The public letters of the Right Hon. John Bright, M. P.

"Addendum: Address to the working men of Rochdale." August, 1842: p. [331]-340.

Audit of consultant physicians' reply letters for referrals to clinics in a tertiary teaching hospital

Background: Doctors referring patients to consultant physicians seek reply letters which both educate and assist in ongoing patient management. Highly desirable attributes in specialist letters include clearly stated and justified: (i) diagnostic formulations, (ii) management regimens, (iii) use of clinical investigations, (iv) prog-nostic statements, (v) contingency plans and (vi) follow-up arrangements. Aim: To explicitly evaluate the quality of reply letters for new patients referred to clinics at a tertiary teaching hospital. Methods: Letters were sampled from outpatient clinics of 10 different medical specialties at Princess Alexandra Hospital in Brisbane, Australia. Reply letters for new patient referrals between 1 August 2000 and 31 October 2000 were retrieved, from which data were abstracted to calculate the proportion of letters satisfying prespecified quality attributes. Results: Of 297 new patient referrals, reply letters were retrieved for 204 (69%). Of these, 147 (72%) referrals were accompanied by a referral letter, mostly (113/147; 77%) from general practitioners. For 120 referrals involving diagnostic issues, 69 (56%) letters stated a diagnostic formulation. Of 114 letters recommending further clinical investigations, 61 (53%) described a rationale for such testing. In 125 cases where therapy was a key issue, 83 (66%) letters recommended changes to current treatment for which reasons were specified in 46 (55%) cases, and contingency plans provided in 13 (16%). Prognosis was mentioned in only 18 (9%) cases. Follow-up arrangements were detailed in 123 (60%) letters. Assessments of patient understanding and likely adherence to therapy were stated in less than 15% of -letters. Conclusions: Opportunities exist for improving quality of consultant physicians' reply letters in terms of greater use of problem lists, contingency plans, prognostic statements and patient-centred assessments, as well as more frequent enunciation of consultants' reasoning behind requests for further tests and changes to current management. Use of structured letter templates may facilitate more consistent inclusion of key information to referring doctors.

Bayesian invariant measurements of generalisation

The problem of evaluating different learning rules and other statistical estimators is analysed. A new general theory of statistical inference is developed by combining Bayesian decision theory with information geometry. It is coherent and invariant. For each sample a unique ideal estimate exists and is given by an average over the posterior. An optimal estimate within a model is given by a projection of the ideal estimate. The ideal estimate is a sufficient statistic of the posterior, so practical learning rules are functions of the ideal estimator. If the sole purpose of learning is to extract information from the data, the learning rule must also approximate the ideal estimator. This framework is applicable to both Bayesian and non-Bayesian methods, with arbitrary statistical models, and to supervised, unsupervised and reinforcement learning schemes.

Structure and regulation of type 2 transglutaminase in relation to its physiological functions and pathological roles

This chapter contains sections titled: Introduction Structure and Regulation Physiologic Functions of TG2 Disruption of TG2 Functions in Pathologic Conditions Perspectives for Pharmacologic Interventions Concluding Comments Acknowledgements References

Alternative Characterization of the Class k-UCV and Related Classes of Univalent Functions

In this paper an alternative characterization of the class of functions called k -uniformly convex is found. Various relations concerning connections with other classes of univalent functions are given. Moreover a new class of univalent functions, analogous to the ’Mocanu class’ of functions, is introduced. Some results concerning this class are derived.

Generalized Problem of Sratlikeness for Products of P-Valent Starlike Functions

∗ Partially supported by grant No. 433/94 NSF of the Ministry of Education and Science of the Republic of Bulgaria 1991 Mathematics Subject Classification:30C45

On Root Arrangements of Polynomial-Like Functions and their Derivatives

2000 Mathematics Subject Classification: 12D10.

CP-036 evaluation of outpatient clinic letters for medication errors

Background - It is well recognised that errors are more likely to occur during transitions of care, especially medicines errors. Clinic letters are used as a communication tool during a transition from hospital (outpatient clinics) to primary care (general practitioners). Little is known about medicines errors in clinic letters, as previous studies in this area have focused on medicines errors in inpatient or outpatient prescriptions. Published studies concerning clinic letters largely focus on perceptions of patients or general practitioners in respect to overall quality. Purpose - To investigate medicines errors contained in outpatient clinic letters generated by prescribers within the Neurology Department of a specialist paediatric hospital in the UK.Materials and methods - Single site, retrospective, cross-sectional review of 100 clinic letters generated during March–July 2013 in response to an outpatient consultation. Clinic letters were conveniently selected from the most recent visit of each patient. An evaluation tool with a 10-point scale, where 10 was no error and 0 was significant error, was developed and refined throughout the study to facilitate identification and characterisation of medicines errors. The tool was tested for a relationship between scores and number of medicines errors using a regression analysis.Results - Of 315 items related to neurology mentioned within the letters, 212 items were associated with 602 errors. Common missing information was allergy (97%, n = 97), formulation (60.3%, n = 190), strength/concentration (59%, n = 186) and weight (53%, n = 53). Ninety-nine letters were associated with at least one error. Scores were in range of 4–10 with 42% of letters scored as 7. Statistically significant relationships were observed between scores and number of medicines errors (R2 = 0.4168, p < 0.05) as well as between number of medicines and number of drug-related errors (R2 = 0.9719, p < 0.05). Conclusions - Nearly all clinic letters were associated with medicines errors. The 10-point evaluation tool may be a useful device to categorise clinic letter errors.

