Clinical performance of a new silicone hydrogel contact lens over 6 months of extended wear

Purpose: Silicone hydrogel contact lenses (CLs) are becoming increasingly popular for daily wear (DW), extended wear (EW) and continuous wear (CW), due to their higher oxygen transmissibility compared to hydrogel CLs. The aim of this study was to investigate the clinical and subjective performance of asmofilcon A (Menicon Co., Ltd), a new surface treated silicone hydrogel CL, during 6-night EW over 6 months (M). Methods: A prospective, randomised, single-masked, monadic study was conducted. N=60 experienced DW soft CL wearers were randomly assigned to wear either asmofilcon A (test: Dk=129, water content (WC)=40%, Nanogloss surface treatment) or senofilcon A (control: Dk=103, WC=38%, PVP internal wetting agent, Vistakon, Johnson & Johnson Vision Care) CLs bilaterally for 6 M on an EW basis. A PHMB-preserved solution (Menicon Co., Ltd) was dispensed for CL care. Evaluations were conducted at CL delivery and after 1 week (W), 4 W, 3 M and 6 M of EW. At each visit, a range of objective and subjective clinical performance measures were assessed. Results: N=50 subjects (83%) successfully completed the study, with the majority of discontinuations due to loss to follow-up (n=3) or moving away/travel (n=5). N=2 subjects experienced adverse events; n=1 unilateral red eye with asmofilcon A and n=1 asymptomatic infiltrate with senofilcon A. There were no significant differences in high or low contrast distance visual acuity (HCDVA or LCDVA) between asmofilcon A and senofilcon A; however, LCDVA decreased significantly over time with both CL types (p<0.05). The two CL types did not vary significantly with respect to any of the objective and subjective measures assessed (p>0.05); CL fitting characteristics and CL surface measurements were very similar and mean bulbar and limbal redness measures were always less than grade 1.0. Superior palpebral conjunctival injection showed a statistically, but not clinically, significant increase over time with both CL types (p<0.05). Corneal staining did not vary significantly between asmofilcon A and senofilcon A (p>0.05), with low median gradings of less than 0.5 observed for all areas assessed. There were no solution-related staining reactions observed with either CL type. The asmofilcon A and senofilcon A CLs were both rated highly with respect to overall comfort, with medians of 14 or 15 hours of comfortable lens wearing time per day reported at each of the study visits (p>0.05). Conclusions: Over 6 months of EW, the asmofilcon A and senofilcon A CLs performed in a similar manner with respect to visual acuity, ocular health and CL performance measures. Some changes over time were observed with both CL types, including reduced LCDVA and increased superior palpebral injection, which warrant further investigation in longer-term EW studies. Asmofilcon A appeared to be equivalent in performance to senofilcon A.

FGFR2 point mutations in 466 Endometrioid Endometrial Tumors : relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations and Clinicopathological features

Mutations in multiple oncogenes including KRAS, CTNNB1, PIK3CA and FGFR2 have been identified in endometrial cancer. The aim of this study was to provide insight into the clinicopathological features associated with patterns of mutation in these genes, a necessary step in planning targeted therapies for endometrial cancer. 466 endometrioid endometrial tumors were tested for mutations in FGFR2, KRAS, CTNNB1, and PIK3CA. The relationships between mutation status, tumor microsatellite instability (MSI) and clinicopathological features including overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier survival analysis and Cox proportional hazard models. Mutations were identified in FGFR2 (48/466); KRAS (87/464); CTNNB1 (88/454) and PIK3CA (104/464). KRAS and FGFR2 mutations were significantly more common, and CTNNB1 mutations less common, in MSI positive tumors. KRAS and FGFR2 occurred in a near mutually exclusive pattern (p = 0.05) and, surprisingly, mutations in KRAS and CTNNB1 also occurred in a near mutually exclusive pattern (p = 0.0002). Multivariate analysis revealed that mutation in KRAS and FGFR2 showed a trend (p = 0.06) towards longer and shorter DFS, respectively. In the 386 patients with early stage disease (stage I and II), FGFR2 mutation was significantly associated with shorter DFS (HR = 3.24; 95% confidence interval, CI, 1.35-7.77; p = 0.008) and OS (HR = 2.00; 95% CI 1.09-3.65; p = 0.025) and KRAS was associated with longer DFS (HR = 0.23; 95% CI 0.05-0.97; p = 0.045). In conclusion, although KRAS and FGFR2 mutations share similar activation of the MAPK pathway, our data suggest very different roles in tumor biology. This has implications for the implementation of anti-FGFR or anti-MEK biologic therapies.

Tooth fracture risk analysis based on a new finite element dental structure models using micro-CT data

The finite element (FE) analysis is an effective method to study the strength and predict the fracture risk of endodontically-treated teeth. This paper presents a rapid method developed to generate a comprehensive tooth FE model using data retrieved from micro-computed tomography (μCT). With this method, the inhomogeneity of material properties of teeth was included into the model without dividing the tooth model into different regions. The material properties of the tooth were assumed to be related to the mineral density. The fracture risk at different tooth portions was assessed for root canal treatments. The micro-CT images of a tooth were processed by a Matlab software programme and the CT numbers were retrieved. The tooth contours were obtained with thresholding segmentation using Amira. The inner and outer surfaces of the tooth were imported into Solidworks and a three-dimensional (3D) tooth model was constructed. An assembly of the tooth model with the periodontal ligament (PDL) layer and surrounding bone was imported into ABAQUS. The material properties of the tooth were calculated from the retrieved CT numbers via ABAQUS user's subroutines. Three root canal geometries (original and two enlargements) were investigated. The proposed method in this study can generate detailed 3D finite element models of a tooth with different root canal enlargements and filling materials, and would be very useful for the assessment of the fracture risk at different tooth portions after root canal treatments.

Canadian Crime Control in the New Millennium: The Influence of Neo-conservative U.S. Policies and Practices

An important issue facing Canadians today is crime control and prevention. Research done in the late 1980s and early 1990s by three sociologists shows that Canadian federal criminal justice policies and practices adopted by the Mulroney government from 1984 to 1990 were inconsistent with US ‘law and order’ models in place at that time. However, since the mid‐1990s, Canadian federal and provincial governments have mimicked some US authoritarian and gender‐blind means of curbing crime. The main objective of this paper is to provide some key examples of criminal justice policy transfer from the USA in Canada. At first glance, Canada may appear to be a ‘kinder, gentler nation,’ but not to the extent assumed by many, if not most, outside observers.

Governing Prostitution: New Formations, Old Agendas

Recent governmentality literature distinguishes between government from above and government “from below” in an attempt to avoid “top-down” analyzes of state-centered government and to acknowledge the multiple and diverse ways in which the governance is achieved. By analyzing key shifts and changes in the regulation of prostitution in the UK in the last three decades, it is possible to complicate the distinction between the two modes of government. Whilst some writers highlight the ways in which government from above and below become increasingly blurred, this article argues that although the agendas and modes of government from above and below are difficult to disentangle, the effects on sex workers are not. Regulation remains rooted within coercive and punitive state-centered criminal justice responses, even though organizations “from below” may well be the very organizations tasked by the state with carried out those responses.