Health and population effects of rare gene knockouts in adult humans with related parents

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British Pakistani-heritage adults with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. We observed 13.7% fewer than expected homozygous knockout genotypes, implying an average load of 1.6 recessive-lethal-equivalent LOF variants per adult. Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate. In this dataset we identified a healthy PRDM9 knockout mother, and performed phased genome sequencing on her, her child and controls, which showed meiotic recombination sites localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform upon essential genetic loci, and demonstrate PRDM9 redundancy in humans.

Watermarking biomedical time series data

This thesis addresses the problem of information hiding in low dimensional digital data focussing on issues of privacy and security in Electronic Patient Health Records (EPHRs). The thesis proposes a new security protocol based on data hiding techniques for EPHRs. This thesis contends that embedding of sensitive patient information inside the EPHR is the most appropriate solution currently available to resolve the issues of security in EPHRs. Watermarking techniques are applied to one-dimensional time series data such as the electroencephalogram (EEG) to show that they add a level of confidence (in terms of privacy and security) in an individual’s diverse bio-profile (the digital fingerprint of an individual’s medical history), ensure belief that the data being analysed does indeed belong to the correct person, and also that it is not being accessed by unauthorised personnel. Embedding information inside single channel biomedical time series data is more difficult than the standard application for images due to the reduced redundancy. A data hiding approach which has an in built capability to protect against illegal data snooping is developed. The capability of this secure method is enhanced by embedding not just a single message but multiple messages into an example one-dimensional EEG signal. Embedding multiple messages of similar characteristics, for example identities of clinicians accessing the medical record helps in creating a log of access while embedding multiple messages of dissimilar characteristics into an EPHR enhances confidence in the use of the EPHR. The novel method of embedding multiple messages of both similar and dissimilar characteristics into a single channel EEG demonstrated in this thesis shows how this embedding of data boosts the implementation and use of the EPHR securely.

A systems approach to public sector budgeting: the case of the planning, programming, budgeting system for the health and personal social services

The aim of this thesis is to examine the specific contextual factors affecting the applicability and development of the planning, programming, budgeting system (P.P.B.S.) as a systems approach to public sector budgeting. The concept of P.P.B.S. as a systems approach to public sector budgeting will first be developed and the preliminary hypothesis that general contextual factors may be classified under political, structural and cognitive headings will be put forward. This preliminary hypothesis will be developed and refined using American and early British experience. The refined hypothesis will then be tested in detail in the case of the English health and personal social services (H.P.S.S.), The reasons for this focus are that it is the most recent, the sole remaining, and the most significant example in British central government outside of defence, and is fairly representative of non-defence government programme areas. The method of data collection relies on the examination of unpublished and difficult to obtain central government, health and local authority documents, and interviews with senior civil servants and public officials. The conclusion will be that the political constraints on, or factors affecting P.P.B.S., vary with product characteristics and cultural imperatives on pluralistic decision-making; that structural constraints vary with the degree of coincidence of programme and organisation structure and with the degree of controllability of the organisation; and finally, that cognitive constraints vary according to product characteristics, organisational responsibilities, and analytical effort.

An evaluative analysis of the practice of teamwork in Health and Personal Social Services

This report describes the practice of teamwork as expressed in case conferences for care of the elderly and evaluates the effectiveness of case conferences in their contribution to care. The study involved the observation of more than two hundred case conferences in sixteen locations throughout the West Midlands, in which one thousand seven hundred and three participants were involved. Related investigation of service outcomes involved an additional ninety six patients who were interviewed in their homes. The pu`pose of the study was to determine whether the practice of teamwork and decision-making in case conferences is a productive and cost effective method of working. Preliminary exploration revealed the extent to which the team approach is part of the organisational culture and which, it is asserted, serves to perpetuate the mythical value of team working. The study has demonstrated an active subscription to the case conference approach, yet has revealed many weaknesses, not least of which is clear evidence that certain team members are inhibited in their contribution. Further, that the decisional process in case conferences has little consequence to care outcome. Where outcomes are examined there is evidence of service inadequacy. This work presents a challenge to professionals to confront their working practices with honesty and with vision, in the quest for the best and most cost effective service to patients.

