Undermining patient and public engagement and limiting its impact:the consequences of the Health and Social Care Act 2012 on collective patient and public involvement

Patient and public involvement has been at the heart of UK health policy for more than two decades. This commitment to putting patients at the heart of the British National Health Service (NHS) has become a central principle helping to ensure equity, patient safety and effectiveness in the health system. The recent Health and Social Care Act 2012 is the most significant reform of the NHS since its foundation in 1948. More radically, this legislation undermines the principle of patient and public involvement, public accountability and returns the power for prioritisation of health services to an unaccountable medical elite. This legislation marks a sea-change in the approach to patient and public involvement in the UK and signals a shift in the commitment of the UK government to patient-centred care. © 2013 John Wiley & Sons Ltd.

Hanchett-Stamford V (1) HM Attorney-General and (2) Dr William Johnston Jordan [2008] Ewhc 330 (CH), 2008 WL 1968855

Casenote considers meaning and impact of ruling of High Court in Hanchett Stamford v HM A.G. The decision of Mr Justice Lewison in Hanchett-Stamford v HM Attorney General and Dr William Johnston Jordan1 provides us with a useful analysis of the legal principles relating to the thorny issues of: (i) how unincorporated associations hold property; (ii) the applicability of the law of charities to unincorporated associations and (iii) the property rights of a declining membership upon the dissolution of such associations.

The value of corporate reputation and the Defamation Act 2013:a brave new world or road to ruin?

Questions whether the focus on freedom of expression under the Defamation Act 2013 could undermine the value of corporate reputation as a commercial asset.

Excipients in medicines for children:scientific and regulatory paradigms

There is an ongoing debate over the use of pharmaceutical excipients in medicines for children, triggered by the increased number of formulations suitable for this target patient population. Pharmaceutical excipients can be regarded as essential / necessary enablers in formulation development. These are materials other than the 'active pharmaceutical ingredient' which are added to the formulation to achieve a specific function1. This may include aiding in the processing or manufacture of the drug delivery system such as lubricants or flow aids, controlling the release of the active ingredient to achieve modified release, enhance patient acceptability by improving taste of medicines or to develop easily swallowed dosage forms.

Reversible oxidation of phosphatase and tensin homolog (PTEN) alters its interactions with signaling and regulatory proteins

Phosphatase and tensin homolog (PTEN) is involved in a number of different cellular processes including metabolism, apoptosis, cell proliferation and survival. It is a redox-sensitive dual-specificity protein phosphatase that acts as a tumor suppressor by negatively regulating the PI3K/Akt pathway. While direct evidence of redox regulation of PTEN downstream signaling has been reported, the effect of PTEN redox status on its protein-protein interactions is poorly understood. PTEN-GST in its reduced and a DTT-reversible H2O2-oxidized form was immobilized on a glutathione-sepharose support and incubated with cell lysate to capture interacting proteins. Captured proteins were analyzed by LC-MSMS and comparatively quantified using label-free methods. 97 Potential protein interactors were identified, including a significant number that are novel. The abundance of fourteen interactors was found to vary significantly with the redox status of PTEN. Altered binding to PTEN was confirmed by affinity pull-down and Western blotting for Prdx1, Trx, and Anxa2, while DDB1 was validated as a novel interactor with unaltered binding. These results suggest that the redox status of PTEN causes a functional variation in the PTEN interactome. The resin capture method developed had distinct advantages in that the redox status of PTEN could be directly controlled and measured.

General and special education teachers' knowledge of and attitudes toward students with HIV/AIDS

