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Patients with chronic kidney disease (CKD) have an increased risk of infection and poorer responses to vaccination. This suggests that CKD patients have an impaired responsiveness to all antigens, even those first encountered before CKD onset. To examine this we evaluated antibody responses against two childhood vaccine antigens, tetanus (TT) and diphtheria toxoids (DT) and two common pathogens, cytomegalovirus (CMV) and Salmonella enterica serovar Enteritidis (SEn) in two independent cohorts consisting of age-matched individuals with and without CKD. Sera were evaluated for antigen-specific IgG titres and the functionality of antibody to SEn was assessed in a serum bactericidal assay. Surprisingly, patients with CKD and control subjects had comparable levels of IgG against TT and DT, suggesting preserved humoral memory responses to antigens encountered early in life. Lipopolysaccharide-specific IgG titres and serum bactericidal activity in patients with CKD were also not inferior to controls. CMV-specific IgG titres in seropositive CKD patients were similar or even increased compared to controls. Therefore, whilst responses to new vaccines in CKD are typically lower than expected, antibody responses to antigens commonly encountered prior to CKD onset are not. The immunodeficiency of CKD is likely characterised by failure to respond to new antigenic challenges and efforts to improve patient outcomes should be focussed here. [ABSTRACT FROM AUTHOR]

Background: Aberrant expression of DNA repair proteins is associated with poor survival in cancer patients. We investigated the combined expression of MRE11 and ATM as a predictive marker of response to radiotherapy in rectal cancer. Methods: MRE11 and ATM expression were examined in tumor samples from 262 rectal cancer patients who underwent surgery for rectal cancer, including a sub-cohort of 54 patients who were treated with neoadjuvant radiotherapy. The relationship between expression of the two-protein panel and tumor regression grade (TRG) was assessed by Mann–Whitney U test and receiver operating characteristics area under curve (ROC-AUC) analysis. The association between expression of the two-protein panel and clinicopathologic variables and survival was examined by Kaplan-Meier methods and Cox regression analysis. Results: A high score for two-protein combined expression in the tumor center (TC) was significantly associated with worse disease-free survival (DFS) (P = 0.035) and overall survival (OS) (P = 0.003) in the whole cohort, and with DFS (P = 0.028) and OS (P = 0.024) in the neoadjuvant subgroup (n = 54). In multivariate analysis, the two-protein combination panel (HR = 2.178, 95% CI 1.115–4.256, P = 0.023) and perineural invasion (HR = 2.183, 95% CI 1.222–3.899, P = 0.008) were significantly associated with DFS. Using ROC-AUC analysis of good versus poor histological tumor response among patients treated preoperatively with radiotherapy, the average ROC-AUC was 0.745 for the combined panel, 0.618 for ATM alone, and 0.711 for MRE11 alone. Conclusions: The MRE11/ATM two-protein panel developed in this study may have clinical value as a predictive marker of tumor response to neoadjuvant radiotherapy, and a prognostic marker for disease-free and overall survival. [ABSTRACT FROM AUTHOR]

Importance: The transition from hospital to home can expose patients to adverse events during the post discharge period. Post discharge care including phone calls may provide support for patients returning home but the impact on care transitions is unknown. Objective: To examine the effect of a 72-hour post discharge phone call on the patient's transition of care experience. Design: Cluster-randomized control trial. Setting: Urban, academic medical center. Participants: General medical patients age 18 and older discharged home after hospitalization. Main Outcomes and Measures: Primary outcome measure was the Care Transition Measure (CTM-3) score, a validated measure of the quality of care transitions. Secondary measures included self-reported adherence to medication and follow up plans, and 30-day composite of emergency department (ED) visits and hospital readmission. Results: 328 patients were included in the study over an 6-month period. 114 (69%) received a post discharge phone call, and 214 of all patients in the study completed the follow outcome survey (65% response rate). A small difference in CTM-3 scores was observed between the intervention and control groups (1.87 points, 95% CI 0.47–3.27, p = 0.01). Self-reported adherence to treatment plans, ED visits, and emergency readmission rates were similar between the two groups (odds ratio 0.57, 95% CI 0.13–2.45, 1.20, 95% CI 0.61–2.37, and 1.18, 95% CI 0.53–2.61, respectively). Conclusions and Relevance: A single post discharge phone call had a small impact on the quality of care transitions and no effect on hospital utilization. Higher intensity post discharge support may be required to improve the patient experience upon returning home. Trial Registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Accurate estimation of biological diversity in environmental DNA samples using high-throughput amplicon pyrosequencing must account for errors generated by PCR and sequencing. We describe a novel approach to distinguish the underlying sequence diversity in environmental DNA samples from errors that uses information on the abundance distribution of similar sequences across independent samples, as well as the frequency and diversity of sequences within individual samples. We have further refined this approach into a bioinformatics pipeline, Amplicon Pyrosequence Denoising Program (APDP) that is able to process raw sequence datasets into a set of validated sequences in formats compatible with commonly used downstream analyses packages. We demonstrate, by sequencing complex environmental samples and mock communities, that APDP is effective for removing errors from deeply sequenced datasets comprising biological and technical replicates, and can efficiently denoise single-sample datasets. APDP provides more conservative diversity estimates for complex datasets than other approaches; however, for some applications this may provide a more accurate and appropriate level of resolution, and result in greater confidence that returned sequences reflect the diversity of the underlying sample. [ABSTRACT FROM AUTHOR]

Estimated phylogenies of evolutionarily diverse taxa will be well supported and more likely to be historically accurate when the analysis contains large amounts of data–many genes sequenced across many taxa. Inferring such phylogenies for non-model organisms is challenging given limited resources for whole-genome sequencing. We take advantage of genomic data from a single species to test the limits of hybridization-based enrichment of hundreds of exons across frog species that diverged up to 250 million years ago. Enrichment success for a given species depends greatly on the divergence time between it and the reference species, and the resulting alignment contains a significant proportion of missing data. However, our alignment generates a well-supported phylogeny of frogs, suggesting that this technique is a practical solution towards resolving relationships across deep evolutionary time. [ABSTRACT FROM AUTHOR]