Single Blast Research Articles

Blast-Mediated Traumatic Brain Injury Exacerbates Retinal Damage and Amyloidosis in the APPswePSENd19e Mouse Model of Alzheimer's Disease.

PurposeTraumatic brain injury (TBI) is a risk factor for developing chronic neurodegenerative conditions including Alzheimer's disease (AD). The purpose of this study was to examine chronic effects of blast TBI on retinal ganglion cells (RGC), optic nerve, and brain amyloid load in a mouse model of AD amyloidosis.MethodsTransgenic (TG) double-mutant APPswePSENd19e (APP/PS1) mice and nontransgenic (Non-TG) littermates were exposed to a single blast TBI (20 psi) at age 2 to 3 months. RGC cell structure and function was evaluated 2 months later (average age at endpoint = 4.5 months) using pattern electroretinogram (PERG), optical coherence tomography (OCT), and the chromatic pupil light reflex (cPLR), followed by histologic analysis of retina, optic nerve, and brain amyloid pathology.ResultsAPP/PS1 mice exposed to blast TBI (TG-Blast) had significantly lower PERG and cPLR responses 2 months after injury compared to preblast values and compared to sham groups of APP/PS1 (TG-Sham) and nontransgenic (Non-TG-Sham) mice as well as nontransgenic blast-exposed mice (Non-TG-Blast). The TG-Blast group also had significantly thinner RGC complex and more optic nerve damage compared to all groups. No amyloid-β (Aβ) deposits were detected in retinas of APP/PS1 mice; however, increased amyloid precursor protein (APP)/Aβ-immunoreactivity was seen in TG-Blast compared to TG-Sham mice, particularly near blood vessels. TG-Blast and TG-Sham groups exhibited high variability in pathology severity, with a strong, but not statistically significant, trend for greater cerebral cortical Aβ plaque load in the TG-Blast compared to TG-Sham group.ConclusionsWhen combined with a genetic susceptibility for developing amyloidosis of AD, blast TBI exposure leads to earlier RGC and optic nerve damage associated with modest but detectable increase in cerebral cortical Aβ pathology. These findings suggest that genetic risk factors for AD may increase the sensitivity of the retina to blast-mediated damage.

PF191 RECLASSIFICATION OF BIPHENOTYPIC ACUTE LEUKEMIA INTO MIXED‐PHENOTYPE ACUTE LEUKEMIA ACCORDING TO WHO CRITERIA REFINES PATIENT CHARACTERIZATION AND PROGNOSIS; DISEASE MARKERS AND IMPACT ON OUTCOME

Background:MPAL is a heterogeneous category in the World Health Organization (WHO) that comprises acute leukemias with discrete admixed populations of myeloid and lymphoid blasts (“bilineal”) or with extensive coexpression of lymphoid and myeloid markers in a single blast population (“biphenotypic”). Mixed phenotype acute leukemia (MPAL) accounts for 2–5% of newly diagnosed acute leukemia. WHO criteria highlight key lineage‐defining markers with particular emphasis on CD19 for B lineage, CD3 for T lineage, and myeloperoxidase (MPO) for myeloid lineage.Aims:Review of classification, biology, clinical features, and treatment approach to MPAL.Methods:We studied retrospectively 1163 consecutive patients diagnosed with acute leukemia at the G. Papanicolaou Hospital, Thessaloniki, Greece, from 1999 until January 2019 subclassified as follows: AML = 854, B‐ALL = 172, T‐ALL = 80, acute undifferentiated leukemia = 9, MPAL/BAL = 44, diagnosed using either the WHO (13/44) or the EGIL (31/44) criteria.Results:Of the 31 patients diagnosed with biphenotypic acute leukemia (BAL) using the EGIL classification 12 did not fulfill the WHO criteria for MPAL. Only 2 B‐Myeloid cases according to the WHO classification did not fulfill EGIL criteria. We reclassified all cases following the WHO criteria and resulted in 32 MPAL cases (2.8% of the cohort; 24/32 B‐Myeloid, 7/32 T‐Myeloid, 1/32 B‐T‐MPAL).Aberrant T‐cell marker expression was seen in 6 patients with B‐Myeloid MPAL, CD7 expression being the most frequent. In T‐Myeloid MPAL, the cytoplasmic CD79a B‐cell marker was aberrantly expressed in 4/7 cases (57%). HLA‐DR was expressed in all MPAL cases. TdT was positive in all Ph+ MPAL, compared to 26% in non‐Ph+ MPAL cases. Seventy‐three percent of the cases were classified as ALL by morphology. Clinical data was available in 25/32 patients; 18 males, 7 females, median age: 32 years (2–79). Median WBC count at presentation was 10.6 × 109/L, hemoglobin 9.3 g/dL, platelets 63 × 109/L, LDH 839 IU/L and marrow blast count 55%. Cytogenetic data available for 29/32 patients were as follows; normal karyotype = 5 (17.2%), t(9;22) translocation = 7 (24.1%), complex karyotype (CK) = 14(48.2%), monosomy 7 = 5 cases (17.2%).Response to treatment and outcome were available for 24 and 29 patients, respectively; 18 received ALL‐type therapy, 3 received AML‐type therapy, 2 a combination of ALL+AML therapy. All Ph+ patients received Tyrosine Kinase Inhibitor (TKI). One died before receiving treatment. ALL‐type treatment induced a response in 13/18 patients (72%), whereas AML‐type in 33.3%; both patients who received combination therapy responded. All refractory patients (7/24) had a complex karyotype. Fourteen patients underwent allogeneic hematopoietic cell transplantation (allo‐HCT). Median overall survival (OS) was 18.7 months; 12 and 27 months for patients with CK and t(9;22) respectively, while the 5‐year survival rate was 12.5%. In contrast, BAL patients classified according to EGIL had median OS 23.3 months.Summary/Conclusion:In our study, reclassification of BAL (EGIL) patients as per WHO, resulted in a more accurate characterization of acute leukemias with mixed phenotypic features. Our study confirms that MPAL/BAL displays a uniformly poor outcome especially in patients with CK. The addition of TKI in the treatment of Ph+ patients probably ameliorates MPAL poor prognosis. Upon validation in larger prospective cohorts, MPAL could be considered as an independent poor risk feature for leukemia patients.

