Photophysical approaches to sensing melanoma

The spectroscopic/structure relationship of melanin is poorly understood which impedes the development of new biomaterials and skin cancer sensing techniques. Current methods for detecting melanoma ether lack the diagnostic capabilities or require high expense and training to use. There is a need for a melanoma diagnostic device that is both simple to use and cost-effective. The intrinsic response of eumelanin and pheomelanin with spectrophotometry, spectrofluorometry and time-correlated single photon counting were measured in order to investigate the photophysics of melanin and find a potential new technique for diagnosing melanoma that could be developed into a point-of-care device.;The optical and radiosensitising properties of gold nanorods make them attractive for biosensing applications. The toxicity of different gold nanorods, with alternative coatings, were investigated in order to establish their viability for development of a melanoma-specific biosensor. The results from the clonogenic toxicity assay and flow cytometry suggest that the gold nanorods induces long term damaging effects to the cells which hinder their viability as a biosensor.;The spectroscopic response of the sheet sensing fluorescent probe thioflavin T was measured during the formation of pheomelanin as the evidence for sheet formation in the red/yellow pigment is not as well established as the brown/black pigment, eumelanin. The increase of the dye molecule's fluorescence intensity provides strong evidence for the presence of sheet structures within pheomelanin and open up the potential use of extrinsic fluorophores as melanoma sensing probes. Successful implementation of extrinsic fluorophores could lead to investigating melanin's structure via super-resolution techniques.The spectroscopic/structure relationship of melanin is poorly understood which impedes the development of new biomaterials and skin cancer sensing techniques. Current methods for detecting melanoma ether lack the diagnostic capabilities or require high expense and training to use. There is a need for a melanoma diagnostic device that is both simple to use and cost-effective. The intrinsic response of eumelanin and pheomelanin with spectrophotometry, spectrofluorometry and time-correlated single photon counting were measured in order to investigate the photophysics of melanin and find a potential new technique for diagnosing melanoma that could be developed into a point-of-care device.;The optical and radiosensitising properties of gold nanorods make them attractive for biosensing applications. The toxicity of different gold nanorods, with alternative coatings, were investigated in order to establish their viability for development of a melanoma-specific biosensor. The results from the clonogenic toxicity assay and flow cytometry suggest that the gold nanorods induces long term damaging effects to the cells which hinder their viability as a biosensor.;The spectroscopic response of the sheet sensing fluorescent probe thioflavin T was measured during the formation of pheomelanin as the evidence for sheet formation in the red/yellow pigment is not as well established as the brown/black pigment, eumelanin. The increase of the dye molecule's fluorescence intensity provides strong evidence for the presence of sheet structures within pheomelanin and open up the potential use of extrinsic fluorophores as melanoma sensing probes. Successful implementation of extrinsic fluorophores could lead to investigating melanin's structure via super-resolution techniques

The prevalence and recognition of depression in elderly patients attending their general practitioners

This thesis reports an attempt to establish the prevalence of depressive states in elderly attenders at certain general practice surgeries, to examine the accuracy with which depression is recognised by general practitioners, and to throw light on the course of such states in this 'community' sample. A discrepancy between age-related prevalence rates of non-psychotic disorders in patients admitted to hospital in the United Kingdom and those not admitted is reported from published data. Using depressive states as an example of this type of disorder, suggested reasons for this discrepancy are examined in the light of a review of the relevant literature- including the possibilities that prevalence declines with age, that older people are less likely to be in contact with general practitioners, that these disorders are less likely to be recognised by general practitioners in older patients, and that older patients with depressive states are less likely to be referred for specialist help and therefore admitted. After consideration of various problems of method, a study of the prevalence of depressive states in 235 attenders over the age of 65 at the surgeries of 12 general practitioners is described. The prevalence of 'significantly depressed states' in this group was determined as 30.6%, and 82.5% of those with such states were recognised as depressed by their general practitioners, although only 1 was referred to psychiatric care. These states were found to be highly correlated with consumption of psychotropic medication and rates of consultation with general practitioners, and one third of them persisted over a 9-month follow-up period, indicating their importance. These results are discussed in the light of other work of a similar nature in younger age-groups, and it is concluded that the cost-effectiveness of efforts to improve general practitioners' rates of recognition of depressive states is likely to be limited, whereas efforts to improve selection for specialist referral would be more profitable, especially if improvement in outcome could be shown as a result of such intervention

Probing pheomelanin synthesis using thioflavin T fluorescence

The fluorescent rotor probe thioflavin T (ThT) is used to investigate the presence of sheet structures in pheomelanin by studying the formation and disassembly of pheomelanin synthesized from L-cysteine, L-DOPA and the enzyme tyrosinase. Brown/black eumelanin and red/yellow pheomelanin are the most common forms of melanin with the former more extensively studied. The conclusion of decades of research is that both melanins possess ill-defined polymeric structures, which are reflected in their complex photophysics. The structural integrity and co-existence of these two forms has significant bearing on their functionality and indeed their spectroscopy offers possibilities as a melanoma biomarker. Extrinsic fluorescence probes have been little used to study melanin, but the evidence from ThT fluorescence is consistent with other techniques in finding that eumelanin’s constituent dihydroxyindoles form a stacked sheet structure akin to graphite. Whether or not such an equivalent sheet structure exists for pheomelanin’s constituent benzothiazines and benzothiazoles is unresolved. On investigating this possibility we find a sigmoidal increase in ThT fluorescence during pheomelanin synthesis is similar to that observed for eumelanin, implying a sheet structure. A red spectral shift in ThT fluorescence in pheomelanin and the emergence of a fluorescence decay component of ~ 5.5 ns, much longer than that of ThT, are interpreted in terms of sites wherein ThT is coupled to pheomelanin’s native structure. Such sites can act as fluorescent traps to which energy is funneled when melanin is excited and the composite fluorescence yield thus increased. However, we find the abundance of this decay component is significantly less for pheomelanin (6%) than eumelanin (11%), suggesting that ThT does not intercalate so readily in pheomelanin. This may reflect less sheet structure or tighter binding of pheomelanin’s sheets, consistent with its low fluorescence quantum yield. Disassembling pheomelanin upon raising pH provides further spectroscopic evidence that ThT is trapped in sheet-like aggregates of smaller oligomeric forms

Thermodynamic efficiency of carbon capture and utilisation in anaerobic batch digestion process

Carbon capture and storage (CCS) in the oil and water industries is becoming common and a significant consumer of energy typically requiring 150–450 °C and or several hundred bar pressure [1] particularly in geological deposition. A biological carbon capture and conversion has been considered in conventional anaerobic digestion processes. The process has been utilised in biological mixed culture, where acetoclastic bacteria and hydrogenophilic methanogens play a major key role in the utilisation of carbon dioxide. However, the bio catalytic microorganisms, hydrogenophilic methanogens are reported to be unstable with acetoclastic bacteria. In this work the biochemical thermodynamic efficiency was investigated for the stabilisation of the microbial process in carbon capture and utilisation. The authors observed that a thermodynamic efficiency of biological carbon capture and utilisation (BCCU) had 32% of overall reduction in yield of carbon dioxide with complimentary increase of 30% in yield of methane, while the process was overall endothermic. Total consumption of energy (≈0.33 MJ l−1) was estimated for the carbonate solubility (0.1 mol l−1) in batched BCCU. This has a major influence on microbial composition in the bioreactor. This thermodynamic study is an essential tool to aid the understanding of the interactions between operating parameters and the mixed microbial culture

Colon polyps in patients with short bowel syndrome before and after teduglutide: post hoc analysis of the STEPS study series

Background & aims: Teduglutide promotes intestinal growth and is approved for the treatment of short bowel syndrome and intestinal failure (SBS-IF). Based on the pharmacologic activity and preclinical findings, teduglutide can potentially induce proliferative colonic mucosal changes. The aim of this study is to report the occurrence of colorectal polyps in adult patients with SBS-IF who received teduglutide in clinical studies conducted to date. Methods: A post hoc analysis of the completed Study of Teduglutide Effectiveness in Parenteral Nutrition-Dependent Short Bowel Syndrome Subjects (STEPS) clinical study series (NCT00798967, EudraCT 2008-006193-15; NCT00930644, EudraCT 2009-011679-65; NCT01560403) evaluated electronic case report form data for baseline colonoscopies (performed before treatment) and for surveillance or end-of-study (performed after treatment with teduglutide 0.05 mg/kg/day for 24 and 36 months) post-exposure procedures. Results: In the STEPS studies, 73 patients treated with teduglutide had a baseline colonoscopy. No post-exposure colonoscopy was scheduled in STEPS. In STEPS-2/3, 50 of 65 patients with remnant colon (77%) underwent a protocol-mandated post-exposure colonoscopy. Colon polyps were reported at baseline in 12% (9/73) of patients and post-exposure in 18% (9/50) of patients. Two had polyps both at baseline and post-exposure. On histology, available for 7 patients, 5 had adenomas (1 serrated, 4 tubular) and none had malignancy or high-grade dysplasia. Conclusion: These data support recommendations for colonoscopic screening before teduglutide therapy and subsequent on-therapy colonoscopic surveillance for patients with SBS-IF. Further studies are required to assess the risk of polyp formation in patients with SBS-IF and the most appropriate colon polyp surveillance strategies

