Among various diagnostic techniques, cervical cytology examination using Pap smear is the mainstay screening technique at present to detect early cervical cytology changes. Apart from detecting early dysplastic changes it also aids in detecting the inflammatory changes and it has been found that chronic persistence of this inflammatory change is a possible indicator of increased cellular turnover and possibly high risk for malignant changes at an earlier age (5) . Hence the role of pap smear in detecting cervical cytology abnormalities is undeniable and also a cost effective technique in low resource countries where expensive screening techniques like HPV DNA testing are practically impossible. A sexually active women is encouraged to undergo this test at a regular basis. Though many studies are available on the same, very limited data regarding cervical cytological in high risk females is available.
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Methods: Information on demographics, medical conditions and treatment, smoking behavior, dietary behavior, and exercise patterns were collected. Physical measurements were also taken. The 10-year risk was calculated using the Framingham model, SCORE (Systematic COronary Risk Evaluation) risk chart for low risk and high risk regions, the general CVD, and simplified general CVD risk score models in 4,354 females aged 20–69 years with no heart disease, diabetes, or stroke at baseline from the third Australian Risk Factor Prevalence Study. Country of birth was used as a surrogate for ethnicity. Nonparametric statistics were used to compare risk levels between ethnic groups.
In men, high LDL levels were found to have a strong prognostic impact where as in women the role of low HDL is more important. Independent of the serum LDL and TG levels, women with low HDL levels had a higher risk for CVD. The risk of CAD decreases by 3% for every 1 mg/dl increase in HDL in women but only 2% in men. In this study, 20 (40%) out of the 50 patients had an LDL above 160, while favourable lipid profile was seen only in 19 patients. 50% of the study group had HDL values below 30.
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Focal adhesion plaques are discrete areas on the cell mem- brane where the cells contact the underlying substratum or each other (36, 75). They are also the sites where multiple protein complexes involved in signaling assemble (15). Focal adhesions appear to represent transmembrane connections be- tween the extracellular matrix and the cytoskeleton. Thus, it is not surprising that disrupted focal adhesions are frequently associated with the transformed phenotype (14). The E6 pro- teins from bovine papillomavirus and high-risk HPV interact with paxillin, another focal adhesion protein (13, 70, 71). This interaction may in part account for the disruption of actin fiber organization when bovine papillomavirus type 1 E6 is overex- pressed in cells (70).
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age do better than older children coincides with the devel- opment of the immune system. At a younger age the immune system depends primarily on the innate immunity whereas in older children the adaptive system has been well developed. In fact, several groups reported that cyto- kines/chemokines such as IL-1b, CXCL12, CXCR4 and IFN-g which are involved in the innate immune responses play a critical role in neuronal differentiation associated with low-risk manifestation of the disease [5-9]. In vitro studies also underscored the innate immune responses by showing that human neuroblastoma cell lines were more susceptible to lysis by NK cells (innate immunity) than by the CD8+ T cells (adaptive immunity) . Moreover, retinoic acid, currently being used in the treatment of minimal residual disease in HR neuroblastoma, was shown to promote innate immune responses and to some extent Th-1 responses leading to the inhibition of neuroblastoma [11,12]. However, it remains elusive whether Th-1 cells may be suppressed by an increased myeloid-derived sup- pressor cells (MDSC) or Tregs in LR patients. These find- ings support our hypothesis that a predominant innate immune response may be associated with LR neuroblas- toma and a favorable outcome.
categories to form an aggregate Risk Total score. The SAVRY includes additional features that may be useful for research and clinical application, such as protective factors, critical items, and an evaluator risk rating which provides a subjective judgment of overall risk, taking all these factors into account. However, the present study focuses only on scores obtained from summing the ratings of the 24 risk factors. In addition to the SAVRY Total score, the risk factors can be used individually to describe certain patterns of risk. For example, the Individual Risk Factors subscale contains items pertaining to attention deficits, anger control, impulsivity, and CU traits. As indicated by the previously reviewed research, these characteristics appear to be important for defining different developmental pathways to early-onset and serious offending.
