Monday, September 30, 2013

Silver – Entering the real battle against resistant bacteria?

Due to the continuing progression of antibiotic resistant bacteria development in the medical community a number of individuals believe it is time to explore how to incorporate silver, a long standing antibacterial agent, into treatment strategies. On its face this appears to be an important new avenue for attacking the growing problem of resistant bacteria and the lack of development of new antibiotics to fight these bacteria. However, this excitement must be stemmed by appropriate knowledge of how silver helps fight bacterial infections and the potential pitfalls to its incorporation into actual antibiotics or other blood based treatment strategies versus its current medical uses as a sterilization and wound dressing tool.

The use of silver in medical and wound management dates back to the 18th century with the application of silver nitrate to treat ulcers.1,2 Anti-microbial activity for silver ions was first scientifically suspected in the 19th century, although anecdotal reasoning can be traced back much earlier.3 However, in the early 20th century the overall effectiveness of penicillin and later discovery of other antibiotics displaced silver use for over two decades. Silver use increased in the 1960s in response to burn treatments through the use of a silver sulfadizine (SSD) cream. In modern times silver is incorporated into wound dressings, antibiotic cream and first-aid plasters to reduce bacterial growth and limit infection.4,5

Both bulk silver and isolated silver nano-particles are effective at killing, not only standard Gram-negative and Gram-positive bacteria, but also antibiotic-resistant strains.6-8 This action also catalyzes antibacterial activity of current antibiotics including penicillin G, amoxicillin, erythromycin, clindamycin, and vancomycin.9 Various mechanisms have been suggested to explain the anti-microbial action of silver: 1) particle penetration of bacterial cell walls and membranes leading to DNA damage and apoptosis possibly due to free radical incursion; 2) alteration of bacterial cell wall and membrane, most likely targeting lipopolysaccharides, forming pits increasing membrane permeability for antibiotics or disrupting respiration for aerobes; 3) lowering probability of biofilm formation increasing the probability of antibiotic effectiveness.10-13

There is no clear evidence regarding whether the anti-microbial effects of silver are found in colloidal silver or ionic silver or both, but some evidence suggests that colloidal silver is much less effective as an anti-microbial agent than ionic silver, especially because only oxidized silver nanoparticles exert a significant antibacterial effect.14,15 If colloidal silver has anti-microbial action its magnitude is largely dictated by the dimensions of the particles where smaller particles have a greater effect due to higher surface area to volume ratios.16-18 The shape of the nano-particle also seems important with truncated triangles having superior activity.19,20

Ionic silver is thought to activate its anti-microbial effects through the formation of complexes with negatively charged sulfur, nitrogen or oxygen functional groups in bacterial enzymes destabilizing the bacteria and preventing normal functions like metabolism and reproduction.15,21 So silver nano-particles may simply be an inert element that eventually degrades creating the actual silver anti-microbial agent with degradation occurring faster at smaller sizes and certain shapes. Therefore, when studying anti-microbial activity and possible silver toxicity it stands to reason that one should focus on oxidized silver versus neutral silver.

While the anti-bacterial properties of silver were suggested in the 19th century, silver resistant bacteria and the basis for that bacterial resistance was first reported much later in 1975, first in Salmonella typhimurium.22,23 This resistance is chiefly born from plasmid development or transfer.24,25 The chief silver resistant plasmid has been labeled pMG101, is 180-182 kb with nine Open Reading frames (seven known and two unknown) in three transcriptional units and like most plasmids is conjugally transferable between bacteria.24,26 In addition to silver, pMG101 grants additional resistance to mercury, tellurite, ampicillin, chloramphenicol, tetracycline, streptomycin, and sulphonamide as well.23,24,27 Note the wide variety and importance of this resistance against not only silver, but other frequently used antibiotics. pMG101 presence can resist up to six times minimum silver lethality for E. coli and more than likely other bacteria species.24,27

Overall silver resistance is driven by encoding two silver efflux pumps (one an ATPase and the other chemiosmotic) and two periplasmic Ag+-binding proteins.26 Basically silver ion uptake is decreased and silver efflux is increased. There is also some belief that an ATP-dependent copper efflux protein can mediate removal of silver ions.1 However, there is no direct evidence that this silver resistance mechanism induces cross-resistance to various antibiotics, but the rate of cross-resistances to other antibiotics and genetic linkage of silver resistance and antibiotic resistance genes provides positive circumstantial evidence.

Various bacteria species that have been identified as having silver resistance are E. cloacae, Enterobacteriaceae, Salmonella typhimurium, Klebsiella pneumoniae, Pseudomonas stutzeri, P. aeruginosa and E. coli.27-35 Resistance is principally generated through sil genes (one of the genes contained in the pMG101 plasmid) with its functions having been assigned due to homologous genes that encode resistance to other genes.22 However, there is question regarding the total level of silver resistance provided by sil genes because some research has demonstrated only partial phenotypic silver resistance, thus providing only partial resistance to silver.22,28,29 The reason for this partial resistance could be driven by lack of complete transcription due to a lack of consistent silver forcing selection pressure. Finally silver resistance has developed from acinetobacter baumannii based on seemingly separate 54 kb plasmid (pUPI199).31

Despite the variety of bacteria that can acquire silver resistance, the high-level and multi-faceted mode of action from silver (cell wall destruction and reduced antibiotic efflux) lead most to believe that the development of silver resistant is unlikely. While silver resistant bacteria appear rare, one of the reasons for this rarity is thought to be that silver is not utilized at high levels for antibacterial purposes similar to current antibiotics and if this were to change so would the rates of silver resistance development.

One of the big problems with regards to determining an accurate accounting of silver resistance is the lack of standardized metrics for this resistance. There is disagreement on the MIC50 breakpoints for bacteria susceptibility.34 When most silver microbial susceptibility studies are performed the conducting researchers tend to assign their own breakpoints to delineate susceptible and resistant strains. For example results from studies that explored MIC values for Staphylococcus aureus ranged from 8 to 80 mg/L32,33 where studies for Pseudomonas aeruginosa produced a range between 8 and 70 mg/L.34,35

Another problem is a general lack of standardization for silver ion anti-microbial testing methods mostly driven by solubility issues that change the rate of available silver ions due to formation of various silver-halide anionic complexes.1 This influence is most noted in the sodium chloride content of the microbiological medium used for susceptibility testing.1 Also the lack of standardization in silver wound dressings creates numerous delivery systems to release silver ions, which include elements beyond simple silver concentration to influence the ability to kill microorganisms.36 These discrepancies create questions regarding how different tests can be compared for similarities or differences in method.

