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Body size is considered to be one of the most important traits of an organism due to its strong links to many ecological and life history traits, and adult body size is often an important indicator of fitness. Recent research suggests that a decrease in body size is a common response to climate warming, particularly in ectotherms. However, my research shows that this is not the case for all species, with some showing the reverse response and others showing no response to temperature at all. My thesis shows that ecological and life history factors are important to consider when assessing the direction and strength of temperature-size responses across ectotherms. The overall aim of this study was to determine which ecological and life history factors may be important for determining ectotherm temperature-size responses using two representative taxa, marine gastropods and butterflies. This was achieved by using a combination of historical museum specimens (covering a temporal range of over 100 years) and modern field data. The results from the study show that factors such as taxon, developmental stage, sex and trophic level and habitat type are important for predicting temperature-size responses in ectotherms. Many species of terrestrial ectotherms, particularly insects, have been shown to increase in size with increasing temperatures. Yet, this study shows that when size is studied in relation to temperatures during each immature stage, that temperature-size responses can vary between life stages. Thus, overall changes in size will rely upon during which stage the individuals are experiencing warm or cool temperatures. Conversely, most aquatic species are expected to decrease in size as temperatures continue to rise. The results presented here, however, show that not all aquatic species respond in this way. None of the species studied decreased in size overtime, but size and shape vary spatially suggesting that the results may be a product of local conditions and not climate warming. Additionally, the work in this thesis highlights the importance of using museum collections in ecological research and the potential future applications given the technological advances such as digital collections and computer vision software.

Introduction: In the UK, more than 55000 women are diagnosed with breast cancer each year. There has been a 50% increase in the number of women undergoing immediate breast reconstruction after mastectomy, greater than 85% of these are implant based. One of the most common and unpredictable long-term complications is capsular contracture, occurring in up to 25% of cases. Acellular dermal matrices (ADM), now commonly used in immediate reconstruction, have been associated with reduced rates of capsular contracture but evidence supporting this is limited. Aims: In patients undergoing immediate implant based breast reconstruction with either Strattice™ or a submuscular technique, to determine and compare i) the incidence of capsular contracture and rates of revision surgery ii) patient reported outcomes iii) cosmetic outcomes and iv) short-term clinical outcomes. In vitro, to compare the implant capsule at the ADM interface and the native tissue (pectoralis muscle) interface. Methods: A retrospective multicentre cohort study of patients who underwent immediate implant based reconstruction with Strattice™ or a submuscular technique between January 2009 and December 2015 across three tertiary UK centres. Clinical examination and tonometry was performed, medical photographs and a comprehensive case note review undertaken. Participants completed the BREASTQ. In patients undergoing revision surgery after immediate implant based sub pectoral Strattice™ reconstruction biopsies were taken from two different areas of the capsule (ADM tissue interface versus pectoral tissue interface) and analysed using histology and immunohistochemistry. Results: The outcomes for 553 Strattice™ reconstructions and 242 submuscular reconstructions were compared. Unplanned explantation rate as a complication of primary surgery was 8.5% in the Strattice™-assisted group compared to 5.4% in the submuscular. Revision rates were equivalent between the groups (46.7% vs. 41.1%) but there were less revisions performed in the Strattice?- assisted group for capsular contracture (5.3% vs. 15.6%, p=<0.001). Capsular contracture occurred in 13.5% of the Strattice™ reconstructions compared to 21.5% of the submuscular (p=0.14). There were significantly higher aesthetic satisfaction scores from all three independent assessors in the Strattice™ group. There was no difference in BREAST-Q scores between the two groups. Capsules from 12 reconstructions were analysed at a median time of 6 months (range 5 – 81.5 months) from the last procedure. No difference in severity of inflammation between the two capsules was demonstrated but a difference in location of inflammation and an absence of the inner synovial like metaplasia layer in the ADM capsule was seen. The percentage of myofibroblasts was greater in the ADM capsules (p=0.04). In capsules older than two years there was higher proportion of elastin in the native capsule (p=0.0086). There was a greater proportion of mature collagen in the ADM capsules older than six months (p=NS). Conclusion: Strattice™ reduces capsular contracture whilst improving aesthetic outcomes in implant based breast reconstruction. ADMs may reduce capsular contracture by creating a barrier between the native tissues and implant, leading to a less intense foreign body response which remains dormant over time.

