bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hospital consultants and workplace based assessments: how foundation doctors view these educational interactions?
Authors: McKavanagh P , Smyth A , Carragher A 
Published: January 2012

Abstract

Aim
To determine how foundation year 2 (F2) doctors view the input of hospital consultants into their workplace based assessments (WPBAs).

Study design
F2 doctors in Northern Ireland participated in an electronic survey to evaluate their experiences of foundation programme WPBAs. The opportunity to participate was available to all F2 doctors. The survey was performed using questions displayed electronically and the responses were collated using Turning Point technology. Two weeks later a focus group was convened to assess the issues raised by the electronic survey.

Results
Consultant input into foundation doctor's WPBAs was an infrequent occurrence. The F2 doctors expressed a clear view that they valued consultant input, when this occurred. The WPBAs gave the foundation doctors an opportunity to have a one to one learning opportunity with their supervising consultants. However, many of the WPBAs were completed by other doctors in training, in the grades immediately above the foundation doctors. It was suggested that friendship could influence these assessments.

Conclusions
Completion of foundation doctors' assessments by hospital consultants is viewed as a low priority. These assessments are being completed to a large extent by fellow doctors in training. The learning opportunities are consequently less educationally productive. F2 doctors want more opportunities for valued consultant interaction with timely feedback. Suggestions are proposed to improve WPBA implementation. The present WPBA process lacks integrity and a change in approach is urgently required.
Junior doctors' reflections on patient safety
Authors: Ahmed Maria , Arora Sonal , Carley Simon , Sevdalis Nick , Neale Graham 
Published: January 2012

Abstract

Aim
To determine whether foundation year 1 (FY1) doctors reflect upon patient safety incidents (PSIs) within their portfolios and the potential value of such reflections for quality of care.

Methods
A cross-sectional retrospective review of every ‘reflective practice’ portfolio entry made by all FY1 doctors within an Acute Teaching Hospital Trust was conducted in February 2010. Entries were reviewed by two independent blinded researchers to determine whether they related to a PSI that is, any unintended or unexpected incident that could have or did lead to patient harm. For all entries rated positive by both reviewers, a content analysis approach was used to code PSI into incident type, contributing factors and patient outcome according to validated frameworks developed by the National Patient Safety Agency.

Results
139 reflective practice entries were completed by 30 trainees (15 men, 15 women, mean age 24 years). Of the 139 entries, 49% reflected on a PSI. Of these, 22% were due to errors in clinical assessment; 22% were due to delayed access to care; 18% were due to infrastructure/staffing deficiencies; and 16% were due to medication errors. The most common contributing factors were team/social factors (23%), patient factors (22%), communication and task factors (both 17%). The majority of PSIs led to no harm. Six entries described PSIs resulting in patient death, the majority of which were attributable to diagnostic errors.

Conclusions
FY1 doctors commonly reflect on PSIs within their professional portfolios. Such critical reflection can encourage learning but may also promote patient safety and the quality of healthcare across all medical specialties.
Age at first anal sex and HIV/STI vulnerability among gay men in Australia
Authors: Lyons Anthony , Pitts Marian , Grierson Jeffrey , Smith Anthony , McNally Stephen , Couch Murray 
Published: January 2012

ObjectivesTo determine whether there is a link between age at first anal intercourse (AFAI) and gay men's HIV/sexually transmissible infection (STI) vulnerability, including tendencies to engage in higher risk sexual behaviour.MethodsA nationwide cross-sectional survey was conducted online involving 845 Australian gay men born between 1944 and 1993.ResultsMedian AFAI fell from 35 years for men born between 1944 and 1953 to 18 years for men born between 1984 and 1993. Of those who reported having had anal intercourse (N=822), HIV-positive men were found to be significantly younger on average when they first had anal intercourse compared with HIV-negative men (18.5 vs 21.3 years, p<0.001). Men with a history of other STIs were also significantly younger. Engaging in higher risk sexual behaviour is a likely factor, with AFAI generally younger among men who reported >10 sexual partners in the past year (p<0.001) and who engaged in group sex (p<0.001), receptive anal intercourse (p=0.008) or were drug or alcohol affected (p=0.06) during their most recent sexual encounter.ConclusionsThere appears to be a strong link between AFAI and infection with HIV/STIs, as well as tendencies to engage in higher risk sexual behaviour. While further research is needed to understand this link, these findings highlight a need for sexuality education aimed at gay-identified youth to ensure their sexual debut does not lead to poorer sexual health outcomes.
Oncogenicity of the Developmental Transcription Factor Sox9
Authors: Matheu Ander , Collado Manuel , Wise Clare , Manterola Lorea , Cekaite Lina , Tye Angela J. , Canamero Marta , Bujanda Luis , Schedl Andreas , Cheah Kathryn S.E. , Skotheim Rolf I. , Lothe Ragnhild A. , López de Munain Adolfo , Briscoe James , Serrano Manuel , Lovell-Badge Robin 
Published: January 2012