Inquiring how a lecturer keeps learning about their teaching:a personal case history on reflective imagination

In order to reverse the use of lecture-based teaching, it is argued that personal reflection can be used as part of the quality assurance process. This paper proposes one response to personal reflection - reflective imagination, which is summarised as an action plan with six activities. It combines two conceptual issues raised in the US, the need to think creatively about learning and the reflective mindset, and one issue raised in the UK, cultivating the entrepreneurial imagination. Reflective imagination is linked to wider social science research, the place of self and reflexivity in scholarship. Finally, a personal history case study is presented which records a visit to Harvard Business School. The visit implements the six activities associated with reflective imagination. This is a method paper exploring reflective imagination.

Analysis of organisational climate to improve the adequacy of primary health care in the State of Kuwait

This study covers two areas of contribution to the knowledge, firstly it tried to investigate rigourously the relationships of a number of factors believed that they may affect the climate perception, classified into three types to arrive to prove a hypothesis of the important role that qualification and personal factors play in shaping the climate perception, this is in contrast with situational factors. Secondly, the study tries to recluster the items of a wide-range applied scale for the measurement of climate named HAY in order to overcome the cross-cultural differences between the Kuwaiti and the American society, and to achieve a modified dimensions of climate for a civil service organisation in Kuwait. Furthermore, the study attempts to carry out a diagnostic test for the climate of the Ministry of Public Health in Kuwait, aiming to diagnose the perceived characteristics of the MoPH organisation, and suggests a number of areas to be given attention if an improvement is to be introduced. The study used extensively the statistical and the computer facilities to make the analysis more representing the field data, on the other hand this study is characterised by the very highly responsive rate of the main survey which would affect the findings reliability. Three main field studies are included, the first one was to conduct the main questionnaire where the second was to measure the "should be" climate by the experts of MoPH using the DELPHI technique, and the third was to conduct an extensive meeting with the very top management team in MoPH. Results of the first stage were subject to CLUSTER analysis for the reconstruction of the HAY tool, whereas comparative analysis was carried on between the results of the second and third stages on one side, the first from the other.

Primary health care management in Nigeria

This research sets out to assess if the PHC system in rural Nigeria is effective by testing the research hypothesis: `PHC can be effective if and only if the Health Care Delivery System matches the attitudes and expectations of the Community'. The field surveys to accomplish this task were carried out in IBO, YORUBA, and HAUSA rural communities. A variety of techniques have been used as Research Methodology and these include questionnaires, interviews and personal observations of events in the rural community. This thesis embraces three main parts. Part I traces the socio-cultural aspects of PHC in rural Nigeria, describes PHC management activities in Nigeria and the practical problems inherent in the system. Part II describes various theoretical and practical research techniques used for the study and concentrates on the field work programme, data analysis and the research hypothesis-testing. Part III focusses on general strategies to improve PHC system in Nigeria to make it more effective. The research contributions to knowledge and the summary of main conclusions of the study are highlighted in this part also. Based on testing and exploring the research hypothesis as stated above, some conclusions have been arrived at, which suggested that PHC in rural Nigeria is ineffective as revealed in people's low opinions of the system and dissatisfaction with PHC services. Many people had expressed the view that they could not obtain health care services in time, at a cost they could afford and in a manner acceptable to them. Following the conclusions, some alternative ways to implement PHC programmes in rural Nigeria have been put forward to improve and make the Nigerian PHC system more effective.

The evaluation and development of the lead authority partnership scheme as a central intervention strategy for health and safety enforcement by local authorities

The research comprises a suite of studies that examines and develops the Lead Authority Partnership Scheme (LAPS) as a central intervention strategy for health and safety by local authority (LA) enforcers. Partnership working is a regulatory concept that in recent years has become more popular but there has been little research conducted to investigate, explore and evaluate its practical application. The study reviewed two contrasting approaches to partnership working between LAs and businesses, both of which were intended to secure improvements in the consistency of enforcement by the regulators and in the health and safety management systems of the participating businesses. The first was a well-established and highly prescriptive approach that required a substantial resource commitment on the part of the LA responsible for conducting a safety management review (SMR) of the business. As a result of his evaluation of the existing ‘full SMR’ scheme, the author developed a second, more flexible approach to partnership working. The research framework was based upon a primarily qualitative methodology intended to investigate and explore the impact of the new flexible arrangements for partnership working. The findings from this study of the flexible development of the scheme were compared and contrasted with those from studies of the established ‘full SMR’ scheme. A substantial degree of triangulation was applied in an attempt to strengthen validity and broaden applicability of the research findings. Key informant interviews, participant observation, document/archive reviews, questionnaires and surveys all their particular part to play in the overall study. The findings from this research revealed that LAPS failed to deliver consistency of LA enforcement across multiple-outlet businesses and the LA enforced business sectors. Improvement was however apparent in the safety management systems of the businesses participating in LAPS. Trust between LA inspector and safety professional was key to the success of the partnerships as was the commitment of these key individuals. Competition for precious LA resources, the priority afforded to food safety over health and safety, the perceived high resource demands of LAPS, and the structure and culture of LAs were identified as significant barriers to LA participation. Flexible approaches, whilst addressing the resource issues, introduced some fresh concerns relating to credibility and delivery. Over and above the stated aims of the scheme, LAs and businesses had their own reasons for participation, notably the personal development of individuals and kudos for the organisation. The research has explored the wider implications for partnership working with the overall conclusion it is most appropriately seen as a strategic level element within a broader structured intervention strategy.

