Loss of Individual MicroRNAs Causes Mutant Phenotypes in Sensitized Genetic Backgrounds in \u3cem\u3eC. elegans\u3c/em\u3e

MicroRNAs (miRNAs) are small, noncoding RNAs that regulate the translation and/or stability of their mRNA targets. Previous work showed that for most miRNA genes of C. elegans, single-gene knockouts did not result in detectable mutant phenotypes. This may be due, in part, to functional redundancy between miRNAs. However, in most cases, worms carrying deletions of all members of a miRNA family do not display strong mutant phenotypes. They may function together with unrelated miRNAs or with non-miRNA genes in regulatory networks, possibly to ensure the robustness of developmental mechanisms. To test this, we examined worms lacking individual miRNAs in genetically sensitized backgrounds. These include genetic backgrounds with reduced processing and activity of all miRNAs or with reduced activity of a wide array of regulatory pathways. With these two approaches, we identified mutant phenotypes for 25 out of 31 miRNAs included in this analysis. Our findings describe biological roles for individual miRNAs and suggest that the use of sensitized genetic backgrounds provides an efficient approach for miRNA functional analysis

L1 and HERV-W retrotransposons are hypomethylated in human ovarian carcinomas

Wide-spread hypomethylation of CpG dinucleotides is characteristic of many cancers. Retrotransposons have been identified as potential targets of hypomethylation during cellular transformation. We report the results of an preliminary examination of the methylation status of CpG dinucleotides associated with the L1 and HERV-W retrotransposons in benign and malignant human ovarian tumors. We find a reduction in the methylation of CpG dinucleotides within the promoter regions of these retroelements in malignant relative to non-malignant ovarian tissues. Consistent with these results, we find that relative L1 and HERV-W expression levels are elevated in representative samples of malignant vs. non-malignant ovarian tissues

A linear domain decomposition method for two-phase flow in porous media

This article is a follow up of our submitted paper [11] in which a decomposition of the Richards equation along two soil layers was discussed. A decomposed problem was formulated and a decoupling and linearisation technique was presented to solve the problem in each time step in a fixed point type iteration. This article extends these ideas to the case of two-phase in porous media and the convergence of the proposed domain decomposition method is rigorously shown.Comment: 8 page

Notes

Notes by Benedict R. Danko, Patrick F. Coughlin, William J. O\u27Connor, John E. Lindberg, Lawrence S. May, Jr., Arthur L. Beaudette, and Mark Harry Berens

Determining Success or Failure After Foot and Ankle Surgery Using Patient Acceptable Symptom State (PASS) and Patient Reported Outcome Information System (PROMIS)

Background: As the role of generic patient-reported outcomes (PROs) expands, important questions remain about their interpretation. In particular, how the Patient Reported Outcome Measurement Instrumentation System (PROMIS) t score values correlate with the patients’ perception of success or failure (S/F) of their surgery is unknown. The purposes of this study were to characterize the association of PROMIS t scores, the patients’ perception of their symptoms (patient acceptable symptom state [PASS]), and determination of S/F after surgery. Methods: This retrospective cohort study contacted patients after the 4 most common foot and ankle surgeries at a tertiary academic medical center (n = 88). Patient outcome as determined by phone interviews included PASS and patients’ judgment of whether their surgery was a S/F. Assessment also included PROMIS physical function (PF), pain interference (PI), and depression (D) scales. The association between S/F and PASS outcomes was evaluated by chi-square analysis. A 2-way analysis of variance (ANOVA) evaluated the ability of PROMIS to discriminate PASS and/or S/F outcomes. Receiver operator curve (ROC) analysis was used to evaluate the ability of pre- (n = 63) and postoperative (n = 88) PROMIS scores to predict patient outcomes (S/F and PASS). Finally, the proportion of individuals classified by the identified thresholds were evaluated using chi-square analysis. Results: There was a strong association between PASS and S/F after surgery (chi-square \u3c0.01). Two-way ANOVA demonstrated that PROMIS t scores discriminate whether patients experienced positive or negative outcome for PASS (P \u3c .001) and S/F (P \u3c .001). The ROC analysis showed significant accuracy (area under the curve \u3e 0.7) for postoperative but not preoperative PROMIS t scores in determining patient outcome for both PASS and S/F. The proportion of patients classified by applying the ROC analysis thresholds using PROMIS varied from 43.0% to 58.8 % for PASS and S/F. Conclusions: Patients who found their symptoms and activity at a satisfactory level (ie, PASS yes) also considered their surgery a success. However, patients who did not consider their symptoms and activity at a satisfactory level did not consistently consider their surgery a failure. PROMIS t scores for physical function and pain demonstrated the ability to discriminate and accurately predict patient outcome after foot and ankle surgery for 43.0% to 58.8% of participants. These data improve the clinical utility of PROMIS scales by suggesting thresholds for positive and negative patient outcomes independent of other factors. Level of Evidence: II, prospective comparative series

