Jane Austen's lifelong health problems and final illness: New evidence points to a fatal Hodgkin's disease and excludes the widely accepted Addison's

Jane Austen is typically described as having excellent health until the age of 40 and the onset of a mysterious and fatal illness, initially identified by Sir Zachary Cope in 1964 as Addison's disease. Her biographers, deceived both by Cassandra Austen's destruction of letters containing medical detail, and the cheerful high spirits of the existing letters, have seriously underestimated the extent to which illness affected Austen's life. A medical history reveals that she was particularly susceptible to infection, and suffered unusually severe infective illnesses, as well as a chronic conjunctivitis that impeded her ability to write. There is evidence that Austen was already suffering from an immune deficiency and fatal lymphoma in January 1813, when her second and most popular novel, Pride and Prejudice, was published. Four more novels would follow, written or revised in the shadow of her increasing illness and debility. Whilst it is impossible now to conclusively establish the cause of her death, the existing medical evidence tends to exclude Addison's disease, and suggests there is a high possibility that Jane Austen's fatal illness was Hodgkin's disease, a form of lymphoma.

Multi-valued control problems and mixture density network

We have proposed a novel robust inversion-based neurocontroller that searches for the optimal control law by sampling from the estimated Gaussian distribution of the inverse plant model. However, for problems involving the prediction of continuous variables, a Gaussian model approximation provides only a very limited description of the properties of the inverse model. This is usually the case for problems in which the mapping to be learned is multi-valued or involves hysteritic transfer characteristics. This often arises in the solution of inverse plant models. In order to obtain a complete description of the inverse model, a more general multicomponent distributions must be modeled. In this paper we test whether our proposed sampling approach can be used when considering an arbitrary conditional probability distributions. These arbitrary distributions will be modeled by a mixture density network. Importance sampling provides a structured and principled approach to constrain the complexity of the search space for the ideal control law. The effectiveness of the importance sampling from an arbitrary conditional probability distribution will be demonstrated using a simple single input single output static nonlinear system with hysteretic characteristics in the inverse plant model.

An appraisal of employment problems and policies at the micro-economic level

This study has concentrated on the development of an impact simulation model for use at the sub-national level. The necessity for the development of this model was demonstrated by the growth of local economic initiatives during the 1970's, and the lack of monitoring and evaluation exercise to assess their success and cost-effectiveness. The first stage of research involved the confirmation that the potential for micro-economic and spatial initiatives existed. This was done by identifying the existence of involuntary structural unemployment. The second stage examined the range of employment policy options from the macroeconomic, micro-economic and spatial perspectives, and focused on the need for evaluation of those policies. The need for spatial impact evaluation exercise in respect of other exogenous shocks, and structural changes was also recognised. The final stage involved the investigation of current techniques of evaluation and their adaptation for the purpose in hand. This led to a recognition of a gap in the armoury of techniques. The employment-dependency model has been developed to fill that gap, providing a low-budget model, capable of implementation at the small area level and generating a vast array of industrially disaggregate data, in terms of employment, employment-income, profits, value-added and gross income, related to levels of United Kingdom final demand. Thus providing scope for a variety of impact simulation exercises.

Eye movement problems and differential diagnosis of the parkinsonian syndromes

Differential clinical diagnosis of the parkinsonian syndromes, viz., Parkinson’s disease (PD), progressive supranuclear palsy (PSP), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) can be difficult. Eye movement problems, however, are a chronic complication of many of these disorders and may be a useful aid to diagnosis. Hence, the presence in PSP of vertical supranuclear gaze palsy, fixation instability, lid retraction, blepharospasm, and apraxia of eyelid opening and closing is useful in separating PD from PSP. Moreover, atypical features of PSP include slowing of upward saccades, moderate slowing of downward saccades, the presence of a full range of voluntary vertical eye movements, a curved trajectory of oblique saccades, and absence of square-wave jerks. Downgaze palsy is probably the most useful diagnostic clinical symptom of PSP. By contrast, DLB patients are specifically impaired in both reflexive and saccadic execution and in the performance of more complex saccadic eye movement tasks. Problems in convergence in DLB are also followed by akinesia and rigidity. Abnormal ocular fixation may occur in a significant proportion of MSA patients along with excessive square-wave jerks, a mild supranuclear gaze palsy, a gaze-evoked nystagmus, a positioning down-beat nystagmus, mild-moderate saccadic hypometria, impaired smooth pursuit movements, and reduced vestibulo-ocular reflex (VOR) suppression. There may be considerable overlap between the eye movement problems characteristic of the various parkinsonian disorders, but taken together with other signs and symptoms, can be a useful aid in differential diagnosis, especially in the separation of PD and PSP.