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Abstract All historical eruptions at Ruapehu have occurred from its Crater Lake, Te Wai ā-moe. This study aims to better understand Crater Lake dynamics by using visible light and long wavelength infrared images of the lake. Over 10,000 images from 1902 – 2021 were analysed to produce a time-series of lake observations. Our results show that visible light observations reveal colour changes on the entire Crater Lake surface from blue to grey, and localised grey, yellow, and black discolourations. Grey discolourations are interpreted as localised upwellings of lake-floor sediment, and yellow and black material to comprise vent-hosted sulphur/sulphides, both transported by volcanic fluids from subaqueous vents to the surface. The locations of upwellings were used to identify five vent locations beneath Crater Lake, three more vents than were previously recognised. Upwellings appeared and disappeared in 10 min. Steam above the lake surface was controlled by both lake temperature and cloud conditions. Blue lakes were most common in summer and autumn, implying a relationship with ice or snow melt entering the lake. Grey lakes were observed in the month before 97% of eruptions, suggesting a correlation between a grey lake and eruption precursors. Crater Lake processes are illustrated by three regimes. Regime 1, a vigorously convecting grey lake associated with steam, eruptions, and more frequently the high end of recorded lake temperatures (within the range of 7 – 69 °C). Regime 2, a blue lake to occasionally green that typically occurs in summer and autumn when ice or snow melt is significant and is associated with generally the low end of lake temperatures and reduced volcanic fluid input. Regime 3, a blue-grey lake, the most observed lake colour in this study and effectively a balance between volcanic and seasonal processes. We suggest that an array of cameras would be useful additions to the current volcano monitoring network at Ruapehu.

Accurate volcanic hazard assessments rely on a detailed understanding of the timing of past eruptions. While radiometric methods like 40Ar/39Ar or K/Ar are by far the most conventional lava flow dating tools, their low resolution for young ( ka) deposits interferes with the development of precise chronologies of recent effusive activity on most volcanoes. Mt Ruapehu (Aotearoa / New Zealand) has produced many lava flows throughout its history, but the precise timing of many recent eruptions remains largely unknown. In this study, we use cosmogenic 3He exposure dating to provide 23 eruption ages of young lava flows at Ruapehu. We then compare our results with existing 40Ar/39Ar and paleomagnetic constraints, highlighting the value of cosmogenic nuclide exposure dating in refining recent eruptive chronologies. Of the 23 sampled flows, 16 provided robust eruption ages (5 %–20 % internal 2σ; n≥3) between ca. 20 and 8 ka, except for one lava flow that erupted at around 43 ka, and their age distribution indicates that, during the last 20 kyr, effusive activity at Ruapehu peaked at 17–12 ka and at 9–7.5 ka. Nearly identical eruption ages of lavas located in different flanks of the volcanic edifice suggest concurrent activity from multiple vents during relatively short time intervals (0–2 kyr) at around 13, 10, and 8 ka. We analysed four individual lava flows previously dated by 40Ar/39Ar, two of which yield eruption ages older than the older limit of the 2σ interval of the radiometric dates, but the good clustering of individual samples from our sites suggests that our results better represent the real eruption age of these flows. Our 3He-based chronology shows excellent agreement with paleomagnetic constraints, suggesting that production rate uncertainties are unlikely to impact the accuracy of our eruption ages. This study demonstrates how cosmogenic nuclide dating can provide greater detail on the recent effusive chronology of stratovolcanoes, helping to resolve the low resolution of and difficulty in applying radiometric dating methods to young lava flows.

IntroductionIntrapleural injections of cholera toxin B conjugated to saporin (CTB-SAP) result in selective respiratory (e.g., phrenic) motor neuron death and mimics aspects of motor neuron disease [(e.g., amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA)], such as breathing deficits. This rodent model allows us to study the impact motor neuron death has on the output of surviving phrenic motor neurons as well as the compensatory mechanisms that are recruited. Microglial density in the phrenic motor nucleus as well as cervical gene expression of markers associated with inflammation (e.g., tumor necrosis factor α; TNF-α) are increased following CTB-SAP-induced phrenic motor neuron death, and ketoprofen (nonsteroidal anti-inflammatory drug) delivery attenuated phrenic long-term facilitation (pLTF) in 7 day (d) CTB-SAP rats but enhanced pLTF in 28d CTB-SAP rats.MethodsHere, we worked to determine the impact of TNF-α in the phrenic motor nucleus by: 1) quantifying TNFR1 (a high affinity transmembrane receptor for TNF-α) expression; 2) investigating astrocytes (glial cells known to release TNF-α) by performing a morphological analysis in the phrenic motor nucleus; and 3) determining whether acute TNFR1 inhibition differentially affects phrenic plasticity over the course of CTB-SAP-induced motor neuron loss by delivering an inhibitor for TNF-α receptor 1 (sTNFR1i) in 7d and 28d male CTB-SAP and control rats.ResultsResults revealed that TNFR1 expression was increased on phrenic motor neurons of 28d CTB-SAP rats (p < 0.05), and that astrocytes were increased and exhibited reactive morphology (consistent with an activated phenotype; p < 0.05) in the phrenic motor nucleus of CTB-SAP rats. Additionally, we found that pLTF was attenuated in 7d CTB-SAP rats but enhanced in 28d CTB-SAP rats (p < 0.05) following intrathecal sTNFR1i delivery.ConclusionThis work suggests that we could harness TNFR1 as a potential therapeutic agent in CTB-SAP rats and patients with respiratory motor neuron disease by increasing compensatory plasticity in surviving neurons to improve phrenic motor neuron function and breathing as well as quality of life. Future studies will focus on microglial and astrocytic cytokine release, the role they play in the differential mechanisms of pLTF utilized by 7d and 28d CTB-SAP rats, and potential therapies that target them.