One of the principle concerns with incorporating silver into antibiotic treatments that directly enter the blood is the potential for serious negative side effects. There are three important factors that govern the ability of a metal to produce systemic toxic effect: 1) the rate of absorption due to the solubility of the metal; 2) the capacity to bind to biological targets in the body; 3) the residence time of the metal after absorption both at biological targets and in the blood stream before elimination through excretion. The form of silver that is introduced to the body influences these three elements. Currently silver is largely applied as either silver nitrate (inorganic silver salts) or as organic compounds like SSD.1

Normal (no medical or heavy industry work) silver concentration in the body is very low with <2.3 ug/L (or 3 nmol/L) in the blood, about 2 ug/day (or < 8 nmol/L) expelled in urine and 0.05 ug/g (wet tissue) in the liver and kidneys.37-39 Some evidence has demonstrated that some SSD treated burn patients have plasma silver concentrations as high as 50 ug/L after 6 hours of treatment and can reach a maximum of 310 ug/L.37 In one particular case a patient that died of renal failure after 8 days of treatment had silver concentrations of 970 ug/g, 14 ug/g and 0.2 ug/g in the cornea, liver and kidney respectively.37,38 Due to silver derived renal toxicity from topical application (from wound bandages) most physicians believe that it is improper to apply topical silver treatments over long periods of time even on burn patients.

However, despite the above information most believe that silver application is generally safe with accumulation occurring in superficial layers of the liver and kidneys with full clearance after 28 days.39,40 Such limited consistent binding and the rate of clearance implies superficial binding and low absorption from a single application. However, there is limited information regarding how organ absorption would change with direct silver application to the blood.

Overall there are still numerous safety and toxicity studies that must be performed before even considering applying silver directly to oral or intravenous antibiotic treatments. Also new policy limiting the application of ionic silver, in either direct or indirect form, to non-medical products for an anti-microbial agent must be created because mass application dramatically increases the probability for widespread resistance development. Such an outcome has already occurred for numerous existing antibiotics and based on the apparent resistance profile for sil genes and their corresponding plasmids the widespread development of silver resistant bacteria could create a pathogen that cannot be effectively managed through modern medicine.

Citations –

1. Chopra, I. “The increasing use of silver-based products as antimicrobial agents –a useful development or a cause for concern?” Journal of Antimicrobial Chemotherapy. 2007. 59:587-590.

2. Klasen, H. “Historical review of the use of silver in the treatment of burns. I. Early uses.” Burns. 2000. 26:117-130.

3. Hugo, W, and Russell, A. “Types of antimicrobial agents. In: Russell, A, Hugo, W, Ayliffe, GAJ eds. Principles and Practice of Disinfection, Preservation and Sterilisation. Oxford, UK: Blackwell Scientific Publications: 1982. 8-106.

4. Fox, C Jr, “Silver sulfadiazine – a new topical therapy for Pseudomonas in burns. Therapy of Pseudomonas infection in burns.” Arch Surg. 1968. 96:184-188.

5. George, N, Faoagali, J, and Muler, M. “Silvazine (silver sulfadiazine and chlorhexidine) activity against 200 clinical isolates.” Burns. 1997. 23:493-495.

6. Burrell, R, et Al. “Efficacy of silver-coated dressings as bacterial barriers in a rodent burn
sepsis model.” Wounds. 1999. 11:64-71.

7. Yin, H, Langford, R, and Burrell, R. “Comparative evaluation of the antimicrobial activity of ACTICOAT anti-microbial barrier dressing.” J Burn Care Rehabil. 1999. 20:195-200.

8. Percival, S, Bowler, P, and Dolman, J. “Anti-microbial activity of silver-containing dressings on wound microorganisms using an in vitro biofilm model.” Int Wound J. 2007. 4:186-191.

9. Shahverdi, A, et Al. “Synthesis and effect of silver nanoparticles on the antibacterial activity of different antibiotics against Staphylococcus aureus and Escherichia coli.” Nanomedicine. 2007. 3:168-171.

10. Sondi, I, and Salopek-Sondi, B. “Silver nanoparticles as anti-microbial agent: A case study on E. coli as a model for Gram negative bacteria.” J Colloid Interface Sci. 2004. 275:177-182.

11. Hwang, E, et Al. “Analysis of the toxic mode of action of silver nanoparticles using stress-specific bioluminescent bacteria.” Small. 2008. 4:746-750.

12. Kim, J, et Al. “Anti-microbial effects of silver nanoparticles.” Nanomedicine. 2007. 3:95-101.

13. Morones-Ramirez, J, et Al. “Silver Enhances Antibiotic Activity Against Gram-Negative Bacteria.” Sci. Transl. Med. 2013. 5:190ra81.

14. Alvarez, J, et Al. “Negligible particle-specific antibacterial activity of silver nanoparticles.” Nano Lett. 2012. 12:4271−4275.

15. Lok, C, et Al. “Silver nanoparticles: Partial oxidation and antibacterial activities.” J Biol Inorg Chem. 2007. 12:527-534.

16. Baker, C, et Al. “Synthesis and antibacterial properties of silver nanoparticles.”
J Nanosci Nanotechnol. 2005. 5:244-249.

17. Panacek, A, et Al. “Silver colloid nanoparticles: Synthesis, characterization, and their antibacterial activity.” J Phys Chem B. 2006. 110:16248-16253.

18. Guzman, M, Dille, J, and Godet, S. “Synthesis of silver nanoparticles by chemical reduction method and their antimicrobrial activity.” Proceedings of World Academy of Science, Engineering and Technology. 2008. 33:367–74.

19. Pal, S, Tak, Y, and Song, J. “Does the antibacterial activity of silver nanoparticles depend on the shape of the nanoparticle? A study of the Gram-negative bacterium Escherichia coli.” Appl Environ Microbiol. 2007. 73:1712-1720.

20. Wiley, B, et Al. “Shape-controlled synthesis of metal nanostructures: The case of silver.” Chem Eur J. 2005. 11:454-463.

21. Damm, C, Munstedt, H, and Rosch, A. “Long-term antimicrobial polyamide silvernanocomposites.” J Mater Sci. 2007. 42:6067–73.

22. Woods, E, Cochrane, C, and Percival, S. “Prevalence of silver resistance genes in bacteria isolated from human and horse wounds.” Veterinary Microbiology. 2009. 138(3-4):325-344.

23. McHugh, G, et Al. “Salmonella typhimurium resistant to silver nitrate, chloramphenicol, and ampicillin.” Lancet. 1975. 1(7901):235-40.

24. Gupta, A, Maynes, M, and Silver S. “Effects of halides on plasmid-mediated silver resistance in Escherichia coli.” App. Environ. Microbiol. 1998. 64(12):5042-5.

25. Davis, I, Richards, H, and Mullany, P. “Isolation of silver- and antibiotic-resistant Enterobacter cloacae from teeth.” Oral Micro and Immunol. 2005. 20(3):191-4.

