Culex quinquefasciatus mosquitoes play an important role in the transmission of vector-borne diseases of public health importance including lymphatic filariasis (LF) as well as many arboviruses. Insecticide-based approaches are one of the most important interventions to mitigate disease burden; nevertheless increased resistance of vectors to insecticides imposes a challenge for the sustainability and effectiveness of both current and future vector control interventions. Hence, understanding the dynamics and likely mechanisms underlying the evolution of resistance will be critical to effective decision-making in insecticide resistance management strategies. The present study was set out to investigate the genetic basis of insecticide resistance in C. quinquefasciatus from Uganda. Two objectives were developed, 1) to investigate patterns of insecticide resistance across the south of the country and how this might reflect local selection and genetic structure and 2) to investigate the basis of the molecular mechanisms underlying resistance to all four classes of insecticides recommended for vector control. The population genetic study compared and contrasted microsatellite markers and two resistance-associated loci (Vgsc-1014F and Ace1-119S). While no significant difference in genetic diversity across populations were detected by microsatellites, higher frequency of Vgsc-1014F compared to the Ace1-119S mutations was observed in all populations suggesting that the Ugandan Eastern – Southwest populations are under a heterogeneous selection pressure, which created a pattern of local adaptation in these populations. Additionally, the copy number (CN) assay developed in this study indicated the presence of CN variation in the voltage gated sodium channel (Vgsc) gene in about 10% of the individuals assayed from these populations. Genotypic/phenotypic association tests conducted on bendiocarb resistant-individuals suggested that this resistant phenotype was not underlying solely by the 119S target-site mutation in the Ace-1 gene. Indeed, synergist bioassays show an increase of mortality of around 25% in mosquitoes pre-exposed to either TTP or PBO, indicating a possible resistance mediated by detoxification enzymes. Using a novel whole-transcriptome microarray we profiled the bendiocarb-resistant phenotype and implicated two P450s (Cyp-Cx1 and Cyp6n23) with the highest up-regulation expression compared to a susceptible strain. Remarkably, the predicted Cyp-Cx1 is closely related to two P450s from the family Cyp6, which were already validated in vitro as insecticide metabolizers in A. gambiae and A. aegypti, which corroborates a likely association of metabolic resistance in the investigated bendiocarb-resistant phenotype. Taken together the results yielded by genomic and transcriptomic experiments provide evidence that Ugandan C. quinquefasciatus mosquitoes are under heterogeneous selection pressure imposed by insecticides from distinct classes, and that the evolution of insecticide resistance is mediated by at least two main genetic mechanisms; target-site mutations (Vgsc-1014F and Ace1-119S) as well as over-expression of detoxification enzymes.

Title: A Comparison of the Equity-supportiveness of Organizational Cultures of (Public) NHS Organizations and (Private) Social Enterprise (SE) Providers Theory: New Public Management (NPM) has been the most influential paradigm in public administration in the last three decades. NPM-driven ideas such as provider competition, privatisation and patient choice have resulted in increased interest from recent UK governments in Social Enterprises (SEs) for delivering public health services. NPM-based changes have been criticized for creating inequitable provision of healthcare and increasing unjust health inequalities. It is worth asking whether equity for patients is promoted equally effectively by public (NHS) organizations and SE providers. Research Aims and Methodology: A mixed methods approach was employed. The quantitative strand used a survey to compare the equity-supportiveness of NHS and SE organizational cultures [124 respondents (68 NHS and 56 SE staff) from 21 organizations (12 NHS and 9 SEs)]. The qualitative strand used semi-structured interviews with 27 SE staff members to examine organizational changes in SEs and the impact of these changes on equity in service provision. Findings: By achieving better alignment with organizational values, reducing bureaucracy, speeding up decision-making, giving staff more autonomy and responsibility, encouraging initiative, risk-taking and innovation, involving staff more actively in strategic decision-making, and making better use of technology, Social Enterprises are promoting equity to an equal or greater degree than public (NHS) organizations. Implications: However, the SE model (currently limited to community healthcare services) remains unclear and problematic, suggesting caution in its use by larger NHS acute Trusts. More research is needed before a policy to support the adoption of the SE model in public service delivery is mainstreamed.

The thesis maps out my experiences of, and thinking about, health promotion over my fifteen-year career as a health promotion specialist and lecturer. It adopts an exploratory, reflective approach starting with an account and analysis of health promotion as I experienced it in practice from the mid 1980's onwards, and ending with an exploration of the way reflexivity works in a medium-sized health promotion department in England. This exploration took place in 2000 at a time when the department like many others were facing an uncertain future and a possible merger with a department of public health. The thesis begins with my reflections on health promotion and its theory, and my personal experience of being managed in a health promotion department. This account forms the first step of a research process, and the role of reflexivity in this process is highlighted. Using qualitative techniques of data analysis, themes emerge relating to the way the accounts were written, the social and psychological processes being acted out; and the emotional tapestry involved. A co-operative research encounter based on the story-dialogue method with a medium-sized health promotion department generated six streams of qualitative data. The separate analyses are combined to produce overall meta-themes which tell a collective story of the hidden scripts and conventions operating in the health promotion department at the time. These include limits to what can be said, associated avoidance and cynicism, and an acknowledged lack of reflexivity. There was an embedded rhetoric about democracy, valuing and consultation that was vulnerable to being over-ridden or diminished. Similarly, there was a lack of specificity about what health promotion as an entity and team working actually means to the department. Within this scenario, staff became individual tacticians and placed high regard on their autonomy. Reflexivity facilitated and legitimised through story-dialogue enabled emotional expression, criticism, and agreement and appreciation. Reflexivity in the encounter translated hope and uncertainty into future-facing and future action. It helped re-establish and specify a collective identity and it provided some detail about nature of health promotion and team working. These meta themes are discussed in relation to changes and movements in contemporary health promotion in England including the life and meaning of 'health promotion' discourse and the creation, reification and impact of 'tribal' discourses in health promotion and public health. These discourses based on difference are shown to be questionable and point to a demise of reflexivity in more recent health promotion discourse. Adherence to this discourse is argued to leave health promotion open to charges of elitism and has hindered searches for common values, language and standards. Moreover, it has meant a failure to articulate a new health promotion.

Community pharmacists are increasingly providing public health services in response to government policies. Published literature regarding the views of the general public related to pharmacy public health services, although important in ensuring uptake of these services, was limited. This study series aim to explore the general public's perspective on how to maximise the appropriate utilisation of community pharmacy services for improving public health. A large study comprising four sequential phases was designed and conducted in Sefton borough. Initially, to gather background information, focus group discussions (FGDs) and semi-structured interviews were undertaken with the general public and key stakeholders. The second phase involved the development and testing of a questionnaire extracted from the qualitative findings and a literature review. The questionnaire focused upon seven pharmacy public health services related to cardiovascular risks as well as views on factors influencing pharmacy use and advertising/promotion techniques. Geodemographic concepts, widely recognised in public health, were also included to identify potential benefits to pharmacy practice research. Next, a large scale survey was administered among the general public using eight survey modes, to additionally evaluate the range of methods available/for gathering public views. Finally, survey findings were evaluated by representatives of survey respondents using a FGD. Results indicated that, although stakeholders considered that community pharmacy can make an extensive contribution in supporting public health, pharmacy public health services are used at a relatively low level by the general public and awareness of services is also low. Survey respondents indicated a willingness to use services in the future. Important factors influencing pharmacy use include loyalty, location and convenient accessibility. Appropriate promotional campaigns are a key facilitator to help raise the public's awareness. The findings will help the profession to increase uptake of pharmacy public health services. The variety of survey modes used proved beneficial in obtaining diverse population demographics, with street survey being the optimal technique, however, the potential for social desirability bias must be considered with this and other interviewer-assisted approaches. MOSAIC™ as a geodemographic tool is potentially useful in helping to target services for specific groups and is recommended for use in further research.

Green hospitals with improved hospital waste recycling practices can be a key solution to the potential problems associated with hospital waste disposal and management. Recycling of household hospital waste could significantly impact on the overall waste disposal management systems and how hospital waste is segregated and eventually disposed. The involvement of hospital staff is of key importance in improving recycling performance, however, the perceptions of hospital workers towards recycling of hospital waste is still not clear and there is a lack of research in this area. The factors that determine the recycling behaviour are not adequately described in the medical literature, and differences between hospital workers perceptions of recycling in developing versus developed countries have not previously been extensively studied. This thesis was designed to examine the factors influencing the knowledge and attitudes of hospital workers towards toward recycling of hospital waste, using a novel questionnaire. A pilot study was first performed to test the efficiency of the questionnaire, conducted via sending the self-administered questionnaires to 12 experts. Their views were considered in the development of the final version of the questionnaires. These were distributed randomly in 2 pre-selected hospitals in the UK and 3 similar hospitals in Libya. A total of 453 questionnaires were returned. The response rates were generally low in both counties (less than 20%). Females and nurses responded significantly more frequently than men and physicians. In general there were relatively low levels of knowledge about waste management and recycling practice. In this study, none of the Libyan hospitals practiced any recycling and the hospital workers in Libya were significantly less enthusiastic towards recycling than their UK counterparts. Training in hospital waste management and education were found to be weak predictors of positive attitudes. Results showed that it is difficult to predict the recycling behaviours among hospital workers, however, waste management staff were more positive towards recycling than those without training in waste management. The study has shown similar results to previous studies, in that hospitals in developed countries generated much less waste compared to hospitals in developed countries. Unexpectedly, knowledge was weakly linked to attitudes in both UK and Libyan hospitals. This may be due to the fact that the attitudes of clinicians and hospital workers are not necessarily related to their knowledge but rather affected mostly by the hard working hours and busy atmosphere which makes recycling more challenging. The study opens doors for further studies to investigate factors influencing recycling attitudes, and encouraging hospitals in developing countries to commence recycling practice and provide whatever infrastructure is needed to make this possible. More education and training on hospital waste management should be encouraged in developing countries. Introducing new technologies in hospital waste management, particularly recycling of hospital house hold waste may change the future prospective of hospital waste disposal in developed and developing countries. More studies intervening with educating the hospital workers in waste management, particularly in recycling of hospital waste and it's relatively safety should be encouraged. Key words: Healthcare waste, hospital household recycling, knowledge, attitudes, hospitals, healthcare workers, waste management.

This thesis focuses on quality improvement in local NHS services in response to national legislation. The preparatory literature search of healthcare, change and quality theories identified the common theme of participation for success as well as a distinct gap in quality management models suitable for healthcare. Action research was used to develop, implement and evaluate such a model, combining qualitative and quantitative methods, enabling ownership of the model by participating stakeholders, and facilitating change by reflection and action. The thesis is organised into three main parts from which key themes emerge. The first section establishes health and its care as the most basic of human needs. Healthcare delivered through public provision has a medically dominated hierarchy of stakeholders with different expectations: users pursue a social model of care, managers a business model, and providers a scientific model. The lack of evidence on which to base provision has resulted in autonomous clinical practice which, without reference to guidelines, is difficult to assure. In a culture of professional awareness, autonomy can provide an opportunity for service improvement The second section describes the development of the Quality Synthesis Model through participant involvement. Recent experiences of change in the NHS provided direction through: the need for clarity and agreement over quality issues, vision and values; a strategic approach; and capacity and empowerment to respond. In addition, these followed generic best practice of a conducive culture, communication, commitment and measures of progress. Finally, in the third section, the empirical chapters describe implementation and analyses of the model in the sample semi-profession service of chiropody with older people. Quantitative and qualitative data was collected through records, repeat surveys and sub sample telephone interview. Evaluation of the model was against: • operational criteria requirements • compatibility with commissioning • sound methodology • changes in stakeholder culture. The results suggest that the Quality Synthesis Model is a cost-effective answer to local quality management in a culture of professional awareness, respecting the influence of the ultimate power of medicine. Together with the principles of change management, and particularly the lessons learned from the implementation of previous initiatives, local NHS units could successfully move towards a sustained responsive culture through the use of the model.

