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"Nicholson, James"
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High-Resolution Patterned Cellular Constructs by Droplet-Based 3D Printing
Bioprinting is an emerging technique for the fabrication of living tissues that allows cells to be arranged in predetermined three-dimensional (3D) architectures. However, to date, there are limited examples of bioprinted constructs containing multiple cell types patterned at high-resolution. Here we present a low-cost process that employs 3D printing of aqueous droplets containing mammalian cells to produce robust, patterned constructs in oil, which were reproducibly transferred to culture medium. Human embryonic kidney (HEK) cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant densities (10
7
cells mL
−1
) and a high droplet resolution of 1 nL. High-resolution 3D geometries were printed with features of ≤200 μm; these included an arborised cell junction, a diagonal-plane junction and an osteochondral interface. The printed cells showed high viability (90% on average) and HEK cells within the printed structures were shown to proliferate under culture conditions. Significantly, a five-week tissue engineering study demonstrated that printed oMSCs could be differentiated down the chondrogenic lineage to generate cartilage-like structures containing type II collagen.
Journal Article
1968 : a pivotal moment in American sports
\"Opening with Vince Lombardi's last win as coach of the Packers in Super Bowl II and closing with Joe Namath's Super Bowl III guarantee, James Nicholson delivers an original portrait of a sensational closing decade in American culture. Controversies on the field and in the ring reflected broader political and social turmoil in the late-sixties United States. With one of the most contentious presidential elections in US history, the ongoing civil rights movement, and the Vietnam War all storming in the background, Nicholson charts a course through the oddly unsettled waters of American sports in 1968: the Masters golf tournament decided by the strict enforcement of an arcane rule to the detriment of a foreign player; the winner of the Kentucky Derby disqualified for a drug violation; Muhammad Ali waiting in sports exile while he appealed a criminal conviction for draft evasion; an unorthodox rendition of the national anthem at the World Series nearly overshadowing the game it preceded; and the silent gesture at the Mexico City Olympics made by Tommie Smith and John Carlos that shocked the nation\"-- Provided by publisher.
Book
Consensus on the management of intracranial germ-cell tumours
The management of intracranial germ-cell tumours is complex because of varied clinical presentations, tumour sites, treatments and outcomes, and the need for multidisciplinary input. Participants of the 2013 Third International CNS Germ Cell Tumour Symposium (Cambridge, UK) agreed to undertake a multidisciplinary Delphi process to identify consensus in the clinical management of intracranial germ-cell tumours. 77 delegates from the symposium were selected as suitable experts in the field and were invited to participate in the Delphi survey, of which 64 (83%) responded to the invitation. Invited participants represented multiple disciplines from Asia, Australasia, Europe, and the Americas. 38 consensus statements encompassing aspects of intracranial germ-cell tumour work-up, staging, treatment, and follow-up were prepared. To achieve consensus, statements required at least 70% agreement from at least 60% of respondents. Overall, 34 (89%) of 38 statements met consensus criteria. This international Delphi approach has defined key areas of consensus that will help guide and streamline clinical management of patients with intracranial germ-cell tumours. Additionally, the Delphi approach identified areas of different understanding and clinical practice internationally in the management of these tumours, areas which should be the focus of future collaborative studies. Such efforts should translate into improved patient outcomes.
Journal Article
The Hejaz railway
\"For the better part of a century the Hejaz Railway has been known for Lawrence of Arabia's celebrated desert campaign, fighting alongside the bedouin in the Arab Revolt during the First World War. Yet perhaps the reputation that it truly deserves is for the epic story of its construction, a monumental feat of engineering, requiring enormous imagination, skill and resolve. Here was something breathtaking, combining the romance of steam locomotion with the grandiose vision of the last years of the mighty Ottoman Empire.\" \"Conceived in the dying days of the nineteenth century and constructed under the Ottoman Sultan Abdulhamid II, the railway followed the overland pilgrim trail from Damascus deep into the heart of Arabia to reach the holy city of Madinah. It was to lay its tracks across pitiless, wadi-fissured deserts and the unforgiving mountains of the Hejaz, from which the line would earn its name.\"--Jacket.
Book
Paediatric extracranial germ-cell tumours
Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.
Journal Article
The concise Oxford dictionary of mathematics
This dictionary contains over 3,000 clear and concise entries updated in line with curriculum and degree requirements. It covers pure and applied mathematics and statistics, features entry-level web links, and includes detailed appendices. -- Source other than Library of Congress.
Book
Antibiotic and chemotherapeutic enhanced three-dimensional printer filaments and constructs for biomedical applications
Three-dimensional (3D) printing and additive manufacturing holds potential for highly personalized medicine, and its introduction into clinical medicine will have many implications for patient care. This paper demonstrates the first application of 3D printing as a method for the potential sustained delivery of antibiotic and chemotherapeutic drugs from constructs for patient treatment. Our design is focused on the on-demand production of anti-infective and chemotherapeutic filaments that can be used to create discs, beads, catheters, or any medical construct using a 3D printing system. The design parameters for this project were to create a system that could be modularly loaded with bioactive agents. All 3D-printed constructs were loaded with either gentamicin or methotrexate and were optimized for efficient and extended antibacterial and cancer growth-inhibiting cytostatic activity. Preliminary results demonstrate that combining gentamicin and methotrexate with polylactic acid forms a composite possessing a superior combination of strength, versatility, and enhanced drug delivery. Antibacterial effects and a reduction in proliferation of osteosarcoma cells were observed with all constructs, attesting to the technical and clinical viability of our composites. In this study, 3D constructs were loaded with gentamicin and methotrexate, but the method can be extended to many other drugs. This method could permit clinicians to provide customized and tailored treatment that allows patient-specific treatment of disease and has significant potential for use as a tunable drug delivery system with sustained-release capacity for an array of biomedical applications.
Journal Article
Reduced kynurenine pathway metabolism and cytokine expression in the prefrontal cortex of depressed individuals
Neuroinflammatory processes are increasingly believed to participate in the pathophysiology of a number of major psychiatric diseases, including depression. Immune activation stimulates the conversion of the amino acid tryptophan to kynurenine, leading to the formation of neuroactive metabolites, such as quinolinic acid and kynurenic acid. These compounds affect glutamatergic neurotransmission, which plays a prominent role in depressive pathology. Increased tryptophan degradation along the kynurenine pathway (KP) has been proposed to contribute to disease etiology.
We used postmortem brain tissue from the ventrolateral prefrontal cortex (VLPFC) to assess tissue levels of tryptophan and KP metabolites, the expression of several KP enzymes and a series of cytokines as well as tissue pathology, including microglial activation. Tissue samples came from nonpsychiatric controls (n = 36) and individuals with depressive disorder not otherwise specified (DD-NOS, n = 45) who died of natural causes, homicide, accident, or suicide.
We found a reduction in the enzymatic conversion of tryptophan to kynurenine, determined using the kynurenine:tryptophan ratio, and reduced messenger RNA expression of the enzymes indoleamine-2,3-dioxygenase 1 and 2 and tryptophan-2,3-dioxygenase in depressed individuals irrespective of the cause of death. These findings correlated with reductions in the expression of several cytokines, including interferon-γ and tumour necrosis factor-α. Notably, quinolinic acid levels were also lower in depressed individuals than controls.
Information on the use of antidepressants and other psychotropic medications was insufficient for statistical comparisons.
Contrary to expectations, the present results indicate that depression, in the absence of medical illness or an overt inflammatory process, is associated with compromised, rather than increased, KP metabolism in the VLPFC.
Journal Article