Living characteristics of the free-radical ring-closing polymerization of diallyldimethylammonium chloride

In this communication we provide the most recent results on RAFT-mediated ring-closing polymerization of diallyldimethylammonium chloride (DADMAC). The polymerization was carried out in aqueous solution employing 2,2′-azobis(2-methylpropionamidine)-dihydrochloride as the free radical initiator and trithiocarbonate RAFT agent (2-{[(dodecylsulfanyl)carbonothioyl sulfanyl]}propanoic acid, DoPAT) as the controlling RAFT agent. The results show that – while the system is not as completely controlled as previously described – it is nevertheless possible to mediate the polymerization of DADMAC and impart some living characteristics onto the system. The initial study on the RAFT-mediated polymerization of DADMAC may have overestimated the degree of livingness within this reaction. However, it is possible – at low conversions – for some living characteristics to be observed, as the evolution of molecular weight with conversion is linear. In addition, polymers with a reasonably narrow polydispersity can be isolated.

Evolving genetic regulatory networks performing as stochastic switches

Recent studies have shown that small genetic regulatory networks (GRNs) can be evolved in silico displaying certain dynamics in the underlying mathematical model. It is expected that evolutionary approaches can help to gain a better understanding of biological design principles and assist in the engineering of genetic networks. To take the stochastic nature of GRNs into account, our evolutionary approach models GRNs as biochemical reaction networks based on simple enzyme kinetics and simulates them by using Gillespie’s stochastic simulation algorithm (SSA). We have already demonstrated the relevance of considering intrinsic stochasticity by evolving GRNs that show oscillatory dynamics in the SSA but not in the ODE regime. Here, we present and discuss first results in the evolution of GRNs performing as stochastic switches.

Quality of life of women with lower-limb lymphedema following gynecological cancer

Secondary lower-limb lymphedema can develop following treatment for gynecological cancers, and has debilitating effects on quality of life (QoL). Lymphedema can limit mobility and ability to perform daily activities, and have adverse effects on psychological and social wellbeing. When assessing the effect of lymphedema treatment methods, the focus is on change in clinically measured lymphedema status, rather than QoL outcomes. Considering that treatment for lymphedema involves a significant and ongoing commitment from patients, it is essential to determine whether the benefits to patients outweigh the burden associated with treatment. This article summarizes the results of studies assessing the impact of lower-limb lymphedema on QoL in women with gynecological cancer, evaluates their methodologies and discusses limitations and priorities for future research.

Improved sensorimotor adaptation after exhaustive exercise is accompanied by altered brain activity

Acute exercise has been shown to exhibit different effects on human sensorimotor behavior; however, the causes and mechanisms of the responses are often not clear. The primary aim of the present study was to determine the effects of incremental running until exhaustion on sensorimotor performance and adaptation in a tracking task. Subjects were randomly assigned to a running group (RG), a tracking group (TG), or a running followed by tracking group (RTG), with 10 subjects assigned to each group. Treadmill running velocity was initially set at 2.0 m s− 1, increasing by 0.5 m s− 1 every 5 min until exhaustion. Tracking consisted of 35 episodes (each 40 s) where the subjects' task was to track a visual target on a computer screen while the visual feedback was veridical (performance) or left-right reversed (adaptation). Resting electroencephalographic (EEG) activity was recorded before and after each experimental condition (running, tracking, rest). Tracking performance and the final amount of adaptation did not differ between groups. However, task adaptation was significantly faster in RTG compared to TG. In addition, increased alpha and beta power were observed following tracking in TG but not RTG although exhaustive running failed to induce significant changes in these frequency bands. Our results suggest that exhaustive running can facilitate adaptation processes in a manual tracking task. Attenuated cortical activation following tracking in the exercise condition was interpreted to indicate cortical efficiency and exercise-induced facilitation of selective central processes during actual task demands.

Comparing the cost-effectiveness of MRSA control strategies between ICU and non-ICU settings

Introduction / objectives Many strategies are used to control MRSA in hospitals. Only a few have been assessed in clinical trials and it is not obvious how findings should be generalised between settings. Uncertainty remains about which strategies represent the most appropriate use of scarce resources. We assess the cost-effectiveness of alternative MRSA screening and infection control strategies in England and Wales and discuss international relevance. Methods Models of MRSA transmission in ICUs and general medical (GM) wards were developed and used to evaluate different screening methods combined with decolonisation or isolation. Strategies were compared in terms of costs and health benefits (quality adjusted life years, QALYs). Different prevalences, proportions of high risk patients and ward sizes were investigated, and probabilistic sensitivity analyses (PSA) conducted. Results Decolonisation strategies were cost-saving in ICUs at a 5% admission prevalence, with admission and weekly PCR screening the most cost-effective (£3,929/QALY). In ICUs, screening and isolation reduced infection rates by ~10%. With admission prevalence ≤5%, targeting screening and isolation to high risk patients was optimal. In GM wards decolonisation and isolation strategies, though able to reduce MRSA infection rates up to ~50%, were not cost-effective. Conclusion The largest reductions in MRSA infection were achieved by screening and decolonisation strategies, and were cost-effective in ICU settings. In comparison, there is limited potential for screening and control strategies to be cost-effective in GM wards due to lower infection and mortality rates.

