Out of the multiple interpretations of cancers, two predominant ones have been (i) somatic evolution of cheater cells that escape replication regulation and (ii) cancers as non-healing wounds. Both ...the interpretations have substantial support as well as glaring anomalies but the two along with other possible interpretations have not been put together to make a coherent synthesis. We argue here that mechanisms and pathways to escape the normal regulation of cell proliferation do not need to evolve _de novo_. Mechanisms to override the normal regulation have already evolved for wound healing and tissue regeneration. Almost all of the hallmarks of cancer are also seen in the wound healing process. This suggests that cancer develops not by any _de novo_ gain of function but by exaptation of pre-evolved wound healing functions. Somatic evolution that makes the wound healing triggers constitutive is not mutation limited but selection limited and the selective forces are dependent on the tissue microenvironment. Some mechanisms for such selection have been suggested. Many more need to be investigated. A series of mechanisms have evolved to minimize the risk of cancers which may fail in an altered lifestyle context. We support our synthesis with multiple lines of evidence and also make differential testable predictions. This evolutionary perspective challenges multiple prevalent ideas, suggests novel lines of research and also has translatable implications for cancer prevention.
Summary An upcoming hypothesis about the evolutionary origins of metabolic syndrome is that of a ‘soldier’ to ‘diplomat’ transition in behaviour and the accompanying metabolic adaptations. ...Theoretical as well as empirical studies have shown that similar to the soldier and diplomat dichotomy, physically aggressive and non-aggressive strategists coexist in animal societies with negative frequency dependent selection. Although dominant individuals have a higher reproductive success obtained through means such as greater access to females, subordinate individuals have alternative means such as sneak-mating for gaining a substantial reproductive success. The alternative behavioural strategies are associated with different neurophysiologic and metabolic states. Subordinate individuals typically have low testosterone, high plasma cholesterol and glucocorticoids and elevated serotonin signalling whereas dominant ones are characterized by high testosterone, low brain serotonin and lower plasma cholesterol. Food and sex are the main natural causes of aggression. However, since aggression increases the risk of injury, aggression control is equally crucial. Therefore chronic satiety in the form of fat should induce aggression control. It is not surprising that the satiety hormone serotonin has a major role in aggression control. Further chronically elevated serotonin signalling in the hypothalamus induces peripheral insulin resistance. Meta-analysis shows that most of the anti-aggression signal molecules are pro-obesity and pro-insulin-resistance. Physical aggression is known to increase secretion of epidermal growth factor (EGF) in anticipation of injuries and EGF is important in pancreatic beta cell regeneration too. In anticipation of injuries aggression related hormones also facilitate angiogenesis and angiogenesis dysfunction is the root cause of a number of co-morbidities of insulin resistance syndrome. Reduced injury proneness typical of ‘diplomat’ life style would also reorient the immune system resulting into delayed wound healing on the one hand and increased systemic inflammation on the other. Diabetes is negatively associated with physically aggressive behaviour. We hypothesize that suppression of physical aggression is the major behavioural cue for the development of metabolic syndrome. Preliminary trials of behavioural intervention indicate that games and exercises involving physical aggression reduce systemic inflammation and improve glycemic control.
