Borderline Grade Research Articles

The influence of candidates’ race on examiners’ ratings in standardised assessments of clinical practice

Purpose Delivering fair and reliable summative assessments in medical education assumes examiner decision making is devoid of bias. We investigated whether candidate racial appearances influenced examiner ratings in undergraduate clinical exams. Methods We used an internet-based design. Examiners watched a randomised set of six videos of three different white candidates and three different non-white (Asian, black and Chinese) candidates taking a clinical history at either fail, borderline or pass grades. We compared the median and interquartile range (IQR) of the paired difference between scores for the white and non-white candidates at each performance grade and tested for statistical significance. Results 160 Examiners participated. At the fail grade, the black and Chinese candidates scored lower than the white candidate, with median paired differences of −2.5 and −1 respectively (both p < 0.001). At the borderline grade, the black and Chinese candidates scored higher than the white candidate, with median paired differences of +2 and +3, respectively (both p < 0.001). At the passing grade, the Asian candidate scored lower than the white candidate (median paired difference −1, p < 0.001). Conclusion The racial appearance of candidates appeared to influence the scores awarded by examiners, but not in a uniform manner.

Sensitive assessment of groundwater-associated, multi-exposure health hazards in a fluoride-enriched region of West Bengal, India

Ninety groundwater samples were collected from Khayrasole and Rajnagar blocks of Birbhum district, West Bengal, India, during pre-monsoon and post-monsoon in 2016 to assess the hazards of fluoride in groundwater. Fluoride concentration fluctuated from 0.3 to 17.6mg/L, with 70% of samples reported beyond the modified regional optimal fluoride level (0.7mg/L) with a statistically significant level of p < 1.7E-24. The average cation and anion concentrations exhibited a descending order of Ca2+ > Mg2+ > Na+ > K+ and HCO3- > Cl- > SO42- > NO3- > F-, respectively. Notably, groundwater quality in 50% of the places ranged from poor to unfit for drinking purposes in terms of water quality index. The mean total hazard index (THI) was 1.1 for adults and 1.9 for children, signifying a greater chance of non-carcinogenic threats to both age groups. In calculating the THI, ingestion and dermal pathways accounted for approximately 96% and 3% health hazards, respectively. The Monte Carlo simulation and sensitivity analysis identified that the diurnal water ingestion rate, exposure duration, and fluoride concentration were the significant sensitive variables that triggered most groundwater-associated non-carcinogenic health issues, signifying more risks among children. Further, dental health surveys (N = 746), following Dean's norms for classification based on regional optimal fluoride level, designated the borderline grade of the community dental hazard. The subsequent hydrogeochemical characterization directed that dissolution from fluoride-bearing minerals and water-rock interaction, such as halite dissolution and calcite-dolomite precipitation, were the governing factors for F- enrichment in groundwater. This study will serve as baseline data for delineating fluoride-induced dental and other health hazards through sensitivity and spatial analysis in the GIS platform for hazard zonation and effective groundwater quality management.

Socioeconomic factors do not impact survival in serous borderline ovarian tumors and low grade serous ovarian cancer

Socioeconomic factors do not impact survival in serous borderline ovarian tumors and low grade serous ovarian cancer

Borderline grades in high stakes clinical examinations: resolving examiner uncertainty

BackgroundObjective Structured Clinical Exams are used to increase reliability and validity, yet they only achieve a modest level of reliability. This low reliability is due in part to examiner variance which is greater than the variance of students. This variance often represents indecisiveness at the cut score with apparent confusion over terms such as “borderline pass”. It is amplified by a well reported failure to fail.MethodsA borderline grade (meaning performance is neither a clear pass nor a clear fail) was introduced in a high stakes undergraduate medical clinical skills exam to replace a borderline pass grade (which was historically resolved as 50%) in a 4 point scale (distinction, pass, borderline, fail). Each Borderline grade was then resolved into a Pass or Fail grade by a formula referencing the difficulty of the station and the performance in the same domain by the student in other stations. Raw pass or fail grades were unaltered. Mean scores and 95%CI were calculated per station and per domain for the unmodified and the modified scores/grades (results are presented on error bars). To estimate the defensibility of these modifications, similar analysis took place for the P and the F grades which resulted from the modification of the B grades.ResultsOf 14,634 observations 4.69% were Borderline. Application of the formula did not impact the mean scores in each domain but the failure rate for the exam increased from 0.7 to 4.1%. Examiners and students expressed satisfaction with the Borderline grade, resolution formula and outcomes. Mean scores (by stations and by domains respectively) of students whose B grades were modified to P were significantly higher than their counterparts whose B grades were modified to F.ConclusionsThis study provides a feasible and defensible resolution to situations where the examinee’s performance is neither a clear pass nor a clear fail, demonstrating the application of the resolution of borderline formula in a high stakes exam. It does not create a new performance standard but utilises real data to make judgements about these small number of candidates. This is perceived as a fair approach to Pass/Fail decisions.

Validity and prognostic significance of sperm protein 17 as a tumor biomarker for epithelial ovarian cancer: a retrospective study

BackgroundPrior small studies have shown increased expression of sperm protein 17 (Sp17) in epithelial ovarian cancer (EOC) tissue and suggest Sp17 as a potential biomarker for EOC. However, how Sp17 expression varies with histology, grade, and stage of EOC and its expression in other ovarian neoplasms has not been defined. It is unknown whether patients with EOC have elevated serum Sp17 levels or if Sp17 expression is associated with survival outcomes.MethodsThe study included 982 patients with benign, borderline, and malignant ovarian neoplasms and normal ovary. There were 878 patients with tissue only, 39 with serum only, and 65 with matching serum and tissue. Immunohistochemical (IHC) staining with anti-Sp17 antibody was performed on tissue specimens and the intensity scored as weak, moderate, or strong. A sandwich enzyme-linked immunosorbent assay (ELISA) was performed to measure Sp17 sera concentrations.ResultsSp17 expression was most commonly seen in serous cystadenomas (83%) and serous borderline tumors (100%). Of the 773 EOC specimens, 223 (30%) expressed Sp17. Grade and histology were significantly associated with Sp17 expression among EOC specimens (p < 0.001) on both univariate and multivariable analysis, with grade 1 serous adenocarcinomas showing the highest expression (51%). Sp17 expression was limited in other benign and non-epithelial malignant neoplasms. Neither Sp17 tissue expression nor serum concentration correlated with survival outcomes. Serum concentrations were higher in patients with Sp17 tissue expression, and the highest concentrations were noted among patients with serous and clear cell adenocarcinomas.ConclusionsSp17 is highly expressed in benign, borderline, and low grade malignant serous ovarian neoplasms and can be quantified in serum. Sp17 expression may have diagnostic significance in this subset of patients.

Spinal epidural lipomatosis presenting to a U.S. Veterans Affairs pain and rehabilitation department: a report of two cases

BackgroundSpinal epidural lipomatosis is an uncommon source of neurogenic claudication. We present two cases of spinal epidural lipomatosis as it relates to diagnosis, management, and a possible association with common medical intervention.Case presentationCase 1: 63-year old male patient presented with neurogenic claudication symptoms, but without evidence of bony central canal stenosis on lumbar computed tomography. He entered a trial of spinal manipulation with transient beneficial gains after seven appointments, but no durable change in neurogenic claudication. An MRI was recommended at this point which revealed grade III spinal epidural lipomatosis at the L5/S1 level.Case 2: 51-year old male patient presented to a pain management physician with radicular symptoms for a series of lumbar epidural steroid injections. He completed a series of three lumbar epidural steroid injections with only short-term benefit. A repeat MRI demonstrated the presence of grade I (borderline grade II) spinal epidural lipomatosis.ConclusionsThe first case illustrates a limitation of ruling out central canal stenosis with computed tomography for patients unable to undergo an MRI. The second case demonstrates a possible association between steroid injections and spinal epidural lipomatosis. An association of this kind has not been established; further research is needed to determine the significance.

