Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer.

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies.

Evaluation of new farming technologies in Ethiopia using the Integrated Decision Support System (IDSS).

This study investigates multi-dimensional impacts of adopting new technology in agriculture at the farm/village and watershed scale in sub-Saharan Africa using the Integrated Decision Support System (IDSS). Application of IDSS as an integrated modeling tool helps solve complex issues in agricultural systems by simultaneously assessing production, environmental, economic, and nutritional consequences of adopting agricultural technologies for sustainable increases in food production and use of scarce natural resources. The IDSS approach was applied to the Amhara region of Ethiopia, where the scarcity of resources and agro-environmental consequences are critical to agricultural productivity of small farm, to analyze the impacts of alternative agricultural technology interventions. Results show significant improvements in family income and nutrition, achieved through the adoption of irrigation technologies, proper use of fertilizer, and improved seed varieties while preserving environmental indicators in terms of soil erosion and sediment loadings. These pilot studies demonstrate the usefulness of the IDSS approach as a tool that can be used to predict and evaluate the economic and environmental consequences of adopting new agricultural technologies that aim to improve the livelihoods of subsistence farmers.

"To Call or Not to Call" Communication Preferences Among Pediatric Hospital Medicine Team Leaders.

OBJECTIVES: Pediatric Hospital Medicine fellowship programs need to abide by Accreditation Council for Graduate Medical Education requirements regarding communication and supervision. Effective communication is critical for safe patient care, yet no prior research has explored optimal communication practices between residents, fellows, and attending hospitalists. Our objective is to explore communication preferences among pediatric senior residents (SRs), Pediatric Hospital Medicine fellows, and hospitalists on an inpatient team during clinical decision-making. METHODS: We conducted a cross-sectional survey study at 6 institutions nationwide. We developed 3 complementary surveys adapted from prior research, 1 for each population: 200 hospitalists, 20 fellows, and 380 SRs. The instruments included questions about communication preferences between the SR, fellow, and hospitalist during clinical scenarios. We calculated univariate descriptive statistics and examined paired differences in percent agreement using χ2 tests, accounting for clustering by institution. RESULTS: Response rates were: 53% hospitalists; 100% fellows; 39% SRs. Communication preferences varied based on role, scenario, and time of day. For most situations, hospitalists preferred more communication with the fellow overnight and when a patient or family is upset than expressed by fellows (P < .01). Hospitalists also desired more communication between the SR and fellow for an upset patient or family than SRs (P < .01), but all respondents agreed the SR should call the fellow for adverse events. More fellows and hospitalists felt that the SR should contact the fellow before placing a consult compared with SRs (95%, 86% vs 64%). CONCLUSIONS: Hospitalists, fellows, and SRs may have differing preferences regarding communication, impacting supervision, autonomy, and patient safety. Training programs should consider such perspectives when creating expectations and communication guidelines.

A targetable pathway to eliminate TRA-1-60+/TRA-1-81+ chemoresistant cancer cells.

Chemoresistance is a primary cause of treatment failure in pancreatic cancer. Identifying cell surface markers specifically expressed in chemoresistant cancer cells (CCCs) could facilitate targeted therapies to overcome chemoresistance. We performed an antibody-based screen and found that TRA-1-60 and TRA-1-81, two 'stemness' cell surface markers, are highly enriched in CCCs. Furthermore, TRA-1-60+/TRA-1-81+ cells are chemoresistant compared to TRA-1-60-/TRA-1-81- cells. Transcriptome profiling identified UGT1A10, shown to be both necessary and sufficient to maintain TRA-1-60/TRA-1-81 expression and chemoresistance. From a high-content chemical screen, we identified Cymarin, which downregulates UGT1A10, eliminates TRA-1-60/TRA-1-81 expression, and increases chemosensitivity both in vitro and in vivo. Finally, TRA-1-60/TRA-1-81 expression is highly specific in primary cancer tissue and positively correlated with chemoresistance and short survival, which highlights their potentiality for targeted therapy. Therefore, we discovered a novel CCC surface marker regulated by a pathway that promotes chemoresistance, as well as a leading drug candidate to target this pathway.

Defining Supervision Preferences and Roles Within a New Subspecialty: Pediatric Hospital Medicine.

