RET,a targetable driver of pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) remains a deadly disease, affecting about 40,000 individuals in the United States annually. We aimed to characterize the role of RET as a co-driver of pancreas tumorigenesis. To assess the role of RET as a co-driver of PDA, we generated a novel triple mutant transgenic mouse based on the cre-activated p53^R172H gene and a constitutively active RET ^M919T mutant (PRC). Survival analysis was performed using Kaplan–Meier analysis. Study of human PDA specimens and Pdx-1-Cre/Kras^G12D /p53^R172H (KPC) mice revealed that RET is upregulated during pancreas tumorigenesis, from inception through precursor lesions, to invasive cancer. We demonstrated that activation of RET is capable of inducing invasive pancreatic carcinomas in the background of the P53 inactivation mutation. Compared to KPC mice, PRC animals had distinct phenotypes, including longer latency to tumor progression, longer survival, and the presence of multiple macrometastases. Enhanced activation of the MAPK pathway was observed as early as the PanIN 2 stage. Sequencing of the exonic regions of KRAS in PRC-derived PDA cells revealed no evidence of KRAS mutations. RET can be an essential co-driver of pancreatic tumorigenesis in conjugation with KRAS activity. These data suggest that RET may be a potential target in the treatment of PDA.     

Violent Crime in the Lives of Homeless Female Ex-Offenders

The cyclical pattern of violence in the lives of homeless female ex-offenders may precipitate ongoing substance use and recidivism; all of which have shown to be mounting public health issues affecting successful reentry. This paper, which analyzed baseline data from a longitudinal study of 126 female ex-offenders in Los Angeles and Pomona, California, highlighted the factors found to be associated with violent crime among homeless female ex-offenders. A multiple logistic regression model for whether or not the last conviction was for a violent offense indicated that poor housing (p = .011) and self-reported anger or hostility (p < .001) were significant correlates. An ordinal regression model for the number of violent offenses also indicated that affectionate support was associated with committing fewer number of violent crimes (p = .001), while positive social interactions (p = .007), and anger/hostility (p = .015) were associated with greater number of violent crimes. Implications for developing a comprehensive array of strategies that can mitigate the pattern of violence often seen in the lives of homeless female who have recently exited jails and prisons is discussed.     

Spatial Trends and Factors Affecting Mercury Bioaccumulation in Freshwater Fishes of Washington State, USA

Twenty-four lakes in Washington State, United States, were sampled for largemouth and smallmouth bass as well as water chemistry parameters during 2005 to 2009 to evaluate trends in mercury (Hg) concentrations. We analyzed spatial patterns in bass Hg levels across a gradient of land and climate types, lake chemistry parameters, and physical watershed characteristics to identify factors influencing Hg bioaccumulation. Across the state, bass Hg levels followed rainfall patterns and were statistically greater on the coastal west side of the state and lowest in the drier eastern region. Lake and watershed variables with the strongest correlations to Hg bioaccumulation in bass were annual watershed precipitation (+) and lake alkalinity (–). Principal component analysis (PCA) explaining 50.3 % of the variance in the dataset indicated that wet, forested landscapes were more likely to contain lakes with greater fish Hg levels than alkaline lakes in drier agriculture-dominated or open space areas. The PCA did not show wetland abundance and lake DOC levels as variables influencing bass Hg levels, but these were generally associated with small, shallow lakes containing greater chlorophyll levels. The effect of in-lake productivity may have counteracted the role of wetlands in Hg bioaccumulation among this study’s lakes.     

A novel host-protein assay outperforms routine parameters for distinguishing between bacterial and viral lower respiratory tract infections

Bacterial and viral lower respiratory tract infections (LRTIs) are often clinically indistinguishable, leading to antibiotic overuse. We compared the diagnostic accuracy of a new assay that combines 3 host-biomarkers (TRAIL, IP-10, CRP) with parameters in routine use to distinguish bacterial from viral LRTIs. Study cohort included 184 potentially eligible pediatric and adult patients. Reference standard diagnosis was based on adjudication by an expert panel following comprehensive clinical and laboratory investigation (including respiratory PCRs). Experts were blinded to assay results and assay performers were blinded to reference standard outcomes. Evaluated cohort included 88 bacterial and 36 viral patients (23 did not fulfill inclusion criteria; 37 had indeterminate reference standard outcome). Assay distinguished bacterial from viral LRTI patients with sensitivity of 0.93 ± 0.06 and specificity of 0.91 ± 0.09, outperforming routine parameters, including WBC, CRP and chest x-ray signs. These findings support the assay's potential to help clinicians avoid missing bacterial LRTIs or overusing antibiotics.     

How does feedback from patients impact upon healthcare student clinical skill development and learning? A systematic review

Background: A key feature of health professionals’ training, irrespective of discipline, is the acquisition and application of clinical and communication skills. Despite this, little is known about the potential role of patient feedback on this process. This systematic review aimed to answer the question: How does feedback from patients impact upon healthcare student clinical skill development and learning?

Design: Systematic review of published literature.

Methods: Electronic databases were searched for studies that explored the effects of patient feedback on student learning and were published before March 2016. Eligible articles underwent methodological evaluation using the McMaster University Critical Evaluation Forms and data extraction.

Results: A total of 237 articles were retrieved following searches of electronic databases and hand searches of reference lists. Twelve (7 quantitative, 2 qualitative, 3 mixed methods) studies met the inclusion criteria. Eleven studies reported that patient feedback improved students’ clinical skills.

Conclusion: Minimal research has explored the impact of patient feedback on student learning. The research to date suggests that direct feedback from patients may be beneficial for the development of students’ communication and clinical skills; however, the wide variety of evaluation methods and the lack of validated tools for patients to provide feedback suggest that further exploration is warranted.