How Organizations Engage with External Complexity: A Political Action Perspective

This paper offers a new insight into how organizations engage with external complexity. It applies a political action perspective that draws attention to the hitherto neglected question of how the relative power organizational leaders enjoy within their environments is significant for the actions they can take on behalf of their organizations when faced with external complexity. It identifies cognitive and relational complexity as two dimensions of the environment with which organizations have to engage. It proposes three modes whereby organizations may engage with environmental complexity that are conditioned by an organization's power within its environment. It also considers the intention associated with each mode, as well as the implications of these modes of engagement for how an organization can learn about its environment and for the use of rationality and intuition in its strategic decision-making. The closing discussion considers how this analysis integrates complexity and political action perspectives in a way that contributes to theoretical development and provides the basis for a dynamic political co-evolutionary approach. © The Author(s) 2011.

Thalidomide for managing cancer cachexia [review paper]

Cancer cachexia is a multidimensional syndrome characterised by wasting, loss of weight, loss of appetite, metabolic alterations, fatigue and reduced performance status. A significant number of patients with advanced cancer develop cachexia before death. There is no identified optimum treatment for cancer cachexia. While the exact mechanism of the action of thalidomide is unclear, it is known to have immunomodulatory and anti-inflammatory properties, which are thought to help reduce the weight loss associated with cachexia. Preliminary studies of thalidomide have demonstrated encouraging results. This review aimed to (1) evaluate the effectiveness of thalidomide, and (2) identify and assess adverse effects from thalidomide for cancer cachexia. Electronic searches were undertaken in CENTRAL, MEDLINE, EMBASE, Web of Science and CINAHL (from inception to April 2011). Reference lists from reviewed articles, trial registers, relevant conference documents and thalidomide manufacturers identified additional literature. This review included randomised controlled trials (RCTs) and non-RCTs. Participants were adults diagnosed with advanced or incurable cancer and weight loss or a clinical diagnosis of cachexia who were administered thalidomide. All titles and abstracts retrieved by electronic searching were downloaded to a reference management database. Duplicates were removed and the remaining citations were read by two review authors and checked for eligibility. Studies that were deemed ineligible for inclusion had clear reasons for exclusion documented. Data were extracted independently by two review authors for all eligible studies. While a meta-analysis was planned for this review, this was not possible due to the small number of studies included and high heterogeneity among them. Thus a narrative synthesis of the findings is presented. The literature search revealed a dearth of large, well conducted trials in this area. This has hindered the review authors' ability to make an informed decision about thalidomide for the management of cancer cachexia. At present, there is insufficient evidence to refute or support the use of thalidomide for the management of cachexia in advanced cancer patients. The review authors cannot confirm or refute previous literature on the use of thalidomide for patients with advanced cancer who have cachexia and there is inadequate evidence to recommend it for clinical practice. Additional, well conducted, large RCTs are needed to test thalidomide both singularly and in combination with other treatment modalities to ascertain its true benefit, if any, for this population. Furthermore, one study (out of the three reviewed) highlighted that thalidomide was poorly tolerated and its use needs to be explored further in light of the frailty of this population

Potentiation of triclabendazole action in vivo against a triclabendazole-resistant isolate of Fasciola hepatica following its co-administration with the metabolic inhibitor, ketoconazole

An in vivo study in the laboratory rat model has been carried out to monitor morphological changes in adult Fasciola hepatica over a 4-day period resulting from co-treatment with triclabendazole (TCBZ) and ketoconazole (KTZ), a cytochrome P450 inhibitor. Rats were infected with the triclabendazole-resistant Oberon isolate of F. hepatica, dosed orally with triclabendazole at a dosage of 10mg/kg live weight and ketoconazole at a dosage of 10mg/kg live weight. Flukes were recovered at 24, 48, 72 and 96 h post-treatment (p.t.) and changes to fluke ultrastructure were assessed using transmission electron microscopy (TEM). Results showed an increase in the severity of changes to the fluke ultrastructure with time p.t. Swelling of the basal infolds and the associated mucopolysaccharide masses became more severe with time. Golgi complexes, if present, were greatly reduced in size and number by 96 h p.t., and sub-tegumental flooding was seen from the 72 h time-period onwards. Some sloughing of the tegumental covering over the spines was observed at 96 h p.t. The results demonstrated that the Oberon isolate is more sensitive to TCBZ action in the presence of KTZ than to TCBZ alone, reinforcing the idea that altered drug metabolism is involved in the resistance mechanism. Moreover, they support the concept that TCBZ+inhibitor combinations (aimed at altering drug pharmacokinetics and potentiating the action of TCBZ) could be used in the treatment of TCBZ-R populations of F. hepatica.