OBJECTIVE: To describe supervision preferences among pediatric hospitalists, Pediatric Hospital Medicine (PHM) fellows, and senior residents (SRs), and to better define the ideal role of a PHM fellow. METHODS: We conducted a cross-sectional survey study at 6 institutions nationwide. We developed 3 complementary surveys, one for each population (hospitalists, fellows, SRs). We calculated univariate descriptive and bivariate statistics for categorical variables using Chi-square tests with the Rao-Scott correction to account for clustering by institution. RESULTS: Survey respondents included 106 of 200 hospitalists (53%), all 20 fellows (100%), and 149 of 380 SRs (39%). Most hospitalists and all fellows preferred the supervising hospitalist to have 3+ years of experience or be fellowship-trained. Nearly all fellows preferred the attending round in-person providing progressive independence; while hospitalists and SRs desired greater attending presence on rounds. Hospitalists and fellows wanted more frequent communication when the attending does not round with the team, and more hospitalists desired at least 2 points of contact regardless of attending presence on rounds. Fifty-five percent of SRs reported experiencing much less/less autonomy when on with a fellow than when supervised by a hospitalist only. Regarding the fellow's role, most participants agreed SRs should lead rounds and contact the fellow first with questions. The majority agreed teaching should be a shared responsibility but lacked consensus about how to provide feedback. CONCLUSIONS: Study results reveal preferences about supervising fellows in this new subspecialty. Hospitalists, fellows, and SRs may have differing opinions regarding workflow, communication, and teaching, impacting team leadership and autonomy.

Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry.

BACKGROUND: Identifying T cell epitopes on pancreatic ductal adenocarcinoma (PDAC) associated antigens or neoantigens has been a challenge. In this study, we attempted to identify PDAC T cell epitopes by mass spectrometry (MS). METHODS: We isolated HLA class I (HLA-I) and HLA class II (HLA-II)-restricted peptides, respectively, from tissues of human PDAC by using the pan-HLA-I or pan-HLA-II affinity purification column and identified T cell epitopes by peptidome analysis with MS. RESULTS: Through peptidome analysis, we identified T cell epitopes shared by multiple patients with different HLA types and those containing sequences of both anti-HLA-I and HLA-II antibodies-affinity purified peptides. The identified epitopes bound non-matched HLA molecules and induced T cell response in peripheral T cells from both HLA-type matched and non-matched patients. Peptides containing both HLA class I and class II epitopes were able to induce polyfunctional cytokine responses in peripheral T cells. CONCLUSIONS: T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients.

Anti-IL-8 antibody activates myeloid cells and potentiates the anti-tumor activity of anti-PD-1 antibody in the humanized pancreatic cancer murine model.

Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy with an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity of aPD-1 and further investigated how the combination affects the immune response by regulating myeloid cells in the tumor microenvironment in a humanized murine model of PDAC with a reconstituted immune system consisting of human T cells and a combination of CD14+ and CD16+ myeloid cells. The results show that the combination of aIL-8 and aPD-1 treatment significantly enhanced antitumor activity following the infusion of myeloid cells. Our results further showed that the target of IL-8 is mainly present in CD16+ myeloid cells and is likely to be granulocytes. FACS analysis showed that aIL-8 treatment increased granulocytic myeloid cells in tumors. Consistently, single-nuclear RNA-sequencing analysis of tumor tissue showed that the innate immune response and cytokine response pathways in the myeloid cell cluster were activated by aIL-8 treatment. This is the first preclinical study using a humanized mouse model for new combination immunotherapeutic development and supports the further clinical testing of aIL-8 in combination with aPD-1 for PDAC treatment. This study also suggests that peripherally derived myeloid cells can potentiate the antitumor response of T cells, likely through the innate immune response, and aIL-8 re-educates tumor-infiltrating myeloid cells by activating the innate immune response.

CCR2/CCR5 inhibitor permits the radiation-induced effector T cell infiltration in pancreatic adenocarcinoma.

