Early stage investing in green SMEs: the case of the UK

How might a Green New Deal be applied to the early stage financing of Cleantechs? Amidst rising interest and adoption of Green New Deals in the US, the paper explores the need for more focused policy to address early stage long horizon financing of Cleantechs. We argue that insufficient focus has been applied to early stage investing into these types of innovative SMEs that could lower CO2 emissions across a range of sectors (including renewable energy, recycling, advanced manufacturing, transport and bio-science). Adopting a resource complementarity lens and borrowing from transaction cost theory, we illustrate and build theory through longitudinal UK case studies. These demonstrate how government policy can scale-up through international collaboration public-private, principally venture capital, cofinance to facilitate cleantech innovation with potentially game changing impacts on reducing CO2 emissions in order to meet the Paris 2015 Climate Change targets

Ireland Is Ireland To Me

https://digitalcommons.library.umaine.edu/mmb-vp/3223/thumbnail.jp

A simple principal stratum estimator for failure to initiate treatment

A common intercurrent event affecting many trials is when some participants do not begin their assigned treatment. For example, in a trial comparing two different methods for fluid delivery during surgery, some participants may have their surgery cancelled. Similarly, in a double-blind drug trial, some participants may not receive any dose of study medication. The commonly used intention-to-treat analysis preserves the randomisation structure, thus protecting against biases from post-randomisation exclusions. However, it estimates a treatment policy effect (i.e. addresses the question "what is the effect of the intervention, regardless of whether the participant actually begins treatment?"), which may not be the most clinically relevant estimand. A principal stratum approach, estimating the treatment effect in the subpopulation of participants who would initiate treatment (regardless of treatment arm), may be a more clinically relevant estimand for many trials. We show that a simple principal stratum estimator based on a "modified intention-to-treat" population, where participants who experience the intercurrent event are excluded, is unbiased for the principal stratum estimand under certain assumptions that are likely to be plausible in many trials, namely that participants who initiate the intervention under one treatment condition would also do so under the other treatment condition. We provide several examples of trials where this assumption is plausible, and several instances where it is not. We conclude that this simple principal stratum estimator can be a useful strategy for handling failure to initiate treatment

Using modified intention-to-treat as a principal stratum estimator for failure to initiate treatment

BACKGROUND: A common intercurrent event affecting many trials is when some participants do not begin their assigned treatment. For example, in a double-blind drug trial, some participants may not receive any dose of study medication. Many trials use a 'modified intention-to-treat' approach, whereby participants who do not initiate treatment are excluded from the analysis. However, it is not clear (a) the estimand being targeted by such an approach and (b) the assumptions necessary for such an approach to be unbiased. METHODS: Using potential outcome notation, we demonstrate that a modified intention-to-treat analysis which excludes participants who do not begin treatment is estimating a principal stratum estimand (i.e. the treatment effect in the subpopulation of participants who would begin treatment, regardless of which arm they were assigned to). The modified intention-to-treat estimator is unbiased for the principal stratum estimand under the assumption that the intercurrent event is not affected by the assigned treatment arm, that is, participants who initiate treatment in one arm would also do so in the other arm (i.e. if someone began the intervention, they would also have begun the control, and vice versa). RESULTS: We identify two key criteria in determining whether the modified intention-to-treat estimator is likely to be unbiased: first, we must be able to measure the participants in each treatment arm who experience the intercurrent event, and second, the assumption that treatment allocation will not affect whether the participant begins treatment must be reasonable. Most double-blind trials will satisfy these criteria, as the decision to start treatment cannot be influenced by the allocation, and we provide an example of an open-label trial where these criteria are likely to be satisfied as well, implying that a modified intention-to-treat analysis which excludes participants who do not begin treatment is an unbiased estimator for the principal stratum effect in these settings. We also give two examples where these criteria will not be satisfied (one comparing an active intervention vs usual care, where we cannot identify which usual care participants would have initiated the active intervention, and another comparing two active interventions in an unblinded manner, where knowledge of the assigned treatment arm may affect the participant's choice to begin or not), implying that a modified intention-to-treat estimator will be biased in these settings. CONCLUSION: A modified intention-to-treat analysis which excludes participants who do not begin treatment can be an unbiased estimator for the principal stratum estimand. Our framework can help identify when the assumptions for unbiasedness are likely to hold, and thus whether modified intention-to-treat is appropriate or not