Abstract
SOX9 [sex-determining region Y (SRY)-box 9 protein], a high mobility group box transcription factor, plays critical roles during embryogenesis and its activity is required for development, differentiation, and lineage commitment in various tissues including the intestinal epithelium. Here, we present functional and clinical data of a broadly important role for SOX9 in tumorigenesis. SOX9 was overexpressed in a wide range of human cancers, where its expression correlated with malignant character and progression. Gain of SOX9 copy number is detected in some primary colorectal cancers. SOX9 exhibited several pro-oncogenic properties, including the ability to promote proliferation, inhibit senescence, and collaborate with other oncogenes in neoplastic transformation. In primary mouse embryo fibroblasts and colorectal cancer cells, SOX9 expression facilitated tumor growth and progression whereas its inactivation reduced tumorigenicity. Mechanistically, we have found that Sox9 directly binds and activates the promoter of the polycomb Bmi1, whose upregulation represses the tumor suppressor Ink4a/Arf locus. In agreement with this, human colorectal cancers showed a positive correlation between expression levels of SOX9 and BMI1 and a negative correlation between SOX9 and ARF in clinical samples. Taken together, our findings provide direct mechanistic evidence of the involvement of SOX9 in neoplastic pathobiology, particularly, in colorectal cancer. Cancer Res; 72(5); 1301–15. ©2012 AACR.
Role of Neurofilament Light Polypeptide in Head and Neck Cancer Chemoresistance
Authors: Chen Baishen , Chen Ju , House Michael G. , Cullen Kevin J. , Nephew Kenneth P. , Guo Zhongmin 
Published: January 2012

AbstractResistance to cisplatin-based chemotherapy is responsible for therapeutic failure of many common human cancers including cancer of head and neck (HNC). Mechanisms underlying cisplatin resistance remain unclear. In this study, we identified neurofilament light polypeptide (NEFL) as a novel hypermethylated gene associated with resistance to cisplatin-based chemotherapy in HNC. Analysis of 14 HNC cell lines revealed that downregulation of NEFL expression significantly correlated with increased resistance to cisplatin. Hypermethylation of NEFL promoter CpG islands was observed in cell lines as examined by bisulfite DNA sequencing and methylation-specific PCR (MSP) and tightly correlated with reduced NEFL mRNA and protein expression. Furthermore, in patient samples with HNC (n = 51) analyzed by quantitative MSP, NEFL promoter hypermethylation was associated with resistance to cisplatin-based chemotherapy [relative risk (RR), 3.045; 95% confidence interval (CI), 1.459–6.355; P = 0.007] and predicted diminished overall and disease-free survival for patients treated with cisplatin-based chemotherapy. Knockdown of NEFL by siRNA in the highly cisplatin-sensitive cell line PCI13 increased (P &lt; 0.01) resistance to cisplatin. In cisplatin-resistant O11 and SCC25cp cells, restored expression of NEFL significantly increased sensitivity to the drug. Furthermore, NEFL physically associated with tuberous sclerosis complex 1 (TSC1), a known inhibitor of the mTOR pathway, and NEFL downregulation led to functional activation of mTOR pathway and consequentially conferred cisplatin resistance. This is the first study to show a role for NEFL in HNC chemoresistance. Our findings suggest that NEFL methylation is a novel mechanism for HNC chemoresistance and may represent a candidate biomarker predictive of chemotherapeutic response and survival in patients with HNC. Mol Cancer Res; 10(3); 305–15. ©2012 AACR.
Migfilin Regulates Esophageal Cancer Cell Motility through Promoting GSK-3β–Mediated Degradation of β-Catenin
Authors: He Huan , Ding Fang , Li Yi , Luo Aiping , Chen Hongyan , Wu Chuanyue , Liu Zhihua 
Published: January 2012

