P ≤ 0.003). In conclusion, we evaluated the oncological outcome of the new grade and AJCC stage groups on biopsy specimens of conservatively treated PCa. These two novel clinically relevant classifications can assist physicians to determine different therapeutic strategies for PCa patients.

Endoscopic methods in the treatment of early-stage esophageal cancer

PubMed Central

2014-01-01

Most patients with early esophageal cancer restricted to the mucosa may be offered endoscopic therapy, which is similarly effective, less invasive and less expensive than esophagectomy. Selection of appropriate relevant treatment and therapy methods should be performed at a specialized center with adequate facilities. The selection of an endoscopic treatment method for high-grade dysplasia and early-stage esophageal adenocarcinoma requires that tumor infiltration is restricted to the mucosa and that there is no neighboring lymph node metastasis. In squamous cell carcinoma, this treatment method is accepted in cases of tumors invading only up to the lamina propria of mucosa (m2). Tumors treated with the endoscopic method should be well or moderately differentiated and should not invade lymphatic or blood vessels. When selecting endoscopic treatments for these lesions, a combination of endoscopic resection and endoscopic ablation methods should be considered. PMID:25097676

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib.

PubMed

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib.

Emerging treatments for HER2-positive early-stage breast cancer: focus on neratinib

PubMed Central

Kourie, Hampig Raphael; El Rassy, Elie; Clatot, Florian; de Azambuja, Evandro; Lambertini, Matteo

2017-01-01

Over the last decades, a better understanding of breast cancer heterogeneity provided tools for a biologically based personalization of anticancer treatments. In particular, the overexpression of the human epidermal growth factor receptor 2 (HER2) by tumor cells provided a specific target in these HER2-positive tumors. The development of the monoclonal antibody trastuzumab, and its approval in 1998 for the treatment of patients with metastatic disease, radically changed the natural history of this aggressive subtype of breast cancer. These findings provided strong support for the continuous research in targeting the HER2 pathway and implementing the development of new anti-HER2 targeted agents. Besides trastuzumab, a series of other anti-HER2 agents have been developed and are currently being explored for the treatment of breast cancer patients, including those diagnosed with early-stage disease. Among these agents, neratinib, an oral tyrosine kinase inhibitor that irreversibly inhibits HER1, HER2, and HER4 at the intracellular level, has shown promising results, including when administered to patients previously exposed to trastuzumab-based treatment. This article aims to review the available data on the role of the HER2 pathway in breast cancer and on the different targeted agents that have been studied or are currently under development for the treatment of patients with early-stage HER2-positive disease with a particular focus on neratinib. PMID:28744140

Fertility sparing surgery in early stage epithelial ovarian cancer

PubMed Central

Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

2014-01-01

Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

Description of the early stage of pandemic (H1N1) 2009 in Germany, 27 April-16 June 2009.

PubMed

2009-08-06

We report characteristics of the early stage of the pandemic (H1N1) 2009 in Germany. Until 16 June 2009, 198 confirmed cases were notified. Almost half of the cases (47%) were imported, mostly from Mexico and the United States. About two third of indigenous cases were outbreak-related (with two large school-associated outbreaks, n=74). According to our results Germany is still in the early stage of the pandemic with limited domestic transmission.

Numerical predictors of arithmetic success in grades 1-6.

PubMed

Lyons, Ian M; Price, Gavin R; Vaessen, Anniek; Blomert, Leo; Ansari, Daniel

2014-09-01

Math relies on mastery and integration of a wide range of simpler numerical processes and concepts. Recent work has identified several numerical competencies that predict variation in math ability. We examined the unique relations between eight basic numerical skills and early arithmetic ability in a large sample (N = 1391) of children across grades 1-6. In grades 1-2, children's ability to judge the relative magnitude of numerical symbols was most predictive of early arithmetic skills. The unique contribution of children's ability to assess ordinality in numerical symbols steadily increased across grades, overtaking all other predictors by grade 6. We found no evidence that children's ability to judge the relative magnitude of approximate, nonsymbolic numbers was uniquely predictive of arithmetic ability at any grade. Overall, symbolic number processing was more predictive of arithmetic ability than nonsymbolic number processing, though the relative importance of symbolic number ability appears to shift from cardinal to ordinal processing. © 2014 John Wiley & Sons Ltd.

Mourning Child Grief Support Group Curriculum: Early Childhood Edition, Kindergarten-Grade 2.

ERIC Educational Resources Information Center

Lehmann, Linda; Jimerson, Shane R.; Gaasch, Ann

The Mourning Child Early Childhood grief support curriculum is intended for use with early elementary-aged children, specifically children in kindergarten through grade two, who have experienced the death of someone special to them. It is designed for use by professionals who work in schools, hospitals, hospices, mental health agencies, or any…

Adjuvant lapatinib for women with early-stage HER2-positive breast cancer: a randomised, controlled, phase 3 trial.

PubMed

Goss, Paul E; Smith, Ian E; O'Shaughnessy, Joyce; Ejlertsen, Bent; Kaufmann, Manfred; Boyle, Frances; Buzdar, Aman U; Fumoleau, Pierre; Gradishar, William; Martin, Miguel; Moy, Beverly; Piccart-Gebhart, Martine; Pritchard, Kathleen I; Lindquist, Deborah; Chavarri-Guerra, Yanin; Aktan, Gursel; Rappold, Erica; Williams, Lisa S; Finkelstein, Dianne M

2013-01-01

Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab-the standard adjuvant treatment. We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis. This study was a placebo-controlled, multicentre, randomised phase 3 trial. Women outpatients from 405 [corrected] centres in 33 countries [corrected] with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were randomly assigned (1:1) to receive daily lapatinib (1500 mg) or daily placebo for 12 months. Randomisation was done with a computer-generated sequence, stratified by time since diagnosis, lymph node involvement at diagnosis, and tumour hormone-receptor status. Investigators, site staff, and patients were masked to treatment assignment. The primary endpoint was disease-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00374322. Between August, 2006, and May, 2008, 3161 women were enrolled and 3147 were assigned to lapatinib (n=1571) or placebo (n=1576). After a median follow-up of 47·4 months (range 0·4-60·0) in the lapatinib group and 48·3 (0·7-61·3) in the placebo group, 210 (13%) disease-free survival events had occurred in the lapatinib group versus 264 (17%) in the placebo group (hazard ratio [HR] 0·83, 95% CI 0·70-1·00; p=0·053). Central review of HER2 status showed that only 2490 (79%) of the randomised women were HER2-positive. 157 (13%) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 (17%) of 1260 in the placebo group had a disease-free survival event (HR 0·82, 95% 0·67-1·00; p=0·04). Serious adverse events occurred in 99 (6%) of 1573 patients taking lapatinib and 77 (5%) of 1574 patients taking placebo, with higher incidences of grade 3-4 diarrhoea (97 [6%] vs nine [<1%]), rash (72 [5%] vs three

Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study.

PubMed

Pirhonen, Juho; Arola, Johanna; Sädevirta, Sanja; Luukkonen, Panu; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Isomäki, Antti; Hukkanen, Mika; Yki-Järvinen, Hannele; Ikonen, Elina

2016-01-01

Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0-4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading.

Bilateral Total Hip Arthroplasty: 1-Stage or 2-Stage? A Meta-Analysis.

PubMed

Shao, Hongyi; Chen, Chi-Lung; Maltenfort, Mitchell G; Restrepo, Camilo; Rothman, Richard H; Chen, Antonia F

2017-02-01

Total hip arthroplasty (THA) is one of the most successful orthopedic surgeries performed in the last 50 years. However, controversies still exist between conducting 1- or 2-stage bilateral THA. Using PubMed, Ovid, Embase, and Cochrane library databases, we searched for papers written between January 1995 and October 2015 that contained the following search terms: "one-stage or two-stage" or "simultaneous or staged," and "hip" and "arthroplasty or replacement." A meta-analysis was conducted with the collected pooled data about major and minor systemic complications, surgical complications, and other perioperative data associated with 1- and 2-stage bilateral THA. Statistical analysis was performed by the Mantel-Haenszel method, and the fixed effect model was used to analyze data. There were 13 studies with 17,762 patients who underwent 1-stage bilateral THA and 46,147 patients who underwent 2-stage bilateral THA. One-stage bilateral THA had a lower risk of major systemic complications, less deep venous thrombosis, and shorter operative time compared with 2-stage bilateral THA. There were no significant differences in death, pulmonary embolism, cardiovascular complication, infections, minor complications, and other surgical complications between procedures. One-stage bilateral THA was superior to 2-stage bilateral THA in terms of major systemic complication, deep venous thrombosis, and surgical time compared with 2-stage bilateral THA. However, this study does not encourage performing 1-stage over 2-stage bilateral THA. Higher evidence level studies are necessary for further analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

Interleukin-4 receptor alpha overexpression in human bladder cancer correlates with the pathological grade and stage of the disease.

PubMed

Joshi, Bharat H; Leland, Pamela; Lababidi, Samir; Varrichio, Frederick; Puri, Raj K

2014-12-01

Previously, we have demonstrated that interleukin-4 receptor α (IL-4Rα) is overexpressed on a variety of human cancers and can serve as target for IL-4 immunotoxin comprised of IL-4 and a mutated Pseudomonas exotoxin. However, its expression and association with grade and clinical stage of bladder cancer has not been studied. IL-4Rα expression was examined in human bladder cancer cell lines, mouse xenografts, and biopsy specimens at mRNA and protein levels by real-time RT-PCR and IHC/ISH techniques. We also examined the effect of IL-4 on proliferation and invasion of bladder carcinoma cell lines. For tissue microarray (TMA) results, we analyzed the precision data using exact binomial proportion with exact two-sided P-values. We used Cochran-Armitage Statistics with exact two-sided P-values to examine the trend analysis of IL-4Rα over grade or stage of the bladder cancer specimens. The influence of age and gender covariates was also analyzed using multiple logistic regression models. IL-4Rα is overexpressed in five bladder cancer cell lines, while normal bladder and human umbilical vein cell lines (HUVEC) expressed at low levels. Two other chains of IL-4 receptor complex, IL-2RγC and IL-13Rα1, were absent or weakly expressed. IL-4 modestly inhibited the cell proliferation, but enhanced cell invasion of bladder cancer cell lines in a concentration-dependent manner. Bladder cancer xenografts in immunodeficient mice also maintained IL-4Rα overexpression in vivo. Analysis of tumor biopsy specimens in TMAs revealed significantly higher IL-4Rα immunostaining (≥ 2+) in Grade 2 (85%) and Grade 3 (97%) compared to Grade 1 tumors (0%) (P ≤ 0.0001). Similarly, 9% stage I tumors were positive for IL-4Rα (≥ 2+) compared to 84% stage II (P ≤ 0.0001) and 100% stages III-IV tumors (P ≤ 0.0001). IL-13Rα1 was also expressed in tumor tissues but at low levels and it did not show any correlation with the grade and stage of disease. However, the IL-2RγC was not

Growth trajectories of early aggression, overactivity, and inattention: Relations to second-grade reading.

PubMed

Gray, Sarah A O; Carter, Alice S; Briggs-Gowan, Margaret J; Jones, Stephanie M; Wagmiller, Robert L

2014-09-01

The link between behavior problems and low academic achievement is well established, but few studies have examined longitudinal relations between early externalizing behaviors before school entry and low academic achievement following transition to formal schooling. Early inattention has been particularly overlooked, despite strong associations between inattention and reading difficulties later in development. Trajectories of infant and toddler aggression, overactivity, and inattention, developed from parent reports about 1- to 3-year-old children, were examined as predictors of direct assessments of 2nd-grade reading in an at-risk epidemiological study subsample (N = 359). Reports of inattentive and overactive behaviors at ages 1-3 years and changes in inattention through toddlerhood predicted reading achievement in 2nd grade. A parallel process model suggested that the effects of early inattention on reading appear to be most robust. Findings underscore the contribution of social-emotional development to school readiness and the importance of early identification of children with externalizing problems, as early interventions designed to reduce externalizing problems may improve later reading skills.

High-Dose and Extended-Field Intensity Modulated Radiation Therapy for Early-Stage NK/T-Cell Lymphoma of Waldeyer's Ring: Dosimetric Analysis and Clinical Outcome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi, Xi-Wen; Li, Ye-Xiong, E-mail: yexiong@yahoo.com; Fang, Hui

2013-12-01

Purpose: To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Methods and Materials: Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV{sub 50}]) and 40 Gy to the negative cervical nodes (PTV{sub 40}). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS)more » were calculated using the Kaplan-Meier method. Results: The median mean doses to the PTV{sub 50} and PTV{sub 40} were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV{sub 50} and 0.9% of the PTV{sub 40} received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. Conclusions: IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL.« less

High-dose and extended-field intensity modulated radiation therapy for early-stage NK/T-cell lymphoma of Waldeyer's ring: dosimetric analysis and clinical outcome.

PubMed

Bi, Xi-Wen; Li, Ye-Xiong; Fang, Hui; Jin, Jing; Wang, Wei-Hu; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Ren, Hua; Dai, Jian-Rong

2013-12-01

To assess the dosimetric benefit, treatment outcome, and toxicity of high-dose and extended-field intensity modulated radiation therapy (IMRT) in patients with early-stage NK/T-cell lymphoma of Waldeyer's ring (WR-NKTCL). Thirty patients with early-stage WR-NKTCL who received extended-field IMRT were retrospectively reviewed. The prescribed dose was 50 Gy to the primary involved regions and positive cervical lymph nodes (planning target volume requiring radical irradiation [PTV50]) and 40 Gy to the negative cervical nodes (PTV40). Dosimetric parameters for the target volume and critical normal structures were evaluated. Locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) were calculated using the Kaplan-Meier method. The median mean doses to the PTV50 and PTV40 were 53.2 Gy and 43.0 Gy, respectively. Only 1.4% of the PTV50 and 0.9% of the PTV40 received less than 95% of the prescribed dose, indicating excellent target coverage. The average mean doses to the left and right parotid glands were 27.7 and 28.4 Gy, respectively. The 2-year OS, PFS, and LRC rates were 71.2%, 57.4%, and 87.8%. Most acute toxicities were grade 1 to 2, except for grade ≥3 dysphagia and mucositis. The most common late toxicity was grade 1-2 xerostomia, and no patient developed any ≥grade 3 late toxicities. A correlation between the mean dose to the parotid glands and the degree of late xerostomia was observed. IMRT achieves excellent target coverage and dose conformity, as well as favorable survival and locoregional control rates with acceptable toxicities in patients with WR-NKTCL. Copyright © 2013 Elsevier Inc. All rights reserved.

Global analysis of host-pathogen interactions that regulate early stage HIV-1 replication

PubMed Central

König, Renate; Zhou, Yingyao; Elleder, Daniel; Diamond, Tracy L.; Bonamy, Ghislain M.C.; Irelan, Jeffrey T.; Chiang, Chih-yuan; Tu, Buu P.; De Jesus, Paul D.; Lilley, Caroline E.; Seidel, Shannon; Opaluch, Amanda M.; Caldwell, Jeremy S.; Weitzman, Matthew D.; Kuhen, Kelli L.; Bandyopadhyay, Sourav; Ideker, Trey; Orth, Anthony P.; Miraglia, Loren J.; Bushman, Frederic D.; Young, John A.; Chanda, Sumit K.

2008-01-01

Human Immunodeficiency Viruses (HIV-1 and HIV-2) rely upon host-encoded proteins to facilitate their replication. Here we combined genome-wide siRNA analyses with interrogation of human interactome databases to assemble a host-pathogen biochemical network containing 213 confirmed host cellular factors and 11 HIV-1-encoded proteins. Protein complexes that regulate ubiquitin conjugation, proteolysis, DNA damage response and RNA splicing were identified as important modulators of early stage HIV-1 infection. Additionally, over 40 new factors were shown to specifically influence initiation and/or kinetics of HIV-1 DNA synthesis, including cytoskeletal regulatory proteins, modulators of post-translational modification, and nucleic acid binding proteins. Finally, fifteen proteins with diverse functional roles, including nuclear transport, prostaglandin synthesis, ubiquitination, and transcription, were found to influence nuclear import or viral DNA integration. Taken together, the multi-scale approach described here has uncovered multiprotein virus-host interactions that likely act in concert to facilitate early steps of HIV-1 infection. PMID:18854154

Significantly greater expression of ER, PR, and ECAD in advanced-stage low-grade ovarian serous carcinoma as revealed by immunohistochemical analysis.

PubMed

Wong, Kwong-Kwok; Lu, Karen H; Malpica, Anais; Bodurka, Diane C; Shvartsman, Hyun S; Schmandt, Rosemarie E; Thornton, Angela D; Deavers, Michael T; Silva, Elvio G; Gershenson, David M

2007-10-01

A 2-tier system that classifies ovarian serous carcinoma (OSC) as low grade or high grade is gaining acceptance. Women with low-grade OSC generally have higher 5-year survival rates than do women with high-grade OSC. We examined the expression of various markers to further understand the molecular differences between low-grade and high-grade OSCs: the potential therapeutic targets or prognostic markers Her-2/neu, estrogen receptor, and progesterone receptor (PR); the metastasis-associated markers cyclin D1 (BCL1), E-cadherin, matrix metalloproteinase (MMP) 2, and MMP-9; and the cell proliferation-associated markers BCL1, Ki-67 antigen (Ki-67), and p53. For this immunohistochemical analysis, we used paraffin-embedded specimens from 47 patients with advanced-stage low-grade OSC and from 49 patients with advanced-stage high-grade OSC. Our results showed that low-grade tumors expressed significantly higher levels of estrogen receptor, PR, and E-cadherin than did high-grade tumors, suggesting the involvement of gonadal steroid hormones, especially in the pathogenesis of low-grade OSC; the PR positivity was also observed in the stromal component of these low-grade tumors. On the other hand, high-grade tumors trended toward increased expression of MMP-9, BCL1, p53, and Ki-67, and robust MMP-9 positivity was observed in the stromal component of these high-grade tumors. These differences may lead to the development of different therapeutic strategies for women with either the low-grade or the high-grade form of OSC.

Consensus Statements for Management of Barrett’s Dysplasia and Early-Stage Esophageal Adenocarcinoma, Based on a Delphi Process

PubMed Central

BENNETT, CATHY; VAKIL, NIMISH; BERGMAN, JACQUES; HARRISON, REBECCA; ODZE, ROBERT; VIETH, MICHAEL; SANDERS, SCOTT; GAY, LAURA; PECH, OLIVER; LONGCROFT–WHEATON, GAIUS; ROMERO, YVONNE; INADOMI, JOHN; TACK, JAN; CORLEY, DOUGLAS A.; MANNER, HENDRIK; GREEN, SUSI; DULAIMI, DAVID AL; ALI, HAYTHEM; ALLUM, BILL; ANDERSON, MARK; CURTIS, HOWARD; FALK, GARY; FENNERTY, M. BRIAN; FULLARTON, GRANT; KRISHNADATH, KAUSILIA; MELTZER, STEPHEN J.; ARMSTRONG, DAVID; GANZ, ROBERT; CENGIA, GIANPAOLO; GOING, JAMES J.; GOLDBLUM, JOHN; GORDON, CHARLES; GRABSCH, HEIKE; HAIGH, CHRIS; HONGO, MICHIO; JOHNSTON, DAVID; FORBES–YOUNG, RICKY; KAY, ELAINE; KAYE, PHILIP; LERUT, TONI; LOVAT, LAURENCE B.; LUNDELL, LARS; MAIRS, PHILIP; SHIMODA, TADAKUZA; SPECHLER, STUART; SONTAG, STEPHEN; MALFERTHEINER, PETER; MURRAY, IAIN; NANJI, MANOJ; POLLER, DAVID; RAGUNATH, KRISH; REGULA, JAROSLAW; CESTARI, RENZO; SHEPHERD, NEIL; SINGH, RAJVINDER; STEIN, HUBERT J.; TALLEY, NICHOLAS J.; GALMICHE, JEAN–PAUL; THAM, TONY C. K.; WATSON, PETER; YERIAN, LISA; RUGGE, MASSIMO; RICE, THOMAS W.; HART, JOHN; GITTENS, STUART; HEWIN, DAVID; HOCHBERGER, JUERGEN; KAHRILAS, PETER; PRESTON, SEAN; SAMPLINER, RICHARD; SHARMA, PRATEEK; STUART, ROBERT; WANG, KENNETH; WAXMAN, IRVING; ABLEY, CHRIS; LOFT, DUNCAN; PENMAN, IAN; SHAHEEN, NICHOLAS J.; CHAK, AMITABH; DAVIES, GARETH; DUNN, LORNA; FALCK–YTTER, YNGVE; DECAESTECKER, JOHN; BHANDARI, PRADEEP; ELL, CHRISTIAN; GRIFFIN, S. MICHAEL; ATTWOOD, STEPHEN; BARR, HUGH; ALLEN, JOHN; FERGUSON, MARK K.; MOAYYEDI, PAUL; JANKOWSKI, JANUSZ A. Z.

2017-01-01

BACKGROUND & AIMS Esophageal adenocarcinoma (EA) is increasingly common among patients with Barrett’s esophagus (BE). We aimed to provide consensus recommendations based on the medical literature that clinicians could use to manage patients with BE and low-grade dysplasia, high-grade dysplasia (HGD), or early-stage EA. METHODS We performed an international, multidisciplinary, systematic, evidence-based review of different management strategies for patients with BE and dysplasia or early-stage EA. We used a Delphi process to develop consensus statements. The results of literature searches were screened using a unique, interactive, Web-based data-sifting platform; we used 11,904 papers to inform the choice of statements selected. An a priori threshold of 80% agreement was used to establish consensus for each statement. RESULTS Eighty-one of the 91 statements achieved consensus despite generally low quality of evidence, including 8 clinical statements: (1) specimens from endoscopic resection are better than biopsies for staging lesions, (2) it is important to carefully map the size of the dysplastic areas, (3) patients that receive ablative or surgical therapy require endoscopic follow-up, (4) high-resolution endoscopy is necessary for accurate diagnosis, (5) endoscopic therapy for HGD is preferred to surveillance, (6) endoscopic therapy for HGD is preferred to surgery, (7) the combination of endoscopic resection and radiofrequency ablation is the most effective therapy, and (8) after endoscopic removal of lesions from patients with HGD, all areas of BE should be ablated. CONCLUSIONS We developed a data-sifting platform and used the Delphi process to create evidence-based consensus statements for the management of patients with BE and early-stage EA. This approach identified important clinical features of the diseases and areas for future studies. PMID:22537613

Quantitative nuclear histomorphometry predicts oncotype DX risk categories for early stage ER+ breast cancer.

PubMed

Whitney, Jon; Corredor, German; Janowczyk, Andrew; Ganesan, Shridar; Doyle, Scott; Tomaszewski, John; Feldman, Michael; Gilmore, Hannah; Madabhushi, Anant

2018-05-30

Gene-expression companion diagnostic tests, such as the Oncotype DX test, assess the risk of early stage Estrogen receptor (ER) positive (+) breast cancers, and guide clinicians in the decision of whether or not to use chemotherapy. However, these tests are typically expensive, time consuming, and tissue-destructive. In this paper, we evaluate the ability of computer-extracted nuclear morphology features from routine hematoxylin and eosin (H&E) stained images of 178 early stage ER+ breast cancer patients to predict corresponding risk categories derived using the Oncotype DX test. A total of 216 features corresponding to the nuclear shape and architecture categories from each of the pathologic images were extracted and four feature selection schemes: Ranksum, Principal Component Analysis with Variable Importance on Projection (PCA-VIP), Maximum-Relevance, Minimum Redundancy Mutual Information Difference (MRMR MID), and Maximum-Relevance, Minimum Redundancy - Mutual Information Quotient (MRMR MIQ), were employed to identify the most discriminating features. These features were employed to train 4 machine learning classifiers: Random Forest, Neural Network, Support Vector Machine, and Linear Discriminant Analysis, via 3-fold cross validation. The four sets of risk categories, and the top Area Under the receiver operating characteristic Curve (AUC) machine classifier performances were: 1) Low ODx and Low mBR grade vs. High ODx and High mBR grade (Low-Low vs. High-High) (AUC = 0.83), 2) Low ODx vs. High ODx (AUC = 0.72), 3) Low ODx vs. Intermediate and High ODx (AUC = 0.58), and 4) Low and Intermediate ODx vs. High ODx (AUC = 0.65). Trained models were tested independent validation set of 53 cases which comprised of Low and High ODx risk, and demonstrated per-patient accuracies ranging from 75 to 86%. Our results suggest that computerized image analysis of digitized H&E pathology images of early stage ER+ breast cancer might be able predict the

Adjuvant intraperitoneal chromic phosphate therapy for women with apparent early ovarian carcinoma who have not undergone comprehensive surgical staging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Soper, J.T.; Berchuck, A.; Clarke-Pearson, D.L.

1991-08-15

Forty-nine women with apparent Stage 1 and 2 ovarian carcinoma received intraperitoneal phosphate 32 as the only adjuvant therapy after primary surgery. In addition to bilateral salpingo-oophorectomy, 40 (82%) had analysis of peritoneal cytology, and 35 (71%) underwent omentectomy. Random peritoneal biopsies and retroperitoneal lymph node sampling were not done in any of these patients. The overall and disease-free survival rates were 86% and 75%, respectively, with no significant differences by stage, histologic grade, histologic type, or low-risk versus high-risk subsets recognized in patients who received comprehensive surgical staging. Seven (58%) of 12 patients had lymph node metastasis as themore » first site of recurrence, including two of three with late recurrences. Significant morbidity related to intraperitoneal chromic phosphate (32P) occurred in one (2%) woman. These results emphasize the need for comprehensive surgical staging of women with apparent early ovarian carcinoma to aid in the selection of appropriate initial adjuvant therapy.« less

Utility of dysphagia grade in predicting endoscopic ultrasound T-stage of non-metastatic esophageal cancer.

PubMed

Fang, T C; Oh, Y S; Szabo, A; Khan, A; Dua, K S

2016-08-01

Patients with non-metastatic esophageal cancer routinely undergo endoscopic ultrasound (EUS) for loco-regional staging. Neoadjuvant therapy is recommended for ≥T3 tumors while upfront surgery can be considered for ≤T2 lesions. The aim of this study was to determine if the degree of dysphagia can predict the EUS T-stage of esophageal cancer. One hundred eleven consecutive patients with non-metastatic esophageal cancer were retrospectively reviewed from a database. Prior to EUS, patients' dysphagia grade was recorded. Correlation between dysphagia grade and EUS T-stage, especially in reference to predicting ≥T3 stage, was determined. The correlation of dysphagia grade with EUS T-stage (Kendall's tau coefficient) was 0.49 (P < 0.001) for the lower and 0.59 (P = 0.008) for the middle esophagus. The sensitivity and specificity of dysphagia grade ≥2 (can only swallow semi-solids/liquids) for T3 cancer were 56% (95% confidence interval [CI] 43-67%) and 93% (95% CI 79-98%), respectively. The sensitivity, specificity, and positive predictive value of dysphagia grade ≥3 (can only swallow liquids or total dysphagia) for T3 lesions were 36% (95% CI 25-48%), 100% (95% CI 89-100%), and 100% (95% CI 83-100%), respectively. Overall, there was a significant positive correlation between dysphagia grade and the EUS T-stage of esophageal cancer. All patients with dysphagia grade ≥3 had T3 lesions. This may have clinical implications for patients who can only swallow liquids or have complete dysphagia by allowing for prompt initiation of neoadjuvant therapy, especially in countries/centers where EUS service is difficult to access in a timely manner or not available. © 2015 International Society for Diseases of the Esophagus.

Correlation between endoscopic forceps biopsies and endoscopic mucosal resection with endoscopic ultrasound in patients with Barrett's esophagus with high-grade dysplasia and early cancer.

PubMed

Thota, Prashanthi N; Sada, Alaa; Sanaka, Madhusudhan R; Jang, Sunguk; Lopez, Rocio; Goldblum, John R; Liu, Xiuli; Dumot, John A; Vargo, John; Zuccarro, Gregory

2017-03-01

Patients with Barrett's esophagus (BE) and high-grade dysplasia (HGD) or intramucosal cancer (IMC) on endoscopic forceps biopsies are referred to endoscopic therapy even though forceps biopsies do not reflect the disease extent accurately. Endoscopic mucosal resection (EMR) and endoscopic ultrasound (EUS) are frequently used for staging prior to endoscopic therapy. Our aims were to evaluate: (1) if endoscopic forceps biopsies correlated with EMR histology in these patients; (2) the utility of EUS compared to EMR; and (3) if accuracy of EUS varied based on grade of differentiation of tumor. This is a retrospective review of patients referred to endoscopic therapy of BE with HGD or early esophageal adenocarcinoma (EAC) who underwent EMR from 2006 to 2011. Age, race, sex, length of Barrett's segment, hiatal hernia size, number of endoscopies and biopsy results and EUS findings were abstracted. A total of 151 patients underwent EMR. In 50 % (75/151) of patients, EMR histology was consistent with endoscopic forceps biopsy findings. EMR resulted in change in diagnosis with upstaging in 21 % (32/151) and downstaging in 29 % (44/151). In patients with HGD on EMR, EUS staging was T0 in 74.1 % (23/31) but upstaged in 25.8 % (8/31). In patients with IMC on EMR, EUS findings were T1a in 23.6 % (9/38), upstaged in 18.4 % (7/38) and downstaged in 57.8 % (22/38). EUS accurately identified EMR histology in all submucosal cancers. Grade of differentiation was reported in 24 cancers on EMR histology. There was no correlation between grade and EUS staging. EUS is of limited utility in accurate staging of BE patients with HGD or early EAC. Endoscopic forceps biopsy correlated with EMR findings in only 50 % of patients. Irrespective of the endoscopic forceps biopsy results, all BE patients with visible lesions should be referred to EMR.