Using Online Computer Games in the ELT Classroom: A Case Study

The purpose of this research was to investigate the effectiveness of computer games in learning English as a foreign language and the extent to which they increase motivation in young students. More particularly, this research investigated the validity of the hypothesis that computer games are a particularly motivating means for young students to learn English vocabulary effectively in comparison to other approaches suggested by the Greek National Curriculum. The grade, in which this research was conducted, was the 4th grade of Primary school as it is a borderline grade in which greater demands are imposed on the students of this age group and language level regarding, mainly, their reading and writing skills as in this class, for the first time, it is explicitly stated by the national curriculum that literacy is one of the three basic axons upon which English language learning should be developed. All in all, the results of this research shed light on the effects which new technologies have on language learning as well as their ability to motivate students to learn English. The results of this research will also be used as a basis upon which specific suggestions for the practical implementation of computer games in the everyday classroom can be made.

Malignant and borderline phyllodes tumor of breast treated with a multi-modality approach in a tertiary cancer care centre in North India

Background:Phyllodes tumor (PT) of the breast can be categorized into benign, borderline and malignant subgroups depending on various histopathological factors. Although malignant PTs may be indolent and controlled by local excision, they frequently show local and distant relapses. Literature reveals local recurrence to be the predominant pattern of failure and thus emphasizes the importance of adjuvant radiation in these tumors. The role of systemic chemotherapy has remained doubtful.Materials and Methods:We have analyzed details of all patients of PT (n = 33) treated with adjuvant multi-modality approach in our institute since 1994–2009. The demographic data, treatment details, recurrence patterns and salvage treatment options were documented.Results:All patients received adjuvant radiation. Seven patients received adjuvant chemotherapy. The mean survival of the entire cohort was 150.618 months. There was a trend for better overall survival with borderline grade (193.6 vs. 160.2 months; P = 0.08, log rank). The disease free survival (DFS) favored borderline grade (193.6 months vs. 82.9 months for high grade; P = 0.02, log rank). The DFS was significantly better in tumors having negative margins on postoperative histopathological examination (DFS rate at 5 years being 100% vs. 69.2% for positive or close margins; P = 0.015). The mode of surgery did not have any impact on survival.Conclusion:Adjuvant Radiation should be discussed taking into account surgical margins, size and various pathological factors of the primary. Adjuvant radiation may be utilized in high risk patients to enhance loco-regional control. Systemic chemotherapy is an option, worth exploring, in cases of systemic failure.

Abstract 881: Association of adult body mass index and height with risk of ovarian cancer in 39,000 women: Results of a Mendelian randomization study

Abstract INTRODUCTION: Observational studies have reported positive associations between higher body mass index (BMI) and risks of borderline ovarian tumors and non-high grade serous ovarian cancer (non-HGSC), but the lack of association observed for HGSC may be due to bias arising from weight loss before diagnosis. Observational studies also suggest a positive association between greater height and ovarian cancer risk, but confounding factors may be obscuring the true relationship. The Mendelian randomization (MR) technique uses genetic markers as proxies for environmental risk factors, and can overcome the limitations of bias and confounding which affect observational studies. AIM / METHODS: This study used MR to elucidate the relationship between body size (BMI and height) and risk of ovarian cancer. We pooled data from 16,395 cases and 23,003 controls, all genetically European, from 39 studies in the Ovarian Cancer Association Consortium. We constructed a weighted genetic risk score (GRS) for each trait, summing trait-increasing alleles at 31 single nucleotide polymorphisms (SNPs) associated with BMI and 609 SNPs associated with height in genome-wide association studies, weighting alleles by published β-coefficients for their effect on the trait. Each GRS was a strong instrument for the trait (F-statistics 33.8 [BMI] and 516 [height]). In a two-stage predictor substitution MR approach, we used multivariate logistic regression to model case-control status on body size predicted by each GRS. Study-specific estimates per 5-unit increase in predicted BMI or height were pooled to generate pooled odds ratios (OR) and 95% confidence intervals (CI) using random-effects meta-analysis. Our primary hypotheses were that genetic BMI would be associated with increased risk of non-HGSC but not HGSC and genetic height would be associated with increased risk of ovarian cancer overall. RESULTS: Higher genetically-predicted BMI was associated with increased risk of non-HGSC cancer (OR 1.37, 95% CI 1.02-1.83 per 5-unit increase) but not HGSC (OR 1.05, 95% CI 0.83-1.33). In secondary analyses stratified by behavior/subtype, the strongest association was seen for low grade/borderline serous cancers (OR 2.02, 95% CI 1.24-3.30). Women with greater genetically-predicted height had a modestly increased risk of all (invasive and borderline) ovarian tumors (OR 1.06, 95% CI 1.01-1.11 per 5 cm). In secondary analyses stratified by histologic subtype, the strongest association was seen for clear cell cancers (OR 1.20, 95% CI 1.04-1.38). CONCLUSION: This study is the first to apply MR to investigate ovarian cancer risk factors. These data confirm results from epidemiologic studies, suggesting that obesity is causally associated with non-HGSC, but does not increase risk of the most common HGSC subtype. They also support an association between height and ovarian cancer. Citation Format: Suzanne C. Dixon, Christina M. Nagle, Aaron P. Thrift, Paul D.P Pharoah, Ailith Pirie, Celeste Leigh Pearce, Wei Zheng, Penelope M. Webb, for the Ovarian Cancer Association Consortium. Association of adult body mass index and height with risk of ovarian cancer in 39,000 women: Results of a Mendelian randomization study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 881. doi:10.1158/1538-7445.AM2015-881