The resistance of pancreatic ductal adenocarcinoma (PDAC) to immune checkpoint inhibitors (ICIs) is attributed to the immune-quiescent and -suppressive tumor microenvironment (TME). We recently found that CCR2 and CCR5 were induced in PDAC following treatment with anti-PD-1 antibody (αPD-1); thus, we examined PDAC vaccine or radiation therapy (RT) as T cell priming mechanisms together with BMS-687681, a dual antagonist of CCR2 and CCR5 (CCR2/5i), in combination with αPD-1 as new treatment strategies. Using PDAC mouse models, we demonstrated that RT followed by αPD-1 and prolonged treatment with CCR2/5i conferred better antitumor efficacy than other combination treatments tested. The combination of RT + αPD-1 + CCR2/5i enhanced intratumoral effector and memory T cell infiltration but suppressed regulatory T cell, M2-like tumor-associated macrophage, and myeloid-derived suppressive cell infiltration. RNA sequencing showed that CCR2/5i partially inhibited RT-induced TLR2/4 and RAGE signaling, leading to decreased expression of immunosuppressive cytokines including CCL2/CCL5, but increased expression of effector T cell chemokines such as CCL17/CCL22. This study thus supports the clinical development of CCR2/5i in combination with RT and ICIs for PDAC treatment.

Inhibition of focal adhesion kinase enhances antitumor response of radiation therapy in pancreatic cancer through CD8+ T cells.

Objective: Pancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy, due in large part to its resistance to conventional therapies, including radiotherapy (RT). Despite RT exerting a modest antitumor response, it has also been shown to promote an immunosuppressive tumor microenvironment. Previous studies demonstrated that focal adhesion kinase inhibitors (FAKi) in clinical development inhibit the infiltration of suppressive myeloid cells and T regulatory (T regs) cells, and subsequently enhance effector T cell infiltration. FAK inhibitors in clinical development have not been investigated in combination with RT in preclinical murine models or clinical studies. Thus, we investigated the impact of FAK inhibition on RT, its potential as an RT sensitizer and immunomodulator in a murine model of PDAC. Methods: We used a syngeneic orthotopic murine model to study the effect of FAKi on hypofractionated RT. Results: In this study we showed that IN10018, a small molecular FAKi, enhanced antitumor response to RT. Antitumor activity of the combination of FAKi and RT is T cell dependent. FAKi in combination with RT enhanced CD8+ T cell infiltration significantly in comparison to the radiation or FAKi treatment alone (P < 0.05). FAKi in combination with radiation inhibited the infiltration of granulocytes but enhanced the infiltration of macrophages and T regs in comparison with the radiation or FAKi treatment alone (P < 0.01). Conclusions: These results support the clinical development of FAKi as a radiosensitizer for PDAC and combining FAKi with RT to prime the tumor microenvironment of PDAC for immunotherapy.

Risk Factors for the Development of Hospital-Associated Venous Thromboembolism in Adult Patients Admitted to a Children's Hospital.

BACKGROUND AND OBJECTIVES: Hospital-associated venous thromboembolism (HA-VTE) is a leading cause of preventable in-hospital mortality in adults. Our objective was to describe HA-VTE and evaluate risk factors for its development in adults admitted to a children's hospital, which has not been previously studied. We also evaluated the performance of commonly used risk assessment tools for HA-VTE. METHODS: A case-control study was performed at a freestanding children's hospital. Cases of HA-VTE in patients ≥18 years old (2013-2017) and age-matched controls were identified. We extracted patient and HA-VTE characteristics and HA-VTE risk factors on the basis of previous literature. Thrombosis risk assessment was performed retrospectively by using established prospective adult tools (Caprini and Padua scores). RESULTS: Thirty-nine cases and 78 controls were identified. Upper extremities were the most common site of thrombosis (62%). Comorbid conditions were common (91.5%), and malignancy was more common among case patients than controls (P = .04). The presence of a central venous catheter (P < .01), longer length of stay (P < .01), ICU admission (P = .005), and previous admission within 30 days (P = .01) were more common among case patients when compared with controls. Median Caprini score was higher for case patients (P < .01), whereas median Padua score was similar between groups (P = .08). CONCLUSIONS: HA-VTE in adults admitted to children's hospitals is an important consideration in a growing high-risk patient population. HA-VTE characteristics in our study were more similar to published data in pediatrics.

Interrogating the immune-modulating roles of radiation therapy for a rational combination with immune-checkpoint inhibitors in treating pancreatic cancer.