SUN-477 Chronic Variable Stress Worsens Effects of Mild Blast Traumatic Brain Injury on the Stress Response

Traumatic brain injury (TBI) affects 10 million people annually, attributes to major psychiatric disorders, and is among the leading causes of death and disability. Blast-induced TBI (bTBI) accounts for approximately 80% of all TBIs. These numbers are rapidly rising due, in part, to the increasing frequency of terrorist bombing attacks. The least studied form of bTBI, perhaps because of delayed symptom onset, is mild bTBI (mbTBI). Nonetheless, mbTBI increases the prevalence of psychiatric disorders, including memory impairment, anxiety, and mood disorders. Virtually every mbTBI in the battlefield is preceded and followed by a constant period of stress. However, how stress can prime the brain to deal with an insult, such as mbTBI, remains unknown. This work aims to identify the brain targets affected by mbTBI and elucidate how chronic stress could prime the brain for worse outcomes after mbTBI. In the first experiment, we examined the effect of mbTBI on resting and restraint-induced limbic-HPA axis reactivity in male and female mice 7-10 days post-injury. Mild bTBI increased anxiety-like behaviors (p<0.05) and dysregulated the stress response in a sex-specific manner. In the paraventricular nucleus of the hypothalamus, mbTBI decreased (p<0.05) activation of non-neuroendocrine corticotropin releasing factor neurons in females, but not males, suggesting a potential link to autonomic dysregulation. To further examine the impact of mbTBI on HPA axis-relevant limbic structures, we assessed neuronal activation via c-Fos-ir or EGR-1-ir markers in the medial prefrontal cortex (mPFC). Mild bTBI blunted the restraint induced neuronal activation observed in male and female infralimbic and prelimbic regions of the mPFC. These data suggest that the mPFC is a potential target of mbTBI in both sexes. In a second experiment, we used the Thy1-eGFP transgenic mouse model to elucidate the effects of mbTBI during a chronic variable stress (CVS) paradigm. This paradigm consisted of two weeks of CVS prior to our single mbTBI model and followed by another week of CVS after the single blast. The adverse effects of mbTBI on anxiety-like behaviors observed following a single mbTBI were further worsened in the animals exposed to CVS when compared to no-CVS animals. These data suggest that CVS makes the system more vulnerable to the effects of mbTBI. Thus, future experiments should consider implementing a stress component when assessing the impact of mbTBI. Our ongoing experiments aim to elucidate the effects of CVS and mbTBI on the dendritic spine architecture of the mPFC. These data will help us understand the mbTBI effects observed in the mPFC and whether the psychiatric disorders seen following mbTBI result from changes in the dendritic connectivity and architecture on the mPFC.