Using Student Ability and Item Difficulty for Making Defensible Pass/Fail Decisions for Borderline Grades

The determination of Pass/Fail decisions over Borderline grades, (i.e., grades which do not clearly distinguish between the competent and incompetent examinees) has been an ongoing challenge for academic institutions. This study utilises the Objective Borderline Method (OBM) to determine examinee ability and item difficulty, and from that reclassifying each Borderline grade as a Pass or Fail. Using the OBM, examinees’ Borderline grades from a clinical examination were reclassified into Pass or Fail. The predictive validity of this method was estimated by comparing the examination original and reclassified grades to each other and to subsequent clinical examination results. The new model appeared as more stringent (p<.0001) than the original decisions. Implications for educators and policy makers are discussed. The OBM2 is found to provide a plausible solution for decision making over borderline grades in non-compensatory assessment systems.

Benign serous ovarian tumour: a redefining moment?

While the paradigm that malignancies arise through a stepwise progression from benign precursors has been established for many malignancies, it remains unclear if this holds true for ovarian cancer. Serous ovarian carcinomas are the predominant clinically important subtype and it has been widely believed that some or all of these arise from precursors derived from the ovarian surface epithelium, such as inclusion cysts or serous benign and borderline tumours. Despite the co-occurrence of benign, borderline and low grade carcinoma epithelial components, direct molecular evidence for the benign lesions as precursors is limited. This study aimed to perform high resolution copy number analysis using a series of benign serous ovarian tumours to identify any underlying genomic changes indicative of early events in tumourigenesis, which could assist in determining if these lesions represent precursors to some invasive serous ovarian carcinomas. This is the first ultra-high resolution copy number analysis of benign serous tumours of the ovary. High resolution copy number analysis was performed on tumour epithelial and fibroblast DNA using the Affymetrix OncoScan and SNP6.0 array platforms. Copy number aberrations (CNAs) were detected in the epithelium of only 5.6% (2/35) of serous cystadenomas and cystadenofibromas. Unexpectedly, CNAs were detected in the tumour fibroblasts in 36% (14/39) of cases, including gain of chromosome 12 in 10 cases. No KRAS or BRAF mutations were detectable in either component of the benign serous tumours. Chromosome 12 trisomy has been previously identified in pure fibromas, supporting the concept that a significant proportion of benign serous tumours are in fact primary fibromas with an associated cystic mass. This study therefore provides a novel perspective on the development of these tumours.

