Baseline Quality-of-Life of Caregivers of Patients With Heart Failure Prior to Advanced Therapies: Findings From the Sustaining Quality of Life of the Aged: Transplant or Mechanical Support (SUSTAIN-IT) Study.

BACKGROUND: We compared health-related quality of life (HRQOL), depressive symptoms, anxiety, and burden in caregivers of older patients with heart failure based on the intended therapy goal of the patient: awaiting heart transplantation (HT) with or without mechanical circulatory support (MCS) or prior to long-term MCS; and we identified factors associated with HRQOL. METHODS: Caregivers (n = 281) recruited from 13 HT and MCS programs in the United States completed measures of HRQOL (EQ-5D-3L), depressive symptoms (PHQ-8), anxiety (STAI-state), and burden (Oberst Caregiving Burden Scale). Analyses included ANOVA, Kruskal-Wallis tests, χ2 tests, and linear regression. RESULTS: The majority of caregivers were female, white spouses with ≤ 2 comorbidities, median [Q1,Q3] age = 62 [57.8, 67.0] years. Caregivers (HT with MCS = 87, HT without MCS = 98, long-term MCS = 96) reported similarly high baseline HRQOL (EQ-5D-3L visual analog scale median score = 90; P = 0.67 for all groups) and low levels of depressive symptoms. STAI-state median scores were higher in the long-term MCS group vs the HT groups with and without MCS, (38 vs 32 vs 31; P < 0.001), respectively. Burden (task: time spent/difficulty) differed significantly among groups. Caregiver factors (number of comorbidities, diabetes and higher anxiety levels) were significantly associated with worse caregiver HRQOL, R2 = 26%. CONCLUSIONS: Recognizing caregiver-specific factors, including comorbidities and anxiety, associated with the HRQOL of caregivers of these older patients with advanced HF may guide support strategies.

Predicting concurrent structural mechanical mechanisms during microstructure evolution.

The interdependence between structural mechanics and microstructure solidification has been widely observed experimentally as a factor leading to undesirable macroscopic properties and casting defects. Despite this, numerical modelling of microstructure solidification often neglects this interaction and is therefore unable to predict key mechanisms such as the development of misoriented grains. This paper presents a numerical method coupling a finite volume structural mechanics solver to a cellular automata solidification solver, where gravity or pressure-driven displacements alter the local orientation and thereby growth behaviour of the solidifying dendrites. Solutions obtained using this model are presented which show fundamental behaviours observed in experiments. The results show that small, localized deformations can lead to significant changes in the crystallographic orientation of a dendrite and ultimately affect the overall microstructure development. This article is part of the theme issue 'Transport phenomena in complex systems (part 2)'.

Full-field strain of regenerated bone tissue in a femoral fracture model.

The mechanical behaviour of regenerated bone tissue during fracture healing is key in determining its ability to withstand physiological loads. However, the strain distribution in the newly formed tissue and how this influences the way a fracture heals it is still unclear. X-ray Computed Tomography (XCT) has been extensively used to assess the progress of mineralised tissues in regeneration and when combined with in situ mechanics and digital volume correlation (DVC) has been proven a powerful tool to understand the mechanical behaviour and full-field three-dimensional (3D) strain distribution in bone. The purpose of this study is therefore to use in situ XCT mechanics and DVC to investigate the strain distribution and load-bearing capacity in a regenerating fracture in the diaphyseal bone, using a rodent femoral fracture model stabilised by external fixation. Rat femurs with 1 mm and 2 mm osteotomy gaps were tested under in situ XCT step-wise compression in the apparent elastic region. High strain was present in the newly formed bone (εp1 and εp3 reaching 29 000 µÎµ and -43 000 µÎµ, respectively), with a wide variation and inhomogeneity of the 3D strain distribution in the regenerating tissues of the fracture gap, which is directly related to the presence of unmineralised tissue observed in histological images. The outcomes of this study will contribute in understanding natural regenerative ability of bone and its mechanical behaviour under loading.

X-ray computed tomography evaluations of additive manufactured multimaterial composites.

