High-Risk Corneal Graft Rejection in the Setting of Previous Corneal Herpes Simplex Virus (HSV)-1 Infection

Acknowledgments The authors thank M. Robertson and R. Fordyce for technical support during the duration of the study. The work performed in Aberdeen was supported by grant from Action Medical Research UK (SP4328; London, England, UK), NHS Grampian Endowment grant (12/49; Aberdeen, Scotland, UK), and Saving Sight in Grampian (Charity No.SC002938; Aberdeen, Scotland, UK). The work performed in Pittsburgh was supported by a Fight for Sight Post-Doctoral Award (JEK; New York, NY, USA); unrestricted grants from the Western Pennsylvania Medical Eye Bank Foundation (Pittsburgh, PA, USA), Research to Prevent Blindness (New York, NY, USA), and the Eye and Ear Foundation of Pittsburgh (RLH; Pittsburgh, PA, USA); and National Institutes of Health Grants P30EY08098 (RLH; Bethesda, MD, USA) and EY10359 (RLH).Peer reviewedPublisher PD

Variability of extracorporeal cardiopulmonary resuscitation utilization for refractory adult out-of-hospital cardiac arrest: an international survey study.

Objective: A growing interest in extracorporeal cardiopulmonary resuscitation (ECPR) as a rescue strategy for refractory adult out-of-hospital cardiac arrest (OHCA) currently exists. This study aims to determine current standards of care and practice variation for ECPR patients in the USA and Korea. Methods: In December 2015, we surveyed centers from the Korean Hypothermia Network (KORHN) Investigators and the US National Post-Arrest Research Consortium (NPARC) on current targeted temperature management and ECPR practices. This project analyzes the subsection of questions addressing ECPR practices. We summarized survey. Results: Overall, 9 KORHN and 4 NPARC centers reported having ECPR programs and had complete survey data available. Two KORHN centers utilized extracorporeal membrane oxygenation only for postarrest circulatory support in patients with refractory shock and were excluded from further analysis. Centers with available ECPR generally saw a high volume of OHCA patients (10/11 centers care for \u3e75 OHCA a year). Location of, and providers trained for cannulation varied across centers. All centers in both countries (KORHN 7/7, NPARC 4/4) treated comatose ECPR patients with targeted temperature management. All NPARC centers and four of seven KORHN centers reported having a standardized hospital protocol for ECPR. Upper age cutoff for eligibility ranged from 60 to 75 years. No absolute contraindications were unanimous among centers. Conclusion: A wide variability in practice patterns exist between centers performing ECPR for refractory OHCA in the US and Korea. Standardized protocols and shared research databases might inform best practices, improve outcomes, and provide a foundation for prospective studies

Spatial Models to Account for Variation in Observer Effort in Bird Atlases

To assess the importance of variation in observer effort between and within bird atlas projects and demonstrate the use of relatively simple conditional autoregressive (CAR) models for analyzing grid-based atlas data with varying effort. Pennsylvania and West Virginia, United States of America. We used varying proportions of randomly selected training data to assess whether variations in observer effort can be accounted for using CAR models and whether such models would still be useful for atlases with incomplete data. We then evaluated whether the application of these models influenced our assessment of distribution change between two atlas projects separated by twenty years (Pennsylvania), and tested our modeling methodology on a state bird atlas with incomplete coverage (West Virginia). Conditional Autoregressive models which included observer effort and landscape covariates were able to make robust predictions of species distributions in cases of sparse data coverage. Further, we found that CAR models without landscape covariates performed favorably. These models also account for variation in observer effort between atlas projects and can have a profound effect on the overall assessment of distribution change. Accounting for variation in observer effort in atlas projects is critically important. CAR models provide a useful modeling framework for accounting for variation in observer effort in bird atlas data because they are relatively simple to apply, and quick to run

Sequential Wnt Agonist then Antagonist Treatment Accelerates Tissue Repair and Minimizes Fibrosis

Tissue fibrosis compromises organ function and occurs as a potential long-term outcome in response to acute tissue injuries. Currently, lack of mechanistic understanding prevents effective prevention and treatment of the progression from acute injury to fibrosis. Here, we combined quantitative experimental studies with a mouse kidney injury model and a computational approach to determine how the physiological consequences are determined by the severity of ischemia injury, and to identify how to manipulate Wnt signaling to accelerate repair of ischemic tissue damage while minimizing fibrosis. The study reveals that Wnt-mediated memory of prior injury contributes to fibrosis progression, and ischemic preconditioning reduces the risk of death but increases the risk of fibrosis. Furthermore, we validated the prediction that sequential combination therapy of initial treatment with a Wnt agonist followed by treatment with a Wnt antagonist can reduce both the risk of death and fibrosis in response to acute injuries

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations