Targeting of anionic membrane species by lanthanide(III) complexes: towards improved MRI contrast agents for apoptosis

No abstract available

Health-related quality of life and physical recovery after a critical illness: a multi-centre randomised controlled trial of a home-based physical rehabilitation program

Introduction: Significant physical sequelae exist for some survivors of a critical illness. There are, however, few studies that have examined specific interventions to improve their recovery, and none have tested a home-based physical rehabilitation program incorporating trainer visits to participants' homes. This study was designed to test the effect of an individualised eight-week home-based physical rehabilitation program on recovery. Methods: A multi-centre randomised controlled trial design was used. Adult intensive care patients (length of stay of at least 48 hours and mechanically ventilated for 24 hours or more) were recruited from 12 Australian hospitals between 2005 and 2008. Graded, individualised endurance and strength training intervention was prescribed over eight weeks, with three physical trainer home visits, four follow-up phone calls, and supported by a printed exercise manual. The main outcome measures were blinded assessments of physical function; SF-36 physical function (PF) scale and six-minute walk test (6MWT), and health-related quality of life (SF-36) conducted at 1, 8 and 26 weeks after hospital discharge. Results: Of the 195 participants randomised, 183, 173 and 161 completed the 1, 8 and 26 weeks assessments, respectively. Study groups were similar at Week 1 post-hospital; for the intervention and control groups respectively, mean norm-based PF scores were 27 and 29 and the 6MWT distance was 291 and 324 metres. Both groups experienced significant and clinically important improvements in PF scores and 6MWT distance at 8 weeks, which persisted at 26 weeks. Mixed model analysis showed no significant group effects (P = 0.84) or group by time interactions (P = 0.68) for PF. Similar results were found for 6MWT and the SF-36 summary scores. Conclusions: This individualised eight-week home-based physical rehabilitation program did not increase the underlying rate of recovery in this sample, with both groups of critically ill survivors improving their physical function over the 26 weeks of follow-up. Further research should explore improving effectiveness of the intervention by increasing exercise intensity and frequency, and identifying individuals who would benefit most from this intervention. Trial registration: Australia and New Zealand Clinical Trials Register ACTRN1260500016667

PEGylation improves the receptor-mediated transfection efficiency of peptide-targeted, self-assembling, anionic nanocomplexes

Non-viral vector formulations comprise typically complexes of nucleic acids with cationic polymers or lipids. However, for in vivo applications cationic formulations suffer from problems of poor tissue penetration, non-specific binding to cells, interaction with serum proteins and cell adhesion molecules and can lead to inflammatory responses. Anionic formulations may provide a solution to these problems but they have not been developed to the same extent as cationic formulations due to difficulties of nucleic acid packaging and poor transfection efficiency. We have developed novel PEGylated, anionic nanocomplexes containing cationic targeting peptides that act as a bridge between PEGylated anionic liposomes and plasmid DNA. At optimized ratios, the components self-assemble into anionic nanocomplexes with a high packaging efficiency of plasmid DNA. Anionic PEGylated nanocomplexes were resistant to aggregation in serum and transfected cells with a far higher degree of receptor-targeted specificity than their homologous non-PEGylated anionic and cationic counterparts. Gadolinium-labeled, anionic nanoparticles, administered directly to the brain by convection-enhanced delivery displayed improved tissue penetration and dispersal as well as more widespread cellular transfection than cationic formulations. Anionic PEGylated nanocomplexes have widespread potential for in vivo gene therapy due to their targeted transfection efficiency and ability to penetrate tissues

Repeatability of the Six-Minute Walk Test and Relation to Physical Function in Survivors of a Critical Illness

Background: The Six-Minute Walk Test (6MWT) is widely used as an outcome measure in exercise rehabilitation. However, the repeatability of the 6MWT performed at home in survivors of a critical illness has not been evaluated. Objective: The purpose of this study was to evaluate, in survivors of a critical illness: (1) the repeatability of the 6MWT performed at home, (2) the effect on estimates of change in functional exercise capacity if only one 6MWT was performed at follow-up assessments, and (3) the relationship between the physical functioning (PF) score of the 36-Item Short-Form Health Survey questionnaire (SF-36) and the 6MWT. Design: Repeated measures of the 6MWT and SF-36 were obtained. Methods: Eligible participants had an intensive care unit (ICU) length of stay of ≥48 hours and were mechanically ventilated for ≥24 hours. Two 6MWTs and the SF-36 were conducted in participants' homes at weeks 1, 8, and 26 after hospital discharge. Results: One hundred seventy-three participants completed the study. The participants had a mean age of 57 years (SD=16), a mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score on admission of 19 (SD=10), a mean ICU length of stay of 9 days (SD=8), and a mean mechanical ventilation time of 140 hours (SD=137). Of the 173 participants, 110 performed two 6MWTs at weeks 1, 8, and 26. There were significant mean increases in 6-minute walk distance in the second test of 15 m (P<.0001) at week 1, 13 m (P<.0001) at week 8, and 9 m (P=.04) at week 26. If only one 6MWT was performed at weeks 8 and 26, the estimate of change in 6-minute walk distance from week 1 was 19 m less (P<.001) at both weeks 8 and 26. There was a moderate to strong correlation between SF-36 PF score and 6-minute walk distance at each assessment (week 1: r=.62, P<.001; week 8: r=.55, P<.001; and week 26: r=.47, P<.001).Limitations: Some study participants were unable to perform a second 6MWT, and these participants may have differed in important aspects of function compared with those individuals who completed two 6MWTs. Conclusions: In survivors of a critical illness, the 6MWT in the home environment should be performed twice at each assessment to give an accurate reflection of change in exercise capacity over time. The SF-36 PF score was a strong indicator of 6-minute walk distance in early recovery from a critical illness

Measurement of the W-boson helicity in top-quark decays from t(t)over-bar production in lepton plus jets events in pp collisions at √s=7 TeV

This is the pre-print version of the final published article that can be accessed at the link below.The W-boson helicity fractions in top-quark decays are measured with tt events in the lepton+jets final state, using proton-proton collisions at a centre-of-mass energy of 7 TeV, collected in 2011 with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 5.0 fb-1. The measured fractions of longitudinal, left-, and right-handed helicity are F0 = 0.682 0.030 (stat.) 0.033 (syst.), FL = 0.310 0.022 (stat.) 0.022 (syst.), and FR = 0.008 0.012 (stat.) 0.014 (syst.), consistent with the standard model predictions. The measured fractions are used to probe the existence of anomalous Wtb couplings. Exclusion limits on the real components of the anomalous couplings gL, gR are also derived

Search for the standard model Higgs boson produced in association with a top-quark pair in pp collisions at the LHC

This is the pre-print version of the final published paper that is available from the link below.A search for the standard model Higgs boson produced in association with a top-quark pair is presented using data samples corresponding to an integrated luminosity of 5.0 fb-1 (5.1 fb-1) collected in pp collisions at the center-of-mass energy of 7TeV (8TeV). Events are considered where the top-quark pair decays to either one lepton+jets (tt→lvqq’bb) or dileptons [tt→l(+)vl(-)vbb], l being an electron or a muon. The search is optimized for the decay mode H → bb. The largest background to the ttH signal is top-quark pair production with additional jets. Artificial neural networks are used to discriminate between signal and background events. Combining the results from the 7TeV and 8TeV samples, the observed (expected) limit on the cross section for Higgs boson production in association with top quark pairs for a Higgs boson mass of 125 GeV is 5.8 (5.2) times the standard model expectatio

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types