Medical hypotheses
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A new collection of ideas from Medical Hypotheses by Roger Dobson is entitled Death can be cured and 99 other Medical Hypotheses. It consists of humorous summaries of Medical Hypotheses articles from the past 30 years. The book's humour derives mainly from the subject matter, although sometimes also from the 'unconventional' approach of the authors with respect to matters such as evidence, argument or inference. ⋯ False positives are more obvious, since the paper will be ignored, refuted, or fail to be replicated--and often attracts criticism and controversy. Editors may therefore take the more cautious path of avoiding false positives more assiduously than false negatives; however, this policy progressively favours less-ambitious science. Consequently, in Medical Hypotheses the 'set point' of risk is nearer to the false positive end of the spectrum than for most journals - and the publication of many apparently-bizarre papers is a natural consequence of this policy.
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Crick and Watson gave complementary advice to the aspiring scientist based on the insight that to do your best work you need to make your greatest possible effort. Crick made the positive suggestion to work on the subject which most deeply interests you, the thing about which you spontaneously gossip - Crick termed this 'the gossip test'. Watson made the negative suggestion of avoiding topics and activities that bore you - which I have termed 'the boredom principle'. ⋯ So, if you pick your scientific problem using the gossip test and the boredom principle, you might also be committing career suicide. This may explain why so few people follow Crick and Watson's advice. The best hope for future biomedical science is that it will evolve towards a greater convergence between individual effort and career success.
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The comorbidity between epilepsy and migraine has been well known for a century, yet it is still not fully understood; the two disorders also share some risk factors, symptoms, and preventive drug therapy. A series of clinical observations and scientific data support the hypothesis of alteration of cortical excitability as a possible mechanism underlying their pathology, with both disorders characterized by transient paroxysmal neurological disturbance. So far, the numerous pathophysiological mechanisms responsible for neuronal hyperexcitability have only been studied in familial hemiplegic migraine (FHM), but they do suggest a link between migraine and epilepsy. ⋯ Taking into account the data in the literature, we hypothesize that several aetiopathological noxae (either environmental or genetics), such as Na+-K+ ATPase pump impairment, converging on a common final pathway represented by neuronal membrane hyperexcitability, could manifest as either epilepsy or headache/migraine, or both. The potential implications arising from this point of view include (a) a revision of headache/migraine diagnostic criteria as the sole ictal epileptic manifestation in international classifications of both epilepsies and headache disorders; (b) the careful follow-up of patients with headache/migraine as a residual feature, taking into consideration a revised concept of "complete seizure control" to avoid mistakes due to inopportune withdrawal of antiepileptic treatment. In addition, we suggest that headache is associated with other ictal-sensitive and motor features (more than those reported); these may be highly underestimated due to impairment of consciousness during complex partial seizures with or without secondary generalization.
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Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system that is initiated by a single genetic alteration (the BCR-ABL fusion gene or Philadelphia chromosome) and progresses in several phases: during the chronic phase the number of cells grows slowly and the fraction of immature cells is low. During the accelerated phase and blast crisis, the population of CML cells and the fraction of immature cells rises sharply. The mechanisms that drive the transition from the chronic phase to blast crisis are not understood, and the requirement of genetic instability and further mutations has been suggested. ⋯ The model also has implications for the outcome of Imatinib treatment. According to the model, treatment can lead to the low level persistence of CML stem cells without assuming that these cells are less susceptible to drug-mediated activity, and this might explain why disease tends to relapse after treatment discontinuation even in the absence of acquired drug resistance. Further, the model defines conditions when Imatinib treatment might lead to the eradication of CML, which is relevant in the context of recent data that show absence of relapse as long as two years after treatment cessation.