Towards the personalization of septic shock resuscitation: the fundamentals of ANDROMEDA-SHOCK-2 trial.

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation. This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.

Using digital chatbots to close gaps in healthcare access during the COVID-19 pandemic.

INTRODUCTION: Chatbots have emerged as a first link to care in recent years. The COVID-19 pandemic, and consequent health system disruptions, expanded their use. Socios En Salud (SES) introduced chatbots in Peru, which experienced one of the highest excess COVID mortalities in the world. METHODS: SES and the government identified unmet population health needs, which could be amenable to virtual interventions. Chatbots were developed to screen individuals for these conditions; we describe the period of deployment, number of screenings, and number of people who received services. RESULTS: Between April 2020 and May 2021, SES deployed nine ChatBots: four for mental health, two for maternal and child health, and three for chronic diseases: breast cancer, hypertension, diabetes mellitus, and obesity. Mental health services were provided to 42,932 people, 99.99% of those offered services. The other ChatBots reached fewer people. Overall, more than 50% of eligible people accepted chatbot-based services. DISCUSSION: ChatBot use was highest for mental health. Chatbots may increase connections between a vulnerable population and health services; this is likely dependent on several factors, including condition, population, and penetration of smart phones. Future research will be critical to understand user experience and preferences and to ensure that chatbots link vulnerable populations to appropriate, high-quality care.

INTRODUCTION: Les chatbots se sont imposés comme un premier lien aux soins ces dernières années. La pandémie de COVID-19, et les perturbations du système de santé qui en ont résultées, ont élargi leur champ d'application. Socios En Salud (SES) a introduit les chatbots au Pérou, qui a connu l'une des surmortalités dues au COVID les plus élevées au monde. MÉTHODES: SES et le gouvernement ont identifié des besoins non satisfaits en matière de santé de la population, qui pourraient faire l'objet d'interventions virtuelles. Des chatbots ont été développés pour dépister des individus pour ces conditions ; nous décrivons la période de leur déploiement, le nombre de dépistages et le nombre de personnes qui ont reçu ces services. RÉSULTATS: Entre avril 2020 et mai 2021, SES a déployé neuf ChatBots : quatre pour la santé mentale, deux pour la santé maternelle et infantile et trois pour les maladies chroniques, comme le cancer du sein, l'hypertension, le diabète et l'obésité. Des services de santé mentale ont été fournis à 42 932 personnes, soit 99,99% des personnes proposées. Les autres ChatBots ont touché moins de personnes. Dans l'ensemble, plus de 50% des personnes éligibles ont accepté les services proposés par les chatbots. DISCUSSION: L'utilisation des ChatBots était la plus élevée pour la santé mentale. Les chatbots peuvent augmenter les connexions entre une population vulnérable et les services de santé, mais cela dépende de plusieurs facteurs, dont la condition, la type de population et la pénétration des smartphones. Les recherches futures seront essentielles pour comprendre l'expérience et les préférences des utilisateurs et pour s'assurer que les chatbots relient les populations vulnérables vulnérables aux soins appropriés et de qualité.

Multisystemic alterations in humans induced by bisphenol A and phthalates: Experimental, epidemiological and clinical studies reveal the need to change health policies.

A vast amount of evidence indicates that bisphenol A (BPA) and phthalates are widely distributed in the environment since these compounds are mass-produced for the manufacture of plastics and plasticizers. These compounds belong to a large group of substances termed endocrine-disrupting chemicals (EDC). It is well known that humans and living organisms are unavoidably and unintentionally exposed to BPA and phthalates from food packaging materials and many other everyday products. BPA and phthalates exert their effect by interfering with hormone synthesis, bioavailability, and action, thereby altering cellular proliferation and differentiation, tissue development, and the regulation of several physiological processes. In fact, these EDC can alter fetal programming at an epigenetic level, which can be transgenerational transmitted and may be involved in the development of various chronic pathologies later in the adulthood, including metabolic, reproductive and degenerative diseases, and certain types of cancer. In this review, we describe the most recent proposed mechanisms of action of these EDC and offer a compelling selection of experimental, epidemiological and clinical studies, which show evidence of how exposure to these pollutants affects our health during development, and their association with a wide range of reproductive, metabolic and neurological diseases, as well as hormone-related cancers. We stress the importance of concern in the general population and the urgent need for the medical health care system to closely monitor EDC levels in the population due to unavoidable and involuntary exposure to these pollutants and their impact on human health.

