Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Large Scale Gene Expression Profiles of Regenerating Inner Ear Sensory Epithelia

Loss of inner ear sensory hair cells (HC) is a leading cause of human hearing loss and balance disorders. Unlike mammals, many lower vertebrates can regenerate these cells. We used cross-species microarrays to examine this process in the avian inner ear. Specifically, changes in expression of over 1700 transcription factor (TF) genes were investigated in hair cells of auditory and vestibular organs following treatment with two different damaging agents and regeneration in vitro. Multiple components of seven distinct known signaling pathways were clearly identifiable: TGFβ, PAX, NOTCH, WNT, NFKappaB, INSULIN/IGF1 and AP1. Numerous components of apoptotic and cell cycle control pathways were differentially expressed, including p27KIP and TFs that regulate its expression. A comparison of expression trends across tissues and treatments revealed identical patterns of expression that occurred at identical times during regenerative proliferation. Network analysis of the patterns of gene expression in this large dataset also revealed the additional presence of many components (and possible network interactions) of estrogen receptor signaling, circadian rhythm genes and parts of the polycomb complex (among others). Equal numbers of differentially expressed genes were identified that have not yet been placed into any known pathway. Specific time points and tissues also exhibited interesting differences: For example, 45 zinc finger genes were specifically up-regulated at later stages of cochlear regeneration. These results are the first of their kind and should provide the starting point for more detailed investigations of the role of these many pathways in HC recovery, and for a description of their possible interactions

Obesity, the Endocannabinoid System, and Bias Arising from Pharmaceutical Sponsorship

Previous research has shown that academic physicians conflicted by funding from the pharmaceutical industry have corrupted evidence based medicine and helped enlarge the market for drugs. Physicians made pharmaceutical-friendly statements, engaged in disease mongering, and signed biased review articles ghost-authored by corporate employees. This paper tested the hypothesis that bias affects review articles regarding rimonabant, an anti-obesity drug that blocks the central cannabinoid receptor.A MEDLINE search was performed for rimonabant review articles, limited to articles authored by USA physicians who served as consultants for the company that manufactures rimonabant. Extracted articles were examined for industry-friendly bias, identified by three methods: analysis with a validated instrument for monitoring bias in continuing medical education (CME); analysis for bias defined as statements that ran contrary to external evidence; and a tally of misrepresentations about the endocannabinoid system. Eight review articles were identified, but only three disclosed authors' financial conflicts of interest, despite easily accessible information to the contrary. The Takhar CME bias instrument demonstrated statistically significant bias in all the review articles. Biased statements that were nearly identical reappeared in the articles, including disease mongering, exaggerating rimonabant's efficacy and safety, lack of criticisms regarding rimonabant clinical trials, and speculations about surrogate markers stated as facts. Distinctive and identical misrepresentations regarding the endocannabinoid system also reappeared in articles by different authors.The findings are characteristic of bias that arises from financial conflicts of interest, and suggestive of ghostwriting by a common author. Resolutions for this scenario are proposed

Is total hip arthroplasty safely performed in lung transplant patients? Current experience from a retrospective study of the Zurich lung transplant cohort

BACKGROUND In recent years, the number of lung transplants has increased rapidly, with higher quality of life and improved survival rates in transplant recipients, including patients with advanced age. This, in turn, means that more transplant recipients will seek musculoskeletal care to treat degenerative joint disease and also trauma incidents. Safety concerns regarding elective and posttraumatic hip arthroplasty in transplant patients include an increased risk of infection, wound healing problems, periprosthetic fractures and loosening of the implants. METHODS Clinical outcomes and safety aspects were retrospectively reviewed for five primary total hip arthroplasties (THA) in lung transplant recipients with minimal follow-up of two years at average of 2.6 (2-11) years. Patients were recruited from the Zurich Lung Transplant Center comprising of a cohort of 253 patients between January 1st, 2004 and December 31st, 2013. RESULTS All five patients subjectively reported excellent outcomes after THA with a final average Harris Hip Score of 97 (86-100). One 71-year-old patient died 26 months after THA unrelated to arthroplasty. One superficial wound healing disturbance was documented. No periprosthetic fractures, no dislocations, no periprosthetic infections, no further revision surgery, no implant loosening was observed. CONCLUSIONS In conclusion, THA can be safely and successfully performed even in lung transplant patients under long-term immunosuppressive therapy and polymedication, provided a multidisciplinary approach can be granted

After Myriad, what makes a gene patent claim 'markedly different' from nature?

Examining the types of claim amendments that have transformed isolated gene claims from patent-ineligible into eligible subject matter provides clarity into the threshold of eligibility for gene-related patents