Towards the Synthesis of Nitrogen Containing Heterocycles

The research undertaken in this thesis aimed at the synthesis of nitrogen containing heterocycles which are a class of molecules highly sought after by chemical industry and academia. Cycloisomerisation reactions of -rich species containing a pendant nitrogen atom was hypothesised as an expedient route to these heterocycles. As well as providing high-value products, such systems provide an arena for furthering the fundamental understanding of cycloisomerisation reactivity. Their synthesis was attempted either by purely organic reactions or mediated by a transition metal catalyst. Azirididines were tested with Ni(0) and Pd(0)–catalysts and allenyl metals reagents in ring opening reactions for the synthesis of -amino allenes. Unfortunately, this reaction proved challenging and an alternative route to -amino allenes was investigated which involved reduction of 1,3-enynes with LiAlH4 and Lewis acid catalysed ring opening of 2-phenyl aziridine with propargylic-TMS. The synthesised -amino allenes were then investigated in cycloisomerisation reactions with Au(I) and Ag(I)–catalysts. The Au(I)–catalysts favoured the formation of pyrrolidines while Ag(I)–catalysts favoured the formation of tetrahydropyridines

Orotracheal intubation in infants performed with a stylet versus without a stylet

Background: Neonatal endotracheal intubation is a common and potentially life-saving intervention. It is a mandatory skill for neonatal trainees, but one that is difficult to master and maintain. Intubation opportunities for trainees are decreasing and success rates are subsequently falling. Use of a stylet may aid intubation and improve success. However, the potential for associated harm must be considered. Objectives To compare the benefits and harms of neonatal orotracheal intubation with a stylet versus neonatal orotracheal intubation without a stylet. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE; Embase; the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and previous reviews. We also searched cross-references, contacted expert informants, handsearched journals, and looked at conference proceedings. We searched clinical trials registries for current and recently completed trials. We conducted our most recent search in April 2017. Selection criteria All randomised, quasi–randomised, and cluster-randomised controlled trials comparing use versus non-use of a stylet in neonatal orotracheal intubation. Data collection and analysis: Two review authors independently assessed results of searches against predetermined criteria for inclusion, assessed risk of bias, and extracted data. We used the standard methods of the Cochrane Collaboration, as documented in the Cochrane Handbook for Systemic Reviews of Interventions, and of the Cochrane Neonatal Review Group. Main results: We included a single-centre non-blinded randomised controlled trial that reported a total of 302 intubation attempts in 232 infants. The median gestational age of enrolled infants was 29 weeks. Paediatric residents and fellows performed the intubations. We judged the study to be at low risk of bias overall. Investigators compared success rates of first-attempt intubation with and without use of a stylet and reported success rates as similar between stylet and no-stylet groups (57% and 53%) (P = 0.47). Success rates did not differ between groups in subgroup analyses by provider level of training and infant weight. Results showed no differences in secondary review outcomes, including duration of intubation, number of attempts, participant instability during the procedure, and local airway trauma. Only 25% of all intubations took less than 30 seconds to perform. Study authors did not report neonatal morbidity nor mortality. We considered the quality of evidence as low on GRADE analysis, given that we identified only one unblinded study. Authors' conclusions: Current available evidence suggests that use of a stylet during neonatal orotracheal intubation does not significantly improve the success rate among paediatric trainees. However, only one brand of stylet and one brand of endotracheal tube have been tested, and researchers performed all intubations on infants in a hospital setting. Therefore, our results cannot be generalised beyond these limitations

Gold- and Silver-Catalysed Cyclisation Reactions of β-Amino Allenes

Herein we report the formation of pyrrolines and tetrahydropyridines from the cyclisation reactions of β-amino allenes by both AuI and AgI catalysts in yields ranging from 5 to 70 %. AuI catalysts favour a 5-endo-dig cyclisation before rapid rearrangement to the 5-exo-dig product, while AgI favours a 6-endo-trig cyclisation. We also report the first known Ag2O catalysed cyclisation reaction of an allene which occurred in good yield (61 %)

Effect of Time of Access to Pasture and the Provision of a Total Mixed Ration on the Performance and Methane Production of High Yielding Dairy Cows

Allowing cows to spend time on pasture may improve their welfare, although high yielding cows are unable to consume sufficient amounts of grass to maintain milk yield and require supplementation (Charlton et al. 2011). The inclusion of grass in the diet of high yielding cows may have benefits as grass contains polyunsaturated fatty acids which can reduce methane production (Martin et al. 2008). Additionally, the soluble carbohydrate content in grass is higher in the afternoon which may increase intake (Trevaskis et al. 2004). The aim of the experiment was to determine the effects of timing of pasture access and the provision of access to total mixed ration (TMR) when at grass on the performance and methane production of high yielding dairy cows

Protocol for the Promoting Resilience in Stress Management (PRISM) Intervention: A Multi-Site Randomized Controlled Trial for Adolescents and Young Adults with Advanced Cancer

Background Adolescents and young adults (AYAs) with cancer are at high risk of poor psychosocial outcomes, and evidence-based interventions designed to meet their psychosocial and communication needs are lacking. The main objective of this project is to test the efficacy of a new adaptation of the Promoting Resilience in Stress Management intervention for AYAs with Advanced Cancer (PRISM-AC). Methods/design The PRISM-AC trial is a 2-arm, parallel, non-blinded, multisite, randomized controlled trial. 144 participants with advanced cancer will be enrolled and randomized to either usual, non-directive, supportive care without PRISM-AC (“control” arm) or with PRISM-AC (“experimental” arm). PRISM is a manualized, skills-based training program comprised of four 30–60 min, one-on-one sessions targeting AYA-endorsed resilience resources (stress-management, goal-setting, cognitive-reframing, and meaning-making). It also includes a facilitated family meeting and a fully equipped smartphone app. The current adaptation includes an embedded advance care planning module. English- or Spanish-speaking individuals 12–24 years old with advanced cancer (defined as progressive, recurrent, or refractory disease, or any diagnosis associated with \u3c 50% survival) receiving care at 4 academic medical centers are eligible. Patients’ caregivers are also eligible to participate in this study if they are able to speak and read English or Spanish, and are cognitively and physically able to participate. Participants in all groups complete surveys querying patient-reported outcomes at the time of enrollment and 3-, 6-, 9-, and 12-months post-enrollment. The primary outcome of interest is patient-reported health-related quality of life (HRQOL) and secondary outcomes of interest include patient anxiety, depression, resilience, hope and symptom burden, parent/caregiver anxiety, depression and health-related quality of life, and family palliative care activation. We will conduct intention-to-treat analysis to compare the group means of primary and secondary outcomes between PRISM-AC arm and control arm with regression models. Discussion This study will provide methodologically rigorous data and evidence regarding a novel intervention to promote resilience and reduce distress among AYAs with advanced cancer. This research has the potential to offer a practical, skills-based curriculum designed to improve outcomes for this high-risk group. Trial registration ClinicalTrials.gov Identifier NCT03668223, September 12, 2018

The Pi-puck extension board: a Raspberry Pi interface for the e-puck robot platform

This paper presents the Pi-puck extension board - an interface between the e-puck robot platform and a Raspberry Pi single-board computer that enhances the processing power, memory capacity, and networking capabilities of the robot at a low cost. It allows high-level control algorithms, wireless communication, and computationally expensive operations such as real-time image processing to be handled by a Raspberry Pi, while the e-puck's microcontroller deals with low-level motor control and sensor interfacing. Although two similar extension boards for the e-puck robot platform already exist, they are now out-dated and expensive in comparison. Our open-source hardware design and supporting software infrastructure offer an inexpensive upgrade to the e-puck robot, transforming it into the Pi-puck – a modern and flexible new platform for mobile robotics research

Quality improvement priorities for safer out-of-hours palliative care: Lessons from a mixed-methods analysis of a national incident-reporting database

Background: Patients receiving palliative care are often at increased risk of unsafe care with the out-of-hours setting presenting particular challenges. The identification of improved ways of delivering palliative care outside working hours is a priority area for policymakers. Aim: To explore the nature and causes of unsafe care delivered to patients receiving palliative care from primary-care services outside normal working hours. Design: A mixed-methods cross-sectional analysis of patient safety incident reports from the National Reporting and Learning System. We characterised reports, identified by keyword searches, using codes to describe what happened, underlying causes, harm outcome, and severity. Exploratory descriptive and thematic analyses identified factors underpinning unsafe care. Setting/participants: A total of 1072 patient safety incident reports involving patients receiving sub-optimal palliative care via the out-of-hours primary-care services. Results: Incidents included issues with: medications (n = 613); access to timely care (n = 123); information transfer (n = 102), and/or non-medication-related treatment such as pressure ulcer relief or catheter care (n = 102). Almost two-thirds of reports (n = 695) described harm with outcomes such as increased pain, emotional, and psychological distress featuring highly. Commonly identified contributory factors to these incidents were a failure to follow protocol (n = 282), lack of skills/confidence of staff (n = 156), and patients requiring medication delivered via a syringe driver (n = 80). Conclusion: Healthcare systems with primary-care-led models of delivery must examine their practices to determine the prevalence of such safety issues (communication between providers; knowledge of commonly used, and access to, medications and equipment) and utilise improvement methods to achieve improvements in care. </jats:sec

First reported detection of the mobile colistin resistance genes, mcr-8 and mcr-9, in the Irish environment