Lung genotoxicity of benzo(a)pyrene in vivo involves reactivation of LINE-1 retrotransposon and early reprogramming of oncogenic regulatory networks.

Several lines of evidence have implicated long interspersed nuclear element-1 (LINE-1) retroelement in the onset and progression of lung cancer. Retrotransposition-dependent mechanisms leading to DNA mobilization give rise to insertion mutations and DNA deletions, whereas retrotransposition-independent mechanisms disrupt epithelial programming and differentiation. Previous work by our group established that tobacco carcinogens such as benzo(a)pyrene (BaP) reactivate LINE-1 in bronchial epithelial cells through displacement of nucleosome remodeling and deacetylase (NuRD) corepressor complexes and interference with retinoblastoma-regulated epigenetic signaling. Whether LINE-1 in coordination with other genes within its regulatory network contributes to the in vivo genotoxic response to BaP remains largely unknown. Evidence is presented here that intratracheal instillation of ORFeusLSL mice with BaP alone or in combination with adenovirus (adeno)-CRE recombinase is genotoxic to the lung and associated with activation of the human LINE-1 transgene present in these mice. LINE-1 reactivation modulated the expression of genes involved in oncogenic signaling, and these responses were most pronounced in female mice compared with males and synergized by adeno-CRE recombinase. This is the first report linking LINE-1 and genes within its oncogenic regulatory network with early sexually dimorphic responses of the lung in vivo.

NADH-linked mitochondrial respiration in the developing mouse brain is sex-, age- and tissue-dependent.

Mitochondria play a major role in the brain. Apart from energy production, mitochondria regulate key factors in the activation of cell signaling pathways such as survival, proliferation, and differentiation. While all these processes occur during the physiological development of the brain, it is surprising that the mitochondrial functions and functioning in the brain during the postnatal development remain poorly explored. In this work, we collected samples of brainstem and cortex of mice at postnatal ages 3 (P3), 21 (P21), and at adulthood (3 months old) and evaluated the mitochondrial oxygen consumption after complex I activation. To do so, we used our oxygraph-2 K system (OROBOROS) that measures the mitochondrial bioenergetics in saponin-permeabilized tissue punches of 2  mg weight. Furthermore, as sex dimorphism in the brain occurs since very early stages of development, we performed experiments in brain samples of male and female mice. Accordingly, the mitochondrial oxygen consumption rate (OCR) was evaluated under activation of complex I (NADH-linked respiration - mitochondrial state 3), and during the inhibition of the complex V (ATP synthase) with oligomycin (mitochondrial state 4). In following, the respiratory control ratio (RCR - state 3/state4) was calculated as an index of mitochondrial oxidative-phosphorylation coupling. Our results show that the activity of the mitochondrial complex I in the brain increases along with the postnatal development in a sex- and tissue-dependent manner, with males showing higher activity than females, and with brainstem tissue showing higher activity than cortex. Our data may contribute to a better understanding of the sex-dependent maturation of the cortex and the cardiorespiratory network located in the brainstem.

A computerized scoring system to improve assessment of heparin-induced thrombocytopenia risk.

Essentials Current risk scores for heparin-induced thrombocytopenia (HIT) are not computer-friendly. We compared a new computerized risk score with the 4Ts score in a large healthcare system. The computerized risk score agrees with the 4Ts score 85% of the time. The new score could potentially improve HIT diagnosis via incorporation into decision support. SUMMARY: Background (HIT) is an immune-mediated adverse drug event associated with life-threatening thrombotic complications. The 4Ts score is widely used to estimate the risk for HIT and guide diagnostic testing, but it is not easily amenable to computerized clinical decision support (CDS) implementation. Objectives Our main objective was to develop an HIT computerized risk (HIT-CR) scoring system that provides platelet count surveillance for timing and degree of thrombocytopenia to identify those for whom diagnostic testing should be considered. Our secondary objective was to evaluate clinical management and subsequent outcomes in those identified as being at risk for HIT. Methods We retrospectively analyzed data from a stratified sample of 150 inpatients treated with heparin to compare the performance of the HIT-CR scoring system with that of a clinically calculated 4Ts score. We took a 4Ts score of ≥ 4 as the gold standard to determine whether HIT diagnostic testing should be performed. Results The best cutoff point of the HIT-CR score was a score of 3, which yielded 85% raw agreement with the 4Ts score and a kappa of 0.69 (95% confidence interval 0.57-0.81). Ninety per cent of patients with 4Ts score of ≥ 4 failed to undergo conventionally recommended diagnostic testing; 38% of these experienced persistent, unexplained thrombocytopenia, and 4% suffered life-threatening thrombotic complications suggestive of undiagnosed HIT. Conclusion The HIT-CR scoring system is practical for computerized CDS, agrees well with the 4Ts score, and should be prospectively evaluated for its ability to identify patients who should be tested for HIT.

