The synthesis and ring-opening polymerisation of novel cyclic esters from malic acid

The work in this thesis is directed towards the preparation of cyclic ester monomers using malic acid as a renewable resource. Their subsequent controlled ring-opening polymerisation (ROP) to yield functionalised poly(ester)s is studied and application in micellar self-assembly reported. Chapter 1 reviews the many synthetic strategies that have been employed in the preparation of functional glycolides, lactides, ε-caprolactones, δ-valerolactones and β-propiolactones. Their subsequent polymerisation and applications are also discussed. Chapter 2 describes the improved synthesis of 3-(S)- [(benzyloxycarbonyl)methyl]- and 3,6-(S)-[di(benzyloxycarbonyl)methyl]-1,4- dioxane-2,5-diones, BMD and malide respectively, from L-malic acid. Controlled organocatalytic ROP of BMD realised functional poly(glycolic acid-co-benzyl α- malate)s (PBMD) with the choice of initiator proving important in determining the resulting molecular weight. Successful hydrogenolysis of these poly(glycolic acid-co-benzyl α-malate)s yielded hydrophilic poly(glycolic acid-co-α-malic acid)s (PGMA) with subsequent degradation studies in H2O observing complete degradation after six days. In Chapter 3, the synthesis of 5-(S)- and 5-(R)-[(benzyloxycarbonyl)methyl]-1,3- dioxolane-2,4-dione (L-malOCA and D-malOCA respectively) from L- and Dmalic acid respectively is reported. ROP of malOCA with a range of pyridine based catalysts enabled the synthesis of functional poly(benzyl α-malate)s (PBMA). Mechanistic studies revealed the formation of several side products that were eliminated via judicious choice of catalyst and column chromatography. Subsequent hydrogenolysis realised hydrophilic poly(α-malic acid)s (PMA) with degradation studies in H2O observing complete degradation after 10 days. Chapter 4 reports the synthesis of novel amphiphilic PEO-b-PBMA block copolymers by the ROP of L-malOCA or D-malOCA from PEO macroinitiators with subsequent self-assembly realising polymeric micelles. Variation in both size dimensions and stability of the micelles through changes in both the hydrophobic and hydrophilic block lengths and their relative ratios was demonstrated. The self-assembly of an equimolar mixture of homochiral PEO-b- P(L-BMA) and PEO-b-P(D-BMA) resulted in the formation of stereocomplexed polymeric micelles. Chapter 5 provides a summary of the findings in chapters 2 – 4 with chapter 6 providing the corresponding experimental data

Storage of Aconidial Strains of Neurospora crassa by Freezing at -80C.

Aconidial strains of N. crassa can be difficult to store for extended periods of time

The synthesis and ring-opening polymerisation of novel cyclic esters from malic acid

