Mediation in the Law Curriculum

Cited by Lord Neuberger in ‘Educating Future Mediators’ at the 4th Civil Mediation Council National Conference, May 201

Differential clonal evolution in oesophageal cancers in response to neo-adjuvant chemotherapy

How chemotherapy affects carcinoma genomes is largely unknown. Here we report whole-exome and deep sequencing of 30 paired oesophageal adenocarcinomas sampled before and after neo-adjuvant chemotherapy. Most, but not all, good responders pass through genetic bottlenecks, a feature associated with higher mutation burden pre-treatment. Some poor responders pass through bottlenecks, but re-grow by the time of surgical resection, suggesting a missed therapeutic opportunity. Cancers often show major changes in driver mutation presence or frequency after treatment, owing to outgrowth persistence or loss of sub-clones, copy number changes, polyclonality and/or spatial genetic heterogeneity. Post-therapy mutation spectrum shifts are also common, particularly C>A and TT>CT changes in good responders or bottleneckers. Post-treatment samples may also acquire mutations in known cancer driver genes (for example, SF3B1, TAF1 and CCND2) that are absent from the paired pre-treatment sample. Neo-adjuvant chemotherapy can rapidly and profoundly affect the oesophageal adenocarcinoma genome. Monitoring molecular changes during treatment may be clinically useful

Development and evaluation of an instrument for the critical appraisal of randomized controlled trials of natural products

<p>Abstract</p> <p>Background</p> <p>The efficacy of natural products (NPs) is being evaluated using randomized controlled trials (RCTs) with increasing frequency, yet a search of the literature did not identify a widely accepted critical appraisal instrument developed specifically for use with NPs. The purpose of this project was to develop and evaluate a critical appraisal instrument that is sufficiently rigorous to be used in evaluating RCTs of conventional medicines, and also has a section specific for use with single entity NPs, including herbs and natural sourced chemicals.</p> <p>Methods</p> <p>Three phases of the project included: 1) using experts and a Delphi process to reach consensus on a list of items essential in describing the identity of an NP; 2) compiling a list of non-NP items important for evaluating the quality of an RCT using systematic review methodology to identify published instruments and then compiling item categories that were part of a validated instrument and/or had empirical evidence to support their inclusion and 3) conducting a field test to compare the new instrument to a published instrument for usefulness in evaluating the quality of 3 RCTs of a NP and in applying results to practice.</p> <p>Results</p> <p>Two Delphi rounds resulted in a list of 15 items essential in describing NPs. Seventeen item categories fitting inclusion criteria were identified from published instruments for conventional medicines. The new assessment instrument was assembled based on content of the two lists and the addition of a Reviewer's Conclusion section. The field test of the new instrument showed good criterion validity. Participants found it useful in translating evidence from RCTs to practice.</p> <p>Conclusion</p> <p>A new instrument for the critical appraisal of RCTs of NPs was developed and tested. The instrument is distinct from other available assessment instruments for RCTs of NPs in its systematic development and validation. The instrument is ready to be used by pharmacy students, health care practitioners and academics and will continue to be refined as required.</p

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Balancing Social and Political Strategies in Emerging Markets: Evidence from India

This article explores the substitution and complementary effects between political and social strategies on firm performance in the context of an emerging market (EM). Using in-depth, historical case-study approach, the article investigates how companies integrate political and social resources in this market. Corporate performance includes traditional measures such as accounting performance and nonfinancial measures like the ease of doing business. The study finds that social strategies are stronger enablers of firm long-term performance than political strategies. The latter have a short-term impact on performance, but their success over time is limited. The main drawback of reliance on political resources in EMs is the lack of political stability, fragmented polity, and weak political coalitions. We identify rather limited evidence of firms using these two strategies as complements. Thus, we suggest that firms should employ both these strategies in the EM

The Risks and Benefits of Myopia Control

Purpose- The prevalence of myopia is increasing around the world, stimulating interest in methods to slow its progression. The primary justification for slowing myopia progression is to reduce the risk of vision loss through sight-threatening ocular pathologic features in later life. The article analyzes whether the potential benefits of slowing myopia progression by 1 diopter (D) justify the potential risks associated with treatments. Methods- First, the known risks associated with various methods of myopia control are summarized, with emphasis on contact lens wear. Based on available data, the risk of visual impairment and predicted years of visual impairment are estimated for a range of incidence levels. Next, the increased risk of potentially sight-threatening conditions associated with different levels of myopia are reviewed. Finally, a model of the risk of visual impairment as a function of myopia level is developed, and the years of visual impairment associated with various levels of myopia and the years of visual impairment that could be prevented with achievable levels of myopia control are estimated. Results- Assuming an incidence of microbial keratitis between 1 and 25 per 10 000 patient-years and that 15% of cases result in vision loss leads to the conclusion that between 38 and 945 patients need to be exposed to 5 years of wear to produce 5 years of vision loss. Each additional 1 D of myopia is associated with a 58%, 20%, 21%, and 30% increase in the risk of myopic maculopathy, open-angle glaucoma, posterior subcapsular cataract, and retinal detachment, respectively. The predicted mean years of visual impairment ranges from 4.42 in a person with myopia of –3 D to 9.56 in a person with myopia of –8 D, and a 1-D reduction would lower these by 0.74 and 1.21 years, respectively. Conclusions- The potential benefits of myopia control outweigh the risks: the number needed to treat to prevent 5 years of visual impairment is between 4.1 and 6.8, whereas fewer than 1 in 38 will experience a loss of vision as a result of myopia control

The United Kingdom Referendum on European Union Membership: The Voting of Conservative Parliamentarians

This paper considers the attitudes of members of the parliamentary Conservative Party (PCP) during the European Union (EU) membership referendum held in the United Kingdom (UK) on the 23rd June 2016. First, the paper identifies the voting positions - remain or leave - of each Conservative parliamentarian in order to assess the strength of opinion within the PCP and place it within its historical context. Second, the paper uses multivariate analysis to test a series of hypotheses about the voting of Conservative parliamentarians. Through this we will aim to identify whether any associations existed between advocates and opponents of Brexit and social variables such as age, schooling, university, occupation and gender; political variables such as constituency marginality, and whether they were a minister, an ex-minister or a permanent backbencher; and the ideological variable of morality – i.e. support for or opposition to same sex marriage

Explaining the behavior of joint and marginal Monte Carlo estimators in latent variable models with independence assumptions

In latent variable models parameter estimation can be implemented by using the joint or the marginal likelihood, based on independence or conditional independence assumptions. The same dilemma occurs within the Bayesian framework with respect to the estimation of the Bayesian marginal (or integrated) likelihood, which is the main tool for model comparison and averaging. In most cases, the Bayesian marginal likelihood is a high dimensional integral that cannot be computed analytically and a plethora of methods based on Monte Carlo integration (MCI) are used for its estimation. In this work, it is shown that the joint MCI approach makes subtle use of the properties of the adopted model, leading to increased error and bias in finite settings. The sources and the components of the error associated with estimators under the two approaches are identified here and provided in exact forms. Additionally, the effect of the sample covariation on the Monte Carlo estimators is examined. In particular, even under independence assumptions the sample covariance will be close to (but not exactly) zero which surprisingly has a severe effect on the estimated values and their variability. To address this problem, an index of the sample's divergence from independence is introduced as a multivariate extension of covariance. The implications addressed here are important in the majority of practical problems appearing in Bayesian inference of multi-parameter models with analogous structures