646 research outputs found
Mesoscopic order and the dimentionality of long-range resonance energy transfer in supramolecular semiconductors
We present time-resolved photoluminescence measurements on two series of
oligo-p-phenylenevinylene materials that self-assemble into supramolecular
nanostructures with thermotropic reversibility in dodecane. One set of
derivatives form chiral, helical stacks while the second set form less
organised, frustrated stacks. Here we study the effects of supramolecular
organisation on the resonance energy transfer rates. We measure these rates in
nanoassemblies formed with mixed blends of oligomers and compare them with the
rates predicted by Foerster theory. Our results and analysis show that control
of supramolecular order in the nanometre lengthscale has a dominant effect on
the efficiency and dimentionality of resonance energy transfer.Comment: 17 Pages, 5 Figures, Submitted to J. Chem. Phy
Late Effects After Haematopoietic Stem Cell Transplantation in ALL, Long-Term Follow-Up and Transition: A Step Into Adult Life
Haematopoietic stem cell transplant (HSCT) can be a curative treatment for children and adolescents with very-high-risk acute lymphoblastic leukaemia (ALL). Improvements in supportive care and transplant techniques have led to increasing numbers of long-term survivors worldwide. However, conditioning regimens as well as transplant-related complications are associated with severe sequelae, impacting patients' quality of life. It is widely recognised that paediatric HSCT survivors must have timely access to life-long care and surveillance in order to prevent, ameliorate and manage all possible adverse late effects of HSCT. This is fundamentally important because it can both prevent ill health and optimise the quality and experience of survival following HSCT. Furthermore, it reduces the impact of preventable chronic illness on already under-resourced health services. In addition to late effects, survivors of paediatric ALL also have to deal with unique challenges associated with transition to adult services. In this review, we: (1) provide an overview of the potential late effects following HSCT for ALL in childhood and adolescence; (2) focus on the unique challenges of transition from paediatric care to adult services; and (3) provide a framework for long-term surveillance and medical care for survivors of paediatric ALL who have undergone HSCT
Influence of eye movement on lens dose and optic nerve target coverage during craniospinal irradiation
PURPOSE: Optic nerves are part of the craniospinal irradiation (CSI) target volume. Modern radiotherapy techniques achieve highly conformal target doses while avoiding organs-at-risk such as the lens. The magnitude of eye movement and its influence on CSI target- and avoidance volumes are unclear. We aimed to evaluate the movement-range of lenses and optic nerves and its influence on dose distribution of several planning techniques. METHODS: Ten volunteers underwent MRI scans in various gaze directions (neutral, left, right, cranial, caudal). Lenses, orbital optic nerves, optic discs and CSI target volumes were delineated. 36-Gy cranial irradiation plans were constructed on synthetic CT images in neutral gaze, with Volumetric Modulated Arc Therapy, pencil-beam scanning proton therapy, and 3D-conventional photons. Movement-amplitudes of lenses and optic discs were analyzed, and influence of gaze direction on lens and orbital optic nerve dose distribution. RESULTS: Mean eye structures’ shift from neutral position was greatest in caudal gaze; −5.8±1.2 mm (±SD) for lenses and 7.0±2.0 mm for optic discs. In 3D-conventional plans, caudal gaze decreased Mean Lens Dose (MLD). In VMAT and proton plans, eye movements mainly increased MLD and diminished D98 orbital optic nerve (D98(OON)) coverage; mean MLD increased up to 5.5 Gy [total ΔMLD range −8.1 to 10.0 Gy], and mean D98(OON) decreased up to 3.3 Gy [total ΔD98(OON) range −13.6 to 1.2 Gy]. VMAT plans optimized for optic disc Internal Target Volume and lens Planning organ-at-Risk Volume resulted in higher MLD over gaze directions. D98(OON) became ≥95% of prescribed dose over 95/100 evaluated gaze directions, while all-gaze bilateral D98(OON) significantly changed in 1 of 10 volunteers. CONCLUSION: With modern CSI techniques, eye movements result in higher lens doses and a mean detriment for orbital optic nerve dose coverage of <10% of prescribed dose
Degenerated cones in cultured human retinas can successfully be optogenetically reactivated
Biblical references aside, restoring vision to the blind has proven to be a major technical challenge. In recent years, considerable advances have been made towards this end, especially when retinal degeneration underlies the vision loss such as occurs with retinitis pigmentosa. Under these conditions, optogenetic therapies are a particularly promising line of inquiry where remaining retinal cells are made into "artificial photoreceptors". However, this strategy is not without its challenges and a model system using human retinal explants would aid its continued development and refinement. Here, we cultured post-mortem human retinas and show that explants remain viable for around 7 days. Within this period, the cones lose their outer segments and thus their light sensitivity but remain electrophysiologically intact, displaying all the major ionic conductances one would expect for a vertebrate cone. We optogenetically restored light responses to these quiescent cones using a lentivirus vector constructed to express enhanced halorhodopsin under the control of the human arrestin promotor. In these 'reactivated' retinas, we show a light-induced horizontal cell to cone feedback signal in cones, indicating that transduced cones were able to transmit their light response across the synapse to horizontal cells, which generated a large enough response to send a signal back to the cones. Furthermore, we show ganglion cell light responses, suggesting the cultured explant's condition is still good enough to support transmission of the transduced cone signal over the intermediate retinal layers to the final retinal output level. Together, these results show that cultured human retinas are an appropriate model system to test optogenetic vision restoration approaches and that cones which have lost their outer segment, a condition occurring during the early stages of retinitis pigmentosa, are appropriate targets for optogenetic vision restoration therapies.Therapeutic cell differentiatio
Exciton bimolecular annihilation dynamics in supramolecular nanostructures of conjugated oligomers
We present femtosecond transient absorption measurements on -conjugated
supramolecular assemblies in a high pump fluence regime.
