Biology of Cryptostroma corticale and the sooty bark disease of sycamore

Imperial Users onl

What goes up must come down: insights from studies on descending controls acting on spinal pain processing

Descending controls link higher processing of noxious signals to modulation of spinal cord responses to their noxious inputs. It has become possible to study one key inhibitory system in animals and humans using one painful stimulus to attenuate another distant response and so eliciting diffuse noxious inhibitory controls (DNIC) or the human counterpart, conditioned pain modulation (CPM). Here, we discuss the neuronal pathways in both species, their pharmacology and examine changes in descending controls with a focus on osteoarthritis. We will also discuss the opposing descending facilitatory system. Strong parallels between DNIC and CPM emphasize the possibility of forward and reverse translation

The lady vanishes: what's missing from the stem cell debate

Most opponents of somatic cell nuclear transfer and embryonic stem cell technologies base their arguments on the twin assertions that the embryo is either a human being or a potential human being, and that it is wrong to destroy a human being or potential human being in order to produce stem cell lines. Proponents’ justifications of stem cell research are more varied, but not enough to escape the charge of obsession with the status of the embryo. What unites the two warring sides in ‘the stem cell wars’ is that women are equally invisible to both: ‘the lady vanishes’. Yet the only legitimate property in the body is that which women possess in their reproductive tissue and the products of their reproductive labour. By drawing on the accepted characterisation in law of property as a bundle of rights, and on a Hegelian model of contract as mutual recognition, we can lessen the impact of the tendency to regard women and their eggs as merely receptacles and women’s reproductive labour as unimportant

Achieving diffraction-limited performance on the Berkeley MET5

The Berkeley MET5, funded by EUREKA, is a 0.5-NA EUV projection lithography tool located at the Advanced Light Source at Berkeley National Lab. Wavefront measurements of the MET5 optic have been performed using a custom in-situ lateral shearing interferometer suitable for high-NA interferometry. In this paper, we report on the most recent characterization of the MET5 optic demonstrating an RMS wavefront 0.31 nm, and discuss the specialized mask patterns, gratings, and illumination geometries that were employed to accommodate the many challenges associated with high-NA EUV interferometry

Characterization of Power Induced Heating and Damage in Fiber Optic Probes for Near-Field Scanning Optical Microscopy

Tip-induced sample heating in near-field scanning optical microscopy (NSOM) is studied for fiber optic probes fabricated using the chemical etching technique. To characterize sample heating from etched NSOM probes, the spectra of a thermochromic polymer sample are measured as a function of probe output power, as was previously reported for pulled NSOM probes. The results reveal that sample heating increases rapidly to ~55–60°C as output powers reach ~50 nW. At higher output powers, the sample heating remains approximately constant up to the maximum power studied of ~450 nW. The sample heating profiles measured for etched NSOM probes are consistent with those previously measured for NSOM probes fabricated using the pulling method. At high powers, both pulled and etched NSOM probes fail as the aluminum coating is damaged. For probes fabricated in our laboratory we find failure occurring at input powers of 3.4 ± 1.7 and 20.7 ± 6.9 mW for pulled and etched probes, respectively. The larger half-cone angle for etched probes (∼15° for etched and ~6° for pulled probes) enables more light delivery and also apparently leads to a different failure mechanism. For pulled NSOM probes, high resolution images of NSOM probes as power is increased reveal the development of stress fractures in the coating at a taper diameter of ~6μm. These stress fractures, arising from the differential heating expansion of the dielectric and the metal coating, eventually lead to coating removal and probe failure. For etched tips, the absence of clear stress fractures and the pooled morphology of the damaged aluminum coating following failure suggest that thermal damage may cause coating failure, although other mechanisms cannot be ruled out

Characterization of power induced heating and damage in fiber optic probes for near-field scanning optical microscopy

This is the published version, also available here: http://dx.doi.org/10.1063/1.2740133.Tip-induced sample heating in near-field scanning optical microscopy (NSOM) is studied for fiber optic probes fabricated using the chemical etching technique. To characterize sample heating from etched NSOM probes, the spectra of a thermochromic polymer sample are measured as a function of probe output power, as was previously reported for pulled NSOM probes. The results reveal that sample heating increases rapidly to ∼55–60°C as output powers reach ∼50nW. At higher output powers, the sample heating remains approximately constant up to the maximum power studied of ∼450nW. The sample heating profiles measured for etched NSOM probes are consistent with those previously measured for NSOM probes fabricated using the pulling method. At high powers, both pulled and etched NSOM probes fail as the aluminumcoating is damaged. For probes fabricated in our laboratory we find failure occurring at input powers of 3.4±1.7 and 20.7±6.9mW for pulled and etched probes, respectively. The larger half-cone angle for etched probes (∼15° for etched and ∼6° for pulled probes) enables more light delivery and also apparently leads to a different failure mechanism. For pulled NSOM probes, high resolution images of NSOM probes as power is increased reveal the development of stress fractures in the coating at a taper diameter of ∼6μm. These stress fractures, arising from the differential heating expansion of the dielectric and the metalcoating, eventually lead to coating removal and probe failure. For etched tips, the absence of clear stress fractures and the pooled morphology of the damaged aluminumcoating following failure suggest that thermal damage may cause coating failure, although other mechanisms cannot be ruled out

Tapentadol at medium to high doses in patients previously receiving strong opioids for the management of cancer pain.