Additive Manufacturing (AM) often produces complex engineered structures by precisely distributing materials in a layer-by-layer fashion. Multimaterial AM is a particularly flexible technique able to combine a range of hard and soft materials to produce designed composites. Critically, the design of AM multimaterial structures requires the development of precise three-dimensional (3D) computed aided design (CAD) files. While such digital design is heavily used, techniques able to validate the physically manufactured composite against the digital design from which it is generated are lacking for AM, especially as any evaluations must be able to distinguish material variation across the 3D space. Nowadays, there is a growing interest in volumetric tools that can provide topological information hidden by the surface of shaped materials. So far, technologies such as Optical microscopy (OM), Scanning Electron Microscopy (SEM), and Coordinate Measuring Machine (CMM) have paved the way into the metrology field to measure the external geometry of physical objects. Currently, alongside conventional metrology tools, X-ray computed tomography (XCT) is emerging to measure the subsurface of the objects but maintaining the integrity of the probed samples. Thereby, the volumetric nature of the XCT investigations and its associated imaging techniques, ensure 3D quantitative measurements comparable to the output data from 2D metrology tools, but above all, supply the missing subsurface description for an exhaustive metrology study. The reward associated with XCT applied to multimaterial AM is a map reflecting the fabricated distribution of materials following CAD, with the benefits of better understanding the mechanical interplay within phases, hence, describing the hidden processes as well as the changes in phases due to a range of mechanical or chemical phenomena. In this study, a nondestructive approach using X-ray computed tomography (XCT) is used to fully evaluate the 3D distribution of multimaterials from an AM process. Specifically, two diverse hard and soft materials are alternatively produced in the form of a fibre embedded in a matrix via ink-jet printing. XCT coupled with imaging evaluation were able to distinguish between the differing materials and, importantly, to demonstrate a reduction in the expected fabricated volumes when compared to the respective CAD designs. LAY DESCRIPTION: Additive Manufacturing (AM) has recently become important in producing complex engineered structures. Using 3D CAD files and/or reconstructed data sets from imaging, hard and soft materials are manufactured independently or in combination, according to geometrical features and shapes in the input data. However, the evaluation of the resultant manufactured parts in comparison with the original 3D drawing is currently lacking. In this sense, X-ray computed tomography (XCT) provides an important metrology tool for mono and multimaterial AM. In this work a volumetric metrology investigation is proposed using higher resolution XCT to provide 3D information comparable to that of the 3D CAD drawings. A commercial high-resolution multijetting material printer (ProJet 5500X, 3D Systems, USA) is used to manufacture single fibre composites, through a complementary deposition of photo sensible polymers. Hard and soft plastics are produced using a UV curable step, resulting in materials of similar attenuation under an X-ray probe. A critical aim of the evaluations is the potential for XCT to distinguish between different UV curable 3D printing materials.

Dendritic growth of ice crystals: a test of theory with experiments.

Motivated by an important application of dendritic crystals in the form of an elliptical paraboloid, which widely spread in nature (ice crystals), we develop here the selection theory of their stable growth mode. This theory enables us to separately define the tip velocity of dendrites and their tip diameter as functions of the melt undercooling. This, in turn, makes it possible to judge the microstructure of the material obtained as a result of the crystallization process. So, in the first instance, the steady-state analytical solution that describes the growth of such dendrites in undercooled one-component liquids is found. Then a system of equations consisting of the selection criterion and the undercooling balance that describes a stable growth mode of elliptical dendrites is formulated and analyzed. Three parametric solutions of this system are deduced in an explicit form. Our calculations based on these solutions demonstrate that the theoretical predictions are in good agreement with experimental data for ice dendrites growing at small undercoolings in pure water.

Thermoelectric magnetohydrodynamic control of melt pool dynamics and microstructure evolution in additive manufacturing.

Large thermal gradients in the melt pool from rapid heating followed by rapid cooling in metal additive manufacturing generate large thermoelectric currents. Applying an external magnetic field to the process introduces fluid flow through thermoelectric magnetohydrodynamics. Convective transport of heat and mass can then modify the melt pool dynamics and alter microstructural evolution. As a novel technique, this shows great promise in controlling the process to improve quality and mitigate defect formation. However, there is very little knowledge within the scientific community on the fundamental principles of this physical phenomenon to support practical implementation. To address this multi-physics problem that couples the key phenomena of melting/solidification, electromagnetism, hydrodynamics, heat and mass transport, the lattice Boltzmann method for fluid dynamics was combined with a purpose-built code addressing solidification modelling and electromagnetics. The theoretical study presented here investigates the hydrodynamic mechanisms introduced by the magnetic field. The resulting steady-state solutions of modified melt pool shapes and thermal fields are then used to predict the microstructure evolution using a cellular automata-based grain growth model. The results clearly demonstrate that the hydrodynamic mechanisms and, therefore, microstructure characteristics are strongly dependent on magnetic field orientation. This article is part of the theme issue 'Patterns in soft and biological matters'.