Background: Depression is a major health problem worldwide and the majority of patients presenting with depressive symptoms are managed in primary care. Current approaches for assessing depressive symptoms in primary care are not accurate in predicting future clinical outcomes, which may potentially lead to over or under treatment. The Allostatic Load (AL) theory suggests that by measuring multi-system biomarker levels as a proxy of measuring multi-system physiological dysregulation, it is possible to identify individuals at risk of having adverse health outcomes at a prodromal stage. Allostatic Index (AI) score, calculated by applying statistical formulations to different multi-system biomarkers, have been associated with depressive symptoms. Aims and Objectives: To test the hypothesis, that a combination of allostatic load (AL) biomarkers will form a predictive algorithm in defining clinically meaningful outcomes in a population of patients presenting with depressive symptoms. The key objectives were: 1. To explore the relationship between various allostatic load biomarkers and prevalence of depressive symptoms in patients, especially in patients diagnosed with three common cardiometabolic diseases (Coronary Heart Disease (CHD), Diabetes and Stroke). 2 To explore whether allostatic load biomarkers predict clinical outcomes in patients with depressive symptoms, especially in patients with three common cardiometabolic diseases (CHD, Diabetes and Stroke). 3 To develop a predictive tool to identify individuals with depressive symptoms at highest risk of adverse clinical outcomes. Methods: Datasets used: ‘DepChron’ was a dataset of 35,537 patients with existing cardiometabolic disease collected as a part of routine clinical practice. ‘Psobid’ was a research data source containing health related information from 666 participants recruited from the general population. The clinical outcomes for 3 both datasets were studied using electronic data linkage to hospital and mortality health records, undertaken by Information Services Division, Scotland. Cross-sectional associations between allostatic load biomarkers calculated at baseline, with clinical severity of depression assessed by a symptom score, were assessed using logistic and linear regression models in both datasets. Cox’s proportional hazards survival analysis models were used to assess the relationship of allostatic load biomarkers at baseline and the risk of adverse physical health outcomes at follow-up, in patients with depressive symptoms. The possibility of interaction between depressive symptoms and allostatic load biomarkers in risk prediction of adverse clinical outcomes was studied using the analysis of variance (ANOVA) test. Finally, the value of constructing a risk scoring scale using patient demographics and allostatic load biomarkers for predicting adverse outcomes in depressed patients was investigated using clinical risk prediction modelling and Area Under Curve (AUC) statistics. Key Results: Literature Review Findings. The literature review showed that twelve blood based peripheral biomarkers were statistically significant in predicting six different clinical outcomes in participants with depressive symptoms. Outcomes related to both mental health (depressive symptoms) and physical health were statistically associated with pre-treatment levels of peripheral biomarkers; however only two studies investigated outcomes related to physical health. Cross-sectional Analysis Findings: In DepChron, dysregulation of individual allostatic biomarkers (mainly cardiometabolic) were found to have a non-linear association with increased probability of co-morbid depressive symptoms (as assessed by Hospital Anxiety and Depression Score HADS-D≥8). A composite AI score constructed using five biomarkers did not lead to any improvement in the observed strength of the association. In Psobid, BMI was found to have a significant cross-sectional association with the probability of depressive symptoms (assessed by General Health Questionnaire GHQ-28≥5). BMI, triglycerides, highly sensitive C - reactive 4 protein (CRP) and High Density Lipoprotein-HDL cholesterol were found to have a significant cross-sectional relationship with the continuous measure of GHQ-28. A composite AI score constructed using 12 biomarkers did not show a significant association with depressive symptoms among Psobid participants. Longitudinal Analysis Findings: In DepChron, three clinical outcomes were studied over four years: all-cause death, all-cause hospital admissions and composite major adverse cardiovascular outcome-MACE (cardiovascular death or admission due to MI/stroke/HF). Presence of depressive symptoms and composite AI score calculated using mainly peripheral cardiometabolic biomarkers was found to have a significant association with all three clinical outcomes over the following four years in DepChron patients. There was no evidence of an interaction between AI score and presence of depressive symptoms in risk prediction of any of the three clinical outcomes. There was a statistically significant interaction noted between SBP and depressive symptoms in risk prediction of major adverse cardiovascular outcome, and also between HbA1c and depressive symptoms in risk prediction of all-cause mortality for patients with diabetes. In Psobid, depressive symptoms (assessed by GHQ-28≥5) did not have a statistically significant association with any of the four outcomes under study at seven years: all cause death, all cause hospital admission, MACE and incidence of new cancer. A composite AI score at baseline had a significant association with the risk of MACE at seven years, after adjusting for confounders. A continuous measure of IL-6 observed at baseline had a significant association with the risk of three clinical outcomes- all-cause mortality, all-cause hospital admissions and major adverse cardiovascular event. Raised total cholesterol at baseline was associated with lower risk of all-cause death at seven years while raised waist hip ratio- WHR at baseline was associated with higher risk of MACE at seven years among Psobid participants. There was no significant interaction between depressive symptoms and peripheral biomarkers (individual or combined) in risk prediction of any of the four clinical outcomes under consideration. Risk Scoring System Development: In the DepChron cohort, a scoring system was constructed based on eight baseline demographic and clinical variables to predict the risk of MACE over four years. The AUC value for the risk scoring system was modest at 56.7% (95% CI 55.6 to 57.5%). In Psobid, it was not possible to perform this analysis due to the low event rate observed for the clinical outcomes. Conclusion: Individual peripheral biomarkers were found to have a cross-sectional association with depressive symptoms both in patients with cardiometabolic disease and middle-aged participants recruited from the general population. AI score calculated with different statistical formulations was of no greater benefit in predicting concurrent depressive symptoms or clinical outcomes at follow-up, over and above its individual constituent biomarkers, in either patient cohort. SBP had a significant interaction with depressive symptoms in predicting cardiovascular events in patients with cardiometabolic disease; HbA1c had a significant interaction with depressive symptoms in predicting all-cause mortality in patients with diabetes. Peripheral biomarkers may have a role in predicting clinical outcomes in patients with depressive symptoms, especially for those with existing cardiometabolic disease, and this merits further investigation.

Human beliefs about health and illness structure the explanations for health and illness in a society and these explanations rationalise preventive or therapeutic strategies. The purpose of this research was to discover, identify and understand the perceptions of health, illness and health seeking behaviour of the Baloch people in a cultural perspective. More specifically, it was to document their perception regarding the origin and cause of illness and disease as revealed in their system of disease-classification and their etiological categories. It was also to describe the context in which Baloch access the traditional health care system as well as conventional health care. Participant observations and in-depth interviews were the tools for data collection in this ethnographic study. Four districts of Pakistani Balochistan were selected for fieldwork. Traditional or folk healers of different categories, medical professionals, sufferers, family heads, community elders, tribal chiefs and medical doctors were interviewed in depth during fieldwork and many socio-cultural phenomena and ritual healing practices were participated in and observed. It was observed that Baloch beliefs regarding health and illness revolve either on the concept of natural causes that are mainly due to humoral imbalance or supernatural causes: spirit possession, sorcery or evil eye. In contemporary Balochistan, despite the availability of the basic health care system in the majority of Baloch settlements, for all practical purposes, Baloch use their traditional medical practices alongside biomedicine. These medical practices mainly consist of herbal remedies and spiritual healing practices. Folk medical beliefs are inseparable from other elements of Baloch cultural life and in this context health planners and medical practitioners in Balochistan, mutually can do much to balance and integrate biomedicine and folk and traditional medicine. Working together, they can optimise the benefits for their client populations.

