Suffering and the Dimensionality of Medical Knowledge: A Critique of Evidence Based Medicine

Evidence Based Medicine (EBM) is a recent philosophy that is highly influential in medicine. EBM is centred on the notion that medical practice should be supported by rigorous clinical research. This thesis explores a “dimensional” framework of knowledge and argues EBM results in the exclusion of certain non-scientific knowledge forms. Since these knowledge forms are essential to the realisation of medicine’s goals, EBM is holding medicine back. I frame the primary goal of medicine as to attend to suffering. There is a tendency to view the goal of medicine as the treatment of disease, but this fails to account for much of what occurs in practice. Suffering incorporates disease and also other humanistic aspects of medicine that may not be investigable in a scientific manner. Medical knowledge determines medical practice, so medicine must have knowledge of what suffering is to effectively attend to suffering. I propose a dimensional theory of knowledge that includes explicit, tacit, general and particular forms of knowledge. Explicated general knowledge includes the knowledge of science. Tacit knowledge is more readily enacted than articulated. Particular knowledge is knowledge that is applicable to specific circumstances and individuals. The existence of tacit and particular knowledge moderates the possibility and need for scientific justification and also means knowledge exists within the knower and not exclusively in abstracted forms. EBM’s philosophical framework excludes tacit and particular knowledge in its selective recognition of explicit-generalised “evidence”. This means that EBM’s conception of knowledge is incomplete and is philosophically inadequate. Though EBM makes useful contributions to clinical research appraisal, its normative assertions of “what counts as knowing” in medicine obscures human suffering and so might harm practice. This thesis presents the foundations for an alternative philosophy to EBM that would see “EBM” reframed as “clinical epidemiology” as a remedy for EBM’s normative restriction of medical knowledge

Consumer acceptance of round steaks tenderized by cubing and papain

Substantial portions of this bulletin are taken from a Master's thesis... submitted to the University of Missouri by Helen McHugh--P. [2].Digitized 2007 AES.Includes bibliographical references (page 20)

Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films

In this study, antioxidant biodegradable films based on pea protein and alpha-tocopherol were successfully developed by solution casting. The effect of both the homogenization conditions (rotor stator and microfluidizer) and the relative humidity (RH) on the microstructure and physical properties (transparency, tensile, oxygen and water vapour barrier properties) of pea protein/alpha-tocopherol-based films was evaluated. The addition of alpha-tocopherol produced minimal changes in the films transparency, while providing them with antioxidant properties and improved water vapour and oxygen barrier properties (up to 30 % in both water vapour and oxygen permeability) when films were at low and intermediate RH. The addition of alpha-tocopherol in microfluidized films gave rise to an increase in their resistance to break and extensibility (up to 27 % in E values) at intermediate and high RH. These results add a new insight into the potential of employing pea protein and alpha-tocopherol in the development of fully biodegradable antioxidant films which are of interest in food packagingThe authors acknowledge the financial support from the Spanish Ministerio de Educacion y Ciencia throughout the project AGL2010-20694, co-funded by FEDER. Author M.J.Fabra is a recipient of a Juan de la Cierva contract from the Spanish Ministerio de Economia y Competitividad.Fabra, MJ.; Jiménez, A.; Talens Oliag, P.; Chiralt, A. (2014). Influence of homogenization conditions on physical properties and antioxidant activity of fully biodegradable pea protein-alpha-tocopherol films. Food and Bioprocess Technology. 7(12):3569-3578. https://doi.org/10.1007/s11947-014-1372-0S35693578712ASTM (1995). Standard test methods for water vapor transmission of materials. Standards Desingnations: E96-95. In: Annual Book of ASTM Standards (pp. 406-413); American Society for Testing and Materials: Philadelphia, PA.ASTM (2001). Standard test method for tensile properties of thin plastic sheeting. Standard D882. In: Annual book of American Standard Testing Methods (pp 162-170). D882. Philadelphia:ASTM.Bertan, L. C., Tanada-Palmu, P. S., Siani, A. C., & Grosso, C. R. F. (2005). Effect of fatty acids and “Brazilian elemi” on composite films based on gelatin. Food Hydrocolloids, 19(1), 73–82.Byun, Y., Kim, Y. T., & Whiteside, S. (2010). Characterization of an antioxidant polylactic acid (PLA) film prepared with alpha-tocopherol, BHT and polyethylene glycol using film cast extruder. Journal of Food Engineering, 100, 239–244.Cerqueira, M. A., Costa, M. J., Fuciños, C., Pastrana, L. M., & Vicente, A. A. (2014). Development of active and nanotechnology-based smart edible packaging systems: physical-chemical characterization. Food and Bioprocess Technology, 7(5), 1472–1482.Choi, W. S., & Han, J. H. (2001). Physical and mechanical properties of pea–protein-based edible films. Journal of Food Science, 66, 319–322.Choi, W. S., & Han, J. H. (2002). Film-forming mechanism and heat denaturation effects on the physical and chemical properties of pea-protein-isolate edible films. Journal of Food Science, 67, 1399–1406.Fabra, M. J., Talens, P., & Chiralt, A. (2009). Microstructure and optical properties of sodium caseinate films containing oleic acidebeeswax mixtures. Food Hydrocolloids, 23, 676–683.Fabra, M. J., Talens, P., & Chiralt, A. (2010). Water sorption isotherms and phase transitions of sodium caseinate–lipid films as affected by lipid interactions. Food Hydrocolloids, 24, 384–391.Fabra, M. J., Hambleton, A., Talens, P., Debeaufort, F., & Chiralt, A. (2011). Effect of ferulic acid and α-tocopherol antioxidants on properties of sodium caseinate edible films. Food Hydrocolloids, 25, 1441–1447.Fabra, M. J., Talens, P., Gavara, R., & Chiralt, A. (2012). Barrier properties of sodium caseinate films as affected by lipid composition and moisture content. Journal of Food Engineering, 109, 372–379.Frankel, E. N., Huang, S. W., Kanner, J., & German, J. B. (1994). Interfacial phenomena in the evaluation of antioxidants: bulk oils vs emulsions. Journal of Agriculture and Food Chemistry, 42(5), 1054–1059.Gómez-Estaca, J., Giménez, B., Montero, P., & Gómez-Guillén, M. C. (2009). Incorporation of antioxidant borage extract into edible films based on sole skin gelatin or a commercial fish gelatin. Journal of Food Engineering, 92, 78–85.Huang, S. W., Frankel, E. N., & German, J. B. (1994). Antioxidant activity of alpha.- and.gamma.-tocopherols in bulk oils and in oil-in-water emulsions. Journal of Agriculture and Food Chemistry, 42(10), 2108–2114.Hutchings, J. B. (1999). Food and colour appearance (2nd ed.). Gaithersburg: Chapman and Hall Food Science Book, Aspen Publication.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2010). Effect of lipid self-association on the microstructure and physical properties of hydroxypropylmethylcellulose edible films containing fatty acids. Carbohydrate Polymers, 82(3), 585–593.Jiménez, A., Fabra, M. J., Talens, P., & Chiralt, A. (2013). Physical properties and antioxidant capacity of starch-sodium caseinate films containing lipids. Journal of Food Engineering, 116(3), 695–702.Jung, M. Y., & Min, D. B. (1990). Effects of alpha-. γ-, and δ-tocopherols on oxidative stability of soybean oil. Journal of Food Science, 55(5), 1464–1465.López-de-Dicastillo, C., Alonso, J. M., Catalá, R., Gavara, R., & Hernández-Muñoz, P. (2010). Improving the antioxidant protection of packaged food by incorporating natural flavonoids into ethylene-vinyl alcohol copolymer (EVOH) films. Journal of Agricultural and Food Chemistry, 58, 10958–10964.Ma, W., Tang, C.-H., Yin, S.-W., Yang, X. Q., Qi, J. R., & Xia, N. (2012). Effect of homogenization conditions on properties of gelatin-olive oil composite films. Journal of Food Engineering, 113(1), 136–142.Mauer, L. J., Smith, D. E., & Labuza, T. P. (2000). Water vapor permeability, mechanical, and structural properties of edible β-casein films. International Dairy Journal, 10(5–6), 353–358.Mc Hugh, T. H., Avena-Bustillos, R., & Krochta, J. M. (1993). Hydrophobic edible films:modified procedure for water vapor permeability and explanation of thickness effects. Journal of Food Science, 58(4), 899–903.McHugh, T. H., & Krochta, J. M. (1994). Dispersed phase particle size effects on water vapour permeability of whey protein–beeswax emulsion films. Journal of Food Processing and Preservation, 18, 173–188.Ozkan, G., Simsek, B., & Kuleasan, H. (2007). Antioxidant activities of Satureja cilicica essential oil in butter and in vitro. Journal of Food Engineering, 79, 1391–1396.Pereira de Abreu, D. A., Paseiro Losada, P., Maroto, J., & Cruz, J. M. (2011). Natural antioxidant active packaging film and its effect on lipid damage in frozen blue shark (Prionace glauca). Innovative Food Science and Emerging Technologies, 12, 50–55.Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., & Rice-Evans, C. (1999). Antioxidant activity applying an improved ABTS radical cation decoloration assay. Free Radical Biology and Medicine, 26, 1231–1237.Roos, Y. H. (1995). Phase transitions in food. San Diego: Academic Press.Salgado, P. R., Molina Ortiz, S. E., Petruccelli, S., & Mauri, A. N. (2010). Biodegradable sunflower protein films naturally activated with antioxidant compounds. Food Hydrocolloids, 24(5), 525–533.Salgado, P. R., Fernández, G. B., Drago, S. R., & Mauri, A. N. (2011). Addition of bovine plasma hydrolysates improves the antioxidant properties of soybean and sunflower protein-based films. Food Hydrocolloids, 25, 1433–1440.Samaranayaka, A. G. P., & Li-Chan, E. C. Y. (2008). Autolysis-assisted production of fish protein hydrolysates with antioxidant properties form Pacific hake (Merluccius productus). Food Chemistry, 107, 768–776.Souza, B. W. S., Cerqueira, A., Casariego, A., Lima, A. M. P., Teixeira, J. A., & Vicente, A. A. (2009). Effect of moderate electric fields in the permeation properties of chitosan coatings. Food Hydrocolloids, 23, 2110–2115

