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The ubiquitous challenge of plastic waste has led to the modern descriptor plastisphere to represent the human-made plastic environment and ecosystem. Here we report a straightforward rapid method for the catalytic deconstruction of various plastic feedstocks into hydrogen and high-value carbons. We use microwaves together with abundant and inexpensive iron-based catalysts as microwave susceptors to initiate the catalytic deconstruction process. The one-step process typically takes 30–90 s to transform a sample of mechanically pulverized commercial plastic into hydrogen and (predominantly) multiwalled carbon nanotubes. A high hydrogen yield of 55.6 mmol g–1plastic is achieved, with over 97% of the theoretical mass of hydrogen being extracted from the deconstructed plastic. The approach is demonstrated on widely used, real-world plastic waste. This proof-of-concept advance highlights the potential of plastic waste itself as a valuable energy feedstock for the production of hydrogen and high-value carbon materials.

We report a bottom-up synthetic biology approach to engineering vesicles with programmable permeabilities. Exploiting the concentration-dependent relationship between constitutively active pores (alpha-hemolysin) and blockers allows blockers to behave as molecular regulators for tuning permeability, enabling us to systematically modulate cargo release kinetics without changing the lipid fabric of the system.

Recent studies of single-atom catalysts open up the prospect of designing exceptionally active and environmentally efficient chemical processes. The stability and durability of such catalysts is governed by the strength with which the atoms are bound to their support and their diffusive behaviour. Here we use aberration-corrected STEM to image the diffusion of single copper adatoms on graphene oxide. We discover that individual atoms exhibit ano malous diffusion as a result of spatial and energetic disorder inherent in the support, and interpret the origins of this behaviour to develop a physical picture for the surface diffusion of single metal atoms.

This thesis is concerned with the development and application of AMPLE, a software pipeline for macromolecular crystallographic Molecular Replacement, to different classes of proteins. The ability of AMPLE to solve protein structures via Molecular Replacement was first explored with two new classes of proteins: coiled-coils and transmembrane helical proteins. The results were very positive, with AMPLE solving 75 of 94 (80%) of the coiled-coil and 10 of 15 (67%) of the transmembrane protein test cases. In both cases the performance of AMPLE was benchmarked against a library of ideal helices. The performance of idea helices was found to be surprisingly good (solving 44 of the coiled-coil and 7 of the transmembrane test cases), but the performance of AMPLE was significantly better. AMPLE's truncation and ensembling pipeline was then applied to the solution of protein structures using very distant homologs, and compared with the performance of the current state-of-the-art in automated Molecular Replacement in MRBUMP. The AMPLE pipeline was able to solve structures that could be be solved using MRBUMP, showing how AMPLE is able to find the evolutionarily conserved structural core from homologs that cannot be accessed using existing protocols. Work was also carried out to optimise AMPLE's cluster and truncate procedure. This has resulted in a significant improvement on AMPLE's ability to solve the structures in a difficult set of test cases (solving 11 of 18 test cases compared with 6 for the original protocol), despite only a modest increase in processing time. As part of this work, AMPLE has been extended from a prototype piece of software consisting of a collection of independent scripts, to a coherent, modularised program incorporating a range of software best practice. AMPLE is also

Active citizens may contribute to the environmental, social, and institutional resilience of cities. This review discusses how citizen initiatives protect biodiversity hotspots, contribute to social cohesion, institutional innovation, and diversity in urban green space management. Challenges related to social inclusiveness, ecological connectivity and continuity suggest government involvement is pertinent, but needs to be refocused. To maximise environmental outcomes of active citizenship, governments may adopt an enabling and stimulating governance style that harnesses the transformative potential of active citizenship. This paper argues for mosaic governance to work with the heterogeneous array of people, institutions, and spatial practices associated with active citizenship. Mosaic governance aims for a context-sensitive way of urban green infrastructure planning, enhancing relationships between the diversity of landscapes and communities across cities.

2-hydroxycarbazole, a compound structurally related to the Ca2+-mobilizing marine toxin 9-methyl-7-bromoeudistomin, has recently been proposed to activate both type 1 and type 2 ryanodine receptors in skeletal and cardiac muscle, respectively. This study was undertaken to evaluate the activity of this compound in the sea urchin egg homogenate, a model system used to characterize intracellular Ca2+ mobilization mechanisms. 2-Hydroxycarbazole was found to potently release Ca2+ in a concentration-dependent manner via a specific mechanism displaying apparent desensitization. Use of selective inhibitors of the Ca2+-mobilizing messengers inositol 1,4,5-trisphosphate, cyclic adenosine diphosphate ribose, and nicotinic acid adenine dinucleotide phosphate, as well as desensitization of homogenates to each of these molecules, failed to inhibit the response to 2-hydroxycarbazole. However, the response to 2-hydroxycarbazole was competitively antagonized by caffeine. Investigation of the Ca2+ stores accessed by 2-hydroxycarbazole revealed Ca2+ release from a thapsigargin-insensitive pool. Finally, 2-hydroxycarbazole failed to enhance [3H]ryanodine binding, suggesting the operation of a nonryanodine receptor mechanism. These results demonstrate that 2-hydroxycarbazole is acting to modulate a Ca2+ release mechanism with distinct pharmacological properties to those previously reported in the sea urchin egg.