Silicic caldera volcanoes present major volcanic and seismic hazards but also host dynamic hydrothermal and groundwater systems and a rich but largely unexplored subsurface biosphere. Many of these volcanoes are hosted in rift settings. The intricate connections and feedbacks among magmatism, rifting, hydrothermal processes, and the biosphere in these complex systems remain poorly understood, necessitating subsurface joint observations that are only enabled by scientific drilling. The CALDERA (Connections Among Life, geo-Dynamics and Eruptions in a Rifting Arc caldera) project workshop funded by the International Continental Scientific Drilling Program (ICDP) gathered multi-disciplinary international experts in January 2023 to advance planning of a scientific drilling project within one of these dynamic, rift-hosted calderas, the Okataina Volcanic Centre (OVC), Aotearoa New Zealand. The OVC's high eruption rate, frequent unrest events and earthquake swarms, location in a densely faulted rapidly extending rift, abundant groundwater–geothermal fluid circulations, and diverse surface hot spring microbiota make it an ideal location for exploring a connected geo-hydro-biosphere via scientific drilling and developing a test bed for novel volcano monitoring approaches. Drilling configurations with at least two boreholes (∼ 200 and ∼ 1000–1500 m deep) were favoured to achieve the multi-disciplinary objectives of the CALDERA project. Decadal monitoring including biosphere activity and composition has the potential to evaluate the response of the hydro-bio system to volcano-tectonic activity. In addition to the OVC caldera-scale datasets already available, site surveys will be conducted to select the best drilling locations. The CALDERA project at the OVC would provide, for the first time, an understanding of volcanic–tectonic–hydrological–biological connections in a caldera–rift system and a baseline for global comparisons with other volcanoes, rifts, and hydrothermal systems. CALDERA would serve as an unprecedented model system to understand how and how quickly the subsurface biosphere responds to geologic activities. Discoveries will improve assessment of volcanic and seismic hazards, guide the sustainable management and/or conservation of groundwater and geothermal resources and microbial ecosystems, and provide a forum for interweaving mātauranga Māori and Western knowledge systems.

Abstract Dating young lava flows is essential for understanding volcano's eruption frequency, yet challenging due to methodological limitations of commonly used dating techniques. Ruapehu (Aotearoa New Zealand) produced many lava flows during the Holocene, but constraints on the timing of these eruptions are scarce. Here, we use paleomagnetic dating to deliver new eruption ages of 18 lava flows with uncertainties ranging between 500 and 2,700 years (at the 95% confidence level). Comparison between lava flows' paleomagnetic directions and a local paleosecular variation record indicates that the large lava flow field located on the Whakapapa area was emplaced during at least three distinct eruptive episodes between 10600 and 7400 BP. Two of these episodes closely followed a large collapse event that affected Ruapehu's northern area and generated large volumes of lava between 10600 and 8800 BP, with the third episode producing less voluminous lava flows between 8100 and 7400 BP. Following a smaller collapse of the southeastern sector of the edifice at ca. 5300 BP, several low‐volume lava flows were emplaced during at least two distinct eruptive episodes prior to ca. 1000 BP, which supplied the Whangaehu valley with lava. The youngest age inferred from our data represents the youngest eruption age provided for a lava flow outside Ruapehu's summit region. This research provides greater detail to the Holocene effusive chronology at Ruapehu, shedding light on partial cone reconstructions after edifice collapses during the Holocene, and the time relationships between trends observed in its effusive and explosive activity.

IntroductionTongue weakness and atrophy can lead to deficits in the vital functions of breathing and swallowing in patients with motor neuron diseases (MNDs; e.g., amyotrophic lateral sclerosis (ALS) and pseudobulbar palsy), often resulting in aspiration pneumonia, respiratory failure, and death. Available treatments for patients with MNDs are largely palliative; thus, there is a critical need for therapies targeting preservation of upper airway function and suggesting a role for tongue exercise in patients with MNDs. Here, we leveraged our inducible rodent model of hypoglossal (XII) motor neuron degeneration to investigate the effects of a strength endurance tongue exercise program on upper airway structure and function. Our model was created through intralingual injection of cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue to induce targeted death of XII motor neurons.MethodsRats in this study were allocated to 4 experimental groups that received intralingual injection of either CTB-SAP or unconjugated CTB + SAP (i.e., control) +/- tongue exercise. Following tongue exercise exposure, we evaluated the effect on respiratory function (via plethysmography), macrostructure [via magnetic resonance imaging (MRI) of the upper airway and tongue], and ultrafine structure [via ex vivo magnetic resonance spectroscopy (MRS) of the tongue] with a focus on lipid profiles.ResultsResults showed that sham exercise-treated CTB-SAP rats have evidence of upper airway restriction (i.e., reduced airflow) and structural changes present in the upper airway (i.e., airway compression) when compared to CTB-SAP + exercise rats and control rats +/- tongue exercise, which was ameliorated with tongue exercise. Additionally, CTB-SAP + sham exercise rats have evidence of increased lipid expression in the tongue consistent with previously observed tongue hypertrophy when compared to CTB-SAP + exercise rats or control rats +/- tongue exercise.ConclusionThese findings provide further evidence that a strength endurance tongue exercise program may be a viable therapeutic treatment option in patients with XII motor neuron degeneration in MNDs such as ALS. Future directions will focus on investigating the underlying mechanism responsible for tongue exercise-induced plasticity in the hypoglossal-tongue axis, particularly inflammatory associated factors such as BDNF.

IntroductionDysmenorrhea is associated with increased risk of chronic pain and hyperalgesia. Menstruating individuals with dysmenorrhea are more likely to have elevated pain reactivity when experiencing experimental pain, than those without. However, no study has examined intragroup differences in reactions to experimentally induced pain for individuals with dysmenorrhea. The main aim of this study was to examine the relative roles of dysmenorrhea severity and interference in the experience of experimentally-induced pain.MethodsParticipants were 120 menstruating individuals involved in a larger research study examining the influence of expectations on experimentally-induced pain. As part of the study, participants completed an online questionnaire regarding demographic and menstrual information and participated in a cold pressor task. Participants were randomized into four groups based on the manipulation of two independent variables: (1) high vs. low expectations about pain severity (pain-expectations); (2) and high vs. low expectations about one's pain tolerance (self-expectations). Participants verbally rated their pain severity throughout the cold pressor task using a 0–10 scale. Regression analyses were conducted examining the relationships between dysmenorrhea experience (i.e., average severity and interference) and cold pressor data [pain severity ratings and pain tolerance (i.e., total time in the cold pressor)], controlling for the manipulated expectations and age. Then, moderation analyses were conducted examining expectation group differences.ResultsWhen controlling for manipulated expectations and age, dysmenorrhea severity significantly predicted initial pain severity rating (p = 0.022) but did not predict final pain severity rating (p = 0.263) or pain tolerance (p = 0.120). Dysmenorrhea interference did not predict initial pain severity rating (p = 0.106), final pain severity rating (p = 0.134), or pain tolerance (p = 0.360). A moderation analysis indicated that the relationship between dysmenorrhea severity and initial pain severity rating was not moderated by pain-expectations, χ2(1) = 0.412, p = 0.521.DiscussionDuring an experimentally-induced pain task, dysmenorrhea severity but not interference predicted initial pain severity rating, such that higher levels of dysmenorrhea severity predicted greater initial pain severity rating. This suggests individuals with more severe dysmenorrhea pain may experience greater initial sensitivity to pain and be at risk for increased sensitivity to acute pain and potentially the development of chronic pain.

