Imaging intact human organs with local resolution of cellular structures using hierarchical phase-contrast tomography.

Imaging intact human organs from the organ to the cellular scale in three dimensions is a goal of biomedical imaging. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique using the European Synchrotron Radiation Facility (ESRF)'s Extremely Brilliant Source (EBS). The spatial coherence of the ESRF-EBS combined with our beamline equipment, sample preparation and scanning developments enabled us to perform non-destructive, three-dimensional (3D) scans with hierarchically increasing resolution at any location in whole human organs. We applied HiP-CT to image five intact human organ types: brain, lung, heart, kidney and spleen. HiP-CT provided a structural overview of each whole organ followed by multiple higher-resolution volumes of interest, capturing organotypic functional units and certain individual specialized cells within intact human organs. We demonstrate the potential applications of HiP-CT through quantification and morphometry of glomeruli in an intact human kidney and identification of regional changes in the tissue architecture in a lung from a deceased donor with coronavirus disease 2019 (COVID-19).

Multiscale three-dimensional imaging of intact human organs down to the cellular scale using hierarchical phase-contrast tomography.

Human organs are complex, three-dimensional and multiscale systems. Spatially mapping the human body down through its hierarchy, from entire organs to their individual functional units and specialised cells, is a major obstacle to fully understanding health and disease. To meet this challenge, we developed hierarchical phase-contrast tomography (HiP-CT), an X-ray phase propagation technique utilising the European Synchrotron Radiation Facility's Extremely Brilliant Source: the world's first high-energy 4 th generation X-ray source. HiP-CT enabled three-dimensional and non-destructive imaging at near-micron resolution in soft tissues at one hundred thousand times the voxel size whilst maintaining the organ's structure. We applied HiP-CT to image five intact human parenchymal organs: brain, lung, heart, kidney and spleen. These were hierarchically assessed with HiP-CT, providing a structural overview of the whole organ alongside detail of the organ's individual functional units and cells. The potential applications of HiP-CT were demonstrated through quantification and morphometry of glomeruli in an intact human kidney, and identification of regional changes to the architecture of the air-tissue interface and alveolar morphology in the lung of a deceased COVID-19 patient. Overall, we show that HiP-CT is a powerful tool which can provide a comprehensive picture of structural information for whole intact human organs, encompassing precise details on functional units and their constituent cells to better understand human health and disease.

Considering the relationship between domestic violence and pet abuse and its significance in the veterinary clinical and educational contexts.

This thematic review examines the literature regarding the relationship between domestic violence (DV) and pet abuse (PA) particularly in the veterinary clinical and educational contexts. It examines the significance of this relationship for the veterinary profession including the veterinarian's role and associated legal and ethical obligations, and relevant current veterinary education standards, to identify future clinical and educational directions. Articles were sourced from online databases by searching the keywords without date restrictions. Overall, 70 articles were retrieved and reviewed. Pet abuse has been identified as a potential risk factor for DV, and DV perpetrators may harm or kill a pet to exert physical, psychological or emotional control over an intimate partner. Given that victims of DV often seek veterinary aid for their pets, veterinarians may act as frontline professionals in the recognition of the link between PA and DV. Veterinarians must assess individual cases for diagnostic indicators of non-accidental injury and consider demographic factors to identify suspected PA and DV. Despite existing legal and ethical obligations of the veterinarian relating to suspected PA and victims of DV, veterinarians have uncertainty and unpreparedness in addressing PA and DV in a clinical context. Many factors may contribute to the lack of veterinary intervention in suspected cases of PA and DV including concern for animal welfare, confusion about the reporting process and uncertainty in differentiating accidental versus non-accidental injuries in pets. Specific published guidelines regarding the recognition and reporting of PA and DV in the veterinary clinical context are required. Limited published evidence exists examining the implementation and success of veterinary training regarding the relationship between DV and PA. Ultimately, veterinary student education is needed to prepare veterinarians for their response to PA and DV in practice. Further research is required to examine the effects of the delivery of content regarding the link between PA and DV in the veterinary curriculum on veterinary student knowledge and attitudes.

3D high resolution imaging for microelectronics: A multi-technique survey on copper pillars.

In microelectronics, recently developed 3D integration offers the possibility to stack the dice or wafers vertically instead of putting their different parts next to one another, in order to save space. As this method becomes of greater interest, the need for 3D imaging techniques becomes higher. We here report a study about different 3D characterization techniques applied to copper pillars, which are used to stack different dice together. Destructive techniques such as FIB/SEM, FIB/FIB, and PFIB/PFIB slice and view protocols have been assessed, as well as non-destructive ones, such as laboratory-based and synchrotron-based computed tomographies. A comparison of those techniques in the specific case of copper pillars is given, taking into account the constraints linked to the microelectronics industry, mainly concerning resolution and sample throughput. Laboratory-based imaging techniques are shown to be relevant in the case of punctual analyses, while synchrotron based tomographies offer highly resolved volumes for larger batches of samples.