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The current meta-analysis aimed to determine all observational studies on the relationship between menopause, and age at menarche with breast cancer. All observational studies including cohort, case-control and cross-sectional studies on the relationship between these risk factors and breast cancer in Iran, published in Persian or English (from 2004 to 2014) were searched. To identify cancer synonyms, the medical subject headings (MeSH) was searched using the keywords of cancer, tumor, neoplasm, neoplasia, carcinoma, malignancy, malignant and benign. A combination of the above-mentioned words were used with OR and then the words Iran and breast were added to the search field using the operator AND.
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Breast cancer is clinically heteregeneous due to mo- lecular differences between histologically similar tumors. Luminal, Her2 enriched, basal-like (Triple-negative) sub- groups were identified and were shown to have different long-term survivals [10,11,60,61]. There were few re- ports about the correlation between lncRNAs and mo- lecular subtype of breast cancer. A newly identified lncRNA, LOC554202, has been found to express abun- dantly in the non-invasive breast cancer cell lines like lu- minal subtype, but the expression is lost in more aggressive triple-negative breast cancer cell lines of basal subtype . It was therefore of interest to determine if our four-lncRNA signature was associated with this strong prognostic factor. As the data on molecular sub- type was only available in GSE21653, we performed the analysis of multivariable Cox regression including risk score and subtype in this testing group. Because of the small sample size in some subgroups, we did not observe significant difference in either univariable or multivari- able Cox regression analysis.
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Results: A total of 404 (63.8%) malignant breast biopsies and 229 (36.2%) benign breast biop- sies were analyzed. Women ≥40 years old (aOR: 6.202, CI 3.497–11.001, P=0.001), hormone- replacement therapy (aOR 24.365, 95% CI 8.606–68.987, P=0.001), postmenopausal (aOR 3.058, 95% CI 1.861–5.024, P=0.001), and with a family history of breast cancer (aOR 2.307, 95% CI 1.142–4.658, P=0.020) were independently associated with an increased risk of breast cancer. This model showed an acceptable fit and had area under the receiver-operating characteristic curve of 0.877 (95% CI 0.851–0.903), with optimism-corrected area under the curve of 0.865. Conclusion: The prediction model developed in this study has a high ability in predicting increased breast cancer risk in our facility. Combining information on age, use of hormone therapy, postmenopausal status, and family history of breast cancer improved the degree of discriminatory accuracy of breast cancer prediction. Our risk model may assist in initiating population-screening programs and prompt clinical decision making to manage cases and prevent unfavorable outcomes.
any other factor to the final tally of 82% eligibility under the Australian guidelines. Inclusion of this weak risk factor is likely to cause substantial misallocation of patients who are not at high risk, but who may suffer hemorrhagic complica- tions of prophylaxis, to the high-risk group. Giving medical thromboprophylaxis on the grounds of age alone is hazardous and unnecessary. It has been shown 13 that when risk factors
In order to further prove the accuracy of the model and the classi ﬁ cation effect of the risk score, we further applied the K-M analysis to display the survival curve of the high- risk group and the low-risk group in the validation dataset and the whole dataset. We found the survival of the two groups is signi ﬁ cantly different in each dataset ( p<0.05) (Figures 3A and 4A). This result further demonstrated the effective performance of the model for classifying patients into two groups with different prognoses. Meanwhile, we showed the follow-up time of the validation dataset and the whole dataset by ascending ranking with risk score (Figures 3B and 4B). Consistently, the seven-gene expres- sion heatmap sorted by risk score was also shown in the ﬁ gures (Figures 3C and D and 4C and D).