Rotaviruses (RVs) are 11-segmented, double-stranded (ds) RNA viruses and important causes of acute gastroenteritis in humans and other animal species. Early RV particle assembly is a multi-step process that includes the assortment, packaging and replication of the 11 genome segments in close connection with capsid morphogenesis. This process occurs inside virally induced, cytosolic, membrane-less organelles called viroplasms. While many viral and cellular proteins play roles during early RV assembly, the octameric nonstructural protein 2 (NSP2) has emerged as a master orchestrator of this key stage of the viral replication cycle. NSP2 is critical for viroplasm biogenesis as well as for the selective RNA–RNA interactions that underpin the assortment of 11 viral genome segments. Moreover, NSP2’s associated enzymatic activities might serve to maintain nucleotide pools for use during viral genome replication, a process that is concurrent with early particle assembly. The goal of this review article is to summarize the available data about the structures, functions and interactions of RV NSP2 while also drawing attention to important unanswered questions in the field.

Abstract Background The survival of coronaviruses are influenced by weather conditions and seasonal coronaviruses are more common in winter months. We examine the seasonality of respiratory infections in England and Wales and the associations between weather parameters and seasonal coronavirus cases. Methods Respiratory virus disease data for England and Wales between 1989 and 2019 was extracted from the Second-Generation Surveillance System (SGSS) database used for routine surveillance. Seasonal coronaviruses from 2012 to 2019 were compared to daily average weather parameters for the period before the patient’s specimen date with a range of lag periods. Results The seasonal distribution of 985,524 viral infections in England and Wales (1989–2019) showed coronavirus infections had a similar seasonal distribution to influenza A and bocavirus, with a winter peak between weeks 2 to 8. Ninety percent of infections occurred where the daily mean ambient temperatures were below 10 °C; where daily average global radiation exceeded 500 kJ/m2/h; where sunshine was less than 5 h per day; or where relative humidity was above 80%. Coronavirus infections were significantly more common where daily average global radiation was under 300 kJ/m2/h (OR 4.3; CI 3.9–4.6; p

Abstract Background Rates of recommending percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) vary across clinicians. Whether clinicians agree on preferred treatment options for multivessel coronary artery disease patients has not been well studied. Methods and results We distributed a survey to 104 clinicians from the Northern New England Cardiovascular Study Group through email and at a regional meeting with 88 (84.6%) responses. The survey described three clinical vignettes of multivessel coronary artery disease patients. For each patient vignette participants selected appropriate treatment options and whether they would use a patient decision aid. The likelihood of choosing PCI only or PCI/CABG over CABG only was modeled using a multinomial regression. Across all vignettes, participants selected CABG only as an appropriate treatment option 24.2% of the time, PCI only 25.4% of the time, and both CABG or PCI as appropriate treatment options 50.4% of the time. Surgeons were less likely to choose PCI over CABG (RR 0.14, 95% CI 0.03, 0.59) or both treatments over CABG only (RR 0.10, 95% CI 0.03, 0.34) relative to cardiologists. Overall, 65% of participants responded they would use a patient decision aid with each vignette. Conclusions There is a lack of consensus on the appropriate treatment options across cardiologists and surgeons for patients with multivessel coronary artery disease. Treatment choice is influenced by both patient characteristics and clinician specialty.

Abstract Evolutionary arms races are broadly prevalent among organisms including bacteria, which have evolved defensive strategies against various attackers. A common microbial aggression mechanism is the type VI secretion system (T6SS), a contact-dependent bacterial weapon used to deliver toxic effector proteins into adjacent target cells. Sibling cells constitutively express immunity proteins that neutralize effectors. However, less is known about factors that protect non-sibling bacteria from T6SS attacks independently of cognate immunity proteins. In this study, we observe that human Escherichia coli commensal strains sensitive to T6SS attacks from Vibrio cholerae are protected when co-cultured with glucose. We confirm that glucose does not impair V. cholerae T6SS activity. Instead, we find that cells lacking the cAMP receptor protein (CRP), which regulates expression of hundreds of genes in response to glucose, survive significantly better against V. cholerae T6SS attacks even in the absence of glucose. Finally, we show that the glucose-mediated T6SS protection varies with different targets and killers. Our findings highlight the first example of an extracellular small molecule modulating a genetically controlled response for protection against T6SS attacks. This discovery may have major implications for microbial interactions during pathogen-host colonization and survival of bacteria in environmental communities.

Oligodendrocytes are the myelinating cell of the CNS and are critical for the functionality of the nervous system. In the packed CNS, we know distinct profiles of oligodendrocytes are present. Here, we used intravital imaging in zebrafish to identify a distinct oligodendrocyte lineage cell (OLC) that resides on the dorsal root ganglia sensory neurons in the spinal cord. Our profiling of OLC cellular dynamics revealed a distinct cell cluster that interacts with peripheral sensory neurons at the dorsal root entry zone (DREZ). With pharmacological, physical and genetic manipulations, we show that the entry of dorsal root ganglia pioneer axons across the DREZ is important to produce sensory located oligodendrocyte lineage cells. These oligodendrocyte lineage cells on peripherally derived sensory neurons display distinct processes that are stable and do not express mbpa. Upon their removal, sensory behavior related to the DRG neurons is abolished. Together, these data support the hypothesis that peripheral neurons at the DREZ can also impact oligodendrocyte development.