Cardiovascular pre-participation screening in sport remains a controversial area. The general consensus is that it should be available given the increased risk of sudden cardiac death with exercise, but debate exists to the format of this screening. Part 1 of this thesis examines the incidence and epidemiology of death in young people to set the context; Part 2 evaluates the results of the Cardiac Assessment in Young Athletes (CAYA) programme in Scotland. Part 1 investigated a database of 41,049 deaths in those aged 0-35 years in Scotland from 1986-2008. Information such as location of death, whether a PM had taken place and cause of death was examined for all subjects with deaths categorised as those which occurred in-hospital or out-of-hospital and by age category and sex. Cardiac deaths (n=2084) were then investigated further. Analysis showed that the majority of deaths in young people in Scotland are due to accidents (27%), self-harm (16.2%) and cancers (11.8%). Coronary artery disease is the largest contributor of cardiac deaths in young people in Scotland (30%) with the greatest number occurring out-of-hospital (55.3%). Only a relatively small number of deaths (0.9% of total) were due to conditions that would be identified and potentially prevented by a cardiac screening programme. Part 2: The CAYA study was based on the Italian Model of screening by personal and family history, physical examination and resting 12-lead ECG, with the addition of an echocardiogram for all participants. Data was available for 1713 subjects from the CAYA study from October 2009-December 2012. Results showed a high incidence of hypertension in this young, athletic population, with a pilot study suggesting that this is likely to be 'white coat hypertension'. Screening with ECG identified 3 subjects with Wolff Parkinson-White syndrome and 1 with Long QT syndrome. Around 5% of subjects demonstrated left ventricular hypertrophy out with normal limits on echo (>13mm), but no structural abnormalities such as cardiomyopathy were diagnosed. Use of the ECG in cardiac screening remains controversial but these results suggest that, although the ECG is not a useful diagnostic tool for identifying those with left ventricular hypertrophy, it has a high negative predictive value meaning it can identify those without pathology. In conclusion, these results do not support the inclusion of echocardiography as a tool in cardiovascular screening in Scotland. The majority of cardiovascular deaths identified in this study were due to undiagnosed coronary heart disease which would not be identified by screening. Other causes of sudden cardiac death which may be identified by screening, such as familial arrhythmias and cardiomyopathies, are rare in Scotland. A screening service with ECG should be available to athletes and young people in Scotland but this should remain voluntary for those with symptoms or a positive family history. Improved first aid education and provision of defibrillators at sporting facilities would perhaps help to reduce the number of fatalities that occur in young athletes.

Ladybird beetles produce a range of alkaloid compounds which are found a high concentration in the haemolymph and released in response to perceived threat. These alkaloids are thought to function as agents of chemical defence and a small number have been shown to antagonise the nicotinic acetylcholine receptor. As intraguild predators, the chemical defence may be under selective pressure from other predatory insects, the alkaloids may therefore have evolved to target insects predominantly. To discover if other ladybird alkaloids show activity at nAChRs and investigate mode of action, alkaloids were extracted from 7-spot, 10-spot, 14-spot, cream spot, pine, orange and harlequin ladybird beetles and purified with acid-base separation. These species are each known to produce a different subset of alkaloids. Their action on nicotinic acetylcholine receptors was investigated by constructing concentration-inhibition plots by co-applying alkaloid extracts with acetylcholine to human embryonic muscle-type of TE671 cells and locust neuronal nAChRs. Peak current, net-charge and late (1 s) current were measured with whole-cell patch-clamp at VH = -75 mV. All alkaloid extracts antagonised the ACh responses of both cell types but potency and selectivity varied. The late current was the most strongly affected current parameter and the most potent antagonists of locust 1 s currents were alkaloids produced