BACKGROUND: In contrast to type 1 diabetes mellitus (T1DM), in type 2 (T2DM) the success of intensive glucose normalisation in arresting diabetic complications is marginal and inconsistent across ...multiple clinical trials. However, glucose regulation still largely remains the main target of treatment for T2DM in clinical practice. OBJECTIVES: We examine the possible causes of inconsistency across studies, the scientific rigour behind the design, conduct and inferences of 6 large institutional clinical trials targeting glucose normalisation and following up for diabetic complications and mortality. STUDY DESIGN: We enumerate the possible flaws in the design, statistical treatment of the results and possible logical traps in making inferences. Further, we evaluate whether the flaws can mislead the conclusions. We also suggest a more sound statistical treatment of the data and interpret results of the trials together in a coherent way. RESULTS: The clinical trials for intensive glucose control suffer from a number of common problems that have not been addressed. The most important being the failure to correct for multiple outcomes. This is recognised by some reviewers but no correction is attempted. The second is the interdependence of the outcomes, owing to which statistics based on the assumption of independence can be misleading. Simulations show that the apparent inconsistency or heterogeneity between trial results can be explained by the violation of assumed independence alone. Further, the problems with placebo control, failure to recognise alternative possibilities, inability to segregate clinical significance from statistical significance and misleading reporting formats point to conformity bias and publication bias. CONCLUSIONS: We find no support for the prevalent belief that glucose normalisation has any benefit in terms of reducing the frequency of any of the complications or mortality. It is time to reconsider the glucocentric line of treatment of T2DM. Rethinking some of the fundamental beliefs about the pathophysiology of diabetic complications and facilitating novel alternative lines of research is the need of the field.
Cancers have been interpreted either as somatic evolution of cheater cells that escape replication regulation or alternatively as non-healing wounds. Both the interpretations have substantial support ...as well as glaring anomalies but the two have not been put together to make a coherent synthesis. We argue here that mechanisms and pathways to escape the normal regulation of cell proliferation do not need to evolve de novo. Mechanisms to override the normal regulation have already evolved for wound healing and tissue regeneration. Almost all of the hallmarks of cancer are also seen in the wound healing process. This suggests that cancer develops not by any de novo gain of function but by exaptation of pre-evolved wound healing functions. Somatic evolution that makes the wound healing triggers constitutive is not mutation limited but selection limited and the selective forces are dependent on the tissue microenvironment. Some mechanisms for such selection have been suggested. Many more need to be investigated. A series of mechanisms have evolved to minimize the risk of cancers which may fail in an altered lifestyle context. We support our synthesis with multiple lines of evidence and also make differential testable predictions. This evolutionary perspective challenges multiple prevalent ideas, suggests novel lines of research and also has translatable implications for cancer prevention.
Conflict caused by wild herbivores damaging crops is an almost universal problem in conservation. We designed and implemented a game‐theory‐based system for supporting farmers whose crops were being ...heavily damaged by wild herbivores. In this community‐operated system, farmers self‐report their production, which is endorsed by neighboring farmers. The average deficit in production is compensated for by a payment that is directly proportional to the average deficit in production of the group and to the individual farmer's productivity. As a result, farmers are compensated for the average damage (support) and rewarded for individual productivity (reward) (i.e., support cum reward SuR). The design of the game is such that only honest reporting gives maximum returns. Farmers who underreport receive less payment because the SuR amount is proportionate to their self‐reported productivity. The endorsing farmers, in their own self‐interest, prevent overreporting. The system involves multiple game situations, the combined result of which is a stable strategy based on honesty and hard work. In 2 villages along the western boundary of Tadoba Andhari Tiger Reserve in central India, we tested the system with 75 farmers over 6 crop seasons. After a few initial attempts to cheat, honesty prevailed throughout the group. Average crop productivity increased 2.5‐fold, in spite of damage, owing to increased effort by farmers. Apart from wildlife conflict resolution, the model offers a promising alternative to crop insurance and a potential behavioral green revolution in agriculture.