Regulating the expression of eEF1A to decipher its non canonical functions in eukaryotic cells

The canonical function of eEF1A is delivery of the aminoacylated tRNA to the A site of the ribosome during protein translation, however, it is also known to be an actin binding protein. As well as this actin binding function, eEF1A has been shown to be involved in other cellular processes such as cell proliferation and apoptosis. It has long been thought that the actin cytoskeleton and protein synthesis are linked and eEF1A has been suggested to be a candidate protein to form this link, though very little is understood about the relationship between its two functions. Overexpression of eEF1A has also been shown to be implicated in many different types of cancers, especially cancers that are metastatic, therefore it is important to further understand how eEF1A can affect both translation and the organisation of the actin cytoskeleton. To this end, we aimed to determine the effects of reduced expression of eEF1A on both translation and its non canonical functions in CHO cells. We have shown that reduced expression of eEF1A in this cell system results in no change in protein synthesis, however results in an increased number of actin stress fibres and other proteins associated with these fibres such as myosin IIA, paxillin and vinculin. Cell motility and attachment are also affected by this reduction in eEF1A protein expression. The organisational and motility phenotypes were found to be specific to eEF1A by transforming the cells with plasmids containing either human eEF1A1 or eEF1A2. Though the mechanisms by which these effects are regulated have not yet been established, this data provides evidence to show that the translation and actin binding functions of eEF1A are independent of each other as well as being suggestive of a role for eEF1A in cell motility as supported by the observation that overexpression of eEF1A protein tends to be associated with the cancer cells that are metastatic.

Data compilation on the biological response to ocean acidification: environmental and experimental context of data sets and related literature

The exponential growth of studies on the biological response to ocean acidification over the last few decades has generated a large amount of data. To facilitate data comparison, a data compilation hosted at the data publisher PANGAEA was initiated in 2008 and is updated on a regular basis (doi:10.1594/PANGAEA.149999). By January 2015, a total of 581 data sets (over 4 000 000 data points) from 539 papers had been archived. Here we present the developments of this data compilation five years since its first description by Nisumaa et al. (2010). Most of study sites from which data archived are still in the Northern Hemisphere and the number of archived data from studies from the Southern Hemisphere and polar oceans are still relatively low. Data from 60 studies that investigated the response of a mix of organisms or natural communities were all added after 2010, indicating a welcomed shift from the study of individual organisms to communities and ecosystems. The initial imbalance of considerably more data archived on calcification and primary production than on other processes has improved. There is also a clear tendency towards more data archived from multifactorial studies after 2010. For easier and more effective access to ocean acidification data, the ocean acidification community is strongly encouraged to contribute to the data archiving effort, and help develop standard vocabularies describing the variables and define best practices for archiving ocean acidification data.

Efficient numerical methods for the random-field Ising model: Finite-size scaling, reweighting extrapolation, and computation of response functions

It was recently shown [Phys. Rev. Lett. 110, 227201 (2013)] that the critical behavior of the random-field Ising model in three dimensions is ruled by a single universality class. This conclusion was reached only after a proper taming of the large scaling corrections of the model by applying a combined approach of various techniques, coming from the zero-and positive-temperature toolboxes of statistical physics. In the present contribution we provide a detailed description of this combined scheme, explaining in detail the zero-temperature numerical scheme and developing the generalized fluctuation-dissipation formula that allowed us to compute connected and disconnected correlation functions of the model. We discuss the error evolution of our method and we illustrate the infinite limit-size extrapolation of several observables within phenomenological renormalization. We present an extension of the quotients method that allows us to obtain estimates of the critical exponent a of the specific heat of the model via the scaling of the bond energy and we discuss the self-averaging properties of the system and the algorithmic aspects of the maximum-flow algorithm used.