Safety and health in mines: the rise of bureaucracy in the coal mining industry and its results as evidenced by the public enquiry into an accident at Houghton Main Colliery

This thesis is concerned with certain aspects of the Public Inquiry into the accident at Houghton Main Colliery in June 1975. It examines whether prior to the accident there existed at the Colliery a situation in which too much reliance was being placed upon state regulation and too Iittle upon personal responsibility. I study the phenomenon of state regulation. This is done (a) by analysis of selected writings on state regulation/intervention/interference/bureaucracy (the words are used synonymously) over the last two hundred years, specifically those of Marx on the 1866 Committee on Mines, and (b) by studying Chadwick and Tremenheere, leading and contrasting "bureaucrats" of the mid-nineteenth century. The bureaucratisation of the mining industry over the period 1835-1954 is described, and it is demonstrated that the industry obtained and now possesses those characteristics outlined by Max Weber in his model of bureaucracy. I analyse criticisms of the model and find them to be relevant, in that they facilitate understanding both of the circumstances of the accident and of the Inquiry . Further understanding of the circumstances and causes of the accident was gained by attendance at the lnquiry and by interviewing many of those involved in the Inquiry. I analyse many aspects of the Inquiry - its objectives. structure, procedure and conflicting interests - and find that, although the Inquiry had many of the symbols of bureaucracy, it suffered not from " too much" outside interference. but rather from the coal mining industry's shared belief in its ability to solve its own problems. I found nothing to suggest that, prior to the accident, colliery personnel relied. or were encouraged to rely, "too much" upon state regulation.

Nurturing health-related online support groups:exploring the experience of patient moderators

The aim of this study was to examine the views of moderators across a diverse and geographically broad range of online support groups about their moderator experiences and to explore both the personal benefits as well as challenges involved. Thirty-three patient moderators completed an online questionnaire which included a series of open-ended questions. Thematic analysis identified three themes: emergence, empowerment, nurturing. Several moderators declared their own diagnosis and for some, being able to share personal insights motivated them to establish the group and in turn offered validation. They felt empowered by helping others and learned more about the condition through accessing the "communal brain". Some felt the group aided patients' access to health services and their ability to communicate with health professionals while others worried about them becoming over-dependent. Moderators described needing to nurture their group to ensure it offered a safe space for members. Clear rules of engagement, trust, organisation skills, compassion and kindness were considered essential. Patient moderated online support groups can be successfully developed and facilitated and can be empowering for both the group member and moderator alike.© 2013 Elsevier Ltd. All rights reserved.

Examining the relationship between risk assessment and risk management in mental health

Risk assessment is crucial for developing risk management plans to prevent or minimize mental health patients' risks that will impede their recovery. Risk assessments and risk management plans should be closely linked. Their content and the extent to which they are linked within one Trust is explored. There is a great deal of variability in the amount and detail of risk information collected by nurses and how this is used to develop risk management plans. Keeping risk assessment information in one place rather than scattered throughout patient records is important for ensuring it can be accessed easily and linked properly to risk management plans. Strengthening the link between risk assessment and management will help ensure interventions and care is tailored to the specific needs of individual patients, thus promoting their safety and well-being. Thorough risk assessment helps in developing risk management plans that minimize risks that can impede mental health patients' recovery. Department of Health policy states that risk assessments and risk management plans should be inextricably linked. This paper examines their content and linkage within one Trust. Four inpatient wards for working age adults (18-65 years) in a large mental health Trust in England were included in the study. Completed risk assessment forms, for all patients in each inpatient ward were examined (n= 43), followed by an examination of notes for the same patients. Semi-structured interviews took place with ward nurses (n= 17). Findings show much variability in the amount and detail of risk information collected by nurses, which may be distributed in several places. Gaps in the risk assessment and risk management process are evident, and a disassociation between risk information and risk management plans is often present. Risk information should have a single location so that it can be easily found and updated. Overall, a more integrated approach to risk assessment and management is required, to help patients receive timely and appropriate interventions that can reduce risks such as suicide or harm to others. © 2011 Blackwell Publishing.

