operational synergy meaning

For example, several antiobesity drugs combining 2 or even 3 receptor domains with the same molecule are currently under development (1–3). Greenway FL, Whitehouse MJ, Guttadauria M, et al. These approaches seem overly simplistic in that they fail to capture the biological complexity underlying endocrine function and, therefore, may divert attention from it. Synergies related to operational metrics are referred to as operating synergies. Operational synergies are not synchronized with the customer/market needs of the combined entities, often requiring supply chain “rework” or savings “erosion.” 3. Estrogen signaling is by no means unique in these respects, and neurotransmitter systems as well as other endocrine systems display similar dynamisms. The search for cytotoxic synergy between anticancer agents: a case of Dorothy and the ruby slippers? 0000006125 00000 n 0000036950 00000 n �(�4E���v ��Ɩ�R��"z�@������8�'��| �w`W� ����$��h������?��9 g�#�hV�w�4`E�J���QMqװ�Ŋ,�*�w(oW��t�.BF�������e����X�s��!�Yޗ��A#,�7�P�D�-�r3R�Ud�͇1��m�l�. gies 1. As a recent critical review by Geary (4) indicates, the classical additivity metrics are neither straightforward nor clearly valid. x��]{�^�U��x���]?�ױ׾���>�{w����IUU%�+Z\'�v� �6T�A*�"QT"U*���"��T�����DE-�P%h@r��RJUJ9g�3�����k����kT�ν�8sΙ3����gVrQ0��y8q����-y�w��5+�Ӯ��8�S���\���Z��7����Hq�����#�W��We�/�e�8w������@@�����?��U��}>q����k���ð���Џ�R��S������*9���7��MQZ���/��}�voO˒�b�:Y A final example relates to temporal dynamics. . This comment briefly describes both problems with existing approaches to supra-additive synergy and an alternative approach. %PDF-1.3 The analysis of dose additivity is somewhat more complex, but equally problematic. 0000029427 00000 n 0000018987 00000 n 0000045494 00000 n 0000044427 00000 n 0000029805 00000 n 0000036454 00000 n But do similar synergies exist in endocrinology and physiology, in which 2 or more biological agents, often with very different molecular mechanisms and temporal dynamics, can affect specific outcomes or responses? If the relevant part of the dose-response curve is accelerating, doubling the dose will result in a much higher than expected response (Figure 1), and if the curve is decelerating, doubling the dose will result in a lower than expected response. Bhide (1993) examined the motives behind 77 acquisitions in 1985 and 1986, and reported that operating synergy was the primary motive in one-third of these takeovers. An example of Loewe transforms leading to such indeterminate additivity is shown in Figure 2. For example, a company may acquire a similar firm, allowing it to expand its product offering and, as a result, increase its sales and revenues. As Geary points out, this form of synergy is now recognized as sufficient for Food and Drug Administration approval of drug combinations. Response additivity can produce erroneous predictions for drugs or biological agents with curvilinear dose-effect relationships. Corporate synergy refers to a financial benefit that a corporation expects to realize when it merges with or acquires another corporation. In fact, due to the concave-up shape of the dose-effect curve in that range, the observed effect of dose 4 is 5.3, or more than twice as large as predicted. This characteristic is captured in a number of classical endocrine concepts, including integration, coactivation and regulation, redundancy, hierarchy, and synergy. %�쏢 This could not have been accomplished had the two firms remained independant. One set of problems concerns the applicability of the concept to complex integrative biological systems. <> A number of studies examine whether synergy exists and, if … His message echoes the conclusions already reached half a century ago by the German pharmacologist Loewe (19) and other scientists since then (20, 21). Researchers interested in neural and endocrine interactions should be aware of this evolution of synergy theory. 0000021093 00000 n Rather, exogenous estradiol will interact with a dynamic endocrine background, the effects of which will be difficult to distinguish from synergy per se. This work was supported by National Institutes of Health Grant DK047348. 0000025382 00000 n In addition, as Geary shows, many variations of dose additivity use different methods to generate additive solutions, but still use the linear isobologram to test whether they are synergistic or not. 0000001161 00000 n Most dose-additivity approaches use what is called “Loewe additivity” to generate additive predictions. Day JW, Ottaway N, Patterson JT, et al. The interaction of two or more agents or forces so that their combined effect is greater than the sum of their individual effects. 