26. Silver, S. “Bacterial silver resistance: molecular biology and uses and misuses of silver
363 compounds.” FEMS microbiol rev 2003. 27(2-3):341-53.

27. Gupta, A, et Al. “Molecular basis for resistance to silver cations in Salmonella.” Nature Med. 1999. 5(2):183-188.

28. Annear, D, Mee, B, and Bailey, M. “Instability and linkage of silver resistance, lactose fermentation, and colony structure in Enterobacter cloacae from burn wounds.” J. Clin Pathol. 1976. 29:441-443.

29. Hendry, A, and Stweart, I. “Silver-resistant Enterobacteriaceas from hospital patents.” Canadian J. Microbiol. 1979. 25:915-921.

30. Bridges, K, et Al. “Gentamicin and silver-resistant Pseudomonas in a burns unit. Br. Med. J. 1979. 1:446-449.

31. Deshpande, L, and Chopade, B. “Plasmid mediated silver resistance in Acinetobacter baurmannii.” Biometals. 1994. 7:49-56.

32. Ug, A, and Ceylan, O. “Occurrence of resistance to antibiotics, metals and plasmids in clinical strains of Staphylococcus spp.” Arch. Med Res. 2003. 34:130-136.

33. Hamilton-Miller, J, Shah, S, Smith, C. “Silver sulphadiazine: a comprehensive in vitro reassessment.” Chemotherapy. 1993. 39:405-409.

34. Vassishta, R, Chhibber, S, Sexena, M. “Heavy metal resistance in clinical isolates of Pseudomonas aeruginosa.” Folia Microbiol (Praha). 1989. 34:448-452.

35. De Vicente, A, et Al. “Resistance to antibiotics and heavy metals of Pseudomonas aeruginosa islated from natural waters.” J. Appl Bacteriol. 1990. 68:625-632.

36. Thomas, S, and McCubbin, P. “A comparison of the anti-microbial effects of four silver-containing dressings on three organisms.” J. Wound Care. 2003. 12:101-107.

37. Wan, A, et Al. “Determination of silver in blood, urine, and tissues of volunteers and burn patients.” Clin Chem. 1991. 37(10 Pt 1):1683–1687.

38. Boosalis, M, et Al. “Serum and urinary silver levels in thermal injury patients.” Surgery. 1992. 101(1):40–43.

39. Coombs, C, et Al. “Do burn patients have a silver lining?” Burns. 1992. 18(3):179–184.

40. Harrison, H. “Pharmacology of sulfadiazine silver. Its attachment to burned humans and rat skin and studies of gastrointestinal absorption and extension.” Arch Surg. 1979. 114(3):281-285.

Tuesday, September 24, 2013

Looking for the Truth Behind the Health Value of Saturated Fat versus Carbohydrates

One of the more dynamic areas of modern research is nutrition and how it relates to biology. While in the past the more popular medium of discussion was through various diet/weight loss books, now the question of saturated fats and their overall influence on health has shifted to areas of more stringent study. Through most of the modern age of nutrition it has been viewed by the majority that saturated fats were largely negative and should be avoided as much as possible. Even the USDA recommends less than 10% of calories be derived from saturated fats1,2 largely based on the premise that increasing saturated fat consumption increases detrimental health outcomes including cardiovascular heart disease (CHD).3-5 However, there are individuals that believe this recommendation is inappropriate for it has not been clearly demonstrated empirically that increased consumption of saturated fat increases CHD or other negative health outcomes.

In fact some cite that while increasing saturated fat does increase total cholesterol, which is a characteristic for an increased rate of CHD, the rate of increase for high density lipoprotein (HDL) exceeds the rate of increase for low density lipoprotein (LDL), thus increasing the HDL/LDL ratio which is thought to be a more important factor to overall health than total cholesterol.6 Therefore, in the eyes of these individuals increasing saturated fatty acid (SFA) consumption in an equal caloric substitution over other types of nutrients like carbohydrates does not increase CHD risk and may even lower it.7-10 Overall the problem with both positions regarding the health effects of saturated fat is that most analysis fails to appreciate the specificity that addressing such an issue demands.

The crux of the question does involve the level at which one consumes saturated fats, but there are four central questions that govern the importance of that change:

First, different individual SFAs do not have the same biological effects despite similar molecular constructs. For example some epidemiological evidence demonstrates that stearic acid is the most detrimental SFA in terms of increasing the probability of CHD.11 Also despite the difficulty distinguishing between the overall effects of different SFAs palmitic acid is thought to be more detrimental to overall health than lauric acid. Not surprisingly in overall cholesterol raising effects stearic acid is neutral while all other long-chain acids increase both HDL and LDL levels versus low quality carbohydrates.12 There are no definitive conclusions regarding the influence of short and medium-chain SFAs due to a lack of study.

One of the reasons stearic and palmitic acid are so bad is that they can provide a negative feedback on acetyl-CoA carboxylase (ACC), the enzyme responsible for the catalysis of acetyl-CoA to malonyl-CoA which is utilized to increase the size of acyl chains reducing palmitic acid processing.13 In some respects there is little difference between trans-fatty acids and these two SFAs.

One would anticipate that it would be difficult to separate different types of SFAs with respect to what foods an individual consumes due to the combination of various SFAs in foods. However, it is feasible to distinguish certain specific foods that have higher percentages of certain SFAs over others and make broad dietary suggestions about those food items. For example palm oil and coconut oil have very high in palmitic and lauric acid concentrations respectively. Therefore, when studying the difference between SFAs and carbohydrates it is important to track what foods are consumed to ensure objectivity regarding certain SFA specific overload foods.

Second, when changing the amount of consumed SFAs some other molecule will replace those calories, thus it is important to consider the nature of that replacement and its specificity. Of the four issues that will be discussed this issue of substitution is the most studied one. There are a wide variety of elements that can replace saturated fat in a diet: protein, poly-unsaturated fat, mono-unsaturated fat, high glycemic index (low-quality/processed) carbohydrates, low glycemic index (high-quality) carbohydrates, “normal”/unsaturated fat and trans fats. Preliminary studies support the belief that rates of CHD decrease when replacing SFAs with poly-unsaturated fat, mono-unsaturated fat and “normal” fat.3,14,15 CHD rates increase when replacing SFAs with trans fats and refined/processed carbohydrates.3,16 Note that the glycemic index is utilized to measure how quickly blood sugar rise after consuming a given food and uses glucose as a upper level (100).