Combinación entre el Pago por Daños a Cultivos y la Recompensa por Productividad para Abordar el Conflicto con la Fauna
Resumen
El conflicto causado por herbívoros silvestres que dañan los cultivos es casi un problema universal para la conservación. Diseñamos e implementamos un sistema basado en la teoría de juegos para apoyar a los agricultores cuyos cultivos estuvieran siendo dañados considerablemente por los herbívoros silvestres. En este sistema operado comunitariamente, los agricultores reportan por sí mismos su producción, la cual es endosada por los agricultores vecinos. El déficit promedio en la producción se compensa con un pago que es directamente proporcional al déficit promedio en la producción del grupo y a la productividad individual del agricultor. Como resultado, los agricultores son compensados por el daño promedio (apoyo) y recompensados por la productividad individual (recompensa) (es decir, apoyo con recompensa SuR). El diseño del juego es tal que solamente la declaración honesta otorga la máxima ganancia. Los agricultores que declaren menos de lo dañado reciben menor pago porque la cantidad SuR es proporcional a su productividad auto declarada. Los agricultores que los endosan, por interés propio, previenen que haya declaraciones por encima de lo realmente producido. El sistema involucra varias situaciones de juego, cuyo resultado combinado es una estrategia estable basada en la honestidad y el trabajo duro. En dos aldeas ubicadas a lo largo de la frontera occidental de la Reserva de Tigres Tadoba Andhari en el centro de la India, pusimos a prueba este sistema con 75 agricultores durante seis temporadas de cultivo. Después de algunos intentos iniciales por hacer trampa, la honestidad prevaleció en todo el grupo. La productividad promedio de cultivos incrementó 2.5 veces su cantidad inicial a pesar del daño, esto debido al incremento en el esfuerzo de los agricultores. Además de la solución del conflicto con la fauna, el modelo ofrece una alternativa prometedora al aseguramiento de cultivos y una potencial revolución verde en el comportamiento agrícola.
Article impact statement: A novel scheme of payment for damage and reward for productivity helped resolve farmer–wildlife conflict.
We constructed a theoretical model of cost–benefit optimization for farmers who face continued economic loss due to crop raiding by wild herbivores, as well as for the wild herbivores that do so. ...Insights obtained from the model include: (i) In sustenance agriculture, a farmer needs to optimize net benefit rather than benefit-to-cost ratio, whereas herbivores need to optimize the benefit-to-cost ratio. (ii) It is imperative for a farmer to disinvest from agricultural inputs when threatened by depredation. (iii) Many mitigation measures that are highly successful on an experimental scale are most likely to fail when used on a mass scale. (iv) The effectiveness of mitigation measures such as fencing, trenching and culling will be non-monotonic, being counterproductive under certain conditions.
Blind fish: An eye opener Ojha, Akanksha; Watve, Milind
Evolution, medicine, and public health,
01/2018, Volume:
2018, Issue:
1
Journal Article
Peer reviewed
Open access
Lay Summary: Different species of vertebrates have conditions similar to human obesity, insulin resistance and type 2 diabetes. Increasing number of studies are now revealing that the causes and ...interrelationships between these states are substantially different in different species. Comparative physiology may turn out to be an eye opener for evolutionary theories of diabetes. Obesity induced insulin resistance is believed to be central to type 2 diabetes. Recent work on Mexican cavefish,
, has revealed a hyperglycemic phenotype similar to human type 2 diabetes but here insulin resistance is the cause of obesity rather than an effect. Instead of developing diabetic complications, the hyperglycemic fish lead a healthy and long life. In addition to fish, insulin resistance in hibernating bears, dolphins, horses, bonnet macaques and chimpanzees demonstrate that the relationship between diet, obesity, insulin sensitivity and diabetes is widely different in different species. Evolutionary hypotheses about type 2 diabetes should explain these differences.
Probability Ratio or Difference? Vidwans, Harshada; Kharate, Rohini; Watve, Milind
Resonance,
11/2021, Volume:
26, Issue:
11
Journal Article
Peer reviewed
In public health literature, the risk of death or disease associated with genetic, dietary, environmental, or behavioral factors is most commonly denoted by the odds ratio (OR), hazard ratio (HR), or ...risk ratio (RR). But how do people intuitively perceive risk? We conducted a small experiment in which respondents of different ages, sex, and education were asked to rank the risks associated with four different habits based on the incidence data of an imaginary deadly disease. Results showed that people judge risk by probability difference rather than probability ratio. Even individuals formally trained to use OR and HR as risk indicators preferred using probability differences over ratios to judge their own risk. This preliminary inquiry into intuitive statistical perception suggests that designing statistical indices based on people’s innate perception may be a better strategy than trying to educate people to understand the indices designed by expert statisticians.
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