Expression of CDX-2 and Ki-67 in different grades of colorectal adenocarcinomas.

PubMed

Sen, Anway; Mitra, Sumit; Das, Ram Narayan; Dasgupta, Shatavisha; Saha, Koushik; Chatterjee, Uttara; Mukherjee, Krishnendu; Datta, Chhanda; Chattopadhyay, Bitan K

2015-01-01

CDX2 is a caudal homeobox gene essential for intestinal differentiation and is specifically expressed in colorectal adenocarcinomas. Its role in colorectal carcinogenesis is not fully elucidated. To study the expression pattern of CDX2 and Ki-67 in different grades of colorectal adenocarcinomas and to observe the relationship of their staining patterns in various tumor stages and to look for correlation if any, between Ki-67 labeling index (Ki-67 LI) and CDX2 expression. A total of 74 cases were enrolled. Detailed clinical profile, peroperative findings, histological grading and staging were noted. Immunohistochemistry for CDX2 and Ki-67 was done, and Ki-67 LI was calculated. CDX2 staining was graded semi-quantitatively, and statistical analysis was done. Age of presentation ranged from 20 to 75 years, and the male:female ratio was 1.83:1. There were 8, 47 and 13 cases of well, moderate and poorly differentiated adenocarcinomas, respectively. The mean Ki-67 LI of well, moderate and poorly differentiated adenocarcinomas were 14.25, 31.34 and 43.08 respectively, and their difference was statistically significant, correlation was also noted with stage. CDX2 expression appeared to be stronger in poorly differentiated cases, but there was no significant difference in its expression in the different grades and stages. There was no correlation between Ki-67 LI and CDX2 immunostaining pattern. The lymph node metastasis showed CDX2 positivity in all the cases. Expression of CDX2 does not significantly change with the grade of colorectal adenocarcinomas. However, it is an important diagnostic marker in metastatic colonic lesions. The Ki-67 LI, on the other hand, showed a strong correlation with histopathological grades.

Continuous Grading of Early Fibrosis in NAFLD Using Label-Free Imaging: A Proof-of-Concept Study

PubMed Central

Pirhonen, Juho; Arola, Johanna; Sädevirta, Sanja; Luukkonen, Panu; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Isomäki, Antti; Hukkanen, Mika

2016-01-01

Background and Aims Early detection of fibrosis is important in identifying individuals at risk for advanced liver disease in non-alcoholic fatty liver disease (NAFLD). We tested whether second-harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS) microscopy, detecting fibrillar collagen and fat in a label-free manner, might allow automated and sensitive quantification of early fibrosis in NAFLD. Methods We analyzed 32 surgical biopsies from patients covering histological fibrosis stages 0–4, using multimodal label-free microscopy. Native samples were visualized by SHG and CARS imaging for detecting fibrillar collagen and fat. Furthermore, we developed a method for quantitative assessment of early fibrosis using automated analysis of SHG signals. Results We found that the SHG mean signal intensity correlated well with fibrosis stage and the mean CARS signal intensity with liver fat. Little overlap in SHG signal intensities between fibrosis stages 0 and 1 was observed. A specific fibrillar SHG signal was detected in the liver parenchyma outside portal areas in all samples histologically classified as having no fibrosis. This signal correlated with immunohistochemical location of fibrillar collagens I and III. Conclusions This study demonstrates that label-free SHG imaging detects fibrillar collagen deposition in NAFLD more sensitively than routine histological staging and enables observer-independent quantification of early fibrosis in NAFLD with continuous grading. PMID:26808140

Sentinel Lymph Node Mapping for Grade 1 Endometrial Cancer: Is it the Answer to the Surgical Staging Dilemma?

PubMed Central

Abu-Rustum, Nadeem R.; Khoury-Collado, Fady; Pandit-Taskar, Neeta; Soslow, Robert A.; Dao, Fanny; Sonoda, Yukio; Levine, Douglas A.; Brown, Carol L.; Chi, Dennis S.; Barakat, Richard R.; Gemignani, Mary L.

2014-01-01

Objective To describe the accuracy of SLN mapping in patients with a preoperative diagnosis of grade 1 endometrial cancer. Methods A prospective, non-randomized study of women with a preoperative diagnosis of endometrial cancer and clinical stage I disease was conducted. A subset analysis of patients with a preoperative diagnosis of grade 1 endometrial endometrioid cancer was performed. All patients had preoperative lymphoscintigraphy with Tc99m on the day of or day before surgery followed by an intraoperative injection of 2cc of isosulfan or methylene blue dye deep into the cervix or both cervix and fundus. All patients underwent hysterectomy, bilateral salpingo-oophorectomy, and regional nodal dissection. Hot and/or blue nodes were labeled as SLNs and sent for histopathological analysis. Results Forty-two patients with a preoperative diagnosis of grade 1 endometrial carcinoma treated from 3/06–8/08 were identified. Twenty-five(60%) had laparoscopic surgery; 17(40%) were treated by laparotomy. Preoperative lymphoscintigraphy visualized SLNs in 30 patients(71%); intraoperative localization of the SLN was possible in 36(86%). A median of 3 SLNs(range, 1–14) and 14.5 non-SLNs(range, 4–55) were examined. In all, 4/36(11%) had positive SLNs—3 seen on H&E and 1 as cytokeratin-positive cells on IHC. All node-positive cases were picked up by the SLN; there were no false-negative cases. The sensitivity of the SLN procedure in the 36 patients who had an SLN identified was 100%. Conclusion Sentinel lymph node mapping using a cervical injection with combined Tc and blue dye is feasible and accurate in patients with grade 1 endometrial cancer and may be a reasonable option for this select group of patients. Regional lymphadenectomy remains the gold standard in many practices, particularly for the approximately 15% of cases with failed SLN mapping. PMID:19232699

Trajectories of Social Withdrawal from Grades 1 to 6: Prediction from Early Parenting, Attachment, and Temperament

ERIC Educational Resources Information Center

Booth-LaForce, Cathryn; Oxford, Monica L.

2008-01-01

From 1,092 children in the NICHD Study of Early Child Care and Youth Development, the authors identified 3 trajectory patterns of social withdrawal from teacher reports in Grades 1-6: a normative consistently low group (86%), a decreasing group (5%) with initially high withdrawal that decreased, and an increasing group (9%) with initially low…

Early Grade Writing Assessment: An Instrument Model.

PubMed

Jiménez, Juan E

The United Nations Educational, Scientific, and Cultural Organization promoted the creation of a model instrument for individual assessment of students' foundational writing skills in the Spanish language that was based on a literature review and existing writing tools and assessments. The purpose of the Early Grade Writing Assessment (EGWA) is to document learners' basic writing skills, mapped in composing units of increasing complexity to communicate meaning. Validation and standardization of EGWA was conducted in the Canary Islands (Spain) in 12 schools using a cross-sectional design with a sample of 1,653 Spanish-speaking students in Grades 1 through 3. The author describes EGWA's internal structure, along with the prevalence of learning disabilities (LD) in transcription and developmental differences in writing between Spanish-speaking children with LD and typical peers. Findings suggest that EGWA's psychometric characteristics are satisfactory, and its internal structure can be attributed to four factors responsible for a high percentage of the variance. The odds ratio indicated that 2 Spanish-speaking children with LD in transcription are identified out of every 100. A comparison between students with and without LD in transcription revealed statistically significant differences concerning sentence and text production across grades. Results are interpreted within current theoretical accounts of writing models.

Relationship of PCNA, C-erbB2 and CD44s expression with tumor grade and stage in urothelial carcinomas of the bladder

PubMed Central

Yıldırım, Ayhan; Kösem, Mustafa; Sayar, İlyas; Gelincik, İbrahim; Yavuz, Alparslan; Bozkurt, Aliseydi; Erkorkmaz, Ünal; Bayram, İrfan

2014-01-01

In the present study, the intention was to reveal the relationship of histological grade and stage with c-erbB2, CD44s, and PCNA immunoreactivity in bladder urothelial carcinomas (UC). In our study, we evaluated 46 items of transurethral resection material of patients submitted by YYU Faculty of Medicine, Main Department of Pathology, with a mass revealed in their bladder after clinical and radiological studies at our laboratories and who were diagnosed with urothelial carcinomas. PCNA, c-erbB2, and CD44s were applied in an immunohistochemical manner comprised from nine low-malignant potential papillary urothelial neoplasia, 23 low-grade papillary urothelial carcinoma, and 14 high-grade papillary urothelial carcinoma. Immunostaining was scored according to the percentage of positive cells. The immunohistochemical study demonstrated that the c-erbB2 and PCNA staining ratio increased when an increase occurred in stage and grade. The CD44s staining ratio decreased. C-erbB2, PCNA, and CD44s appear to be a useful marker in the assessment of the prognosis and treatment options in urothelial carcinomas. PMID:25035774

Balancing risk and benefit in early-stage classical Hodgkin lymphoma.

PubMed

Bröckelmann, Paul J; Sasse, Stephanie; Engert, Andreas

2018-04-12

With defined chemotherapy and radiotherapy (RT) and risk-adapted treatment, early-stage classical Hodgkin lymphoma (HL) has become curable in a majority of patients. Hence, a major current goal is to reduce treatment-related toxicity while maintaining long-term disease control. Patients with early-stage favorable disease (ie, limited stage without risk factors [RFs]) are frequently treated with 2 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (2×ABVD) followed by 20-Gy involved-field or involved-site RT (IF/ISRT). In patients with early-stage unfavorable disease (ie, limited stage with RFs), 4 cycles of chemotherapy are usually consolidated with 30-Gy IF/ISRT. Compared with 4×ABVD, 2 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (2×BEACOPP escalated ) followed by 2×ABVD improved 5-year progression-free survival (PFS), with similar 5-year overall survival. Recently, treatment strategies based on [ 18 F]fluorodeoxyglucose positron emission tomography (PET) response were evaluated. In early-stage unfavorable HL, a majority of patients achieved a negative interim PET after 2×ABVD and an excellent outcome after 4×ABVD, whereas in those with a positive interim PET, 2×BEACOPP escalated improved 5-year PFS. Furthermore, a PET-guided RT approach was evaluated to decrease long-term toxicity. Although both the RAPID and H10 trials reported poorer disease control without RT, PET-guided omission of RT can constitute a valid therapeutic option in patients with an increased risk of RT-associated toxicity (eg, because of sex, age, or disease localization). Implementation of drugs such as the anti-CD30 antibody-drug conjugate brentuximab vedotin or the anti-programmed death 1 antibodies nivolumab or pembrolizumab might allow further reduction of overall mortality and improve quality of life in affected patients. © 2018 by The American Society of Hematology.

Polymorphisms in ARMS2/HTRA1 and Complement Genes and Age-Related Macular Degeneration in India: Findings from the INDEYE Study

PubMed Central

Sundaresan, Periasamy; Vashist, Praveen; Ravindran, Ravilla D.; Shanker, Ashwini; Nitsch, Dorothea; Nonyane, Bareng A. S.; Smeeth, Liam; Chakravarthy, Usha; Fletcher, Astrid E.

2012-01-01

Purpose. Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India. Methods. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1–3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center. Results. Of 3569 participants, 53.2% had no signs of AMD, 45.6% had features of early AMD, and 1.2% had late AMD. CFH (rs1061170), C2 (rs547154), or CFB (rs438999) was not associated with early or late AMD. In the ARMS2 locus, rs10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13–1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15–2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02–1.23; P = 0.02); rs10490923 was not associated with early or late AMD. Conclusions. Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India. PMID:23060141

Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage.

PubMed

Liu, Jie; Jin, Xinchun; Liu, Ke J; Liu, Wenlan

2012-02-29

Blood-brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here, we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran and promoted the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis.

Associations of adiponectin and leptin with stage and grade of PSA-detected prostate cancer: the ProtecT study.

PubMed

Burton, Anya; Martin, Richard M; Holly, Jeff; Lane, J Athene; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Tilling, Kate

2013-02-01

Obesity has been associated with an increased risk of advanced and fatal prostate cancer; adipokines may mediate this association. We examined associations of the adipokines leptin and adiponectin with the stage and grade of PSA-detected prostate cancer. We conducted a nested case-control study comparing 311 men with mainly locally advanced (≥T3, N1, or M1 cases) vs. 413 men with localized (T ≤2 & NX-0 & M0 controls) PSA-detected prostate cancer, recruited 2001-2009 from 9 UK regions to the ProtecT study. Associations of body mass index and adipokine levels with prostate cancer stage were determined by conditional logistic regression and with grade (Gleason score ≥7 vs. ≤6) by unconditional logistic regression. Adiponectin was inversely associated with prostate cancer stage in overweight and obese men (OR 0.62; 95 % CI 0.42-0.90; p = 0.01), but not in normal weight men (OR 1.48; 0.77-2.82; p = 0.24) (p for interaction 0.007), or all men (OR 0.86; 0.66-1.11; p = 0.24). There was no compelling evidence of associations between leptin or leptin to adiponectin ratio and prostate cancer stage. No strong associations of adiponectin, leptin, or leptin:adiponectin ratio with grade were seen. This study provides some evidence that adiponectin levels may be associated with prostate cancer stage, dependent on the degree of adiposity of the man. Our results are consistent with adiponectin countering the adverse effects of obesity on prostate cancer progression.

Variations in Receipt of Curative-Intent Surgery for Early-Stage Non-Small Cell Lung Cancer (NSCLC) by State.

PubMed

Sineshaw, Helmneh M; Wu, Xiao-Cheng; Flanders, W Dana; Osarogiagbon, Raymond Uyiosa; Jemal, Ahmedin

2016-06-01

Previous studies reported racial and socioeconomic disparities in receipt of curative-intent surgery for early-stage non-small cell lung cancer (NSCLC) in the United States. We examined variation in receipt of surgery and whether the racial disparity varies by state. Patients in whom stage I or II NSCLC was diagnosed from 2007 to 2011 were identified from 38 state and the District of Columbia population-based cancer registries compiled by the North American Association of Central Cancer Registries. Percentage of patients receiving curative-intent surgery was calculated for each registry. Adjusted risk ratios were generated by using modified Poisson regression to control for sociodemographic (e.g., age, sex, race, insurance) and clinical (e.g., grade, stage) factors. Non-Hispanic (NH) whites and Massachusetts were used as references for comparisons because they had the lowest uninsured rates. In all registries combined, 66.4% of patients with early-stage NSCLC (73,475 of 110,711) received curative-intent surgery. Receipt of curative-intent surgery for early-stage NSCLC varied substantially by state, ranging from 52.2% to 56.1% in Wyoming, Louisiana, and New Mexico to 75.2% to 77.2% in Massachusetts, New Jersey, and Utah. In a multivariable analysis, the likelihood of receiving curative-intent surgery was significantly lower in all but nine states/registries compared with Massachusetts, ranging from 7% lower in California to 25% lower in Wyoming. Receipt of curative-intent surgery for early-stage NSCLC was lower for NH blacks than for NH whites in every state, although statistically significant in Florida and Texas. Receipt of curative-intent surgery for early-stage NSCLC varies substantially across states in the United States, with northeastern states generally showing the highest rates. Further, receipt of treatment appeared to be lower in NH blacks than in NH whites in every state, although statistically significant in Florida and Texas. Copyright © 2016

Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood brain barrier damage in early ischemic stroke stage

PubMed Central

Liu, Jie; Jin, Xinchun; Liu, Ke J.; Liu, Wenlan

2012-01-01

Blood brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran, and promoted the secretion of metalloproteinase-2 and 9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2-h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis. PMID:22378877

Validation of Biomarkers for the Early Detection of Colorectal Adenocarcinoma (GLNE 010) — EDRN Public Portal

Cancer.gov

We propose a Phase 2 (large cross-sectional) PRoBE-compliant validation trial of stool-based and serum-based tests for the detection of colorectal neoplasia (1). The trial is powered to detect early stage colorectal adenocarcinoma or high grade dysplasia. This is the most stringent, conservative approach to the early diagnosis of colonic neoplasia and addresses the most important endpoint of identifying individuals with curable, early stage cancer and those with very high risk non-invasive neoplasia (high grade dysplasia).

Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

PubMed Central

Meyerson, Nicholas R.; Sharma, Amit; Wilkerson, Gregory K.

2015-01-01

ABSTRACT Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCE Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals

Tumor biology of non-metastatic stages of clear cell renal cell carcinoma; overexpression of stearoyl desaturase-1, EPO/EPO-R system and hypoxia-related proteins.

PubMed

Stoyanoff, Tania Romina; Rodríguez, Juan Pablo; Todaro, Juan Santiago; Espada, Joaquín Diego; Colavita, Juan Pablo Melana; Brandan, Nora Cristina; Torres, Adriana Mónica; Aguirre, María Victoria

2016-10-01

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinomas. There is great interest to know the molecular basis of the tumor biology of ccRCC that might contribute to a better understanding of the aggressive biological behavior of this cancer and to identify early biomarkers of disease. This study describes the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (hypoxia-inducible factor (HIF)-1α, erythropoietin (EPO), vascular endothelial growth factor (VEGF)), their receptors (EPO-R, VEGFR-2), and stearoyl desaturase-1 (SCD-1) in early stages of ccRCC. Tissue samples were obtained at the Urology Unit of the J.R. Vidal Hospital (Corrientes, Argentina), from patients who underwent radical nephrectomy for renal cancer between 2011 and 2014. Four experimental groups according to pathological stage and nuclear grade were organized: T1G1 (n = 6), T2G1 (n = 4), T1G2 (n = 7), and T2G2 (n = 7). The expression of HIF-1α, EPO, EPO-R, VEGF, VEGFR-2, Bcl-x L , and SCD-1 were evaluated by immunohistochemistry, Western blotting, and/or RT-PCR. Apoptosis was assessed by the TUNEL in situ assay, and tumor proliferation was determined by Ki-67 immunohistochemistry. Data revealed that HIF-1α, EPO, EPO-R, VEGF, and VEGF-R2 were overexpressed in most samples. The T1G1 group showed the highest EPO levels, approximately 200 % compared with distal renal tissue. Bcl-x L overexpression was concomitant with the enhancement of proliferative indexes. SCD-1 expression increased with the tumor size and nuclear grade. Moreover, the direct correlations observed between SCD-1/HIF-1α and SCD-1/Ki-67 increments suggest a link among these molecules, which would determine tumor progression in early stages of ccRCC. Our results demonstrate the relationship among proliferation, survival, and apoptosis with the expression of key molecules related to tumoral hypoxia (HIF-1α, EPO, VEGF), their

Early Grade Repetition and Inattention Associated with Neurofibromatosis Type 1

ERIC Educational Resources Information Center

Coude, Francois X.; Mignot, Claire; Lyonnet, Stanislas; Munnich, Arnold

2007-01-01

Objective: The authors analyze the occurrence of grade repetition and inattention in children diagnosed with neurofibromatosis type 1 (NF1). Method: The participant group consisted of 310 patients with NF1 and a control group of 242 individuals. The number of grade repetitions for each participant during his or her time in elementary, middle, and…

Correlation study between facet joint cartilage and intervertebral discs in early lumbar vertebral degeneration using T2, T2* and T1ρ mapping

PubMed Central

Zhang, Yi; Hu, Jianzhong; Duan, Chunyue; Hu, Ping; Lu, Hongbin; Peng, Xianjing

2017-01-01

Recent advancements in magnetic resonance imaging have allowed for the early detection of biochemical changes in intervertebral discs and articular cartilage. Here, we assessed the feasibility of axial T2, T2* and T1ρ mapping of the lumbar facet joints (LFJs) to determine correlations between cartilage and intervertebral discs (IVDs) in early lumbar vertebral degeneration. We recruited 22 volunteers and examined 202 LFJs and 101 IVDs with morphological (sagittal and axial FSE T2-weighted imaging) and axial biochemical (T2, T2* and T1ρ mapping) sequences using a 3.0T MRI scanner. IVDs were graded using the Pfirrmann system. Mapping values of LFJs were recorded according to the degeneration grades of IVDs at the same level. The feasibility of T2, T2* and T1ρ in IVDs and LFJs were analyzed by comparing these mapping values across subjects with different rates of degeneration using Kruskal-Wallis tests. A Pearson’s correlation analysis was used to compare T2, T2* and T1ρ values of discs and LFJs. We found excellent reproducibility in the T2, T2* and T1ρ values for the nucleus pulposus (NP), anterior and posterior annulus fibrosus (PAF), and LFJ cartilage (intraclass correlation coefficients 0.806–0.955). T2, T2* and T1ρ mapping (all P<0.01) had good Pfirrmann grade performances in the NP with IVD degeneration. LFJ T2* values were significantly different between grades I and IV (PL = 0.032, PR = 0.026), as were T1ρ values between grades II and III (PL = 0.002, PR = 0.006) and grades III and IV (PL = 0.006, PR = 0.001). Correlations were moderately negative for T1ρ values between LFJ cartilage and NP (rL = −0.574, rR = −0.551), and between LFJ cartilage and PAF (rL = −0.551, rR = −0.499). T1ρ values of LFJ cartilage was weakly correlated with T2 (r = 0.007) and T2* (r = −0.158) values. Overall, we show that axial T1ρ effectively assesses early LFJ cartilage degeneration. Using T1ρ analysis, we propose a link between LFJ degeneration and IVD NP or

Exploring the Relationship between Early Childhood and Elementary Grade-Level Overlap and Early Childhood Teacher Output

ERIC Educational Resources Information Center

Fowler, R. Clarke

2017-01-01

This study explores the relationship between grade-level overlap between elementary education (ELED) and early childhood education (ECED) licenses and ECED teacher output. Analysis of Title 2 data indicates that ECED/ELED overlap is extensive, as evidenced by the number of states with grade-level overlaps of 5 (n = 2), 4 (n = 24), 3 (n = 10), and…

ALBI versus Child-Pugh grading systems for liver function in patients with hepatocellular carcinoma.

PubMed

Na, Seong K; Yim, Sun Y; Suh, Sang J; Jung, Young K; Kim, Ji H; Seo, Yeon S; Yim, Hyung J; Yeon, Jong E; Byun, Kwan S; Um, Soon H

2018-04-01

The prognostic performance of the albumin-bilirubin (ALBI) grade in hepatocellular carcinoma (HCC) as an objective method of assessing liver function was investigated. Data from 2099 patients with HCC in Korea were collected and analyzed retrospectively. The discriminative performance of ALBI grade was compared with Child-Pugh (C-P) grade for different stages or treatments. The median follow up duration was 16.2 months (range: 1.0-124.9). The median survival times were 49.7 months for C-P grade A (65.8%), 12.4 months for C-P grade B (25.5%), and 4.2 months for C-P grade C (8.6%) (P < 0.001). The median survival times were 84.2 months for ALBI grade 1 (32.8%), 25.5 months for ALBI grade 2 (53.5%), and 7.7 months for ALBI grade 3 (13.7%) (P < 0.001). In early UICC stages, ALBI grade showed better discriminative performance than C-P grade. In curative treatments, ALBI grade also showed better discriminative performance than C-P grade (Harrell's C: 0.624 (C-P grade) vs 0.667 [ALBI grade]). ALBI grade provided better prognostic performance in survival analysis and better distribution of the grades than C-P grade in HCC, suggesting that ALBI grade could be a good alternative grading system for liver function in patients with HCC. © 2018 Wiley Periodicals, Inc.

An Examination of Principals' Leadership and Its Impact on Early Elementary Grades

ERIC Educational Resources Information Center

Hallissey, Megan

2017-01-01

This exploratory, qualitative multiple-site case study examined principals' expectations of teaching practices and children's learning for early elementary grade levels (K, 1st, 2nd, and 3rd). Specifically, this study investigated principals' understanding of developmentally appropriate practices regarding instructional methods, curriculum…

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

PubMed

Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

From conventionally fractionated radiation therapy to hyperfractionated radiation therapy alone and with concurrent chemotherapy in patients with early-stage nonsmall cell lung cancer.

PubMed

Jeremić, Branislav; Milicić, Biljana

2008-02-15

The authors' single-institution experience in patients with early-stage (I and II) nonsmall cell lung cancer (NSCLC) who were treated between 1980 and 1998 with either conventionally fractionated (CF) radiation therapy (RT), or hyperfractionated (HFX) RT, or HFX RT with concurrent paclitaxel/carboplatin (HFX RT-Pac/C) was reviewed. Seventy-eight patients received 60 grays (Gy) in 30 daily fractions (CF), 116 patients received 69.6 Gy (1.2 Gy twice daily), and 56 patients received 67.6 Gy (1.3 Gy twice daily) with concurrent, low-dose, daily C (25 mg/m2) and Pac (10 mg/m2). Biologically equivalent doses for the 3 groups were 72 Gy, 78 Gy, and 76 Gy, respectively, for acute effects (alpha/beta = 10 Gy) and 120 Gy, 111 Gy, and 111 Gy, respectively, for late effects (alpha/beta = 2 Gy). For all 250 patients, the overall median survival was 27 months, the cause-specific survival was 27 months, the local progression-free survival was 32 months, and distant metastasis-free survival was not achieved; and the respective 5-year survival rates were 27%, 32%, 45%, and 68%. CF achieved significantly inferior survival than either HFX RT alone or HFX RT-Pac/C (P = .0332 and P = .0013, respectively), and no difference was observed between the 2 HFX RT regimens (P = .1934). Only acute hematologic high-grade toxicity (grade >or=3) was more frequent with HFX RT-Pac/C than with either RT alone, whereas other toxicities were similar between the 3 treatment groups. HFX RT with or without concurrent chemotherapy may be better than CF in patients with early-stage NSCLC. The role of chemotherapy deserves further investigation, because the group that received chemotherapy in the current study had a higher incidence of acute high-grade hematologic toxicity. Cancer 2008. (c) 2008 American Cancer Society.

IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

PubMed

Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

2017-02-15

The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

PubMed

Sanguedolce, Francesca; Cormio, Antonella; Massenio, Paolo; Pedicillo, Maria C; Cagiano, Simona; Fortunato, Francesca; Calò, Beppe; Di Fino, Giuseppe; Carrieri, Giuseppe; Bufo, Pantaleo; Cormio, Luigi

2018-04-01

The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

Climatic factors affecting quantity and quality grade of in vivo derived embryos of cattle.

PubMed

Chinchilla-Vargas, Josué; Jahnke, Marianna M; Dohlman, Tyler M; Rothschild, Max F; Gunn, Patrick J

2018-05-01

The present study investigated the effects of climatic variables on the quality grade and quantity of in vivo derived cattle embryos in the Midwestern United States. Climatic information included greatest and least daily temperature, average daily wind speed and average temperature-humidity index for each of the 765 records. The response variables included the number of ovarian structures, viable embryos, quality grade 1 embryos, quality grade 2 embryos, quality grade 3 embryos, freezable embryos (sum of quality grade 1 and quality grade 2 embryos), transferable embryos (sum of quality grade 1-3 embryos), degenerate embryos and unfertilized ova. Measures for variables among the breeds of donors and sires grouped by geographical origin were compared. A negative effect of greater temperatures during the early embryonic development stage tended (P < 0.10) to be associated with a decrease in the quality of embryos recovered. Interestingly, the greater the Temperature-Humidity Index (THI) during the early ovarian antral follicular development stage 40-45 days prior to ovulation was associated with a tendency for greater numbers of total number of freezable and transferable embryos recovered per uterine flushing (P < 0.10). Increased wind speed at the early antral follicular phase 40-45 days prior to ovulation was associated with an increase in the percentage of quality grade 1 embryos recovered (P < 0.05). Wind speed during the estrous synchronization period was also associated with a lesser number of embryos recovered (P < 0.05). This retrospective study confirms that climatic variables have significant effects on the in vivo production of cattle embryos and that wind speed should be considered in future analyses of factors affecting embryo quality. Copyright © 2018 Elsevier B.V. All rights reserved.