However, with regards to the carbohydrates since a large number of the carbohydrates that are consumed in modern society are of high glycemic variety if one were to guess it stands to reason that most, if not all, carbohydrate studies involved processed carbohydrates instead of quality carbohydrates. For example some proponents of SFAs like to cite studies that conclude a switch from SFAS to carbohydrates increases CHD probability. However, these studies do not typically differentiate between carbohydrate types. There is a large biological difference between low glycemic and high glycemic carbohydrates; without differentiating between carbohydrates any results born from substituting SFAs with a caloric equivalent amount of carbohydrates are inherently suspect. Think of it this way anyone who concludes that there is no biological and nutritional difference between consuming 150 calories of traditional rolled oats oatmeal versus 150 calories of Twinkie should not have their opinion taken into consideration.

In addition substitution studies must take appropriate caloric equivalency into account. For example if SFAs makes up 300 calories of a person’s daily caloric intake suitable comparison would demand that some percentage of that value be replaced with an equal value of the replacement (carbohydrates, poly unsaturated fat, etc.). It is sometimes difficult to track this equivalency feature if individuals are simply trying to recall what they consume over a given period of time versus keeping a food diary and having nutritionists correct for imbalances. Finally there is almost no information pertaining to replacing SFAs with protein or low glycemic index carbohydrates with regards to influence on CHD rates further limiting the value of substitution studies, an important exclusion that must be corrected for a definitive statement can be made regarding substitution. In the current environment the burden of proof is on those that believe SFAs are neutral or even better for health than processed carbohydrates, thus they need to ensure the quality of these substitution studies if they want to make the above contention.

Third, one of the biggest problems with comparing health effects between consumption of different food elements is a lack of comparison between subject microbiota. In short the microbiota is the concentration and type of bacteria population in an individual’s gastro-intestinal system. Numerous studies have demonstrated that the type of bacteria in an individual’s intestinal system have a significant impact on the ability to process and absorb nutrients.17-21 One of the biggest comparisons in microbiota is between Firmicutes and Bacteroidetes, which generally identifies obese individuals and non-obese individuals where Firmicutes is at larger concentrations in the obese and Bacteroidetes is at larger concentrations in the non-obese, usually with a 100%+ change.17,18 Note that this relationship is obviously not perfect, but is generally a good rule of thumb.

Evidence has shown that prolonged high SFAs feeding induced inflammation, impaired barrier function and changed microbiota profiles.22 The change in profiles lead to increased concentrations of Firmicutes and Oscillibacter and reduced concentrations of Bacteroidetes and Lactobacillus, thus high SFA feedings change the microbiota to one more seen in obese individuals. Clearly obesity is known for numerous detrimental health conditions, thus possessing a similar microbiota can be rationally viewed as a detrimental outcome versus a beneficial one.

Gut microbiota is important relative to carbohydrate processing as well in the rates and what types of carbohydrates are digestible.23,24 Fermentation occurring in the gut also leads to an increase in GLP-1 synthesis and insulin metabolism, thus rats fed a high fiber diet have higher plasma GLP-1, insulin and c-peptide levels after an oral glucose load.17 Various bacteria breakdown carbohydrates in fermentation reactions producing short chain fatty acids (SCFAs) like acetate, propionate and butyrate.25 Butyrate largely provides energy for colonic epithelia, propionate is taken up by the liver and is a precursor for gluconeogenesis, protein synthesis and liponeogenesis26,27 and acetate is metabolized by peripheral tissues and used as a substrate for cholesterol synthesis.28

The ratio of which SCFAs are produced is largely dependent on the ratio of bacteria in the gut. Evidence suggests that Firmicutes is able to produce about 25% more SCFAs than Bacteroidetes.19,20 Firmicutes appears to produce more butyrate and propionate with Bacteroidetes producing more acetate.29 There is question whether or not higher amounts of SCFAs are linked to obesity, but the evidence favors the affirmative: that increased SCFAs increase obesity probability.18,21,30 Also Firmicutes may increase the rate of malonyl-CoA activation over Bacteroidetes, which reduces the rate of carnitine palmitoyl transferase-1 reducing the amount of mitochondrial fatty acid oxidation.31 Overall while there is still a lot of information that needs to be deduced from the relationship between microbiota and health in general, especially obesity, the exclusion of any relationship in substitution studies is inappropriate.

Fourth, with regards to carbohydrate substitution, physical and aerobic conditioning of the research subject must be taken into consideration. Consistent exercise results in the increased direct and indirect consumption of carbohydrates as an energy source. Indirect consumption occurs through the increased production of specific enzymes, which favor the conversion of certain carbohydrates to glycogen versus SFAs like stearic or palmitic acid. Basically if one is substituting carbohydrates for SFAs in overweight and/or inactive research subjects the biological reduction of SFA consumption is heavily handicapped because the substituted carbohydrates are less likely to be used as short-term energy, but instead are converted to SFAs for long term energy storage.

One of the important elements when distinguishing between biological effects of SFAs and carbohydrates is the synthesis and consumption of glycogen. Glycogen is a multi-branched polysaccharide consisting of various glucose derivative molecules bound together and is used for long-term energy storage in a more compact form over triglycerides.

Glycogen is principally isolated within muscles, the liver and red blood cells32,33 and its rate of storage is dependant on physical training, basal metabolic rate and eating habits. Storage begins when blood glucose levels rise and insulin concentrations increase stimulating the action of hepatocytes leading to glycogen synthesis. As long as glucose and insulin remain in high relative concentrations glycogen synthesis continues. In periods of low glucose the pancreas secretes glucagons which catalyzes glycogenolysis.

Not surprisingly glycogen synthesis is exogonic, where UTP reacting with glucose-1-phosphate to drive the formation of UDP-glucose that eventually combine to lengthen glycogen through catalyzation by glycogen synthase forming from a base created by glycogenin.33 Glycogen consumption is endergonic where sections are cleaved by glycogen phosphorylase to produce glucose-1-phosphate monomers, which are later converted to glucose-6-phosphate by phosphoglucomutase. Glucose-6-phosphate produced from glycogen can enter the glycolysis pathway, the pentose phosphate pathway or be dephosphorylated back to glucose.33

A history of exercise, especially endurance training, enhances lipid and carbohydrate oxidation and decrease SNS activity during present time exercising in part due to increased muscle glycogenolysis and increased recruitment of skeletal muscle.34-38 Increasing exercise intensity increases the level of energy demand from the muscles and brain resulting in a faster crossover from lipids to carbohydrates as a source of energy. While some believe that there are special exercise-dietary regimens to enhance muscle glycogen storage/consumption rates when appropriate, there is no doubt that individuals who exercise consistently have higher rates of glycogen conversion of glucose and other sugars versus rates of glucose conversion to SFAs opposed to the rates found in overweight or obese individuals.34,39,40

One of the advantages of this difference is in the short period of time after exercise (24 hrs) is that rate of glycogen synthesis is indiscriminate the type of carbohydrate, be it simple or complex.40 Note that there is still an insulin concentration rise for simple carbohydrates over complex, but while the increase for complex is smaller the duration is longer.40 The fate of consumed carbohydrates is also influenced by the time between consumption and exercise.41 Therefore, individuals that are “in shape” are more likely to burn off consumed carbohydrates versus storing them as either glycogen or SFAs. Again comparison studies between SFAs and substitutions, especially carbohydrates, tend to exclude the influence of exercise.