Handling varying amounts of missing data when classifying mental-health risk levels

One of the main challenges of classifying clinical data is determining how to handle missing features. Most research favours imputing of missing values or neglecting records that include missing data, both of which can degrade accuracy when missing values exceed a certain level. In this research we propose a methodology to handle data sets with a large percentage of missing values and with high variability in which particular data are missing. Feature selection is effected by picking variables sequentially in order of maximum correlation with the dependent variable and minimum correlation with variables already selected. Classification models are generated individually for each test case based on its particular feature set and the matching data values available in the training population. The method was applied to real patients' anonymous mental-health data where the task was to predict the suicide risk judgement clinicians would give for each patient's data, with eleven possible outcome classes: zero to ten, representing no risk to maximum risk. The results compare favourably with alternative methods and have the advantage of ensuring explanations of risk are based only on the data given, not imputed data. This is important for clinical decision support systems using human expertise for modelling and explaining predictions.

Medical students' personal experience of high-stakes failure:case studies using interpretative phenomenological analysis

Abstract (provisional): Background Failing a high-stakes assessment at medical school is a major event for those who go through the experience. Students who fail at medical school may be more likely to struggle in professional practice, therefore helping individuals overcome problems and respond appropriately is important. There is little understanding about what factors influence how individuals experience failure or make sense of the failing experience in remediation. The aim of this study was to investigate the complexity surrounding the failure experience from the student’s perspective using interpretative phenomenological analysis (IPA). Methods The accounts of 3 medical students who had failed final re-sit exams, were subjected to in-depth analysis using IPA methodology. IPA was used to analyse each transcript case-by-case allowing the researcher to make sense of the participant’s subjective world. The analysis process allowed the complexity surrounding the failure to be highlighted, alongside a narrative describing how students made sense of the experience. Results The circumstances surrounding students as they approached assessment and experienced failure at finals were a complex interaction between academic problems, personal problems (specifically finance and relationships), strained relationships with friends, family or faculty, and various mental health problems. Each student experienced multi-dimensional issues, each with their own individual combination of problems, but experienced remediation as a one-dimensional intervention with focus only on improving performance in written exams. What these students needed to be included was help with clinical skills, plus social and emotional support. Fear of termination of the their course was a barrier to open communication with staff. Conclusions These students’ experience of failure was complex. The experience of remediation is influenced by the way in which students make sense of failing. Generic remediation programmes may fail to meet the needs of students for whom personal, social and mental health issues are a part of the picture.

Improving the management of behaviour that challenges associated with dementia in care homes:protocol for pharmacy-health psychology intervention feasibility study

INTRODUCTION: The inappropriate use of antipsychotics in people with dementia for behaviour that challenges is associated with an estimated 1800 deaths annually. However, solely focusing on antipsychotics may transfer prescribing to other equally dangerous psychotropics. Little is known about the role of pharmacists in the management of psychotropics used to treat behaviours that challenge. This research aims to determine whether it is feasible to implement and measure the effectiveness of a combined pharmacy-health psychology intervention incorporating a medication review and staff training package to limit the prescription of psychotropics to manage behaviour that challenges in care home residents with dementia. METHODS/ANALYSIS: 6 care homes within the West Midlands will be recruited. People with dementia receiving medication for behaviour that challenges, or their personal consultee, will be approached regarding participation. Medication used to treat behaviour that challenges will be reviewed by the pharmacist, in collaboration with the general practitioner (GP), person with dementia and carer. The behavioural intervention consists of a training package for care home staff and GPs promoting person-centred care and treating behaviours that challenge as an expression of unmet need. The primary outcome measure is the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Other outcomes include quality of life (EQ-5D and DEMQoL), cognition (sMMSE), health economic (CSRI) and prescribed medication including whether recommendations were implemented. Outcome data will be collected at 6 weeks, and 3 and 6 months. Pretraining and post-training interviews will explore stakeholders' expectations and experiences of the intervention. Data will be used to estimate the sample size for a definitive study. ETHICS/DISSEMINATION: The project has received a favourable opinion from the East Midlands REC (15/EM/3014). If potential participants lack capacity, a personal consultee will be consulted regarding participation in line with the Mental Capacity Act. Results will be published in peer-reviewed journals and presented at conferences.