Multivariate evaluation of blast damage from emulsion explosives in tunnels excavated in crystalline rock

Blast damage in tunnels is usually regulated in Swedish infrastructure contracts as it can influence the quality and lifecycle cost for tunneling projects. The topic is important for underground constructions with a long operation period such as tunnels for public transport, permanent access tunnels in mines or underground repositories for nuclear waste. This paper aims to evaluate the influence of design and geology variables on the resulting blast fracture length and frequency by means of multivariate data analysis. The analysis was based on data from five field investigations carried out at tunnel sites in Sweden and Finland where emulsion explosives were used. Data was compiled and analyzed using Principal Component Analysis (PCA). Charge concentration was found to be the most influential design variable and hole spacing had limited influence on blast fracturing. Results from the PCA suggest that blast fractures length could be dependent also on geology and natural fractures. Three main groups of fracture patterns were identified, one group with relatively few and short blast fractures, a group with several longer blast fractures and a group with few or a single long blast fracture. The result shows differences in fracture length between the column and bottom charge part of the contour holes, with blast fracture lengths up to approx. 40 cm for the column charge and up to approx. 60 cm for the bottom charge.

Repeated blast model of mild traumatic brain injury alters oxycodone self-administration and drug seeking.

Each year, traumatic brain injuries (TBI) affect millions worldwide. Mild TBIs (mTBI) are the most prevalent and can lead to a range of neurobehavioral problems, including substance abuse. A single blast exposure, inducing mTBI alters the medial prefrontal cortex, an area implicated in addiction, for at least 30days post injury in rats. Repeated blast exposures result in greater physiological and behavioral dysfunction than single exposure; however, the impact of repeated mTBI on addiction is unknown. In this study, the effect of mTBI on various stages of oxycodone use was examined. Male Sprague Dawley rats were exposed to a blast model of mTBI once per day for 3days. Rats were trained to self-administer oxycodone during short (2h) and long (6h) access sessions. Following abstinence, rats underwent extinction and two cued reinstatement sessions. Sham and rbTBI rats had similar oxycodone intake, extinction responding and cued reinstatement of drug seeking. A second group of rats were trained to self-administer oxycodone with varying reinforcement schedules (fixed ratio (FR)-2 and FR-4). Under an FR-2 schedule, rbTBI-exposed rats earned fewer reinforcers than sham-exposed rats. During 10 extinction sessions, the rbTBI-exposed rats exhibited significantly more seeking for oxycodone than the sham-injured rats. There was a positive correlation between total oxycodone intake and day 1 extinction drug seeking in sham, but not in rbTBI-exposed rats. Together, this suggests that rbTBI-exposed rats are more sensitive to oxycodone-associated cues during reinstatement than sham-exposed rats and that rbTBI may disrupt the relationship between oxycodone intake and seeking.

Minimal Residual Disease Risk-Stratification in Pediatric Mixed Phenotype Acute Leukemia: Results of a Multi-Center Cohort Study