AIDS education is mandated in schools throughout the United States to educate students about the disease. Teachers are expected to assume the major role of disseminating this information; therefore it is reasonable to question how knowledgeable teachers are about HIV/AIDS and where their information is coming from. This study explored the knowledge and attitudes of general and special education teachers toward students with HIV/AIDS and investigated whether a relationship between knowledge and attitudes existed. Information was collected using the AIDS Knowledge and Attitude Survey (AKAS). The sample was limited to certified teachers resulting in 318 participants.^ Research questions were analyzed using descriptive statistics, frequencies, t-tests, one-way analysis of variance (ANOVA), Scheffe post hoc analysis, and Pearson Product-Moment Correlation. Results indicated that general and special education teachers did not have complete knowledge about HIV/AIDS. Participants were knowledgeable regarding modes of transmission which may be the area of greatest concern for teachers, however, deficiencies were present within teachers' knowledge of general statements and facts and pathology. Among the ten demographic variables analyzed, six (gender, race/ethnicity, level of education, certification, instructional level taught, and classroom AIDS instruction) contained statistical significance.^ Analysis of attitudes indicated that general and special education teachers' overall attitudes toward students with HIV/AIDS were generally positive within clusters of Instruction and Fear, but not within Sensitivity and Communication. Among the ten demographic variables used for analysis only three (age, graduate enrollment status, and classroom AIDS instruction) produced statistical significance. Results found statistically significant relationships between Total Knowledge, all knowledge subtests, Fear, and Overall Attitudes. Statistical significance was also located on Total Knowledge, Pathology and Transmission knowledge subtests, and Sensitivity, as well as between Pathology and Instruction, and General Statements and Facts and Communication.^ The only variable determined to have statistical significance on both knowledge and attitudes was classroom AIDS instruction. Participants with previous AIDS instruction showed greater knowledge and possessed more positive attitudes. A review of previous research indicated training to be effective in increasing knowledge and fostering more favorable behavior toward persons with AIDS. Therefore, this study finds AIDS training to be beneficial for all teachers and is recommended during preservice education or through inservices for teachers already in the field. ^

Combined analysis of variation in core, accessory and regulatory genome regions provides a super-resolution view into the evolution of bacterial populations

The use of whole-genome phylogenetic analysis has revolutionized our understanding of the evolution and spread of many important bacterial pathogens due to the high resolution view it provides. However, the majority of such analyses do not consider the potential role of accessory genes when inferring evolutionary trajectories. Moreover, the recently discovered importance of the switching of gene regulatory elements suggests that an exhaustive analysis, combining information from core and accessory genes with regulatory elements could provide unparalleled detail of the evolution of a bacterial population. Here we demonstrate this principle by applying it to a worldwide multi-host sample of the important pathogenic E. coli lineage ST131. Our approach reveals the existence of multiple circulating subtypes of the major drug–resistant clade of ST131 and provides the first ever population level evidence of core genome substitutions in gene regulatory regions associated with the acquisition and maintenance of different accessory genome elements.

The Life of an Author: Samuel Egerton Brydges and the Copyright Act 1814

The history of literary copyright in nineteenth century Britain is dominated - understandably perhaps - by a preoccupation with the passing and impact of the Copyright Amendment Act 1842, so ably lobbied for by Sir Thomas Noon Talfourd. This article, however, draws attention away from the 1842 Act towards the Copyright Act 1814, the first legislative provision within British copyright law to introduce a lifetime term of protection for the author. Why and on what basis did the legislature do so?
In bringing a renewed attention to this often overlooked legislative measure, we consider the context and logic that underpinned to grant of a copyright term that was tethered to the life of the author. In doing so, we might also find a useful prism through which to look afresh at current copyright debates concerning the appropriate nature and scope of copyright protection in the 21st century.

A study of the effects of the Comprehensive Occupational Safety and Health Reform Act (H.R. 1280).

"April 1994."

Prevalence of General and Abdominal Obesity in a Nationally Representative Sample of Iranian Children and Adolescents: The CASPIAN-IV Study

Background: Pediatric obesity is one of the predisposing risk factors for many non-communicable diseases. Objectives: The purpose of this study was to estimate the national prevalence of general and abdominal obesity among Iranian children and adolescents. Patients and Methods: This cross-sectional nation-wide study was performed in 30 provinces in Iran among 14880 school students aged 6 – 18 years, selected by multistage random cluster sampling. The World Health Organization growth curve was used to categorize Body Mass Index (BMI). Obesity was defined as BMI equal to or higher than the age- and gender-specific 95th percentile; abdominal obesity was considered as waist-to-height ratio of more than 0.5. Results: Data of 13486 out of 14880 invited students were complete (response rate of 90.6%). They consisted of 6543 girls and 75.6% urban residents, and had a mean age of 12.45 (95% CI: 12.40 - 12.51) years. The prevalence rate of general and abdominal obesity was 11.89% (13.58% of boys vs. 10.15% of girls) and 19.12% (20.41% of boys vs. 17.79% of girls), respectively. The highest frequency of obesity was found in the middle school students (13.87% general and 20.84% abdominal obesity). The highest prevalence of general obesity was found in Boushehr (19%) followed by Guilan and Mazandaran (18.3%, 18.3%), while the lowest prevalence was observed in Hormozgan (2.6%). The highest frequency of abdominal obesity was found in Mazandaran (30.2%), Ardabil (29.2%) and Tehran (27.9%). Provinces such as Sistan-Baloochestan (8.4%), Hormozagan (7.4%), and Kerman (11.4%) had the lowest prevalence of abdominal obesity. The Southern and South Eastern provinces had the lowest prevalence of general obesity (2.6% and 5.6%) and abdominal obesity (7.4% and 8.8%). Moreover, the highest prevalence of obesity was found in North and North West Iran by maximum frequency of 18.3% general obesity and 30.2% of abdominal obesity. Conclusions: The results showed a high prevalence of general and abdominal obesity among boys living in the Northern provinces of Iran. The present study provides insights that policy makers should consider action-oriented interventions for prevention and control of childhood obesity at national and sub-national level.