Abstract
Migfilin, a protein component of focal adhesions, has been implicated in regulation of cell–extracellular matrix adhesion and motility but the underlying mechanisms are not fully elucidated. In this study, we have determined the functions of migfilin in esophageal cancer cells and the mechanisms involved. We show that the expression level of migfilin is negatively associated with clinical metastasis, and enforced expression of migfilin suppressed cell motility through decreased free β-catenin level. Overexpression of migfilin resulted in destabilization of β-catenin in concomitance with reduction of its transcriptional activity. Knockdown of migfilin by siRNA, transfection of a mutant β-catenin at Ser37 which is a critical phosphorylation site of GSK-3β, GSK-3β inhibitor LiCl, or proteasome inhibitor MG132 reversed the migfilin-mediated β-catenin degradation and transcription inhibition. Moreover, migfilin promoted β-catenin degradation by reinforcing the association between β-catenin and GSK-3β. In addition, exogenously expressed β-catenin partially restored migfilin-induced suppression of cell invasion. Collectively, these results suggest that the expression level of migfilin in ESCCs is inversely correlated with clinical metastasis status, and migfilin inhibits ESCC cell invasion at least in part through promoting degradation of β-catenin. Mol Cancer Res; 10(3); 273–81. ©2012 AACR.
Increased PARP-1 Association with DNA in Alkylation Damaged, PARP-Inhibited Mouse Fibroblasts
Authors: Kedar Padmini S. , Stefanick Donna F. , Horton Julie K. , Wilson Samuel H. 
Published: January 2012

Abstract
Treatment of base excision repair–proficient mouse fibroblasts with the DNA alkylating agent methyl methanesulfonate (MMS) and a small molecule inhibitor of PARP-1 results in a striking cell killing phenotype, as previously reported. Earlier studies showed that the mechanism of cell death is apoptosis and requires DNA replication, expression of PARP-1, and an intact S-phase checkpoint cell signaling system. It is proposed that activity-inhibited PARP-1 becomes immobilized at DNA repair intermediates, and that this blocks DNA repair and interferes with DNA replication, eventually promoting an S-phase checkpoint and G2-M block. Here we report studies designed to evaluate the prediction that inhibited PARP-1 remains DNA associated in cells undergoing repair of alkylation-induced damage. Using chromatin immunoprecipitation with anti–PARP-1 antibody and qPCR for DNA quantification, a higher level of DNA was found associated with PARP-1 in cells treated with MMS plus PARP inhibitor than in cells without inhibitor treatment. These results have implications for explaining the extreme hypersensitivity phenotype after combination treatment with MMS and a PARP inhibitor. Mol Cancer Res; 10(3); 360–8. ©2012 AACR.
Effect of 2-Month Controlled Green Tea Intervention on Lipoprotein Cholesterol, Glucose, and Hormone Levels in Healthy Postmenopausal Women
Authors: Wu Anna H. , Spicer Darcy , Stanczyk Frank Z. , Tseng Chiu-Chen , Yang Chung S. , Pike Malcolm C. 
Published: January 2012

Abstract
There have been no controlled intervention studies to investigate the effects of green tea on circulating hormone levels, an established breast cancer risk factor. We conducted a double-blind, randomized, placebo-controlled intervention study to investigate the effect of the main green tea catechin, epigallocatechin gallate (EGCG), taken in a green tea extract, polyphenon E (PPE). Postmenopausal women (n = 103) were randomized into three arms: placebo, 400-mg EGCG as PPE, or 800-mg EGCG as PPE as capsules per day for 2 months. Urinary tea catechin and serum estrogen, androgen, lipid, glucose-related markers, adiponectin, and growth factor levels were measured at baseline and at the end of months 1 and 2 of intervention. On the basis of urinary tea catechin concentrations, compliance was excellent. Supplementation with PPE did not produce consistent patterns of changes in estradiol (E2), estrone (E1), or testosterone (T) levels. Low-density lipoprotein (LDL)-cholesterol decreased significantly in both PPE groups but was unchanged in the placebo group; the change in LDL-cholesterol differed between the placebo and PPE groups (P = 0.02). Glucose and insulin levels decreased nonsignificantly in the PPE groups but increased in the placebo group; statistically significant differences in changes in glucose (P = 0.008) and insulin (P = 0.01) were found. In summary, green tea (400- and 800-mg EGCG as PPE; ∼5–10 cups) supplementation for 2 months had suggestive beneficial effects on LDL-cholesterol concentrations and glucose-related markers. Cancer Prev Res; 5(3); 393–402. ©2012 AACR.
Effects of Energy Restriction and Wheel Running on Mammary Carcinogenesis and Host Systemic Factors in a Rat Model
Authors: Zhu Zongjian , Jiang Weiqin , Zacher Jarrod H. , Neil Elizabeth S. , McGinley John N. , Thompson Henry J. 
Published: January 2012