The tongue plays a crucial role in the swallowing process, and impairment can lead to dysphagia, particularly in motor neuron diseases (MNDs) resulting in hypoglossal-tongue axis degeneration (e.g., amyotrophic lateral sclerosis and progressive bulbar palsy). This study utilized our previously established inducible rodent model of dysphagia due to targeted degeneration of the hypoglossal-tongue axis. This model was created by injecting cholera toxin B conjugated to saporin (CTB-SAP) into the genioglossus muscle of the tongue base for retrograde transport to the hypoglossal (XII) nucleus via the hypoglossal nerve, which provides the sole motor control of the tongue. Our goal was to investigate the effect of high-repetition/low-resistance tongue exercise on tongue function, strength, and structure in four groups of male rats: (1) control + sham exercise (n = 13); (2) control + exercise (n = 10); (3) CTB-SAP + sham exercise (n = 13); and (4) CTB-SAP + exercise (n = 12). For each group, a custom spout with adjustable lick force requirement for fluid access was placed in the home cage overnight on days 4 and 6 post-tongue injection. For the two sham exercise groups, the lick force requirement was negligible. For the two exercise groups, the lick force requirement was set to ∼40% greater than the maximum voluntary lick force for individual rats. Following exercise exposure, we evaluated the effect on hypoglossal-tongue axis function (via videofluoroscopy), strength (via force-lickometer), and structure [via Magnetic Resonance Imaging (MRI) of the brainstem and tongue in a subset of rats]. Results showed that sham-exercised CTB-SAP rats had significant deficits in lick rate, swallow timing, and lick force. In exercised CTB-SAP rats, lick rate and lick force were preserved; however, swallow timing deficits persisted. MRI revealed corresponding degenerative changes in the hypoglossal-tongue axis that were mitigated by tongue exercise. These collective findings suggest that high-repetition/low-resistance tongue exercise in our model is a safe and effective treatment to prevent/diminish signs of hypoglossal-tongue axis degeneration. The next step is to leverage our rat model to optimize exercise dosing parameters and investigate corresponding treatment mechanisms of action for future translation to MND clinical trials.

Abstract Background Disaccharides such as lactose and sucrose are sugars commonly found in human diet. They are broken down by mucosal disaccharidases in the duodenum. Previous small studies found no associations between gastrointestinal (GI) symptoms and combined low disaccharidase activity. We aim to explore the associations of low activity of disaccharidase and combinations of low activity of different disaccharidases with general GI symptom presentations in a large cohort of pediatric patients. Methods We examined a cohort (0–21 yrs.) who have undergone esophagogastroduodenoscopy and received disaccharidase activity assay from duodenal biopsy in the time period 2010 to 2012. Disaccharidase assays tested for activity of lactase, sucrase, maltase, and palatinase. GI symptoms were grouped into four categories, abdominal pain, diarrhea, weight loss, and gastroesophageal reflux. Results Of the 347 subjects, we found an association between low lactase activity and abdominal pain (OR = 1.78; 95% CI = 1.07–2.97; p

Despite recent advances in reaction methodologies, organic synthesis remains complex and challenging. Many of the fundamental processes in use have not changed in over 100 years, with a large proportion of the work being carried out manually, using lengthy procedures and difficult or hazardous reaction conditions. As such, organic synthesis still presents a bottle-neck in discovery research. Endeavours to automate synthesis in discovery, through robotic platforms, have so far not been widely successful because the highly complex nature of such machines, and the level of skill required for their operation, presents a barrier too great for most discov- ery chemists. Synple Chem has developed a safe, easy to use, efficiency-enhancing automated technology for the acceleration of discovery research. The automated flow-batch hybrid system utilises a range of innovative pre-packed reagent cartridges for different reaction classes, along with pre-programmed, highly optimised but editable reaction protocols. The combination of these three key elements, provides users with a convenient, easy to use, time-saving technology that makes the synthesis of molecules far simpler, faster and more efficient. The described technology offers all discovery chemists access to real synthesis automation without any of the barriers that have previously restricted its utility.

Magma ascending in the Earth’s crust can undergo oscillations in pressure, from ultra-low frequency changes associated with tectonics, to relatively higher frequency oscillations associated with seismicity. Seismic waves travelling through shallow magma bodies can lead to a range of unrest phenomena and potentially trigger volcanic eruptions. The mechanisms by which pressure oscillations can induce unrest or eruption remain debated. Here, we experimentally impose pressure oscillations on magma and study how they affect vesiculation processes. We use cylindrical samples (4.00 mm long, 4.85 mm diameter) of hydrous rhyolitic obsidian (0.11 ± 0.01 wt% H2O) placed in alumina (AL23) crucibles and vary pressure by the uniaxial loading of an alumina plunger in a thermo-mechanical analyzer. We monitor vesiculation at temperatures of 950–990°C and confining pressure of 177 kPa. We perform two types of experiment: 1) “static” experiments (at constant pressure) and 2) “oscillating” experiments in which we impose sinusoidal pressure oscillations of up to 71 kPa upon the static pressure (i.e., between 106 and 250 kPa). In both cases, we dilatometrically observe sample expansion driven by vesiculation. Post-experimental bubble textures reveal that bubbles formed preferentially at the sample margins. For the oscillating experiments, the sample expansion rate is lower than in the static experiments, and there are fewer vesicles at the sample margins. We examine the constituent processes of bubble formation (nucleation, growth, coalescence) and gas loss (diffusion, permeable flow) occurring during static experiments and with the added element of pressure oscillations. The most likely mechanism responsible for reduced sample expansion is that pressure oscillations drive the sample in and out of water saturation conditions and thus reduce the fraction of residence time over which bubble nucleation and/or growth are driven. Future work will be needed to confirm this hypothesis. These results are relevant to the study of earthquake-volcano interactions, where a magma body that sits close to volatile saturation is subject to pressure fluctuations.

Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug-sensing fluorescent reporters (iDrugSnFRs) for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives – 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by >30-fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.

Abstract Basaltic lavas sample recycled crustal materials from their mantle source. Constraining the location and residence time of these recycled materials in the mantle is critical to understand global mantle dynamics. In this study, we present new whole‐rock major and trace element abundances, Sr‐Nd‐Mo‐Os isotopes, water contents and He isotopes of volcanic glasses, U‐Pb ages of zircons, and compositions of melt inclusions, spinels and olivines from the South China Sea (SCS) seamounts lavas. These new data are compared with literature data from intraplate volcanism of similar age from Southeast (SE) Asia. The isotope data of late Cenozoic lavas from the SCS seamounts and SE Asia can be explained by mixing between enriched mantle 2 (EM2) and depleted mid‐ocean ridge basalt mantle components. Our data are consistent with the EM2 signature of late Cenozoic lavas derived from recycled young oceanic crust and sediments. The compositions of olivine phenocrysts indicate an olivine‐dominated (peridotitic) mantle source. There is currently no evidence for a high‐3He/4He mantle plume component beneath the SCS. Our results combined with geophysical data and plate reconstructions suggest that the late Cenozoic magmatism is related to the upwelling of instabilities from the mantle transition zone (MTZ) triggered by a stagnant slab. The SCS seamount lavas sample an enriched MTZ containing young recycled materials, consistent with regional past subduction. Our study provides additional evidence that storage and recycling of crustal materials in or near the MTZ is an important mechanism to develop global mantle heterogeneities sampled by intraplate volcanoes.