CaV channels and cancer: canonical functions indicate benefits of repurposed drugs as cancer therapeutics

The importance of ion channels in the hallmarks of many cancers is increasingly recognised. This article reviews current knowledge of the expression of members of the voltage-gated calcium channel family (CaV) in cancer at the gene and protein level and discusses their potential functional roles. The ten members of the CaV channel family are classified according to expression of their pore-forming α-subunit; moreover, co-expression of accessory α2δ, β and γ confers a spectrum of biophysical characteristics including voltage dependence of activation and inactivation, current amplitude and activation/inactivation kinetics. CaV channels have traditionally been studied in excitable cells including neurones, smooth muscle, skeletal muscle and cardiac cells, and drugs targeting the channels are used in the treatment of hypertension and epilepsy. There is emerging evidence that several CaV channels are differentially expressed in cancer cells compared to their normal counterparts. Interestingly, a number of CaV channels also have non-canonical functions and are involved in transcriptional regulation of the expression of other proteins including potassium channels. Pharmacological studies show that CaV canonical function contributes to the fundamental biology of proliferation, cell-cycle progression and apoptosis. This raises the intriguing possibility that calcium channel blockers, approved for the treatment of other conditions, could be repurposed to treat particular cancers. Further research will reveal the full extent of both the canonical and non-canonical functions of CaV channels in cancer and whether calcium channel blockers are beneficial in cancer treatment.

Exotic dynamics in a firing rate model of neural tissue with threshold accommodation

Many of the equations describing the dynamics of neural systems are written in terms of firing rate functions, which themselves are often taken to be threshold functions of synaptic activity. Dating back to work by Hill in 1936 it has been recognized that more realistic models of neural tissue can be obtained with the introduction of state-dependent dynamic thresholds. In this paper we treat a specific phenomenological model of threshold accommodation that mimics many of the properties originally described by Hill. Importantly we explore the consequences of this dynamic threshold at the tissue level, by modifying a standard neural field model of Wilson-Cowan type. As in the case without threshold accommodation classical Mexican-Hat connectivity is shown to allow for the existence of spatially localized states (bumps) in both one and two dimensions. Importantly an analysis of bump stability in one dimension, using recent Evans function techniques, shows that bumps may undergo instabilities leading to the emergence of both breathers and traveling waves. Moreover, a similar analysis for traveling pulses leads to the conditions necessary to observe a stable traveling breather. In the regime where a bump solution does not exist direct numerical simulations show the possibility of self-replicating bumps via a form of bump splitting. Simulations in two space dimensions show analogous localized and traveling solutions to those seen in one dimension. Indeed dynamical behavior in this neural model appears reminiscent of that seen in other dissipative systems that support localized structures, and in particular those of coupled cubic complex Ginzburg-Landau equations. Further numerical explorations illustrate that the traveling pulses in this model exhibit particle like properties, similar to those of dispersive solitons observed in some three component reaction-diffusion systems. A preliminary account of this work first appeared in S Coombes and M R Owen, Bumps, breathers, and waves in a neural network with spike frequency adaptation, Physical Review Letters 94 (2005), 148102(1-4).

Covariant Spectator Theory of heavy–light and heavy mesons and the predictive power of covariant interaction kernels

The Covariant Spectator Theory (CST) is used to calculate the mass spectrum and vertex functions of heavy–light and heavy mesons in Minkowski space. The covariant kernel contains Lorentz scalar, pseudoscalar, and vector contributions. The numerical calculations are performed in momentum space, where special care is taken to treat the strong singularities present in the confining kernel. The observed meson spectrum is very well reproduced after fitting a small number of model parameters. Remarkably, a fit to a few pseudoscalar meson states only, which are insensitive to spin–orbit and tensor forces and do not allow to separate the spin–spin from the central interaction, leads to essentially the same model parameters as a more general fit. This demonstrates that the covariance of the chosen interaction kernel is responsible for the very accurate prediction of the spin-dependent quark–antiquark interactions.

Victorian letter writing and its representation in literature and painting: the case study of love letters

One of the main features of nineteenth-century fiction is the quasi-total disappearance of the epistolary novel that had had its heydays in the previous century. For this reason, some scholars have declared the “death” of the letter in literature after the transitional romantic period. However, Victorian novels overflow with letters that are embedded, quoted in part or described and commented on by narrators or characters. Even when its content is not revealed to the reader, the letter becomes a signifier loaded with meanings, also and particularly so, when it is burnt, torn, hidden, found or buried. The Postal Reform of 1839-40 caused the number of letters sent every year in Britain to grow from 75 to 410 million in only 14 years, and the mediatic campaign that supported it drew the attention of the population to the material aspects concerning this means of communication. Newspapers became more affordable too and they promoted a taste for sensationalism that often involved the “spectacularization” of private correspondence. Starting from an excursus on the history of the letter aimed at identifying the key aspects of the genre, this work deals with some real love correspondences from people belonging to different classes in the period from 1840 to the 1870s, to then analyse their fictional and pictorial counterparts. The general picture that emerges from this analysis is that of a Victorian society where letters were able to break down the boundaries between high and low forms of cultural expressions and where, more than ever, letters were present in people’s everyday lives as well as in the art and literature they enjoyed.