Temperament in early childhood and peer interactions in third grade: the role of teacher-child relationships in early elementary grades.

PubMed

Rudasill, Kathleen Moritz; Niehaus, Kate; Buhs, Eric; White, Jamie M

2013-12-01

Children's interactions with peers in early childhood have been consistently linked to their academic and social outcomes. Although both child and classroom characteristics have been implicated as contributors to children's success, there has been scant research linking child temperament, teacher-child relationship quality, and peer interactions in the same study. The purpose of this study is to examine children's early temperament, rated at preschool age, as a predictor of interactions with peers (i.e., aggression, relational aggression, victimization, and prosociality) in third grade while considering teacher-child relationship quality in kindergarten through second grades as a moderator and mediator of this association. The sample (N=1364) was drawn from the NICHD Study of Early Child Care and Youth Development. Results from structural equation models indicated that teacher-child conflict in early elementary grades mediated links between children's temperament and later peer interactions. Findings underscore the importance of considering children's temperament traits and teacher-child relationship quality when examining the mechanisms of the development of peer interactions. © 2013.

Arizona Academic Standards, Grade 2

ERIC Educational Resources Information Center

Arizona Department of Education, 2009

2009-01-01

This publication contains Arizona public schools' academic standards for grade 2. The contents of this document include the following: (1) The Arts Standard 2006--Grade 2; (2) Comprehensive Health Education/Physical Activity Standards 1997--Foundations (Grades 1-3); (3) Foreign and Native Language Standards 1997--Foundations (Grades 1-3); (4)…

The effect of caudal vs intravenous morphine on early extubation and postoperative analgesic requirements for stage 2 and 3 single-ventricle palliation: a double blind randomized trial.

PubMed

Stuth, Eckehard A E; Berens, Richard J; Staudt, Susan R; Robertson, Frederick A; Scott, John P; Stucke, Astrid G; Hoffman, George M; Troshynski, Todd J; Tweddell, James S T; Zuperku, Edward J

2011-04-01

High-dose single-shot caudal morphine has been postulated to facilitate early extubation and to lower initial analgesic requirements after staged single-ventricle (SV) palliation. With Institutional Review Board approval and written informed parental consent, 64 SV children aged 75-1667 days were randomized to pre-incisional caudal morphine-bupivacaine (100 μg·kg(-1) morphine (concentration 0.1%), mixed with 0.25% bupivacaine with 1 : 200,000 epinephrine, total 1 ml·kg(-1)) and postcardiopulmonary bypass (CPB) intravenous (IV) droperidol (75 μg·kg(-1)) ('active caudal group') or pre-incisional caudal saline (1 ml·kg(-1)) and post-CPB IV morphine (150 μg·kg(-1)) with droperidol (75 μg·kg(-1)) ('active IV group'). Assignment remained concealed from families and the care teams throughout the trial. Early extubation failure rates (primary or reintubation within 24 h), time to first postoperative rescue morphine analgesia, and 12-h postoperative morphine requirements were assessed for extubated patients. Thirty-one (12 stage 2) SV patients received caudal morphine and 32 (15 stage 2) received IV morphine. Extubation failure rates were 6/31 (19%) for caudal and 5/32 (16%) for IV morphine. For successfully extubated patients (n = 54), active caudal treatment significantly delayed the need for postoperative rescue morphine in stage 3 patients (P = 0.02) but not in stage 2 patients (P = 0.189) (Kaplan-Meier survival analysis with LogRank test). The reduction in 12-h postoperative morphine requirements with active caudal treatment did not reach significance (P = 0.085) but morphine requirements were significantly higher for stage 2 compared with stage 3 patients (P < 0.001) (two-way anova in n = 50 extubated patients). High-dose caudal morphine with bupivacaine delayed the need for rescue morphine analgesia in stage 3 patients. All stage 2 patients required early rescue morphine and had significantly higher postoperative 12-h morphine requirements than stage 3

[Expansion of secretory cells in the fallopian tubal epithelium in the early stages of the pathogenesis of ovarian serous carcinomas].

PubMed

Asaturova, A V; Ezhova, L S; Faizullina, N M; Adamyan, L V; Khabas, G N; Sannikova, M V

to investigate the frequency of the types of fallopian tubal secretory cell expansion (SCE) in diseases of the reproductive organs and to determine the immunophenotype and biological role of the cells in the early stages of the pathogenesis of high-grade ovarian serous carcinomas (HGOSC). The investigation enrolled 287 patients with extraovarian diseases and ovarian serous tumors varying in grade, whose fallopian tubes were morphologically and immunohistochemically examined using p53, Ki-67, PAX2, Bcl-2, beta-catenin, and ALDH1 markers. The material was statistically processed applying the Mann-Whitney test and χ2 test. The rate of secretory cell proliferation (SCP) (more than 10 consecutive secretory cells) and that of secretory cell overgrowth (SCO) (more than 30 consecutive secretory cells) increase with age in all investigated reproductive system diseases. The rate of SCP in the corpus fimbriatum of the patients with HGOSC was 5.9 times higher than that in those with extraovarian disease (p<0.01); when comparing the same patient groups, that of SCO was 3.4 times higher (p<0.05). The immunohistochemical characteristics of the investigated lesions (in scores) were as follows: PAX2 was expressed in the intact epithelium (2.8), in SCP (1.3), in SCO (1.2), in serous tubal intraepithelial carcinoma (STIC) (1.0), and in HGOSC (0.9); Bcl-2 was in the intact epithelium (2.2), in SCP (2.1), STIC (0.9), and in HGOSC (0.6), β-catenin was in the intact epithelium (0.5), in SCP (2.85), in SCO (2.95), in STIC (0.6), and in HGOSC (0.5); ALDH1 was in the intact epithelium (0.5), in SCP (2.91), in SCO (2.92), in STIC (1.2), and in HGOSC (0.6). There were statistically significant differences with a 95% confidence interval (p<0.05) for: 1) PAX2 between the intact epithelium and pathology (fallopian tube lesions and HGOSC); 2) Bcl-2 between the intact epithelium and SCE (SCP and SCO) and between SCE and HGOSC; 3) beta-catenin between the intact epithelium and SCE (SCP and SCO

A noncanonical role for dynamin-1 in regulating early stages of clathrin-mediated endocytosis in non-neuronal cells

PubMed Central

Bhave, Madhura; Chen, Zhiming; Chen, Ping-Hung; Wang, Xinxin; Danuser, Gaudenz

2018-01-01

Dynamin Guanosine Triphosphate hydrolases (GTPases) are best studied for their role in the terminal membrane fission process of clathrin-mediated endocytosis (CME), but they have also been proposed to regulate earlier stages of CME. Although highly enriched in neurons, dynamin-1 (Dyn1) is, in fact, widely expressed along with Dyn2 but inactivated in non-neuronal cells via phosphorylation by glycogen synthase kinase-3 beta (GSK3β) kinase. Here, we study the differential, isoform-specific functions of Dyn1 and Dyn2 as regulators of CME. Endogenously expressed Dyn1 and Dyn2 were fluorescently tagged either separately or together in two cell lines with contrasting Dyn1 expression levels. By quantitative live cell dual- and triple-channel total internal reflection fluorescence microscopy, we find that Dyn2 is more efficiently recruited to clathrin-coated pits (CCPs) than Dyn1, and that Dyn2 but not Dyn1 exhibits a pronounced burst of assembly, presumably into supramolecular collar-like structures that drive membrane scission and clathrin-coated vesicle (CCV) formation. Activation of Dyn1 by acute inhibition of GSK3β results in more rapid endocytosis of transferrin receptors, increased rates of CCP initiation, and decreased CCP lifetimes but did not significantly affect the extent of Dyn1 recruitment to CCPs. Thus, activated Dyn1 can regulate early stages of CME that occur well upstream of fission, even when present at low, substoichiometric levels relative to Dyn2. Under physiological conditions, Dyn1 is activated downstream of epidermal growth factor receptor (EGFR) signaling to alter CCP dynamics. We identify sorting nexin 9 (SNX9) as a preferred binding partner to activated Dyn1 that is partially required for Dyn1-dependent effects on early stages of CCP maturation. Together, we decouple regulatory and scission functions of dynamins and report a scission-independent, isoform-specific regulatory role for Dyn1 in CME. PMID:29668686

Driving behaviors in early stage dementia: a study using in-vehicle technology.

PubMed

Eby, David W; Silverstein, Nina M; Molnar, Lisa J; LeBlanc, David; Adler, Geri

2012-11-01

According to the Alzheimer's Association (2011), (1) in 8 people age 65 and older, and about one-half of people age 85 and older, have Alzheimer's disease in the United States (US). There is evidence that drivers with Alzheimer's disease and related dementias are at an increased risk for unsafe driving. Recent advances in sensor, computer, and telecommunication technologies provide a method for automatically collecting detailed, objective information about the driving performance of drivers, including those with early stage dementia. The objective of this project was to use in-vehicle technology to describe a set of driving behaviors that may be common in individuals with early stage dementia (i.e., a diagnosis of memory loss) and compare these behaviors to a group of drivers without cognitive impairment. Seventeen drivers with a diagnosis of early stage dementia, who had completed a comprehensive driving assessment and were cleared to drive, participated in the study. Participants had their vehicles instrumented with a suite of sensors and a data acquisition system, and drove 1-2 months as they would under normal circumstances. Data from the in-vehicle instrumentation were reduced and analyzed, using a set of algorithms/heuristics developed by the research team. Data from the early stage dementia group were compared to similar data from an existing dataset of 26 older drivers without dementia. The early stage dementia group was found to have significantly restricted driving space relative to the comparison group. At the same time, the early stage dementia group (which had been previously cleared by an occupational therapist as safe to drive) drove as safely as the comparison group. Few safety-related behavioral errors were found for either group. Wayfinding problems were rare among both groups, but the early stage dementia group was significantly more likely to get lost. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dual odontogenic origins develop at the early stage of rat maxillary incisor development.

PubMed

Kriangkrai, Rungarun; Iseki, Sachiko; Eto, Kazuhiro; Chareonvit, Suconta

2006-03-01

Developmental process of rat maxillary incisor has been studied through histological analysis and investigation of tooth-related gene expression patterns at initial tooth development. The tooth-related genes studied here are fibroblast growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium and/or ectomesenchyme at the stage of epithelial thickening to the early bud stage of tooth development. Both the histological observation and tooth-related gene expression patterns during early stage of maxillary incisor development demonstrate that dual odontogenic origins aligned medio-laterally in the medial nasal process develop, subsequently only single functional maxillary incisor dental placode forms. The cascade of tooth-related gene expression patterns in rat maxillary incisor studied here is quite similar to those of the previous studies in mouse mandibular molar, even though the origins of oral epithelium and ectomesenchyme involved in development of maxillary incisor and mandibular molar are different. Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development.

Occurrence of lymph node metastasis in early-stage parotid gland cancer.

PubMed

Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

2012-02-01

Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

A Four-Stage Method for Developing Early Interventions for Alcohol among Aboriginal Adolescents

ERIC Educational Resources Information Center

Mushquash, Christopher J.; Comeau, M. Nancy; McLeod, Brian D.; Stewart, Sherry H.

2010-01-01

This paper details a four-stage methodology for developing early alcohol interventions for at-risk Aboriginal youth. Stage 1 was an integrative approach to Aboriginal education that upholds Aboriginal traditional wisdom supporting respectful relationships to the Creator, to the land and to each other. Stage 2 used quantitative methods to…

The associations of TERT-CLPTM1L variants and TERT mRNA expression with the prognosis of early stage non-small cell lung cancer.

PubMed

Chen, Z; Wang, J; Bai, Y; Wang, S; Yin, X; Xiang, J; Li, X; He, M; Zhang, X; Wu, T; Xu, P; Guo, H

2017-01-01

Lung cancer is the leading cause of cancer-related death in the world. Several genome-wide association studies (GWAS) have identified TERT-CLPTM1L as plausible causative locus for lung cancer development. This study aimed to investigate the associations of genetic variations in TERT-CLPTM1L and the expression level of TERT with the survival of early stage non-small cell lung cancer (NSCLC) patients. We selected three single-nucleotide polymorphisms of TERT-CLPTM1L (rs2853669, rs2736108 and rs31490) and genotyped in 140 early stage NSCLC patients by TaqMan assay. Associations between these variations and survival outcome of early stage NSCLC patients were further investigated. We also used TCGA data to evaluate the associations of TERT messenger RNA (mRNA) expression and survival outcome of early stage NSCLC patients. Survival analysis showed that, compared with early NSCLC patients carrying TERT rs2853669 TT+TC genotypes, patients with rs2853669 CC genotype had significantly longer median survival time (MST=102.2 vs 52.4 months; log-rank P=0.028) and lower death risk [hazard ratio (HR) with 95% confidence interval (CI))=0.38(0.17-0.82), P=0.014]. Early NSCLC patients carrying TERT rs2736108 AA genotype had significantly shorter MST (MST=29.0 vs 63.3 months; log-rank P=0.020) and increased death risk [HR (95% CI)=2.22(1.01-5.80), P=0.046], when compared with patients carrying rs2736108 GG genotypes. TCGA data revealed that early NSCLC patients with higher expression level of TERT mRNA in lung tumor tissues had a longer MST and decreased death risk than those with low expression level of TERT mRNA [MST=54.4 vs 49.0 months; log-rank P=0.041; adjusted HR (95% CI)=0.68(0.50-0.94)]. These findings may add potential evidence to understand the prognostic value of TERT and provide a new prospect of individualized prevention and treatment for early stage NSCLC.

Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

PubMed Central

2011-01-01

Introduction Detection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients. Methods We used a microarray platform of 60mer MUC1 glycopeptides, to confirm the presence of autoantibodies to cancer associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans at specific sites. Based on these results, larger amounts of an extended repertoire of defined MUC1 glycopeptides were synthesised, printed on microarrays, and screened with sera from a large cohort of breast cancer patients (n = 395), patients with benign breast disease (n = 108) and healthy controls (n = 99). All sera were collected in the 1970s and 1980s and complete clinical follow-up of breast cancer patients is available. Results The presence and level of autoantibodies was significantly higher in the sera from cancer patients compared with the controls, and a highly significant correlation with age was observed. High levels of a subset of autoantibodies to the core3MUC1 (GlcNAcβ1-3GalNAc-MUC1) and STnMUC1 (NeuAcα2,6GalNAc-MUC1) glycoforms were significantly associated with reduced incidence

Changes in verbal and visuospatial working memory from Grade 1 to Grade 3 of primary school: Population longitudinal study.

PubMed

Nicolaou, E; Quach, J; Lum, J; Roberts, G; Spencer-Smith, M; Gathercole, S; Anderson, P J; Mensah, F K; Wake, M

2018-05-01

Adaptive working memory training is being implemented without an adequate understanding of developmental trajectories of working memory. We aimed to quantify from Grade 1 to Grade 3 of primary school (1) changes in verbal and visuospatial working memory and (2) whether low verbal and visuospatial working memory in Grade 1 predicts low working memory in Grade 3. The study design includes a population-based longitudinal study of 1,802 children (66% uptake from all 2,747 Grade 1 students) at 44 randomly selected primary schools in Melbourne, Australia. Backwards Digit Recall (verbal working memory) and Mister X (visuospatial working memory) screening measures from the Automated Working Memory Assessment (M = 100; SD = 15) were used to assess Grades 1 and 3 (ages 6-7 and 8-9 years) students. Low working memory was defined as ≥1 standard deviation below the standard score mean. Descriptive statistics addressed Aim 1, and predictive parameters addressed Aim 2. One thousand seventy (59%) of 1802 Grade 1 participants were reassessed in Grade 3. As expected for typically developing children, group mean standard scores were similar in Grades 1 and 3 for verbal, visuospatial, and overall working memory, but group mean raw scores increased markedly. Compared to "not low" children, those classified as having low working memory in Grade 1 showed much larger increases in both standard and raw scores across verbal, visuospatial, and overall working memory. Sensitivity was very low for Grade 1 low working memory predicting Grade 3 low classifications. Although mean changes in working memory standard scores between Grades 1 and 3 were minimal, we found that individual development varied widely, with marked natural resolution by Grade 3 in children who initially had low working memory. This may render brain-training interventions ineffective in the early school year ages, particularly if (as population-based programmes usually mandate) selection occurs within a screening

Arizona Academic Standards, Grade 1

ERIC Educational Resources Information Center

Arizona Department of Education, 2009

2009-01-01

This publication contains Arizona public schools' academic standards for Grade 1. The contents of this document include the following: (1) The Arts Standard 2006--Grade 1; (2) Comprehensive Health Education/Physical Activity Standards 1997--Foundations (Grades 1-3); (3) Foreign and Native Language Standards 1997--Foundations (Grades 1-3); (4)…

Longitudinal Prediction of 1st and 2nd Grade English Oral Reading Fluency in English Language Learners: Which Early Reading and Language Skills Are Better Predictors?

ERIC Educational Resources Information Center

Solari, Emily J.; Aceves, Terese C.; Higareda, Ignacio; Richards-Tutor, Cara; Filippini, Alexis L.; Gerber, Michael M.; Leafstedt, Jill

2014-01-01

This study investigates the relation between Spanish and English early literacy skills in kindergarten and first grade, and English oral reading fluency at the end of first and second grade in a sample of 150 Spanish-speaking English language learners. Students were assessed in kindergarten, first, and second grades on a broad bilingual academic…

Attenuation of p38-mediated miR-1/133 expression facilitates myoblast proliferation during the early stage of muscle regeneration.

PubMed

Zhang, Duo; Li, Xihua; Chen, Chuchu; Li, Yuyin; Zhao, Lei; Jing, Yanyan; Liu, Wei; Wang, Xiaoyun; Zhang, Ying; Xia, Hongfeng; Chang, Yaning; Gao, Xiang; Yan, Jun; Ying, Hao

2012-01-01

Myoblast proliferation following myotrauma is regulated by multiple factors including growth factors, signal pathways, transcription factors, and miRNAs. However, the molecular mechanisms underlying the orchestration of these regulatory factors remain unclear. Here we show that p38 signaling is required for miR-1/133a clusters transcription and both p38 activity and miR-1/133 expression are attenuated during the early stage of muscle regeneration in various animal models. Additionally, we show that both miR-1 and miR-133 reduce Cyclin D1 expression and repress myoblast proliferation by inducing G1 phase arrest. Furthermore, we demonstrate that miR-133 inhibits mitotic progression by targeting Sp1, which mediates Cyclin D1 transcription, while miR-1 suppresses G1/S phase transition by targeting Cyclin D1. Finally, we reveal that proproliferative FGF2, which is elevated during muscle regeneration, attenuates p38 signaling and miR-1/133 expression. Taken together, our results suggest that downregulation of p38-mediated miR-1/133 expression by FGF2 and subsequent upregulation of Sp1/Cyclin D1 contribute to the increased myoblast proliferation during the early stage of muscle regeneration.

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

PubMed

Yamanishi, Tadashi; Nishio, Juntaro; Sako, Michiyo; Kohara, Hiroshi; Hirano, Yoshiko; Yamanishi, Yukiko; Adachi, Tadafumi; Miya, Shigenori; Mukai, Takao

2011-02-01

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm': ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N'-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N': ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S': ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2

Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer.

PubMed

Chang, Joe Y; Komaki, Ritsuko; Lu, Charles; Wen, Hong Y; Allen, Pamela K; Tsao, Anne; Gillin, Michael; Mohan, Radhe; Cox, James D

2011-10-15

The authors sought to improve the toxicity of conventional concurrent chemoradiation therapy for stage III nonsmall cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. They report early results of a phase 2 study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. Forty-four patients with stage III NSCLC were treated with 74 grays (radiobiologic equivalent) proton therapy with weekly carboplatin (area under the curve, 2 U) and paclitaxel (50 mg/m(2)). Disease was staged with positron emission tomography/computed tomography (CT), and treatments were simulated with 4-dimensional (4D) CT to account for tumor motion. Protons were delivered as passively scattered beams, and treatment simulation was repeated during the treatment process to determine the need for adaptive replanning. Median follow-up time was 19.7 months (range, 6.1-44.4 months), and median overall survival time was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n = 5), esophagitis (n = 5), and pneumonitis (n = 1). Nine (20.5%) patients experienced local disease recurrence, but only 4 (9.1%) had isolated local failure. Four (9.1%) patients had regional lymph node recurrence, but only 1 (2.3%) had isolated regional recurrence. Nineteen (43.2%) patients developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. Concurrent high-dose proton therapy and chemotherapy are well tolerated, and the median survival time of 29.4 months is encouraging for unresectable stage III NSCLC. Copyright © 2011 American Cancer Society.

Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

PubMed Central

Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

2016-01-01

Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

Food-grade antimicrobials potentiate the antibacterial activity of 1,2-hexanediol.

PubMed

Yogiara; Hwang, S J; Park, S; Hwang, J-K; Pan, J-G

2015-05-01

Preservative agents determining the shelf life of cosmetic products must have effective antimicrobial activity while meeting safety requirements for topical use. In this study, we determined the antimicrobial activity of 1,2-hexanediol against several Gram-positive and Gram-negative bacteria. Antimicrobial susceptibility tests have shown that 1,2-hexanediol exhibits broad-spectrum activity against Gram-positive and Gram-negative bacteria with MICs of 0·5-2% (v/v). The bactericidal concentration of 1,2-hexanediol was ranging from 1 to 2 × MIC as demonstrated by time-kill curve assay. A membrane depolarization assay showed that 1,2-hexanediol disrupted the cytoplasmic membrane potential. A checkerboard assay indicated that the effective concentration of 1,2-hexanediol was reduced up to 0·25-0·5 × MIC when combined with macelignan and octyl gallate against Gram-positive bacteria. However, this combination was not effective against Gram-negative bacteria. A turbidity reduction assay demonstrated that the combination of a high concentration of 1,2-hexanediol with food-grade antimicrobial compounds could trigger lytic activity towards Bacillus cereus cells. The remaining cell turbidity was 24·6 and 22·2% when 2% of 1,2-hexanediol was combined with 8 mg l(-1) octyl gallate or with 32 mg l(-1) macelignan respectively. This study showed that food-grade antimicrobial compounds may be used in combination with 1,2-hexanediol to increase its efficacy as a preservative agent in cosmetics. The antimicrobial activity of 1,2-hexanediol against Gram-positive and Gram-negative bacteria was potentiated with food-grade antimicrobials including xanthorrhizol, macelignan, panduratin A and octyl gallate, which have already been reported to display anti-inflammatory and other beneficial activities related to cosmetics. Therefore, the combination of 1,2-hexanediol and these food-grade antimicrobial agents would have benefits not only for increasing the antimicrobial activity

Literacy Learning of At-Risk First-Grade Students in the Reading Recovery Early Intervention

ERIC Educational Resources Information Center

Schwartz, Robert M.

2005-01-01

This study investigated the effectiveness and efficiency of the Reading Recovery early intervention. At-risk 1st-grade students were randomly assigned to receive the intervention during the 1st or 2nd half of the school year. High-average and low-average students from the same classrooms provided additional comparisons. Thirty-seven teachers from…

Cold-air investigation of a 4 1/2 stage turbine with stage-loading factor of 4.66 and high specific work output. 2: Stage group performance

NASA Technical Reports Server (NTRS)

Whitney, W. J.; Behning, F. P.; Moffitt, T. P.; Hotz, G. M.

1980-01-01

The stage group performance of a 4 1/2 stage turbine with an average stage loading factor of 4.66 and high specific work output was determined in cold air at design equivalent speed. The four stage turbine configuration produced design equivalent work output with an efficiency of 0.856; a barely discernible difference from the 0.855 obtained for the complete 4 1/2 stage turbine in a previous investigation. The turbine was designed and the procedure embodied the following design features: (1) controlled vortex flow, (2) tailored radial work distribution, and (3) control of the location of the boundary-layer transition point on the airfoil suction surface. The efficiency forecast for the 4 1/2 stage turbine was 0.886, and the value predicted using a reference method was 0.862. The stage group performance results were used to determine the individual stage efficiencies for the condition at which design 4 1/2 stage work output was obtained. The efficiencies of stages one and four were about 0.020 lower than the predicted value, that of stage two was 0.014 lower, and that of stage three was about equal to the predicted value. Thus all the stages operated reasonably close to their expected performance levels, and the overall (4 1/2 stage) performance was not degraded by any particularly inefficient component.

Treatment of early non-small cell lung cancer, stage IA, by image-guided robotic stereotactic radioablation--CyberKnife.

PubMed

Brown, William T; Wu, Xiaodong; Amendola, Beatriz; Perman, Mark; Han, Hoke; Fayad, Fahed; Garcia, Silvio; Lewin, Alan; Abitbol, Andre; de la Zerda, Alberto; Schwade, James G

2007-01-01

To evaluate the efficacy of using image-guided robotic stereotactic radioablation as an alternative treatment modality for patients with surgically resectable, but medically inoperable, T1 N0 M0, stage IA non-small cell lung cancer. Between January 2004 and May 2006, 19 patients, 11 women and 8 men ranging in age from 52 to 88 years, with stage IA non-small cell lung cancer were treated. Tumor volume ranged from 1.7 to 13 mL. Total doses ranged from 24 to 60 Gy delivered in 3 fractions. Eleven patients received 60 Gy. Real-time target localization was accomplished by radiographic detection of fiducial marker(s) implanted within the tumor combined with respiratory motion tracking. All patients tolerated radioablation well with fatigue as the main side effect. Fourteen patients are alive from 1 to 25 months posttreatment. Four patients died: 2 of comorbid disease and 2 of cancer progression (status post 60 and 55.5 Gy). Three patients developed grade I radiation pneumonitis. Two patients have stable disease. In 3 patients, cancer recurred in the planning treatment volume: in 2 patients after treatment with 60 Gy and in 1 patient after treatment with 55.5 Gy. One patient had local control in the target volume but developed metastasis to the ipsilateral hilum. Nine patients had a complete response and show no evidence of disease. In our early experience, stereotactic radioablation using the CyberKnife system appears to be a safe, minimally invasive, and effective modality for treating early stage lung cancer in patients with medically inoperable disease. Dose escalation and/or increasing the treatment volumes, with the aid of the high conformality of this technique, may help to achieve further improvements in these promising results.

The elemental composition of purple sea urchin (Strongylocentrotus purpuratus) calcite and potential effects of pCO2 during early life stages

NASA Astrophysics Data System (ADS)

LaVigne, M.; Hill, T. M.; Sanford, E.; Gaylord, B.; Russell, A. D.; Lenz, E. A.; Hosfelt, J. D.; Young, M. K.

2013-06-01

Ocean acidification will likely have negative impacts on invertebrates producing skeletons composed of calcium carbonate. Skeletal solubility is partly controlled by the incorporation of "foreign" ions (e.g. magnesium) into the crystal lattice of these skeletal structures, a process that is sensitive to a variety of biological and environmental factors. Here we explore effects of life stage, oceanographic region of origin, and changes in the partial pressure of carbon dioxide in seawater (pCO2) on trace elemental composition in the purple sea urchin (Strongylocentrotus purpuratus). We show that, similar to other urchin taxa, adult purple sea urchins have the ability to precipitate skeleton composed of a range of biominerals spanning low- to high-Mg calcites. Mg / Ca and Sr / Ca ratios were substantially lower in adult spines compared to adult tests. On the other hand, trace elemental composition was invariant among adults collected from four oceanographically distinct regions spanning a range of carbonate chemistry conditions (Oregon, Northern California, Central California, and Southern California). Skeletons of newly settled juvenile urchins that originated from adults from the four regions exhibited intermediate Mg / Ca and Sr / Ca between adult spine and test endmembers, indicating that skeleton precipitated during early life stages is more soluble than adult spines and less soluble than adult tests. Mean skeletal Mg / Ca or Sr / Ca of juvenile skeleton did not vary with source region when larvae were reared under present-day, global-average seawater carbonate conditions (400 μatm; pHT = 8.02 ± 0.03 1 SD; Ωcalcite = 3.3 ± 0.2 1 SD). However, when reared under elevated pCO2 (900 μatm; pHT = 7.73 ± 0.03; Ωcalcite = 1.8 ± 0.1), skeletal Sr / Ca in juveniles exhibited increased variance across the four regions. Although larvae from the northern populations (Oregon, Northern California, Central California) did not exhibit differences in Mg or Sr

FIGO stage IIIC endometrial cancer identification among patients with complex atypical hyperplasia, grade 1 and 2 endometrioid endometrial cancer: laparoscopic indocyanine green sentinel lymph node mapping versus frozen section of the uterus, why get around the problem?