Abstract Background Campylobacteriosis is a major public health concern. The weather factors that influence spatial and seasonal distributions are not fully understood. Methods To investigate the impacts of temperature and rainfall on Campylobacter infections in England and Wales, cases of Campylobacter were linked to local temperature and rainfall at laboratory postcodes in the 30 days before the specimen date. Methods for investigation included a comparative conditional incidence, wavelet, clustering, and time series analyses. Results The increase of Campylobacter infections in the late spring was significantly linked to temperature two weeks before, with an increase in conditional incidence of 0.175 cases per 100,000 per week for weeks 17 to 24; the relationship to temperature was not linear. Generalized structural time series model revealed that changes in temperature accounted for 33.3% of the expected cases of Campylobacteriosis, with an indication of the direction and relevant temperature range. Wavelet analysis showed a strong annual cycle with additional harmonics at four and six months. Cluster analysis showed three clusters of seasonality with geographic similarities representing metropolitan, rural, and other areas. Conclusions The association of Campylobacteriosis with temperature is likely to be indirect. High-resolution spatial temporal linkage of weather parameters and cases is important in improving weather associations with infectious diseases. The primary driver of Campylobacter incidence remains to be determined; other avenues, such as insect contamination of chicken flocks through poor biosecurity should be explored.

The fundamental mechanism of how sensory axons traverse a spinal cord glia limitans remains debatable, with some suggesting a role for boundary cap cells at the dorsal root entry zone (DREZ). Here, authors use time-lapse imaging of DRG axons at the DREZ to show that pioneer axons enter the DREZ before the presence of boundary cap cells, and that this entry is critically dependent on the development of actin-rich invasion structures reminiscent of invadopodia.

Host genetic variation plays an important role in the structure and function of heritable microbial communities. Recent studies have shown that insects use immune mechanisms to regulate heritable symbionts. Here we test the hypothesis that variation in symbiont density among hosts is linked to intraspecific differences in the immune response to harboring symbionts. We show that pea aphids (Acyrthosiphon pisum) harboring the bacterial endosymbiont Regiella insecticola (but not all other species of symbionts) downregulate expression of key immune genes. We then functionally link immune expression with symbiont density using RNAi. The pea aphid species complex is comprised of multiple reproductively-isolated host plant-adapted populations. These 'biotypes' have distinct patterns of symbiont infections: for example, aphids from the Trifolium biotype are strongly associated with Regiella. Using RNAseq, we compare patterns of gene expression in response to Regiella in aphid genotypes from multiple biotypes, and we show that Trifolium aphids experience no downregulation of immune gene expression while hosting Regiella and harbor symbionts at lower densities. Using F1 hybrids between two biotypes, we find that symbiont density and immune gene expression are both intermediate in hybrids. We propose that in this system, Regiella symbionts are suppressing aphid immune mechanisms to increase their density, but that some hosts have adapted to prevent immune suppression in order to control symbiont numbers. This work therefore suggests that antagonistic coevolution can play a role in host-microbe interactions even when symbionts are transmitted vertically and provide a clear benefit to their hosts. The specific immune mechanisms that we find are downregulated in the presence of Regiella have been previously shown to combat pathogens in aphids, and thus this work also highlights the immune system's complex dual role in interacting with both beneficial and harmful microbes.

Plants evolve innate immunity including resistance genes to defend against pest and pathogen attack. Our previous studies in cotton (Gossypium spp.) revealed that one telomeric segment on chromosome (Chr) 11 in G. hirsutum cv. Acala NemX (rkn1 locus) contributed to transgressive resistance to the plant parasitic nematode Meloidogyne incognita, but the highly homologous segment on homoeologous Chr 21 had no resistance contribution. To better understand the resistance mechanism, a bacterial chromosome (BAC) library of Acala N901 (Acala NemX resistance source) was used to select, sequence, and analyze BAC clones associated with SSR markers in the complex rkn1 resistance region. Sequence alignment with the susceptible G. hirsutum cv. TM-1 genome indicated that 23 BACs mapped to TM-1-Chr11 and 18 BACs mapped to TM-1-Chr 21. Genetic and physical mapping confirmed less BAC sequence (53–84%) mapped with the TM-1 genome in the rkn1 region on Chr 11 than to the homologous region (>89%) on Chr 21. A 3.1-cM genetic distance between the rkn1 flanking markers CIR316 and CIR069 was mapped in a Pima S-7 × Acala NemX RIL population with a physical distance ∼1 Mbp in TM-1. NCBI Blast and Gene annotation indicated that both Chr 11 and Chr 21 harbor resistance gene-rich cluster regions, but more multiple homologous copies of Resistance (R) proteins and of adjacent transposable elements (TE) are present within Chr 11 than within Chr 21. (CC)-NB-LRR type R proteins were found in the rkn1 region close to CIR316, and (TIR)-NB-LRR type R proteins were identified in another resistance rich region 10 cM from CIR 316 (∼3.1 Mbp in the TM-1 genome). The identified unique insertion/deletion in NB-ARC domain, different copies of LRR domain, multiple copies or duplication of R proteins, adjacent protein kinases, or TE in the rkn1 region on Chr 11 might be major factors contributing to complex recombination and transgressive resistance.

In this exploratory mixed methods survey study, we assess preservice teachers’ (n=379) experiences with and beliefs about their high-stakes testing experiences and analyze how they relate to their beliefs about the role and efficacy of high-stakes testing in education and their future profession. Using Likert, vignette, and open-ended response opportunities, we gauged preservice teachers’ beliefs about accountability and the role of high-stakes testing in three ways: (a) what are their personal experiences with high-stakes testing, (b) what are their their beliefs about accountability and high-stakes testing in general, and (c) what role does accountability (and testing pressures) play in their future workplace preferences? Results indicate that preservice teachers’ experiences with and beliefs about high-stakes testing accountability vary based on gender, ethnicity, and previous experiences with high-stakes tests. Importantly, although in aggregate our participants reported they generally disliked the high-stakes tests they personally had to take in high school, subgroup analyses reveal that for those who took them during the NCLB era, they also saw high-stakes tests as good thing for education overall. Preservice teachers who were younger and “grew up” under NCLB and the height of high-stakes testing believed high-stakes tests to be a waste of time for them personally, but a useful way to evaluate teachers as an educational policy. Vignette and qualitative analyses of workplace preferences and rationales underscore some of the assumptions our preservice teachers hold about high-stakes testing as a policy mechanism to help explain this finding. We conclude with implications for policy and future research.