Modeling of dendrite growth from undercooled nickel melt: sharp interface model versus enthalpy method.

The dendritic growth of pure materials in undercooled melts is critical to understanding the fundamentals of solidification. This work investigates two new insights, the first is an advanced definition for the two-dimensional stability criterion of dendritic growth and the second is the viability of the enthalpy method as a numerical model. In both cases, the aim is to accurately predict dendritic growth behavior over a wide range of undercooling. An adaptive cell size method is introduced into the enthalpy method to mitigate against 'narrow-band features' that can introduce significant error. By using this technique an excellent agreement is found between the enthalpy method and the analytic theory for solidification of pure nickel.

Hierarchical electrospun tendon-ligament bioinspired scaffolds induce changes in fibroblasts morphology under static and dynamic conditions.

The regeneration of injured tendons and ligaments is challenging because the scaffolds needs proper mechanical properties and a biomimetic morphology. In particular, the morphological arrangement of scaffolds is a key point to drive the cells growth to properly regenerate the collagen extracellular matrix. Electrospinning is a promising technique to produce hierarchically structured nanofibrous scaffolds able to guide cells in the regeneration of the injured tissue. Moreover, the dynamic stretching in bioreactors of electrospun scaffolds had demonstrated to speed up cell shape modifications in vitro. The aim of the present study was to combine different imaging techniques such as high-resolution X-ray tomography (XCT), scanning electron microscopy (SEM), fluorescence microscopy and histology to investigate if hierarchically structured poly (L-lactic acid) and collagen electrospun scaffolds can induce morphological modifications in human fibroblasts, while cultured in static and dynamic conditions. After 7 days of parallel cultures, the results assessed that fibroblasts had proliferated on the external nanofibrous sheath of the static scaffolds, elongating themselves circumferentially. The dynamic cultures revealed a preferential axial orientation of fibroblasts growth on the external sheath. The aligned nanofibre bundles inside the hierarchical scaffolds instead, allowed a physiological distribution of the fibroblasts along the nanofibre direction. Inside the dynamic scaffolds, cells appeared thinner compared with the static counterpart. This study had demonstrated that hierarchically structured electrospun scaffolds can induce different fibroblasts morphological modifications during static and dynamic conditions, modifying their shape in the direction of the applied loads. LAY DESCRIPTION: To enhance the regeneration of injured tendons and ligaments cells need to growth on dedicated structures (scaffolds) with mechanical properties and a fibrous morphology similar to the natural tissue. In particular, the morphological organisation of scaffolds is fundamental in leading cells to colonise them, regenerating the collagen extracellular matrix. Electrospinning is a promising technique to produce fibres with a similar to the human collagen fibres, suitable to design complex scaffolds able to guide cells in the reconstruction of the natural tissue. Moreover, it is well established that the cyclic stretching of these scaffolds inside dedicated systems called bioreactors, can speed up cells growth and their shape modification. The aim of the present study was to investigate how hierarchically structured electrospun scaffolds, made of resorbable material such as poly(L-lactic acid) and collagen, could induce morphological changes in human fibroblasts, while cultured during static and dynamic conditions. These scaffolds were composed by an external electrospun membrane that grouped inside it a ring-shaped bundle, made of axially aligned nanofibres, resembling the morphological arrangement of tendon and ligament tissue. After 7 days of parallel cultures, the scaffolds were investigated using the following imaging techniques: (i) high-resolution X-ray tomography (XCT); (ii) scanning electron microscopy (SEM); (iii) fluorescence microscopy and (iv) histology. The results showed that fibroblasts were able to grow on the external nanofibrous sheath of the static scaffolds, by elongating themselves along their circumference. The dynamic cultures revealed instead a preferential axial orientation of fibroblasts grown on the external sheath. The aligned nanofibre bundles inside the hierarchical scaffolds allowed an axial distribution of the fibroblasts along the nanofibres direction. This study has demonstrated that the electrospun hierarchically structured scaffolds investigated can modify the fibroblasts morphology both in static and dynamic conditions, in relation with the direction of the applied loads.