Key actors in driving behavioural change in relation to on-farm biosecurity; a Northern Ireland perspective

Background: Agriculture and farming are valued contributors to local economy in Northern Ireland (NI). There is limited knowledge about farmers’ behaviours and attitudes towards disease biosecurity measures. As part of a larger project, a scenario-based workshop with key stakeholders was organised by the Agri-Food and Biosciences Institute (AFBI)-NI in December 2015. Results: A total of 22 participants belonging to 12 different institutions took part in the workshop. Participants were presented with an overview of previously conducted biosecurity research in NI and England. In small groups, participants were subsequently asked to discuss and give their opinions about a series of questions across four key areas in a semi-structured approach with an external facilitator. The key areas were 1- disease risk perception at the farm level; 2-perceived barriers to implementing on farm biosecurity measures; 3- avenues to successful behaviour change and 4-key industry responsibilities and roles. The discussion showed that training in biosecurity for farmers is important and necessary. Training was recommended to be provided by veterinary surgeons, preferably via a face-to-face format. The discussion addressing disease disclosure proved particularly challenging between those who were prospective buyers of cattle, and those who sold cattle. Conclusions: This workshop provided a unique and invaluable insight into key issues regarding farm level biosecurity activities. From a policy perspective, delivering improved on-farm biosecurity must be addressed via a multidisciplinary approach. This can only be achieved with active involvement, commitment and support of a number of key industry and government stakeholders

Diclofenac Mouthwash as a potential therapy for reducing pain and discomfort in chemo-radiotherapy-induced oral mucositis

AIMS: Oral and/or oropharyngeal acute mucositis during and after chemo-radiotherapy (chemo-RT) for head and neck squamous cell carcinoma (HNSCC) can be extremely painful, sometimes requiring nasogastric feeding to enable adequate nutrition. The MASCC/ISOO evidence- based guidelines recommend benzydamine mouthwash for mucositis prevention in RT (recently updated to include chemo-RT), and a Cochrane systematic review found other agents to be effective in prophylaxis. Diclofenac mouthwash is licenced for painful oral mucosal inflammatory conditions but to our knowledge has not been assessed in chemo-RT associated oral mucositis. METHOD: A clinical observation and service evaluation study in 10 patients undergoing chemo-RT for HNSCC to assess the potential value of diclofenac mouthwash (0.74mg/ml) in reducing symptoms. Patients used 20ml of mouthwash up to 4 times a day starting in week 3 (of a 6 week course of treatment), recording pain and discomfort scores using a visual analogue scale on days 0, 1,7 and 14 (until the end of week 4). As per our current clinical practice, oral mucositis was not clinically scored as an outcome. Statistical analysis was performed using a one-way ANOVA. RESULTS: Using diclofenac mouthwash, 9/10 patients experienced pain score reduction from day 0 (mean score 6.75 +/- SD 1.83) to day 2 (5.05 +/- SD 1.62) and day 14 (4.09 +/- SD 1.96). CONCLUSIONS: Diclofenac mouthwash may be beneficial for managing chemo-RT-induced oral mucositis. While a prospective randomised clinical trial is needed, it can be prescribed for this condition within its current licence

The transition from medical student to junior doctor: today's experiences of Tomorrow's Doctors.