Cross-talk and regulatory interactions between the essential response regulator RpaB and cyanobacterial circadian clock output

The response regulator RpaB (regulator of phycobilisome associated B), part of an essential two-component system conserved in cyanobacteria that responds to multiple environmental signals, has recently been implicated in the control of cell dimensions and of circadian rhythms of gene expression in the model cyanobacterium Synechococcus elongatus PCC 7942. However, little is known of the molecular mechanisms that underlie RpaB functions. In this study we show that the regulation of phenotypes by RpaB is intimately connected with the activity of RpaA (regulator of phycobilisome associated A), the master regulator of circadian transcription patterns. RpaB affects RpaA activity both through control of gene expression, a function requiring an intact effector domain, and via altering RpaA phosphorylation, a function mediated through the N-terminal receiver domain of RpaB. Thus, both phosphorylation cross-talk and coregulation of target genes play a role in the genetic interactions between the RpaA and RpaB pathways. In addition, RpaB∼P levels appear critical for survival under light:dark cycles, conditions in which RpaB phosphorylation is environmentally driven independent of the circadian clock. We propose that the complex regulatory interactions between the essential and environmentally sensitive NblS-RpaB system and the SasA-RpaA clock output system integrate relevant extra- and intracellular signals to the circadian clock.

Methods and tools for analysis and management of risks and regulatory compliance in the healthcare sector: the hospital at home – HaH

Changing or creating an organisation means creating a new process. Each process involves many risks that need to be identified and managed. The main risks considered here are procedural and legal risks. The former are related to the risks of errors that may occur during processes, while the latter are related to the compliance of processes with regulations. Managing the risks implies proposing changes to the processes that allow the desired result: an optimised process. In order to manage a company and optimise it in the best possible way, not only should the organisational aspect, risk management and legal compliance be taken into account, but it is important that they are all analysed simultaneously with the aim of finding the right balance that satisfies them all. This is the aim of this thesis, to provide methods and tools to balance these three characteristics, and to enable this type of optimisation, ICT support is used. This work isn’t a thesis in computer science or law, but rather an interdisciplinary thesis. Most of the work done so far is vertical and in a specific domain. The particularity and aim of this thesis is not to carry out an in-depth analysis of a particular aspect, but rather to combine several important aspects, normally analysed separately, which however have an impact and influence each other. In order to carry out this kind of interdisciplinary analysis, the knowledge base of both areas was involved and the combination and collaboration of different experts in the various fields was necessary. Although the methodology described is generic and can be applied to all sectors, the case study considered is a new type of healthcare service that allows patients in acute disease to be hospitalised to their home. This provide the possibility to perform experiments using real hospital database.