Thermal dependence of large-scale freckle defect formation.

The fundamental mechanisms governing macroscopic freckle defect formation during directional solidification are studied experimentally in a Hele-Shaw cell for a low-melting point Ga-25 wt.% In alloy and modelled numerically in three dimensions using a microscopic parallelized Cellular Automata Lattice Boltzmann Method. The size and distribution of freckles (long solute channels, or chimneys) are shown to be strongly dependent on the thermal profile of the casting, with flat, concave and convex isotherms being considered. For the flat isotherm case, no large-scale freckles form, while for concave or convex isotherms, large freckles appear but in different locations. The freckle formation mechanism is as expected buoyancy-driven, but the chimney stability, its long-term endurance and its location are shown to depend critically on the detailed convective transport through the inter-dendritic region. Flow is generated by curved isopleths of solute concentration. As solute density is different from that of the bulk fluid, gravity causes 'uphill' or 'downhill' lateral flow from the sample centre to the edges through the mush, feeding the freckle. An excellent agreement is obtained between the numerical model and real-time X-ray observations of a solidifying sample under strictly controlled temperature conditions. This article is part of the theme issue 'Heterogeneous materials: metastable and non-ergodic internal structures'.

Chronic immunosuppressant use in colorectal cancer patients worsens postoperative morbidity and mortality through septic complications in a propensity-matched analysis.

AIM: Chronic immunosuppressant use increases the risk of septic complications after colectomy; however, adverse effects on other organ systems remain poorly understood. The aim of this study was to evaluate the multisystem organ effect(s) of chronic immunosuppressant(s) in colorectal cancer patients. METHODS: This was a retrospective study. The American College of Surgeons National Surgical Quality Improvement database (2005-2012) was queried. The primary end-points were 30-day mortality and 30-day morbidity after colectomy in patients on chronic immunosuppressant(s) compared to a non-immunosuppressant cohort. RESULTS: In total, 50 766 patients were identified, with 1203 (2.4%) taking chronic immunosuppressant(s). After propensity matching, 1197 patients in each cohort were evaluated with no differences seen in age, body mass index, male sex, wound classification, emergency case status, the presence of preoperative sepsis or operative time. On outcome analysis, 30-day mortality (5.7% vs 3.4%, P < 0.001) and 30-day overall morbidity (35.4% vs 29.0%, P = 0.001) were higher in patients on chronic immunosuppressant(s). Septic complications (10.6% vs 7.9%, P = 0.02) and surgical site infections (15.3% vs 12.3%, P = 0.03) were elevated with chronic immunosuppressant(s). There were no differences in cardiovascular, pulmonary, renal or neurological complications. Chronic immunosuppressant patients demonstrated longer total hospital stay (11.4 ± 11.7 vs 9.5 ± 9.4 days, P < 0.001) and postoperative length of stay (9.4 ± 9.2 vs 8.1 ± 7.6 days, P < 0.001). The limitation was that this was a retrospective study using a clinical dataset. CONCLUSION: In this study, immunosuppressant use is associated with worsened infective complications, without contributing to organ-specific complications following colectomy. Significant thought should be given to anastomosis vs stoma creation to possibly prevent worsened morbidity and mortality. Future study is required to determine specific pathways for risk reduction.

MELD-Na score associated with postoperative complications in hernia repair in non-cirrhotic patients.