PROMIS Pain Interference Is Superior vs Numeric Pain Rating Scale for Pain Assessment in Foot and Ankle Patients

Background: The Numeric Pain Rating Scale (NPRS) is a popular method to assess pain. Recently, the Patient-Reported Outcomes Measurement Information System (PROMIS) has been suggested to be more accurate in measuring pain. This study aimed to compare NPRS and PROMIS Pain Interference (PI) scores in a population of foot and ankle patients to determine which method demonstrated a stronger correlation with preoperative and postoperative function, as measured by PROMIS Physical Function (PF). Methods: Prospective PROMIS PF and PI and NPRS data were obtained for 8 common elective foot and ankle surgical procedures. Data were collected preoperatively and postoperatively at a follow-up visit at least 6 months after surgery. Spearman correlation coefficients were calculated to determine the relationship among NPRS (0-10) and PROMIS domains (PI, PF) pre- and postoperatively. A total of 500 patients fit our inclusion criteria. Results: PROMIS PF demonstrated a stronger correlation to PROMIS PI in both the pre- and postoperative settings (preoperative: ρ = −0.66; postoperative: ρ = −0.69) compared with the NPRS (preoperative: ρ = −0.32; postoperative: ρ = −0.33). Similar results were found when data were grouped by Current Procedural Terminology (CPT) code. Conclusion: PROMIS PI was a superior tool to gauge a patient’s preoperative level of pain and functional ability. This information may assist surgeons and patients in setting postoperative functional expectations and pain management. Level of Evidence: Level II, prognosti

Is there a Difference in Outcomes between Patients who Received a Double or Triple Arthrodesis for Hindfoot Arthritis?

Introduction/Purpose: Triple arthrodesis has historically been considered the standard of treatment for arthritis of the hindfoot with or without deformity. The complications of this surgery including non-union, malunion, nerve injury, infection and wound healing problems can occur at any of the three joints. Double arthrodesis is capable of producing a similar reduction in degrees of motion and correction of foot deformity but may also cause less patient morbidity in regard to these complications due to one less joint being incorporated into the fusion procedure. What is unknown is the patient reported outcomes, specifically physical function (PF) and pain interference (PI) between these two procedures. The purpose of this study is to evaluate the clinical outcomes for hindfoot deformity using a triple compared to a double arthrodesis

Indirect learning: how emerging-market firms grow in developed markets

Some emerging-market firms have recently achieved substantial growth in developed markets despite having had little prior experience in these markets. What explains the performance of these firms? Building on the organizational learning literature, the authors argue that indirect learning (i.e., learning from the experience of others) plays a crucial role in explaining this phenomenon. Specifically, they propose that emerging-market firms that grow in developed markets overcome their lack of direct experience in such markets by learning indirectly through their leaders, competitors, and interfirm networks. The authors test their thesis by comparing the international growth in developed markets of a sample of emerging-market firms (116 Indian firms) with a sample of developed-market firms (160 U.K. firms). The results support the authors' thesis about the importance of indirect learning in explaining the international growth of emerging-market (relative to developed-market) firms in developed markets. The authors discuss the implications of these findings for policy makers in the areas of higher education, competition policy, and international trade as well as for managers in the areas of middle-management recruitment, competitor analysis and tracking, and managing interfirm networks