BACKGROUNDMixed phenotype acute leukemia (MPAL) is a rare form of leukemia in children. Current evidence supports the use of acute lymphoblastic leukemia (ALL)-directed regimens as initial therapy for MPAL; Children's Oncology Group (COG) ALL regimens are commonly used for pediatric ALL in the United States. Data for the predictive value of minimal residual disease (MRD) to risk-stratify therapy for pediatric MPAL is sparse overall and currently unknown in the context of COG ALL regimens. The primary objective for this study was to therefore examine the predictive value of MRD for event-free and overall survival (EFS, OS) in a centrally-reviewed, strictly-defined pediatric MPAL cohort treated according to COG ALL regimens. METHODSA retrospective cohort of pediatric MPAL treated from 2008-2016 was assembled from six institutions in the United States. All sites submitted primary diagnostic flow cytometry for central review. Two independent hematopathologists blinded to clinical outcomes confirmed the diagnosis of MPAL according to the WHO2008 and/or WHO2016 classification and assigned a MPAL phenotype. MRD was assessed by multi-parameter flow cytometry (“negative” defined as <0.01%). Endpoints of interest included presenting features of MPAL, MRD levels at end of induction and consolidation (EOI, EOC), role of hematopoietic stem cell transplantation (HSCT) in complete remission (CR), EFS, and OS. Kaplan-Meier analyses were performed stratified by predictors of interest. Stepwise multivariable Cox proportional hazard models inclusive of MRD and candidate predictors were used to evaluate EFS and OS for patients with complete data. Analyses were repeated in the subset of patients with “neutral” cytogenetics (i.e. no favorable [double trisomy, ETV6-RUNX1] or adverse [hypodiploid, BCR-ABL1, KMT2Ar, Ph-like, iAMP21, FLT3-ITD] features). All tests were 2-sided with significance set at p <0.05. RESULTSOf the 112 cases diagnosed by institutions as MPAL, 94 (84%) fulfilled strict WHO criteria. The majority of MPAL patients were B/Myeloid (89%), with a single blast population (87%), and without hyperleukocytosis (WBC≥50K/uL) or central nervous system involvement at presentation (Table 1). Within the cohort, 85/94 were treated with a COG ALL regimen with EOI MRD available (1/85 suffered an induction death prior to MRD assessment). ALL induction therapy resulted in a MRD-negative CR in 72% (61/85); three MRD-negative patients nonetheless converted to non-ALL therapy. Of those EOI MRD+ (≥0.01%), 12 of 14 who continued with COG ALL therapy achieved an EOC MRD-negative CR (i.e. 70/85 [82%] were MRD-negative by EOC). Induction failure (IF) occurred in 7% (6/85) and was defined as disease progression prior to EOI (n=2) or by EOI MRD ≥5% (n=4). The two patients with early disease progression were successfully “salvaged” with AML therapy (<21 days from initial diagnosis) and achieved a MRD-negative CR following one cycle. Patients achieving MRD-negative remissions at EOI and/or EOC with ALL chemotherapy had excellent EFS and OS (Figure 1). Multivariable analysis confirmed the predictive value of MRD at EOI (hazard ratio ±SE for EFS and OS = 3.77±1.67 and 3.54±2.09; p=0.032 and p=0.024 respectively). Only a few patients receiving ALL therapy proceeded to HSCT in CR1, all were alive at time of reporting. Use of HSCT was not associated with improved EFS or OS (p>0.50 for both); five-year EFS and OS for ALL chemotherapy without HSCT (n=73) were 78±6% and 90±4%, respectively. The presence of multiple blast populations of distinct lineages at diagnosis was similarly rare and was potentially associated with worse OS on multivariable analysis (p=0.024). No other candidate predictors were associated with EFS or OS. No difference in the predictive value of MRD was present when analyses were limited to patients with “neutral” cytogenetics. CONCLUSIONIn a retrospective analysis of pediatric MPAL, the majority of patients treated with ALL chemotherapy achieved a MRD-negative CR by EOC (~week 12 of therapy); overall survival in this group was excellent. Further prospective validation of MRD is essential to refine risk-stratified therapy for pediatric MPAL. Optimal salvage for those who fail to achieve remission with ALL chemotherapy is unknown and requires further study. DisclosuresO'Gorman:Becton Dickinson: Consultancy.

Finite element method simulation of explosive compaction in saturated loose sandy soils

Explosive Compaction (EC) is a deep soil treatment method for saturated sands with low density. Beside soil characteristics, its efficiency remarkably depends on charges weight, placement pattern and placement depth. Various empirical equations have been proposed by many researchers for selecting of such parameters, but their lack of accuracy makes adopting of a more precise tool for design and evaluation of engaging parameters in EC method essential. Therefore, the present study was devoted to the application of an advanced finite element simulation scheme called arbitrary Lagrangian-Eulerian (ALE) formulation in LS-DYNA as an alternative approach to enhance EC design procedure. SOIL_AND_FOAM material model in LS-DYNA was used for soil and explosives were defined with HIGH_EXPLOSIVE_BURN material model and JWL equation of state. The developed model was validated by using the existing single borehole blast test result. Subsequently, the effectiveness of EC was evaluated by assessing the maximum soil settlement and pore water pressure (PWP) dissipation for different cases where soil permeability, charge weight, depth and detonation delay were varied. Consequently, results suggested that multiple small charges with detonation delays increases EC effectiveness regarding the final settlement and reaching liquefaction during the explosion. Moreover, when charges are placed on lower half of soil layer, more compaction and less heave are achieved. The findings also show that an increase in permeability value of the soil increases the resulting settlement, however, this difference is negligible. Furthermore, based on the obtained results, using more charge weight increases both surface heave and compaction of lower layers. Thus, an optimum weight of explosives should be chosen in this case.

Numerical simulation of stress wave interaction in short-delay blasting with a single free surface.