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The American Society of Clincal Oncology (ASCO) recommends that CEA is performed every three months for the first three years in patients with stage II or III disease if the patient is a candidate for surgery or systemic therapy, and that raised CEA levels (> 5 µg/L, confirmed by a repeat test) warrant further evaluation for metastatic disease (Locker 2006). Unlike ASCO, ESMO does not specify a threshold nor limit testing to specific tumour stages. The European Group on Tumour Markers (EGTM) specify CEA mea- surement at baseline and then every two to three months for three years, then six-monthly for five years in patients with stage II to III disease who would tolerate further surgery or systemic therapy. EGTM recommend that any increase in CEA (confirmed by a repeat test) should trigger further investigations (Duffy 2013b). The National Institute for Health and Clinical Excellence (NICE) recommended follow-up from four to six weeks following cura- tive treatment, for all patients who could tolerate and accept the balance of risk and benefits of further treatment, including CEA measurement at least every six months in the first three years, two CT scans of the chest and abdomen in the first three years, and colonoscopy at one year and five years (NICE 2011).
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In this study, we comprehensively analyzed autophagy- related genes in GBM. First, we collected autophagy-related gene data and identi ﬁ ed 14 genes related to patient prog- nosis. These 14 genes could stratify patients into two groups with signi ﬁ cant molecular and prognostic differences, sug- gesting a correlation with glioblastoma malignancy. Hence, we constructed 14 gene autophagy-related signature with good prognostic value and which can serve as an indepen- dent prognostic indicator in GBM. Moreover, functional analysis revealed the elevation of immune and in ﬂ ammatory responses in GBM samples classi ﬁ ed as high-risk using our 14 gene signature, which was directly related to tumor malignancy and poor prognosis. In conclusion, our study con ﬁ rms the correlation between autophagy status and glio- blastoma malignancy and prognosis, providing new insights relevant to individualized treatment.
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and at least one psychosocial risk factor was identified in 90%. The SOABR is not yet validated, but like the ORT includes questions about patients’ peer group, excessive impulsivity, and pathologic gambling. The authors note that as pediatric cancer survival rates continue to rise, survivors may face chronic cancer- or treatment-related pain that requires opioid therapy, and AYAs with aberrant behavior may be more susceptible to addiction and drug abuse later in life.
Fondaparinux also inhibits clot-bound Factor Xa, but not Factor Xa within the prothrombinase complex. When released from ATIII, fondaparinux can exert its action again; each molecule of fondaparinux mediates the inhibition of several molecules of Factor Xa. The highest therapeutic doses of fondaparinux (which result in fondaparinux plasma concentrations up to 1.2 μm at 10 mg once daily) do not saturate plasma ATIII, the plasma concentration of which is 2–3 μm. By increasing the ability of ATIII to inhibit Factor Xa, a factor situated at the junction of the intrinsic and extrinsic pathways of the coagulation cascade, fondaparinux efficiently inhibits thrombin generation. Its synthetic nature eliminates the theoretical risk of pathogen contamination and assures batch-to-batch consistency. 39
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this four-gene classifier panel in the current study due to limitations of DNA samples availability. Similar to our findings in the AS PCa patient cohort, we found that methylation frequencies of APC and GSTP1 in urinary sediment were lower compared to those reported in tissue samples. Lastly, it is difficult to assess the additive value of ProCUrE to PSA for identifying patients based on the CAPRA score and D’ Amico criteria, since both nomograms are calculated using PSA leading to strong association with PSA with these risk groups. Both CAPRA and D’Amico criteria are limited in that they require prostate biopsy to calculate risk. ProCUrE is advantageous in this regard since risk assessment can be performed prior to biopsy.
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Possible steps used to initiate and plan a quality risk management process might include: (a) Define the problem and/or risk question, including pertinent assumptions identifying the potential for risk; (b) Assemble background information and/ or data on the potential hazard, harm or human health impact relevant to the risk assessment; (c) Identify a leader and necessary resources; (d) Specify a timeline, deliverables and appropriate level of decision making for the risk management process 2,
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A bank’s first defense against excessive credit risk is the initial credit-granting process − sound underwriting standards, an efficient, balanced approval process, and a competent lending staff. Because a bank cannot easily overcome borrowers with questionable capacity or character, these factors exert a strong influence on credit quality. Borrowers whose financial performance is poor or marginal, or whose repayment ability is dependent upon unproven projections can quickly become impaired by personal or external economic stress. Management of credit risk, however, must continue after a loan has been made, for sound initial credit decisions can be undermined by improper loan structuring or inadequate monitoring.