Another side issue that must be considered when making comparison studies between SFAs and substitutes is the concentration of epinephrine due to its lipolytic, glycogenolytic and insulin-suppressive effects.42 Past training through exercise seems to reduce epinephrine concentrations in both at rest and during present exercise.42,43 Therefore, measurement of epinephrine needs to be conducted to act as a control point to make more accurate comparisons in substitution studies.

Overall there are clearly scientific and accuracy concerns regarding claims made by individuals who believe that SFAs are no more harmful to CHD rates than carbohydrates. Unfortunately such claims are typically made by individuals who are trying to justify a certain nutritional lifestyle versus individuals who actually care about proper nutrition. This is not to say that all forms of carbohydrates are guaranteed to be healthier than SFAs; the problem is that SFAs proponents have not produced evidence to demonstrate this conclusion that satisfies the four above concerns. Therefore, until this evidence is produced it is irresponsible of individuals to suggest that substituting SFAs for carbohydrates produces no detrimental change to CHD rates.

Citations –

1. Hoenselaar, R. “Saturated fat and cardiovascular disease: The discrepancy between the scientific literature and dietary advice.” Nutrition. 2012. 28:118-123.

2. U.S. Department of Agriculture (USDA) Food Guide or the Dietary Approaches to Stop Hypertension (DASH) Eating Plan.

3. Jakobsen, et Al. “Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies.” Am J Clin Nutr. 2009. 89:1425–32.

4. Dayton, S, et Al. “A controlled clinical trial of a diet high in unsaturated fat in preventing complications of atherosclerosis.” Circulation. 1969. 40(suppl 2):1–63.

5. Turpeinen, O, et Al. “Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study.” Int J Epidemiol. 1979. 8:99–118.

6. Prospective Studies Collaboration. “Blood cholesterol and vascular mortality by age, sex and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths.” Lancet. 2007. 370:1829–39.

7. Astrup, A, et Al. “The role of reducing intakes of saturated fat in the prevention of cardiovascular disease: where does the evidence stand in 2010?” Am. J. Clin. Nutr. 2011. 93:684-688.

8. Frantz, I Jr, et Al. “Test of effect of lipid lowering by diet on cardiovascular risk. The Minnesota Coronary Survey.” Arteriosclerosis. 1989. 9:129–35.

9. Siri-Tarino, P, et Al. “Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease.” Am. J. Clin. Nutr. 2010. 91:535–546.

10. Skeaff, C, and Miller, J. “Dietary fat and coronary heart disease: summary of evidence from prospective cohort and randomised controlled trials.” Ann Nutr Metab. 2009. 55:173–201.

11. Hu, F, et Al. “Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women.” Am J Clin Nutr. 1999. 70:1001–8.

12. Hunter, J, Zhang, J, Kris-Etherton, P. “Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review.” Am J Clin Nutr. 2010. 91:46–63

13. Wikipedia - Palmitic acid Entry.

14. Laaksonen, D, et Al. “Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids.” Arch Intern Med. 2005. 165:193–9.

15. Soinio, M, et Al. “Dietary fat predicts coronary heart disease events in subjects with type 2 diabetes.” Diabetes Care. 2003. 26:619–24.

16. Danaei, G, et Al. “The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors.” PLoS Med. 2009. 6:e1000058.

17. Cani, P, and Delzenne, N. “The role of the gut microbiota in energy metabolism and metabolic disease.” Current Pharmaceutical Design. 2009. 15:1546-1558.

18. Ley, R, et Al. “Microbial ecology: human gut microbes associated with obesity.” Nature. 2006. 444:1022-3.

19. Schwietz, A, et Al. “Microbiota and SCFA in lean and overweight healthy subjects.” Obesity. 2009. 18:190-195.

20. Bajzer, M, and Seeley, R. “Physiology: obesity and gut flora.” Nature. 2006. 444:1009–1010.

21. Turnbaugh, P, et Al. “An obesity-associated gut microbiome with increased capacity for energy harvest.” Nature. 2006. 444:1027–1031.

22. Lam, Y, et Al. “Increased gut permeability and microbiota change associate with mesenteric fat inflammation and metabolic dysfunction in diet-induced obese mice.” PloS ONE. 2012. 7(3):e34233.

23. Goodlad, R, et Al. “Effects of an elemental diet, inert bulk and different types of dietary fibre on the response of the intestinal epithelium to refeeding in the rat and relationship to plasma gastrin, enteroglucagon, and PYY concentrations.” Gut. 1987. 28: 171-80.

24. Goodlad, R, et Al. “Proliferative effects of 'fibre' on the intestinal epithelium: relationship to gastrin, enteroglucagon and PYY.” Gut. 1987. 28(Suppl): 221-6.

25. Macfarlane, G, and Gibson, G. “Carbohydrate fermentation, energy transduction and gas metabolism in the human large intestine.” In: Mackie RI, White BA (eds). Gastrointestinal Microbiology. Chapman & Hall: New York, USA, 1997. 269–317.

26. Wolever, T, Spadafora, P, and Eshuis, H. “Interaction between colonic acetate and propionate in humans.” Am J Clin Nutr. 1991. 53:681–687.

27. Vernay, M. “Origin and utilization of volatile fatty acids and lactate in the rabbit: influence of the faecal excretion pattern.” Br J Nutr. 1987. 57:371–381.

28. Wolever, T, et Al. “Effect of rectal infusion of short chain fatty acids in human subjects.” Am J Gastroenterol. 1989. 84:1027–1033.

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Tuesday, September 17, 2013

Leadership in Large Societal Movements

Numerous treatises have been written about leadership, its origins and supposedly how to develop it. Unfortunately many of these discussions are limited in importance for most people because they focus on small environments where the consequences are who gets marketing account A or wins the debate B. Even the larger environments of democratic elections are limited in their scope because of term limits and the general reversibility of a vast majority of accomplishments, be it beneficial or detrimental. The true importance of leadership comes from those attempting to lead movements against large organizations or government, especially those leaders that do not come from some form of seat of power.