PubMed

Papadia, Andrea; Gasparri, Maria Luisa; Siegenthaler, Franziska; Imboden, Sara; Mohr, Stefan; Mueller, Michael D

2017-03-01

To compare two surgical strategies used to identify lymph node metastases in patients with preoperative diagnosis of complex atypical hyperplasia (CAH), grade 1 and 2 endometrial cancer (EC). Data on patients with preoperative diagnosis of CAH, grade 1 and 2 EC undergoing laparoscopic indocyanine green (ICG) sentinel lymph node (SLN) mapping followed by frozen section of the uterus were collected. When risk factors were identified at frozen section, patients were subjected to a systematic lymphadenectomy. False negative (FN) rates, negative predictive values (NPV), positive predictive values (PPV) and correlation with stage IIIC EC were calculated for the systematic lymphadenectomy based on frozen section of the uterus and for the SLN mapping. Six (9.5%) out of 63 patients had lymph nodal metastases. Based on frozen section of the uterus, 22 (34.9%) and 15 (22.2%) patients underwent a pelvic and a pelvic and paraaortic lymphadenectomy, respectively. Five patients with stage IIIC disease were identified with a FN rate of 16.7% and a NPV and PPV of 97.6 and 27.3%, respectively. Overall and bilateral detection rates of ICG SLN mapping were 100 and 97.6%, respectively; no FN were recorded. The identification of patients with stage IIIC disease with ICG SLN mapping showed a NPV and PPV of 100%. Correlation between indication to lymphadenectomy and stage IIIC disease was poor (κ = 0.244) when based on frozen section of the uterus and excellent (κ = 1) when based on SLN mapping. ICG SLN mapping reduces the number of unnecessary systematic lymphadenectomies and the risk of underdiagnosing patients with metastatic lymph nodes.

All-optical photoacoustic imaging and detection of early-stage dental caries

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

2015-02-01

Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

The Relationship of Piaget's Stages of Cognitive Development to First Grade Reading Achievement.

ERIC Educational Resources Information Center

Borucki, Diane Marie

The relationship between level of cognitive functioning at the beginning of first grade and level of reading achievement at the end of first grade was investigated in a sample of 325 children. The EITS Concept Assessment Kit-Conservation was used to classify the children as being in the preconceptual stage, the intuitive stage, or the concrete…

VHL and HIF-1α: gene variations and prognosis in early-stage clear cell renal cell carcinoma.

PubMed

Lessi, Francesca; Mazzanti, Chiara Maria; Tomei, Sara; Di Cristofano, Claudio; Minervini, Andrea; Menicagli, Michele; Apollo, Alessandro; Masieri, Lorenzo; Collecchi, Paola; Minervini, Riccardo; Carini, Marco; Bevilacqua, Generoso

2014-03-01

Von Hipple-Lindau gene (VHL) inactivation represents the most frequent abnormality in clear cell renal cell carcinoma (ccRCC). Hypoxia-inducible factor-1α (HIF-1α) expression is regulated by O2 level. In normal O2 conditions, VHL binds HIF-1α and allows HIF-1α proteasomal degradation. A single-nucleotide polymorphism (SNP) has been found located in the oxygen-dependent degradation domain at codon 582 (C1772T, rs11549465, Pro582Ser). In hypoxia, VHL/HIF-1α interaction is abolished and HIF-1α activates target genes in the nucleus. This study analyzes the impact of genetic alterations and protein expression of VHL and the C1772T SNP of HIF-1α gene (HIF-1α) on prognosis in early-stage ccRCC (pT1a, pT1b, and pT2). Mutational analysis of the entire VHL sequence and the genotyping of HIF-1α C1772T SNP were performed together with VHL promoter methylation analysis and loss of heterozygosis (LOH) analysis at (3p25) locus. Data obtained were correlated with VHL and HIF-1α protein expression and with tumor-specific survival (TSS). VHL mutations, methylation status, and LOH were detected in 51, 11, and 12% of cases, respectively. Our results support the association between biallelic alterations and/or VHL silencing with a worse TSS. Moreover, we found a significant association between the HIF-1α C1772C genotype and a worse TSS. The same association was found when testing the presence of HIF-1α protein in the nucleus. Our results highlight the role of VHL/HIF-1α pathway in RCC and support the molecular heterogeneity of early-stage ccRCC. More important, we show the involvement of HIF-1α C1772T SNP in ccRCC progression.

EARLY SENESCENCE1 Encodes a SCAR-LIKE PROTEIN2 That Affects Water Loss in Rice1[OPEN

PubMed Central

Rao, Yuchun; Yang, Yaolong; Xu, Jie; Li, Xiaojing; Leng, Yujia; Dai, Liping; Huang, Lichao; Shao, Guosheng; Ren, Deyong; Hu, Jiang; Guo, Longbiao; Pan, Jianwei; Zeng, Dali

2015-01-01

The global problem of drought threatens agricultural production and constrains the development of sustainable agricultural practices. In plants, excessive water loss causes drought stress and induces early senescence. In this study, we isolated a rice (Oryza sativa) mutant, designated as early senescence1 (es1), which exhibits early leaf senescence. The es1-1 leaves undergo water loss at the seedling stage (as reflected by whitening of the leaf margin and wilting) and display early senescence at the three-leaf stage. We used map-based cloning to identify ES1, which encodes a SCAR-LIKE PROTEIN2, a component of the suppressor of cAMP receptor/Wiskott-Aldrich syndrome protein family verprolin-homologous complex involved in actin polymerization and function. The es1-1 mutants exhibited significantly higher stomatal density. This resulted in excessive water loss and accelerated water flow in es1-1, also enhancing the water absorption capacity of the roots and the water transport capacity of the stems as well as promoting the in vivo enrichment of metal ions cotransported with water. The expression of ES1 is higher in the leaves and leaf sheaths than in other tissues, consistent with its role in controlling water loss from leaves. GREEN FLUORESCENT PROTEIN-ES1 fusion proteins were ubiquitously distributed in the cytoplasm of plant cells. Collectively, our data suggest that ES1 is important for regulating water loss in rice. PMID:26243619

Loss of corticospinal tract integrity in early MS disease stages

PubMed Central

Neumann, Jens; Kaufmann, Jörn; Heidel, Jan; Stadler, Erhard; Sweeney-Reed, Catherine; Sailer, Michael; Schreiber, Stefanie

2017-01-01

Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages. Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study. Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified. Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy. PMID:28959706

Assessing Reading Rate in the Primary Grades (1-3)

ERIC Educational Resources Information Center

Morris, Darrell; Trathen, Woodrow; Gill, Tom; Schlagal, Robert; Ward, Devery; Frye, Elizabeth M.

2017-01-01

In this study we explore students' reading rates in grades 1-3. We begin with a short history of reading rate as an assessment measure in the early grades. Next, we share rate data from a recent study (N = 305) where children's contextual reading was assessed with a traditional passage-reading inventory. A comparison of our average grade-level…

Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

PubMed Central

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

2013-01-01

Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

An Analysis of Kohlberg's "Stage 4 1/2" within an Enhanced Framework of Moral Stages.

ERIC Educational Resources Information Center

Minnameier, Gerhard

This paper discusses a well-known problem of stage categorization within Kohlberg's theory of moral stages (L. Kohlberg, 1973), that of "Stage 4 1/2." Some subjects previously scored at stage 4 in Kohlberg's framework took on some characteristics of stage 2 reasoning, which suggested the possibility of regression. To reconcile this…

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahimi, Asal, E-mail: asal.rahimi@utsouthwestern.edu; Thomas, Kimberly; Spangler, Ann

Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohortmore » to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S

Attenuation of p38-Mediated miR-1/133 Expression Facilitates Myoblast Proliferation during the Early Stage of Muscle Regeneration

PubMed Central

Zhang, Duo; Li, Xihua; Chen, Chuchu; Li, Yuyin; Zhao, Lei; Jing, Yanyan; Liu, Wei; Wang, Xiaoyun; Zhang, Ying; Xia, Hongfeng; Chang, Yaning; Gao, Xiang; Yan, Jun; Ying, Hao

2012-01-01

Myoblast proliferation following myotrauma is regulated by multiple factors including growth factors, signal pathways, transcription factors, and miRNAs. However, the molecular mechanisms underlying the orchestration of these regulatory factors remain unclear. Here we show that p38 signaling is required for miR-1/133a clusters transcription and both p38 activity and miR-1/133 expression are attenuated during the early stage of muscle regeneration in various animal models. Additionally, we show that both miR-1 and miR-133 reduce Cyclin D1 expression and repress myoblast proliferation by inducing G1 phase arrest. Furthermore, we demonstrate that miR-133 inhibits mitotic progression by targeting Sp1, which mediates Cyclin D1 transcription, while miR-1 suppresses G1/S phase transition by targeting Cyclin D1. Finally, we reveal that proproliferative FGF2, which is elevated during muscle regeneration, attenuates p38 signaling and miR-1/133 expression. Taken together, our results suggest that downregulation of p38-mediated miR-1/133 expression by FGF2 and subsequent upregulation of Sp1/Cyclin D1 contribute to the increased myoblast proliferation during the early stage of muscle regeneration. PMID:22911796

Important Text Characteristics for Early-Grades Text Complexity

ERIC Educational Resources Information Center

Fitzgerald, Jill; Elmore, Jeff; Koons, Heather; Hiebert, Elfrieda H.; Bowen, Kimberly; Sanford-Moore, Eleanor E.; Stenner, A. Jackson

2015-01-01

The Common Core set a standard for all children to read increasingly complex texts throughout schooling. The purpose of the present study was to explore text characteristics specifically in relation to early-grades text complexity. Three hundred fifty primary-grades texts were selected and digitized. Twenty-two text characteristics were identified…

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

PubMed Central

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-01-01

Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

Laminarin improves developmental competence of porcine early stage embryos by inhibiting oxidative stress.

PubMed

Jiang, Hao; Liang, Shuang; Yao, Xue-Rui; Jin, Yong-Xun; Shen, Xing-Hui; Yuan, Bao; Zhang, Jia-Bao; Kim, Nam-Hyung

2018-04-23

Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group. Notably, LMA attenuated the intracellular reactive oxygen species generation induced by H 2 O 2 . Furthermore, LMA not only increased intracellular glutathione levels, but also ameliorated mitochondrial membrane potential. In addition, the expression of a zygotic genome activation related gene (YAP1), pluripotency-related genes (OCT4, NANOG, and SOX2), and hatching-related genes (COX2, GATA4, and ITGA5) were up-regulated following LMA supplementation during porcine early stage embryo development. These results demonstrate that LMA has beneficial effects on the development of porcine early stage embryos via regulation of oxidative stress. This evidence provides a novel method for embryo development improvement associated with exposure to LMA. Copyright © 2018 Elsevier Inc. All rights reserved.

U.S. Food and Drug Administration Approval: Neratinib for the Extended Adjuvant Treatment of Early Stage HER2-Positive Breast Cancer.

PubMed

Singh, Harpreet; Walker, Amanda J; Amiri-Kordestani, Laleh; Cheng, Joyce; Tang, Shenghui; Balcazar, Pamela; Barnett-Ringgold, Kimberly; Palmby, Todd R; Cao, Xianhua; Zheng, Nan; Liu, Qi; Yu, Jingyu; Pierce, William F; Daniels, Selena R; Sridhara, Rajeshwari; Ibrahim, Amna; Kluetz, Paul G; Blumenthal, Gideon M; Beaver, Julia A; Pazdur, Richard

2018-03-09

On July 17, 2017, the Food and Drug Administration (FDA) approved neratinib (NERLYNX, Puma Biotechnology, Inc) for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. Approval was based on data from ExteNET, a randomized, double-blind, placebo-controlled multicenter trial. Women with early-stage HER2-positive breast cancer and within two years of completing adjuvant trastuzumab were randomized to neratinib (n=1420) or placebo (n=1420) for one year. The primary endpoint was invasive disease-free survival (iDFS) defined as the time between randomization date to first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distance recurrence, or death from any cause, with two years and 28 days of follow up. The trial showed a statistically significant treatment effect favoring neratinib with a stratified hazard ratio of 0.66 (95% CI: 0.49, 0.90, p=0.008). Estimated iDFS rate at 2-years was 94.2% (95% CI: 92.6%, 95.4%) in patients treated with neratinib vs. 91.9% (95% CI: 90.2%, 93.2%) in those receiving placebo. Diarrhea was the most common adverse event (AE) with a 40% incidence of Grade 3 or 4 diarrhea and represents the most common AE leading to treatment discontinuation. Other frequent AEs (>10% incidence) were nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, and muscle spasms. Other than diarrhea, neratinib is associated with a low incidence of severe AEs; toxicities are generally reversible and manageable with dose interruptions, dose reductions, and/or standard medical care. This article summarizes FDA decision-making and data supporting the neratinib approval. Copyright ©2018, American Association for Cancer Research.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

2016-11-01

We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

PubMed Central

Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

2017-01-01

SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

New concept in histopathological grading and staging of chronic hepatitis C infection at Sharkia Governorate, Egypt.

PubMed

Mangoud, Amal M; Eissa, Mostafa H; Sabee, Essam I; Ibrahem, Ibrahem A; Ismail, Alaa; Morsy, Tosson A; Nor Edin, Essam; Mostafa, Yousry; Abuel-Magd, Yousry; Afefy, Afefy F; el-Shorbagy, Eman; el-Sadawy, Mahmoud; Ragab, Hosnia; Mahrous, Seham; Abdel Menem, Amal; Etewa, Samia; Hassan, Mostafa I; Lakouz, Khalid; Abdel-Aziz, Khalid; Saber, Mahmoud; el-Hady, Gaber

2004-04-01

Hepatitis C virus (HCV) has been estimated by the WHO to infect 170 million patients worldwide, with a high prevalence rate (about 24.5%) among Egyptians. The disease could be presented with variable hepatic lesions ranging from mild inflammation, fibrosis, cirrhosis to even end stage liver disease and hepatocellular carcinoma. The Knodell histology activity index, published in 1981, was the first system of its type and is widely regarded as the benchmark for objective, semi-quantitative reproducible description of the various morphological lesions of chronic hepatitis. Other proposals for semi-quantitative evaluation have followed. In this study, when applying these systems on the present cases (109 liver biopsies taken from Egyptian patients infected with HCV), the authors found that the presented histopathological features may be unusual for any of the known scoring systems. Therefore, they suggested a new system for grading and staging of liver diseases in Egyptian patients infected with HCV. Accordingly, the degrees of necroinflammations are classified into 3 grades (1-3) and the progression of fibrosis is classified into 3 stages (1-3). The reduced numbers of grades and stages proposed in this study may be attributed to the rapid course among Egyptians who differ in environmental circumstances from abroad.

Nasolabial esthetics in children with complete unilateral cleft lip and palate after 1- versus 3-stage treatment protocols.

PubMed

Fudalej, Piotr; Katsaros, Christos; Bongaarts, Catharina; Dudkiewicz, Zofia; Kuijpers-Jagtman, Anne Marie

2009-08-01

Facial esthetics play an important role in social interactions. However, children with a repaired complete unilateral cleft lip and palate usually show some disfigurement of the nasolabial area. To date, few studies have assessed the nasolabial appearance after different treatment protocols. The aim of the present study was to compare the nasolabial esthetics after 1- and 3-stage treatment protocols. Four components of the nasolabial appearance (nasal form, nasal deviation, mucocutaneous junction, and profile view) were assessed by 4 raters in 108 consecutively treated children who had undergone either 1-stage closure (Warsaw group, 41 boys and 19 girls, mean age 10.8 years, SD 2.0) or 3-stage (Nijmegen group, 30 boys and 18 girls, mean age 8.9 years, SD 0.7). A 5-grade esthetic index of Asher-McDade was used, in which grade 1 indicates the most esthetic and grade 5 the least esthetic outcome. The nasal form was judged the least esthetic in both groups and graded 3.1 (SD 1.1) and 3.2 (SD 1.1). The nasal deviation, mucocutaneous junction, and profile view were scored from 2.1 (SD 0.8) to 2.3 (SD 1.0) in both groups. The treatment outcome after the Warsaw and Nijmegen protocols was comparable. Neither overall nor any of the 4 components of the nasolabial appearance showed intercenter differences (P > .1). The nasolabial appearance after the Warsaw (1-stage) and Nijmegen (3-stage) protocols was comparable. The technique of lip repair (triangular flap in Warsaw and Millard rotation advancement in Nijmegen) gave comparable results for the esthetics of the nasolabial area.

Survival is Better After Breast Conserving Therapy than Mastectomy for Early Stage Breast Cancer: A Registry-Based Follow-up Study of Norwegian Women Primary Operated Between 1998 and 2008.

PubMed

Hartmann-Johnsen, Olaf Johan; Kåresen, Rolf; Schlichting, Ellen; Nygård, Jan F

2015-11-01

Breast-conserving therapy (BCT) and mastectomy (MTX) has been considered to have a similar long-time survival. However, better survival in women undergoing BCT compared with MTX is found in two recent register studies from the United States. The purpose of this study was to compare survival after BCT and MTX for women with early-stage breast cancer in Norway. Women with invasive, early-stage breast cancer (1998-2008) where BCT and MTX were considered as equally beneficial treatments were included for a total of 13,015 women. Surgery was divided in two main cohorts (primary BCT, primary MTX) and five subcohorts. Analyses were stratified into T1N0M0, T2N0M0, T1N1M0, T2N1M0, and age groups (<50, 50-69, ≥70). Overall survival and breast cancer-specific survival (BCSS) were calculated in life tables, hazard ratios by Cox regression, and sensitivity analyses. Five-year BCSS for women who underwent primary BCT or primary MTX was 97 and 88 %, respectively. Women who underwent primary MTX had a hazard ratio of 1.64 (95 % confidence interval 1.43-1.88) for breast cancer death compared with women who underwent primary BCT after adjusting for the year of diagnosis, age at diagnosis, stage, histology, and grade. Survival was better or equal after breast-conserving therapy than mastectomy in all early stages, surgical subcohorts, and age groups. This advantage could not only be attributed to differences in tumor biology.

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas.

PubMed

Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Soyama, Hiroaki; Aoyama, Tadashi; Ishibashi, Hiroki; Kato, Kento; Iwahashi, Hideki; Matuura, Hiroko; Yoshikawa, Tomoyuki; Suzuki, Ayako; Hirata, Junko; Furuya, Kenichi

2017-01-01

Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1. © 2017 S. Karger AG, Basel.

Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

PubMed Central

Chahal, Harinder S.; Marseille, Elliot A.; Tice, Jeffrey A.; Pearson, Steve D.; Ollendorf, Daniel A.; Fox, Rena K.; Kahn, James G.

2016-01-01

IMPORTANCE Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained

Photons from the early stages of relativistic heavy-ion collisions

NASA Astrophysics Data System (ADS)

Oliva, L.; Ruggieri, M.; Plumari, S.; Scardina, F.; Peng, G. X.; Greco, V.

2017-07-01

We present results about photon-production in relativistic heavy-ion collisions. The main novelty of our study is the calculation of the contribution of the early-stage photons to the photon spectrum. The initial stage is modeled by an ensemble of classical gluon fields which decay to a quark-gluon plasma via the Schwinger mechanism, and the evolution of the system is studied by coupling classical field equations to relativistic kinetic theory; photon production is then computed by including the pertinent collision processes into the collision integral. We find that the contribution of the early-stage photons to the direct photon spectrum is substantial for pT≈2 GeV and higher, the exact value depending on the collision energy; therefore, we identify this part of the photon spectrum as the sign of the early stage. Moreover, the amount of photons produced during the early stage is not negligible with respect to those produced by a thermalized quark-gluon plasma: We support the idea that there is no dark age in relativistic heavy-ion collisions.

Association of Marital Status With T Stage at Presentation and Management of Early-Stage Melanoma.

PubMed

Sharon, Cimarron E; Sinnamon, Andrew J; Ming, Michael E; Chu, Emily Y; Fraker, Douglas L; Karakousis, Giorgos C

2018-05-01

Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients. This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017. Marital status, categorized as married, never married, divorced, or widowed. Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm. A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married

New application of 18F-fluoride PET for the detection of bone remodeling in early-stage osteoarthritis of the hip.

PubMed

Kobayashi, Naomi; Inaba, Yutaka; Tateishi, Ukihide; Yukizawa, Yohei; Ike, Hiroyuki; Inoue, Tomio; Saito, Tomoyuki

2013-10-01

Recent studies have reported the acceleration of subchondral bone remodeling during the development of osteoarthritis (OA). However, it is not possible to evaluate such molecular abnormalities using conventional radiographic techniques. We have applied 18F-fluoride PET to the analysis of painful or dysplastic hips at various stages of OA and then compared this with radiographic findings and clinical findings. A consecutive series of 65 joints from 48 patients (average age, 40 years; range, 19-72 years) with a hip joint complaint or radiographic dysplastic hip were enrolled in this study. Twenty-five contralateral joints without any evidence of OA or clinical symptoms were assigned as a normal control group. Radiographic evaluations were performed on the basis of Kellgren and Lawrence grade and the minimum joint space. Clinical evaluations were performed using the grading scale for pain severity and the SUVmax was measured for each joint. The association between SUVmax and the radiographic or clinical findings was evaluated. 18F-fluoride PET shows a significantly higher uptake value for progressive-stage OA cases than for early-stage cases and also shows a significantly higher uptake value in cases with severe pain. Even in early-OA-stage patients who do not show joint space narrowing on a plain x-ray, cases with severe pain show a significantly higher uptake value. 18F-fluoride PET has great potential as an imaging method for diagnosing early-stage OA without any marked radiographic changes.

Runx2 is required for early stages of endochondral bone formation but delays final stages of bone repair in Axin2-deficient mice

PubMed Central

McGee-Lawrence, Meghan E.; Carpio, Lomeli R.; Bradley, Elizabeth W.; Dudakovic, Amel; Lian, Jane B.; van Wijnen, Andre J.; Kakar, Sanjeev; Hsu, Wei; Westendorf, Jennifer J.

2014-01-01

Runx2 and Axin2 regulate skeletal development. We recently determined that Axin2 and Runx2 molecularly interact in differentiating osteoblasts to regulate intramembranous bone formation, but the relationship between these factors in endochondral bone formation was unresolved. To address this, we examined the effects of Axin2 deficiency on the cleidocranial dysplasia (CCD) phenotype of Runx2+/− mice, focusing on skeletal defects attributed to improper endochondral bone formation. Axin2 deficiency unexpectedly exacerbated calvarial components of the CCD phenotype in the Runx2+/− mice; the endocranial layer of the frontal suture, which develops by endochondral bone formation, failed to mineralize in the Axin2−/−:Runx2+/− mice, resulting in a cartilaginous, fibrotic and larger fontanel than observed in Runx2+/− mice. Transcripts associated with cartilage development (e.g., Acan, miR140) were expressed at higher levels, whereas blood vessel morphogenesis transcripts (e.g., Slit2) were suppressed in Axin2−/−:Runx2+/− calvaria. Cartilage maturation was impaired, as primary chondrocytes from double mutant mice demonstrated delayed differentiation and produced less calcified matrix in vitro. The genetic dominance of Runx2 was also reflected during endochondral fracture repair, as both Runx2+/− and double mutant Axin2−/−:Runx2+/− mice had enlarged fracture calluses at early stages of healing. However, by the end stages of fracture healing, double mutant animals diverged from the Runx2+/− mice, showing smaller calluses and increased torsional strength indicative of more rapid end stage bone formation as seen in the Axin2−/− mice. Taken together, our data demonstrate a dominant role for Runx2 in chondrocyte maturation, but implicate Axin2 as an important modulator of the terminal stages of endochondral bone formation. PMID:24973690

Effects of education on the progression of early- versus late-stage mild cognitive impairment.

PubMed

Ye, Byoung Seok; Seo, Sang Won; Cho, Hanna; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Back, Joung Hwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, Sangyun; Han, Seol-Heui; Lee, Jae-Hong; Cheong, Hae-Kwan; Na, Duk L

2013-04-01

Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

PubMed

Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

2016-12-29

The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH 4 /H 2 S/H 2 O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

TOXICITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TO EARLY LIFE STAGE BROOK TROUT (SALVELINUS FONTINALIS) FOLLOWING PARTENTAL DIETARY EXPOSURE

EPA Science Inventory

The toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the early life stages of F1 generation brook trout (Salvelinus fontinalis) was determined, when dosed by maternal transfer.Effects were compared across six treatments, including a control.The experimental groups, based...

Risk of fatal cerebrovascular accidents after external beam radiation therapy for early-stage glottic laryngeal cancer.

PubMed

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O'Malley, Bert; Weinstein, Gregory S; Bekelman, Justin E

2014-05-01

This study compared the risk of fatal cerebrovascular accidents (CVAs) in patients with early-stage glottic laryngeal cancer receiving surgery or external beam radiation therapy (EBRT). Using a competing risks survival analysis, we compared the risk of death because of CVA among patients with early-stage glottic laryngeal cancer receiving surgery or EBRT in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8%; 95% confidence interval [CI], 2.3% to 3.4%) compared to surgery (1.5%; 95% CI, 0.8% to 2.3%; p = .024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted hazard ratio [HR], 1.75; 95% CI, 1.04-2.96; p = .037). Treatment for early-stage glottic laryngeal cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. Copyright © 2013 Wiley Periodicals, Inc.

Collective screening tools for early identification of dyslexia

PubMed Central

Andrade, Olga V. C. A.; Andrade, Paulo E.; Capellini, Simone A.

2015-01-01

Current response to intervention models (RTIs) favor a three-tier system. In general, Tier 1 consists of evidence-based, effective reading instruction in the classroom and universal screening of all students at the beginning of the grade level to identify children for early intervention. Non-responders to Tier 1 receive small-group tutoring in Tier 2. Non-responders to Tier 2 are given still more intensive, individual intervention in Tier 3. Limited time, personnel and financial resources derail RTI’s implementation in Brazilian schools because this approach involves procedures that require extra time and extra personnel in all three tiers, including screening tools which normally consist of tasks administered individually. We explored the accuracy of collectively and easily administered screening tools for the early identification of second graders at risk for dyslexia in a two-stage screening model. A first-stage universal screening based on collectively administered curriculum-based measurements was used in 45 7 years old early Portuguese readers from 4 second-grade classrooms at the beginning of the school year and identified an at-risk group of 13 academic low-achievers. Collectively administered tasks based on phonological judgments by matching figures and figures to spoken words [alternative tools for educators (ATE)] and a comprehensive cognitive-linguistic battery of collective and individual assessments were both administered to all children and constituted the second-stage screening. Low-achievement on ATE tasks and on collectively administered writing tasks (scores at the 25th percentile) showed good sensitivity (true positives) and specificity (true negatives) to poor literacy status defined as scores ≤1 SD below the mean on literacy abilities at the end of fifth grade. These results provide implications for the use of a collectively administered screening tool for the early identification of children at risk for dyslexia in a classroom setting

Trajectories of Social Withdrawal from Grades 1 to 6: Prediction from Early Parenting, Attachment, and Temperament

PubMed Central

Booth-LaForce, Cathryn; Oxford, Monica L.

2015-01-01

From 1092 children in the NICHD Study of Early Child Care and Youth Development, we identified three trajectory patterns of social withdrawal from teacher reports in Grades 1-6: A Normative consistently low group (86%); a Decreasing group (5%) with initially high withdrawal that decreased; and an Increasing group (9%) with initially low withdrawal that increased. Prediction models supported the role of early dysregulated temperament, insensitive parenting, and attachment. Preschool shy temperament was a specific pathway to decreasing withdrawal, and poor inhibitory control, to increasing withdrawal. Children on the increasing pathway were more lonely, solitary, and excluded by peers. Results suggest differentiated pathways to varying trajectories of social withdrawal and highlight the importance of identification of longitudinal patterns in relation to risk. PMID:18793064

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

1986-03-01

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

Older Patients With Early-stage Breast Cancer: Adjuvant Radiation Therapy and Predictive Factors for Cancer-related Death.

PubMed

Nagar, Himanshu; Yan, Weisi; Christos, Paul; Chao, K S Clifford; Nori, Dattatreyudu; Ravi, Akkamma

2017-06-01

Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0

Urinary Biomarkers at Early ADPKD Disease Stage

PubMed Central

Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

2015-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

More than Letters: Literacy Activities for Preschool, Kindergarten, and First Grade.

ERIC Educational Resources Information Center

Moomaw, Sally; Hieronymus, Brenda

Noting that the early enjoyment of reading and writing provides a foundation for a lifetime of ongoing learning, this book details a literacy curriculum for preschool, kindergarten, and first grade. Chapter 1 describes the stages of writing development and discusses how early childhood teachers can facilitate emergent reading and writing. Chapter…

The CD147/MMP-2 signaling pathway may regulate early stage cardiac remodelling in spontaneously hypertensive rats.