A suspected case of intermediate syndrome in a dog with carbamate toxicosis.

CASE REPORT: A 7-year-old female spayed Labrador Retriever was managed for suspected carbamate toxicosis after confirmed ingestion of a large amount of methiocarb. Therapy included decontamination, supportive care and management for aspiration pneumonia. On the third day of hospitalisation, after an initial clinical improvement, the dog developed respiratory muscle weakness, inspiratory dyspnoea and pronounced cervical muscle weakness. These delayed clinical signs were consistent with the 'intermediate syndrome' described in some cases of organophosphate and carbamate toxicoses in humans and also described in one case of organophosphate toxicosis in the dog. Intermediate syndrome has not been reported in carbamate toxicosis in the dog. CONCLUSION: This case report highlights the necessity for veterinarians to monitor for additional complications not commonly considered in acute carbamate toxicoses.

Growth and setting of gas bubbles in a viscoelastic matrix imaged by X-ray microtomography: the evolution of cellular structures in fermenting wheat flour dough.

X-ray tomography is a relevant technique for the dynamic follow-up of gas bubbles in an opaque viscoelastic matrix, especially using image analysis. It has been applied here to pieces of fermenting wheat flour dough of various compositions, at two different voxel sizes (15 and 5 µm). The resulting evolution of the main cellular features shows that the creation of cellular structures follows two regimes that are defined by a characteristic time of connectivity, tc [30 and 80 min]: first (t ≤ tc), bubbles grow freely and then (t ≥ tc) they become connected since the percolation of the gas phase is limited by liquid films. During the first regime, bubbles can be tracked and the local strain rate can be measured. Its values (10(-4)-5 × 10(-4) s(-1)) are in agreement with those computed from dough viscosity and internal gas pressure, both of which depend on the composition. For higher porosity, P = 0.64 in our case, and thus occurring in the second regime, different cellular structures are obtained and XRT images show deformed gas cells that display complex shapes. The comparison of these images with confocal laser scanning microscopy images suggests the presence of liquid films that separate these cells. The dough can therefore be seen as a three-phase medium: viscoelastic matrix/gas cell/liquid phase. The contributions of the different levels of matter organization can be integrated by defining a capillary number (C = 0.1-1) that makes it possible to predict the macroscopic dough behavior.

Differentiation of irradiation and cetuximab induced skin reactions in patients with locally advanced head and neck cancer undergoing radioimmunotherapy: the HICARE protocol (head and neck cancer: immunochemo and radiotherapy with erbitux) - a multicenter phase IV trial.

BACKGROUND: In order to improve the clinical outcome of patients with locally advanced squamous cell carcinoma of the head and neck (LASCCHN) not being capable to receive platinum-based chemoradiation, radiotherapy can be intensified by addition of cetuximab, a monoclonal antibody that blocks the epidermal growth factor receptor (EGFR). The radioimmunotherapy with cetuximab is a feasible treatment option showing a favourable toxicity profile. The most frequent side effect of radiotherapy is radiation dermatitis, the most common side effect of treatment with cetuximab is acneiform rash. Incidence and severity of these frequent, often overlapping and sometimes limiting skin reactions, however, are not well explored. A clinical and molecular differentiation between radiogenic skin reactions and skin reactions caused by cetuximab which may correlate with outcome, have never been described before. METHODS/DESIGN: The HICARE study is a national, multicenter, prospective phase IV study exploring the different types of skin reactions that occur in patients with LASCCHN undergoing radioimmun(chemo)therapy with the EGFR inhibitor cetuximab. 500 patients with LASCCHN will be enrolled in 40 participating sites in Germany. Primary endpoint is the rate of radiation dermatitis NCI CTCAE grade 3 and 4 (v. 4.02). Radioimmunotherapy will be applied according to SmPC, i.e. cetuximab will be administered as loading dose and then weekly during the radiotherapy. Irradiation will be applied as intensity-modulated radiation therapy (IMRT) or 3D-dimensional radiation therapy. DISCUSSION: The HICARE trial is expected to be one of the largest trials ever conducted in head and neck cancer patients. The goal of the HICARE trial is to differentiate skin reactions caused by radiation from those caused by the monoclonal antibody cetuximab, to evaluate the incidence and severity of these skin reactions and to correlate them with outcome parameters. Besides, the translational research program will help to identify and confirm novel peripheral blood based molecular predictors and surrogates for treatment response and resistance. TRIAL REGISTRATION: Clinical Trial Identifier, NCT01553032 (clinicaltrials.gov)EudraCT number: 2010-019748-38.