PURPOSE: In patients with cirrhosis, the Model for End-Stage Liver Disease Sodium (MELD-Na) score is a validated predictor of outcomes after transplant and non-transplant surgical procedures. This study investigates the association of MELD-Na score with complications following elective ventral hernia repair in non-cirrhotic patients. METHODS: The ACS NSQIP database was queried (2005-2016) for all elective laparoscopic and open ventral hernia procedures in patients without ascites or esophageal varices. Postoperative outcomes were compared by MELD-Na score using Chi-square tests. Multivariate logistic regression was used to control for potentially confounding variables. RESULTS: A total of 48,955 elective hernia repairs were identified; 68.7% were open repairs. The overall complication rate (Clavien-Dindo ≥ 1) was 14.3%, with a wound complication rate of 5.5%, and major complication rate (Clavien-Dindo ≥ 3) of 4.3%. A preoperative MELD-Na score ≥ 10 was present in 29.4%. Incremental increases in MELD-Na score (10-14, 15-19, and ≥ 20) were associated with increased overall complications (OR 1.25, CI 1.31-1.37; OR 1.53, CI 1.30-1.80; OR 1.70, CI 1.24-2.31, respectively), major complications (OR 1.42, CI 1.20-1.69; OR 1.85, CI 1.43-2.39; OR 2.13, CI 1.35-3.38, respectively), 30-day mortality (OR 1.58, CI 1.05-2.37; OR 2.34, CI 1.39-3.96; OR 3.16, CI 1.37-7.28, respectively), and return to the operating room (OR 1.19, CI 1.01-1.41; OR 1.38, CI 1.05-1.81; OR 1.78, CI 1.10-2.90, respectively). CONCLUSION: MELD-Na score is independently associated with postoperative complications in ventral hernia repair. As an objective and simple predictive model, it may be useful in preoperative risk calculations for complex patients.

Perforated diverticulitis in the setting of ulcerative colitis: An unusual case report.

INTRODUCTION: The association of diverticulitis with ulcerative colitis (UC) is rare and not well described. The sequelae of inflammatory bowel disease (IBD) such as perforation and fistula formation can mimic diverticular complications. Therefore, in an IBD patient, it can be difficult to distinguish the etiology of such complications and render definitive care. PRESENTATION OF CASE: A 43-year-old man with a long history of UC presented with spontaneous sigmoid perforation and subsequent complications of colovesicular and colocutaneous fistulae requiring multiple procedural interventions. Ultimately, the etiology was confirmed as perforated diverticulitis superimposed on severe ulcerative colitis. DISCUSSION: As perforated diverticulitis superimposed on UC is a rare entity in the current literature and there are many diagnostic difficulties that complicate this scenario. It is important to rule out other entities such as misdiagnosis of IBD or segmental colitis associated with diverticula (SCAD) that may have overlapping features. CONCLUSION: Although diverticulitis in the setting of UC is an uncommon presentation, it remains important for medical practitioners to consider this scenario when encountering patients who may present in a similar fashion. As such, we put forth a process to aid in a diagnosis and management such that definitive care may not be delayed.

Automatic diameter and orientation distribution determination of fibrous materials in micro X-ray CT imaging data.

Fibrous nanomaterials such as electrospun materials have many uses ranging from tissue engineering to biosensors. High-resolution imaging is an important component in the characterization of these materials. Important parameters required to predict and study the properties of fibre rich materials include diameter and orientation distribution as well as fibre spacing. The orientations and the relative dimensions of the fibres can be measured via specially designed imaging software. Difficulties in this measurement process can arise if fibres are distributed in close proximity to each other in relation to the resolution of the imaging modality. For example, if some automation is required in the measurement process and, particularly, if the automated processes are not designed for situations where the fibres are in close proximity to each other. This work is therefore concerned with the development of automated measurement techniques to provide estimates of the diameters of fibres and also the orientation distribution. The software automatically detects special points in the fibrous materials where fibres can be considered to have some delineation from surrounding fibres. These sparse points are considered to be points at which estimates of the fibres' properties can be quantified. Aligned and randomly distributed electrospun poly(caprolactone) nanofibres were prepared. Imaging of these materials was performed with an X-ray Computer Tomography system with an image voxel size of 0.15 × 0.15 × 0.15 µm3 . Scanning Electron Microscopy images were also obtained. Fibre diameters estimated using images from both modalities using the developed techniques were found to be in agreement. Orientation distribution was summarized with multiscale entropy and found to be consistent with visual observation across different scales. LAY DESCRIPTION: Fibres are present in many types of materials which can include, for some materials, very small fibres e.g. a few nanometres in diameter. Very small fibres are present in collagen and elastin which are common tissues of many organs in many types of living things. The sizes of these very small fibres and how they are arranged are important information that can help in the understanding of the overall properties of these materials. Materials with very small fibres can also be synthesized using specialised techniques. The properties of these synthesized fibrous materials are also important to help in understanding how the materials will perform in various different applications. Applications are many and can range from tissue engineering to drug delivery. Some properties of these materials can be shown, visually, with the aid of 3D imaging techniques such as X-ray Computer Tomography (XCT) or in 2D, with Scanning Electron Microscopy (SEM) but at a higher magnification. The work described here is centred around the development of computer algorithms to automatically determine material properties from 3D XCT images. Tests are performed with material samples, where the fibres are aligned (in semi-parallel fashion) and another where the fibres are randomly oriented (criss-crossing). The tests show that the developed algorithms are able to successfully and relatively accurately determine the diameters of the fibres. The tests also show that it is possible to quantify the relative randomness of the orientations of the fibres.