by 10-spot, 7-spot, pine and harlequin ladybird with IC50s ranging from 0.29–0.76 μg/mL. The 14-spot, cream spot and orange ladybird alkaloids had higher IC50s, ranging from 1.6-4.9 μg/mL. The IC50 values calculated for all species with, the exception of harlequin and orange ladybirds were significantly lower for locust than human nAChRs and these ranged from 1.3–47.8 μg/mL. The alkaloid extract that showed the highest selectivity for locust nAChRs was that of the 7-spot ladybird, with an IC50 value 58.4 fold lower. The alkaloids of the 10-spot, 14-spot, cream spot and pine ladybird also showed significantly higher potency for locust nAChRs over human nAChRs with IC50s 10.3–35 fold lower. Orange and harlequin ladybird alkaloids did not show higher potency for locust nAChRs. Harlequin ladybird alkaloids were highly potent to the nAChRs of both cell types whereas orange ladybird alkaloids showed low activity. The differences in potency correspond with differences in ecology, with the species that showed highest insect potency often found in close association with other predatory ladybird species. Those that showed low insect potency are arboreal specialists that are less likely to encounter insect predators. To investigate mode of action, ACh concentration-response curves in the presence and absence of harlequin ladybird alkaloid extract were constructed using TE671 cells. Increasing ACh concentrations were unable to overcome the inhibition caused by this alkaloid extract, indicating non-competitive action. Fitting the Woodhull equation to IC50 values calculated at holding potentials of 50, -50, -75, -100 and -120 mV revealed that the antagonism caused by this alkaloid extract was voltagedependent (P = 0.012), with late current IC50s of 23.1, 15.5 and 6 μg/mL at holding potentials of +50, -50 and -120 mV respectively. These data indicate that the active alkaloid(s) within this extract bind at an allosteric site and the strong voltagedependence of inhibition suggests mode of action is open-channel block rather than enhancement of desensitisation. The alkaloid harmonine was separated from other components of the alkaloid extract by thin-layer chromatography and the inhibitory activity tested against both human and locust nAChRs at VH = -75 mV. Both fractions were found to be active and displayed similar inhibitory activity towards human nAChRs with IC50s of 1.68 μg/mL for harmonine and 4.77 μg/mL for other alkaloid compounds. Harmonine was found to be significantly more potent towards locust nAChRs with an IC50 of 0.072 μg/mL as opposed to 3.23 μg/mL. This could indicate that harlequin ladybirds produce several alkaloids with different functions; harmonine may act as a chemical defence compound targeted towards insect predators. The alkaloid extract of the 10-spot ladybird was found to show significantly higher potency towards locust nAChRs than human. One of two alkaloids produced by this species is (-)-adaline. Synthetic (-)-adaline displayed identical inhibitory activity towards both cell types as the alkaloid extract of the 10-spot ladybird. Potency was significantly higher towards locust nAChRs than human, with IC50s of 10.26–45.83 μM against human and 0.55–2.97 μM against locust nAChRs. ACh concentration-response curves showed that (-)-adaline acts non-competitively and IC50 values at different holding potentials reveal that it is strongly voltage-dependent (P = 0.003 in human and P = 0.007 in locust nAChRs) and inactive at positive holding potentials. As with the alkaloid extract of the harlequin ladybird, this alkaloid acts as a non-competitive negative allosteric modulator which shows higher potency for locust over human nAChRs and strong voltage-dependence of inhibition, consistent with open-channel block. A structurally diverse range of ladybird alkaloids displayed inhibitory activity towards both human and insect nAChRs. This inhibition was non-competitive and voltage-dependent for both harlequin ladybird alkaloid extract and adaline, indicating that these alkaloids act as negative allosteric modulators, possibly open-channel blockers. The majority of ladybird alkaloid extracts tested were significantly more potent towards insect than human nAChRs. It remains to be seen whether the activity of these compounds is restricted to the nAChRs, or whether they act as non-selective pore blockers. Ladybird alkaloids appear to represent a library of novel nAChR antagonists, some of which could be further investigated as potential insecticide leads.