Safety, feasibility and effects of an individualised walking intervention for women undergoing chemotherapy for ovarian cancer : a pilot study

Background: Exercise interventions during adjuvant cancer therapy have been shown to increase functional capacity, relieve fatigue and distress and may assist rates of chemotherapy completion. These studies have been limited to breast, gastric and mixed cancer groups and it is not yet known if a similar intervention is even feasible among women with ovarian cancer. We aimed to assess safety, feasibility and potential effect of a walking intervention in women undergoing chemotherapy for ovarian cancer. Methods: Women newly diagnosed with ovarian cancer were recruited to participate in an individualised walking intervention throughout chemotherapy and were assessed pre-and post-intervention. Feasibility measures included session adherence, compliance with exercise physiologist prescribed walking targets and self-reported program acceptability. Changes in objective physical functioning (6 minute walk test), self-reported distress (Hospital Anxiety and Depression Scale), symptoms (Memorial Symptom Assessment Scale - Physical) and quality of life (Functional Assessment of Cancer Therapy - Ovarian) were calculated, and chemotherapy completion and adverse intervention effects recorded. Results: Seventeen women were enrolled (63% recruitment rate). Mean age was 60 years (SD = 8 years), 88% were diagnosed with FIGO stage III or IV disease, 14 women underwent adjuvant and three neo-adjuvant chemotherapy. On average, women adhered to > 80% of their intervention sessions and complied with 76% of their walking targets, with the majority walking four days a week at moderate intensity for 30 minutes per session. Meaningful improvements were found in physical functioning, physical symptoms, physical well-being and ovarian cancerspecific quality of life. Most women (76%) completed ≥85% of their planned chemotherapy dose. There were no withdrawals or serious adverse events and all women reported the program as being helpful. Conclusions: These positive preliminary results suggest that this walking intervention for women receiving chemotherapy for ovarian cancer is safe, feasible and acceptable and could be used in development of future work. Trial registration: ACTRN12609000252213

Evaluation of novel Streptococcus pyogenes vaccine candidates incorporating multiple conserved sequences from the C-repeat region of the M-protein

A major challenge for Streptococcus pyogenes vaccine development is the identification of epitopes that confer protection from infection by multiple S. pyogenes M-types. Here we have identified and characterised the distribution of common variant sequences from individual repeat units of the C-repeat region (CRR) of M-proteins representing 77 different M-types. Three polyvalent fusion vaccine candidates (SV1, SV2 and SV3) incorporating the most common variants were subsequently expressed and purified, and demonstrated to be alpha-helical by Circular Dichroism (CD), a secondary conformational characteristic of the CRR in the M-protein. Antibodies raised against each of these constructs recognise M-proteins that vary in their CRR, and bind to the surface of multiple S. pyogenes isolates. Antibodies raised against SV1, containing five variant sequences, also kill heterologous S. pyogenes isolates in in vitro bactericidal assays. Further structural characterisation of this construct demonstrated the conformation of SV1 was stable at different pHs, and thermal unfolding of SV1 a reversible process. Our findings demonstrate that linkage of multiple variant sequences into a single recombinant construct overcomes the need to embed the variant sequences in foreign helix promoting flanking sequences for conformational stability, and demonstrates the viability of the polyvalent candidates as global S. pyogenes vaccine candidates.

Project-based organization as adaptation to risk and opportunity in small firms

Recent years have seen a rapid increase in SMEs working collaboratively in inter-organizational projects. But what drives the emergence of such projects, and what types of industries breed them the most? To address these questions, this paper extends the long running literature on the firm and industry antecedents of new venturing and alliance formation to the domain of project-based organization by SMEs. Based on survey data collected among 1,725 small and medium sized organizations and longitudinal industry data, we find an overall pattern that indicates that IOPV participation is primarily determined by a focal SME’s scope of innovative activities, and the munificence, dynamism and complexity of its environment. Unexpectedly, these variables have different effects on whether SMEs are likely to engage in IOPVs, compared to with how many there are in their portfolio at a time. Implications for theory development are discussed.