Imaging the dome of Santa Maria del Fiore using cosmic rays.

The dome of Santa Maria del Fiore, Florence Cathedral, was built between 1420 and 1436 by architect Filippo Brunelleschi and it is now cracking under its own weight. Engineering efforts are under way to model the dome's structure and reinforce it against further deterioration. According to some scholars, Brunelleschi might have built reinforcement structures into the dome itself; however, the only known reinforcement is a wood chain 7.75 m above the springing of the Cupola. Multiple scattering muon radiography is a non-destructive imaging method that can be used to image the interior of the dome's wall and therefore ascertain the layout and status of any iron substructure in it. A demonstration measurement was performed at the Los Alamos National Laboratory on a mock-up wall to show the feasibility of the work proposed, and a lightweight and modular imaging system is currently under construction. We will discuss here the results of the demonstration measurement and the potential of the proposed technique, describe the imaging system under construction and outline the plans for the measurement.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

Line-1: Implications in the etiology of cancer, clinical applications, and pharmacologic targets.

Long interspersed nuclear elements-1 (Line-1 or L1) accounts for approximately 17% of the human genome. The majority of L1s are inactive, but ∼100 remain retrotransposon competent (RC-L1) and able to retrotranspose through RNA intermediates to different locations of the genome. L1 is involved in both disease initiation and progression via retrotransposition dependent and independent mechanisms. Retrotransposed L1 sequences disrupt genetic loci at sites of insertion, while the activities of L1 si/piRNAs, mRNAs, and ORF1 and ORF2 proteins, and have been implicated in the etiology and progression of several human diseases. Despite these relationships, little is known about the clinical utility of L1 as a biomarker of disease initiation and progression, or the utility of small molecules to inhibit and reverse the harmful effects of L1. In this review, we discuss the life cycle of L1, somatic and germline inhibitions, the mechanisms of L1 retrotransposition dependent and independent disease initiation and progression, clinical utilities, and potential of L1s as pharmacologic targets for the treatment of cancer.

Preparing to launch the 'Thinking Healthy Programme' perinatal depression intervention in Urban Lima, Peru: experiences from the field.

BACKGROUND: An estimated 19-25% of perinatal women in low- and middle-income countries are affected by depression which, untreated, is associated with multiple health problems for mothers and children. Nonetheless, few perinatal women have access to depression care. The Thinking Healthy Programme (THP), promoted by the World Health Organization (WHO), is an evidence-based, non-specialist delivered depression intervention that addresses this care gap. However, the WHO THP manual explains intervention delivery but not the antecedents to implementation. Here, we describe a principled, planned approach leading to the implementation of THP in Lima, Peru by the non-profit organization Socios En Salud with community health workers (CHW) to inform its implementation in other settings. METHODS: The Replicating Effective Programs (REP) framework guided THP implementation, following four phases: (I) pre-conditions; (II) pre-implementation; (III) implementation; and (IV) maintenance and evolution. This paper centers on REP phases I and II, including (1) documented high perinatal depression rates in Peru; (2) designation of perinatal depression as a government priority; (3) THP Implementation Team orientation and training; (4) data collection plan development; (5) public health system coordination; (6) CHW selection and training; and (7) THP launch. RESULTS: Between December 2016 and March 2017, a THP training program was developed and seven CHW were trained to deliver the intervention to 10 perinatal women, the first of whom was enrolled on 17 April 2017. CONCLUSIONS: THP was rapidly implemented by a community-based organization with no prior experience in delivering non-specialist perinatal depression care. The steps followed may inform the implementation of THP in other settings.

Simultaneous characterisation of silver nanoparticles and determination of dissolved silver in chicken meat subjected to in vitro human gastrointestinal digestion using single particle inductively coupled plasma mass spectrometry.

