deficiency modulates the stromal environment in the pretumorigenic rat mammary gland.

Background: Neurofibromin, coded by the tumor suppressor gene, is the main negative regulator of the RAS pathway and is frequently mutated in various cancers. Women with Neurofibromatosis Type I (NF1)-a tumor predisposition syndrome caused by a germline mutation-have an increased risk of developing aggressive breast cancer with poorer prognosis. The mechanism by which mutations lead to breast cancer tumorigenesis is not well understood.

Ex Vivo Patient-Derived Explant Model for Neurofibromatosis Type 1-Related Cutaneous Neurofibromas.

Cutaneous neurofibromas (CNFs) are benign tumors that occur in the dermis of individuals with the inherited tumor predisposition disorder, neurofibromatosis type 1. CNFs cause disfigurement, pain, burning, and itching, resulting in substantially reduced QOL in patients with neurofibromatosis type 1. CNFs are benign tumors that exhibit cellular and molecular heterogeneity, making it difficult to develop tractable in vitro or in vivo models.

NF1 deficiency drives metabolic reprogramming in ER+ breast cancer.

Objective: NF1 is a tumor suppressor gene and its protein product, neurofibromin, is a negative regulator of the RAS pathway. NF1 is one of the top driver mutations in sporadic breast cancer such that 27 % of breast cancers exhibit damaging NF1 alterations. NF1 loss-of-function is a frequent event in the genomic evolution of estrogen receptor (ER)+ breast cancer metastasis and endocrine resistance.

Dissecting the Rat Mammary Gland: Isolation, Characterization, and Culture of Purified Mammary Epithelial Cells and Fibroblasts.

With the advent of CRISPR-Cas and the ability to easily modify the genome of diverse organisms, rat models are being increasingly developed to interrogate the genetic events underlying mammary development and tumorigenesis. Protocols for the isolation and characterization of mammary epithelial cell subpopulations have been thoroughly developed for mouse and human tissues, yet there is an increasing need for rat-specific protocols. To date, there are no standard protocols for isolating rat mammary epithelial subpopulations.

Distinctive epigenomic alterations in NF1-deficient cutaneous and plexiform neurofibromas drive differential MKK/p38 signaling.

Benign peripheral nerve sheath tumors are the clinical hallmark of Neurofibromatosis Type 1. They account for substantial morbidity and mortality in NF1. Cutaneous (CNF) and plexiform neurofibromas (PNF) share nearly identical histology, but maintain different growth rates and risk of malignant conversion.

Isoform-Specific Destabilization of the Active Site Reveals a Molecular Mechanism of Intrinsic Activation of KRas G13D.

Ras GTPases are mutated at codons 12, 13, and 61, with different frequencies in KRas, HRas, and NRas and in a cancer-specific manner. The G13D mutant appears in 25% of KRas-driven colorectal cancers, while observed only rarely in HRas or NRas. Structures of Ras G13D in the three isoforms show an open active site, with adjustments to the D13 backbone torsion angles and with disconnected switch regions.

Post-Discharge Mortality of Older Adults with Traumatic Brain Injury or Other Trauma.

Objectives: Prior studies of mortality following traumatic brain injury (TBI) have not focused specifically on older adults compared with a non-TBI trauma cohort or included specific causes of death. The objectives of this study were, among adults aged 65 years and older, to (1) generate standardized mortality ratios (SMRs) by cause of death for TBI and a non-TBI trauma cohort compared with a general population, and (2) assess risk of mortality associated with TBI compared with a non-TBI trauma cohort.

Design: Retrospective cohort study of adults aged 65 years and older who were treated at an urban trauma center from 1997 to 2008.

deficiency correlates with estrogen receptor signaling and diminished survival in breast cancer.

The key negative regulatory gene of the RAS pathway, , is mutated or deleted in numerous cancer types and is associated with increased cancer risk and drug resistance. Even though women with neurofibromatosis (germline mutations) have a substantially increased breast cancer risk at a young age and is commonly mutated in sporadic breast cancers, we have a limited understanding of the role of in breast cancer. We utilized CRISPR-Cas9 gene editing to create rat models to evaluate the effect of deficiency on tumorigenesis.

Effect of Maryland's 2011 Alcohol Sales Tax Increase on Alcohol-Positive Driving.

Introduction: The 2011 Maryland alcohol sales tax increase from 6% to 9% provided an opportunity to evaluate the impact on rates of alcohol-positive drivers involved in injury crashes.

Methods: Maryland police crash reports from 2001 to 2013 were analyzed using an interrupted time series design and a multivariable analysis employing generalized estimating equations models with a negative binomial distribution. Data were analyzed in 2014-2015.

On equal footing: Trends in ankle/foot injuries for men vs. women.

Objectives: The objective of the current study was to examine trends in ankle/foot (A/F) injuries during the period 2001-2014, in order to determine whether the incidence of these injuries has changed and whether a previously identified difference in risk by gender still existed. In addition, other driver and crash-related risk factors were examined separately for men and women.

Methods: Passenger vehicle drivers aged 16+ were identified from NASS-CDS; weighted data were analyzed for model years 2001-2014.

S-100β does not predict outcome after mild traumatic brain injury.

Objective: To determine the usefulness of S-100β, a marker for central nervous system damage, in the prediction of long-term outcomes after mild traumatic brain injury (MTBI) Hypothesis: Mid- and long-term outcomes of MTBI (i.e. 3, 6 and 12 months post-injury and return-to-work or school (RTWS)) may be predicted based on pre-injury and injury factors as well as S-100β.

Declining statewide trends in motor vehicle crashes and injury-related hospital admissions.