The sad reality when it comes to individualized power is that it is essential to accomplishing anything substantial over a long period of time without resorting to violence. Some may take offense to this statement citing numerous events in history where the “downtrodden”, powerless and oppressed banded together and rose up against their oppressors without requiring violence like the civil rights movement (sans the Black Panthers) in the United States and the movements supporting India Independence. However, when looking at these events in earnest, past the “underdog” hype and mythos, those that eventually succeeded over the long-term required either the intervention of individuals with power or their apathy in fight against the movement.

For example based on known elements at the time and in the future, it is unlikely that the Civil Rights Act of 1964 would have been passed effectively codifying the success of the civil rights movement if Richard Nixon had won the U.S. presidency in 1960. Also when viewing John F. Kennedy’s unwillingness to aggressively address the “black equality” question and difficulty confronting the Southern Democrats, it can be argued that had Kennedy not been assassinated in 1963 it is unlikely the Civil Rights Act would have been passed either, at least until a much later date. Numerous people underestimate the commitment that then president Lyndon B. Johnson had towards resolving the level of inequality for blacks in the South, a commitment that was lacking in both Nixon and Kennedy. In fact a number of historians give Johnson credit for pushing the Kennedy administration to address civil rights. Clearly if Johnson had not been president at the time, granting him the ability to wield a large level of power, it is unlikely that the civil rights movement at the time would have been successful while remaining non-violent and the probability of winning when turning to violence was almost zero.

Similarly India acquired its independence from British rule largely because it was calculated that the detriments from keeping India as a colony exceeded the benefits regardless of the movement clamoring for independence. For numerous foreign “revolutions” in the modern era intervention by powerful outside parties, like the United States, is principally involved in tipping the scale for example recently in Libya, the “rebels” were on the brink of annihilation before the intervention of NATO. However, the common denominator in all of these revolutions is the administration of power, brought on by those who inherently had it or through violence.

When there is a lack of individuals with significant power and a movement elects not to resort to violence how can a movement expect to accomplish its goals? Normally it will not accomplish those goals, a result that can be seen over numerous event through history most recently in the currently failing 2nd Egyptian revolution now that the army is actually interested in maintaining the status quo and the short-lived, but highly publicized, Occupy Wall Street (OWS) movement in the United States. So is there a way for these movements to have success without applying power from the above sources?

The first critical element to any societal movement regardless of the amount of possessed power is the realization of sacrifice. Note that for the purposes of this discussion a “societal movement” is defined as: “a movement that aims to significantly influence the workings of a given society on a large scale”. OWS accomplished almost nothing worthwhile largely because the greatest level of defiance that most of its members were willing to undertake was cause a small amount of annoyance for those in certain positions of power in New York. Some could spin the accomplishments of the movement to include improved unity or societal clarity that expanded beyond New York, but those individuals are simply grasping at straws in their attempt to defend OWS. One could argue that the movement was about little more than the ego of the participants and pointless steam venting versus actually solving the problem of growing wealth inequality in the U.S. Would a legitimate devotion to sacrifice and the elimination from the movement anyone who was not willing to undertake the same mindset have changed the result?

From this presumption an interesting question arises. Suppose at the time of the OWS protest (fall of 2011) 5000 random individuals involved were asked whether or not he/she would be willing to be incarcerated for 15 years at a medium security prison in the general population in exchange for the passage of Fictional Bill 104 (FB 104). FB 104 would establish a real time maximum asset cap for individuals of 20 million dollars and for corporations a maximum yearly profit cap of 150 million dollars. The government would tax 100% of all income/earnings/wages/assets/etc over either cap. The IRS would be given much greater authority to pursue and charge tax cheats/thieves and all tax cheats found guilty would receive jail terms in medium security prisons with minimum sentences equating to 1 year per $100,000 that was concealed. Also U.S. foreign policy would place emphasis on pressuring notorious tax havens to open their books regarding banking by U.S. citizens, similar to the tactics recently used against Switzerland. Taxes accrued from this ceiling tax would be used to fund food banks, education, apprenticeships and small business loans to increase both the job pool and the number of qualified applicants.

So given this general outline of FB 104, which should go a long way to limiting the equality gap in the United States, how many of the 5000 polled protesters would actually sacrifice their freedom for 15 years to accomplish this goal? Sad to say probably not many of them, if any at all. What if unless at least 75% of those asked accept the terms the bill would not become law? Note that in the above example 15 years in prison signifies a tradeoff for the bill and is supposed to represent some of the real sacrifice that OWS protesters could have engaged in, various elements of economic disruption, which could have “persuaded” the federal government into actually doing something about the problem.

Another problem with the OWS movement was their “strategy”, if one could even say they had one, was not realistic relative to the general psychological makeup of society. While the overall initial goal, before it basically became a mouthpiece for every non-conservative societal complaint, was never fully clear; the argument against increasing financial inequality due to the application of superficial importance to certain occupations and the minimization of importance of others implies that OWS wanted the formation of a genuine meritocracy with appropriate handicap measurements for individualized starting positions. Note that the above statement is a rather mouthful so what exactly does it mean?

Most individuals are familiar with a meritocracy. A meritocracy is a school of thought that believes power and influence should be vested in individuals according to potential and accomplishment not class/rank, blood, connections, etc. In addition occupations and roles that foster positive societal development and stability take precedence over occupations that do not. For example in such an environment entertainers and stockbrokers would make considerably less money than physicians, teachers and engineers.

The appropriate handicap measurement element is basically a socio-economical version of the original premise behind affirmative action. The original idea behind affirmative action was to create an evaluation system, which extrapolated performance in similar opportunities between candidates even if only one participated in the specific opportunity. Basically certain individuals due to socio-economic, racial and/or ethnic background will not be afforded certain educational and/or occupational opportunities. Note that the “not” in the previous sentence is important because these individuals did not fail at the opportunity or fail to accept the opportunity, but never had the option of accepting the opportunity in the first place.

The key aspect of affirmative action was to use the written information (usually in the resume or other requested items) to create an effective questioning session for the interview to extract the necessary information to make the comparison extrapolation. Unfortunately for whatever reason, more than likely simple laziness, this original intent has devolved into quasi-quota systems (because actual quota systems are illegal) or free points in a rating system, stripping the value and fairness of affirmative action.

The affirmative action aspect of the meritocracy is necessary because clearly not all individuals have similar resources. Not everyone has loving parents that are dedicated to teaching their children about the rigors of existence and giving them the tools, focus and guidance to become successful adults. Not everyone has parents with sufficient capital to provide resources and opportunities to significantly increase the probability of success. For example would someone like Taylor Swift really be the success she currently is at the moment if she was born to a single parent household where the guardian parent was working two minimum wage jobs just to get by? For such a circumstance it is highly unlikely that Miss. Swift would have become a successful entertainer instead being relegated to a waitress or service minimum wage job herself; note while Miss. Swift is talented at entertaining the fact that her parents had time to spend with her and large amounts of wealth to spend on her heavily tilted the scales of success in her favor.