It is generally believed that stress wave superposition does occur and plays an important role in cutting blasting with a single free surface, in which explosive columns of several blast holes with short spacing are simultaneously initiated. However, considering the large scatter of pyrotechnic delay detonators that are used in most underground metal mines in China, the existence of stress wave superposition and the influence of this effect on rock fragmentation are questionable. In the present study, the stress wave interaction in short-delay blasting with a single free surface was studied through the use of the LS-DYNA code. Stress waves induced by two blast holes blasting with different delays were compared with the single blast hole case, and the effects of delay time, detonating location and spacing on stress wave superposition were investigated. The numerical results showed that for blast holes with a 1 m spacing, stress wave interaction only occurs when the delay time is 0 ms and does not occur for blasting with delays of more than 1 ms. An increase in the duration of a stress wave via optimizing the detonation location does not improve the stress wave interaction. For a 1 ms delay, stress wave superposition only occurs when the spacing is more than 4 m, which is a rare case in practice. The results indicated that the occurrence of stress wave superposition for blasting with a single free surface is strictly limited to conditions that would be difficult to achieve under the existing delay accuracy of detonators. Therefore, it is unrealistic to improve fragmentation via the stress wave interaction in field blasting. Furthermore, the numerical results of the stress wave interaction also show that there would be a great potential to reduce the hazardous vibrations induced by short-delay blasting by using electronic detonators with better control of delays in an order of several milliseconds.

Hemostatic nanoparticles increase survival, mitigate neuropathology and alleviate anxiety in a rodent blast trauma model

Explosions account for 79% of combat related injuries and often lead to polytrauma, a majority of which include blast-induced traumatic brain injuries (bTBI). These injuries lead to internal bleeding in multiple organs and, in the case of bTBI, long term neurological deficits. Currently, there are no treatments for internal bleeding beyond fluid resuscitation and surgery. There is also a dearth of treatments for TBI. We have developed a novel approach using hemostatic nanoparticles that encapsulate an anti-inflammatory, dexamethasone, to stop the bleeding and reduce inflammation after injury. We hypothesize that this will improve not only survival but long term functional outcomes after blast polytrauma. Poly(lactic-co-glycolic acid) hemostatic nanoparticles encapsulating dexamethasone (hDNPs) were fabricated and tested following injury along with appropriate controls. Rats were exposed to a single blast wave using an Advanced Blast Simulator, inducing primary blast lung and bTBI. Survival was elevated in the hDNPs group compared to controls. Elevated anxiety parameters were found in the controls, compared to hDNPs. Histological analysis indicated that apoptosis and blood-brain barrier disruption in the amygdala were significantly increased in the controls compared to the hDNPs and sham groups. Immediate intervention is crucial to mitigate injury mechanisms that contribute to emotional deficits.

Dietary Zinc Modulates Matrix Metalloproteinases in Traumatic Brain Injury.

Animal models of mild traumatic brain injury (mTBI) provide opportunity to examine the extent to which dietary interventions can be used to improve recovery after injury. Animal studies also suggest that matrix metalloproteinases (MMPs) play a role in tissue remodeling post-TBI. Because dietary zinc (Zn) improved recovery in nonblast mTBI models, and the MMPs are Zn-requiring enzymes, we evaluated the effects of low- (LoZn) and adequate-Zn (AdZn) diets on MMP expression and behavioral responses, subsequent to exposure to a single blast. MMP messenger RNA expression in soleus muscle and frontal cortex tissues were quantified at 48 h and 14 days post-blast. In muscle, blast resulted in significant upregulation of membrane-type (MT)-MMP, MMP-2, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 at 48 h post-injury in rats consuming AdZn. At 14 days post-blast, there were no blast or dietary effects observed on MMP levels in muscle, supporting the existence of a Zn-responsive, functional repair and remodeling mechanism. In contrast, blast resulted in a significant downregulation of MT-MMP, TIMP-1, and TIMP-2 and a significant upregulation of MMP-3 levels at 48 h post-injury in cortex tissue, whereas at 14 days post-blast, MT-MMP, MMP-2, and TIMP-2 were all downregulated in response to blast, independent of diet, and TIMP-1 were significantly increased in rats fed AdZn diets despite the absence of elevated MMPs. Because the blast injuries occurred while animals were under general anesthesia, the increased immobility observed post-injury in rats consuming LoZn diets suggest that blast mTBI can, in the absence of any psychological stressor, induce post-traumatic stress disorder-related traits that are chronic, but responsive to diet. Taken together, our results support a relationship between marginally Zn-deficient status and a compromised regenerative response post-injury in muscle, likely through the MMP pathway. However, in neuronal tissue, changes in MMP/TIMP levels after blast indicate a variable response to marginally Zn-deficient diets that may help explain compromised repair mechanism(s) previously associated with the systemic hypozincemia that develops in patients with TBI.