High-resolution x-ray tomographic morphological characterisation of electrospun nanofibrous bundles for tendon and ligament regeneration and replacement.

Repair of ligaments and tendons requires scaffolds mimicking the spatial organisation of collagen in the natural tissue. Electrospinning is a promising technique to produce nanofibres of both resorbable and biostable polymers with desired structural and morphological features. The aim of this study was to perform high-resolution x-ray tomography (XCT) scans of bundles of Nylon6.6, pure PLLA and PLLA-Collagen blends, where the nanofibres were meant to have a predominant direction. Characterisation was carried out via a dedicated methodology to firmly hold the specimen during the scan and a workflow to quantify the directionality of the nanofibres in the bundle. XCT scans with 0.4 and 1.0 µm voxel size were successfully collected for all bundle compositions. Better image quality was achieved for those bundles formed by thicker nanofibres (i.e. 0.59 µm for pure PLLA), whereas partial volume effect was more pronounced for thinner nanofibres (i.e. 0.26 µm for Nylon6.6). As expected, the nanofibres had a predominant orientation along the axis of the bundles (more than 20% of the nanofibres within 3° and more than 60% within 18° from the bundle axis), with a Gaussian-like dispersion in the other directions. The directionality assessment was validated by comparison against a similar analysis performed on SEM images: the XCT analysis overestimated the amount of nanofibres very close to the bundle axis, especially for the materials with thinnest nanofibres, but adequately identified the amount of nanofibres within 12°. LAY DESCRIPTION: Repair of ligaments and tendons requires dedicated materials (scaffolds) mimicking the spatial organisation of the collagen (the main material composing such natural tissue). Electrospinning is a promising technique that allows production of fibres with nanometric dimension using high voltage to stretch very tiny drops of polymeric solutions. Electrospinning allows processing both polymers that can be resorbed by the host tissue, and nonresorbable ones, to obtain the desired structural and morphological features by arranging the nanofibres in bundles. The aim of this study was to perform high-resolution x-ray computed tomography (XCT) scans of bundles, where the nanofibres were meant to have a predominant direction. The investigation included bundles of different compositions: a biostable polymer (Nylon) and bioresorbable ones (pure Poly-L-lactic acid (PLLA) and PLLA-Collagen blends). The electrospun bundles were produced using a validated method (Sensini et al 2017: https://doi.org/10.1088/1758-5090/aa6204). To this end, we developed a dedicated methodology to scan such small specimens, and a workflow to quantify the directionality of the nanofibres in the bundle. For all the compositions, XCT scans with extremely high resolution (i.e. down to 0.4 µm) were successfully collected. As expected, better images were obtained for those bundles where the nanofibres were thicker than the scanning resolution (i.e. 0.59 µm for pure PLLA). The images of the thinnest nanofibres (i.e. 0.26 µm for Nylon) were poorer because the fibre diameter was smaller than the resolution (partial volume effect). The nanofibres had a predominant orientation along the axis of the bundles (more than 60% of the nanofibres were within 18° from the bundle axis). The nanofibres had a Gaussian-like dispersion in the other directions. As this is the first time that XCT is used to quantify the directionality of this kind of bundles, the directionality assessment was further validated by comparison against a similar analysis performed on SEM images. Overall, this study has demonstrated the usefulness and reliability of using high-resolution x-ray computed tomography (XCT) scans to investigate the morphology of polymeric scaffolds made of electrospun nanofibres.

Thermoelectric magnetohydrodynamic effects on the crystal growth rate of undercooled Ni dendrites.