S-nitrosylation homeostasis in plants: key enzymes and regulatory pathways

The nitrosylated form of glutathione (GSNO) has been acknowledged to be the most important nitrosylating agent of the plant cell, and the tuning of its intracellular concentration is of pivotal importance for photosynthetic life. During my time as a PhD student, I focused my attention on the enzymatic systems involved in the degradation of GSNO. Hence, we decided to study the structural and catalytic features of alcohol dehydrogenases (GSNOR and ADH1) from the model land plant Arabidopsis thaliana (At). These enzymes displayed a very similar 3D structure except for their active site which might explain the extreme catalytic specialization of the two enzymes. They share NAD(H) as a cofactor, but only AtGSNOR was able to catalyze the reduction of GSNO whilst being ineffective in oxidizing ethanol. Moreover, our study on the enzyme from the unicellular green alga Chlamydomonas reinhardtii (Cr) revealed how this S-nitrosoglutathione reductase (GSNOR) specifically use NADH to catalyze GSNO reduction and how its activity responds to thiol-based post-translational modifications. Contextually, the presence of NADPH-dependent GSNO-degrading systems in algal protein extract was highlighted and resulted to be relatively efficient in this model organism. This activity could be ascribed to several proteins whose contribution has not been defined yet. Intriguingly, protein extract from GSNOR null mutants of Arabidopsis displayed an increased NADPH-dependent ability to degrade GSNO and our quantitative proteome profiling on the gsnor mutant revealed the overexpression of two class 4 aldo-keto reductases (AKR), specifically AtAKR4C8 and AtAKR4C9. Later, all four class 4 AKRs showed to possess a NADPH-dependent GSNO-degrading activity. Finally, we initiated a preliminary analysis to determine the kinetic parameters of several plant proteins, including GSNOR, AKR4Cs, and thioredoxins. These data suggested GSNOR to be the most effective enzyme in catalyzing GSNO reduction because of its extremely high catalytic proficiency compared to NADPH-dependent systems.

Multi-Principal Agency and the Compliance with Professional Guidelines in Health Systems: Economic and Regulatory Perspectives

Amid the trend of rising health expenditure in developed economies, changing the healthcare delivery models is an important point of action for service regulators to contain this trend. Such a change is mostly induced by either financial incentives or regulatory tools issued by the regulators and targeting service providers and patients. This creates a tripartite interaction between service regulators, professionals, and patients that manifests a multi-principal agent relationship, in which professionals are agents to two principals: regulators and patients. This thesis is concerned with such a multi-principal agent relationship in healthcare and attempts to investigate the determinants of the (non-)compliance to regulatory tools in light of this tripartite relationship. In addition, the thesis provides insights into the different institutional, economic, and regulatory settings, which govern the multi-principal agent relationship in healthcare in different countries. Furthermore, the thesis provides and empirically tests a conceptual framework of the possible determinants of (non-)compliance by physicians to regulatory tools issued by the regulator. The main findings of the thesis are first, in a multi-principal agent setting, the utilization of financial incentives to align the objectives of professionals and the regulator is important but not the only solution. This finding is based on the heterogeneity in the financial incentives provided to professionals in different health markets, which does not provide a one-size-fits-all model of financial incentives to influence clinical decisions. Second, soft law tools as clinical practice guidelines (CPGs) are important tools to mitigate the problems of the multi-principal agent setting in health markets as they reduce information asymmetries while preserving the autonomy of professionals. Third, CPGs are complex and heterogeneous and so are the determinants of (non-)compliance to them. Fourth, CPGs work but under conditions. Factors such as intra-professional competition between service providers or practitioners might lead to non-compliance to CPGs – if CPGs are likely to reduce the professional’s utility. Finally, different degrees of soft law mandate have different effects on providers’ compliance. Generally, the stronger the mandate, the stronger the compliance, however, even with a strong mandate, drivers such as intra-professional competition and co-management of patients by different professionals affected the (non-)compliance.

Distributed argumentation technology: advancing risk analysis and regulatory compliance of distributed ledger technologies for transaction and management of securities

Distributed argumentation technology is a computational approach incorporating argumentation reasoning mechanisms within multi-agent systems. For the formal foundations of distributed argumentation technology, in this thesis we conduct a principle-based analysis of structured argumentation as well as abstract multi-agent and abstract bipolar argumentation. The results of the principle-based approach of these theories provide an overview and guideline for further applications of the theories. Moreover, in this thesis we explore distributed argumentation technology using distributed ledgers. We envision an Intelligent Human-input-based Blockchain Oracle (IHiBO), an artificial intelligence tool for storing argumentation reasoning. We propose a decentralized and secure architecture for conducting decision-making, addressing key concerns of trust, transparency, and immutability. We model fund management with agent argumentation in IHiBO and analyze its compliance with European fund management legal frameworks. We illustrate how bipolar argumentation balances pros and cons in legal reasoning in a legal divorce case, and how the strength of arguments in natural language can be represented in structured arguments. Finally, we discuss how distributed argumentation technology can be used to advance risk management, regulatory compliance of distributed ledgers for financial securities, and dialogue techniques.