Correlations of Hormone Receptors (ER and PR), Her2/neu and p53 Expression in Breast Ductal Carcinoma Among Yemeni Women

Aims: The purpose of this study was to determine if any relationship exists between Estrogen Receptor (ER),Progesterone Receptor (PR), Her2/neu, P53, and clinicopathological factors in female breast ductal carcinoma. Materials and Methods: One hundred and thirty seven (IDC=124, NIDC=13) ductal carcinomas were clinicopathologically and immunohistochemically analyzed and compared with 20 control cases of benign breast lesions in which assessment of Her-2/neu, ER, PR, and P53 has been performed, prospectively. Chi-square analysis was then used to correlate the above observations. Results: The overall immunoexpression of ER, PR, Her2/neu and P53 were 43.8%, 27%, 30.6% and 48.9%, respectively, of the 137 ductal carcinomas. A significant Positive association between ER or PR expression with lymph node involvement was found ( p= 0.004, p= 0.022 respectively), while p53 was found to be negatively associated with lymph nodes involvement (p= 0.03, 0.02, respectively). P53 also associated negatively to lymph node status (P=0.03) and positively with borderline tumor grade (p= 0.03). Conclusion: There are high rates of positive expression of ER, PR, Her2/neu and P53 among Yamani women with breast ductal carcinoma.

Abstract LB-271: Benign ovarian serous tumors: A redefining moment

Abstract Ovarian cancer is a very significant health burden and the fifth leading cause of cancer death in women. At the time of diagnosis, women often have advanced disease and as a consequence their prognosis is extremely poor. Our understanding of the progression of ovarian cancer through precursor stages and the molecular genetic events underlying these changes is currently limited. Although a number of candidate precursor lesions have been identified it remains to confirm the true contribution of these precursor lesions to the onset of ovarian cancer. Epithelial tumors account for 70–80% of all ovarian tumors and the serous subtype accounts for approximately 53% of ovarian epithelial tumors. Serous cystadenomas and cystadenofibromas are common ovarian lesions, accounting for 25% of all benign ovarian tumors and 58% of the ovarian serous tumors. Although there is little definitive molecular or histopathological evidence, ovarian serous cystadenomas and cystadenofibromas have been presumed by many to be the precursor lesions to serous borderline tumors and low grade serous carcinomas. Using the ultra high-resolution Affymetrix SNP6.0 microarray (&amp;gt;1.8M probes) and the high-resolution Molecular Inversion Probe (MIP) assay (&amp;gt;330k probes) we performed copy number (CN) and loss of heterozygosity analysis on 14 ovarian serous cystadenomas and 20 ovarian serous cystadenofibromas. Each tumour was microdissected to allow analysis of tumour epithelium and adjacent stroma with matching lymphocyte DNA for each case. CN alterations were only detected in the epithelial component in 2 of 34 cases (5.9%) but surprisingly alterations were seen in 35% of the stromal components (2/14 cystadenomas and 10/20 cystadenofibromas). Notably, 9/12 of these cases carried a chromosome 12 gain, which has been previously identified as characteristic of the fibroma-thecoma group of ovarian stromal tumors. One of 34 cases (2.9%) was biphasic with CN alterations in both the epithelium and stroma. The lack of identifiable CN alterations or KRAS and BRAF mutations in the epithelium of the vast majority of the ovarian serous cystadenomas and cystadenofibromas supports the notion that these lesions have limited neoplastic potential. These findings are consistent with the predictions of Seidman and Mehrotra (2005) that the majority of benign ovarian serous tumors are potentially cystically dilated glandular inclusions and misclassified fibromas with epithelial inclusions. This would considerably deflate the frequency of the serous subtype within ovarian epithelial tumors and alter the significance of the other epithelial subtypes, with compelling implications for studies of serous ovarian “precursor” lesions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-271. doi:10.1158/1538-7445.AM2011-LB-271