Hypoxic pulmonary vasoconstriction is unique to pulmonary arteries and serves to match lung perfusion to ventilation. However, in disease states this process can promote hypoxic pulmonary hypertension. Hypoxic pulmonary vasoconstriction is associated with increased NADH levels in pulmonary artery smooth muscle and with intracellular Ca(2+) release from ryanodine-sensitive stores. Because cyclic ADP-ribose (cADPR) regulates ryanodine receptors and is synthesized from beta-NAD(+), we investigated the regulation by beta-NADH of cADPR synthesis and metabolism and the role of cADPR in hypoxic pulmonary vasoconstriction. Significantly higher rates of cADPR synthesis occurred in smooth muscle homogenates of pulmonary arteries, compared with homogenates of systemic arteries. When the beta-NAD(+):beta-NADH ratio was reduced, the net amount of cADPR accumulated increased. This was due, at least in part, to the inhibition of cADPR hydrolase by beta-NADH. Furthermore, hypoxia induced a 10-fold increase in cADPR levels in pulmonary artery smooth muscle, and a membrane-permeant cADPR antagonist, 8-bromo-cADPR, abolished hypoxic pulmonary vasoconstriction in pulmonary artery rings. We propose that the cellular redox state may be coupled via an increase in beta-NADH levels to enhanced cADPR synthesis, activation of ryanodine receptors, and sarcoplasmic reticulum Ca(2+) release. This redox-sensing pathway may offer new therapeutic targets for hypoxic pulmonary hypertension.

Tuberculosis is a common problem in South Africa, and provides a number of challenges for the anaesthetist. Patients may present in a variety of ways. Constitutional and pulmonary symptoms are the most common. These may impact on fitness for surgery and choice of anaesthesia. Tuberculosis treatment has the potential for a number of significant drug interactions. These are primarily mediated through induction of the cytochrome P450 enzyme system by rifampicin. Guidelines for the prevention of tuberculosis in the theatre environment need to be followed to avoid placing staff and other patients in danger.Keywords: tuberculosis, antitubercular agents, drug interactions, transmission, bacterial filter

cADP-ribose (cADPR), a naturally occurring metabolite of NAD(+), has been shown to be an important regulator of intracellular Ca(2+) release. Considerable evidence suggests that cADPR is the endogenous modulator of the ryanodine receptor (RyR), which mediates Ca(2+)-induced Ca(2+) release (CICR). Indeed, cADPR-mediated Ca(2+) release is subject to functional regulation by other modulators of CICR, including Ca(2+), caffeine and calmodulin. However, the underlying basis behind the effect of such agents on cADPR activity (in particular whether they regulate cADPR binding), as well as the precise nature of the cADPR receptor remains unclear. In the present study, use of (32)P-radiolabelled cADPR has enabled a detailed pharmacological characterization of cADPR-binding sites in sea urchin egg homogenates. We report that cADPR binds specifically to a single class of high affinity receptor. Retainment of binding to membranes after a high-salt wash suggests the involvement of either an integral membrane protein (possibly the RyR itself) or a peripheral protein tightly associated to the membrane. Insensitivity of [(32)P]cADPR binding to either FK506 or rapamycin suggests that this does not concern the FK506-binding protein. Significantly, binding is highly robust, being relatively insensitive to both endogenous and pharmacological modulators of RyR-mediated CICR. In turn, this suggests that such agents modulate cADPR-mediated Ca(2+) release primarily by tuning the 'gain' of the CICR system, upon which cADPR acts, rather than influencing the interaction of cADPR with its target receptor. The exception to this is calmodulin, for which our results indicate an additional role in facilitating cADPR binding.

Full Title: Intraoperative neurophysiological monitoring for the anaesthetist Part 2: A review of anaesthesia and its implications for intraoperative neurophysiological monitoringThe use of intraoperative neurophysiological monitoring (INM) during spinal orthopaedic and neurosurgical procedures provides a challenge to the attending anaesthesiologist. Since all anaesthetic agents affect synaptic function, the choice of agent will be determined by the type of surgery and the INM modality employed. Halogenated volatile agents decrease evoked potential (EP) amplitude and increase latency, and should be avoided in modalities that pass through cortical tracts. The effect on EPs is apparent at minimum alveolar concentrations of 0.3-0.5. Intravenous agents affect EPs in a dose-dependent manner, and should be titrated to response. Total intravenous anaesthesia with propofol and remifentanyl is the preferred technique. The risk of propofol infusion syndrome has not been shown to affect the choice of this agent. Compound muscle action potentials are abolished by barbiturates, and should be avoided during motor-evoked potential (MEP) monitoring. Although somatosensory-evoked potentials are unaffected by muscle relaxants, they prevent the monitoring of MEPs and should be avoided during multimodal use. When paralysis is required to ensure patient safety, the train-of-four ratio should be kept at 2/4 twitches and a T1 response at 10-20% of baseline, with use of a closed-loop system.Keywords: evoked potentials, intraoperative monitoring, brain mapping