There is a lack of current research to support the efficacy of a combination of equine-assisted activities (EAA) and brain building activities to influence motor skill competencies in youth with neurodevelopmental disorders (ND). The primary objective of this study was to quantify changes in motor skill proficiency before and after 8 weeks of EAA and brain-building activities in youth with ND. A secondary objective was to quantify changes in motor skill proficiency before and after 1 year of EAA and brain-building activities in youth with ND. Twenty-five youth completed the same 32-week protocol that was separated into 4, 8-week blocks, in the following order: (1) control; (2) EAA-only; (3) washout; (4) GaitWay block (EAA and brain building activities). Before and after each block, motor skills were assessed using the Short Form of the Bruininks-Oseretsky Test of Motor Proficiency-Version 2 (BOT-2). Seven youth continued with the GaitWay intervention for one additional year, and the BOT-2 Short Form was also administered following this intervention. A repeated-measures analysis-of-variance was performed to compare BOT-2 subtest and overall scores between interventions with a significance of 0.05. Manual dexterity was higher at Post-Washout [3.3 (2.4)] vs. Pre-Control [2.2 (2.1); p = 0.018] and Post-Control [2.6 (2.0); p = 0.024], and at Post-GaitWay vs. Pre-Control [3.2 (2.4) vs. 2.2 (2.1); p = 0.037]. Upper-limb coordination was higher at Post-GaitWay vs. Post-Control [6.0 (4.1) vs. 3.9 (3.8); p = 0.050]. When compared to Pre-Control [3.2 (3.0)], strength was higher at Post-EAA [4.9 (3.5); p = 0.028] and at Post-GaitWay [5.2 (2.9); p = 0.015]. Overall scores were higher at Post-GaitWay [39.1 (22.2)] when compared to Pre-Control [32.4 (21.6); p = 0.003] and Post-Control [32.5 (21.9); p = 0.009]. Additionally, motor skills were maintained for 1 year following the Post-GaitWay testing session among seven participants. This is the first known study to include and demonstrate the short-term and long-term effects of a combination of EAA and brain building activities with motor proficiency in youth with ND.Clinical Trial Registration: Motor Skill Proficiency After Equine-Assisted Activities and Brain-building Tasks; www.ClinicalTrials.gov, identifier: NCT04158960.

Youth with perinatally-acquired HIV (PHIV) experience specific and global cognitive deficits at increased rates compared to typically-developing HIV-uninfected youth. In youth with PHIV, HIV infects the brain early in development. Neuroimaging studies have demonstrated altered grey matter morphometry in youth with PHIV compared to typically-developing youth. This study examined cortical thickness, surface area, and gyrification of grey matter in youth (age 11–20 years old) with PHIV (n = 40) from the Pediatric HIV/AIDS Cohort Study (PHACS) compared to typically-developing presumed HIV uninfected and unexposed youth (n = 80) from the Pediatric Imaging, Neurocognition and Genetics Study (PING) using structural magnetic resonance imaging. This study also examined the relationship between grey matter morphometry and age. Youth with PHIV had reduced cortical thickness, surface area, and gyrification compared to typically-developing youth. In addition, an inverse relationship between age and grey matter volume was found in typically-developing youth, but was not observed in youth with PHIV. Longitudinal studies are necessary to understand the neurodevelopmental trajectory of youth with PHIV.

Summary: Regeneration following spinal root avulsion is broadly unsuccessful despite the regenerative capacity of other PNS-located nerves. By combining focal laser lesioning to model root avulsion in zebrafish, time-lapse imaging, and transgenesis, we identify that regenerating DRG neurons fail to recapitulate developmental paradigms of actin-based invasion after injury. We demonstrate that inducing actin reorganization into invasive components via pharmacological and genetic approaches in the regenerating axon can rescue sensory axon spinal cord entry. Cell-autonomous induction of invasion components using constitutively active Src induces DRG axon regeneration, suggesting an intrinsic mechanism can be activated to drive regeneration. Furthermore, analyses of neuronal activity and animal behavior show restoration of sensory circuit activity and behavior upon stimulating axons to re-enter the spinal cord via invasion. Altogether, our data identify induction of invasive components as sufficient for functional sensory root regeneration after injury. : Dorsal root ganglion (DRG) sensory axons are unable to regenerate into the spinal cord after injury. Nichols and Smith demonstrate in zebrafish that injured DRG axons do not initiate actin-based invasion components during re-entry into the spinal cord. Pharmacological and cell-autonomous genetic manipulations that promote actin-mediated cell invasion to restore sensory behavior. Keywords: regeneration, DREZ, invasion, OBPI, DRG, behavior, actin, spinal cord, zebrafish

Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM. Mean number of DG/platelet (plt), percentage of plts without DG, platelet count (PC), mean platelet volume (MPV), immature platelet fraction (IPF), and plt light transmission aggregometry analyses were measured on blood samples from 113 healthy donors. Quantile regression was used to estimate the reference range for DG/plt, and linear regression was used to assess the association of DG/plt with other plt measurements. All PTEM procedures were standardized using commercially available materials and reagents. DG interpretation criteria were established based on previous publications and expert consensus, and resulted in improved operator agreement. Mean DG/plt was stable for 2 days after blood sample collection. The median within patient coefficient of variation for mean DG/plt was 22.2%; the mean DG/plt reference range (mid-95th %) was 1.2–4.0. Mean DG/plt was associated with IPF (p = .01, R2 = 0.06) but not age, sex, PC, MPV, or plt maximum aggregation or primary slope of aggregation (p > .17, R2

Abstract Background Glial cell ensheathment of specific components of neuronal circuits is essential for nervous system function. Although ensheathment of axonal segments of differentiated neurons has been investigated, ensheathment of neuronal cell somas, especially during early development when neurons are extending processes and progenitor populations are expanding, is still largely unknown. Methods To address this, we used time-lapse imaging in zebrafish during the initial formation of the dorsal root ganglia (DRG). Results Our results show that DRG neurons are ensheathed throughout their entire lifespan by a progenitor population. These ensheathing cells dynamically remodel during development to ensure axons can extend away from the neuronal cell soma into the CNS and out to the skin. As a population, ensheathing cells tile each DRG neuron to ensure neurons are tightly encased. In development and in experimental cell ablation paradigms, the oval shape of DRG neurons dynamically changes during partial unensheathment. During longer extended unensheathment neuronal soma shifting is observed. We further show the intimate relationship of these ensheathing cells with the neurons leads to immediate and choreographed responses to distal axonal damage to the neuron. Conclusion We propose that the ensheathing cells dynamically contribute to the shape and position of neurons in the DRG by their remodeling activity during development and are primed to dynamically respond to injury of the neuron.