In this study, a chicken meat containing AgNPs (candidate reference material Nanolyse 14) has been used as a model matrix to study the fate and behaviour of AgNPs upon oral ingestion following an in vitro model that included saliva, gastric and intestinal digestions. The behaviour of a 40nm AgNPs standard solution during the three digestion steps was also evaluated. Sample preparation conditions were optimised to prevent AgNPs oxidation and/or aggregation and to ensure the representativeness of the reported results. Total silver released from the test sample and the evaluated AgNP standard was determined by inductively coupled plasma mass spectrometry (ICPMS). The presence of both AgNPs and dissolved silver in the extracts was confirmed by single particle (SP)-ICPMS analysis. AgNPs were sized and the particle number concentration determined in the three digestion juices. Experimental results demonstrated differentiated behaviours for AgNP from the standard solution and the meat sample highlighting the relevance of using physiological conditions for accurate risk assessment. In the most realistic scenario assayed (i.e., spiked chicken meat analysis), only 13% of the AgNPs present in the reference material would reach the intestine wall. Meanwhile, other bioaccessible dissolved forms of silver would account for as much as 44% of the silver initially spiked to the meat paste.

Free Energy Based Equation of State for Pentaerythritol Tetranitrate.

An equation of state for the energetic molecular crystal pentaerythritol tetranitrate (PETN) has been developed from a parametrized model for its Helmholtz free energy. The ion motion contribution to the free energy is represented by a sum of Debye models for the vibrational modes of mainly lattice phonon and intramolecular character. The dependence of the frequencies of the normal modes on density is captured using the quasi-harmonic approximation whereby the Debye temperatures for both populations of modes depend explicitly on specific volume. The dependence of the Debye temperatures on specific volume was parametrized to normal-mode frequencies computed from solid state dispersion-corrected density functional theory. The model provides a good description of the thermophysical properties of PETN. The equation of state has been applied to the calculation of thermodynamic states along the principal Hugoniot of single crystal PETN.

A study of CR-39 plastic charged-particle detector replacement by consumer imaging sensors.

Consumer imaging sensors (CIS) are examined for real-time charged-particle detection and CR-39 plastic detector replacement. Removing cover glass from CIS is hard if not impossible, in particular for the latest inexpensive webcam models. We show that $10-class CIS are sensitive to MeV and higher energy protons and α-particles by using a 90Sr ß-source with its cover glass in place. Indirect, real-time, high-resolution detection is also feasible when combining CIS with a ZnS:Ag phosphor screen and optics. Noise reduction in CIS is nevertheless important for the indirect approach.

Silver speciation and characterization of nanoparticles released from plastic food containers by single particle ICPMS.

Silver migration from a commercial baby feeding bottle and a food box containing AgNPs, as confirmed by SEM-EDX analysis, was evaluated using food simulant solutions [i.e., water, 3% (v/v) acetic acid, and 10% and 90% (v/v) ethanol]. Silver release was investigated at temperatures in the 20-70°C range using contact times of up to 10 days. Migration of silver from the food box was in all cases 2 to 3 orders of magnitude higher than that observed for the baby bottle, although the total silver content in the original box material was half of that found in the baby bottle. As expected, for both food containers, silver migration depended on both the nature of the tested solution and the applied conditions. The highest release was observed for 3% acetic acid at 70°C for 2h, corresponding to 62ngdm(2) and 1887ngdm(-2) of silver for the baby bottle and the food box, respectively. Single particle-inductively coupled plasma mass spectrometry (SP-ICPMS) was used to characterise and quantify AgNPs in the food simulants extracts. Sample preparation was optimized to preserve AgNPs integrity. The experimental parameters affecting AgNPs detection, sizing and quantification by SP-ICPMS were also optimised. Analyses of water and acidic extracts revealed the presence of both dissolved silver and AgNPs. Small AgNPs (in the 18-30nm range) and particle number concentrations within the 4-1510 10(6)L(-1) range were detected, corresponding to only 0.1-8.6% of the total silver released from these materials. The only exception was AgNPs migrated into water at 40°C and 70°C from the food box, which accounted for as much as 34% and 69% of the total silver content, respectively.

Óleos essenciais e vegetais no controle in vitro de Colletotrichum gloeosporioides / Essential and vegetal oils in the in vitro control of Colletotrichum gloeosporioides