Oligo(\emph{p}-phenylenevinylene) monofunctionalized with
ureido-\emph{s}-triazine (MOPV) self-assembles into chiral stacks in dodecane
solution below 75C at a concentration of M. We
observe exciton bimolecular annihilation in MOPV stacks at high excitation
fluence, indicated by the fluence-dependent decay of B-exciton
spectral signatures, and by the sub-linear fluence dependence of time- and
wavelength-integrated photoluminescence (PL) intensity. These two
characteristics are much less pronounced in MOPV solution where the phase
equilibrium is shifted significantly away from supramolecular assembly,
slightly below the transition temperature. A mesoscopic rate-equation model is
applied to extract the bimolecular annihilation rate constant from the
excitation fluence dependence of transient absorption and PL signals. The
results demonstrate that the bimolecular annihilation rate is very high with a
square-root dependence in time. The exciton annihilation results from a
combination of fast exciton diffusion and resonance energy transfer. The
supramolecular nanostructures studied here have electronic properties that are
intermediate between molecular aggregates and polymeric semiconductors
A Review of Acute and Long-Term Neurological Complications Following Haematopoietic Stem Cell Transplant for Paediatric Acute Lymphoblastic Leukaemia
Despite advances in haematopoietic stem cell transplant (HSCT) techniques, the risk of serious side effects and complications still exists. Neurological complications, both acute and long term, are common following HSCT and contribute to significant morbidity and mortality. The aetiology of neurotoxicity includes infections and a wide variety of non-infectious causes such as drug toxicities, metabolic abnormalities, irradiation, vascular and immunologic events and the leukaemia itself. The majority of the literature on this subject is focussed on adults. The impact of the combination of neurotoxic drugs given before and during HSCT, radiotherapy and neurological complications on the developing and vulnerable paediatric and adolescent brain remains unclear. Moreover, the age-related sensitivity of the nervous system to toxic insults is still being investigated. In this article, we review current evidence regarding neurotoxicity following HSCT for acute lymphoblastic leukaemia in childhood. We focus on acute and long-term impacts. Understanding the aetiology and long-term sequelae of neurological complications in children is particularly important in the current era of immunotherapy for acute lymphoblastic leukaemia (such as chimeric antigen receptor T cells and bi-specific T-cell engager antibodies), which have well-known and common neurological side effects and may represent a future treatment modality for at least a fraction of HSCT-recipients
Androgen deprivation therapy for androgen receptor-positive advanced salivary duct carcinoma:A nationwide case series of 35 patients in The Netherlands
Background: Salivary duct carcinoma, an aggressive subtype of salivary gland cancer, is mostly androgen receptor-positive. Only limited data are available on androgen deprivation therapy (ADT). Methods: Patients with advanced androgen receptor-positive salivary duct carcinoma treated with first-line ADT were retrospectively evaluated for clinical benefit (ie, partial response [PR] and stable disease, progression-free survival [PFS] and overall survival [OS]). The OS was compared with patients with advanced salivary duct carcinoma who received best supportive care. Results: Thirty-four of 35 patients who were ADT-treated were evaluable: 6 patients had a PR (18%) and 11 had stable disease (32%) leading to a clinical benefit ratio of 50%. The median PFS for the ADT-treated patients was 4 months and the median duration of clinical benefit was 11 months. The median OS was 17 months versus 5 months in 43 patients receiving best supportive care (P=.02). Conclusion: We recommend ADT in advanced androgen receptor-positive salivary duct carcinoma given its response and clinical benefit
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