The small quinolone derived compound HT61 enhances the effect of tobramycin against Pseudomonas aeruginosa in vitro and in vivo.

HT61 is a small quinolone-derived compound previously demonstrated to exhibit bactericidal activity against gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). When combined with the classical antibiotics and antiseptics neomycin, gentamicin, mupirocin and chlorhexidine, HT61 demonstrated synergistic bactericidal activity against both MSSA and MRSA infections in vitro. In this study, we investigated the individual antimicrobial activity of HT61 alongside its capability to increase the efficacy of tobramycin against both a tobramycin sensitive laboratory reference strain (PAO1) and tobramycin resistant clinical isolates (RP73, NN2) of the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa). Using broth microdilution methods, the MICs of HT61 against all strains were assessed, as well as the effect of HT61 in combination with tobramycin using both the chequerboard method and bacterial time-kill assays. A murine model of pulmonary infection was also used to evaluate the combination therapy of tobramycin and HT61 in vivo. In these studies, we demonstrated significant synergism between HT61 and Tobramycin against the tobramycin resistant P. aeruginosa strains RP73 and NN2, whilst an additive/intermediate effect was observed for P. aeruginosa strain PA01 which was further confirmed using bacterial time kill analysis. In addition, the enhancement of tobramycin by HT61 was also evident in in vitro assays of biofilm eradication. Finally, in vivo studies revealed analogous effects to those observed in vitro with HT61 when administered in combination with tobramycin against each of the three P. aeruginosa strains at the highest tested dose (10 mg/kg)

Women's experiences of postnatal distress: a qualitative study

Women can experience a range of psychological problems after birth, including anxiety, depression and adjustment disorders. However, research has predominantly focused on depression. Qualitative work on women's experiences of postnatal mental health problems has sampled women within particular diagnostic categories so not looked at the range of potential psychological problems. The aims of this study were to explore how women experienced and made sense of the range of emotional distress states in the first postnatal year

Examining the effects of adjuvant chemotherapy on cognition and the impact of any cognitive impairment on quality of life in colorectal cancer patients: study protocol

Background: Research suggests that chemotherapy can cause deficits in both patients’ objectively measured and self-reported cognitive abilities which can in turn affect their quality of life (QoL). The majority of research studies have used post-treatment retrospective designs or have not included a control group in prospective cohorts. This has limited the conclusions that can be drawn from the results. There have also been a disproportionate number of studies focussed on women with breast cancer, which has limited the generalisability of the results to other cancer populations. Aim: This study aims to identify the extent and impact of chemotherapy-induced cognitive decline in colorectal cancer patients. Possible associations with poorer QoL will also be explored. Design: This will be a longitudinal controlled cohort study. Questionnaires measuring subjective cognitive functioning, QoL, fatigue and mood, and neuropsychological assessments of objective cognitive function will be collected pre-, mid- and post- chemotherapy treatment from a consecutive sample of 78 colorectal cancer patients from five London NHS Trusts. A further 78 colorectal cancer surgery only patients will be assessed at equivalent time points; this will allow the researchers to compare the results of patients undergoing surgery, but not chemotherapy against those receiving both treatments. Pre- and post-chemotherapy difference scores will be calculated to detect subtle changes in cognitive function as measured by the objective neuropsychological assessments and the self-reported questionnaires. A standardised zscore will be computed for every patient on each neuropsychological test, and for each test at each time point. The post-chemotherapy score will then be subtracted from the pre-chemotherapy score to produce a relative difference score for each patient. ANCOVA will be used to compare mean difference z-scores between the chemotherapy and surgery-only groups while controlling for the effects of gender, age, depression, anxiety, fatigue and education. Discussion: The result from this study will indicate whether a decline in cognitive functioning can be attributed to chemotherapy or to disease, surgical or some other confounding factor. Identification of risk factors for cognitive deficits may be used to inform targeted interventions, in order to improve QoL and help patients’ cope