BACKGROUND: Radiation therapy (RT) has the potential to enhance the efficacy of immunotherapy, such as checkpoint inhibitors, which has dramatically altered the landscape of treatments for many cancers, but not yet for pancreatic ductal adenocarcinoma (PDAC). Our prior studies demonstrated that PD ligand-1 and indoleamine 2,3-dioxygenase 1 (IDO1) were induced on tumor epithelia of PDACs following neoadjuvant therapy including RT, suggesting RT may prime PDAC for PD-1 blockade antibody (αPD-1) or IDO1 inhibitor (IDO1i) treatments. In this study, we investigated the antitumor efficacy of the combination therapies with radiation and PD-1 blockade or IDO1 inhibition or both. METHODS: We developed and used a mouse syngeneic orthotopic model of PDAC suitable for hypofractionated RT experiments. RESULTS: The combination therapy of αPD-1 and RT improved survival. The dual combination of RT/IDO1i and triple combination of RT/αPD-1/IDO1i did not improve survival compared with RT/αPD-1, although all of these combinations offer similar local tumor control. RT/αPD-1 appeared to result in the best systemic interferon-γ response compared with other treatment groups and the highest local expression of immune-activation genes, including Cd28 and Icos. CONCLUSION: Our RT model allows examining the immune-modulatory effects of RT alone and in combination with immune-checkpoint inhibitors in the pancreas/local microenvironment. This study highlights the importance of choosing the appropriate immune-modulatory agents to be combined with RT to tip the balance toward antitumor adaptive immune responses.

Precision medicine in pancreatic cancer: treating every patient as an exception.

Patients with pancreatic cancer have not benefited from recent improvements in overall survival brought about by precision medicine in other malignancies. This failure is not due to a dearth of precision-medicine research in pancreatic ductal adenocarcinoma (PDAC), the main type of pancreatic cancer. In fact, the stalled progress in precision therapies for this type of cancer is due to the absence of agents that are able to target the common genetic alterations in PDAC. Several studies have attempted to phenotypically stratify PDAC at the transcriptional level. However, the value of such classifications will only be revealed through prospective studies and, crucially, only after development of new treatment options for this disease. Therefore, it is essential to learn from breakthrough discoveries in other cancer types that could benefit subpopulations of patients with PDAC and convert them from ordinary to exceptional responders. Identifying these exceptional patients will help to bring PDAC in line with other cancer types in terms of availability of precision therapies. Thus, the true challenge to precision medicine for PDAC might be the poor consensus on which genetic and phenotypic alterations across the spectrum of this disease are actionable; not the absence of actionable variables themselves. To reach consensus, knowledge and tools must be developed and disseminated for individuals who provide pancreatic cancer care, to enable the real-time identification of exceptional patients, more precise subgroup classifications, and effective disease management strategies; all informed by immediate feedback from clinical outcome data.

Using Quality Improvement to Introduce and Standardize the National Early Warning Score (NEWS) for Adult Inpatients at a Children's Hospital.

INTRODUCTION: The population of adults with childhood-onset chronic illness is growing across children's hospitals and constitutes a high risk population. National Early Warning Score (NEWS) is among the most recently validated adult early warning scores (EWSs) for early recognition of and response to clinical deterioration. Our aim was to implement and standardize NEWS scoring in 80% of patients age 21 and older admitted to a children's hospital. METHODS: Our intervention was tested on a single unit of our children's hospital. The primary process measure was the percentage of NEWS documented within 1 hour of routine nursing assessments, and was tracked using a run chart. Improvement activities focused on effective training, key stakeholder buy-in, increased awareness, real-time mitigation of failures, accountability for adherence, and action-oriented response. We also tracked the distribution of NEWS values and medical emergency team calls. RESULTS: The percentage of NEWS documented with routine nursing assessments for patients age 21 and over increased from 0% to 90% within 15 weeks and remained at 77% or greater for 17 weeks. Our distribution of NEWS values was similar to previously reported NEWS distribution. CONCLUSIONS: A nurse-driven adult early warning system for inpatients age 21 and older at a children's hospital can be achieved through a standardized EWS assessment process, incorporation into the electronic health record, and charge nurse and key stakeholder oversight. Furthermore, implementation of an adult EWS being used at a pediatric institution and our distribution of NEWS values were comparable to distribution published from adult hospitals.