Abstract
Limiting energy availability via diet or physical activity has health benefits; however, it is not known whether these interventions have similar effects on the development of cancer. Two questions were addressed as follows: (i) Does limiting energy availability by increasing physical activity have the same effect on mammary carcinogenesis as limiting caloric intake? and (ii) Are host systemic factors, implicated as risk biomarkers for breast cancer, similarly affected by these interventions? Female Sprague Dawley rats were injected with 50-mg 1-methyl-1-nitrosourea per kg body weight at 21 days of age and randomized to one of five groups (30 rats per group) as follows: (i) sham running wheel control; (ii) restricted fed to 85% of the sham control; (iii and iv) voluntary running in a motorized activity wheel (37 m/min) to a maximum of 3,500 m/d or 1,750 m/d; and (v) sedentary ad libitum fed control with no access to a running wheel. The three energetics interventions inhibited the carcinogenic response, reducing cancer incidence (P = 0.01), cancer multiplicity (P &lt; 0.001), and cancer burden (P &lt; 0.001) whereas prolonging cancer latency (P = 0.004) although differences among energetics interventions were not significant. Of the plasma biomarkers associated with the development of cancer, the energetics interventions reduced bioavailable insulin-like growth factor-1 (IGF-1), insulin, interleukin-6, serum amyloid protein, TNF-α, and leptin and increased IGF-binding protein 3 (IGFBP-3) and adiponectin. Plasma-fasting glucose, C-reactive protein, estradiol, and progesterone were unaffected. The plasma biomarkers of greatest value in predicting the carcinogenic response were adiponectin &gt; IGF-1/IGFBP-3 &gt; IGFBP-3 &gt; leptin &gt; IGF-1. Cancer Prev Res; 5(3); 414–22. ©2012 AACR.
Risk Factors for Malignant Melanoma in White and Non-White/Non–African American Populations: The Multiethnic Cohort
Authors: Park Sungshim Lani , Le Marchand Loïc , Wilkens Lynne R. , Kolonel Laurence N. , Henderson Brian E. , Zhang Zuo-Feng , Setiawan Veronica Wendy 
Published: January 2012

AbstractIt is unknown whether the established risk factors for malignant melanoma in whites influence malignant melanoma risk in non-whites. We examined the risk factors for melanoma among 39,325 whites and 101,229 non-whites/multiracials [Japanese American (47.5%), Latino American (34.8%), Native Hawaiian (2.1%), and multiracial (15.6%), excluding African Americans] in the Multiethnic Cohort study. With an average follow-up of 12.7 years, 581 invasive malignant melanoma (IMM) and 412 melanoma in situ (MIS) cases were identified, of which 107 IMM and 74 MIS were among non-whites/multiracials. The relative risks (RR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards models using days from cohort entry as the underlying time variable. Among non-white/multiracial males, location of IMM tumors differed from those of white males (P &lt; 0.001); and non-white/multiracial females were more likely to be diagnosed with later stage of disease (P &lt; 0.001). After adjusting for potential confounders, age at cohort entry, male sex, higher education, and sunburn susceptibility phenotypes were associated with an increased risk of IMM in non-whites/multiracials (P &lt; 0.05). The risk estimates for age at cohort entry and lighter hair and eye color were greater in non-whites/multiracials than in whites (Pheterogeneity = 0.062, 0.016, and 0.005, respectively). For MIS risk, RRs between whites and non-whites/multiracials also differed for study location and education (Pheterogeneity ≤ 0.015). In conclusion, similar to whites, age at cohort entry, male sex, and susceptibility to sunburn phenotypes may be predictive of malignant melanoma risk in non-white populations excluding African Americans. Cancer Prev Res; 5(3); 423–34. ©2012 AACR.
Uterine Serous Carcinoma: Increased Familial Risk for Lynch-Associated Malignancies
Authors: Dewdney Summer B. , Kizer Nora T. , Andaya Abegail A. , Babb Sheri A. , Luo Jingqin , Mutch David G. , Schmidt Amy P. , Brinton Louise A. , Broaddus Russell R. , Ramirez Nilsa C. , Huettner Phyllis C. , McMeekin Donald Scott , Darcy Kathleen , Ali Shamshad , Judson Patricia L. , Mannel Robert S. , Lele Shashikant B. , O'Malley David M. , Goodfellow Paul J. 
Published: January 2012