Abstract Abstract Objective: The aim of this study was to assess the efficacy and tolerability of tapentadol (TP) for a period of 4 weeks in patients who were already treated by opioids. Methods: A convenience sample of 30 patients was selected for a prospective observational cohort study. Cancer patients who were receiving at least 60 mg of oral morphine equivalents were selected. Patients discontinued their previous opioid analgesics before starting TP, in doses calculated according the previous opioid consumption (1:3.3 ratio with oral morphine equivalents). The subsequent doses were changed according to the patients' needs for a period of 4 weeks. Oral morphine was offered as a breakthrough pain medication. Pain and symptom intensity were recorded at weekly intervals. Distress score (DS) was calculated from the sum of symptom intensities. TP opioid escalation indexes (TPEI) for the study period were calculated. Results: Nineteen patients were male, and the mean age was 63.5 years (±11.5). The mean Karnofsky status was 62.9 (±10). The mean dose of oral morphine equivalents before switching to TP was 112 mg (±57) and the initial mean dose of TP was 343 mg (±150). Pain intensity significantly decreased. Tapentadol escalation index in percentage was 1.26 (TPEI% ± 2.6) and Tapentadol escalation index in mg was 2.76 (TPEImg ± 4.96). No significant relationships were found with primary tumor (TPEI%, p = 0.204; TPEImg, p = 0.180), pain mechanism (TPEI%, p = 0.863; TPEImg, p = 0.846), age (TPEI%, p = 0.882; TPEImg, p = 0.884), or gender (TPEI%, p = 0.287; TPEImg, p = 0.325). DS decreased, but non-significantly (p = 0.1). Ten patients did not complete the study period: five patients discontinued TP for uncontrolled pain, despite increasing doses of TP over 600 mg/day. Two patients discontinued TP for adverse effects and three patients dropped out, one patient for poor compliance and two patients for unrecorded reasons. Conclusion: In our sample, TP used in doses of 350-450 mg/day was well tolerated and effective in opioid tolerant patients with cancer pain and could be considered as a flexible drug to be used for the management of moderate to severe cancer pain. Like most studies in patients with cancer pain, it was limited by its open-label, uncontrolled design, the number of patients lost in follow-up, and discontinuation of the treatment for several reasons. Further studies in a large number of patients should confirm these preliminary results

Electrophysiological characterization of activation state-dependent Cav2 channel antagonist TROX-1 in spinal nerve injured rats

AbstractPrialt, a synthetic version of Cav2.2 antagonist ω-conotoxin MVIIA derived from Conus magus, is the first clinically approved voltage-gated calcium channel blocker for refractory chronic pain. However, due to the narrow therapeutic window and considerable side effects associated with systemic dosing, Prialt is only administered intrathecally. N-triazole oxindole (TROX-1) is a novel use-dependent and activation state-selective small-molecule inhibitor of Cav2.1, 2.2 and 2.3 calcium channels designed to overcome the limitations of Prialt. We have examined the neurophysiological and behavioral effects of blocking calcium channels with TROX-1. In vitro, TROX-1, in contrast to state-independent antagonist Prialt, preferentially inhibits Cav2.2 currents in rat dorsal root ganglia (DRG) neurons under depolarized conditions. In vivo electrophysiology was performed to record from deep dorsal horn lamina V/VI wide dynamic range neurons in non-sentient spinal nerve-ligated (SNL) and sham-operated rats. In SNL rats, spinal neurons exhibited reduced responses to innocuous and noxious punctate mechanical stimulation of the receptive field following subcutaneous administration of TROX-1, an effect that was absent in sham-operated animals. No effect was observed on neuronal responses evoked by dynamic brushing, heat or cold stimulation in SNL or sham rats. The wind-up response of spinal neurons following repeated electrical stimulation of the receptive field was also unaffected. Spinally applied TROX-1 dose dependently inhibited mechanically evoked neuronal responses in SNL but not sham-operated rats, consistent with behavioral observations. This study confirms the pathological state-dependent actions of TROX-1 through a likely spinal mechanism and reveals a modality selective change in calcium channel function following nerve injury

Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats.

Pro-nociceptive ON-cells in the rostral ventromedial medulla (RVM) facilitate nociceptive processing and contribute to descending serotonergic controls. We use RVM injections of neurotoxic dermorphin-saporin (Derm-SAP) in rats to evaluate the role of putative ON-cells, or μ-opioid receptor-expressing (MOR) neurones, in visceral pain processing. Our immunohistochemistry shows that intra-RVM Derm-SAP locally ablates a substantial proportion of MOR and serotonergic cells. Given the co-localization of these neuronal markers, some RVM ON-cells are serotonergic. We measure visceromotor responses in the colorectal distension (CRD) model in control and Derm-SAP rats, and using the 5-HT(3) receptor antagonist ondansetron, we demonstrate pro-nociceptive serotonergic modulation of visceral nociception and a facilitatory drive from RVM MOR cells. The α(2)δ calcium channel ligand pregabalin produces state-dependent analgesia in neuropathy and osteoarthritis models relating to injury-specific interactions with serotonergic facilitations from RVM MOR cells. Although RVM MOR cells mediate noxious mechanical visceral input, we show that their presence is not a permissive factor for pregabalin analgesia in acute visceral pain