Supervised group Lasso with applications to microarray data analysis

BACKGROUND: A tremendous amount of efforts have been devoted to identifying genes for diagnosis and prognosis of diseases using microarray gene expression data. It has been demonstrated that gene expression data have cluster structure, where the clusters consist of co-regulated genes which tend to have coordinated functions. However, most available statistical methods for gene selection do not take into consideration the cluster structure. RESULTS: We propose a supervised group Lasso approach that takes into account the cluster structure in gene expression data for gene selection and predictive model building. For gene expression data without biological cluster information, we first divide genes into clusters using the K-means approach and determine the optimal number of clusters using the Gap method. The supervised group Lasso consists of two steps. In the first step, we identify important genes within each cluster using the Lasso method. In the second step, we select important clusters using the group Lasso. Tuning parameters are determined using V-fold cross validation at both steps to allow for further flexibility. Prediction performance is evaluated using leave-one-out cross validation. We apply the proposed method to disease classification and survival analysis with microarray data. CONCLUSION: We analyze four microarray data sets using the proposed approach: two cancer data sets with binary cancer occurrence as outcomes and two lymphoma data sets with survival outcomes. The results show that the proposed approach is capable of identifying a small number of influential gene clusters and important genes within those clusters, and has better prediction performance than existing methods

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Dellen formation as a complication of subconjunctival silicone oil following microincision vitrectomy

Mohamed M Mahgoub,1,2 Maged M Roshdy,1,2 Sherine S Wahba1,2 1Ophthalmology Department, Ain Shams University, 2Ophthalmology Department, Al Watany Eye Hospital, Cairo, Egypt Purpose: To study the subconjunctival silicone oil (SCSO) parameters associated with dellen formation following microincision vitrectomy (MIV).Patients and methods: This was a case&ndash;control study of 20 eyes with SCSO following MIV. Ten of them suffered postoperative dellen formation. Dellen occurrence, their sizes, number of loci, and distance between SCSO and the limbus were recorded. The outcome after silicone-oil removal was evaluated.Results: The SCSO was at 3.1&plusmn;1.2 mm from the limbus. All cases with dellen had SCSO within 2 mm of the limbus (P&lt;0.001). No other factors were found to be associated with dellen formation (age, P=0.414; sex, P=0.656; laterality, P=1; indication for pars plana vitrectomy, P=0.655; instrument gauge, P=0.211; circumference involved by SCSO, P=0.252). All the dellen healed after surgical evacuation of SCSO (P&lt;0.001), leaving scars.Conclusion: Dellen can be associated with MIV secondary to SCSO near the limbus. Resolution with scarring occurred following SCSO evacuation. Therefore, SCSO should be evacuated as early as possible to avoid long-term peripheral corneal morbidity. Keywords: silicone oil-removal, subconjunctival silicone oil, dellen, vitrectom

Microcapillary sign of flap alignment in femtosecond laser-assisted in situ keratomileusis

Fathy Fawzy,1,2 Sherine S Wahba,1,3 Nader Fawzy1,4 1Al Watany Eye Hospital, 2Ophthalmology Department, Military Medical Academy, 3Ophthalmology Department, Ain Shams University, Cairo, Egypt; 4Sehkraft Augenzentrum, Cologne, Germany Abstract: We present an observational sign that ensures perfect alignment during femtosecond laser-assisted in situ keratomileusis (FS LASIK). Alignment is assured when a microsponge is used to dry the flap and the area of dryness exceeds the area of direct touch of the microsponge. The area might even reach the whole circumference of the flap at the first touch. This sign of alignment can be explained by microcapillary action. This sign was not elicited in flaps created by a microkeratome. Keywords: capillarity, femtosecond LASIK flap, corneal flap alignmen

Visual performance of the Tecnis one-piece lens ZCB00

Sherein S Wahba, Riad F Riad, Fathy F Morkos, Abdallah K Hassouna, Maged M RoshdyNational Eye Hospital and Ain Shams University, Cairo, EgyptSynopsis: The aspheric, one-piece design of the Tecnis&amp;reg; ZCB00 intraocular lens provided higher mesopic contrast sensitivity and relatively constant refraction at different pupil sizes compared to the Sensar&amp;reg; AR40e.Purpose: Comparing the impact on functional vision of the aspheric Tecnis&amp;reg; ZCB00 one-piece lens compared to the spherical Sensar&amp;reg; AR40e three-piece lens.Setting: National Eye Hospital, Cairo, Egypt.Methods: In this prospective study, we implanted 32 Tecnis ZCB00 (Abbott Medical Optics, Santa Ana, CA) and 30 Sensar AR40e (Pharamacia and Upjohn LLC, North Peapack, NJ) lenses. Twenty-three patients in the ZCB00 group and 13 patients in the AR40e group provided reliable, reproducible data, and were therefore included in the statistical analysis. After 8 weeks, we measured photopic contrast sensitivity (PCS) at 85 cd/m&amp;sup2; and mesopic contrast sensitivity (MCS) at 5 cd/m&amp;sup2;. Uncorrected and best-corrected visual acuity were measured. Myopic shift was analyzed by comparing the manifest refraction spherical equivalent at 3 days and 8 weeks after surgery in the normal and dilated pupil.Results: The Tecnis ZCB00 group showed significantly better MCS than the Sensar AR40e group at a spatial frequency of six cycles per degree (cpd) (P = 0.037), but not at 3, 12, or 18 cpd (P = 0.299, P = 0.226, and P = 0.396, respectively). There were no significant differences between groups in corrected distance visual acuity (P = 0.175) or PCS at 3, 6, 12, or 18 cpd spatial frequencies (P = 0.440, P = 0.176, P = 0.365, and P = 0.251, respectively). The ZCB00 group showed less myopic shift in normal and dilated pupils between 3 days and 8 weeks after surgery compared to the AR40e group, but this difference was not significant.Conclusion: The Tecnis one-piece ZCB00 provided higher MCS at moderate spatial frequency than the three-piece Sensar AR40e, and was associated with relatively constant refraction at different pupil sizes.Keywords: Tecnis ZCB00, Sensar AR40e, contrast sensitivity, myopic shif