PubMed

Li, Bowei; Zhou, Wanxing; Yang, Xiaorong; Zhou, Yuliang; Tan, Yongjing; Yuan, Congcong; Song, Yulan; Chen, Xiao; Zhang, Wei

2016-11-01

Previous studies have reported that decreased matrix metalloproteinase-2 (MMP-2) is associated with early stage (age 8-16 weeks) ventricular remodelling in spontaneously hypertensive rats (SHR). We hypothesized that inhibited CD147/MMP-2 signalling might down-regulate MMP-2 expression and augment remodelling in spontaneously hypertensive rats. Twenty-nine male SHR (8 weeks) were randomly assigned to SHR, CD147, and CD147+DOX groups. The control group included eight age-matched WKY rats. CD147 and CD147+DOX groups received recombinant human CD147 (600 ng/kg in 1.5 mL saline, weekly). The SHR and WKY groups received the vehicle. The CD147+DOX group also received doxycycline, an inhibitor of MMPs (daily, 30 mg/kg in 1.5 mL saline, iG). On day 56 echocardiography and left ventricular mass index (LVWI) measurements were collected and histological sections were stained for cell and collagen content. Myocardium MMP-2, TIMP-1, CD147, and collagens types I and III were estimated by western blot. CD147 and the ratio of MMP-2/TIMP-1 were lower in SHR than WKY rats (P<.05). Myocyte hypertrophy, partial fibre breaks, plasmolysis, necrosis and collagen content (collagen volume fraction [CVF], I and III) in SHR were above control levels (P<.05). CD147 rats showed CD147, MMP-2 and MMP-2/TIMP-1 were increased (P<.05), CVF, LVWI, and collagen I and III were decreased (P<.05) and myocyte morphology was improved. CD147 levels did not differ between CD147+DOX and CD147 groups, CVF, collagens type I and III and partial fiber breaks were more abundant in CD147+DOX (P<.05). In summary, an inhibited CD147/MMP-2 pathway was associated with early stage cardiac remodelling, and CD147 supplementation may attenuate this response. © 2016 John Wiley & Sons Australia, Ltd.

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

PubMed

Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

2016-04-01

Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of elevated carbon dioxide (CO2) concentrations on early developmental stages of the marine copepod Calanus finmarchicus Gunnerus (Copepoda: Calanoidae).

PubMed

Pedersen, Sindre Andre; Våge, Vegard Thorset; Olsen, Anders Johny; Hammer, Karen Marie; Altin, Dag

2014-01-01

Ocean acidification poses an ongoing threat to marine organisms, and early life stages are believed to be particularly sensitive. The boreal calanoid copepod Calanus finmarchicus seasonally dominates the standing stock of zooplankton in the northern North Sea and North Atlantic, and due to its size and abundance is considered an ecological key species linking energy from primary producers to higher trophic levels. To examine whether the early stages of C. finmarchicus are particularly vulnerable to elevated levels of CO2, eggs and nauplii were subjected to different levels of CO2-acidified seawater for 1 wk. The first experiment, with eggs as the starting point, revealed no marked effect on hatching success, but a significant reduction in nauplii survival during incubation at 8800 ppm CO2. In addition, a significant decrease in ontogenetic development rate during incubation at 8800 ppm CO2 was observed in this experiment. In the second experiment, where third-stage nauplii represented the starting point, no significant effects on ontogenetic development and survival following exposure to pCO2 ≥ 7700 ppm were observed. Data suggest that the two first nauplii stages, which are fed endogenously, may be more vulnerable and therefore likely to represent the "bottleneck" for this species in a more acidic ocean. However, the absence of significant effects in the most sensitive stages during exposure to 2800 ppm CO2, a level that is well above worst-case scenario predictions for year 2300 (approximately 2000 ppm CO2), suggests that this species may be generally robust to direct effects of ocean acidification.

Proteomics Identification of Potential Candidates Involved in Cell Proliferation for Early Stage of Brain Regeneration in the Adult Zebrafish.

PubMed

Lim, Fei Tieng; Ogawa, Satoshi; Smith, A Ian; Parhar, Ishwar S

2017-02-01

The central nervous system (CNS) of the non-mammalian vertebrates has better neuroregenerative capability as compared with the mammalian CNS. Regeneration of habenula was observed 40 days after damage in zebrafish. During the early stage of regeneration, we found a significant increase of apoptotic cells on day-1 post-damage and of proliferative cells on day-3 post-damage. To identify the molecular factor(s) involved in the early stages of neuroregeneration, differentially expressed proteins during sham, 20- and 40-h post-habenula damage were investigated by proteomic approach by using two-dimensional differential gel electrophoresis (2D-DIGE) coupled with Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight (MALDI-ToF) and tandem mass spectrometry. Protein profiles revealed 17 differentially (>1.5-fold) expressed proteins: 10 upregulated, 4 downregulated, 2 proteins were found to be downregulated at the early stage but upregulated at a later stage, and 1 protein was found to be upregulated at 2 different time points. All proteins identified can be summarized under few molecular processes involved in the early stages of neuroregeneration in zebrafish CNS: apoptosis regulation (Wnt inhibitory factor 1 [WIF1]), neuroprotection (metallothionein), cell proliferation (Spred2, ependymin, Lhx1, and Wnts), differentiation (Spred2, Lhx9, and Wnts), and morphogenesis (cytoplasmic actins and draculin). These protein profiling results suggest that drastic molecular changes occur in the neuroregenerative process during this period, which includes cell proliferation, differentiation, and protection.

Growth Trajectories of Early Aggression, Overactivity, and Inattention: Relations to Second Grade Reading

PubMed Central

Gray, Sarah A. O.; Carter, Alice S.; Briggs-Gowan, Margaret J.; Jones, Stephanie M.; Wagmiller, Robert L.

2015-01-01

The link between behavior problems and low academic achievement is well established, but few studies have examined longitudinal relations between early externalizing behaviors before school entry and low academic achievement following transition to formal schooling. Early inattention has been particularly overlooked, despite strong associations between inattention and reading difficulties later in development. Trajectories of infant/toddler aggression, overactivity, and inattention, developed from parent reports about 1- to 3-year-old children, were examined as predictors of direct assessments of second grade reading in an at-risk epidemiological study subsample (N = 359). Reports of inattentive and overactive behaviors at age 1-to-3 years and changes in inattention through toddlerhood predicted reading achievement in second grade. A parallel process model suggested that the effects of early inattention on reading appear to be most robust. Findings underscore the contribution of social-emotional development to school readiness and the importance of early identification of children with externalizing problems, as early interventions designed to reduce externalizing problems may improve later reading skills. PMID:25046126

An improved prognostic model for stage T1a and T1b prostate cancer by assessments of cancer extent

PubMed Central

Rajab, Ramzi; Fisher, Gabrielle; Kattan, Michael W; Foster, Christopher S; Møller, Henrik; Oliver, Tim; Reuter, Victor; Scardino, Peter T; Cuzick, Jack; Berney, Daniel M

2013-01-01

Treatment decisions on prostate cancer diagnosed by trans-urethral resection (TURP) of the prostate are difficult. The current TNM staging system for pT1 prostate cancer has not been re-evaluated for 25 years. Our objective was to optimise the predictive power of tumor extent measurements in TURP of the prostate specimens. A total of 914 patients diagnosed by TURP of the prostate between 1990 and 1996, managed conservatively were identified. The clinical end point was death from prostate cancer. Diagnostic serum prostate-specific antigen (PSA) and contemporary Gleason grading was available. Cancer extent was measured by the percentage of chips infiltrated by cancer. Death rates were compared by univariate and multivariate proportional hazards models, including baseline PSA and Gleason score. The percentage of positive chips was highly predictive of prostate cancer death when assessed as a continuous variable or as a grouped variable on the basis of and including the quintiles, quartiles, tertiles and median groups. In the univariate model, the most informative variable was a four group-split (≤ 10%, >10–25%, > 25–75% and > 75%); (HR = 2.08, 95% CI = 1.8–2.4, P < 0.0001). The same was true in a multivariate model (ΔX2 (1 d.f.) = 15.0, P = 0.0001). The current cutoff used by TNM (< = 5%) was sub-optimal (ΔX2 (1 d.f.) = 4.8, P = 0.023). The current TNM staging results in substantial loss of information. Staging by a four-group subdivision would substantially improve prognostication in patients with early stage disease and also may help to refine management decisions in patients who would do well with conservative treatments. PMID:20834240

Stage Presentation, Care Patterns, and Treatment Outcomes for Squamous Cell Carcinoma of the Penis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burt, Lindsay M.; Shrieve, Dennis C.; Tward, Jonathan D., E-mail: Jonathan.Tward@hci.utah.edu

Purpose: Penile squamous cell carcinoma (SCC) is a rare entity, with few published series on outcomes. We evaluated the stage distributions and outcomes for surgery and radiation therapy in a U.S. population database. Methods and Materials: Subjects with SCC of the penis were identified using the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program database between 1988 and 2006. Descriptive statistics were performed, and cause-specific survival (CSS) was estimated using Kaplan-Meier analysis. Comparisons of treatment modalities were analyzed using multivariate Cox regression. Subjects were staged using American Joint Committee on Cancer, sixth edition, criteria. Results: There were 2458more » subjects identified. The median age was 66.8 years (range, 17-102 years). Grade 2 disease was present in 94.5% of cases. T1, T2, T3, T4, and Tx disease was present in 64.8%, 17.1%, 9.5%, 2.1%, and 6.5% of cases, respectively. N0, N1, N2, N3, and Nx disease was noted in 61.6%, 6.9%, 4.0%, 3.7%, and 23.8% of cases, respectively. M1 disease was noted in 2.5% of subjects. Individuals of white ethnicity accounted for 85.1% of cases. Lymphadenectomy was performed in 16.7% of cases. The CSS for all patients at 5 and 10 years was 80.8% and 78.6%. By multivariable analysis grades 2 and 3 disease, T3 stage, and positive lymph nodes were adverse prognostic factors for CSS. Conclusion: SCC of the penis often presents as early-stage T1, N0, M0, grade 1, or grade 2 disease. The majority of patients identified were treated with surgery, and only a small fraction of patients received radiation therapy alone or as adjuvant therapy.« less

Early Numeracy Intervention Program for First-Grade Students with Mathematics Difficulties

ERIC Educational Resources Information Center

Bryant, Diane Pedrotty; Bryant, Brian R.; Roberts, Greg; Vaughn, Sharon; Pfannenstiel, Kathleen Hughes; Porterfield, Jennifer; Gersten, Russell

2011-01-01

The purpose of this study was to determine the effects of an early numeracy preventative Tier 2 intervention on the mathematics performance of first-grade students with mathematics difficulties. Researchers used a pretest-posttest control group design with randomized assignment of 139 students to the Tier 2 treatment condition and 65 students to…

High-Resolution Adaptive Optics Retinal Image Analysis at Early Stage Central Areolar Choroidal Dystrophy With PRPH2 Mutation.

PubMed

Gocho, Kiyoko; Akeo, Keiichiro; Itoh, Naoko; Kameya, Shuhei; Hayashi, Takaaki; Katagiri, Satoshi; Gekka, Tamaki; Ohkuma, Yasuhiro; Tsuneoka, Hiroshi; Takahashi, Hiroshi

2016-12-01

To report the clinical features of Japanese patients at Stage 1 and 2 of central areolar choroidal dystrophy (CACD). Five family members had comprehensive ophthalmic examinations including adaptive optics (AO) retinal imaging. Mutation analysis of the PRPH2 gene was performed by Sanger sequencing. The protocol conformed to the tenets of the Declaration of Helsinki and was approved by the institutional review board of The Jikei University School of Medicine. Four family members had a heterozygous PRPH2 mutation, p.R172Q; however, one member with a mutation did not show any ophthalmological abnormalities. Two patients had mild parafoveal retinal dystrophy and a reduction of cone density determined by AO analysis. The results indicate that the parafoveal cone photoreceptors can be affected even at the early stage of CACD. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1115-1126.]. Copyright 2016, SLACK Incorporated.

L1CAM in early-stage type I endometrial cancer: results of a large multicenter evaluation.

PubMed

Zeimet, Alain G; Reimer, Daniel; Huszar, Monica; Winterhoff, Boris; Puistola, Ulla; Azim, Samira Abdel; Müller-Holzner, Elisabeth; Ben-Arie, Alon; van Kempen, Léon C; Petru, Edgar; Jahn, Stephan; Geels, Yvette P; Massuger, Leon F; Amant, Frédéric; Polterauer, Stephan; Lappi-Blanco, Elisa; Bulten, Johan; Meuter, Alexandra; Tanouye, Staci; Oppelt, Peter; Stroh-Weigert, Monika; Reinthaller, Alexander; Mariani, Andrea; Hackl, Werner; Netzer, Michael; Schirmer, Uwe; Vergote, Ignace; Altevogt, Peter; Marth, Christian; Fogel, Mina

2013-08-07

Despite the excellent prognosis of Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage I, type I endometrial cancers, a substantial number of patients experience recurrence and die from this disease. We analyzed the value of immunohistochemical L1CAM determination to predict clinical outcome. We conducted a retrospective multicenter cohort study to determine expression of L1CAM by immunohistochemistry in 1021 endometrial cancer specimens. The Kaplan-Meier method and Cox proportional hazard model were applied for survival and multivariable analyses. A machine-learning approach was used to validate variables for predicting recurrence and death. Of 1021 included cancers, 17.7% were rated L1CAM-positive. Of these L1CAM-positive cancers, 51.4% recurred during follow-up compared with 2.9% L1CAM-negative cancers. Patients bearing L1CAM-positive cancers had poorer disease-free and overall survival (two-sided Log-rank P < .001). Multivariable analyses revealed an increase in the likelihood of recurrence (hazard ratio [HR] = 16.33; 95% confidence interval [CI] = 10.55 to 25.28) and death (HR = 15.01; 95% CI = 9.28 to 24.26). In the L1CAM-negative cancers FIGO stage I subdivision, grading and risk assessment were irrelevant for predicting disease-free and overall survival. The prognostic relevance of these parameters was related strictly to L1CAM positivity. A classification and regression decision tree (CRT)identified L1CAM as the best variable for predicting recurrence (sensitivity = 0.74; specificity = 0.91) and death (sensitivity = 0.77; specificity = 0.89). To our knowledge, L1CAM has been shown to be the best-ever published prognostic factor in FIGO stage I, type I endometrial cancers and shows clear superiority over the standardly used multifactor risk score. L1CAM expression in type I cancers indicates the need for adjuvant treatment. This adhesion molecule might serve as a treatment target for the fully humanized anti-L1CAM antibody currently

Learning in the Early Grades: Parents and Teachers Talk.

ERIC Educational Resources Information Center

Leavitt, Midge, Ed.

This booklet contains four articles, from the perspective of both parents and teachers, concerned with learning in the early grades. "From Kindergarten to Grade One: Making the Transition" (J. Ward), is a teacher's narrative on the importance of creating a child-centered classroom and an integrated, play-based curriculum. This article…

Comparative performances of staging systems for early hepatocellular carcinoma.

PubMed

Nathan, Hari; Mentha, Gilles; Marques, Hugo P; Capussotti, Lorenzo; Majno, Pietro; Aldrighetti, Luca; Pulitano, Carlo; Rubbia-Brandt, Laura; Russolillo, Nadia; Philosophe, Benjamin; Barroso, Eduardo; Ferrero, Alessandro; Schulick, Richard D; Choti, Michael A; Pawlik, Timothy M

2009-08-01

Several staging systems for patients with hepatocellular carcinoma (HCC) have been proposed, but studies of their prognostic accuracy have yielded conflicting conclusions. Stratifying patients with early HCC is of particular interest because these patients may derive the greatest benefit from intervention, yet no studies have evaluated the comparative performances of staging systems in patients with early HCC. A retrospective cohort study was performed using data on 379 patients who underwent liver resection or liver transplantation for HCC at six major hepatobiliary centres in the USA and Europe. The staging systems evaluated were: the Okuda staging system, the International Hepato-Pancreato-Biliary Association (IHPBA) staging system, the Cancer of the Liver Italian Programme (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging system, the Japanese Integrated Staging (JIS) score and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging system, 6th edition. A recently proposed early HCC prognostic score was also evaluated. The discriminative abilities of the staging systems were evaluated using Cox proportional hazards models and the bootstrap-corrected concordance index (c). Overall survival of the cohort was 74% at 3 years and 52% at 5 years, with a median survival of 62 months. Most systems demonstrated poor discriminatory ability (P > 0.05 on Cox proportional hazards analysis, c approximately 0.5). However, the AJCC/UICC system clearly stratified patients (P < 0.001, c = 0.59), albeit only into two groups. The early HCC prognostic score also clearly stratified patients (P < 0.001, c = 0.60) and identified three distinct prognostic groups. The early HCC prognostic score is superior to the AJCC/UICC staging system (6th edition) for predicting the survival of patients with early HCC after liver resection or liver transplantation. Other major HCC staging systems perform poorly in patients with early HCC.

Intensity Modulated Radiation Therapy for Early-Stage Primary Gastric Diffuse Large B-Cell Lymphoma: Dosimetric Analysis, Clinical Outcome, and Quality of Life

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xin; Fang, Hui; Tian, Yuan

Purpose: To evaluate the dosimetric superiority, efficacy, toxicity, and quality of life (QOL) data of intensity modulated radiation therapy (IMRT) in patients with primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods and Materials: Forty-six consecutive patients with early-stage PG-DLBCL underwent IMRT after chemotherapy. The majority of patients (61.5%) were subclassified as the non-germinal center B cell–like subtype. Dosimetric parameters of the planning target volume (PTV) and organs at risk were assessed. Survival rates were depicted with the Kaplan-Meier method and compared with the log-rank test. Quality of life was evaluated using the QLQ-C30-STO22 questionnaires at the last follow-up contact. Results: Themore » median PTV mean dose was 41.6 Gy. Only 0.73% of the PTV received <95% of the prescribed dose, indicating excellent target coverage. The median kidney V20 and liver V30 were 14.1% and 16.1%, respectively. The 5-year overall survival (OS), progression-free survival, and locoregional control rates for all patients were 80.4%, 75.0%, and 93.2%, respectively. Stage, lactate dehydrogenase level, and immunophenotype were significant prognostic factors for OS, and only stage was a significant factor for locoregional control. Consolidation IMRT in patients with complete response after chemotherapy resulted in significantly better OS and progression-free survival than salvage IMRT in patients with non-complete response. Two of 8 patients who had chronic liver disease experienced grade 4 or grade 5 acute hepatic failure after 4 to 5 cycles of rituximab-based chemotherapy and IMRT (40 Gy). No other serious acute or late toxicity was observed. The long-term global and functional QOL scales were excellent, with negligible symptom scales. Conclusions: Intensity modulated radiation therapy yielded excellent target coverage and critical tissue sparing and achieved favorable outcomes with acceptable toxicity and good long-term QOL in early-stage

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.

PubMed

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-04-01

To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. © 2016 Associated Professional Sleep Societies, LLC.

Comparing the Effects of Symbiotic Algae (Symbiodinium) Clades C1 and D on Early Growth Stages of Acropora tenuis

PubMed Central

Yuyama, Ikuko; Higuchi, Tomihiko

2014-01-01

Reef-building corals switch endosymbiotic algae of the genus Symbiodinium during their early growth stages and during bleaching events. Clade C Symbiodinium algae are dominant in corals, although other clades — including A and D — have also been commonly detected in juvenile Acroporid corals. Previous studies have been reported that only molecular data of Symbiodinium clade were identified within field corals. In this study, we inoculated aposymbiotic juvenile polyps with cultures of clades C1 and D Symbiodinium algae, and investigated the different effect of these two clades of Symbiodinium on juvenile polyps. Our results showed that clade C1 algae did not grow, while clade D algae grew rapidly during the first 2 months after inoculation. Polyps associated with clade C1 algae exhibited bright green fluorescence across the body and tentacles after inoculation. The growth rate of polyp skeletons was lower in polyps associated with clade C1 algae than those associated with clade D algae. On the other hand, antioxidant activity (catalase) of corals was not significantly different between corals with clade C1 and clade D algae. Our results suggested that clade D Symbiodinium algae easily form symbiotic relationships with corals and that these algae could contribute to coral growth in early symbiosis stages. PMID:24914677

Improved early outcome for end-stage dilated cardiomyopathy in children.

PubMed

McMahon, Anne-Marie; van Doorn, Carin; Burch, Michael; Whitmore, Pauline; Neligan, Sophie; Rees, Philip; Radley-Smith, Rosemary; Goldman, Allan; Brown, Katherine; Cohen, Gordon; Tsang, Victor; Elliott, Martin; de Leval, Marc R

2003-12-01

To review the impact of management changes on the early outcomes of end-stage dilated cardiomyopathy in children. We conducted a retrospective study of all consecutive children with end-stage dilated cardiomyopathy who received hospital treatment since 1992. Over the past 3 years the following management changes were made: (1) more aggressive use of mechanical cardiac assistance; (2) high priority listing for transplantation; and (3) ABO incompatible transplants for infants. Outcomes for 46 patients admitted between 1992 and 1999 (group I) were compared with 53 patients between 2000 and March 2003 (group II). In group I, 12 (26%) patients received mechanical support with recovery in 3 and transplantation in 5 (1 died). In group II, 19 (36%) patients received extracorporeal membrane oxygenation, with recovery in 5 and transplantation in 12 (all survived). The use of mechanical assistance was associated with high morbidity related to bleeding, end-organ failure, and long-term mechanical ventilation. Five patients in group II received ABO incompatible transplants and all survived. There have been no episodes of rejection or need for increased immunosuppressive therapy. Hospital mortality has been significantly reduced (group I, 37% vs group II, 11%; P <.05). Recent refinements in the management of end-stage dilated cardiomyopathy in children have significantly reduced early mortality. Identification of markers of early myocardial recovery and development of mechanical devices for longer term and more physiologic support are essential to achieve further improvements in outcome.

Concurrent Data Elicitation Procedures, Processes, and the Early Stages of L2 Learning: A Critical Overview

ERIC Educational Resources Information Center

Leow, Ronald P.; Grey, Sarah; Marijuan, Silvia; Moorman, Colleen

2014-01-01

Given the current methodological interest in eliciting direct data on the cognitive processes L2 learners employ as they interact with L2 data during the early stages of the learning process, this article takes a critical and comparative look at three concurrent data elicitation procedures currently employed in the SLA literature: Think aloud (TA)…

Early presentation of primary glioblastoma.

PubMed

Faguer, R; Tanguy, J-Y; Rousseau, A; Clavreul, A; Menei, P

2014-08-01

Clinical and neuroimaging findings of glioblastomas (GBM) at an early stage have rarely been described and those tumors are most probably under-diagnosed. Furthermore, their genetic alterations, to our knowledge, have never been previously reported. We report the clinical as well as neuroimaging findings of four early cases of patients with GBM. In our series, early stage GBM occurred at a mean age of 57 years. All patients had seizures as their first symptom. In all early stages, MRI showed a hyperintense signal on T2-weighted sequences and an enhancement on GdE-T1WI sequences. A hyperintense signal on diffusion sequences with a low ADC value was also found. These early observed occurrences of GBM developed rapidly and presented the MRI characteristics of classic GBM within a few weeks. The GBM size was multiplied by 32 in one month. Immunohistochemical analysis indicated the de novo nature of these tumors, i.e. absence of mutant IDH1 R132H protein expression, which is a diagnostic marker of low-grade diffuse glioma and secondary GBM. A better knowledge of early GBM presentation would allow a more suitable management of the patients and may improve their prognosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

The expression and prognostic value of protein tyrosine kinase 6 in early-stage cervical squamous cell cancer.

PubMed

Wang, Xiao-Jing; Xiong, Ying; Ma, Ze-Biao; Xia, Jian-Chuan; Li, Yan-Fang

2016-06-16

Protein tyrosine kinase 6 (PTK6) is overexpressed in many epithelial tumors and predicts poor prognosis. However, PTK6 expression status and its role in cervical squamous cell cancer are unknown. This study aimed to investigate the expression level and clinical significance of PTK6 in early-stage cervical squamous cell cancer. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blotting analysis were performed to detect PTK6 mRNA and protein expression levels in 10 freshly frozen, early-stage cervical squamous cell cancer specimens and adjacent non-tumorous cervical tissues. The expression of PTK6 was detected using immunohistochemical staining in 150 formalin-fixed, paraffin-embedded, early-stage cervical squamous cell cancer sections and 10 normal cervical tissue sections. The mRNA and protein levels of PTK6 in cancer tissues were higher than those in adjacent non-tumorous cervical tissues. Immunohistochemical analysis showed that PTK6 was not expressed in normal cervical tissues but was overexpressed in the cytoplasm of cervical squamous cell cancer cells. The level of PTK6 expression was significantly associated with tumor grade (P = 0.020). The 5-year overall survival rate of patients with high PTK6 expression was lower than that of patients with low PTK6 expression (81.3% vs. 96.2%, P = 0.008). Multivariate Cox regression analysis showed that the expression level of PTK6 in cervical squamous cell cancer was an independent prognostic factor for patient survival (hazard ratio = 5.999, 95% confidence interval 1.622-22.191, P < 0.05). PTK6 is overexpressed in cervical squamous cell cancer. Increased PTK6 expression is associated with reduced 5-year overall survival. PTK6 expression is an independent prognostic predictor for cervical cancer.

From Thought to Words to Print: Early Literacy Development in Grade 2

ERIC Educational Resources Information Center

Roessingh, Hetty; Elgie, Susan

2014-01-01

This study examines the relationship of the underlying skills of printing, spelling and vocabulary choices as they influence the quality of writing at the end of Grade 2. Four classes of Grade 2 (N = 85) writing in response to an expository prompt were scored holistically on a trait based rubric, then scored for spelling accuracy and…

The early stages of duplicate gene evolution

PubMed Central

Moore, Richard C.; Purugganan, Michael D.

2003-01-01

Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8–20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes. PMID:14671323

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

PubMed

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

PubMed Central

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

PubMed

Park, Jin-Young; Heo, Eun Jin; Lee, Jeong-Won; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-03-01

Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

PubMed Central

Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

2016-01-01

Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

Analysis of NUAK1 and NUAK2 expression during early chick development reveals specific patterns in the developing head.

PubMed

Bekri, Abdelhamid; Billaud, Marc; Thélu, Jacques

2014-01-01

Several human diseases are associated with the NUAK1 and NUAK2 genes. These genes encode kinases, members of the AMPK-related kinases (ARK) gene family. Both NUAK1 and NUAK2 are known targets of the serine threonine kinase LKB1, a tumor suppressor involved in regulating cell polarity. While much is known about their functions in disease, their expression pattern in normal development has not been extensively studied. Here, we present the expression patterns for NUAK1 and NUAK2 in the chick during early-stage embryogenesis, until day 3 (Hamburger and Hamilton stage HH20). Several embryonic structures, in particular the nascent head, showed distinct expression levels. NUAK1 expression was first detected at stage HH6 in the rostral neural folds. It was then expressed (HH7-11) throughout the encephalalon, predominantly in the telencephalon and mesencephalon. NUAK1 expression was also detected in the splanchnic endoderm area at HH8-10, and in the vitellin vein derived from this area, but not in the heart. NUAK2 expression was first detected at stage HH6 in the neural folds. It was then found throughout the encephalon at stage HH20. Particular attention was paid in this study to the dorsal ectoderm at stages HH7 and HH8, where a local deficit or accumulation of NUAK2 mRNA were found to correlate with the direction of curvature of the neural plate. This is the first description of NUAK1 and NUAK2 expression patterns in the chick during early development; it reveals non-identical expression profiles for both genes in neural development.

Effect of Habits and Nutritional Status on Clinical Grading and Histopathological Staging in Patients with Oral Sub Mucous Fibrosis.

PubMed

Singh, Abhayjeet; Lanke, Rama Brahmam; Shetty, Rakhith; Akifuddin, Syed; Sahu, Manish; Singh, Navneet; Kaur, Gagandeep; Goyal, Garish

2015-10-01

Oral submucous fibrosis (OSMF) is a chronic progressive debilitating disease affecting the oral, oropharyngeal and sometimes the oesophageal mucosa resulting in inability to eat due to burning, ulcers and stiffness. The study was undertaken, to evaluate the correlation of clinical staging, histological grading and nutritional status using body mass index (BMI) with gutkha (habit) index in OSMF patients. The study group comprised of 50 patients clinically diagnosed and histopathologically confirmed cases of OSMF. Habit (gutkha) index was calculated by multiplying duration and frequency. Body mass index was calculated by dividing weight in kilograms and height in centimetres of the patient. Male to female ratio was 2.8:1. Clinical grading increased with increase in gutkha index, patients with gutkha index 1-50, maximum were in mild stage; with gutkha index 51-100, maximum in moderate and patients with gutkha index 101-150, all were in severe stage. Histological staging showed direct correlation with gutkha index, it increased with increase in gutkha index with p <0.05. Site analysis showed that buccal mucosa and retromolar area were involved in all the patient and floor of mouth in 46% of patients Body mass index analysis revealed that out of 27 patients with moderate clinical staging 3 was underweight; out of 3 with severe clinical staging, 2 was underweight. The duration and frequency of areca nut product use effects on the incidence and severity of OSMF and the patient becomes unable to eat due to burning, ulcers and inability to open mouth which affect the health of the individual. Thus it is important to access the nutritional status to improve the survival rate of patients.

Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.

PubMed

Lee, William M; Hynan, Linda S; Rossaro, Lorenzo; Fontana, Robert J; Stravitz, R Todd; Larson, Anne M; Davern, Timothy J; Murray, Natalie G; McCashland, Timothy; Reisch, Joan S; Robuck, Patricia R

2009-09-01

N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure. In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation. A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031). Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.

Recommendation for axillary lymph node dissection in women with early breast cancer and sentinel node metastasis: A systematic review and meta-analysis of randomized controlled trials using the GRADE system.

PubMed

Huang, Tsai-Wei; Kuo, Ken N; Chen, Kee-Hsin; Chen, Chiehfeng; Hou, Wen-Hsuan; Lee, Wei-Hwa; Chao, Tsu-Yi; Tsai, Jo-Ting; Su, Chih-Ming; Huang, Ming-Te; Tam, Ka-Wai

2016-10-01

In 2014, the American Society of Clinical Oncology published an updated clinical practice guideline on axillary lymph node dissection (ALND) for early-stage breast cancer patients. However, these recommendations have been challenged because they were based on data from only one randomized controlled trial (RCT). We evaluated the rationale of these recommendations by systematically reviewing RCTs using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. We searched articles in the PubMed, EMBASE, CINAHL, Scopus, and Cochrane databases. The primary endpoints were overall survival (OS) and disease-free survival (DFS). The secondary endpoints were recurrence rate and surgical complications of axillary dissection. The quality of evidence was assessed using the GRADE profiler. Five eligible studies were retrieved and analyzed. We divided sentinel lymph node (SLN) metastasis into two categories: SLN micrometastasis and SLN macrometastasis. In patients with 1 or 2 SLN micrometastasis, no significant difference was observed in OS, DFS, or recurrence rate between the ALND and non-ALND groups. For patients with 1 or 2 SLN marcometastasis, only one trial with a moderate risk of bias was included, and non-ALND was the preferred management overall. However, ALND might be appropriate for patients who placed a greater emphasis on longer-term survival at any cost. We recommend non-ALND management for early breast cancer patients with 1 or 2 SLN micrometastasis or macrometastasis on the basis of a systematic review of the current evidence conducted using the GRADE system. However, the optimal practice of evidence-based medicine should incorporate patient preferences, particularly when evidence is limited. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study.

PubMed

Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

2016-01-01

Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m 2 on days 1-14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C-E) and CTCAE (grade 2-4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of neuropathy.

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

PubMed

García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

2016-01-01

Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Fluorouracil and dose-dense chemotherapy in adjuvant treatment of patients with early-stage breast cancer: an open-label, 2 × 2 factorial, randomised phase 3 trial.

PubMed

Del Mastro, Lucia; De Placido, Sabino; Bruzzi, Paolo; De Laurentiis, Michele; Boni, Corrado; Cavazzini, Giovanna; Durando, Antonio; Turletti, Anna; Nisticò, Cecilia; Valle, Enrichetta; Garrone, Ornella; Puglisi, Fabio; Montemurro, Filippo; Barni, Sandro; Ardizzoni, Andrea; Gamucci, Teresa; Colantuoni, Giuseppe; Giuliano, Mario; Gravina, Adriano; Papaldo, Paola; Bighin, Claudia; Bisagni, Giancarlo; Forestieri, Valeria; Cognetti, Francesco

2015-05-09

Whether addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel (EC-P) is favourable in adjuvant treatment of patients with node-positive breast cancer is controversial, as is the benefit of increased density of dosing. We aimed to address these questions in terms of improvements in disease-free survival. In this 2 × 2 factorial, open-label, phase 3 trial, we enrolled patients aged 18-70 years with operable, node positive, early-stage breast cancer from 81 Italian centres. Eligible patients were randomly allocated in a 1:1:1:1 ratio with a centralised, interactive online system to receive either dose-dense chemotherapy (administered intravenously every 2 weeks with pegfilgrastim support) with fluorouracil plus EC-P (FEC-P) or EC-P or to receive standard-interval chemotherapy (administered intravenously every 3 weeks) with FEC-P or EC-P. The primary study endpoint was disease-free survival, assessed with the Kaplan-Meier method in the intention-to-treat population. Our primary comparisons were between dose schedule (every 2 weeks vs every 3 weeks) and dose type (FEC-P vs EC-P). This study is registered with ClinicalTrials.gov, number NCT00433420. Between April 24, 2003, and July 3, 2006, we recruited 2091 patients. 88 patients were enrolled in centres that only provided standard-intensity dosing. After a median follow-up of 7·0 years (interquartile range [IQR] 4·5-6·3), 140 (26%) of 545 patients given EC-P every 3 weeks, 157 (29%) of 544 patients given FEC-P every 3 weeks, 111 (22%) of 502 patients given EC-P every 2 weeks, and 113 (23%) of 500 patients given FEC-P every 2 weeks had a disease-free survival event. For the dose-density comparison, disease-free survival at 5 years was 81% (95% CI 79-84) in patients treated every 2 weeks and 76% (74-79) in patients treated every 3 weeks (HR 0·77, 95% CI 0·65-0·92; p=0·004); overall survival rates at 5 years were 94% (93-96) and 89% (87-91; HR 0·65, 0·51-0·84; p=0·001) and for the

B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

PubMed

Wang, Jiasheng; He, Gan; Yang, Qiang; Bai, Lian; Jian, Bin; Li, Qugang; Li, Zhongfu

2018-06-01

The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (P<0.001). Spearman's rank correlation analysis revealed that Bcl-2 expression was negatively correlated with pathological grade and Tumor-Node-Metastasis (TNM) stage (-0.827 and -0.388, respectively; P<0.05). Bcl-2 expression was revealed to be a significant prognostic indicator of colorectal carcinoma [relative risk (95% CI), 0.703 (0.552-0.895); P<0.05]. The log-rank test revealed a significant association between low Bcl-2 expression and reduced overall survival (P=0.039), as well as a significant association between older age (>55 years) and reduced overall survival (P<0.001) in Chinese patients with colorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer.

PubMed

Clarke, Charlotte H; Yip, Christine; Badgwell, Donna; Fung, Eric T; Coombes, Kevin R; Zhang, Zhen; Lu, Karen H; Bast, Robert C

2011-09-01

The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P=0.015, McNemar's test). Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. Copyright © 2011. Published by Elsevier Inc.

Proteomic Biomarkers Apolipoprotein A1, Truncated Transthyretin and Connective Tissue Activating Protein III Enhance the Sensitivity of CA125 for Detecting Early Stage Epithelial Ovarian Cancer

PubMed Central

Clarke, Charlotte H.; Yip, Christine; Badgwell, Donna; Fung, Eric T.; Coombes, Kevin R.; Zhang, Zhen; Lu, Karen H.; Bast, Robert C.

2011-01-01

Objective The low prevalence of ovarian cancer demands both high sensitivity (>75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers. Methods Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls. Results In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P= 0.015, McNemar's test). Conclusion Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer. PMID:21708402

Relationships between biomarkers of cartilage, bone, synovial metabolism and knee pain provide insights into the origins of pain in early knee osteoarthritis.

PubMed

Ishijima, Muneaki; Watari, Taiji; Naito, Kiyohito; Kaneko, Haruka; Futami, Ippei; Yoshimura-Ishida, Kaori; Tomonaga, Akihito; Yamaguchi, Hideyo; Yamamoto, Tetsuro; Nagaoka, Isao; Kurosawa, Hisashi; Poole, Robin A; Kaneko, Kazuo

2011-02-14

We tested the hypothesis that there exist relationships between the onset of early stage radiographically defined knee osteoarthritis (OA), pain and changes in biomarkers of joint metabolism. Using Kellgren-Lawrence (K/L) grading early radiographic knee OA (K/L 2) was detected in 16 of 46 patients. These grades (K/L 1 is no OA and K/L 2 is early OA) were divided into two groups according to the presence or absence of persistent knee pain. Sera (s) and urines (u) were analysed with biomarkers for cartilage collagen cleavage (sC2C and uCTX-II) and synthesis (sCPII), bone resorption (uNTx) and synovitis (hyaluronic acid: sHA). sCPII decreased and sC2C/sCPII, uCTX-II/sCPII and sHA increased with onset of OA (K/L 2 versus K/L 1) irrespective of joint pain. In contrast, sC2C and uCTX-II remained unchanged in early OA patients. Of the patients with K/L grades 1 and 2 sC2C, sCPII, sHA, uNTX and uCTX-II were all significantly increased in patients with knee pain independent of grade. Among the K/L grade 2 subjects, only uCTX-II and uCTX-II/sCPII were increased in those with knee pain. In grade 1 patients both sC2C and sCPII were increased in those with knee pain. No such grade specific changes were seen for the other biomarkers including sHA. These results suggest that changes in cartilage matrix turnover detected by molecular biomarkers may reflect early changes in cartilage structure that account directly or indirectly for knee pain. Also K/L grade 1 patients with knee pain exhibit biomarker features of early OA.

Early Grade Writing Assessment: An Instrument Model

ERIC Educational Resources Information Center

Jiménez, Juan E.

2017-01-01

The United Nations Educational, Scientific, and Cultural Organization promoted the creation of a model instrument for individual assessment of students' foundational writing skills in the Spanish language that was based on a literature review and existing writing tools and assessments. The purpose of the "Early Grade Writing Assessment"…

Minimally Invasive Surgical Staging in Early-stage Ovarian Carcinoma: A Systematic Review and Meta-analysis.

PubMed

Bogani, Giorgio; Borghi, Chiara; Leone Roberti Maggiore, Umberto; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Lopez, Carlos; Sabatucci, Ilaria; Scaffa, Cono; Indini, Alice; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

Few studies investigated the efficacy and safety of minimally invasive surgery for the treatment of early-stage epithelial ovarian cancer (eEOC). In this context, we aimed to review the current evidence comparing laparoscopy and the laparotomic approach for staging procedures in eEOC. This systematic review was registered in the International Prospective Register of Systematic Reviews. Overall, 3065 patients were included: 1450 undergoing laparoscopy and 1615 undergoing laparotomic staging. Patients undergoing laparoscopy experienced a longer (but not statistically significant) operative time (weighted mean difference [WMD] = 28.3 minutes; 95% confidence interval [CI], -2.59 to 59.2), a lower estimated blood loss (WMD = -156.5 mL; 95% CI, -216.4 to -96.5), a shorter length of hospital stay (WMD = -3.7 days; 95% CI, -5.2 to -2.1), and a lower postoperative complication rate (odds ratio [OR] = 0.48; 95% CI, 0.29-0.81) than patients undergoing laparotomy. The upstaging (OR = 0.81; 95% CI, 0.55-1.20) and cyst rupture (OR = 1.32; 95% CI, 0.52-3.38) rates were similar between groups. Laparoscopic staging is associated with a shorter time to chemotherapy than laparotomic procedures (WMD = -5.16 days; 95% CI, -8.68 to -1.64). Survival outcomes were not influenced by the route of surgery. Pooled data suggested that the minimally invasive surgical approach is equivalent to laparotomy for the treatment of eEOC and may be superior in terms of perioperative outcomes. However, because of the low level of evidence of the included studies, further randomized trials are warranted. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

PubMed Central

Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

2013-01-01

Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

Practice patterns and long-term survival for early-stage rectal cancer.

PubMed

Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Mastering Reading and Mathematics in the Early Grades. Challenge to Lead Series

ERIC Educational Resources Information Center

Lord, Joan; Wade, Robin; Creech, Joseph

2004-01-01

The "Challenge to Lead" goal for early grades students is first about student achievement in reading and mathematics. The goal is that students in the early grades, regardless of their economic status, school location, ethnicity or gender will be as proficient in reading and mathematics as youngsters anywhere in the nation. "Challenge to Lead"…

The effect of maternal and child early life factors on grade repetition among HIV exposed and unexposed children in rural KwaZulu-Natal, South Africa.

PubMed

Mitchell, J M; Rochat, T J; Houle, B; Stein, A; Newell, M L; Bland, R M

2016-04-01

Receiving an education is essential for children living in poverty to fulfil their potential. Success in the early years of schooling is important as children who repeat grade one are particularly at risk for future dropout. We examined early life factors associated with grade repetition through logistic regression and explored reasons for repeating a grade through parent report. In 2012-2014 we re-enrolled children aged 7-11 years in rural KwaZulu-Natal who had been part of an early life intervention. Of the 894 children included, 43.1% had repeated a grade, of which 62.9% were boys. Higher maternal education (aOR 0.44; 95% CI 0.2-0.9) and being further along in the birth order (aOR 0.46; 95% CI 0.3-0.9) reduced the odds of grade repetition. In addition, maternal HIV status had the strongest effect on grade repetition for girls (aOR 2.17; 95% CI 1.3-3.8), whereas for boys, it was a fridge in the household (aOR 0.59; 95% CI 0.4-1.0). Issues with school readiness was the most common reason for repeating a grade according to parental report (126/385, 32.7%), while school disruptions was an important reason among HIV-exposed boys. Further research is needed to elucidate the pathways through which HIV affects girls' educational outcomes and potentially impacts on disrupted schooling for boys. Our results also highlight the importance of preparation for schooling in the early years of life; future research could focus on gaining a better understanding of mechanisms by which to improve early school success, including increased quality of reception year and investigating the protective effect of older siblings.

HIV-1 Nef sequesters MHC-I intracellularly by targeting early stages of endocytosis and recycling

PubMed Central

Dirk, Brennan S.; Pawlak, Emily N.; Johnson, Aaron L.; Van Nynatten, Logan R.; Jacob, Rajesh A.; Heit, Bryan; Dikeakos, Jimmy D.

2016-01-01

A defining characteristic of HIV-1 infection is the ability of the virus to persist within the host. Specifically, MHC-I downregulation by the HIV-1 accessory protein Nef is of critical importance in preventing infected cells from cytotoxic T-cell mediated killing. Nef downregulates MHC-I by modulating the host membrane trafficking machinery, resulting in the endocytosis and eventual sequestration of MHC-I within the cell. In the current report, we utilized the intracellular protein-protein interaction reporter system, bimolecular fluorescence complementation (BiFC), in combination with super-resolution microscopy, to track the Nef/MHC-I interaction and determine its subcellular localization in cells. We demonstrate that this interaction occurs upon Nef binding the MHC-I cytoplasmic tail early during endocytosis in a Rab5-positive endosome. Disruption of early endosome regulation inhibited Nef-dependent MHC-I downregulation, demonstrating that Nef hijacks the early endosome to sequester MHC-I within the cell. Furthermore, super-resolution imaging identified that the Nef:MHC-I BiFC complex transits through both early and late endosomes before ultimately residing at the trans-Golgi network. Together we demonstrate the importance of the early stages of the endocytic network in the removal of MHC-I from the cell surface and its re-localization within the cell, which allows HIV-1 to optimally evade host immune responses. PMID:27841315

Financial Implication of Radioactive Iodine Therapy for Early-Stage Papillary Thyroid Cancer.

PubMed

Al-Qurayshi, Zaid; Bu Ali, Daniah; Srivastav, Sudesh; Kandil, Emad

2017-01-01

The aim of this study was to evaluate disease-specific survival and cost related to radioactive iodine therapy (RAI) utilization in patients with early-stage papillary thyroid carcinoma (PTC). This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2012. A total of 38,374 patients with PTC were identified. Of those, 56.3% had adjuvant RAI. RAI administration was not associated with a survival advantage in patients with PTC stage I (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.11, 14.54; p = 0.85) or stage II (HR 0.50, 95% CI 0.05, 4.88; p = 0.55). Patients with PTC stage III who underwent adjuvant RAI had an improved survival (HR 0.30, 95% CI 0.10, 0.91; p = 0.033). In 2012, RAI was used in 45.5% of patients with stage I and in 71.4% of patients with stage II. The total expenditure on adjuvant RAI for PTC stage I throughout the study period was estimated to be USD 82.3 million with an annual average of USD 9.1 (±2.0) million/year. If the decline rate in the utilization of RAI continued, the model projected that the annual expenditure would decrease by USD 0.14 million/year. There is a high prevalence of adjuvant RAI utilization for early-stage PTC that is causing financial burden on the health system with no evidence of survival benefit. © 2017 S. Karger AG, Basel.

Multimodal imaging findings in 'hyper-early' stage MEWDS.

PubMed

Cahuzac, Armelle; Wolff, Benjamin; Mathis, Thibaud; Errera, Marie-Hélène; Sahel, José-Alain; Mauget-Faÿsse, Martine

2017-10-01

To describe a new stage of multiple evanescent white dot syndrome (MEWDS), occurring at a very early phase of the disease. Retrospective analysis of clinical, angiographic and tomographic findings in four patients with 'hyper-early' stage MEWDS. In four patients seen within 1 week of the onset of symptoms, fundus analysis revealed macular granity and the classic yellow-white dots, some having no corresponding hyperautofluorescent pattern. Spectral-domain optical coherence tomography (SD-OCT) showed central foveal disruption of the ellipsoid zone (EZ) and interdigitation layer with a hyper-reflective dome-shaped lesion. In two patients, fluorescein angiography (FA) revealed an intermediate hypofluorescent perimacular halo, whereas late indocyanine green angiography (ICGA) showed a hyperfluorescent halo as well as the classic MEWDS features. After a few days, the EZ disruption appeared complete on OCT and fundus autofluorescence (FAF) in all patients. Visual acuity, OCT and FAF findings had fully recovered within 3 months. We have shown a new feature of MEWDS on FAF, OCT, FA and ICGA, corresponding to a very early stage of the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary Emphysema.

PubMed

Hellbach, Katharina; Yaroshenko, Andre; Meinel, Felix G; Yildirim, Ali Ö; Conlon, Thomas M; Bech, Martin; Mueller, Mark; Velroyen, Astrid; Notohamiprodjo, Mike; Bamberg, Fabian; Auweter, Sigrid; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz

2015-07-01

The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema. Female 8- to 10-week-old C57Bl/6N mice were used throughout all experiments. Pulmonary emphysema was induced by orotracheal injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control mice (n = 11) received orotracheal injection of phosphate-buffered saline. To monitor the temporal patterns of emphysema development over time, the mice were imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered saline. X-ray transmission and dark-field images were acquired with a prototype grating-based small-animal scanner. In vivo pulmonary function tests were performed before killing the animals. In addition, lungs were obtained for detailed histopathological analysis, including mean cord length (MCL) quantification as a parameter for the assessment of emphysema. Three blinded readers, all of them experienced radiologists and familiar with dark-field imaging, were asked to grade the severity of emphysema for both dark-field and transmission images. Histopathology and MCL quantification confirmed the introduction of different stages of emphysema, which could be clearly visualized and differentiated on the dark-field radiograms, whereas early stages were not detected on transmission images. The correlation between MCL and dark-field signal intensities (r = 0.85) was significantly higher than the correlation between MCL and transmission signal intensities (r = 0.37). The readers' visual ratings for dark-field images correlated significantly better with MCL (r = 0.85) than visual ratings for transmission images (r = 0.36). Interreader agreement and the diagnostic accuracy of both quantitative and visual assessment were significantly higher

Surgical Staging of Early Stage Endometrial Cancer: Comparison Between Laparotomy and Laparoscopy

PubMed Central

Api, Murat; Kayatas, Semra; Boza, Aysen Telce; Nazik, Hakan; Adiguzel, Cevdet; Guzin, Kadir; Eroglu, Mustafa

2013-01-01

Background The aim of the present study was to compare the laparotomy (LT) and laparoscopy (LS) in patients who undergone surgical staging for early stage endometrium cancer. Methods Retrospective data were collected and analyzed for amount of intraoperative bleeding, complication rates, total resected and laterality specific number of lymph nodes and duration of operation in patients operated with either LT or LS. Results Seventy-nine stage I endometrium cancer patients were found to be eligible for the trial purposes: 58 (73.4%) treated by LT and 21 (26.6%) treated by LS. The number of lymph nodes was similar in LT (8.9 ± 5.3) and LS (9.2 ± 4.8) (P = 0.8). In LT group, there was no difference in the number of lymph nodes between the right and left sides (10 ± 5.8 and 8.7 ± 4.8 respectively, P = 0.19); in LS group, the number of lymph nodes resected from the right side was higher than the left side (9.8 ± 5 and 7 ± 3.5 respectively, P = 0.039). The amount of intraoperative bleeding and hospitalization period were significantly higher in LT group. Seventy-nine patients had a median follow-up of 30 months. The two groups were similar for disease-free survival (P = 0.46, log rank test). Conclusions There was no significant difference between the two methods in terms of number of total resected lymph nodes. In early stage endometrial carcinoma, LS has provided adequate staging and similar survival rates with LT. PMID:29147363

Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Woolston, Caroline M.; Al-Attar, Ahmad; Storr, Sarah J.

2011-04-01

Purpose: Early-stage invasive breast cancer patients have commonly undergone breast-conserving surgery and radiotherapy. In a large majority of these patients, the treatment is effective; however, a proportion will develop local recurrence. Deregulated redox systems provide cancer cells protection from increased oxidative stress, such as that induced by ionizing radiation. Therefore, the expression of redox proteins was examined in tumor specimens from this defined cohort to determine whether such expression could predict response. Methods and Materials: The nuclear and cytoplasmic expression of nine redox proteins (glutathione, glutathione reductase, glutaredoxin, glutathione peroxidase 1, 3, and 4, and glutathione S-transferase-{theta}, -{pi}, and -{alpha})more » was assessed using conventional immunohistochemistry on a tissue microarray of 224 tumors. Results: A high cytoplasmic expression of glutathione S-transferase-{theta} significantly correlated with a greater risk of local recurrence (p = .008) and, when combined with a low nuclear expression (p = .009), became an independent predictive factor (p = .002) for local recurrence. High cytoplasmic expression of glutathione S-transferase-{theta} also correlated with a worse overall survival (p = .009). Low nuclear and cytoplasmic expression of glutathione peroxidase 3 (p = .002) correlated with a greater risk of local recurrence and was an independent predictive factor (p = .005). These proteins did not correlate with tumor grade, suggesting their function might be specific to the regulation of oxidative stress rather than alterations of tumor phenotype. Only nuclear (p = .005) and cytoplasmic (p = .001) expression of glutathione peroxidase 4 correlated with the tumor grade. Conclusions: Our results support the use of redox protein expression, namely glutathione S-transferase-{theta} and glutathione peroxidase 3, to predict the response to radiotherapy in early-stage breast cancer patients. If incorporated

7 CFR 28.461 - Leaf Grade 1.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Leaf Grade 1. 28.461 Section 28.461 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Upland Cotton § 28.461 Leaf Grade 1. Leaf Grade 1 is leaf which is within the range represented by...

7 CFR 28.461 - Leaf Grade 1.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Leaf Grade 1. 28.461 Section 28.461 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Upland Cotton § 28.461 Leaf Grade 1. Leaf Grade 1 is leaf which is within the range represented by...

7 CFR 28.461 - Leaf Grade 1.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Leaf Grade 1. 28.461 Section 28.461 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Upland Cotton § 28.461 Leaf Grade 1. Leaf Grade 1 is leaf which is within the range represented by...

7 CFR 28.461 - Leaf Grade 1.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Leaf Grade 1. 28.461 Section 28.461 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Upland Cotton § 28.461 Leaf Grade 1. Leaf Grade 1 is leaf which is within the range represented by...

7 CFR 28.461 - Leaf Grade 1.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Leaf Grade 1. 28.461 Section 28.461 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Upland Cotton § 28.461 Leaf Grade 1. Leaf Grade 1 is leaf which is within the range represented by...

76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

... SMALL BUSINESS ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage... Webinars regarding its proposed Early Stage Small Business Investment Companies (Early Stage SBIC) rule. The proposed Early Stage SBIC rule defines a new sub-category of small business investment companies...

OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.

PubMed

Tweddle, D A; Pinkerton, C R; Lewis, I J; Ellershaw, C; Cole, M; Pearson, A D

2001-01-01

This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age. Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5 mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600 mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was haematological recovery. Seventy out of ninety-five (74%) patients completed seven or more courses and were evaluable for toxicity. Of these 70 patients, 33% had more than three episodes of fever and sepsis, 35% required more than five blood or platelet transfusions, 36% had grade 2 or more gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death. OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age.

Morphogenesis of early stage melanoma

NASA Astrophysics Data System (ADS)

Chatelain, Clément; Amar, Martine Ben

2015-08-01

Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy.

PubMed

Akthar, Adil S; Ferguson, Mark K; Koshy, Matthew; Vigneswaran, Wickii T; Malik, Renuka

2017-02-01

primary tumor maximum standard uptake value, histology, grade, or interval between positron emission tomography-computed tomography and surgery. Our results support pathologic assessment of N1 lymph nodes in patients with stage Inon-small cell lung cancer considered for stereotactic body radiotherapy, with the greatest benefit in patients with central and T2 tumors. Diagnostic evaluation with endoscopic bronchial ultrasound should be considered in the evaluation of stereotactic body radiotherapy candidates.

Limitations of PET/CT in the Detection of Occult N1 Metastasis in Clinical Stage I(T1-2aN0) Non-Small Cell Lung Cancer for Staging Prior to Stereotactic Body Radiotherapy

PubMed Central

Akthar, Adil S.; Ferguson, Mark K.; Koshy, Matthew; Vigneswaran, Wickii T.

2016-01-01

%, respectively. Occult lymph node involvement was not associated with primary tumor maximum standard uptake value, histology, grade, or interval between positron emission tomography–computed tomography and surgery. Conclusion: Our results support pathologic assessment of N1 lymph nodes in patients with stage Inon-small cell lung cancer considered for stereotactic body radiotherapy, with the greatest benefit in patients with central and T2 tumors. Diagnostic evaluation with endoscopic bronchial ultrasound should be considered in the evaluation of stereotactic body radiotherapy candidates. PMID:26792491

Characterization of xylan in the early stages of secondary cell wall formation in tobacco bright yellow-2 cells.

PubMed

Ishii, Tadashi; Matsuoka, Keita; Ono, Hiroshi; Ohnishi-Kameyama, Mayumi; Yaoi, Katsuro; Nakano, Yoshimi; Ohtani, Misato; Demura, Taku; Iwai, Hiroaki; Satoh, Shinobu

2017-11-15

The major polysaccharides present in the primary and secondary walls surrounding plant cells have been well characterized. However, our knowledge of the early stages of secondary wall formation is limited. To address this, cell walls were isolated from differentiating xylem vessel elements of tobacco bright yellow-2 (BY-2) cells induced by VASCULAR-RELATED NAC-DOMAIN7 (VND7). The walls of induced VND7-VP16-GR BY-2 cells consisted of cellulose, pectic polysaccharides, hemicelluloses, and lignin, and contained more xylan and cellulose compared with non-transformed BY-2 and uninduced VND7-VP16-GR BY-2 cells. A reducing end sequence of xylan containing rhamnose and galaturonic acid- residues is present in the walls of induced, uninduced, and non-transformed BY-2 cells. Glucuronic acid residues in xylan from walls of induced cells are O-methylated, while those of xylan in non-transformed BY-2 and uninduced cells are not. Our results show that xylan changes in chemical structure and amounts during the early stages of xylem differentiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early stages of soldering reactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lord, R.A.; Umantsev, A.

2005-09-15

An experiment on the early stages of intermetallic compound layer growth during soldering and its theoretical analysis were conducted with the intent to study the controlling factors of the process. An experimental technique based on fast dipping and pulling of a copper coupon in liquid solder followed by optical microscopy allowed the authors to study the temporal behavior of the sample on a single micrograph. The technique should be of value for different areas of metallurgy because many experiments on crystallization may be described as the growth of a layer of intermediate phase. Comparison of the experimental results with themore » theoretical calculations allowed one to identify the kinetics of dissolution as the rate-controlling mechanism on the early stages and measure the kinetic coefficient of dissolution. A popular model of intermetallic compound layer structure coarsening is discussed.« less

[Relationship between visual field index and visual field morphological stages of glaucoma and their diagnostic value].