Abstract Background To understand the impact of weather on infectious diseases, information on weather parameters at patient locations is needed, but this is not always accessible due to confidentiality or data availability. Weather parameters at nearby locations are often used as a proxy, but the accuracy of this practice is not known. Methods Daily Campylobacter and Cryptosporidium cases across England and Wales were linked to local temperature and rainfall at the residence postcodes of the patients and at the corresponding postcodes of the laboratory where the patient’s specimen was tested. The paired values of daily rainfall and temperature for the laboratory versus residence postcodes were interpolated from weather station data, and the results were analysed for agreement using linear regression. We also assessed potential dependency of the findings on the relative geographic distance between the patient’s residence and the laboratory. Results There was significant and strong agreement between the daily values of rainfall and temperature at diagnostic laboratories with the values at the patient residence postcodes for samples containing the pathogens Campylobacter or Cryptosporidium. For rainfall, the R-squared was 0.96 for the former and 0.97 for the latter, and for maximum daily temperature, the R-squared was 0.99 for both. The overall mean distance between the patient residence and the laboratory was 11.9 km; however, the distribution of these distances exhibited a heavy tail, with some rare situations where the distance between the patient residence and the laboratory was larger than 500 km. These large distances impact the distributions of the weather variable discrepancies (i.e. the differences between weather parameters estimated at patient residence postcodes and those at laboratory postcodes), with discrepancies up to ±10 °C for the minimum and maximum temperature and 20 mm for rainfall. Nevertheless, the distributions of discrepancies (estimated separately for minimum and maximum temperature and rainfall), based on the cases where the distance between the patient residence and the laboratory was within 20 km, still exhibited tails somewhat longer than the corresponding exponential fits suggesting modest small scale variations in temperature and rainfall. Conclusion The findings confirm that, for the purposes of studying the relationships between meteorological variables and infectious diseases using data based on laboratory postcodes, the weather results are sufficiently similar to justify the use of laboratory postcode as a surrogate for domestic postcode. Exclusion of the small percentage of cases where there is a large distance between the residence and the laboratory could increase the precision of estimates, but there are generally strong associations between daily weather parameters at residence and laboratory.

Hermansky-Pudlak syndrome (HPS) − characterized by the distinct clinical phenotypes of both oculocutaneous albinism and mild bleeding diathesis–is caused by mutations in genes that have crucial roles in the assembly of cellular organelles (skin melanosomes, platelet delta [dense] granules, lung lamellar bodies, and cytotoxic T-cell lymphocyte granules). Immunodeficiency, pulmonary fibrosis and granulomatous colitis are associated with some, but not all subtypes of HPS, with varying degrees of clinical severity. We describe a patient diagnosed with platelet dense granule storage pool deficiency (DG-SPD) at age 38 years after he presented with spontaneous intracranial hemorrhage. His mild oculocutaneous hypopigmentation was subtle. In the following 27 years, he did not develop severe bleeding nor pulmonary or gastrointestinal complications. A novel homozygous c.1960A>T; p.Lys654* mutation in the HPS-5 protein gene (HPS5) was identified through next generation sequencing, (NGS) which is consistent with the patient’s clinical and laboratory phenotypes. This case underscores the importance of recognizing the mild clinical phenotype of HPS-5 and utilization of both laboratory and molecular testing for diagnosis, prognostication, and surveillance for end organ damage in patients affected with HPS.

Abstract Xanthomonas citri pv. malvacearum is a major pathogen of cotton, Gossypium hirsutum L.. In this study we report the complete genome of the X. citri pv. malvacearum strain MSCT1 assembled from long read DNA sequencing technology. The MSCT1 genome is the first X. citri pv. malvacearum genome with complete coding regions for X. citri pv. malvacearum transcriptional activator-like effectors. In addition functional and structural annotations are presented in this study that will provide a foundation for future pathogenesis studies with MSCT1.

Abstract Background Delayed graft function (DGF) is traditionally defined as the requirement for dialysis during the first week after transplantation. DGF is a common complication of renal transplantation, and it negatively affects short- and long-term graft outcomes. Ischaemia reperfusion injury (IRI) is a prime contributor to the development of DGF. It is well established that complement system activation plays a pivotal role in the pathogenesis of IRI. Mirococept is a highly effective complement inhibitor that can be administered ex vivo to the donor kidney just before transplantation. Preclinical and clinical evidence suggests that Mirococept inhibits inflammatory responses that follow IRI. The EMPIRIKAL trial (REC 12/LO/1334) aims to evaluate the efficacy of Mirococept in reducing the incidence of DGF in cadaveric renal transplantation. Methods/design EMPIRIKAL is a multicentre double-blind randomised case-control trial designed to test the superiority of Mirococept in the prevention of DGF in cadaveric renal allografts, as compared to standard cold perfusion fluid (Soltran®). Patients will be randomised to Mirococept or placebo (Pbo) and will be enrolled in cohorts of N = 80 with a maximum number of 7 cohorts. The first cohort will be randomised to 10 mg of Mirococept or Pbo. After the completion of each cohort, an interim analysis will be carried out in order to evaluate the dose allocation for the next cohort (possible doses: 5–25 mg). Immunosuppression therapy, antibiotic and antiviral prophylaxis will be administered as per local centre protocols. The enrolment will take approximately 24 months, and patients will be followed for 12 months. The primary endpoint is DGF, defined as the requirement for dialysis during the first week after transplantation. Secondary endpoints include duration of DGF, functional DGF, renal function at 12 months, acute rejection episodes at 6 and 12 months, primary non-function and time of hospital stay on first admission and in the first year following transplant. Safety evaluation will include the monitoring of laboratory data and the recording of all adverse events. Discussion The EMPIRIKAL trial is the first study to evaluate the efficacy of an ex vivo administered complement inhibitor (Mirococept) in preventing DGF in cadaveric human renal transplantation. Mirococept has a unique ‘cytotopic’ property that permits its retention in the organ microvasculature. Trial registration ISRCTN registry, ISRCTN49958194 . Registered on 3 August 2012.