CONTEXT Medical education in the UK has recently undergone radical reform. Tomorrow's Doctors has prescribed undergraduate curriculum change and the Foundation Programme has overhauled postgraduate education. OBJECTIVES This study explored the experiences of junior doctors during their first year of clinical practice. In particular, the study sought to gain an understanding of how junior doctors experienced the transition from the role of student to that of practising doctor and how well their medical school education had prepared them for this. METHODS The study used qualitative methods comprising of semi-structured interviews and audio diary recordings with newly qualified doctors based at the Peninsula Foundation School in the UK. Purposive sampling was used and 31 of 186 newly qualified doctors self-selected from five hospital sites. All 31 participants were interviewed once and 17 were interviewed twice during the year. Ten of the participants also kept audio diaries. Interview and audio diary data were transcribed verbatim and thematically analysed with the aid of a qualitative data analysis software package. RESULTS The findings show that, despite recent curriculum reforms, most participants still found the transition stressful. Dealing with their newly gained responsibility, managing uncertainty, working in multi-professional teams, experiencing the sudden death of patients and feeling unsupported were important themes. However, the stress of transition was reduced by the level of clinical experience gained in the undergraduate years. CONCLUSIONS Medical schools need to ensure that students are provided with early exposure to clinical environments which allow for continuing 'meaningful' contact with patients and increasing opportunities to 'act up' to the role of junior doctor, even as students. Patient safety guidelines present a major challenge to achieving this, although with adequate supervision the two aims are not mutually exclusive. Further support and supervision should be made available to junior doctors in situations where they are dealing with the death of a patient and on surgical placements

Limits on Replenishment of the Resting CD4+ T Cell Reservoir for HIV in Patients on HAART

Whereas cells productively infected with human immunodeficiency virus type 1 (HIV-1) decay rapidly in the setting of highly active antiretroviral therapy (HAART), latently infected resting CD4+ T cells decay very slowly, persisting for the lifetime of the patient and thus forming a stable reservoir for HIV-1. It has been suggested that the stability of the latent reservoir is due to low-level viral replication that continuously replenishes the reservoir despite HAART. Here, we offer the first quantitative study to our knowledge of inflow of newly infected cells into the latent reservoir due to viral replication in the setting of HAART. We make use of a previous observation that in some patients on HAART, the residual viremia is dominated by a predominant plasma clone (PPC) of HIV-1 not found in the latent reservoir. The unique sequence of the PPC serves as a functional label for new entries into the reservoir. We employ a simple mathematical model for the dynamics of the latent reservoir to constrain the inflow rate to between 0 and as few as 70 cells per day. The magnitude of the maximum daily inflow rate is small compared to the size of the latent reservoir, and therefore any inflow that occurs in patients on HAART is unlikely to significantly influence the decay rate of the reservoir. These results suggest that the stability of the latent reservoir is unlikely to arise from ongoing replication during HAART. Thus, intensification of standard HAART regimens should have minimal effects on the decay of the latent reservoir

Evolutionary engineering improves tolerance for replacement jet fuels in Saccharomyces cerevisiae

Monoterpenes are liquid hydrocarbons with applications ranging from flavor and fragrance to replacement jet fuel. Their toxicity, however, presents a major challenge for microbial synthesis. Here we evolved limonene-tolerant Saccharomyces cerevisiae strains and sequenced six strains across the 200-generation evolutionary time course. Mutations were found in the tricalbin proteins Tcb2p and Tcb3p. Genomic reconstruction in the parent strain showed that truncation of a single protein (tTcb3p(1-989)), but not its complete deletion, was sufficient to recover the evolved phenotype improving limonene fitness 9-fold. tTcb3p(1-989) increased tolerance toward two other monoterpenes (beta-pinene and myrcene) 11- and 8-fold, respectively, and tolerance toward the biojet fuel blend AMJ-700t (10% cymene, 50% limonene, 40% farnesene) 4-fold. tTcb3p(1-989) is the first example of successful engineering of phase tolerance and creates opportunities for production of the highly toxic C-10 alkenes in yeast