Scleroderma and related disorders: 223. Long Term Outcome in a Contemporary Systemic Sclerosis Cohort

Background: We have previously compared outcome in two groups of systemic sclerosis (SSc) patients with disease onset a decade apart and we reported data on 5 year survival and cumulative incidence of organ disease in a contemporary SSc cohort. The present study examines longer term outcome in an additional cohort of SSc followed for 10 years. Methods: We have examined patients with disease onset between years 1995 and 1999 allowing for at least 10 years of follow-up in a group that has characteristics representative for the patients we see in contemporary clinical practice. Results: Of the 398 patients included in the study, 252 (63.3%) had limited cutaneous (lc) SSc and 146 (36.7%) had diffuse cutaneous (dc) SSc. The proportion of male patients was higher among the dcSSc group (17.1% v 9.9%, p = 0.037) while the mean age of onset was significantly higher among lcSSc patients (50 ± 13 v 46 ± 13 years ± SD, p = 0.003). During a 10 year follow-up from disease onset, 45% of the dcSSc and 21% of the lcSSc subjects developed clinically significant pulmonary fibrosis, p < 0.001. Among them approximately half reached the endpoint within the first 3 years (23% of dcSSc and 10% of lcSSc) and over three quarters within the first 5 years (34% and 16% respectively). There was a similar incidence of pulmonary hypertension (PH) in the two subsets with a steady rate of increase over time. At 10 years 13% of dcSSc and 15% of lcSSc subjects had developed PH (p=0.558), with the earliest cases observed within the first 2 years of disease. Comparison between subjects who developed PH in the first and second 5 years from disease onset demonstrated no difference in demographic or clinical characteristics, but 5-year survival from PH onset was better among those who developed this complication later in their disease (49% v 24%), with a strong trend towards statistical significance (p = 0.058). Incidence of SSc renal crisis (SRC) was significantly higher among the dcSSc patients (12% v 4% in lcSSc, p = 0.002). As previously observed, the rate of development of SRC was highest in the first 3 years of disease- 10% in dcSSc and 3% in lcSSc. All incidences of clinically important cardiac disease developed in the first 5 years from disease onset (7% in dcSSc v 1% in lcSSc, p < 0.001) and remained unchanged at 10 years. As expected, 10-year survival among lcSSc subjects was significantly higher (81%) compared to that of dcSSc patients (70%, p = 0.006). Interestingly, although over the first 5 years the death rate was much higher in the dcSSc cohort (16% v 6% in lcSSc), over the following years it became very similar for both subsets (14% and 13% between years 5 and 10, and 18% and 17% between years 10 and 15 for dcSSc and lcSSc respectively). Conclusions: Even though dcSSc patients have higher incidence for most organ complications compared to lcSSc subjects, the worse survival among them is mainly due to higher early mortality rate. Mortality rate after first 5 years of disease becomes comparable in the two disease subsets. Disclosure statement: The authors have declared no conflicts of interes

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Suffering and the Dimensionality of Medical Knowledge: A Critique of Evidence Based Medicine

Evidence Based Medicine (EBM) is a recent philosophy that is highly influential in medicine. EBM is centred on the notion that medical practice should be supported by rigorous clinical research. This thesis explores a “dimensional” framework of knowledge and argues EBM results in the exclusion of certain non-scientific knowledge forms. Since these knowledge forms are essential to the realisation of medicine’s goals, EBM is holding medicine back. I frame the primary goal of medicine as to attend to suffering. There is a tendency to view the goal of medicine as the treatment of disease, but this fails to account for much of what occurs in practice. Suffering incorporates disease and also other humanistic aspects of medicine that may not be investigable in a scientific manner. Medical knowledge determines medical practice, so medicine must have knowledge of what suffering is to effectively attend to suffering. I propose a dimensional theory of knowledge that includes explicit, tacit, general and particular forms of knowledge. Explicated general knowledge includes the knowledge of science. Tacit knowledge is more readily enacted than articulated. Particular knowledge is knowledge that is applicable to specific circumstances and individuals. The existence of tacit and particular knowledge moderates the possibility and need for scientific justification and also means knowledge exists within the knower and not exclusively in abstracted forms. EBM’s philosophical framework excludes tacit and particular knowledge in its selective recognition of explicit-generalised “evidence”. This means that EBM’s conception of knowledge is incomplete and is philosophically inadequate. Though EBM makes useful contributions to clinical research appraisal, its normative assertions of “what counts as knowing” in medicine obscures human suffering and so might harm practice. This thesis presents the foundations for an alternative philosophy to EBM that would see “EBM” reframed as “clinical epidemiology” as a remedy for EBM’s normative restriction of medical knowledge