Study on the long-hole raising technique using one blast based on vertical crater retreat multiple deck shots

Backfilling inaccessible cavity through raise can provide underground support for the active open-pit operations and the raise must be taken down in a single blast for safety reasons. Conventional raising techniques are not economically and technically feasible, and the maximum advance depth in one blast is limited. In this paper, small-scale crater tests were carried out in a site with cavities and field blasting test data were measured and evaluated to obtain the basic data for raise-scale blast designs. The raising design parameters with 250-mm hole diameter, including charge weight and height for each slice, slice height, hole spacing and delay interval, were derived. A scheme of multiple deck blasting based on vertical crater retreat (VCR) drop-raising method was designed for an abandoned cavity with 30-m cover. The lower 12-m cover was first blasted to investigate the practical blast performance. Charging and timing patterns were adjusted accordingly and the left 18-m cover was successfully opened up. Through raising tests, it is shown that the advantage of two available free surfaces up and down should be maximized, and smaller slice height and alternate initiation sequence are benefit for raising extension. A numerical model is then developed and it is calibrated against the 12-m raising test. By combining the calibrated numerical model with the raising test results, the effects of hole layout and in-slice delay are examined. It is shown that circular pattern and in-slice delay are positive for multiple-deck raising blast. Based on the foregoing analysis, the hole layout, charging and timing patterns are optimized. The optimized scheme was applied to field raising blast and a 32-m raise was successfully excavated in one blast.

Long-Term Functional and Structural Consequences of Primary Blast Overpressure to the Eye.

Acoustic blast overpressure (ABO) injury in military personnel and civilians is often accompanied by delayed visual deficits. However, most animal model studies dealing with blast-induced visual defects have focused on short-term (≤1 month) changes. Here, we evaluated long-term (≤8 months) retinal structure and function deficits in rats with ABO injury. Adult male Long-Evans rats were subjected to ABO from a single blast (approximately 190 dB SPL, ∼63 kPa, @80 psi), generated by a shock tube device. Retinal function (electroretinography; ERG), visual function (optomotor response), retinal thickness (spectral domain-optical coherence tomography; SD-OCT), and spatial cognition/exploratory motor behavior (Y-maze) were measured at 2, 4, 6, and 8 months post-blast. Immunohistochemical analysis of glial fibrillary acidic protein (GFAP) in retinal sections was performed at 8 months post-blast. Electroretinogram a- and b-waves, oscillatory potentials, and flicker responses showed greater amplitudes with delayed implicit times in both eyes of blast-exposed animals, relative to controls. Contrast sensitivity (CS) was reduced in both eyes of blast-exposed animals, whereas spatial frequency (SF) was decreased only in ipsilateral eyes, relative to controls. Total retinal thickness was greater in both eyes of blast-exposed animals, relative to controls, due to increased thickness of several retinal layers. Age, but not blast exposure, altered Y-maze outcomes. GFAP was greatly increased in blast-exposed retinas. ABO exposure resulted in visual and retinal changes that persisted up to 8 months post-blast, mimicking some of the visual deficits observed in human blast-exposed patients, thereby making this a useful model to study mechanisms of injury and potential treatments.

Effects of Prior Psychosocial Trauma on Subsequent Immune Response After Experimental Thorax Trauma.

Overshooting inflammation during the early phase after blunt thorax trauma promotes the development of acute respiratory distress syndrome, multiple organ failure, and subsequent mortality. Given that individuals diagnosed with stress-related disorders are characterized by chronic low-grade inflammation, we hypothesize that "psychosocial traumatic preload" poses a risk factor for the abovementioned complications after thorax trauma.Here, we used the chronic subordinate colony housing (CSC) paradigm to induce "psychosocial traumatic preload" and systemic low-grade immune activation in male mice, indicated by elevated plasma concentrations of different inflammatory mediators. Subsequent thorax trauma was induced in anaesthetized mice by a single blast wave centered on the thorax; SHAM animals were exposed to anesthesia only. Mice were killed 2, 6, and 24 h after thorax trauma or SHAM treatment.Independent of thorax trauma, CSC caused an increase in adrenal weight, and a decrease in thymus weight, indicating that the stress paradigm worked reliably. Moreover, although lung histology was not affected by prior stress, CSC exposure aggravated the early immune response after thorax trauma, indicated by elevated myeloperoxidase lung concentrations in thorax trauma-exposed CSC versus respective single-housed control (SHC) mice (2 h). Furthermore, thorax trauma caused an increase in total bronchoalveolar lavage fluid (BAL) protein (24 h), BAL C5a (2 h), BAL cell counts (24 h), and BAL keratinocyte chemoattractant (6 h and 24 h) in CSC but not SHC mice.Our data indicate that repeated psychosocial traumatization during adulthood moderately aggravates the local immune response toward thorax trauma, but overall may be considered as a rather minor risk factor in terms of thorax trauma-associated complications.

Vestibular Injury After Low-Intensity Blast Exposure.