The work in this thesis is directed towards the preparation of cyclic ester monomers using malic acid as a renewable resource. Their subsequent controlled ring-opening polymerisation (ROP) to yield functionalised poly(ester)s is studied and application in micellar self-assembly reported. Chapter 1 reviews the many synthetic strategies that have been employed in the preparation of functional glycolides, lactides, ε-caprolactones, δ-valerolactones and β-propiolactones. Their subsequent polymerisation and applications are also discussed. Chapter 2 describes the improved synthesis of 3-(S)- [(benzyloxycarbonyl)methyl]- and 3,6-(S)-[di(benzyloxycarbonyl)methyl]-1,4- dioxane-2,5-diones, BMD and malide respectively, from L-malic acid. Controlled organocatalytic ROP of BMD realised functional poly(glycolic acid-co-benzyl α- malate)s (PBMD) with the choice of initiator proving important in determining the resulting molecular weight. Successful hydrogenolysis of these poly(glycolic acid-co-benzyl α-malate)s yielded hydrophilic poly(glycolic acid-co-α-malic acid)s (PGMA) with subsequent degradation studies in H2O observing complete degradation after six days. In Chapter 3, the synthesis of 5-(S)- and 5-(R)-[(benzyloxycarbonyl)methyl]-1,3- dioxolane-2,4-dione (L-malOCA and D-malOCA respectively) from L- and Dmalic acid respectively is reported. ROP of malOCA with a range of pyridine based catalysts enabled the synthesis of functional poly(benzyl α-malate)s (PBMA). Mechanistic studies revealed the formation of several side products that were eliminated via judicious choice of catalyst and column chromatography. Subsequent hydrogenolysis realised hydrophilic poly(α-malic acid)s (PMA) with degradation studies in H2O observing complete degradation after 10 days. Chapter 4 reports the synthesis of novel amphiphilic PEO-b-PBMA block copolymers by the ROP of L-malOCA or D-malOCA from PEO macroinitiators with subsequent self-assembly realising polymeric micelles. Variation in both size dimensions and stability of the micelles through changes in both the hydrophobic and hydrophilic block lengths and their relative ratios was demonstrated. The self-assembly of an equimolar mixture of homochiral PEO-b- P(L-BMA) and PEO-b-P(D-BMA) resulted in the formation of stereocomplexed polymeric micelles. Chapter 5 provides a summary of the findings in chapters 2 – 4 with chapter 6 providing the corresponding experimental data.EThOS - Electronic Theses Online ServiceEngineering and Physical Sciences Research Council (EPSRC)GBUnited Kingdo

Use of the Randox Evidence Investigator immunoassay system for near-body drug screening during post-mortem examination in 261 forensic cases

BackgroundThis paper describes the performance of four Randox drug arrays, designed for whole blood, for the near-body analysis of drugs in a range of post-mortem body specimens.MethodsLiver, psoas muscle, femoral blood, vitreous humor and urine from 261 post-mortem cases were screened in the mortuary and results were obtained within the time taken to complete a post-mortem. Specimens were screened for the presence of amfetamine, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, cannabinoids, dextropropoxyphene, fentanyl, ketamine, lysergide, methadone, metamfetamine, methaqualone, 3,4-methylenedioxymetamfetamine, opioids, paracetamol, phencyclidine, salicylate, salicylic acid, zaleplon, zopiclone and zolpidem using the DOA I, DOA I+, DOA II and Custom arrays.ResultsLiver and muscle specimens were obtained from each of the 261 post-mortem cases; femoral blood, vitreous humor and urine were available in 98%, 92% and 72% of the cases, respectively. As such, the equivalent of 12,978 individual drug-specific, or drug-group, immunoassay tests were undertaken. Overall >98% of the 12,978 screening tests undertaken agreed with laboratory confirmatory tests performed on femoral blood.ConclusionsThere is growing interest in the development of non-invasive procedures for determining the cause of death using MRI and CT scanning however these procedures are, in most cases, unable to determine whether death may have been associated with drug use. The Randox arrays can provide qualitative and semi-quantitative results in a mortuary environment enabling pathologists to decide whether to remove specimens from the body and submit them for laboratory analysis. Analysis can be undertaken on a range of autopsy specimens which is particularly useful when conventional specimens such as blood are unavailable

A Variational Method to Retrieve the Extinction Profile in Liquid Clouds Using Multiple Field-of-View Lidar

While liquid clouds playa very important role in the global radiation budget, it's been very difficult to remotely determine their internal cloud structure. Ordinary lidar instruments (similar to radars but using visible light pulses) receive strong signals from such clouds, but the information is limited to a thin layer near the cloud boundary. Multiple field-of-view (FOV) lidars offer some new hope as they are able to isolate photons that were scattered many times by cloud droplets and penetrated deep into a cloud before returning to the instrument. Their data contains new information on cloud structure, although the lack of fast simulation methods made it challenging to interpret the observations. This paper describes a fast new technique that can simulate multiple-FOV lidar signals and can even estimate the way the signals would change in response to changes in cloud properties-an ability that allows quick refinements in our initial guesses of cloud structure. Results for a hypothetical airborne three-FOV lidar suggest that this approach can help determine cloud structure for a deeper layer in clouds, and can reliably determine the optical thickness of even fairly thick liquid clouds. The algorithm is also applied to stratocumulus observations by the 8-FOV airborne "THOR" lidar. These tests demonstrate that the new method can determine the depth to which a lidar provides useful information on vertical cloud structure. This work opens the way to exploit data from spaceborne lidar and radar more rigorously than has been possible up to now