Mutant p53 Together with TGFß Signaling Influence Organ-Specific Hematogenous Colonization Patterns of Pancreatic Cancer.

Purpose: TP53 and the TGFß pathway are major mediators of pancreatic cancer metastasis. The mechanisms by which they cause hematogenous metastasis have not been fully explored.Experimental Design:KPC (LSL-KRASG12D/+;LSL-Trp53R172H/+; Ptf1aCre/+) mice were generated, and the frequency and morphology of organ-specific hematogenous metastases compared with that seen in KPTC and KTC littermates (Tgfbr2+/-). Key findings were validated in primary cells from each genotype and samples of human pancreatic cancer liver metastases.Results: The frequency of hematogenous metastasis in KPTC mice was significantly lower than for KPC mice (41% vs. 68%, P < 0.05), largely due to a reduction in liver metastases. No differences were found between KPC and KPTC lung metastases, whereas liver metastases in KPTC mice showed a profound extravasation deficiency characterized by sinusoidal growth and lack of desmoplastic stroma. Analogous findings were confirmed in liver samples from patients indicating their clinical relevance. Portal vein colonization as a direct mode of access to the liver was observed in both mice and humans. Secretome analyses of KPC cells revealed an abundance of secreted prometastatic mediators including Col6A1 and Lcn2 that promoted early steps of metastatic colonization. These mediators were overexpressed in primary tumors but not metastases, suggesting that the ability to colonize is, in part, developed within the primary site, a phenomenon we refer to as the "Cinderella effect."Conclusions: These findings establish a novel paradigm for understanding pancreatic cancer metastasis and the observed clinical latencies of liver versus lung metastases specifically. Clin Cancer Res; 23(6); 1607-20. ©2016 AACR.

Real-Time Genomic Profiling of Pancreatic Ductal Adenocarcinoma: Potential Actionability and Correlation with Clinical Phenotype.

Purpose: Molecular profiling in cancer has identified potential actionable drug targets that have prompted attempts to discover clinically validated biomarkers to guide therapeutic decision-making and enrollment to clinical trials. We evaluated whether comprehensive genetic analysis of patients with pancreatic adenocarcinoma is feasible within a clinically relevant timeframe and whether such analyses provide predictive and/or prognostic information along with identification of potential targets for therapy.Experimental Design: Archival or prospectively acquired FFPE samples and matched normal DNA from N = 336 patients with pancreatic cancer were analyzed using a hybridization capture-based, next-generation sequencing assay designed to perform targeted deep sequencing of all exons and selected introns of 410 key cancer-associated genes. Demographic and treatment data were prospectively collected with the goal of correlating treatment outcomes and drug response with molecular profiles.Results: The median time from protocol consent to reporting of the genomic results was 45 days with a median time from tissue delivery of 20 days. All genetic alterations identified were stratified based upon prior evidence that the mutation is a predictive biomarker of drug response using the MSKCC OncoKB classification. Three of 225 patients (1%) received a matched therapy based upon the sequencing results.Conclusions: The practical application of molecular results to guide individual patient treatment is currently limited in patients with pancreatic adenocarcinoma. Future prospective molecular profiling efforts should seek to incorporate routine germline genetic analysis and the identification of DNA profiles that predict for clinical benefit from agents that target DNA damage repair and or immunotherapy. Clin Cancer Res; 23(20); 6094-100. ©2017 AACR.

Experimental biomechanical study of head injuries in lateral falls with skateboard helmet.