The target for the “rapid” (100-fold selectivity over other ligands tested, including R-ketamine. We targeted each of the sensors to either the plasma membrane (PM) or the endoplasmic reticulum (ER). Measurements on these biosensors expressed in Neuro2a cells and in human dopaminergic neurons differentiated from induced pluripotent stem cells (iPSCs) show that S-ketamine enters the ER within a few seconds after appearing in the external solution near the PM, then leaves as rapidly after S-ketamine is removed from the extracellular solution. In cells, S-slopes for the ER and PM-targeted sensors differ by

Host plant resistance is the most practical approach to control the Southern root-knot nematode (Meloidogyne incognita; RKN), which has emerged as one of the most serious economic pests of Upland cotton (Gossypium hirsutum L.). Previous QTL analyses have identified a resistance locus on chromosome 11 (qMi-C11) affecting galling and another locus on chromosome-14 (qMi-C14) affecting egg production. Although these two QTL regions were fine mapped and candidate genes identified, expression profiling of genes would assist in further narrowing the list of candidate genes in the QTL regions. We applied the comparative transcriptomic approach to compare expression profiles of genes between RKN susceptible and resistance genotypes at an early stage of RKN development that coincides with the establishment of a feeding site and at the late stage of RKN development that coincides with RKN egg production. Sequencing of cDNA libraries produced over 315 million reads of which 240 million reads (76%) were mapped on to the Gossypium hirsutum genome. A total of 3,789 differentially expressed genes (DEGs) were identified which were further grouped into four clusters based on their expression profiles. A large number of DEGs were found to be down regulated in the susceptible genotype at the late stage of RKN development whereas several genes were up regulated in the resistant genotype. Key enriched categories included transcription factor activity, defense response, response to phyto-hormones, cell wall organization, and protein serine/threonine kinase activity. Our results also show that the DEGs in the resistant genotype at qMi-C11 and qMi-C14 loci displayed higher expression of defense response, detoxification and callose deposition genes, than the DEGs in the susceptible genotype.

Highly efficacious and tolerable treatments that cure hepatitis C viral (HCV) infection exist today, increasing the feasibility of disease elimination. However, large healthcare systems may not be fully prepared for supporting recommended actions due to knowledge gaps, inadequate infrastructure and uninformed policy direction. Additionally, the HCV cascade of care is complex, with many embedded barriers, and a significant number of patients do not progress through the cascade and are thus not cured. The aim of this retrospective cohort study was to evaluate a large healthcare system's HCV screening rates, linkage to care efficiency, and provider testing preferences. Patients born during 1945-1965, not previously HCV positive or tested from within the Electronic Health Record (EHR), were identified given that three-quarters of HCV-infected persons in the United States are from this Birth Cohort (BC). In building this HCV testing EHR prompt, non-Birth Cohort patients were excluded as HCV-specific risk factors identifying this population were not usually captured in searchable, structured data fields. Once completed, the BC prompt was released to primary care locations. From July 2015 through December 2016, 11.5% of eligible patients (n = 9,304/80,556) were HCV antibody tested (anti-HCV), 3.8% (353/9,304) anti-HCV positive, 98.1% (n = 311/317) HCV RNA tested, 59.8% (n = 186/311) HCV RNA positive, 86.6% (161/186) referred and 76.4% (n = 123/161) seen by a specialist, and 34.1% (n = 42/123) cured of their HCV. Results from the middle stages of the cascade in this large healthcare system are encouraging; however, entry into the cascade-HCV testing-was performed for only 11% of the birth cohort, and the endpoint-HCV cure-accounted for only 22% of all infected. Action is needed to align current practice with recommendations for HCV testing and treatment given that these are significant barriers toward elimination.

Understanding the physicochemical conditions extant and mechanisms operative during explosive volcanism is essential for reliable forecasting and mitigation of volcanic events. Rhyolitic pumices reflect highly vesiculated magma whose bubbles can serve as a strain indicator for inferring the state of stress operative immediately prior to eruptive fragmentation. Obtaining the full kinematic picture reflected in bubble population geometry has been extremely difficult, involving dissection of a small number of delicate samples. The advent of reliable high-resolution tomography has changed this situation radically. Here we demonstrate via the use of tomography how a statistically powerful picture of the shapes and connectivity of thousands of individual bubbles within a single sample of tube pumice emerges. The strain record of tube pumice is modelled using empirical models of bubble geometry and liquid rheology, reliant on a constraint of magmatic water concentration. FTIR analysis reveals an imbalance in water speciation, suggesting post-eruption hydration, further supported by hydrogen and oxygen isotope measurements. Our work demonstrates that the strain recorded in the tube pumice dominated by simple shear (not pure shear) in the late deformational history of vesicular magma before eruption. This constraint in turn implies that magma ascent is conditioned by a velocity gradient (across the conduit) at the point of origin of tube pumice. Magma ascent accompanied by simple shear should enhance high eruption rates inferred independently for these highly viscous systems.

Bacillus anthracis spores that are re-aerosolized from surface deposits after initial contamination present significant health risks for personnel involved in decontamination. To model repeated exposure to low dose B. anthracis spores, three groups of seven rabbits were challenged with multiple low-doses of B. anthracis spores 5 days a week for 3 weeks. Mortality, body temperature, heart and respiration rates, hematology, C-reactive protein, bacteremia, and serum protective antigen were monitored for 21 days post-exposure after the last of multiple doses. All rabbits exposed to a mean daily dose of 2.91 × 102 colony forming units (CFU) survived and showed minimal physiological changes attributable to exposure. One of seven rabbits receiving a mean daily dose of 1.22 × 103 CFU died and four of seven receiving a mean daily dose of 1.17 × 104 CFU died. The LD50 was calculated to be 8.1 × 103 CFU of accumulated dose. Rabbits that succumbed to the higher dose exhibited bacteremia and increases above baseline in heart rate, respiration rate, and body temperature. Two rabbits in the mean daily dose group of 1.17 × 104 CFU exhibited clinical signs of inhalation anthrax yet survived. This study provides a description of lethality, pathophysiology, and pathology in a controlled multiple low-dose inhalation exposure study of B. anthracis in the rabbit model. The data suggest that the accumulated dose is important in survival outcome and that a subset of rabbits may show clinical signs of disease but fully recover without therapeutic intervention