The increased use of close range explosives has led to a higher incidence of exposure to blast-related head trauma. Exposure to primary blast waves is a significant cause of morbidity and mortality. Active service members and civilians who have experienced blast waves report high rates of vestibular dysfunction, such as vertigo, oscillopsia, imbalance, and dizziness. Accumulating evidence suggests that exposure to blast-wave trauma produces damage to both the peripheral and central vestibular system; similar to previous findings that blast exposure results in damage to auditory receptors. In this study, mice were exposed to a 63 kPa peak blast-wave over pressure and were examined for vestibular receptor damage as well as behavioral assays to identify vestibular dysfunction. We observed perforations to the tympanic membrane in all blast animals. We also observed significant loss of stereocilia on hair cells in the cristae and macule up to 1 month after blast-wave exposure; damage that is likely permanent. Significant reductions in the ability to perform the righting reflex and balance on a rotating rod that lasted several weeks after blast exposure were prominent behavioral effects. We also observed a significant reduction in horizontal vestibuloocular reflex gain and phase lags in the eye movement responses that lasted many weeks following a single blast exposure event. OKN responses were absent immediately following blast exposure, but began to return after several weeks’ recovery. These results show that blast-wave exposure can lead to peripheral vestibular damage (possibly central deficits as well) and provides some insight into causes of vestibular dysfunction in blast-trauma victims.

A VLA Study of High-redshift GRBs. I. Multiwavelength Observations and Modeling of GRB 140311A

Abstract We present the first results from a recently concluded study of GRBs at z ≳ 5 with the Karl G. Jansky Very Large Array (VLA). Spanning 1 to 85.5 GHz and 7 epochs from 1.5 to 82.3 days, our observations of GRB 140311A are the most detailed joint radio and millimeter observations of a GRB afterglow at z ≳ 5 to date. In conjunction with optical/near-IR and X-ray data, the observations can be understood in the framework of radiation from a single blast wave shock with energy erg expanding into a constant density environment with density, . The X-ray and radio observations require a jet break at days, yielding an opening angle of and a beaming-corrected blast wave kinetic energy of erg. The results from our radio follow-up and multiwavelength modeling lend credence to the hypothesis that detected high-redshift GRBs may be more tightly beamed than events at lower redshift. We do not find compelling evidence for reverse shock emission, which may be related to fast cooling driven by the moderately high circumburst density.

Dynamic response of mine pit walls

Any wall control program at a mine site should naturally include an understanding of the dynamic response of a pit wall to blast loads. If blasts are fired close to the base of the pit wall and have sufficient energy over an appropriate frequency range then they could induce dynamic motion of a significant portion of the wall. In this regard it is important to determine the natural (resonant) behaviour of a pit wall. Unfortunately, this resonant behaviour cannot be determined using a full-scale blast simply because the natural response is contaminated by the spectral influence of the blast delay sequence. Thus the pit wall of interest is loaded (at its base) by a single blast event simulated as a short duration, broadband displacement pulse. In the present investigation, the wall response to such a load is determined using the dynamic finite element method (DFEM). The DFEM results from two- and three-dimensional models show that even for the elastic case it is not possible to excite the wall in any strongly resonant modes. This weak (lossy) resonance is due to significant radiation damping, whereby vibrational energy dissipates into the surrounding medium and does not remain trapped near the wall region. Detailed responses were obtained for walls of elastic and viscoelastic material as well as walls with horizontal layers and a damaged crest zone; in all cases the most significant motions were invariably found in the wall crest regions. However, due to the weak resonances, it is not possible to unambiguously identify wall resonant behaviour in any practical sense, and this is shown to be consistent with field measurements taken for the firing of single (seed) blastholes. In light of such results it is shown that, irrespective of the delay accuracy in any full-scale blast, there is little potential to control the wall response by varying the blast delay sequence.

Autonomic responses to blast overpressure can be elicited by exclusively exposing the ear in rats

Blast overpressure has become an increasing cause of brain injuries in both military and civilian populations. Though blast's direct effects on the cochlea and vestibular organs are active areas of study, little attention has been given to the ear's contribution to the overall spectrum of blast injury. Acute autonomic responses to blast exposure, including bradycardia and hypotension, can cause hypoxia and contribute to blast-induced neurotrauma. Existing literature suggests that these autonomic responses are elicited through blast impacting the thorax and lungs. We hypothesize that the unprotected ear also provides a vulnerable locus for blast to cause autonomic responses. We designed a blast generator that delivers controlled overpressure waves into the ear canal without impacting surrounding tissues in order to study the ear's specific contribution to blast injury. Anesthetized adult rats' left ears were exposed to a single blast wave ranging from 0 to 110 PSI (0–758 kPa). Blast exposed rats exhibited decreased heart rates and blood pressures with increased blast intensity, similar to results gathered using shock tubes and whole-body exposure in the literature. While rats exposed to blasts below 50 PSI (345 kPa) exhibited increased respiratory rate with increased blast intensity, some rats exposed to blasts higher than 50 PSI (345 kPa) stopped breathing immediately and ultimately died. These autonomic responses were significantly reduced in vagally denervated rats, again similar to whole-body exposure literature. These results support the hypothesis that the unprotected ear contributes to the autonomic responses to blast.

