Combining linear regression models: When and how?

Model-combining (i.e., mixing) methods have been proposed in recent years to deal with uncertainty in model selection. Even though advantages of model combining over model selection have been demonstrated in simulations and data examples, it is still unclear to a large extent when model combining should be preferred. In this work, first we propose an instability measure to capture the uncertainty of model selection in estimation, called perturbation instability in estimation (PIE), based on perturbation of the sample. We demonstrate that estimators from model selection can have large PIE values and that model combining substantially reduces the instability for such cases. Second, we propose a model combining method, adaptive regression by mixing with model screening (ARMS), and derive a theoretical property. In ARMS, a screening step is taken to narrow down the list of candidate models before combining, which not only saves computing time, but also can improve estimation accuracy. Third, we compare ARMS with EBMA (an empirical Bayesian model averaging) and model selection methods in a number of simulations and real data examples. The comparison shows that model combining produces better estimators when the instability of model selection is high and that ARMS performs better than EBMA in most such cases in our simulations. With respect to the choice between model selection and model combining, we propose a rule of thumb in terms of PIE. The empirical results support that PIE is a sensible indicator of model selection instability in estimation and is useful for understanding whether model combining is a better choice over model selection for the data at hand

Topical Delivery of Low-Cost Protein Drug Candidates Made in Chloroplasts for Biofilm Disruption and Uptake by Oral Epithelial Cells

Protein drugs (PD) are minimally utilized in dental medicine due to high cost and invasive surgical delivery. There is limited clinical advancement in disrupting virulent oral biofilms, despite their high prevalence in causing dental caries. Poor efficacy of antimicrobials following topical treatments or to penetrate and disrupt formed biofilms is a major challenge. We report an exciting low-cost approach using plant-made antimicrobial peptides (PMAMPs) retrocyclin or protegrin with complex secondary structures (cyclic/hairpin) for topical use to control biofilms. The PMAMPs rapidly killed the pathogen Streptococcus mutans and impaired biofilm formation following a single topical application of tooth-mimetic surface. Furthermore, we developed a synergistic approach using PMAMPs combined with matrix-degrading enzymes to facilitate their access into biofilms and kill the embedded bacteria. In addition, we identified a novel role for PMAMPs in delivering drugs to periodontal and gingival cells, 13–48 folds more efficiently than any other tested cell penetrating peptides. Therefore, PDs fused with protegrin expressed in plant cells could potentially play a dual role in delivering therapeutic proteins to gum tissues while killing pathogenic bacteria when delivered as topical oral formulations or in chewing gums. Recent FDA approval of plant-produced PDs augurs well for clinical advancement of this novel concept

Expression and clinical significance of serum complement and IL-25 in systemic lupus erythematosus

Objective To determine the differences in the expression of serum complement （C） and IL-25 in systemic lupus erythematosus （SLE） involved with single or multi-organ systems， and analyze the correlation between serum C3， C4， CH50， IL-25， C-reactive protein （CRP） and anti-dsDNA antibody. Methods A total of 151 SLE patients were included in this study. According to the organ involvement status， all patients were divided into the SLE alone （n = 58）， SLE complicated with single organ injury （n = 67， 51 cases of lupus nephritis， 13 cases of blood system injury and 3 cases of other organ injury）， and SLE complicated with multi-organ injury groups （n = 26， 25 cases of lupus nephritis complicated with other organ injury and 1 blood system complicated with brain injury）. The levels of serum C3， C4， CH50， IL-25 and CRP， and positive rate of anti-dsDNA antibody were detected among three groups. The correlation among these indexes was analyzed. Results There was no significant difference in the C4， CH50， IL-25 and CRP levels among three groups. There were significant differences in the C3 level and positive rate of anti-dsDNA antibody among three groups （all P < 0.05）. In the multi-organ injury group， C3 level was significantly lower， whereas positive rate of anti-dsDNA antibody was significantly higher compared with those in the remaining two groups （all P < 0.017）. Spearman rank correlation test indicated that C3 level was positively correlated with C4 （rs = 0.73， P < 0.001） and CH50 levels （rs = 0.81， P < 0.01）， whereas negatively correlated with IL-25 level （rs = -0.14， P < 0.001）. Conclusions In SLE patients with multi-organ involvement， serum C3 level is significantly decreased， whereas positive rate of anti-dsDNA antibody is significantly increased. Detection of serum complement levels is of clinical significance for the prediction of multi-organ injury in SLE patients

Heat shock transcription factor 1 preserves cardiac angiogenesis and adaptation during pressure overload

To examine how heat shock transcription factor 1 (HSF1) protects against maladaptive hypertrophy during pressure overload, we subjected HSF1 transgenic (TG), knockout (KO) and wild type (WT) mice to a constriction of transverse aorta (TAC), and found that cardiac hypertrophy, functions and angiogenesis were well preserved in TG mice but were decreased in KO mice compared to WT ones at 4 weeks, which was related to HIF-1 and p53 expression. Inhibition of angiogenesis suppressed cardiac adaptation in TG mice while overexpression of angiogenesis factors improved maladaptive hypertrophy in KO mice. In vitro formation of vasculatures by microvascular endothelial cells was higher in TG mice but lower in KO mice than in WT ones. A siRNA of p53 but not a HIF-1 gene significantly reversed maladaptive hypertrophy in KO mice whereas a siRNA of HIF-1 but not a p53 gene induced maladaptive hypertrophy in TG mice. Heart microRNA analysis showed that miR-378 and miR-379 were differently changed among the three mice after TAC, and miR-378 or siRNA of miR-379 could maintain cardiac adaptation in WT mice. These results indicate that HSF1 preserves cardiac adaptation during pressure overload through p53-HIF-1-associated angiogenesis, which is controlled by miR-378 and miR-379

Outcomes of Early Endoscopic Realignment Versus Suprapubic Cystostomy and Delayed Urethroplasty for Pelvic Fracture-related Posterior Urethral Injuries : A Systematic Review

Peer reviewedPostprin

Is There Outcome Reporting Heterogeneity in Trials That Aim to Assess the Effectiveness of Surgical Treatments for Stress Urinary Incontinence in Women?

Peer reviewedPostprin

Holocene climate change and anthropogenic activity records in Svalbard: a unique perspective based on Chinese research from Ny-Ålesund

Climate change in the Arctic region is more rapid than that in other areas owing to Arctic amplification. To better understand climate change and the driving mechanisms, long-term historical reconstructions throughout the Holocene and high-resolution records of the past few hundred years are required. Intense anthropogenic activities in the Arctic have had a great impact on the local environment. Here, we review the Holocene climate change record, responses of the ecosystems to climate change, and the anthropogenic impacts on the environment based mainly on Chinese research from Ny-Ålesund. Climate reconstruction studies from Svalbard have revealed several cold episodes during the Holocene, which are consistent with ice rafting events in the North Atlantic region and glacier activity from Greenland, Iceland, and Svalbard. The ecosystem also showed corresponding responses to climate change, especially during the late Holocene. Over recent decades, anthropogenic activities have caused serious pollution and deterioration to the local environment in Svalbard in areas frequented by people. Greater environmental protection is therefore needed to reduce the anthropogenic impacts on the local environment