This project was concerned with investigating the electrophilic cyclisation reactions of 3-phenylpenta-1,4-diyn-3-ols possessing either an ortho-N-linked-or an ortho-S-linked-sulfonamide function. Cyclisations of both series of sulfonamides meditated by alkynophilic initiators [e.g. I2, ICl, AgOAc or In(OTf)3] provided access to novel functionalised heterocycles. Thus, addition of methyl 2-(arenesulfonamido)benzoates to alkynyllithium reagents furnished 3-[(2-arenesulfonamido)phenyl]penta-1,4-diyn-3-ols in which the alkyne termini possess identical substituents. Dialkynols having unsymmetrical alkyne terminal groups have been obtained from the addition of an alkynyllithium reagent or HC≡CMgBr to 3-aryl-1-(2-tosylamidophenyl)prop-2-yn-1-ones. The ortho-S-linked sulfonamides have been accessed directly from N-substituted saccharins that readily add alkynyllithiums to provide 3-(2-sulfamoylphenyl)penta-1,4-diyn-3-ols in good yields. Desilylation (5M NaOH in MeOH) of 1,5-bis(trimethylsilyl)-3-(2-tosylamidophenyl)penta-1,4-diyn-3-ol also triggered cyclisation via a 5-exo-digpathway and gave a quantitative yield of 3-ethynyl-2-methylene-1-tosylindolin-3-ol. However, when both silyl functions were replaced with either a propyl-or a phenyl-group, cyclisation to the 1-tosylindolin-3-ol did not occur with base. A quantitative yield of 3-(phenylethynyl)-1-tosyl-1H-indol-2-yl(1-phenyl)methanol was obtained from treatment of 1,5-diphenyl-3-(2-tosylamidophenyl)penta-1,4-diyn-3-ol with AgOAc in MeCN. The analogous reaction with 6-(2-tosylamidophenyl)undeca-4,7-diyn-6-ol, provided 1-[3-(pent-1-yn-1-yl]-1-tosyl-1H-indol-2-yl)butan-1-ol, together with smaller amounts of (E)-2-but-1-en-1-yl-3-pentyn-1-yl-1-tosyl-1H-indole and 4-pentyn-1-yl-2-propylquinoline. It was found that when 3-(2-tosylamidophenyl)penta-1,4-diyn-3-ols possessed bulky groups on the alkyne units, the reaction followed an alternative course giving access to the(Z)-2-benzylidene-, (Z)-2-(2,2-dimethylpropylidene)-and (Z)-2-(trimethylsilylmethylene)-derivatives of 3-alkynyl-1-tosylindolin-3-ols. Mechanisms to account for these outcomes have been proposed. Contrasting behavior was observed from the In(OTf)3-mediated cyclisation of 1,5-diphenyl-3-(2-tosylaminophenyl)penta-1,4-diyn-3-ol, which promoted an unexpected and remarkable cascade pathway leading to 2,4-diphenyl-1-tosyl-4,5-dihydrofuro[2,3-c]quinoline, albeit in moderate yield. Attempted iodocyclisation (ICl in MeCN) of 1,5-diphenyl-3-[2-(N-methylsulfamoyl)phenyl]penta-1,4-diyn-3-ol resulted only in cyclodehydration to give the novel 3,3-bis(phenylethynyl)-2-methyl-1,2-benzisothiazole 1,1-dioxide. However, application of these conditions to 1,5-diphenyl-3-[2-(N-p-tolylsulfamoyl)phenyl]penta-1,4-diyn-3-ol provided a novel derivative of the unusual 1,2-benzisothiazolo[2,3-a]quinoline system that was characterised by X-ray crystallography; the corresponding 2-aryl-3,3-di(alkynyl)-1,2-benzisothiazole 1,1-dioxide was also formed. The latter also underwent iodocyclisation to give the 1,2-benzisothiazolo[2,3-a]quinolines. It was established that the 3,3-di(alkynyl)-1,2-benzisothiazole 1,1-dioxides could be generated most efficiently by treatment of the 3-[2-(sulfamoyl)phenyl]penta-1,4-diyn-3-ols with In(OTf)3in DCM. Iodocyclisation (ICl in MeCN) of 3-(2-tosylamidophenyl)penta-1,4-diyn-3-ols having symmetrical alkyne substituents afforded novel 4-alkynyl-3-iodoquinolines. However, the unsymmetrically-substituted pentadiynols cyclised less efficiently to give, in some cases, mixtures of regioisomeric 3-iodoquinolines. The cyclisation of 1-(4-methoxyphenyl)-5-phenyl-3-(2-tosylamidophenyl)penta-1,4-diyn-3-ol regiospecifically generated 3-iodo-2-(4-methoxyphenyl)-4-(phenylethynyl)quinoline, as anticipated. Silver-catalysed cyclisation (AgOAc in MeCN) of 3-[2-(N-arylsulfamoyl)phenyl]penta-1,4-diyn-3-ols proceeds stereoselectively to (Z)-3-alkylidene-4-alkynyl-2-aryl-and (Z)-4-alkynyl-2-aryl-3-arylidene-1,2-benzothiazin-4-ol 1,1-dioxides via a 6-endo-digpathway in good to excellent yields, constituting a new approach to this ring system. Two of the pentadiynols also furnished 1,2-benzothiazepine 1,1-dioxides derived via a 7-endo-digring closure. Mechanisms for the formation of these novel compounds are proposed. With a range of heterocycles to hand some were subjected to functionalisation or annulation reactions. Of note is the Pd-mediated domino-amination-hydroamination of 4-alkynyl-3-iodoquinolines with a range of primary amines. This approach was exploited to access novel 2,3,4-trisubstituted pyrrolo[2,3-c]quinolines, analogues of the biologically active Marinoquinolines. However, in some instances the hydroamination step was suppressed and the major or exclusive product was a 4-alkynyl-3-amino-2-arylquinoline. Suzuki-Miyaura couplings to 4-alkynyl-2-iodo-3-arylquinolines and efforts to effect iodocyclisations of the products are also described.