Abstract
Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for patients with serous uterine carcinoma, focusing on Lynch syndrome malignancies. Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair (MMR) abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second-stage analysis was undertaken using data from Gynecologic Oncology Group (GOG)-210. Incidence data for cancers reported in relatives of 348 patients with serous and mixed epithelial and 624 patients with endometrioid carcinoma were compared. Nineteen of 29 (65.5%) patients in the single-institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly overrepresented and a high number of probands (6 of 29, 20.7%) reported pancreatic cancers. None of the probands' tumors had DNA MMR abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case–control study. Pancreatic cancers were, however, significantly more common in relatives of patients with serous cancer [OR, 2.39; 95% confidence interval (CI), 1.06–5.38]. We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of patients with serous cancer in a single-institution study. Follow-up studies suggest that only pancreatic cancers are overrepresented in relatives. DNA MMR defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers. Cancer Prev Res; 5(3); 435–43. ©2012 AACR.
Altered Systemic Hemodynamic and Baroreflex Response to Angiotensin II in Postural Tachycardia Syndrome
Authors: Mustafa Hossam I. , Raj Satish R. , Diedrich André , Black Bonnie K. , Paranjape Sachin Y. , Dupont William D. , Williams Gordon H. , Biaggioni Italo , Robertson David 
Published: January 2012

Background—
Postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia and significant functional disability. We have previously found that patients with POTS have increases in plasma angiotensin II (Ang II) that are twice as high as healthy subjects despite normal blood pressures (BPs). In this study, we assess systemic and renal hemodynamic and functional responses to Ang II infusion in patients with POTS compared with healthy controls.

Methods and Results—

Following a 3-day sodium-controlled diet, we infused Ang II (3 ng/kg per minute) for 1 hour in patients with POTS (n=15) and healthy controls (n=13) in the supine position. All study subjects were women with normal BP. Ages were similar for patients with POTS and controls (mean±SEM, 30±2 versus 26±1 years;
P
=0.11). We measured the changes from baseline mean arterial pressure, renal plasma flow, plasma renin activity, aldosterone, urine sodium, and baroreflex sensitivity in both groups. In response to Ang II infusion, patients with POTS had a blunted increase compared with controls in mean arterial pressure (10±1 versus 14±1 mm Hg,
P
=0.01) and diastolic BP (9±1 versus 13±1 mm Hg,
P
=0.01) but not systolic BP (13±2 versus 15±2 mm Hg,
P
=0.40). Renal plasma flow decreased similarly with Ang II infusion in patients with POTS versus controls (−166±20 versus −181±17 mL/min per 1.73 kg/m
2
,
P
=0.58). Postinfusion, the decrease in plasma renin activity (−0.9±0.2 versus −0.6±0.2 ng/mL per hour,
P
=0.43) and the increase in aldosterone (17±1 versus 15±2 pg/mL,
P
=0.34) were similar in both groups. The decrease in urine sodium excretion was similar in patients with POTS and controls (−49±12 versus −60±16 mEq/g creatinine,
P
=0.55). The spontaneous baroreflex sensitivity at baseline was significantly lower in patients with POTS compared with controls (10.1±1.2 versus 16.8±1.5 ms/mm Hg,
P
=0.003), and it was further reduced with Ang II infusion.

Conclusions—
Patients with POTS have blunted vasopressor response to Ang II and impaired baroreflex function. This impaired vasoconstrictive response might be exaggerated with upright posture and may contribute to the subsequent orthostatic tachycardia that is the hallmark of this disorder.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00962949.