In the undercooled solidification of pure metals, the dendrite tip velocity has been shown experimentally to have a strong dependence on the intensity of an external magnetic field, exhibiting several maxima and minima. In the experiments conducted in China, the undercooled solidification dynamics of pure Ni was studied using the glass fluxing method. Visual recordings of the progress of solidification are compared at different static fields up to 6 T. The introduction of microscopic convective transport through thermoelectric magnetohydrodynamics is a promising explanation for the observed changes of tip velocities. To address this problem, a purpose-built numerical code was used to solve the coupled equations representing the magnetohydrodynamic, thermal and solidification mechanisms. The underlying phenomena can be attributed to two competing flow fields, which were generated by orthogonal components of the magnetic field, parallel and transverse to the direction of growth. Their effects are either intensified or damped out with increasing magnetic field intensity, leading to the observed behaviour of the tip velocity. The results obtained reflect well the experimental findings.This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'.

Morphological and Mechanical Biomimetic Bone Structures.

Cortical bone is an example of a mineralized tissue containing a compositional distribution of hard and soft phases in 3-dimensional space for mechanical function. X-ray computed tomography (XCT) is able to describe this compositional and morphological complexity but methods to provide a physical output with comparable mechanical function is lacking. A workflow is presented here to establish a method of using high contrast XCT to establish a virtual model of cortical bone that is manufactured using a multiple material capable 3D printer. Resultant 3D printed structures were produced based on more and less remodelled bone designs exhibiting a range of secondary osteon density. Variation in resultant mechanical properties of the 3D printed composite structures for each bone design was achieved using a combination of material components and reasonable prediction of elastic modulus provided using a Hashin-Shtrikman approach. The ability to 3D print composite structures using high contrast XCT to distinguish between compositional phases in a biological structure promises improved anatomical models as well as next-generation mechano-mimetic implants.

The Influence of Prebiotics on Neurobiology and Behavior.

Manipulating the intestinal microbiota for the benefit of the brain is a concept that has become widely acknowledged. Prebiotics are nondigestible nutrients (i.e., fibers, carbohydrates, or various saccharides) that proliferate intrinsic, beneficial gut bacteria, and so provide an alternative strategy for effectively altering the enteric ecosystem, and thence brain function. Rodent studies demonstrating neurobiological changes following prebiotic intake are slowly emerging, and have thus far revealed significant benefits in disease models, including antiinflammatory and neuroprotective actions. There are also compelling data showing the robust and favorable effects of prebiotics on several behavioral paradigms including, anxiety, learning, and memory. At present, studies in humans are limited, though there is strong evidence for prebiotics modulating emotional processes and the neuroendocrine stress response that may underlie the pathophysiology of anxiety. While the mechanistic details linking the enteric microbiota to the central nervous system remain to be elucidated, there are a number of considerations that can guide future studies. These include the modulation of intestinal endocrine systems and inflammatory cascades, as well as direct interaction with the enteric nervous system and gut mucosa. Our knowledge of gut microbiome-brain communication is steadily progressing, and thorough investigations validating the use of prebiotics in the treatment of neuropsychiatric disorders would be highly valued and are encouraged.

Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease.

We have sequenced the complete genomes of 72 individuals affected with early-onset familial Alzheimer's disease caused by an autosomal dominant, highly penetrant mutation in the presenilin-1 (PSEN1) gene, and performed genome-wide association testing to identify variants that modify age at onset (AAO) of Alzheimer's disease. Our analysis identified a haplotype of single-nucleotide polymorphisms (SNPs) on chromosome 17 within a chemokine gene cluster associated with delayed onset of mild-cognitive impairment and dementia. Individuals carrying this haplotype had a mean AAO of mild-cognitive impairment at 51.0 ± 5.2 years compared with 41.1 ± 7.4 years for those without these SNPs. This haplotype thus appears to modify Alzheimer's AAO, conferring a large (~10 years) protective effect. The associated locus harbors several chemokines including eotaxin-1 encoded by CCL11, and the haplotype includes a missense polymorphism in this gene. Validating this association, we found plasma eotaxin-1 levels were correlated with disease AAO in an independent cohort from the University of California San Francisco Memory and Aging Center. In this second cohort, the associated haplotype disrupted the typical age-associated increase of eotaxin-1 levels, suggesting a complex regulatory role for this haplotype in the general population. Altogether, these results suggest eotaxin-1 as a novel modifier of Alzheimer's disease AAO and open potential avenues for therapy.