RESUMO O objetivo deste trabalho foi avaliar a atividade antifúngica de óleos essenciais e vegetais no controle in vitro de Colletotrichum gloeosporioides, agente causal da antracnose em pós-colheita de frutíferas. Treze óleos essenciais foram utilizados em concentrações de 0,00%, 0,40%, 0,80%, 1,70%, 3,20%, 6,25%, 12,50%, 25,00%, 50,00% e 100,00%, e uma linhagem padrão de Colletotrichum gloeosporioides. Foram avaliadas a concentração inibitória mínima e a concentração mínima fungicida a fim de caracterizar o potencial de cada um dos óleos essenciais avaliados. Verificou-se que os óleos utilizados apresentaram atividade fungicida em diferentes concentrações, as quais variaram de 0,80% (melaleuca), 3,20%, (eucalipto), 6,25% (limão, capim limão, cravo da índia, canela e nim), 12,5% (hortelã e citronela), 25% (copaíba), 50% (coco e gengibre) e 100% (manjericão). O óleo de nim apresentou maior redução da carga microbiana em função do tempo de exposição, sendo necessários 30 minutos para anulação da contagem microbiana. O efeito antifúngico dos óleos essenciais, para controle de Colletotrichum gloeosporioides, depende da planta e da concentração empregada.

ABSTRACT This study aimed to evaluate the antifungal effect of essential and vegetal oils in the in vitro control of Colletotrichum gloeosporioides, a causal agent of anthracnose in fruit postharvest. Thirteen essential oils were used at concentrations of 0.00%, 0.40%, 0.80%, 1.70%, 3.20%, 6.25%, 12.50%, 25.00%, 50.00%, and 100.00%, and also a standard strain of Colletotrichum gloeosporioides, The minimum inhibitory concentration and minimum fungicidal concentration were assessed to characterize the potential of each of the essential oils tested. We found that used oils showed fungicidal activity at different concentrations, which varied in 0.80% (Melaleuca alternifólia), 3.20%, (Eucalyptus globulus), 6.25% (Citrus limonium, Cymbopogon citratus, Syzygium aromaticum, Cinnamomum zeylanicum, and Azadirachta indica), 12.5% (Mentha piperita and Cymbopogon winterianus), 25% (Copaifera langsdorfii), 50% (Cocos nucifera and Zingiber officinale), and 100% (Ocimum basilicum). The Azadirachta indica oil showed greater reduction of microbial load because of the exposure time, and took 30 minutes for annulment of microbial count. The antifungal effect of essential oils to control Colletotrichum gloeosporioides depends on the plant and quantity of concentration.

Migration and characterisation of nanosilver from food containers by AF4-ICP-MS.

In this work, silver migration from commercial food containers was evaluated according to European Regulation 10/2011. Several experimental parameters affected silver release: food simulant, temperature, exposition time and sampled bag area. Results demonstrated a significant silver nanoparticle (AgNP) migration into aqueous and acidic simulants. The amount of silver migrated increased with storage time and temperature although, in general, silver showed a low tendency to migrate into food simulants (17 ng/g). However, the food simulant did not seem to be a really outstanding variable for long term storage. AF(4)-ICP MS was used to confirm the presence of AgNPs in the simulants. The low limit of detection achieved (0.4 µg L(-1)) allowed the identification of AgNPs and their size characterisation (40-60 nm). Finally, scanning electron microscopy/energy-dispersive X-ray analysis suggested a possible transformation of the AgNPs detected in the extracts, due to association with other ligands, such as chlorine and sulphur, present in the original containers.

Characterization and quantification of silver nanoparticles in nutraceuticals and beverages by asymmetric flow field flow fractionation coupled with inductively coupled plasma mass spectrometry.

This study evaluated the feasibility of asymmetric flow field flow fractionation coupled with inductively coupled plasma mass spectrometry (AF4-ICP-MS) for separation, characterization and quantification of silver nanoparticles (AgNPs) in complex nutraceutical and beverage samples. For improved determination, different analysis conditions were proposed depending on the NP size, i.e. below 20 nm and in the 20-60 nm range. After optimization of the different experimental parameters affecting the AF4 separation process and the analyte detection, the proposed methods showed a wide dynamic linear range (i.e., in the 10-1000 µg L(-1)) and limits of detection below 28 ng L(-1). A previous probe ultrasonication for 90 s (corresponding to 45 pulses of 2 s) of the tested samples resulted in complete AgNPs disaggregation. As a result, a fast accurate determination was achieved (complete analysis was done in ca. 37 min). The practicality of the proposed methodology for the intended determination was demonstrated by successful determination of the AgNPs present in a variety of nutraceuticals and a beverage at concentration levels in the 0.7-29.5×10(3) µg L(-1) range. A good agreement was observed among these concentration data and those determined by more conventional sample preparation techniques, such as ultracentrifugation and acid digestion. Also, the estimated NP sizes using AF4 compared satisfactorily with those determined by image techniques, i.e. transmission electron microscopy (TEM). All together demonstrated the utility of this novel analytical methodology for the analysis of AgNPs of different size in complex matrices.