Incidence and clinical implications of intraoperative BITA grafts conversion. Insights from the Arterial Revascularization Trial

Background: The arterial revascularization trial (ART) has been designed to answer the question whether the use of bilateral internal thoracic arteries (BITA) can improve 10-year outcomes when compared to single internal thoracic artery (SITA). In the ART, a significant proportion of patients initially allocated to BITA received other conduit strategies. We sought to investigate the incidence and clinical implication of BITA grafts conversion in the ART. Methods: Among patients enrolled in the ART (n=3102), we excluded those allocated to SITA (n=1554), those who did not undergo surgery (n=16) and those operated on but withdrew after randomization (n=7). Propensity score matching was used to compare converted vs non-converted BITA groups. Results: A total of 1525 patients were operated with intention to receive BITA grafting. Of those, 233 (15.3%) were converted to other conduit selection strategies. Incidence of conversion largely varied across 28 centres involved (from 0% to 42.9%). The most common reason for BITA grafts conversion was the evidence of at least one internal thoracic artery not suitable which was reported in 77 cases. Patients with intraoperative BITA graft conversion received a lower number of grafts (2.95±0.84 vs 3.21±0.74; P<0.001). However, hospital mortality rate was comparable to those who did not require BITA graft conversion (0 vs 1.6%; P=0.1) as well as the incidence of major complications. At 5 years we found a non-significant excess of deaths (11.9% vs 8.4%; P=0.1) and major adverse events (17.1% 13.2%; P=0.1) mainly driven by an excess of revascularization in patients requiring conversion. Conclusions: The incidence of intraoperative BITA graft conversion is not irrelevant . BITA graft conversion is not associated with increased operative morbidity but its effect on late outcomes remain uncertain

Impact of dual antiplatelet therapy after coronary artery bypass surgery on 1-year outcomes in the Arterial Revascularization Trial

OBJECTIVES: There is still little evidence to boldport routine dual antiplatelet therapy (DAPT) with P2Y12 antagonists following coronary artery bypass grafting (CABG). The Arterial Revascularization Trial (ART) was designed to compare 10-year survival after bilateral versus single internal thoracic artery grafting. We aimed to get insights into the effect of DAPT (with clopidogrel) following CABG on 1-year outcomes by performing a post hoc ART analysis. METHODS: Among patients enrolled in the ART (n  = 3102), 609 (21%) and 2308 (79%) were discharged on DAPT or aspirin alone, respectively. The primary end-point was the incidence of major adverse cerebrovascular and cardiac events (MACCE) at 1 year including cardiac death, myocardial infarction, cerebrovascular accident and reintervention; safety end-point was bleeding requiring hospitalization. Propensity score (PS) matching was used to create comparable groups. RESULTS: Among 609 PS-matched pairs, MACCE occurred in 34 (5.6%) and 34 (5.6%) in the DAPT and aspirin alone groups, respectively, with no significant difference between the 2 groups [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.59-1.59; P  = 0.90]. Only 188 (31%) subjects completed 1 year of DAPT, and in this subgroup, MACCE rate was 5.8% (HR 1.11, 95% CI 0.53-2.30; P  = 0.78). In the overall sample, bleeding rate was higher in DAPT group (2.3% vs 1.1%; P  = 0.02), although this difference was no longer significant after matching (2.3% vs 1.8%; P  = 0.54). CONCLUSIONS: Based on these findings, when compared with aspirin alone, DAPT with clopidogrel prescribed at discharge was not associated with a significant reduction of adverse cardiac and cerebrovascular events at 1 year following CABG