Abstract 4854: Mutations activating proliferation pathways in ovarian cancer

Abstract Ovarian malignancies may arise through different mechanisms of oncogenesis, which influence their treatment and are important for prognosis. Essential to carcinogenesis is the activation of proliferation pathways such as those directed by PI3 kinase or KRAS. New sequencing technologies may improve the detection of somatic mutations in tumor tissue, which is complicated by the low representation of a mutation within a tissue sample inevitably containing normal cells and subpopulations of malignant cells. We analyzed selected exons in PIK3CA, PIK3R, KRAS, BRAF, EGFR and ERBB2 in 34 primary malignant ovarian tumors, including 10 serous, 4 borderline, 11 endometrioid, and 9 mixed or rare subtypes. DNA was extracted from flash-frozen tumor tissues, amplified, and sequenced on a 454-GS-Flx Genome Sequencer. Expression of PTEN, p53, Bcl2, ALDH and Ki67 were assessed by immunohistochemistry on formalin-fixed tissues. Nine mutations were observed in PIK3CA, 5 in BRAF, 4 in KRAS, and 2 in EGFR. SNPs present in the amplicons analyzed allowed allelic imbalance to be estimated, showing possible amplification of EGFR in 9 of 20 informative samples, and of PIK3CA in 6 of 19 informative samples, none of which contained a point mutation. Endometrioid tumors frequently showed anomalies in PIK3CA, Bcl2 expression, and not p53 overexpression. P53 overexpression was typical of serous tumors, and was associated with the absence of mutations in any of the genes sequenced. Borderline and low grade tumors were characterized by BRAF mutation, no imbalance at EGFR, no anomalies at PIK3CA, and less frequent p53 overexpression. The absence of BRAF mutations in high grade tumors suggested that they do not evolve from borderline tumors. PIK3CA mutations were not mutually exclusive with KRAS mutations, confirming the non-redundancy of these intertwined signaling pathways. PTEN extinction was not significantly negatively associated with either point mutations or allelic imbalance at PIK3CA, consistent with different roles for PTEN loss and PI3-kinase activation at different stages of tumorogenesis, in spite of the close association of PTEN with the PI3-kinase pathway. No significant associations were observed between ALDH and Ki67 and any parameters measured. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4854. doi:10.1158/1538-7445.AM2011-4854

Prophylaxis of acute renal allograft rejection using FTY720 in combination with subtherapeutic doses of cyclosporine.

In rodent transplant models, FTY720 exerts a synergistic affect with cyclosporine (CsA) to prolong allograft survival. The present experiments sought to test this combination in subhuman primates. Cynomolgus monkeys were transplanted with kidney allografts that were incompatible in mixed lymphocyte culture reactions. The animals were treated with daily intramuscular injections of CsA using doses selected to maintain whole blood trough concentrations at therapeutic values between 40 and 200 ng/ml. The 4 experimental groups included CsA without or with 0.1, 0.3, or 1 mg/kg/day FTY720 delivered daily by intravenous bolus injection. Therapeutic effects were suggested both by the graft histology of biopsy within the first 10 posttransplant days and by the length of host survival. Whereas recipients treated with CsA alone rejected kidney allografts at a median survival time of 8.5 days (n=4), those treated with either 0.1 or 0.3 mg/kg/day FTY720 in addition to CsA showed significant prolongation of kidney allograft survival to 71 days (n=3; P<0.04) or 63 days (n=5; P<0.05), respectively. The hosts in the 1.0 mg/kg/day FTY720 group survived 48 days, with 2 of 5 recipients succumbing at 9 or 17 days postgraft, suggesting possible complications caused by overimmunosuppression. Biopsies of the 0.1 mg/kg/day FTY720 group on posttransplant day 7 documented mild to moderate rejection (grade I), indicated by multiple focal areas of tubular destruction. The histology results of transplants in the 0.3 or 1 mg/kg/day FTY720 group showed only minimal interstitial inflammatory infiltrates (borderline grade), with no evidence of tubular or arterial damage. Serum creatinine values among the animals in the 0.1 mg/kg/day FTY720 group showed increases in 2 of 3 recipients by day 20 and in the third by day 41 postgraft. Among the 0.3 mg/kg/day FTY720 group, 3 of 5 recipients maintained baseline creatinine values to 45 days postgraft; 1 recipient had stable kidney function for 120 days postgraft. Addition of FTY720 therapy to a subtherapeutic CsA immunosuppressive regimen delays the rejection of renal allografts in subhuman primates.