Terahertz emitters based on microcavity dipolaritons

We propose the use of dipolaritons -- quantum well excitons with large dipole moment, coupled to a planar microcavity -- for generating terahertz (THz) radiation. This is achieved by exciting the system with two THz detuned lasers that leads to dipole moment oscillations of the exciton polariton at the detuning frequency, thus generating a THz emission. We have optimized the structural parameters of a system with microcavity embedded AlGaAs double quantum wells and shown that the THz emission intensity is maximized if the laser frequencies both match different dipolariton states. The influence of the electronic tunnel coupling between the wells on the frequency and intensity of the THz radiation is also investigated, demonstrating a trade-off between the polariton dipole moment and the Rabi splitting.Comment: 4 pages, 4 figures. This article has been submitted to Applied Physics Letter

The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun

© 2020 The Author(s). Background: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells. Methods: We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species. Results: AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC). Conclusions: This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action

An Empirical Investigation Into the Role of Values in Occupational Therapy Decision-making

The importance of values in occupational therapy is generally agreed, however there is no consensus about their nature or their influence on practice. It is widely assumed that occupational therapists hold and act on a body of shared values, yet there is a lack of evidence to support this. The research tested the hypothesis that occupational therapists’ responses to ethically challenging situations would reveal common values specific to the occupational therapy profession. 156 occupational therapists were asked to decide what should be done in 5 common-place yet ethically complex situations, presented as scenarios for debate. The results show that while most occupational therapists share very general values, they frequently disagree about what to do in practice situations, often justifying their choices with different and sometimes conflicting specific values. In some cases, the same respondents espouse contradictory values in similar situations. The extensive literature about decision-making - together with the study’s results – confirm that when occupational therapists make decisions, they draw on multiple factors, consciously and unconsciously. These factors vary between individuals. Value judgements are one part only of a complex process which includes personal experience, intuition, social influences, culture, psychological influences and relationships with both colleagues and clients

Targeting BRCA1-BER deficient breast cancer by ATM or DNA-PKcs blockade either alone or in combination with cisplatin for personalized therapy

BRCA1, a key factor in homologous recombination repair may also regulate base excision repair (BER). Targeting BRCA1-BER deficient cells by blockade of ATM and DNA-PKcs could be a promising strategy in breast cancer. We investigated BRCA1, XRCC1 and pol β protein expression in two cohorts (n=1602 sporadic and n=50 germ-line BRCA1 mutated) and mRNA expression in two cohorts (n=1952 and n=249). Artificial neural network analysis for BRCA1-DNA repair interacting genes was conducted in 249 tumours. Pre-clinically, BRCA1 proficient and deficient cells were DNA repair expression profiled and evaluated for synthetic lethality using ATM and DNA-PKcs inhibitors either alone or in combination with cisplatin. In human tumours, BRCA1 negativity was strongly associated with low XRCC1, and low pol β at mRNA and protein levels (p<0.0001). In patients with BRCA1 negative tumours, low XRCC1 or low pol β expression was significantly associated with poor survival in univariate and multivariate analysis compared to high XRCC1 or high pol β expressing BRCA1 negative tumours (ps<0.05). Pre-clinically, BRCA1 negative cancer cells exhibit low mRNA and low protein expression of XRCC1 and pol β. BRCA1-BER deficient cells were sensitive to ATM and DNA-PKcs inhibitor treatment either alone or in combination with cisplatin and synthetic lethality was evidenced by DNA double strand breaks accumulation, cell cycle arrest and apoptosis. We conclude that XRCC1 and pol β expression status in BRCA1 negative tumours may have prognostic significance. BRCA1-BER deficient cells could be targeted by ATM or DNA-PKcs inhibitors for personalized therapy

Can the Revised UK Code Direct Practice?

The Nursing and Midwifery Council, the United Kingdom regulator of nursing and midwifery has recently revised its professional code of practice. This paper begins by arguing that a professional code must be capable of sustaining close reading and of action guidance. Using four exemplar clauses it is argued that the new revised code does not met this purpose. First, I show that in setting out requirements for consent and documentation, the meaning of the relevant clause has changed significantly during the editing process so that a literal reading of the final document bears little relation to established professional practice. Second, I argue that the clause concerning the nature of professional relationships has also been altered during the editing process so that it is inconsistent with other professional groups and established accounts of the professional nurse-patient relationship. Third, I argue that the clause concerning disclosure of confidential information, which survived revision and editing with its meaning intact is nevertheless factually incorrect and inconsistent with UK law and authoritative guidance. Finally, fourth, I argue that use of the word ‘inappropriate’ is inappropriate as it amounts to meaningless circularity, discussed in relation to a clause on expressing personal beliefs. Taken together, these examples demonstrate that the Code is seriously flawed and does not fulfil its purpose. One way that simple prescriptive clauses in the Code can be usefully understood is through the provision of detailed guidance. I argue that the NMC has changed its position on its view of the value of guidance and has significantly reduced the amount of written guidance and advice is provides. The paper concludes by arguing that in order to meet its action directing function, further clarifying revision and the provision of detailed guidance is required