PubMed

Hou, X R; Qin, J Y; Ren, Z Q

2017-02-11

Objective: To investigate the rationality of visual field morphological stages of glaucoma, its relationship with visual field index and their diagnostic value. Methods: Retrospective series case study. Two hundred and seventy-four glaucoma patients and 100 normal control received visual field examination by Humphrey perimeter using standard automatic perimetry (SAP) program from March 2014 to September 2014. Glaucoma patients were graded into four stages according to characteristic morphological damage of visual field, distribution of mean defect (MD) and visual field index (VFI) of each stage were plotted and receiver operation characteristic curve (ROC) was used to explore its correlation with MD and VFI. The diagnostic value of MD and VFI was also compared. For the comparison of general data of subjects, categorical variables were compared using χ(2) test, numerical variables were compared using F test. MD and VFI were compared using ANOVA among stages according to visual field, followed by multiple comparisons using LSD method. The correlation between MD and VFI and different stages according to visual field defined their diagnostic value, and compared using area under the curve (AUC) of ROC. Results: No characteristic visual field damage was found in normal control group, and MD and VFI was (-0.06±1.24) dB and (99.15±0.76)%, respectively. Glaucomatous visual field damage was graded into early, medium, late and end stage according to morphological characteristic. MD for each stage were (-2.83±2.00) dB, (-9.70±3.68) dB, (-18.46±2.90) dB, and (-27.96±2.76) dB, respectively. VFI for each stage were (93.84±3.61)%, (75.16±10.85)%, (49.36±11.26)% and (17.65±10.59)%, respectively. MD and VFI of each stage of glaucomatous group and normal control group were all significantly different ( F= 1 165.53 and P <0.01 for MD; F= 1 028.04 and P <0.01 for VFI). AUC of ROC was A(MD)=0.91 and Se(MD)=0.01 (95% confident interval was 0.89-0.94) for MD, and A(VFI)=0

Early cancer diagnoses through BRCA1/2 screening of unselected adult biobank participants

PubMed Central

Buchanan, Adam H; Manickam, Kandamurugu; Meyer, Michelle N; Wagner, Jennifer K; Hallquist, Miranda L G; Williams, Janet L; Rahm, Alanna Kulchak; Williams, Marc S; Chen, Zong-Ming E; Shah, Chaitali K; Garg, Tullika K; Lazzeri, Amanda L; Schwartz, Marci L B; Lindbuchler, D'Andra M; Fan, Audrey L; Leeming, Rosemary; Servano, Pedro O; Smith, Ashlee L; Vogel, Victor G; Abul-Husn, Noura S; Dewey, Frederick E; Lebo, Matthew S; Mason-Suares, Heather M; Ritchie, Marylyn D; Davis, F Daniel; Carey, David J; Feinberg, David T; Faucett, W Andrew; Ledbetter, David H; Murray, Michael F

2018-01-01

Purpose The clinical utility of screening unselected individuals for pathogenic BRCA1/2 variants has not been established. Data on cancer risk management behaviors and diagnoses of BRCA1/2-associated cancers can help inform assessments of clinical utility. Methods Whole-exome sequences of participants in the MyCode Community Health Initiative were reviewed for pathogenic/likely pathogenic BRCA1/2 variants. Clinically confirmed variants were disclosed to patient–participants and their clinicians. We queried patient–participants’ electronic health records for BRCA1/2-associated cancer diagnoses and risk management that occurred within 12 months after results disclosure, and calculated the percentage of patient–participants of eligible age who had begun risk management. Results Thirty-seven MyCode patient–participants were unaware of their pathogenic/likely pathogenic BRCA1/2 variant, had not had a BRCA1/2-associated cancer, and had 12 months of follow-up. Of the 33 who were of an age to begin BRCA1/2-associated risk management, 26 (79%) had performed at least one such procedure. Three were diagnosed with an early-stage, BRCA1/2-associated cancer—including a stage 1C fallopian tube cancer—via these procedures. Conclusion Screening for pathogenic BRCA1/2 variants among unselected individuals can lead to occult cancer detection shortly after disclosure. Comprehensive outcomes data generated within our learning healthcare system will aid in determining whether population-wide BRCA1/2 genomic screening programs offer clinical utility. PMID:29261187

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Association of medial meniscal extrusion with medial tibial osteophyte distance detected by T2 mapping MRI in patients with early-stage knee osteoarthritis.

PubMed

Hada, Shinnosuke; Ishijima, Muneaki; Kaneko, Haruka; Kinoshita, Mayuko; Liu, Lizu; Sadatsuki, Ryo; Futami, Ippei; Yusup, Anwajan; Takamura, Tomohiro; Arita, Hitoshi; Shiozawa, Jun; Aoki, Takako; Takazawa, Yuji; Ikeda, Hiroshi; Aoki, Shigeki; Kurosawa, Hisashi; Okada, Yasunori; Kaneko, Kazuo

2017-09-12

Medial meniscal extrusion (MME) is associated with progression of medial knee osteoarthritis (OA), but no or little information is available for relationships between MME and osteophytes, which are found in cartilage and bone parts. Because of the limitation in detectability of the cartilage part of osteophytes by radiography or conventional magnetic resonance imaging (MRI), the rate of development and size of osteophytes appear to have been underestimated. Because T2 mapping MRI may enable us to evaluate the cartilage part of osteophytes, we aimed to examine the association between MME and OA-related changes, including osteophytes, by using conventional and T2 mapping MRI. Patients with early-stage knee OA (n = 50) were examined. MRI-detected OA-related changes, in addition to MME, were evaluated according to the Whole-Organ Magnetic Resonance Imaging Score. T2 values of the medial meniscus and osteophytes were measured on T2 mapping images. Osteophytes surgically removed from patients with end-stage knee OA were histologically analyzed and compared with findings derived by radiography and MRI. Medial side osteophytes were detected by T2 mapping MRI in 98% of patients with early-stage knee OA, although the detection rate was 48% by conventional MRI and 40% by radiography. Among the OA-related changes, medial tibial osteophyte distance was most closely associated with MME, as determined by multiple logistic regression analysis, in the patients with early-stage knee OA (β = 0.711, p < 0.001). T2 values of the medial meniscus were directly correlated with MME in patients with early-stage knee OA, who showed ≥ 3 mm of MME (r = 0.58, p = 0.003). The accuracy of osteophyte evaluation by T2 mapping MRI was confirmed by histological analysis of the osteophytes removed from patients with end-stage knee OA. Our study demonstrates that medial tibial osteophyte evaluated by T2 mapping MRI is frequently observed in the patients with early-stage knee

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

PubMed

Duffy, T A; Iwanowicz, L R; McCormick, S D

2014-07-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage cancer of the larynx: Phase Ib study.

PubMed

Shafirstein, Gal; Rigual, Nestor R; Arshad, Hassan; Cooper, Michele T; Bellnier, David A; Wilding, Gregory; Tan, Wei; Merzianu, Mihai; Henderson, Barbara W

2016-04-01

The purpose of this study was for us to report results regarding the safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses. A single-institution, phase Ib, open label, noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response. Twenty-nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH-PDT at MTD. HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377-E383, 2016. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc.

The Relation between 1st Grade Grey Matter Volume and 2nd Grade Math Competence

PubMed Central

Price, Gavin R.; Wilkey, Eric D.; Yeo, Darren J.; Cutting, Laurie E.

2015-01-01

Mathematical and numerical competence is a critical foundation for individual success in modern society yet the neurobiological sources of individual differences in math competence are poorly understood. Neuroimaging research over the last decade suggests that neural mechanisms in the parietal lobe, particularly the intraparietal sulcus (IPS) are structurally aberrant in individuals with mathematical learning disabilities. However, whether those same brain regions underlie individual differences in math performance across the full range of math abilities is unknown. Furthermore, previous studies have been exclusively cross-sectional, making it unclear whether variations in the structure of the IPS are caused by or consequences of the development of math skills. The present study investigates the relation between grey matter volume across the whole brain and math competence longitudinally in a representative sample of 50 elementary school children. Results show that grey matter volume in the left IPS at the end of 1st grade relates to math competence a year later at the end of 2nd grade. Grey matter volume in this region did not change over that year, and was still correlated with math competence at the end of 2nd grade. These findings support the hypothesis that the IPS and its associated functions represent a critical foundation for the acquisition of mathematical competence. PMID:26334946

Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy.

PubMed

Srinivasan, Sangeetha; Dehghani, Cirous; Pritchard, Nicola; Edwards, Katie; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

2017-12-01

To examine the neuronal structural integrity of cornea and retina as markers for neuronal degeneration in nonproliferative diabetic retinopathy (NPDR). Participants were recruited from the broader Brisbane community, Queensland, Australia. Two hundred forty-one participants (187 with diabetes and 54 nondiabetic controls) were examined. Diabetic retinopathy (DR) was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), corneal nerve fiber tortuosity (CNFT), full retinal thickness, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), focal (FLV) and global loss volumes (GLV), hemoglobin A1c (HbA1c), nephropathy, neuropathy, and cardiovascular measures were examined. The central zone (P = 0.174), parafoveal thickness (P = 0.090), perifovea (P = 0.592), RNFL (P = 0.866), GCC (P = 0.798), and GCC GLV (P = 0.338) did not differ significantly between the groups. In comparison to the control group, those with very mild NPDR and those with mild NPDR had significantly higher focal loss in GCC volume (P = 0.036). CNFL was significantly lower in those with mild NPDR (P = 0.004) in comparison to the control group and those with no DR. The CNBD (P = 0.094) and CNFT (P = 0.458) did not differ between the groups. Both corneal and retinal neuronal degeneration may occur in early stages of diabetic retinopathy. Further studies are required to examine these potential markers for neuronal degeneration in the absence of clinical signs of DR.

Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ichimura, Ryohei, E-mail: red0828@hotmail.co.j; Mizukami, Sayaka, E-mail: non_sugar_life@hotmail.co.j; Takahashi, Miwa, E-mail: mtakahashi@nihs.go.j

2010-08-01

To clarify the involvement of signaling of transforming growth factor (TGF)-{beta} during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P{sup +} foci, while Smad4, a nuclear transporter ofmore » Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P{sup +} lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P{sup +} foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P{sup -} foci induced by promotion with agonists of peroxisome proliferator-activated receptor-{alpha} did not change Smad expression, suggesting an aberration in the Smad

Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Dun; Orthopedic Department, Taizhou Hospital, Wenzhou Medical College, Linhai, Zhejiang 317000; Chen, Hai-Xiao, E-mail: Hxchen-1@163.net

Bone remodeling relies on a dynamic balance between bone formation and resorption, mediated by osteoblasts and osteoclasts, respectively. Under certain stimuli, osteoprogenitor cells may differentiate into premature osteoblasts and further into mature osteoblasts. This process is marked by increased alkaline phosphatase (ALP) activity and mineralized nodule formation. In this study, we induced osteoblast differentiation in mouse osteoprogenitor MC3T3-E1 cells and divided the process into three stages. In the first stage (day 3), the MC3T3-E1 cell under osteoblast differentiation did not express ALP or deposit a mineralized nodule. In the second stage, the MC3T3-E1 cell expressed ALP but did not formmore » a mineralized nodule. In the third stage, the MC3T3-E1 cell had ALP activity and formed mineralized nodules. In the present study, we focused on morphological and proteomic changes of MC3T3-E1 cells in the early stage of osteoblast differentiation - a period when premature osteoblasts transform into mature osteoblasts. We found that mean cell area and mean stress fiber density were increased in this stage due to enhanced cell spreading and decreased cell proliferation. We further analyzed the proteins in the signaling pathway of regulation of the cytoskeleton using a proteomic approach and found upregulation of IQGAP1, gelsolin, moesin, radixin, and Cfl1. After analyzing the focal adhesion signaling pathway, we found the upregulation of FLNA, LAMA1, LAMA5, COL1A1, COL3A1, COL4A6, and COL5A2 as well as the downregulation of COL4A1, COL4A2, and COL4A4. In conclusion, the signaling pathway of regulation of the cytoskeleton and focal adhesion play critical roles in regulating cell spreading and actin skeleton formation in the early stage of osteoblast differentiation.« less

SSX2-4 expression in early-stage non-small cell lung cancer.

PubMed

Greve, K B V; Pøhl, M; Olsen, K E; Nielsen, O; Ditzel, H J; Gjerstorff, M F

2014-05-01

The expression of cancer/testis antigens SSX2, SSX3, and SSX4 in non-small cell lung cancers (NSCLC) was examined, since they are considered promising targets for cancer immunotherapy due to their immunogenicity and testis-restricted normal tissue expression. We characterized three SSX antibodies and performed immunohistochemical staining of 25 different normal tissues and 143 NSCLCs. The antibodies differed in binding to two distinctive splice variants of SSX2 that exhibited different subcellular staining patterns, suggesting that the two splice variants display different functions. SSX2-4 expression was only detected in 5 of 143 early-stage NSCLCs, which is rare compared to other cancer/testis antigens (e.g. MAGE-A and GAGE). However, further studies are needed to determine whether SSX can be used as a prognostic or predictive biomarker in NSCLC. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Activation of p62-keap1-Nrf2 antioxidant pathway in the early stage of acetaminophen-induced acute liver injury in mice.

PubMed

Shen, Zhenyu; Wang, Yu; Su, Zhenhui; Kou, Ruirui; Xie, Keqin; Song, Fuyong

2018-02-25

Acetaminophen (APAP) overdose can cause severe liver failure even death. Nearly half of drug-induced liver injury is attributed to APAP in the US and many European countries. Oxidative stress has been validated as a critical event involved in APAP-induced liver failure. p62/SQSTM1, a selective autophagy adaptor protein, is reported to regulate Nrf2-ARE antioxidant pathway in response to oxidative stress. However, the exact role of p62-keap1-Nrf2 antioxidant pathway in APAP-induced hepatotoxicity remains unknown. In the present study, the dose-response and time-course model in C57/BL6 mice were established by intraperitoneal injection of APAP. The results of serum alanine/aspartate aminotransferases (ALT/AST) and histological examination demonstrated that APAP overdose resulted in the severe liver injury. In the meantime, the levels of p62, phospho-p62 and nuclear Nrf2 were significantly increased by APAP in mice liver, suggesting an activation of p62-keap1-Nrf2 pathway. In addition, the expression of GSTA1 mRNA was increased in a dose-dependent manner, while the mRNA levels of HO-1 and GCLC were decreased with the increase of APAP dose. Our further investigation found that expression of HO-1 and GCLC peaked at 3 h∼6 h, and then were decreased gradually. Taken together, these results indicated that p62-keap1-Nrf2 antioxidant pathway was primarily activated in the early stage of APAP hepatotoxicity, which might play a protective role in the process of APAP-induced acute liver injury. Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical defense of early life stages of benthic marine invertebrates.

PubMed

Lindquist, Niels

2002-10-01

Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

French Multicenter Study Evaluating the Risk of Lymph Node Metastases in Early-Stage Endometrial Cancer: Contribution of a Risk Scoring System.

PubMed

Bendifallah, Sofiane; Canlorbe, Geoffroy; Arsène, Emmanuelle; Collinet, Pierre; Huguet, Florence; Coutant, Charles; Hudry, Delphine; Graesslin, Olivier; Raimond, Emilie; Touboul, Cyril; Daraï, Emile; Ballester, Marcos

2015-08-01

This study was designed to develop a risk scoring system (RSS) for predicting lymph node (LN) metastases in patients with early-stage endometrial cancer (EC). Data of 457 patients with early-stage EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from a prospective, multicentre database (training set). A risk model based on factors impacting LN metastases was developed. To assess the discrimination of the RSS, both internal by the bootstrap approach and external validation (validation set) were adopted. Overall the LN metastasis rate was 11.8 % (54/457). LN metastases were associated with five variables: age ≥60 years, histological grade 3 and/or type 2, primary tumor diameter ≥1.5 cm, depth of myometrial invasion ≥50 %, and the positive lymphovascular space involvement status. These variables were included in the RSS and assigned scores ranging from 0 to 9. The discrimination of the RSS was 0.81 [95 % confidence interval (CI) 0.78-0.84] in the training set. The area under the curve of the receiver-operating characteristics for predicting LN metastases after internal and external validation was 0.80 (95 % CI 0.77-0.83) and 0.85 (95 % CI 0.81-0.89), respectively. A total score of 6 points corresponded to the optimal threshold of the RSS with a rate of LN metastases of 7.5 % (29/385) and 34.7 % (25/72) for low-risk (≤6 points) and high-risk patients (>6 points), respectively. At this threshold, the diagnostic accuracy was 83 %. This RSS could be useful in clinical practice to determine which patients with early-stage EC should benefit from secondary surgical staging including complete lymphadenectomy.

Preoperative Albumin-Bilirubin Grade Predicts Recurrences After Radical Gastrectomy in Patients with pT2-4 Gastric Cancer.

PubMed

Kanda, Mitsuro; Tanaka, Chie; Kobayashi, Daisuke; Uda, Hiroaki; Inaoka, Kenichi; Tanaka, Yuri; Hayashi, Masamichi; Iwata, Naoki; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Murotani, Kenta; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-03-01

The albumin-bilirubin (ALBI) score was initially developed for assessing liver dysfunction severity and was suggested to have prognostic value in patients with hepatocellular carcinoma. We aimed to evaluate the prognostic impact of ALBI grade in patients with advanced gastric cancer (GC) after radical gastrectomy. This study included 283 patients who underwent radical gastrectomy for pT2-4 GC without preoperative treatment. ALBI was calculated as follows: (log 10 bilirubin (μmol/L) × 0.66) + (albumin (g/L) × -0.0852) and categorized into grades 1 (≤-2.60), 2 (-2.60<, ≤-1.39) and 3 (-1.39<). The median ALBI score was -2.96, and a number of patients in ALBI grades 1, 2 and 3 were 228, 55 and 0, respectively. Patients with ALBI grade 2 had a lower administration rate of adjuvant chemotherapy than those with ALBI grade 1, whereas no significant differences were found in morbidity rate and disease stage. The ALBI grade 2 group was more likely to have shorter disease-specific and disease-free survival compared with the ALBI grade 1 group. Multivariable analysis identified ALBI grade 2 as an independent prognostic factor for disease-free survival (hazard ratio 1.97, 95% confidence interval 1.10-3.47, p = 0.0242). Survival differences between ALBI grade 1 and 2 groups were increased in the patient subset that received adjuvant chemotherapy. ALBI grade 2 was correlated with a shortened duration of administration of postoperative S-1 adjuvant. ALBI grade serves as a simple and promising predictive factor for disease-free and disease-specific survival in patients with pT2-4 GC after radical gastrectomy.

Study design and early result of a phase I study of SABR for early-stage glottic cancer.

PubMed

Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

2018-05-14

Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Feasibility of sequential adjuvant chemotherapy with a 3-month oxaliplatin-based regimen followed by 3 months of capecitabine in patients with stage III and high-risk stage II colorectal cancer: JSWOG-C2 study

PubMed Central

Tsuruta, Atsushi; Yamashita, Kazuki; Tanioka, Hiroaki; Tsuji, Akihito; Inukai, Michio; Yamakawa, Toshiki; Yamatsuji, Tomoki; Yoshimitsu, Masanori; Toyota, Kazuhiro; Yamano, Taketoshi; Nagasaka, Takeshi; Okajima, Masazumi

2016-01-01

Background Six months of oxaliplatin-based chemotherapy is the standard adjuvant chemotherapy for completely resected stage III colorectal cancer (CRC). Also, patients with stage II CRC who are considered to be at high risk of disease recurrence often receive the same adjuvant chemotherapy treatment. We prospectively investigated the extent and degree of neuropathy suffered by stage III and high-risk stage II resectable CRC patients who underwent sequential approach involving 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine. Patients and methods Patients with completely resected stage III and high-risk stage II CRC aged ≥20 years were eligible. Patients were treated with folinic acid, fluorouracil, and oxaliplatin (FOLFOX) or capecitabine and oxaliplatin (CAPOX) for 3 months followed by capecitabine (2,500 mg/m2 on days 1–14 every 3 weeks) for 3 months. Primary end points were frequency and the grade of oxaliplatin-induced neurotoxicity as evaluated using the physician-based Common Terminology Criteria for Adverse Events version 4.0 (CTCAE) grading and the patient-based scale, self-reported Patient Neurotoxicity Questionnaire. Results Ninety-one patients were enrolled and 86 patients assessed. Eighty-four percent of patients completed the planned oxaliplatin-based therapy for 3 months, and 63% of patients completed all treatments for the full 6 months. Overall incidences of grade 3 or 4 peripheral sensory or motor neuropathy according to the CTCAE were 3.5% and 1.2%, respectively. Regarding the peripheral sensory neuropathy, the proportion of Patient Neurotoxicity Questionnaire (grade C–E) and CTCAE (grade 2–4) at months 1.5/3/6 were 11.3/22.1/29.4% and 5.3/4.4/11.3%, respectively (Spearman correlation coefficient: 0.47). Conclusion A sequential approach to adjuvant chemotherapy with 3 months of an oxaliplatin-based regimen followed by 3 months of capecitabine was tolerated by patients and associated with a low incidence of

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

Early Childhood Reading Skills and Proficiency in NAEP Eighth-Grade Reading Assessment

ERIC Educational Resources Information Center

Dogan, Enis; Ogut, Burhan; Kim, Young Yee

2015-01-01

The relationship between reading skills in earlier grades and achieving "Proficiency" on the National Assessment of Educational Progress (NAEP) grade 8 reading assessment was examined by establishing a statistical link between NAEP and the Early Childhood Longitudinal Study (ECLS) grade 8 reading assessments using data from a common…

Recommendations for neoadjuvant pathologic staging (ypTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

PubMed

Rice, Thomas W; Ishwaran, Hemant; Kelsen, David P; Hofstetter, Wayne L; Apperson-Hansen, Carolyn; Blackstone, Eugene H

2016-11-01

We report analytic and consensus processes that produced recommendations for neoadjuvant pathologic stage groups (ypTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration provided data for 22,654 patients with epithelial esophageal cancers; 7,773 had pathologic assessment after neoadjuvant therapy. Risk-adjusted survival for each patient was developed. Random forest analysis identified data-driven neoadjuvant pathologic stage groups wherein survival decreased monotonically with increasing group, was distinctive between groups, and homogeneous within groups. An additional analysis produced data-driven anatomic neoadjuvant pathologic stage groups based only on ypT, ypN, and ypM categories. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced consensus neoadjuvant pathologic stage groups. Grade and location were much less discriminating for stage grouping ypTNM than pTNM. Data-driven stage grouping without grade and location produced nearly identical groups for squamous cell carcinoma and adenocarcinoma. However, ypTNM groups and their associated survival differed from pTNM. The need for consensus process was minimal. The consensus groups, identical for both cell types were as follows: ypStage I comprised ypT0-2N0M0; ypStage II ypT3N0M0; ypStage IIIA ypT0-2N1M0; ypStage IIIB ypT3N1M0, ypT0-3N2, and ypT4aN0M0; ypStage IVA ypT4aN1-2, ypT4bN0-2, and ypTanyN3M0; and ypStage IVB ypTanyNanyM1. Absence of equivalent pathologic (pTNM) categories for the peculiar neoadjuvant pathologic categories ypTisN0-3M0 and ypT0N0-3M0, dissimilar stage group compositions, and markedly different early- and intermediate-stage survival necessitated a unified, unique set of stage grouping for patients of either cell type who receive neoadjuvant therapy. © 2016 International Society for Diseases of the Esophagus.

Relationships between immunophenotype, Ki-67 index, microvascular density, Ep-CAM/P-cadherin, and MMP-2 expression in early-stage invasive ductal breast cancer.

PubMed

Niemiec, Joanna A; Adamczyk, Agnieszka; Małecki, Krzysztof; Majchrzyk, Kaja; Ryś, Janusz

2012-12-01

There is still a lack of complete consensus on immunohistochemical surrogate markers for luminal A (LA) and luminal B (LB), HER2, and basal-like subtypes of breast carcinomas and their correlation with cancer cell adhesion and invasion-promoting factors. Therefore, early-stage invasive ductal breast cancer patients (N=209) were recruited to the study and divided into 4 subtypes, on the basis of the expression of the estrogen/progesterone receptor and HER2 (LA: 74.4% of cases; LB: 7.8%; HER2: 5.6%; and triple-negative phenotype: 12.2%). Regardless of the above-mentioned classification, we divided all carcinomas into 2 groups: carcinomas expressing at least 1 basal marker [cytokeratine (CK)5/6, CK5, vimentin, epidermal growth factor receptor, or aberrant CK8/18 expression-membranous or in <10% of cells] versus carcinomas negative for basal markers. Then we studied the relationships between the above subtypes (2 classifications) and (i) the expression of adhesion molecules (Ep-CAM, P-cadherin), (ii) matrix metalloproteinases (MMP)-2, (iii) the proliferation index (MIB-1 LI), and (iv) the microvascular density. We confirmed that triple-negative phenotypes are characterized by basal marker expression, a high tumor grade, and high MIB-1 LI. In this subtype, we found MMP-2 expression in stromal leukocytes less frequently. Both LA carcinomas and carcinomas negative for basal markers were more often negative for epithelial cell adhesion molecule (Ep-CAM) and P-cadherin. Moreover, we noted a higher mean value of microvascular density in CK5/6 and Ep-CAM-immunopositive tumors, carcinomas with aberrant CK8/18 expression, and carcinomas with no or strong expression of MMP-2 in stromal fibroblast-like cells. These results might suggest that mechanisms of stroma remodeling and carcinogenesis (Ep-CAM is the suggested marker of breast progenitors) may differ between breast cancer subtypes.

Early stages of figure-ground segregation during perception of the face-vase.

PubMed

Pitts, Michael A; Martínez, Antígona; Brewer, James B; Hillyard, Steven A

2011-04-01

The temporal sequence of neural processes supporting figure-ground perception was investigated by recording ERPs associated with subjects' perceptions of the face-vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects' figure-ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ∼ 150-200 msec) when that region was perceived as figure versus background. These components likely reflect an early "border ownership" stage, and a subsequent "figure-ground segregation" stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure-ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure-ground perception, each which are subject to modifications by selective attention.

An egg injection method for assessing early life stage mortality of polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in rainbow trout, (Oncorhynchus mykiss)

USGS Publications Warehouse

Walker, M.K.; Hufnagle, L.C.; Clayton, M.K.; Peterson, R.E.

1992-01-01

To characterize the risk that polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) pose to salmonid early life stage survival, we developed a method to expose rainbow trout (Oncorhynchus mykiss) eggs to graded doses of PCDD, PCDF, and PCB congeners, using 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as a prototype. Rainbow trout eggs were injected 24–50 h post-fertilization with 0.2 μl of 50 mM phosphatidylcholine (PC) liposomes (control) or 0.2 μl of 5–7 graded doses of TCDD incorporated into 50 mM PC liposomes. Injection volume never exceeded 0.6% egg volume. Immediately following injection, the injection site was sealed with Super glue®, resulting in 92–97% of TCDD dose retained by the egg. Following both egg injection and waterborne egg exposure. TCDD toxicity in rainbow trout was manifested by half-hatching mortality but predominantly by sac fry mortality associated with hemorrhages, pericardial edema, and yolk sac edema. TCDD LD50s, following injection and waterborne exposure of rainbow trout eggs, were 421 (331–489) and 439 (346–519) pg TCDD/g egg (LD50, 95% fiducial limits), respectively. As in rainbow trout, TCDD toxicity in lake trout (Salvelinus namaycush) following the same two routes of exposure was manifested by half-hatching mortality but predominantly by sac fry mortality preceded by hemorrhages and yolk sac edema. LD50s, based on the dose of TCDD in lake trout eggs, were 47 (21–65) and 65 (60–71) pg/g following injection and waterborne exposure, respectively. The egg injection method is ideal for assessing the relationship between early life stage mortality in rainbow trout and graded egg doses of individual PCDD, PCDF, or PCB congeners.

TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

EPA Science Inventory

Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

Spiritual Diversity and Living with Early-Stage Dementia.

PubMed

McGee, Jocelyn Shealy; Zhao, Holly Carlson; Myers, Dennis R; Seela Eaton, Hannah

2018-01-01

Attention to spiritual diversity is necessary for the provision of culturally informed clinical care for people with early-stage dementia and their family members. In this article, an evidence-based theoretical framework for conceptualizing spiritual diversity is described in detail (Pargament, 2011). The framework is then applied to two clinical case studies of people living with early-stage dementia to elucidate the multilayered components of spiritual diversity in this population. The case studies were selected from a larger mixed-methods study on spirituality, positive psychological factors, health, and well-being in people living with early-stage dementia and their family members. To our knowledge this is the first systematic attempt to apply a theoretical framework for understanding spiritual diversity in this population. Implications for clinical practice are provided.

Vowel Diphthongs. Fun with Phonics! Book 10. Grades 1-2.

ERIC Educational Resources Information Center

Daniel, Claire

This book provides hands-on activities for grades 1-2 that make phonics instruction easy and fun for teachers and children in the classroom. The book offers methods for practice, reinforcement, and assessment of phonics skills. A poem is used to introduce the phonics element of this book, vowel diphthongs. The poem is duplicated so children can…

Low-grade disease activity in early life precedes childhood asthma and allergy.