Sentinel node biopsy (SNB) has been promoted by claims of a survival advantage after early lymphadenectomy in patients with a positive result. The pivotal paper states that SNB “identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy.”1 An earlier paper by Morton and colleagues states, “Our data suggest a significant therapeutic benefit for immediate …

A five-year-old girl, weighing 42 kg and with a diagnosis of Cushing’s disease, presented for bilateral, laparoscopic adrenalectomy.South Afr J Anaesth Analg 2011;17(6):396-399

It is a basic tenet of the sentinel lymph-node biopsy procedure that all positive sentinel lymph nodes will inevitably progress to palpable nodal recurrence if not removed. Comparison of survival is, therefore, considered permissible among patients with positive sentinel lymph nodes who undergo early lymphadenectomy with that among patients who have delayed lymphadenectomy for palpable regional node metastasis, providing that survival is calculated from the date of wide local excision of the primary tumor. Here, that fundamental assumption is contested and evidence is presented to show that a positive sentinel lymph node might have no adverse prognostic relevance in up to one-third of patients. Furthermore, in the same patients, progression to palpable nodal disease might not have occurred even if the positive sentinel node had not been removed. The term prognostic false-positivity is used to describe this phenomenon. Such patients are incorrectly up-staged, are given inaccurate prognostic information and can undergo unnecessary completion lymphadenectomy and unnecessary adjuvant therapy.

No Abstract. South African Medical Journal Vol. 96(9) (Part 2) 2006: 880-888

Background Postoperative portal vein infusion (PVI) of 5-fluorouracil (5-FU) is a well tolerated and widely applicable treatment for colorectal cancer that might have an enormous public health impact, even if it produced survival benefits of just a few per cent. Very large trials are required to detect such differences, and the Adjuvant X-ray and 5-FU Infusion Study (AXIS) is the largest such trial yet reported. Methods Consenting patients with presumed colorectal cancer were randomized to surgery with or without 7 days of PVI (1 g 5-FU plus 5000 units heparin in 1 litre 5 per cent dextrose infused over each 24-h period). In addition, patients with rectal cancer could be randomized to radiotherapy or no radiotherapy to be given either before or after surgery. Results Between November 1989 and December 1997, 3583 patients were randomized with respect to PVI. The survival hazard ratios (95 per cent confidence interval (c.i.)) in all patients randomized and in the curatively resected subgroup (71·2 per cent of patients) were 1·00 (0·92 to 1·11) and 0·94 (0·83 to 1·06) respectively. Tests for heterogeneity suggested a greater treatment benefit for patients with colonic cancer than for patients with rectal cancer with respect to disease-free survival (hazard ratio 0·79 versus 1·03; P = 0·07), and there was a non-significant trend with respect to overall survival (hazard ratio 0·87 versus 1·03; P = 0·17). No survival benefit was seen in the 761 patients randomized with respect to radiotherapy; although not statistically significant, the impact on local recurrence rates was similar to that reported in the literature. Conclusion No overall benefit of PVI was established in AXIS when colonic and rectal cancers were considered together, but the evidence suggesting a differential treatment effect according to site of cancer in AXIS was strongly supported by a meta-analysis incorporating the previous trials. Combining the data gave hazard ratios of 0·82 and 1·00 for colonic and rectal tumours respectively (test for interaction, P = 0·024), equating to an absolute survival benefit for patients with colonic cancer of 5·8 (95 per cent c.i. 2·8 to 8·5) per cent, a level close to that seen for prolonged systemic therapy.

Sentinel node biopsy has been enthusiastically adopted into clinical practice without a clear understanding of its benefit, which is often assumed rather than proved. Recently, the status of the sentinel node has been shown to be the most important predictor of recurrence and survival for patients with malignant melanoma. The proportion of patients who have had a negative sentinel node biopsy and who are free of disease at three years is 88.5% compared with 55.8% of patients with a positive biopsy; these groups have overall survival rates of 93% and 67%, respectively.1 2 The thickness of the tumour and whether there is ulceration remain important prognostic discriminators in patients with a negative biopsy.1 But is the ability to stratify patients prognostically enough to justify the widespread use of sentinel node biopsy or should we wait for evidence of a survival benefit after selective node dissection in patients who have had a positive sentinel node on biopsy? Several reasons have been given to justify the use of sentinel node biopsy. Firstly, it is cheaper and causes less morbidity than elective lymph node dissection. The total cost per patient, including the cost of wide local excision, is $19 285 (£12 856) for elective lymph node dissection compared with $13 835 for sentinel node biopsy under …

We report a metastatic cutaneous melanoma of the medial rectus muscle of the right orbit which presented with diplopia, exophthalmos and retrobulbar pain. Radioimmunoscintigraphy using melanoma-specific monoclonal antibody was used to confirm the diagnosis and to show the presence of disseminated disease in other areas. Effective palliation was achieved with external beam irradiation.