Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.Comment: 27 pages, 8 figures, one supplementary figure. Three supplementary video files available on request. Version commensurate with published text in PLoS Comput. Bio

Clinical and radiological evaluation of Trabecular Metal and the Smith–Robinson technique in anterior cervical fusion for degenerative disease: a prospective, randomized, controlled study with 2-year follow-up

A prospective, randomized, controlled study was carried out to compare the radiological and clinical outcomes after anterior cervical decompression and fusion (ACDF) with Trabecular Metal™ (TM) to the traditional Smith–Robinson (SR) procedure with autograft. The clinical results of cervical fusion with autograft from the iliac crest are typically satisfactory, but implications from the donor site are frequently reported. Alternative materials for cervical body interfusion have shown lower fusion rates. Trabecular Metal is a porous tantalum biomaterial with structure and mechanical properties similar to that of trabecular bone and with proven osteoconductivity. As much as 80 consecutive patients planned for ACDF were randomized for fusion with either TM or tricortical autograft from the iliac crest (SR) after discectomy and decompression. Digitized plain radiographic images of 78 (98%) patients were obtained preoperatively and at 2-year follow-up and were subsequently evaluated by two senior radiologists. Fusion/non-fusion was classified by visual evaluation of the A–P and lateral views in forced flexion/extension of the cervical spine and by measuring the mobility between the fused vertebrae. MRI of 20 TM cases at 2 years was successfully used to assess the decompression of the neural structures, but was not helpful in determining fusion/non-fusion. Pain intensity in the neck, arms and pelvis/hip were rated by patients on a visual analog scale (VAS) and neck function was rated using the Neck Disability Index (NDI) the day before surgery and 4, 12 and 24 months postoperatively. Follow-ups at 12 and 24 months were performed by an unbiased observer, when patients also assessed their global outcome. Fusion rate in the SR group was 92%, and in the TM group 69% (P < 0.05). The accuracy of the measurements was calculated to be 2.4°. Operating time was shorter for fusion with TM compared with autograft; mean times were 100 min (SD 18) and 123 min (SD 23), respectively (P = 0.001). The patients’ global assessments of their neck and arm symptoms 2 years postoperatively for the TM group were rated as 79% much better or better after fusion with TM and 75% using autograft. Pain scores and NDI scores were significantly improved in both groups when compared with baseline at all follow-ups, except for neck pain at 1 year for the TM group. There was no statistically significant difference in clinical outcomes between fusion techniques or between patients who appeared radiologically fused or non-fused. There was no difference in pelvic/hip pain between patients operated on with or without autograft. In our study, Trabecular Metal showed a lower fusion rate than the Smith–Robinson technique with autograft after single-level anterior cervical fusion without plating. There was no difference in clinical outcomes between the groups. The operative time was shorter with Trabecular Metal implants

ICP curve morphology and intracranial flow-volume changes: a simultaneous ICP and cine phase contrast MRI study in humans

Background: The intracranial pressure (ICP) curve with its different peaks has been extensively studied, but the exact physiological mechanisms behind its morphology are still not fully understood. Both intracranial volume change (ΔICV) and transmission of the arterial blood pressure have been proposed to shape the ICP curve. This study tested the hypothesis that the ICP curve correlates to intracranial volume changes. Methods: Cine phase contrast magnetic resonance imaging (MRI) examinations were performed in neuro-intensive care patients with simultaneous ICP monitoring. The MRI was set to examine cerebral arterial inflow and venous cerebral outflow as well as flow of cerebrospinal fluid over the foramen magnum. The difference in total flow into and out from the cranial cavity (Flowtot) over time provides the ΔICV. The ICP curve was compared to the Flowtot and the ΔICV. Correlations were calculated through linear and logarithmic regression. Student’s t test was used to test the null hypothesis between paired samples. Results: Excluding the initial ICP wave, P1, the mean R2 for the correlation between the ΔICV and the ICP was 0.75 for the exponential expression, which had a higher correlation than the linear (p = 0.005). The first ICP peaks correlated to the initial peaks of Flowtot with a mean R2 = 0.88. Conclusion: The first part, or the P1, of the ICP curve seems to be created by the first rapid net inflow seen in Flowtot while the rest of the ICP curve seem to correlate to the ΔICV

Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans

Bile acids are synthesized from cholesterol in the liver and subjected to multiple metabolic biotransformations in hepatocytes, including oxidation by cytochromes P450 (CYPs) and conjugation with taurine, glycine, glucuronic acid, and sulfate. Mice and rats can hydroxylate chenodeoxycholic acid (CDCA) at the 6β-position to form α-muricholic acid (MCA) and ursodeoxycholic acid (UDCA) to form β-MCA. However, MCA is not formed in humans to any appreciable degree and the mechanism for this species difference is not known. Comparison of several Cyp-null mouse lines revealed that α-MCA and β-MCA were not detected in the liver samples from Cyp2c-cluster null (Cyp2c-null) mice. Global bile acid analysis further revealed the absence of MCAs and their conjugated derivatives, and high concentrations of CDCA and UDCA in Cyp2c-null mouse cecum and feces. Analysis of recombinant CYPs revealed that α-MCA and β-MCA were produced by oxidation of CDCA and UDCA by Cyp2c70, respectively. CYP2C9-humanized mice have similar bile acid metabolites as the Cyp2c-null mice, indicating that human CYP2C9 does not oxidize CDCA and UDCA, thus explaining the species differences in production of MCA. Because humans do not produce MCA, they lack tauro-β-MCA, a farnesoid X receptor antagonist in mouse that modulates obesity, insulin resistance, and hepatosteatosis

The global biopharma industry and the rise of Indian drug multinationals: implications for Australian generics policy

This article provides a synopsis of the new dynamics of the global biopharma industry. The emergence of global generics companies with capabilities approximating those of 'big pharma' has accelerated the blurring of boundaries between the innovator and generics sectors. Biotechnology-based products form a large and growing segment of prescription drug markets and regulatory pathways for biogenerics are imminent. Indian biopharma multinationals with large-scale efficient manufacturing plants and growing R&D capabilities are now major suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across both developed and developing countries. In response to generic competition, innovator companies employ a range of life cycle management techniques, including the launch of 'authorised generics'. The generics segment in Australia will see high growth rates in coming years but the prospect for local manufacturing is bleak. The availability of cheap generics in international markets has put pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new policy direction was announced in November 2006. Lower generics prices will have a negative impact on some incumbent suppliers but industrial renewal policies for the medicines industry in Australia are better focused on higher value R&D activities and niche manufacturing of sophisticated products

Health problems and disability in long-term sickness absence: ICF coding of medical certificates

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to test the feasibility of International Classification of Functioning, Disability and Health (ICF) and to explore the distribution, including gender differences, of health problems and disabilities as reflected in long-term sickness absence certificates.</p> <p>Methods</p> <p>A total of 433 patients with long sick-listing periods, 267 women and 166 men, were included in the study. All certificates exceeding 28 days of sick-listing sent to the local office of the Swedish Social Insurance Administration of a municipality in the Stockholm area were collected during four weeks in 2004-2005. ICD-10 medical diagnosis codes in the certificates were retrieved and free text information on disabilities in body function, body structure or activity and participation were coded according to ICF short version.</p> <p>Results</p> <p>In 89.8% of the certificates there were descriptions of disabilities that readily could be classified according to ICF. In a reliability test 123/131 (94%) items of randomly chosen free text information were identically classified by two of the authors. On average 2.4 disability categories (range 0-9) were found per patient; the most frequent were 'Sensation of pain' (35.1% of the patients), 'Emotional functions' (34.1%), 'Energy and drive functions' (22.4%), and 'Sleep functions' (16.9%). The dominating ICD-10 diagnostic groups were 'Mental and behavioural disorders' (34.4%) and 'Diseases of the musculoskeletal system and connective tissue' (32.8%). 'Reaction to severe stress and adjustment disorders' (14.7%), and 'Depressive episode' (11.5%) were the most frequent diagnostic codes. Disabilities in mental functions and activity/participation were more commonly described among women, while disabilities related to the musculoskeletal system were more frequent among men.</p> <p>Conclusions</p> <p>Both ICD-10 diagnoses and ICF categories were dominated by mental and musculoskeletal health problems, but there seems to be gender differences, and ICF classification as a complement to ICD-10 could provide a better understanding of the consequences of diseases and how individual patients can cope with their health problems. ICF is feasible for secondary classifying of free text descriptions of disabilities stated in sick-leave certificates and seems to be useful as a complement to ICD-10 for sick-listing management and research.</p