Three-dimensional rigid multiphase networks providing high-temperature strength to cast AlSi10Cu5Ni1-2 piston alloys.

The three-dimensional (3-D) architecture of rigid multiphase networks present in AlSi10Cu5Ni1 and AlSi10Cu5Ni2 piston alloys in as-cast condition and after 4 h spheroidization treatment is characterized by synchrotron tomography in terms of the volume fraction of rigid phases, interconnectivity, contiguity and morphology. The architecture of both alloys consists of α-Al matrix and a rigid long-range 3-D network of Al(7)Cu(4)Ni, Al(4)Cu(2)Mg(8)Si(7), Al(2)Cu, Al(15)Si(2)(FeMn)(3) and AlSiFeNiCu aluminides and Si. The investigated architectural parameters of both alloys studied are correlated with room-temperature and high-temperature (300 °C) strengths as a function of solution treatment time. The AlSi10Cu5Ni1 and AlSi10Cu5Ni2 alloys behave like metal matrix composites with 16 and 20 vol.% reinforcement, respectively. Both alloys have similar strengths in the as-cast condition, but the AlSi10Cu5Ni2 is able to retain ∼15% higher high temperature strength than the AlSi10Cu5Ni1 alloy after more than 4 h of spheroidization treatment. This is due to the preservation of the 3-D interconnectivity and the morphology of the rigid network, which is governed by the higher degree of contiguity between aluminides and Si.

Application of feces extracts and synthetic analogues of the host marking pheromone of Anastrepha ludens significantly reduces fruit infestation by A. obliqua in tropical plum and mango backyard orchards.

We determined the efficacy of three potential oviposition deterrents in reducing fruit infestation by Anastrepha obliqua in tropical plum and mango orchards. These were: (1) Extracts of feces of Mexican fruit fly, Anastrepha ludens, known to contain the A. ludens host marking pheromone (HMP) and (2) two fully synthetic simplified analogues of the naturally occurring compound, which we have named desmethyl A. ludens HMP (DM-HMP) and Anastrephamide. Two applications of feces extracts 2 or 3 wk before fruit color break reduced A. obliqua infestation in plums by 94.1, 75.9, and 72% when measured 8, 14, and 25 d, respectively, after application. The natural A. ludens-HMP containing extract retained its effectiveness despite considerable rainfall (112.5 mm) and high A. obliqua populations. The synthetic desmethyl HMP derivative (DM-HMP) also reduced infestation in plums by 53.3 and 58.7% when measured, 18 and 26 d, respectively, after application. Finally, applications of Anastrephamide resulted in fruit loss cut by half and an 80% reduction in numbers of fly larvae per fruit. Our results confirm previous findings indicating that there is interspecific cross-recognition of the HMP in two of the most pestiferous Anastrepha species and open the door for the development of a highly selective, biorational Anastrepha management scheme.

Host marking pheromone ofRhagoletis cerasi: Foraging behavior in response to synthetic pheromonal isomers.

We studied the foraging behavior ofRhagoletis cerasi females in trees treated with synthetic cherry fruit fly host marking pheromone (HMP) under seminatural conditions (potted trees enclosed in a screen cage). Results show that synthetic HMP (particularly the 8RS-@#@ 15R isomer configuration (racemic mixture)) was highly effective in eliciting behavioral responses similar to those reported in studies using natural HMP. Flies exposed to synthetic pheromone exhibited short tree residence times (i.e., emigrated faster), increased flight frequency rates (measured as number of alightings per/minute), higher irritation indices while on a tree or a fruit, and oviposited fewer eggs per fruit visit than flies exposed to clean trees and fruit (not treated with synthetic HMP). Furthermore, we provide evidence showing that when flies were continuously exposed to an HMP-saturated environment, they exhibited an increased tendency to lay eggs in marked fruit.

An economic and rapid diagnostic procedure for the detection of salmonella/shigella using the polyvalent salmonella phage O-1.

An easy, rapid and economic two-step procedure is described for the detection of Salmonella/Shigella. In the first step the susceptibility of suspected colonies for the phage O-1 of FELIX and CALLOW is tested. Positive cultures are serologically confirmed. The test is performed on Triple Sugar Iron Agar and lasts 4-6 hrs. Phage negative cultures which are lactose- and sucrose negative are tested for lysine decarboxylase and, if Shigella is possible (i.e. in human material on primary plates), for indol production and motility in a semisolid tryptophane agar. Of 22880 Salmonella straine 21977, i.e. 96.1% were phage-sensitive. Strains belonging to certain O-groups (OE) or species are lysed at a lower percentage. However, since they are lysine decarboxylase positive they are not lost and can be submitted to a serological examination.