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The dynamic model Nitrogen Dynamics in Crop rotations in Ecological Agriculture (NDICEA) was used to assess the nitrogen (N), phosphorus (P) and potassium (K) balance of long-term organic cropping trials and typical organic crop rotations on a range of soil types and rainfall zones in the UK. The measurements of soil N taken at each of the organic trial sites were also used to assess the performance of NDICEA. The modeled outputs compared well to recorded soil N levels, with relatively small error margins. NDICEA therefore seems to be a useful tool for UK organic farmers. The modeling of typical organic rotations has shown that positive N balances can be achieved, although negative N balances can occur under high rainfall conditions and on lighter soil types as a result of leaching. The analysis and modeling also showed that some organic cropping systems rely on imported sources of P and K to maintain an adequate balance and large deficits of both nutrients are apparent in stockless systems. Although the K deficits could be addressed through the buffering capacity of minerals, the amount available for crop uptake will depend on the type and amount of minerals present, current cropping and fertilization practices and the climatic environment. A P deficit represents a more fundamental problem for the maintenance of crop yields and the organic sector currently relies on mined sources of P which represents a fundamental conflict with the International Federation of Organic Agriculture Movements organic principles.
Abnormalities in the anterior inter-hemispheric connectivity have previously been implicated in major depressive disorder. Disruptions in fractional anisotropy in the callosum and fornix have been reported in schizophrenia and major depressive disorder. Oligodendrocyte density and overall size of the callosum and fornix show no alteration in either illness, suggesting that gross morphology is unchanged but more subtle organizational disruption may exist within these brain regions in mood and affective disorders.
Method
Using high-resolution oil-immersion microscopy we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath, and using standard high-resolution light microscopy we measured the density of myelinated axons. These measurements were made in the genu of the corpus callosum and the medial body of the fornix at its most dorsal point. Measures were taken in the sagittal plane in the callosal genu and in the coronal plane at the most dorsal part of the fornix body.
Results
Cases of major depressive disorder had significantly greater mean myelin cross-sectional area (p = 0.017) and myelin thickness (p = 0.004) per axon in the genu than in control or schizophrenia groups. There was no significant change in the density of myelinated axons, and no changes observed in the fornix.
Conclusion
The results suggest a clear increase of myelin in the axons of the callosal genu in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin.
In 1990, Fontan, Kirklin, and colleagues published equations for survival after the so-called “Perfect Fontan” operation. After 1988, we evolved a protocol using an internal or external polytetraflouroethylene tube of 16 to 19 millimetres diameter placed from the inferior caval vein to either the right or left pulmonary artery along with a bidirectional cava-pulmonary connection. The objective of this study was to test the hypothesis that a “perfect” outcome is routinely achievable in the current era when using a standardized surgical procedure.
Methods
Between 1 January, 1988, and 12 December, 2005, 112 patients underwent the Fontan procedure using an internal or external polytetraflouroethylene tube plus a bidirectional cava-pulmonary connection, the latter usually having been constructed as a previous procedure. This constituted 45% of our overall experience in constructing the Fontan circulation between 1988 and 1996, and 96% of the experience between 1996 and 2005. Among all surviving patients, the median follow-up was 7.3 years. We calculated the expected survival for an optimal candidate, given from the initial equations, and compared this to our entire experience in constructing the Fontan circulation.
Results
An internal tube was utilized in 61 patients, 97% of whom were operated prior to 1998, and an external tube in 51 patients, the latter accounting for 95% of all operations since 1999. At 1, 5, 10 and 15 years, survival of the entire cohort receiving polytetraflouroethylene tubes is superimposable on the curve calculated for a “perfect” outcome. Freedom from replacement or revision of the tube was 97% at 10 years.
Conclusion
Using a standardized operative procedure, combining a bidirectional cavopulmonary connection with a polytetraflouroethylene tube placed from the inferior caval vein to the pulmonary arteries for nearly all patients with functionally univentricular hearts, early and late survival within the “perfect” outcome as predicted by the initial equations of Fontan and Kirklin is routinely achievable in the current era. The need for late revision or replacement of the tube is rare.
Prescription-event monitoring (PEM) is one of two national systems of drug safety monitoring practised in Britain. The objective of this PEM study was to assess the safety of fluvoxamine and to monitor the occurrence of untoward and other events during treatment. A total of 10 401 patients treated with the drug in general practices throughout England were studied and data were analysed in the Drug Safety Research Unit, Southampton. The main outcome measures were the overall incidence of events per 1000 patients; the incidence during the first month of treatment; the mean incidence for months 2–6 of treatment; and the ratio of these rates as a signal that an event could be drug related. The most commonly reported category of events was neuropsychiatric while the most commonly reported individual events were nausea and vomiting. Fluvoxamine was shown to be a safe drug and no unexpected or previously undetected drug-related events were encountered. There was a relatively high incidence of gastro-intestinal symptoms, but other adverse reactions often encountered during treatment with tricyclic antidepressants were not frequently reported.
‘Prescription-event monitoring’ (PEM) is one of two national systems of post-marketing surveillance in operation in Britain. It identified 22 065 patients who had received NHS prescriptions for alprazolam, and data available on 10 895 of these were analysed. The main reasons for treatment with alprazolam were anxiety and depression. The patients provided 3360 patient-years of treatment and 7540 patient-years of follow-up. No serious events clearly associated with treatment were recorded. The main events reported during treatment, albeit infrequently, were drowsiness and depression, although depression is more likely to be due to the disorder being treated than to the drug. Some of the other alleged unwanted effects of alprazolam in published reports were not encountered. Since PEM is unable to determine the dependence potential of alprazolam, further evaluation of this problem is called for.
I should like to comment very briefly on the Kuhn-Popper disagreement over the essential nature of science and the genesis of scientific revolutions. If I understand Sir Karl Popper correctly, science is basically and constantly potentially on the verge of revolution. A refutation, at least if it is big enough, constitutes such a revolution. Professor Kuhn argues, on the other hand, that most of the time devoted to the pursuit of science is what he calls ‘normal’ science—that is, problem solving, or working out chains of argument implicit in previous work. Thus, for Kuhn, a scientific revolution is a long time a-building and occurs only rarely because most people are not trying to refute current theories. Both sides have presented their positions in considerable detail but there seems to me to be a very important gap in both theories. It is, simply, how do we know what science is all about? The question may sound startlingly naive, but I shall now attempt to justify it.
There are, essentially, two respectable scholarly ways to go about answering the question. One is sociological; the scientific community may be treated like any other community and subjected to sociological analysis. Note that this ‘may’ be done, but that it has not yet been done. To put it another way, most scientific activity may be directed toward refutation or toward ‘problem solving’, but we don't know whether it is or not.