Effects on Neurons and Hippocampal Slices by Single and Multiple Primary Blast Pressure Waves From Detonating Spherical Cyclotrimethylenetrinitramine (RDX) Explosive Charges.

Threshold shock-impulse levels required to induce cellular injury and cumulative effects upon single and/or multiple exposures are not well characterized. Currently, there are few in vitro experimental models with blast pressure waves generated by using real explosives in the laboratory for investigating the effects of primary blast-induced traumatic brain injury. An in vitro indoor experimental platform is developed using real military explosive charges to accurately represent battlefield blast exposure and to probe the effects of primary explosive blast on dissociated neurons and tissue slices. Preliminary results indicate that physical insults altered membrane permeability, impacted cellular viability, created axonal beadings, and led to synaptic protein loss in hippocampal slice cultures. Injuries from blast under the conditions that were examined did not appear to cause immediate or sustained damage to the cells. Three consecutive primary blasts failed to disrupt the overall cellular integrity in the hippocampal slice cultures and produced a unique type of pathology comprised with distinct reduction in synaptic proteins before cellular deterioration set in. These observed changes might add to the challenges in regard to enhancing our understanding of the complex biochemical and molecular mechanisms caused by primary blast-induced injury.

Long Term Temporal Changes in Structure and Function of Rat Visual System After Blast Exposure.

We identify long-term ocular sequelae subsequent to experimental blast exposure. Male Long-Evans rats were exposed to 230 kPa side-on primary blast overpressure using a compressed air driven shock tube. Visual system function and structure were assessed for 8 weeks after exposure using optokinetic nystagmus and optical coherence tomography. Vitreous protein expression and histology (TUNEL, H&E) were performed at 1 day and 1, 4, and 8 weeks. IOP was recorded bilaterally during blast in a subset of animals. Blast pressure profiles resembled the Friedlander waveform indicative of an open field blast. Peak IOP in directly-exposed eyes (240 kPa) was similar to peak blast overpressure, but IOP in indirectly-exposed eyes was 30% lower. Contrast sensitivity of blast-exposed animals decreased significantly by 20% 1 day after blast and did not recover by 8 weeks. Significant swelling and structural damage to the corneal epithelial and stromal layers were observed 2 weeks after blast exposure. Swollen corneas increased 254 ± 143 μm from baseline by 6 weeks, and scarring developed by 8 weeks. Histology revealed additional lens pathology 1 week after blast, suggestive of cataract development. Endothelial cell density increased significantly in blast-exposed animals between 1 and 4 weeks. Neurofilament heavy chain significantly increased after blast and returned to near baseline values by 8 weeks. Inflammatory cytokine changes corroborated ocular pathology findings. These data demonstrate immediate visual dysfunction and biochemical responses, but delayed structural pathology, in response to single primary blast exposure. The delayed pathology time course may provide a window to implement treatment strategies for improved visual outcome.

Stacking of blast resistance orthologue genes in susceptible indica rice line improves resistance against Magnaporthe oryzae.

The emergence of new strains of Magnaporthe oryzae (M. oryzae) is associated with recurrent failure of resistance response mediated by single resistance (R) gene in rice. Therefore, stacking or combining of multiple R genes could improve the durability of resistance against multiple strains of M. oryzae. To achieve this, in the present study, intragenic stacking of rice blast resistance orthologue genes Pi54 and Pi54rh was performed through co-transformation approach. Both these genes were expressed under the control of independent promoters and blast susceptible indica rice line IET17021 was used for transformation. The highly virulent M. oryzae strain Mo-ei-ger1 that could knock down most of the major single blast R genes including Pi54 and exhibiting 89% virulence spectrum was used for phenotypic analysis. The stacked transgenic IET17021 lines (Pi54+Pi54rh) have shown complete resistance to Mo-ei-ger1 strain in comparison to non-transgenic lines. These two R gene stacked indica transgenic lines could serves as a novel germplasm for rice blast resistance breeding programmes.