Numbers of crashes, rates of police-reported injury severity, and hospital admission rates were calculated for the ten year period between 2001 and 2010 in Maryland. Comparisons were made for two 5-year periods of 2001-2005 and 2006-2010. Crash characteristics remained similar for the two five-year periods, but there was a significant increase in occupant age.

Changes in the Severity and Injury Sources of Thoracic Aorta Injuries due to Vehicular Crashes.

Research using the National Automotive Sampling System-Crashworthiness Data System (NASS-CDS) suggested a decreased adjusted risk of thoracic aorta injuries (TAI) for newer vehicles during near-side crashes and an increased adjusted TAI risk during frontal crashes. This study attempted to explore possible explanations of these findings. Adult front seat occupants in the Crash Injury Research and Engineering Network (CIREN) database through June 2012 were studied.

A comparison of KABCO and AIS injury severity metrics using CODES linked data.

Objective: The research objective is to compare the consistency of distributions between crash assigned (KABCO) and hospital assigned (Abbreviated Injury Scale, AIS) injury severity scoring systems for 2 states. The hypothesis is that AIS scores will be more consistent between the 2 studied states (Maryland and Utah) than KABCO.

Methods: The analysis involved Crash Outcome Data Evaluation System (CODES) data from 2 states, Maryland and Utah, for years 2006-2008.

Aortic injuries in newer vehicles.

The occurrence of AI was studied in relation to vehicle model year (MY) among front seat vehicular occupants, age≥16 in vehicles MY≥1994, entered in the National Automotive Sampling System Crashworthiness Data System between 1997 and 2010 to determine whether newer vehicles, due to their crashworthiness improvements, are linked to a lower risk of aortic injuries (AI). MY was categorized as 1994-1997, 1998-2004, or 2005-2010 reflecting the introduction of newer occupant protection technology. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals for the association between AI and MY independent of possible confounders.

Causation and outcomes of diaphragmatic injuries in vehicular crashes.

Background: This study aimed to identify vehicular and crash factors associated with diaphragmatic injuries (DIs).

Methods: DI presence was analyzed among Crash Injury Research and Engineering Network vehicular occupants (age ≥ 16 years) in relation to occupant and crash factors. Contact points (i.

Does helicopter transport improve outcomes independently of emergency medical system time?

Background: Helicopter emergency medical systems (HEMS) have been reported to improve trauma survival. This study seeks to determine HEMS effect on survival across different subpopulations in relation to injury severity, degree of physiologic derangement, and transportation time (TT).

Methods: The 2007 National Trauma Data Bank adult patients transported directly to hospitals by ground ambulance or HEMS were compared in relation to their survival with discharge and other possible confounders.

Degree of urbanization and mortality from motor vehicular crashes.

Purpose: : The purpose of this study is to establish whether motor vehicular crash (MVC) case fatality varies across different urbanization levels in the USA using a representative sample of crashes.

Methods: : Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between urbanization level [i.e.

Frailty and injury causation.

Purpose: : The current study will attempt to elucidate whether frailty has a role in motor vehicle crash injury causation.

Methods: : The association between frailty and injury was studied among Crash Injury Research Engineering Network (CIREN) cases. The baseline "physical functioning" (PF) score of the SF-36 was used as a marker of frailty (i.

Epidemiology of abusive abdominal trauma hospitalizations in United States children.

Objectives: (1) To estimate the incidence of abusive abdominal trauma (AAT) hospitalizations among US children age 0-9 years. (2) To identify demographic characteristics of children at highest risk for AAT.

Design: Secondary data analysis of a cross-sectional, national hospitalization database.

Improving trauma triage using basic crash scene data.

Objective: to analyze the occurrence of severe injuries and deaths among crash victims transported to hospitals in relation to occupant and scene characteristics, including on-scene patient mobility, and their potential use in triaging patients to the appropriate level of care.

Methods: the occurrence of death and ISS>15 were studied in relation to occupant, crash and mobility data readily available to EMS at the scene, using weighted NASS-CDS data. Data set was randomly split in two for model development and evaluation.

Prescription medication usage and crash culpability in a population of injured drivers.

Unlabelled: There has been increasing concern regarding the role of prescription drug use in the causation of traffic crashes. The goal of this research is to describe the prevalence of prescription drug use among injured trauma patients and determine the association between classes of drugs and crash culpability, a surrogate measure of crash risk.

Methods: Patient records, including chronic medication usage, for all drivers admitted to a trauma center following a traffic collision in 2008 (N=1,558) were linked with police crash reports to determine crash culpability.

Crash-related mortality and model year: are newer vehicles safer?

Objective: The objective of this study was to determine whether occupants of newer vehicles experience a lower risk of crash-related mortality.

Methods: The occurrence of death was studied in relation to vehicle model year (MY) among front seat vehicular occupants, age ≥ 16 captured in the National Automotive Sampling System Crashworthiness Data System (NASS-CDS) between 2000 and 2008. The associations between death and other occupant, vehicular and crash characteristics were also explored.

Disparities in trauma center access of older injured motor vehicular crash occupants.

Background: To evaluate whether older injured motor vehicular crash (MVC) occupants' access to trauma centers (TC) reflects the lower threshold suggested in triaging recommendations.

Methods: Adult front seat occupants of MVCs transported to a hospital from 1999 through 2006 included in the National Automotive Sampling System (NASS) were studied. Cases were classified by their age in years (≤60 years or >60 years).

Scene mobility status as a predictor of injury severity and mortality due to vehicular crashes.

Background: To examine the association of scene mobility status (SMS) and injury severity and mortality among motor vehicular crash (MVC) victims.

Methods: Adult MVC victims transported to medical facilities between 1997 and 2008 and included in the National Automotive Sampling System were studied. SMS was classified as follows: "ejected," "self-exited," "exited with assistance," "removed from the vehicle with decreased mental status," "removed due to perceived serious injury," and "removed for other reasons.