PubMed

Chawes, Bo Lund Krogsgaard

2016-08-01

for promotion of or protection against asthma and allergies. Therefore, preventive initiatives to restore immune health, such as vitamin D supplementation, should be directed to the fetus and the earliest postnatal life. The eosinophil granulocyte has a major role in the allergic inflammatory cascade and eosinophilia is considered a hallmark of many allergic phenotypes. In paper III, we examined neonatal urinary biomarkers including eosinophil protein X (u-EPX), which is contained in the eosinophil granules. Elevated u-EPX in asymptomatic neonates was associated with development of allergic sensitization and nasal eosinophilia, but not with wheezing or asthma (III). These findings suggest the presence of an ongoing low-grade disease process in early life characterized by eosinophil activation prior to appearance of allergy-related conditions. In papers IV-V, we investigated perinatal and genetic predictors of neonatal fractional exhaled nitric oxide (FeNO) and the relationship between neonatal FeNO and wheezing later in child-hood. The a priori selected determinants encompassed asthma genetic risk variants, anthropometrics, demographics, socioeconomics, parental asthma and allergy, maternal smoking, paracetamol and antibiotic usage during pregnancy, and neonatal bacterial airway colonization. Among those, only the DENND1B risk allele and paternal history of asthma and allergy were associated with increased FeNO values (V) suggesting that raised FeNO in neonatal life is primarily an inherited trait. The neonatal FeNO levels were widely dispersed (1-67 ppb) and children with values in the upper quartile were at increased risk of recurrent wheezing in early childhood, but not persistent wheezing, reduced lung function or allergy-related endpoints (IV). This suggests that elevated neonatal FeNO represents an early asymptomatic low-grade disease process other than congenitally small airway calibre contributing to a transient wheezing phenotype. Reduced lung function in

Addition of Rice Bran Arabinoxylan to Curcumin Therapy May Be of Benefit to Patients With Early-Stage B-Cell Lymphoid Malignancies (Monoclonal Gammopathy of Undetermined Significance, Smoldering Multiple Myeloma, or Stage 0/1 Chronic Lymphocytic Leukemia)

PubMed Central

Golombick, Terry; Diamond, Terrence H.; Manoharan, Arumugam; Ramakrishna, Rajeev

2016-01-01

Hypothesis. Prior studies on patients with early B-cell lymphoid malignancies suggest that early intervention with curcumin may lead to delay in progressive disease and prolonged survival. These patients are characterized by increased susceptibility to infections. Rice bran arabinoxylan (Ribraxx) has been shown to have immunostimulatory, anti-inflammatory, and proapoptotic effects. We postulated that addition of Ribraxx to curcumin therapy may be of benefit. Study design. Monoclonal gammopathy of undetermined significance (MGUS)/smoldering multiple myeloma (SMM) or stage 0/1 chronic lymphocytic leukemia (CLL) patients who had been on oral curcumin therapy for a period of 6 months or more were administered both curcumin (as Curcuforte) and Ribraxx. Methods. Ten MGUS/SMM patients and 10 patients with stage 0/1 CLL were administered 6 g of curcumin and 2 g Ribraxx daily. Blood samples were collected at baseline and at 2-month intervals for a period of 6 months, and various markers were monitored. MGUS/SMM patients included full blood count (FBC); paraprotein; free light chains/ratio; C-reactive protein (CRP)and erythrocyte sedimentation rate (ESR); B2 microglobulin and immunological markers. Markers monitored for stage 0/1 CLL were FBC, CRP and ESR, and immunological markers. Results. Of 10 MGUS/SMM patients,5 (50%) were neutropenic at baseline, and the Curcuforte/Ribraxx combination therapy showed an increased neutrophil count, varying between 10% and 90% among 8 of the 10 (80%) MGUS/SMM patients. An additional benefit of the combination therapy was the potent effect in reducing the raised ESR in 4 (44%) of the MGUS/SMM patients. Conclusion. Addition of Ribraxx to curcumin therapy may be of benefit to patients with early-stage B-cell lymphoid malignancies. PMID:27154182

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

CCSSM: Getting Started in K-Grade 2

ERIC Educational Resources Information Center

White, Jeanne; Dauksas, Linda

2012-01-01

Rather than feeling overwhelmed at the thought of integrating the new Common Core State Standards for Mathematics (CCSSI 2010) into their teaching practice, teachers might view this as an opportunity to deeply embed mathematics into the K-grade 2 curriculum in the same way that literacy has long been rooted into early learning environments.…

[Grading of tumors in the tubular digestive tract : Esophagus, stomach, colon and rectum].

PubMed

Bläker, H

2016-07-01

Grading of tumors located in the tubular digestive tract is an integral component of pathology assessment reports but is subordinate to the histological typing of tumors with respect to the prognostic significance. Tumor grading has not been shown to be an independent prognostic marker for most tumor entities in the gastrointestinal tract; however, it may be relevant for further routine treatment decision making in early Union Internationale Contre le Cancer (UICC) stage cancers in which the prognosis for patients is less dominated by advanced tumor spread. Owing to the more favorable prognosis of microsatellite instability in colorectal cancer, the World Health Organization (WHO) has recommended that poorly differentiated tumors should be tested and graded as low grade (G1/G2) when microsatellite instability is detected. This recommendation has been integrated into the German S3 guidelines for colorectal cancers. Accordingly, microsatellite instability testing for grading purposes should become routine practice.

76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

... respect to geographic location. SBA's primary concern in terms of geography is to ensure that the Early... SBICs is the primary source of cash used to service their SBA debt. SBA expects that some Early Stage...--Early Stage SBICs AGENCY: U.S. Small Business Administration. ACTION: Proposed rule. SUMMARY: In this...

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients

PubMed Central

Hoogendam, Jacob P.; Zweemer, Ronald P.; Verkooijen, Helena M.; de Jong, Pim A.; van den Bosch, Maurice A. A. J.; Verheijen, René H. M.; Veldhuis, Wouter B.

2015-01-01

Aim Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. Methods All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 – September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Results Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman – with advanced pre-radiograph stage (IVA) disease – showed findings consistent with pulmonary metastases. Radiographs of 7 other women – 4 early, 3 advanced stage disease – were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Conclusion Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years. PMID:26135733

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients.

PubMed

Hoogendam, Jacob P; Zweemer, Ronald P; Verkooijen, Helena M; de Jong, Pim A; van den Bosch, Maurice A A J; Verheijen, René H M; Veldhuis, Wouter B

2015-01-01

Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years.

Use of the sentinel node procedure to stage endometrial cancer.

PubMed

Ballester, Marcos; Dubernard, Gil; Rouzier, Roman; Barranger, Emmanuel; Darai, Emile

2008-05-01

Lymph node status is a major prognostic factor and a criterion for adjuvant therapy in endometrial cancer. The sentinel lymph node (SN) procedure has emerged as a possible alternative to systematic lymphadenectomy. The aims of this study were to determine the detection rate and the false-negative rate of the SN procedure, and its contribution to the staging of women with endometrial cancer. Forty-six patients with endometrial cancer underwent the sentinel node procedure followed by pelvic lymphadenectomy. SNs were detected with a dual or single labelling method in 39 and 7 cases, respectively. All SNs were analysed by both hematoxylin and eosin (H&E) staining and immunochemistry. SNs were identified in 40 patients (87%), whose mean number of SN was 2.6 (range 1-5). The SN detection rate was significantly lower with the single label than with the dual label (p = 0.01). Ten women (25%) had a positive SN on final histology (i.e. there were no false negatives). A correlation was observed between lymph node involvement and both histological grade (p = 0.01) and lymphovascular space involvement (p = 0.001). The stage predicted by magnetic resonance (MR) imaging correlated poorly with the Federation International of Gynaecology and Obstetrics (FIGO) stage. Among the ten women with a positive SN, three of the four women with a grade 1 tumour at biopsy had grade 2-3 disease on final histology. Seven of the ten women with a positive SN underwent external pelvic radiotherapy, based solely on their SN involvement. The SN procedure can reliably determine lymph node status in women with endometrial cancer. Given the limited capacity of MR imaging to detect myometrial invasion, and of biopsy to determine histological grade, our results support the systematic use of the SN procedure in women with endometrial cancer, including those with presumed early-stage disease and/or well-differentiated tumours.

Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis.

PubMed

Bogani, Giorgio; Fucà, Giovanni; Maltese, Giuseppa; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Sabatucci, Ilaria; Lecce, Francesca; Raspagliesi, Francesco; Lorusso, Domenica

2016-11-01

We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested. Copyright © 2016 Elsevier Inc. All rights reserved.

Dissection and Downstream Analysis of Zebra Finch Embryos at Early Stages of Development

PubMed Central

Murray, Jessica R.; Stanciauskas, Monika E.; Aralere, Tejas S.; Saha, Margaret S.

2014-01-01

The zebra finch (Taeniopygiaguttata) has become an increasingly important model organism in many areas of research including toxicology1,2, behavior3, and memory and learning4,5,6. As the only songbird with a sequenced genome, the zebra finch has great potential for use in developmental studies; however, the early stages of zebra finch development have not been well studied. Lack of research in zebra finch development can be attributed to the difficulty of dissecting the small egg and embryo. The following dissection method minimizes embryonic tissue damage, which allows for investigation of morphology and gene expression at all stages of embryonic development. This permits both bright field and fluorescence quality imaging of embryos, use in molecular procedures such as in situ hybridization (ISH), cell proliferation assays, and RNA extraction for quantitative assays such as quantitative real-time PCR (qtRT-PCR). This technique allows investigators to study early stages of development that were previously difficult to access. PMID:24999108

2.9, 2.36, and 1.96 Ga zircons in orthogneiss south of the Red River shear zone in Viet Nam: evidence from SHRIMP U-Pb dating and tectonothermal implications

NASA Astrophysics Data System (ADS)

Nam, Tran Ngoc; Toriumi, Mitsuhiro; Sano, Yuji; Terada, Kentaro; Thang, Ta Trong

2003-05-01

Orthogneissic rocks coexisting with migmatites and containing small amphibolite lenses are exposed in the center of the metamorphic belt which runs parallel to the Day Nui Con Voi-Red River shear zone in northern Viet Nam. The orthogneiss complex has given some radiogenic dates of Early Proterozoic and Late Archean, which are the oldest ages ever registered for the Southeast Asian continent. Zircon grains separated from three samples of the orthogneiss complex have been dated to establish the protolith age and the timing of high-grade tectonothermal events in the complex. Sixty-five SHRIMP U-Th-Pb analyses of these zircons define three age groups of 2.84-2.91, 2.36, and 1.96 Ga. The age groups correspond to three periods of zircon generation. The oldest ˜2.9 Ga cores indicate a minimum age for the protolith of the orthogneiss complex. Two younger generations (including ˜2.36 Ga outer-cores and ˜1.96 Ga rims) probably grew during later high-grade tectono-metamorphic events, which were previously suggested by K-Ar and 40Ar/ 39Ar cooling ages of ˜2.0 Ga for synkinematic hornblendes. An early thermal history of the orthogneiss complex has been constrained, including a primary magma-crystallization stage starting at ˜2.9 Ga, followed by two Early Proterozoic (˜2.36 and ˜1.96 Ga) high-grade tectonothermal events. The ca. 2.9 Ga protolith age of the orthogneiss complex documented in this study provides new convincing evidence for the presence of Archean rocks in Indochina, and clearly indicates that the crustal evolution of northern Viet Nam started as early as Late Archean time.

Suppression of E-cadherin function drives the early stages of Ras-induced squamous cell carcinoma through up-regulation of FAK and Src

PubMed Central

Alt-Holland, Addy; Sowalsky, Adam; Szwec-Levin, Yonit; Shamis, Yulia; Hatch, Harold; Feig, Larry A.; Garlick, Jonathan A.

2011-01-01

Advanced stages of epithelial carcinogenesis involve the loss of intercellular adhesion, but it remains unclear how proteins that regulate alterations in cell-cell and cell-matrix adhesion are deregulated to promote the early stages of cancer development. To address this, a three-dimensional human tissue model that mimics the incipient stages of Squamous Cell Carcinoma (SCC) was used to study how E-cadherin suppression promotes tumor progression in Ras-expressing human keratinocytes. We found that E-cadherin suppression triggered elevated mRNA and protein expression levels of Focal Adhesion Kinase (FAK), and increased FAK and Src activities above the level seen in Ras-expressing E-cadherin-competent keratinocytes. sh-RNA-mediated depletion of FAK and Src restored E-cadherin expression levels by increasing its stability in the membrane, and blocked tumor cell invasion in tissues. Surface transplantation of these tissues to mice resulted in reversion of the tumor phenotype to low-grade tumor islands in contrast to control tissues that manifested an aggressive, high-grade SCC. These findings suggest that the tumor-promoting effect of E-cadherin suppression, a common event in SCC development, is exacerbated by enhanced E-cadherin degradation induced by elevated FAK and Src activities. Furthermore, they imply that targeting FAK or Src in human epithelial cells with neoplastic potential may inhibit the early stages of SCC. PMID:21716326

Downregulation of GLUT4 contributes to effective intervention of estrogen receptor-negative/HER2-overexpressing early stage breast disease progression by lapatinib

PubMed Central

Acharya, Sunil; Xu, Jia; Wang, Xiao; Jain, Shalini; Wang, Hai; Zhang, Qingling; Chang, Chia-Chi; Bower, Joseph; Arun, Banu; Seewaldt, Victoria; Yu, Dihua

2016-01-01

Tamoxifen and aromatase inhibitors (AIs) have shown efficacy in prevention of estrogen receptor-positive (ER+) breast cancer; however, there exists no proven prevention strategy for estrogen receptor-negative (ER-) breast cancer. Up to 40% of ER- breast cancers have human epidermal growth factor receptor 2 overexpression (HER2+), suggesting HER2 signaling might be a good target for chemoprevention for certain ER- breast cancers. Here, we tested the feasibility of the HER2-targeting agent lapatinib in prevention and/or early intervention of an ER-/HER2+ early-stage breast disease model. We found that lapatinib treatment forestalled the progression of atypical ductal hyperplasia (ADH)-like acini to ductal carcinoma in situ (DCIS)-like acini in ER-/HER2+ human mammary epithelial cells (HMECs) in 3D culture. Mechanistically, we found that inhibition of HER2/Akt signaling by lapatinib led to downregulation of GLUT4 and a reduced glucose uptake in HER2-overexpressing cells, resulting in decreased proliferation and increased apoptosis of these cells in 3D culture. Additionally, our data suggest that HER2-driven glycolytic metabolic dysregulation in ER-/HER2+ HMECs might promote early-stage breast disease progression, which can be reversed by lapatinib treatment. Furthermore, low-dose lapatinib treatment, starting at the early stages of mammary grand transformation in the MMTV-neu* mouse model, significantly delayed mammary tumor initiation and progression, extended tumor-free survival, which corresponded to effective inhibition of HER2/Akt signaling and downregulation of GLUT4 in vivo. Taken together, our results indicate that lapatinib, through its inhibition of key signaling pathways and tumor-promoting metabolic events, is a promising agent for the prevention/early intervention of ER-/HER2+ breast cancer progression. PMID:27293993

Effects of genistein on early-stage cutaneous wound healing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

2011-07-08

Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These

Cost implications of unwarranted imaging for distant metastasis in women with early-stage breast cancer in Ontario.

PubMed

Thavorn, K; Wang, Z; Fergusson, D; van Katwyk, S; Arnaout, A; Clemons, M

2016-02-01

Despite the publication of multiple evidence-based guidelines recommending against routine imaging for distant metastasis in patients with early-stage (i/ii) breast cancer, such imaging is frequently performed. The present retrospective cohort study was conducted to estimate the cost of unnecessary imaging tests in women with stage i and ii breast cancer diagnosed between 1 January 2007 and 31 December 2012 in Ontario. We obtained patient-level demographic and tumour data from a large provincial dataset. The total cost of unwarranted imaging tests (in 2015 Canadian dollars) was considered to be equal to the sum of imaging costs incurred between 2007 and 2012 and was stratified by disease stage, imaging modality, and body site. Of the 26,547 identified patients with early-stage breast cancer, 22,811 (85.9%) underwent at least 1 imaging test, with an average of 3.7 tests per patient (3.2 for stage i patients and 4.0 for stage ii patients) over 5 years. At least 1 imaging test was performed in 79.6% of stage i and 92.7% of stage ii patients. During a 5-year period, the cost of unwarranted imaging in patients with early-stage breast cancer ranged from CA$4,418,139 to CA$6,865,856, depending on guideline recommendations. Our study highlights the substantial cost of excess imaging that could be saved and re-allocated to patient care if evidence-based guidelines are followed. Future studies should assess strategies to ensure that evidence-based guidelines are followed and to increase awareness of the cost implications of nonadherence to guidelines.

Grade-Level Differences in Future-Oriented Self-Concept During Early Adolescence: Potential Relevance to School Nursing

PubMed Central

2016-01-01

The middle school and early high school years are a time of significant development, including an increasing ability to envision oneself in the future. Little is known about how adolescents’ future-oriented self-concept (i.e., possible selves) differs across grade levels, although this knowledge may aid in establishing rapport with students and building effective health-promotion and risk reduction interventions. Therefore, this study explored grade-level differences in hoped for and feared possible selves in a sample of 6th – 9th grade students (n = 2,498; Mage = 12.72, SD = 1.15; 51.3% female). Findings suggest that adolescents list a variety of possible selves, and the content differs according to grade-level. These findings offer helpful insight for intervention work aimed at improving student outcomes and preventing risk behavior. Understanding what adolescents hope and fear for themselves in the future may be particularly beneficial for school nurses in identifying the unique challenges students experience and tailoring health-promotion efforts. PMID:27222444

Grade-Level Differences in Future-Oriented Self-Concept During Early Adolescence: Potential Relevance to School Nursing.

PubMed

Stoddard, Sarah A; Pierce, Jennifer; Schmidt, Carissa J

2016-12-01

The middle school and early high school years are a time of significant development, including an increasing ability to envision oneself in the future. Little is known about how adolescents' future-oriented self-concept (i.e., possible selves) differs across grade levels, although this knowledge may aid in establishing rapport with students and building effective health promotion and risk reduction interventions. Therefore, this study explored grade-level differences in hoped for and feared possible selves in a sample of sixth- to ninth-grade students (n = 2,498; M age = 12.72, SD = 1.15; 51.3% female). Findings suggest that adolescents list a variety of possible selves, and the content differs according to grade level. These findings offer helpful insight for intervention work aimed at improving student outcomes and preventing risk behavior. Understanding what adolescents hope and fear for themselves in the future may be particularly beneficial for school nurses in identifying the unique challenges students experience and tailoring health promotion efforts. © The Author(s) 2016.

Immunoreactivities of human nonmetastatic clone 23 and p53 products are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients.

PubMed

Tee, Y T; Wang, P H; Ko, J L; Chen, G D; Chang, H; Lin, L Y

2007-01-01

To assess the relation between expressions of human nonmetastatic clone 23 (nm23-H1) and p53 in cervical cancer, their relationships with lymph node metastasis, and further to examine their predictive of lymph node metastases. nm23-H1 and p53 expression profiles were visualized by immunohistochemistry in early-stage cervical cancer specimens. Immunoreactivities of nm23-H1 and p53 were disassociated. The independent variables related with lymph node metastases were grade of cancer cell differentiation (p < 0.029) and stromal invasion (p < 0.039). Sensitivity, specificity, positive and negative predictive values, and accuracy for lymph node metastasis were calculated to be 91.7%, 13.5%, 25.6%, 83.3%, and 32.7% for nm23-H1 and 66.7%, 51.4%, 30.8%, 82.6%, and 55.1% for p53. Nm23-H1 and p53 are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients. However, stromal invasion and cell differentiation can predict lymph node metastasis.

Decrease in Urinary Creatinine Excretion in Early Stage Chronic Kidney Disease

PubMed Central

Tynkevich, Elena; Flamant, Martin; Haymann, Jean-Philippe; Metzger, Marie; Thervet, Eric; Boffa, Jean-Jacques; Vrtovsnik, François; Houillier, Pascal; Froissart, Marc; Stengel, Bénédicte

2014-01-01

Background Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population. Methods We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by 51Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time. Results Baseline mean urinary creatinine excretion decreased from 15.3±3.1 to 12.1±3.3 mmol/24 h (0.20±0.03 to 0.15±0.04 mmol/kg/24 h) in men, with mGFR falling from ≥60 to <15 mL/min/1.73 m2, and from 9.6±1.9 to 7.6±2.5 (0.16±0.03 to 0.12±0.03) in women. In addition to mGFR, an older age, diabetes, and lower levels of body mass index, proteinuria, and protein intake assessed by urinary urea were associated with lower mean urinary creatinine excretion at baseline. Mean annual decline in mGFR was 1.53±0.12 mL/min/1.73 m2 per year and that of urinary creatinine excretion rate, 0.28±0.02 mmol/24 h per year. Patients with fast annual decline in mGFR of 5 mL/min/1.73 m2 had a decrease in urinary creatinine excretion more than twice as big as in those with stable mGFR, independent of changes in urinary urea as well as of other determinants of low muscle mass. Conclusions Decrease in 24-hour urinary creatinine excretion rate may appear early in CKD patients, and is greater the more mGFR declines independent of lowering protein intake assessed by 24-hour urinary urea. Normalizing urine analytes for creatininuria may overestimate their concentration in patients with reduced kidney function and low muscle mass. PMID:25401694

7 CFR 28.511 - Leaf Grade No. 1.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 2 2010-01-01 2010-01-01 false Leaf Grade No. 1. 28.511 Section 28.511 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Pima Cotton § 28.511 Leaf Grade No. 1. Leaf grade No. 1 shall be American Pima cotton which in...

7 CFR 28.511 - Leaf Grade No. 1.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 2 2011-01-01 2011-01-01 false Leaf Grade No. 1. 28.511 Section 28.511 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Pima Cotton § 28.511 Leaf Grade No. 1. Leaf grade No. 1 shall be American Pima cotton which in...

7 CFR 28.511 - Leaf Grade No. 1.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 2 2014-01-01 2014-01-01 false Leaf Grade No. 1. 28.511 Section 28.511 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Pima Cotton § 28.511 Leaf Grade No. 1. Leaf grade No. 1 shall be American Pima cotton which in...

7 CFR 28.511 - Leaf Grade No. 1.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 2 2013-01-01 2013-01-01 false Leaf Grade No. 1. 28.511 Section 28.511 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Pima Cotton § 28.511 Leaf Grade No. 1. Leaf grade No. 1 shall be American Pima cotton which in...

7 CFR 28.511 - Leaf Grade No. 1.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 2 2012-01-01 2012-01-01 false Leaf Grade No. 1. 28.511 Section 28.511 Agriculture..., TESTING, AND STANDARDS Standards Official Cotton Standards of the United States for the Leaf Grade of American Pima Cotton § 28.511 Leaf Grade No. 1. Leaf grade No. 1 shall be American Pima cotton which in...

Whose Disease Will Recur After Mastectomy for Early Stage, Node-Negative Breast Cancer? A Systematic Review.

PubMed

Kent, Collin; Horton, Janet; Blitzblau, Rachel; Koontz, Bridget F

2015-12-01

Effective local control is associated with improved overall survival, particularly for women with early-stage cancers. No other local therapy is typically offered to women with T1-2 N0 breast cancer after mastectomy, although in select women the 5-year local recurrence rate can be as high as 20%. Therefore, accurately predicting the women who are at highest risk for recurrence after mastectomy will identify those who might benefit from more aggressive adjuvant treatment. A systematic search was conducted identifying risk factors associated with locoregional recurrence, including age, menopausal status, receptor status, lymphovascular invasion (LVI), margin status, use of systemic therapy, size, grade, and genomic classifer score. Although associations varied among studies, the risk factors most consistently identified were age ≤ 40 years, LVI, positive/close margin, and larger tumor size. In women with multiple high risk factors, risk of local recurrence was as high as 20% at 10 years. Additional multicenter studies are needed to investigate risk factors for locoregional recurrence after mastectomy without radiotherapy in T1-2N0 breast cancer. Consideration of additional adjuvant local therapy might be warranted in a subset of women at high risk of local recurrence. Copyright © 2015 Elsevier Inc. All rights reserved.

Early Stages of Figure–Ground Segregation during Perception of the Face–Vase

PubMed Central

Pitts, Michael A.; Martínez, Antígona; Brewer, James B.; Hillyard, Steven A.

2011-01-01

The temporal sequence of neural processes supporting figure–ground perception was investigated by recording ERPs associated with subjects’ perceptions of the face–vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects’ figure–ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ~150–200 msec) when that region was perceived as figure versus background. These components likely reflect an early “border ownership” stage, and a subsequent “figure–ground segregation” stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure–ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure–ground perception, each which are subject to modifications by selective attention. PMID:20146604

Living with early-stage dementia: a review of qualitative studies.

PubMed

Steeman, Els; de Casterlé, Bernadette Dierckx; Godderis, Jan; Grypdonck, Mieke

2006-06-01

This paper presents a literature review whose aim was to provide better understanding of living with early-stage dementia. Even in the early stages, dementia may challenge quality of life. Research on early-stage dementia is mainly in the domain of biomedical aetiology and pathology, providing little understanding of what it means to live with dementia. Knowledge of the lived experience of having dementia is important in order to focus pro-active care towards enhancing quality of life. Qualitative research is fundamentally well suited to obtaining an insider's view of living with early-stage dementia. We performed a meta-synthesis of qualitative research findings. We searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the references of pertinent articles, the references cited in a recently published book on the subjective experience of dementia, one thesis, and the journal Dementia. Thirty-three pertinent articles were identified, representing 28 separate studies and 21 different research samples. Findings were coded, grouped, compared and integrated. Living with dementia is described from the stage a person discovers the memory impairment, through the stage of being diagnosed with dementia, to that of the person's attempts to integrate the impairment into everyday life. Memory loss often threatens perceptions of security, autonomy and being a meaningful member of society. At early stages of memory loss, individuals use self-protecting and self-adjusting strategies to deal with perceived changes and threats. However, the memory impairment itself may make it difficult for an individual to deal with these changes, thereby causing frustration, uncertainty and fear. Our analysis supports the integration of proactive care into the diagnostic process, because even early-stage dementia may challenge quality of life. Moreover, this care should actively involve both the individual with dementia and their family so that both parties can adjust positively

Early-stage Node-negative (T1-T2N0) Anal Cancer Treated with Simultaneous Integrated Boost Radiotherapy and Concurrent Chemotherapy.

PubMed

Franco, Pierfrancesco; Arcadipane, Francesca; Ragona, Riccardo; Mistrangelo, Massimiliano; Cassoni, Paola; Rondi, Nadia; Morino, Mario; Racca, Patrizia; Ricardi, Umberto

2016-04-01

To report clinical outcomes of a consecutive series of patients with early-stage (T1-T1N0) anal cancer treated with intensity-modulated radiotherapy (IMRT) and a simultaneous integrated boost (SIB) approach similarly to the RTOG 05-29 trial. A cohort of 43 patients underwent SIB-IMRT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumor volume and 42 Gy/28 fractions to the elective nodal volumes for cT1N0 cases, and 54 Gy/30 fractions and 45 Gy/30 fractions to the same volumes for cT2N0 cases. Chemotherapy was administered concurrently following Nigro's regimen. The primary endpoint was colostomy-free survival (CFS). Secondary endpoints were locoregional control (LRC), disease-free (DFS), cancer-specific (CSS) and overall (OS) survival. Median follow-up was 39.7 months. The actuarial 3-year CFS was 79.4% [95% confidence interval (CI)=61.4-89.7%]. Actuarial 3-year OS and CSS were 90.8% (95% CI=74.1-96.9%) and 93.8% (95% CI=77.3-98.4%), while DFS was 75.5% (95% CI=56.4-87.1%). Actuarial 3-year LRC was 86.1% (95% CI=69.6-94%). On multivariate analysis, tumor size >3 cm showed a trend towards significance in predicting CFS [hazard ratio (HR)=8.6, 95% CI=84.7-88.1%; p=0.069]. Maximum detected adverse events included: skin (G3): 18%; gastrointestinal tract (G2): 67%; genitourinary tract (G3): 3%; genitalia (G2): 30%; anemia (G2): 7%; leukopenia (G3): 26%, leukopenia (G4):7%; neutropenia (G3): 15%; neutropenia (G4): 12%; thrombocytopenia (G3): 9%. Our clinical results support the use of SIB-IMRT in the combined modality treatment of patients with anal cancer. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Massachusetts Early Warning Indicator System (EWIS). "Technical Descriptions of Risk Model Development": Middle and High School Age Groupings (Grades 7-12)

ERIC Educational Resources Information Center

Massachusetts Department of Elementary and Secondary Education, 2013

2013-01-01

The Massachusetts Department of Elementary and Secondary Education (Department) created the grades 1-12 Early Warning Indicator System (EWIS) in response to district interest in the Early Warning Indicator Index (EWII) that the Department previously created for rising grade 9 students. Districts shared that the EWII data were helpful, but also…