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Dose additivity analyses are usually done by plotting all the dose combinations that should lead to a particular specified additive effect on a graph the x-axis of which is the dose of the first hormone and the y-axis is the dose of the other. 0000001091 00000 n Hans-Rudolf Berthoud, Synergy: A Concept in Search of a Definition, Endocrinology, Volume 154, Issue 11, 1 November 2013, Pages 3974–3977, https://doi.org/10.1210/en.2013-1420. Is a slightly subadditive interaction less interesting than a supra-additive interaction, and does it necessarily result from a qualitatively different mechanism? Another problem with isobolograms occurs if the maximum effect of one hormone exceeds that of the other; in this case, the Loewe transformation cannot be done for effects exceeding the lower maximum. Furthermore, an adaptation of the method is to identify drug combinations that lead to the largest difference between therapeutically desirable effects and undesirable side effects. This type of synergy is a nearly ubiquitous feature of corporate mergers and acquisitions and is a negotiating point between the buyer and seller that impacts the final price both parties agree to. Operational and Conceptual Definitions • Conceptual definition –A dictionary definition; the common meaning of a word Hunger A strong desire or need for food Hungry:Experiencing a desire or need for food. Synergy: A Concept in Search of a Definition Hans-Rudolf Berthoud 1 Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana … Synergy is often one of the goals of a merger or acquisition. Receptor multiplicity and dynamism lead to similar problems. However, this is not the case when the dose-response relationship is nonlinear. These considerations question whether supra-additive synergy is a helpful concept in the analysis of endocrine interactions. Introduction According to Basmah and Rahatullah (2014), mergers happen when organizations verify that consolidating their business operations with an alternate venture is of profit. 17). Closer inspection suggests that this is not the case. 0000020256 00000 n Completion thyroidectomy-Have we made appropriate decisions? In a nutshell, after careful evaluation of the theoretical and mathematical bases and combing through more than 170 references, many in this journal, he argues persuasively that almost all supra-additive synergy analyses lack validity; the emperor is not wearing clothes! This is another characteristic endocrine effect that is not captured by synergy models designed to describe the simultaneous application of different agents. 7–9]). Divestopedia explains Operating Synergy Operating synergies can arise from the following: Adapted from Geary (4) with permission. For example, a company may acquire a similar firm, allowing it to expand its product offering and, as a result, increase its sales and revenues. Therefore, the wisest choice might be to simply report interactions for what they are worth, changes in effect, and not hide behind “voodoo-mathematics” as justification to make additive predictions and claim supra-additive synergy. Synergy can be reflected in increased revenues and/or lower expenses. B, Note that different additive predictions are generated for combination of doses 1 of A plus 1 of B when the A-equivalent dose of B is used (full lines; 1.3 units of A yields effect of 5.2) than when the B-equivalent dose of A is used (dashed lines; 4.2 units of B yields effect of 6.3) is used. The problems, in Geary's view, are so intractable that supra-additive synergy should be abandoned in favor of a simpler approach that does not rely on additive predictions but rather rests on defining synergy as simply an increase in effect. 0000029128 00000 n The food synergy hypothesis implies that it is relevant to the eater how the food survives its own life cycle. It seems logical that interfering simultaneously with several interacting mechanisms would have a larger effect on the outcome measure than targeting just one. A clear example of superadditive synergy can be found in catalytic chemistry, when a very small amount (dose) of a catalyst that by itself cannot produce an effect drastically amplifies a chemical reaction.

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