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The LXXLL and PDZ binding motifs contribute to HPV16 E6 activation of cap-dependent translation. To evaluate sequences in HPV16 E6 that contribute to enhancing cap-dependent trans- lation, we tested two HPV16 E6 mutants, Y54D and I128T, that disrupt the LXXLL binding motif and are therefore defective for E6AP binding (11) as well as an HPV16 E6 mutant with a trunca- tion of the PDZ binding domain (⌬PDZ) in bicistronic luciferase reporter assays in primary HFKs. Compared to wild-type HPV16 E6, the HPV16 E6 Y54D and I128T LXXLL binding motif-defec- tive mutants activated cap-dependent translation at a significantly reduced level (wild-type HPV16 E6, 1.80 ⫾ 0.08-fold, and HPV16 E6 Y54D, 1.26 ⫾ 0.23-fold, P ⫽ 0.125 relative to control and P ⫽ 0.0177 relative to HPV16 E6; HPV16 E6 I128T, 1.16 ⫾ 0.11-fold, P ⫽ 0.0873 relative to control and P ⫽ 0.0013 relative to HPV16 E6) (Fig. 2). The HPV16 E6 ⌬PDZ mutant was also significantly FIG 1 Mucosal but not cutaneous HPV E6 proteins increase cap-dependent translation. (A) U2OS cells were transiently cotransfected with the pFR_CrPV_xb bicistronic reporter construct and cytomegalovirus promoter-driven expression vectors for high-risk mucosal HPV E6 proteins (HPV16, HPV18), low-risk mucosal HPV E6 proteins (HPV6b, HPV11), cutaneous HPV E6 proteins (HPV5, HPV8), or empty vector (C) as a control. (B) Primary HFKs were transiently cotransfected with the pFR_CrPV_xb construct and human ␤ -actin promoter-driven E6 expression vectors. Cells were lysed, and Renilla and firefly luciferase activities were measured at 48 h posttransfection. Firefly and Renilla luciferase values were normalized to the values for control vector-transfected cells and are presented as the fold change of normalized firefly luciferase relative to normalized Renilla luciferase (FF/Ren). The bar graphs depict averages and standard deviations of four independent experiments for U2OS and five independent experiments for HFKs. *, statistical significance (P ⱕ 0.01 and P ⬍ 0.05 for U2OS and HFKs, respectively). (C) Immunoblot analysis of various HPV E6 proteins after transient transfection of U2OS cells with lentiviral expression plasmids. An actin blot is shown as a loading control.
In this paper, we study the safety level and system congestion in a risk-based inspection system with three types of security-check lanes, named as Green Lane, Normal Lane, and Selectee Lane (as shown in Figure 1). Based on the assessed threat values of incoming passengers and two risk thresholds managed by the security administrations, passengers can be classified into three risk classes: Trusted passengers at the low-risk class, Regular passengers at the medium-risk class, and Risky passengers at the high-risk class. The assessment of each passenger' risk level is identified by the government intelligence systems, which is based on the information and data collected by the government or the Customs. We assume each passenger is characterized by an assessed threat value Θ with the range 0 < Θ < 1. Based on two risk thresholds 0 < a(f) < a(s) < 1, incoming passengers are differentiated by their perceived risk levels (low-risk class, medium-risk class, and high-risk class), and then go to the corresponding inspection lanes (Green Lane, Normal Lane, and Selectee Lane) for security-check procedures. We assume the overall arrival rate of passengers to the security checkpoints is Λ. Given two risk thresholds a(f) and a(s), the average arrival rate to Green Lane can be determined as λ f , and