Traumatic brain injuries (TBI) are common in sports accidents. Helmets are generally known to provide protection to the head. However, the effectiveness of helmets in mitigating a TBI may be compromised due to the impact location and impact speed. Although it is known that the helmet decreases the linear head accelerations and the resulting head injury potential, to the best of our knowledge, limited research effort has been devoted to the study of the biomechanics of TBI in side impact conditions. The present work is designed to delineate the biomechanics of TBI in a fall impacting the parietal/temporal regions. A standing Hybrid III male dummy with pedestrian pelvis was used. The dummy was placed on a swinging platform for the fall simulation. The drop was achieved by stopping the platform with a block. The platform was swung from a predetermined height and stopped to allow the free fall of the dummy. The test was conducted with and without a skate board helmet. The impact on the dummy’s head was in the parietal and temporal regions. The head impact speed with the floor was approximately 24 kph (6.7 m/sec) The dummy was instrumented with tri-axial linear and tri-axial angular head accelerometers to measure the biomechanical injury responses. Results from three tests were compared. The linear head CG acceleration, Head Injury Criteria (HIC) and angular head accelerations were compared. Results suggest that the helmet reduced the linear head acceleration, HIC and angular head acceleration compared to the impact without a helmet. Although the linear head accelerations and HIC were reduced, the angular head accelerations even with the helmet were above nearly all proposed rotational head injury threshold in the literature. The higher angular head accelerations indicate a higher probability of concussion, acute subdural hematoma and diffuse axonal injuries. The present study is an additional step to better understand the biomechanics of TBI and the role of protective headgear systems in sports and recreational accidents.

Biomechanical analysis of pediatric injuries and child restraint system.

Airbag related injuries to infants in rear facing child seats are common in frontal crashes. Several vehicular modifications such as deactivated passenger airbags, manual cut-off switches, depowered airbags and smart airbags have been advanced to mitigate the effect of airbag deployment on child seats. However, there is limited research effort to address the biomechanics of airbag injuries due to modification in child restraint systems. The purpose of this research is to evaluate the biomechanical effects of a protective barrier between the rear facing child restraint and the frontal passenger airbag of the vehicle. An experimental study was conducted using an Anthropometric Test Dummy (ATD) in a vehicular partial structure (buck). The rear facing child seat was placed in the right front passenger seat of the vehicle. The child seat was restrained using the three-point restraint in the vehicle. The six-month-old instrumented ATD was restrained in the child seat. The ATD was instrumented with the head tri-axial and two uni-axial linear accelerometers. The uni-axial linear acceleration was used to calculate the angular acceleration. Two different rear facing child seats, the standard rear facing infant seat and the rear facing infant seat inside the protective barrier structure were tested. In each test, the Head Injury Criteria (HIC) and angular head acceleration were measured. Results show that the HIC was reduced by 95% and the angular head acceleration was reduced by 85% by the protective barrier. The head injury values were well below the tolerance limit for the child with the barrier. The protective barrier deflected the airbag away from the ATD’s head and also acted as a shield to minimize airbag force on the child seat. In the typical infant seat, the airbag contacted the ATD’s head and exerted significant force on the child seat which rotated the seat rearward. These kinematic responses may explain the clinical observation of severe head injuries by infants in rear facing seats due to forces transmitted through the child seat and downward force from the top of the head. The present study is a first step in better understanding the injury mitigating aspects of the safety protective structure in child restraints.

Inverted drop testing as a mechanism to evaluate rollover occupant injury potential.

The National Highway Traffic Safety Administration (NHTSA) has concluded that there is a relationship between roof intrusion and the risk of injury to belted occupants in rollovers events [1]. Previous testing on many different production vehicle types indicates that damage consistent with field rollover accidents can be achieved through inverted drop testing from small drop heights. It has been shown in previous drop test pairs with Hybrid III dummies, that the amount of roof intrusion is related to occupant neck injury [2,3]. In 1990, a study was reported by General Motors which involved 8 dolly rollover tests and 5 inverted drop tests performed on both production and rollcaged vehicles with Hybrid III dummies [4]. These studies were conducted to investigate the relationship between roof strength and occupant injury potential. In this paper, the authors further analyze the relationship between roof intrusion and occupant neck injury potential through inverted drop testing performed on Ford Econoline E-350 15-Passenger production and reinforced vans. Each of these van tests used Hybrid III test dummies in order to evaluate the resulting occupant injury potential in relation to the roof intrusion. The resulting roof intrusion and occupant neck loading experienced during the reinforced van drop test were significantly less than that of the production van test. As previously observed, the results of these tests indicate that the reduction of roof crush resulted in a direct reduction in neck loading and therefore an increase in occupant protection. Additionally, the inverse relationship between restraint loading and neck loading of the dummies was confirmed.