People marvel at the rare exceptional cases of individual A becoming a successful… say neurosurgeon, despite growing up with an incarcerated father and an alcoholic mother or some similar hardship, but they conveniently fail to consider the vast majority of individuals who are unable to overcome such handicaps. It is completely inappropriate for society to chastise those that are unable to overcome hardships simply because a very select few are lucky enough to do so. Is it right to punish the 3rd generation for the sins, incompetence and/or bad luck of the 1st and/or 2nd generation? Therefore to create a genuine meritocracy, society must provide resources to eliminate the most crippling handicaps: everyone must receive sufficient shelter, food and an education otherwise society can never be a genuine meritocracy (it certainty is not one at present).

However, the original question was: can a meritocracy even come into existence in the first place based on the current structure and personality of society? There is a refrain that oddly rings of jealousy when rich individuals complain about the government providing food stamps for the poor when said rich individuals have the “great” burden of diverting a part of their $150,000+ a year salary to buy food. Taking the temperature of society it appears that most of the so-called “winners” forget that generational influence creates unequal starting positions instead believing that whether or not someone is successful is entirely of an individual’s making, a rationality that has been previously identified as foolish. Unfortunately this rationality is used to back a strong self-serving ego and will continuously provide a barrier to creating a genuine meritocracy.

It is difficult to understand the mindset that facilitates cries of “no fair” from individuals born into upper middle class or rich families towards individuals born into poor families who receive government assistance, but there seems to be one explanation that must be a part of the whole picture. Psychologically there are two perspectives that influence the concept of personal self-worth: absolute or relative. An absolute perspective of self-worth focuses on the individual in a vacuum and any judgment is applied along fixed concepts or values. A good example of this mindset is whether or not an individual believes scoring an 80% on a test in school is good (for some it is while for others it is not). A relative perspective of self-worth focuses on the individual when compared against other individuals and fixed concepts have far less importance in the evaluation. Returning to the above test example for a relative perspective an individual can score a 46% and still classify it as good if the class average was 33% even though 46% is by all accounts a failure on an absolute level.

Unfortunately it seems like too many people in society judge their self-worth on a relative level, a concept supported by the common refrain of “keeping up with the Joneses”; this mindset can create an underlying fear that providing assistance to individuals who are judged as “below” these relative thinking individuals could eventually lead to these assistance receivers surpassing the relative thinking individuals thus lowering their own self-worth all because the government had the audacity to help feed them. It is unclear what psychological aspects of the mind create a divergence between absolute self-worth and relative self-worth judgments, but one possibility is that those who judge on relative self-worth have little natural self-esteem and are scared of the truth about the limited significance of their actual character and accomplishments, thus they have to mitigate those limitations behind the failings of others. Sadly there does not appear to be any easy way of changing relative worth mindsets to absolute worth.

The meritocracy problem is not the only significant problem in a movement with a goal like OWS. Similar to almost everything in life, certainty or the probability of occurrence of the event is a critical element to whether or not someone will undertake a given action. However, certainty is especially important for group movements driven by ideas because of the tiered time elements. Most decisions have immediate or short-term time expirations like playing the lottery or criminal actions like shoplifting where all realistic possible outcomes from the decision making process are resolved shortly after the decision is made. For idea movements like the OWS continuous pressure must be applied by the proponents of the new idea in order to dethrone the existing idea beyond the new idea simply being a better idea because there are parties that benefit from the existing idea who would not benefit from the new idea. This pressure must continue even after acceptance of the new idea to ward off challenges from previously defeated inferior ideas or other new ideas that are not as beneficial to society. Therefore, proponents for societal ideas must be prepared to sacrifice over a long time period and even suffer multiple grievances, thus proponents must be even more committed.

Realizing the need for sacrifice societal movements need strong leaders that will inspire other individuals in the movement to make sacrifices. Some individuals believe that a hierarchical system utilizing leaders and followers is not appropriate, some even cite this feature as a strength of the OWS movement, but to hold this belief is to support a philosophy that will eternally have a low probability of accomplishing anything significant. As discussed above focus and commitment are important elements for successful movements and these elements are difficult to acquire if individuals are left to their own devices and expected to coordinate with each other to accomplish anything meaningful over a long period of time. The lack of a direct recognizable leadership hierarchy was one of the major reasons why the OWS movement collapsed, at least in the public eye, after it was removed from its initial base of operations.

What can a leader do to inspire individuals to fight for their common ideals? Despite what movies and television try to instill as quality leadership, simply giving a rousing inspirational speech is only useful in the short-term. When the consequences start hitting the fan non-zealous followers will quickly lose faith in leaders that only elect to orate from the sidelines. Such a characteristic is why President Obama is currently a poor leader. Instead the leader must act as a counterweight to the negative aspects of the consequences. One obvious means to neutralize this dissident element is for the leader to experience the sacrifices with the followers. The clear advantage of this strategy is that followers see that the leaders are also willing to sacrifice for the ideal building a greater level of trust. The disadvantage is that the scale of detriment rises with the magnitude of resistance.

For example some might argue that the detriment to the leader accepting similar consequence to the followers is that it is difficult to “lead” from a jail cell. However, looking over history no significant non-centralized power-based movement succeeded when the highest consequence was simply spending a few nights in jail. When the chief consequence is simply very short-term incarceration the opponents of the movement are not taking the movement seriously and realize that it has no real probability of success. However, when the opposition starts taking the movement seriously the consequences become more severe: longer jail terms, lawsuits, physical injury or even death, hence the real detriment. These results will lead to a difficult question: which is more damaging to the movement, leaders being maimed and killed or followers losing faith in their leaders? The answer is only something the particular movement can decide.

Instead of directly involving themselves in the consequence, leaders can alleviate or neutralize the consequence for their followers through effective legal arguments or counter negotiations with the third parties or the opposition party. One concern with this indirect strategy is that there are times when the opposing party begins to exert significant consequences and do not always allow for due process and other rights or in cases of movements outside the United States, such rights may not exist at all. Therefore, utilizing legal tactics to lessen or eliminate consequences may fail solely because the opposition does not allow them to succeed. Of course a leader could attempt to retain some credibility by blaming the failure of these avenues on opposition driven blockage.