Preferential transcription of the mutated allele in NPM1 mutated acute myeloid leukaemia

Nucleophosmin is commonly both over-expressed and mutated in acute myeloid leukemia (AML). NPM1 mutations are always heterozygous. In addition, NPM1 has a number of different splice variants with the major variant encoded by exons 1–9 and 11–12 (NPM1.1). Further variants include NPM1.2 which lacks exons 8 and 10 and NPM1.3 which comprises exons 1–10 (and so lacks the region of sequence mutated in AML). In this study we quantified the expression of these three variants in 108 AML patient samples with and without NPM1 mutations and also assessed the level of expression from the wild-type and mutant alleles in variants NPM1.1 and NPM1.2. The results show that NPM1.1 is the most commonly expressed variant, however transcripts from wild-type and mutated alleles do not occur at equal levels, with a significant bias toward the mutated allele. Considering the involvement of mutant nucleophosmin in the progression and maintenance of AML, a bias towards mutated transcripts could have a significant impact on disease maintenance

Apparent quality-of-life in nations : how long and happy people live

Quality-of-life in nations can be measured by how long and happy people live. This is assessed by combining data on life expectancy drawn from civil registration with survey data on subjective enjoyment of life as a whole. This measure of 'apparent' quality-of-life is a good alternative to current indexes of 'assumed' quality-of-life such as the Human Development Index. Data are available for 67 nations in the 1990s. The number of Happy-Life-Years varies considerably across nations. Switzerland is at the top with 63.0 years and Moldavia at the bottom with 20.5 years. China is in the middle with an average of 46.7. Happy lifetime has risen considerably in advanced nations over the last decade. People live longer and happier in nations characterised by economic affluence, freedom and justice. Together these three societal qualities explain 66% of the cross-national variance in Happy-Life-Years. Income equality and generous social security do not appear to be required for a long and happy life

What facilitates the delivery of dignified care to older people? A survey of health care professionals Geriatrics

Background: Whilst the past decade has seen a growing emphasis placed upon ensuring dignity in the care of older people this policy objective is not being consistently achieved and there appears a gap between policy and practice. We need to understand how dignified care for older people is understood and delivered by the health and social care workforce and how organisational structures and policies can promote and facilitate, or hinder, the delivery of such care. Methods: To achieve our objective of understanding the facilitators and to the delivery of dignified care we undertook a survey with health and social care professionals across four NHS Trusts in England. Participants were asked provide free text answers identifying any facilitators/barriers to the provision of dignified care. Survey data was entered into SPSSv15 and analysed using descriptive statistics. These data provided the overall context describing staff attitudes and beliefs about dignity and the provision of dignified care. Qualitative data from the survey were transcribed verbatim and categorised into themes using thematic analysis. Results: 192 respondents were included in the analysis. 79 % of respondents identified factors within their working environment that helped them provide dignified care and 68 % identified barriers to achieving this policy objective. Facilitators and barriers to delivering dignified care were categorised into three domains: 'organisational level'; 'ward level' and 'individual level'. Within the these levels, respondents reported factors that both supported and hindered dignity in care including 'time', 'staffing levels', training',' 'ward environment', 'staff attitudes', 'support', 'involving family/carers', and 'reflection'. Conclusion: Facilitators and barriers to the delivery of dignity as perceived by health and social care professionals are multi-faceted and range from practical issues to interpersonal and training needs. Thus interventions to support health and social care professionals in delivering dignified care, need to take a range of issues into account to ensure that older people receive a high standard of care in NHS Trusts.Professor David Oliver, Professor Andree le May, Dr. Sally Richards, Dr Wendy Marti

Children's play space and safety management: rethinking the role of play equipment standards

The provision of stimulating and engaging play space for children and young people is increasingly recognized as an important societal goal, not the least because it provides the young with opportunities to develop and gain experience in experimenting with risk. Research in several disciplines now suggests that achievement of this goal has however been impeded in recent decades, and reasons commonly cited have included fear of injury and avoidance of litigation. International standards on play equipment have also been promulgated and justified in terms of securing young people’s “safety,” most usually narrowly defined as injury reduction. There appears to be a widespread presumption that measures aimed at injury prevention are necessarily beneficial overall for young people’s welfare. In this article, we subject European standards for play equipment and surfacing to scrutiny. In particular, we examine underlying motives, consistency of purpose, use of evidence, philosophical leanings, scope, practicalities of application, systems of management, and legal ramifications. From this, we identify a number of fundamental issues that suggest that as a consequence of compartmentalized thinking and misunderstandings, these standards have invaded areas of decision making beyond their legitimate territory. The consequence of this is that play provision is skewed away from what are properly play provision objectives. In such circumstances, local decision makers are often disempowered, and their ability to provide optimal play spaces thereby circumscribed