How taphonomic alteration affects the detection and imaging of striations in stab wounds

Stabbing with a kitchen knife is a common methodof homicide in Europe. Serrated knives may leave tool mark-ings (striations) in tissues. Documentation of striations is nec-essary for their use as forensic evidence. Traditional methods(physical casting and photography) have significant limita-tions, and micro-computed tomography (micro-CT) has beentrialled in cartilage toBvirtually cast^wounds. Previous re-search has shown the proportion of striations in cartilage fallsfollowing decomposition. This project has investigated theeffects of taphonomic alteration and documentation methodsof striations in porcine skin. Fresh, decomposed, mummified,burnt and waterlogged stab wounds in a porcine analoguewere excised and imaged using photography, stereo-opticalmicroscopy and micro-CT. The proportion of striations ineach taphonomic group was determined from the images byindependent analysts. Striations were observed more frequent-ly in serrated blade wounds, although they were also identifiedin non-serrated blade wounds. The proportion of woundsshowing striations declined following decomposition. An in-versely proportional linear correlation between advancing de-composition and proportion of striations existed. Dehydration(mummification and burning) rendered serrated and non-serrated blade wounds indistinguishable. Water compositionaffected the preservation of striations. Identification ofstriations gradually declined after decomposition in tap water,but persisted to a point when left in brackish water. All threetechniques imaged striations; however, the optimum tech-nique was stereo-optical microscopy due to practical advan-tages and specific limitations affecting photography and mi-cro-CT. This study demonstrates the effects of taphonomicalteration on striations and suggests stereo-optical microscopyis the optimum method for their documentation

Implementing a 48 h EWTD-compliant rota for junior doctors in the UK does not compromise patients’ safety : assessor-blind pilot comparison

Background: There are currently no field data about the effect of implementing European Working Time Directive (EWTD)-compliant rotas in a medical setting. Surveys of doctors’ subjective opinions on shift work have not provided reliable objective data with which to evaluate its efficacy. Aim: We therefore studied the effects on patient's safety and doctors’ work-sleep patterns of implementing an EWTD-compliant 48 h work week in a single-blind intervention study carried out over a 12-week period at the University Hospitals Coventry & Warwickshire NHS Trust. We hypothesized that medical error rates would be reduced following the new rota. Methods: Nineteen junior doctors, nine studied while working an intervention schedule of <48 h per week and 10 studied while working traditional weeks of <56 h scheduled hours in medical wards. Work hours and sleep duration were recorded daily. Rate of medical errors (per 1000 patient-days), identified using an established active surveillance methodology, were compared for the Intervention and Traditional wards. Two senior physicians blinded to rota independently rated all suspected errors. Results: Average scheduled work hours were significantly lower on the intervention schedule [43.2 (SD 7.7) (range 26.0–60.0) vs. 52.4 (11.2) (30.0–77.0) h/week; P < 0.001], and there was a non-significant trend for increased total sleep time per day [7.26 (0.36) vs. 6.75 (0.40) h; P = 0.095]. During a total of 4782 patient-days involving 481 admissions, 32.7% fewer total medical errors occurred during the intervention than during the traditional rota (27.6 vs. 41.0 per 1000 patient-days, P = 0.006), including 82.6% fewer intercepted potential adverse events (1.2 vs. 6.9 per 1000 patient-days, P = 0.002) and 31.4% fewer non-intercepted potential adverse events (16.6 vs. 24.2 per 1000 patient-days, P = 0.067). Doctors reported worse educational opportunities on the intervention rota. Conclusions: Whilst concerns remain regarding reduced educational opportunities, our study supports the hypothesis that a 48 h work week coupled with targeted efforts to improve sleep hygiene improves patient safety