Another issue for these types of movements in a democracy is that they must have the interests of the majority at heart. The “dark side” of democracy is that the majority is supposed to get what it wants, even if what it wants is wrong and/or foolish, and the minority is simply supposed to take it. This reality was not a large problem in the past for the minority because logical arguments could be made to break through and defeat inaccurate preconceived notions not backed by logic or evidence and convince members of the majority that a current idea was inferior to another idea. Unfortunately in the modern polarized global political system (which is not simply isolated to the United States) most people have developed the attitude that changing their opinion about anything is tantamount to complete failure so they resist change making it more difficult for the minority to induce change through dialogue. Fortunately for a movement like OWS the general goal of defeating income inequality is inherently favorable to the majority because it addresses a system where the minority can oppress the majority

Another way to associate goals of the movement to the will of the majority is the demonstration of belief both through altruism and accomplishment. As society has modernized it appears to have created a greater gap between what some would regard as the basics of humanity or human decency. Certainty there is a large outcry of assistance from strangers to strangers after natural disasters, but there is little caring or assistance during periods of normalcy. Therefore, a societal movement must demonstrate to bystanders that they should at least “root” for the success of the movement, if not join it themselves. Basically the general apathy and indifference that consumes people regarding the suffering of others must be defeated (i.e. I don’t care unless it is happening to me or someone directly associated with me). The accomplishment aspect bleeds into the certainty aspect in that people in the movement need to have the belief that they can actually win. Therefore, besides the overall goal of the movement sub-goals must be established that can be broadcast: recruitment goals, funding goals, opposition disruption goals, etc; some tangible metric that can be used by supporters to suggest that they are winning.

One of the trickier elements for a movement like OWS is their general goal when it comes to the distribution of power. Normally when a revolution type movement form the goal is to overthrow the current power structure and install one lead by the movement where individuals in the movement become the powerbrokers. In the case of OWS the presumed goal is to overthrow the current power structure and install a system where there is no guarantee that they will be powerbrokers, only allow for everyone to have a fair chance at becoming one. When thinking of it in a numerical sense in most revolutions the powerbrokers start at 10 and the revolutionaries at 1-2 and if the “rebels” win they go to 10 and the former powerbrokers go to 1-2. In the OWS situation the initial conditions are similar, but upon winning the “rebels” go to 5 and the former powerbrokers go to 4-6.

The chief problem with this change in the end result is that for most people in the movement the idea of acquiring power over the individuals/groups that will be disposed with a victory is a significant motivating factor, a reward for the sacrifices that are made to achieve victory. Such a mindset has played out numerous times in history with the oppressed overthrowing the oppressors and then becoming the oppressors themselves, especially against the former oppressors. Therefore, how much will members of a OWS like movement be willing to sacrifice for a seat at the table if that table will be open for everyone, especially if individuals who do not sacrifice receive the same general benefits? Ironically a leader of such a movement could motivate such sacrifice by tapping into the relative self-worth mindset by arguing that those who participate and sacrifice for the movement will enhance their legacies while those who don’t will be looked down upon even though the absolute tangible gains from the movement will be similar for all repressed parties.

The final issue is actually winning without centralized power or violence. The only genuine way to accomplish a victory in this situation is the effective use of numbers. Society has become dependent on an economic system that is a pyramid structure where a movement with numbers can simply collapse the entire system. Of course such a strategy relies on invoking Zappa’s philosophy of it being better to die on one’s feet than live on one’s knees. This ideal is important because for a movement without centralized power the highest probability of victory comes from a mutual assured destruction (MAD) strategy.

MAD works on two levels. First, it acts as a deterrent, as most know from the Cold War, neither side acts against the norm creating a stable, but stressed situation. Second, one party acts to trigger a response from the opponents significantly damaging, if not effectively eliminating, both sides. In the case for such a strategy with an OWS movement millions of individuals would simply need to stop working and buy only the bare minimum to survive. This reaction would create a self-catalyzing economic collapse that would erode the foundation of the global economy, especially if such action occurred in the United States. The powerbrokers would not be able to neutralize such an action and their “penthouse” positions would come crashing down along with the base, for despite some of the attitude possessed by the rich demographic if the base of the building collapses the penthouse will not “magically” remain aloft through levitation.

However, the crux of a MAD strategy, hence the clever and useful acronym, is who would be willing to destroy themselves in effort to induce certain changes? What typically prevents non-zealots from executing extreme actions: fear. Non-zealots fear that their sacrifices are not sufficient to accomplish the end goal, thus they are “throwing their life away” for no genuine progress. Therefore, to execute a MAD strategy one must eliminate this fear. Religious revolutionary leaders do so through promises of beneficial positions in the afterlife, i.e. defeat those heathens that hold Jerusalem and God will welcome you to heaven or blow yourself up to kill those Zionists and Allah will grant you virgins. An OWS movement really has zero religious zeal, despite the feelings of Jesus the Christ towards the poor (something forgotten by most rich people who claim to be Christian), so the most empirically relevant element for overcoming MAD trepidation is not available.

The magnitude of the sacrifice and movement have to be significant enough, so a few dedicated individuals who elect to bare the burden of sacrifice themselves as a flash/rallying point will simply result in needless sacrifice that will soon be forgotten. For example who remembers the names of the Tibetan monks that occasionally immolate themselves in the name of Tibetan independence? Interestingly there are millions of people that could be candidates for joining a movement that does not have a centralized power structure, thus will more than likely need to rely on MAD. Sadly their involvement could be regarded as controversial.

Those who are depressed have loosened their opinions of the value of life making them more amenable to taking risks and sacrifices with it for what could be viewed as a great purpose. In addition the relative self-worthy pendulum swings in the movement’s favor in that the depressed see little value in their lives so participating in such a magnifying movement may tap into their deflated ego. It must be noted that to some there would be clear moral pauses to incorporating individuals of such psychological states into such a movement in that will they simply be pawns as a means to an end? Also such incorporation could create a negative backlash against the movement whether justified or not. However, there is something to be said that depressed individuals are not mentally incompetent, thus they could freely decide whether or not to participate in a societal movement and what level of sacrifice they would be willing to devote to it.

Overall for a movement like OWS to succeed it requires one of three elements: 1) Numerous advocates in the current centralized power structure that will change the current system to be accommodate the goals of the movement; 2) Utilize violence to create an environment where the proposed goals of the movement provide less of a detriment to those in power than the detriment provided by the violence; 3) Execute a non-violent MAD strategy involving task and consumer elimination that threatens to collapse the entire economic system unless the demands of the movement are met. Some could argue that there is a fourth option in that millions could elect individuals to power in a democracy catalyzing the formation of option 1. However, this argument is difficult because the civil rights movement had a seasoned leader in LBJ with decades in government with time in both houses of Congress, an ability to effectively understand and play the political game and numerous friends, allies and even people just willing to listen; there is no such person with those characteristics with regards to income inequality and genuine meritocracy (Bernie Sanders does not have anywhere near the necessary clout). In the end unfortunately for OWS backers that particular movement elected to embark on a “none of the above” strategy, thus explaining why it has faded quickly and quietly into obscurity.