Implementing a system of quality-of-life diagnosis and therapy for breast cancer patients: results of an exploratory trial as a prerequisite for a subsequent RCT

A system for quality-of-life diagnosis and therapy (QoL system) was implemented for breast cancer patients. The system fulfilled the criteria for complex interventions (Medical Research Council). Following theory and modeling, this study contains the exploratory trial as a next step before the randomised clinical trial (RCT) answering three questions: (1) Are there differences between implementation sample and general population? (2) Which amount and type of disagreement exist between patient and coordinating practitioners (CPs) in assessed global QoL? (3) Are there empirical reasons for a cutoff of 50 points discriminating between healthy and diseased QoL? Implementation was successful: 74% of CPs worked along the care pathway. However, CPs showed preferences for selecting patients with lower age and UICC prognostic staging. Patients and CPs disagreed considerably in values of global QoL, despite education in QoL assessment by outreach visits, opinion leaders and CME: Zero values of QoL were only expressed by patients. Finally, the cutoff of 50 points was supported by the relationship between QoL in single items and global QoL: no patients with values above 50 dropped global QoL below 50, but values below 50 and especially at 0 points in single items, induced a dramatic fall of global QoL down to below 50. The exploratory trial was important for defining the complex intervention in the definitive RCT: control for age and prognostic stage grading, support for a QoL unit combining patient's and CP's assessment of QoL and support for the 50-point cutoff criterion between healthy and diseased QoL

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

Human Analogue Safe Haven Effect of the Owner : Behavioural and Heart Rate Response to Stressful Social Stimuli in Dogs

The secure base and safe haven effects of the attachment figure are central features of the human attachment theory. Recently, conclusive evidence for human analogue attachment behaviours in dogs has been provided, however, the owner’s security-providing role in danger has not been directly supported. We investigated the relationship between the behavioural and cardiac response in dogs (N = 30) while being approached by a threatening stranger in separation vs. in the presence of the owner, presented in a balanced order. Non-invasive telemetric measures of heart rate (HR) and heart rate variability (HRV) data during the threatening approaches was compared to periods before and after the encounters. Dogs that showed distress vocalisation during separation (N = 18) and that growled or barked at the stranger during the threatening approach (N = 17) were defined as behaviourally reactive in the given situation. While characteristic stress vocalisations were emitted during separations, the absence of the owner did not have an effect on dogs’ mean HR, but significantly increased the HRV. The threatening approach increased dogs’ mean HR, with a parallel decrease in the HRV, particularly in dogs that were behaviourally reactive to the encounter. Importantly, the HR increase was significantly less pronounced when dogs faced the stranger in the presence of the owner. Moreover, the test order, whether the dog encountered the stranger first with or without its owner, also proved important: HR increase associated with the encounter in separation seemed to be attenuated in dogs that faced the stranger first in the presence of their owner. We provided evidence for human analogue safe haven effect of the owner in a potentially dangerous situation. Similarly to parents of infants, owners can provide a buffer against stress in dogs, which can even reduce the effect of a subsequent encounter with the same threatening stimuli later when the owner is not present