Activation of adult rat CNS endothelial cells by opioid-induced toll-like receptor 4 (TLR4) signaling induces proinflammatory, biochemical, morphological, and behavioral sequelae.

CNS immune signaling contributes to deleterious opioid effects including hyperalgesia, tolerance, reward, and dependence/withdrawal. Such effects are mediated by opioid signaling at toll-like receptor 4 (TLR4), presumptively of glial origin. Whether CNS endothelial cells express TLR4 is controversial. If so, they would be well positioned for activation by blood-borne opioids, contributing to opioid-induced pro-inflammatory responses. These studies examined adult primary rat CNS endothelial cell responses to (-)-morphine or its mu opioid receptor (MOR)-inactive metabolite morphine-3-glucuronide (M3G), both known TLR4 agonists. We demonstrate that adult rat CNS endothelial cells express functional TLR4. M3G activated nuclear factor kappaB (NF-κB), increased tumor necrosis factor-α (TNFα) and cyclooxygenase-2 (COX2) mRNAs, and released prostaglandin E2 (PGE2) from these cells. (-)-Morphine-induced upregulation of TNFα mRNA and PGE2 release were unmasked by pre-treatment with nalmefene, a MOR antagonist without TLR4 activity (unlike CTAP, shown to have both MOR- and TLR4-activity), suggestive of an interplay between MOR and TLR4 co-activation by (-)-morphine. In support, MOR-dependent Protein Kinase A (PKA) opposed TLR4 signaling, as PKA inhibition (H-89) also unmasked (-)-morphine-induced TNFα and COX2 mRNA upregulation. Intrathecal injection of CNS endothelial cells, stimulated in vitro with M3G, produced TLR4-dependent tactile allodynia. Further, cortical suffusion with M3G in vivo induced TLR4-dependent vasodilation. Finally, endothelial cell TLR4 activation by lipopolysaccharide and/or M3G was blocked by the glial inhibitors AV1013 and propentofylline, demonstrating endothelial cells as a new target of such drugs. These data indicate that (-)-morphine and M3G can activate CNS endothelial cells via TLR4, inducing proinflammatory, biochemical, morphological, and behavioral sequelae. CNS endothelial cells may have previously unanticipated roles in opioid-induced effects, in phenomena blocked by presumptive glial inhibitors, as well as TLR4-mediated phenomena more broadly.

Line-imaging velocimetry for observing spatially heterogeneous mechanical and chemical responses in plastic bonded explosives during impact.

A line-imaging velocity interferometer was implemented on a single-stage light gas gun to probe the spatial heterogeneity of mechanical response, chemical reaction, and initiation of detonation in explosives. The instrument is described in detail, and then data are presented on several shock-compressed materials to demonstrate the instrument performance on both homogeneous and heterogeneous samples. The noise floor of this diagnostic was determined to be 0.24 rad with a shot on elastically compressed sapphire. The diagnostic was then applied to two heterogeneous plastic bonded explosives: 3,3(')-diaminoazoxyfurazan (DAAF) and PBX 9501, where significant spatial velocity heterogeneity was observed during the build up to detonation. In PBX 9501, the velocity heterogeneity was consistent with the explosive grain size, however in DAAF, we observed heterogeneity on a much larger length scale than the grain size that was similar to the imaging resolution of the instrument.

Impact system for ultrafast synchrotron experiments.

The impact system for ultrafast synchrotron experiments, or IMPULSE, is a 12.6-mm bore light-gas gun (<1 km/s projectile velocity) designed specifically for performing dynamic compression experiments using the advanced imaging and X-ray diffraction methods available at synchrotron sources. The gun system, capable of reaching projectile velocities up to 1 km/s, was designed to be portable for quick insertion/removal in the experimental hutch at Sector 32 ID-B of the Advanced Photon Source (Argonne, IL) while allowing the target chamber to rotate for sample alignment with the beam. A key challenge in using the gun system to acquire dynamic data on the nanosecond time scale was synchronization (or bracketing) of the impact event with the incident X-ray pulses (80 ps width). A description of the basic gun system used in previous work is provided along with details of an improved launch initiation system designed to significantly reduce the total system time from launch initiation to impact. Experiments were performed to directly measure the gun system time and to determine the gun performance curve for projectile velocities ranging from 0.3 to 0.9 km/s. All results show an average system time of 21.6 ± 4.5 ms, making it possible to better synchronize the gun system and detectors to the X-ray beam.