Early intensive hand rehabilitation after spinal cord injury ("Hands On"): a protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Loss of hand function is one of the most devastating consequences of spinal cord injury. Intensive hand training provided on an instrumented exercise workstation in conjunction with functional electrical stimulation may enhance neural recovery and hand function. The aim of this trial is to compare usual care with an 8-week program of intensive hand training and functional electrical stimulation.</p> <p>Methods/design</p> <p>A multicentre randomised controlled trial will be undertaken. Seventy-eight participants with recent tetraplegia (C2 to T1 motor complete or incomplete) undergoing inpatient rehabilitation will be recruited from seven spinal cord injury units in Australia and New Zealand and will be randomised to a control or experimental group. Control participants will receive usual care. Experimental participants will receive usual care and an 8-week program of intensive unilateral hand training using an instrumented exercise workstation and functional electrical stimulation. Participants will drive the functional electrical stimulation of their target hands via a behind-the-ear bluetooth device, which is sensitive to tooth clicks. The bluetooth device will enable the use of various manipulanda to practice functional activities embedded within computer-based games and activities. Training will be provided for one hour, 5 days per week, during the 8-week intervention period. The primary outcome is the Action Research Arm Test. Secondary outcomes include measurements of strength, sensation, function, quality of life and cost effectiveness. All outcomes will be taken at baseline, 8 weeks, 6 months and 12 months by assessors blinded to group allocation. Recruitment commenced in December 2009.</p> <p>Discussion</p> <p>The results of this trial will determine the effectiveness of an 8-week program of intensive hand training with functional electrical stimulation.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01086930">NCT01086930</a> (12^thMarch 2010)</p> <p><a href="http://www.anzctr.org.au/ACTRN12609000695202.aspx">ACTRN12609000695202</a> (12^thAugust 2009)</p

Inflammatory cytokines and aromatase inhibitor-associated musculoskeletal syndrome: a case–control study

The aromatase inhibitor (AI)-associated musculoskeletal syndrome (AIMSS) occurs in approximately 50% of AI-treated patients. Inflammatory mediators are associated with oestrogen signalling and may change with oestrogen depletion. We hypothesised that AIMSS may be associated with changes in circulating inflammatory markers

Crown Plasticity and Competition for Canopy Space: A New Spatially Implicit Model Parameterized for 250 North American Tree Species

BACKGROUND: Canopy structure, which can be defined as the sum of the sizes, shapes and relative placements of the tree crowns in a forest stand, is central to all aspects of forest ecology. But there is no accepted method for deriving canopy structure from the sizes, species and biomechanical properties of the individual trees in a stand. Any such method must capture the fact that trees are highly plastic in their growth, forming tessellating crown shapes that fill all or most of the canopy space. METHODOLOGY/PRINCIPAL FINDINGS: We introduce a new, simple and rapidly-implemented model--the Ideal Tree Distribution, ITD--with tree form (height allometry and crown shape), growth plasticity, and space-filling, at its core. The ITD predicts the canopy status (in or out of canopy), crown depth, and total and exposed crown area of the trees in a stand, given their species, sizes and potential crown shapes. We use maximum likelihood methods, in conjunction with data from over 100,000 trees taken from forests across the coterminous US, to estimate ITD model parameters for 250 North American tree species. With only two free parameters per species--one aggregate parameter to describe crown shape, and one parameter to set the so-called depth bias--the model captures between-species patterns in average canopy status, crown radius, and crown depth, and within-species means of these metrics vs stem diameter. The model also predicts much of the variation in these metrics for a tree of a given species and size, resulting solely from deterministic responses to variation in stand structure. CONCLUSIONS/SIGNIFICANCE: This new model, with parameters for US tree species, opens up new possibilities for understanding and modeling forest dynamics at local and regional scales, and may provide a new way to interpret remote sensing data of forest canopies, including LIDAR and aerial photography