The emergence and dissemination of mobile colistin resistance (mcr) genes across the globe poses a significant threat to public health, as colistin remains one of the last line treatment options for multi-drug resistant infections. Environmental samples (157 water and 157 wastewater) were collected in Ireland between 2018 and 2020. Samples collected were assessed for the presence of antimicrobial resistant bacteria using Brilliance ESBL, Brilliance CRE, mSuperCARBA and McConkey agar containing a ciprofloxacin disc. All water and integrated constructed wetland influent and effluent samples were filtered and enriched in buffered peptone water prior to culture, while wastewater samples were cultured directly. Isolates collected were identified via MALDI-TOF, were tested for susceptibility to 16 antimicrobials, including colistin, and subsequently underwent whole genome sequencing. Overall, eight mcr positive Enterobacterales (one mcr-8 and seven mcr-9) were recovered from six samples (freshwater (n = 2), healthcare facility wastewater (n = 2), wastewater treatment plant influent (n = 1) and integrated constructed wetland influent (piggery farm waste) (n = 1)). While the mcr-8 positive K. pneumoniae displayed resistance to colistin, all seven mcr-9 harbouring Enterobacterales remained susceptible. All isolates demonstrated multi-drug resistance and through whole genome sequencing analysis, were found to harbour a wide variety of antimicrobial resistance genes i.e., 30 ± 4.1 (10-61), including the carbapenemases, blaOXA-48 (n = 2) and blaNDM-1 (n = 1), which were harboured by three of the isolates. The mcr genes were located on IncHI2, IncFIIK and IncI1-like plasmids. The findings of this study highlight potential sources and reservoirs of mcr genes in the environment and illustrate the need for further research to gain a better understanding of the role the environment plays in the persistence and dissemination of antimicrobial resistance

Endovascular management of pelvic trauma

Traumatic pelvic injuries are an important group of acquired pathologies given their frequent association with significant vascular compromise. Potentially fatal as a consequence of rapid hemorrhage, achievement of early hemostasis is a priority; endovascular management of traumatic pelvic arterial injuries is an important potential option for treatment. Precipitated by any number of mechanisms of trauma, pelvic vascular injury necessitates timely patient assessment. Variable patterns of arterial injury may result from blunt, penetrating or iatrogenic trauma. Selection of the most appropriate imaging modality is a priority, ensuring streamlined access to treatment. In the case of CT, this is complemented by acquisition of the most appropriate phase of imaging; review of both arterial and delayed phase imaging improves the accuracy of detection of low-flow hemorrhage. In cases where surgical intervention is not deemed appropriate, endovascular treatment provides an alternative means for cessation of hemorrhage associated with pelvic injuries. This may be achieved in a selective or nonselective manner depending on the patient's clinical status and time constraints. Consequently, a detailed understanding of vascular anatomy is essential, including an appreciation of the normal variant anatomy between males and females. Additional consideration must be given to variant anatomy which may co-exist in both sexes. This review article aims to provide a synopsis of endovascular management of pelvic vascular injury. Through case examples, available treatment options will be discussed, including thrombin injection and transcatheter arterial embolization. Furthermore, potential adverse complications of pelvic arterial embolization will be highlighted. Finally, in view of the potential severity of these injuries, a brief overview of initial management of the hemodynamically unstable patient is provided

Comparison of frailty screening instruments in the emergency department

Early identification of frailty through targeted screening can facilitate the delivery of comprehensive geriatric assessment (CGA) and may improve outcomes for older inpatients. As several instruments are available, we aimed to investigate which is the most accurate and reliable in the Emergency Department (ED). We compared the ability of three validated, short, frailty screening instruments to identify frailty in a large University Hospital ED. Consecutive patients aged ≥70 attending ED were screened using the Clinical Frailty Scale (CFS), Identification of Seniors at Risk Tool (ISAR), and the Programme on Research for Integrating Services for the Maintenance of Autonomy 7 item questionnaire (PRISMA-7). An independent CGA using a battery of assessments determined each patient’s frailty status. Of the 280 patients screened, complete data were available for 265, with a median age of 79 (interquartile ±9); 54% were female. The median CFS score was 4/9 (±2), ISAR 3/6 (±2), and PRISMA-7 was 3/7 (±3). Based upon the CGA, 58% were frail and the most accurate instrument for separating frail from non-frail was the PRISMA-7 (AUC 0.88; 95% CI:0.83–0.93) followed by the CFS (AUC 0.83; 95% CI:0.77–0.88), and the ISAR (AUC 0.78; 95% CI:0.71–0.84). The PRISMA-7 was statistically significantly more accurate than the ISAR (p = 0.008) but not the CFS (p = 0.15). Screening for frailty in the ED with a selection of short screening instruments, but particularly the PRISMA-7, is reliable and accurate