Growth Strategies of Tropical Tree Species: Disentangling Light and Size Effects

An understanding of the drivers of tree growth at the species level is required to predict likely changes of carbon stocks and biodiversity when environmental conditions change. Especially in species-rich tropical forests, it is largely unknown how species differ in their response of growth to resource availability and individual size. We use a hierarchical Bayesian approach to quantify the impact of light availability and tree diameter on growth of 274 woody species in a 50-ha long-term forest census plot in Barro Colorado Island, Panama. Light reaching each individual tree was estimated from yearly vertical censuses of canopy density. The hierarchical Bayesian approach allowed accounting for different sources of error, such as negative growth observations, and including rare species correctly weighted by their abundance. All species grew faster at higher light. Exponents of a power function relating growth to light were mostly between 0 and 1. This indicates that nearly all species exhibit a decelerating increase of growth with light. In contrast, estimated growth rates at standardized conditions (5 cm dbh, 5% light) varied over a 9-fold range and reflect strong growth-strategy differentiation between the species. As a consequence, growth rankings of the species at low (2%) and high light (20%) were highly correlated. Rare species tended to grow faster and showed a greater sensitivity to light than abundant species. Overall, tree size was less important for growth than light and about half the species were predicted to grow faster in diameter when bigger or smaller, respectively. Together light availability and tree diameter only explained on average 12% of the variation in growth rates. Thus, other factors such as soil characteristics, herbivory, or pathogens may contribute considerably to shaping tree growth in the tropics

Magnetosphere and Plasma Science with the Jupiter Icy Moons Explorer

The Jupiter Icy Moons Explorer (JUICE) is a European Space Agency mission to explore Jupiter and its three icy Galilean moons: Europa, Ganymede, and Callisto. Numerous JUICE investigations concern the magnetised space environments containing low-density populations of charged particles that surround each of these bodies. In the case of both Jupiter and Ganymede, the magnetic field generated internally produces a surrounding volume of space known as a magnetosphere. All these regions are natural laboratories where we can test and further our understanding of how such systems work, and improved knowledge of the environments around the moons of interest is important for probing sub-surface oceans that may be habitable. Here we review the magnetosphere and plasma science that will be enabled by JUICE from arrival at Jupiter in July 2031. We focus on the specific topics where the mission will push forward the boundaries of our understanding through a combination of the spacecraft trajectory through the system and the measurements that will be made by its suite of scientific instruments. Advances during the initial orbits around Jupiter will include construction of a comprehensive picture of the poorly understood region of Jupiter’s magnetosphere where rigid plasma rotation with the planet breaks down, and new perspectives on how Jupiter’s magnetosphere interacts with both Europa and Callisto. The later orbits around Ganymede will dramatically improve knowledge of this moon’s smaller magnetosphere embedded within the larger magnetosphere of Jupiter. We conclude by outlining the high-level operational strategy that will support this broad science return

Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management

Aromatase inhibitors are widely used as adjuvant therapy in postmenopausal women with hormone receptor-positive breast cancer. While the agents are associated with slightly improved survival outcomes when compared to tamoxifen alone, bone and musculoskeletal side effects are substantial and often lead to discontinuation of therapy. Ideally, the symptoms should be prevented or adequately treated. This review will focus on bone and musculoskeletal side effects of aromatase inhibitors, including osteoporosis, fractures, and arthralgias. Recent advances have been made in identifying potential mechanisms underlying these effects. Adequate management of symptoms may enhance patient adherence to therapy, thereby improving breast cancer-related outcomes

Update on the use of aromatase inhibitors in early-stage breast cancer

Aromatase inhibitors are currently included in the 'optimal' management of early-stage breast cancer. Uncertainty remains, however, as to the most appropriate treatment strategy, particularly for newly diagnosed women as they seek to trade off the cost, toxicities and efficacy of the treatment options. Recent publications provide conflicting advice on the role of aromatase inhibitors in the treatment of postmenopausal patients with early-stage hormone receptor-positive breast cancer. This review provides updates on the clinical trials of aromatase inhibitors in early breast cancer and tries to provide practical clinical guidance on their optimal use