Reversal of hepatorenal syndrome type 1 with terlipressin plus albumin vs. placebo plus albumin in a pooled analysis of the OT-0401 and REVERSE randomised clinical studies

Background The goal of hepatorenal syndrome type 1 (HRS-1) treatment is to improve renal function. Terlipressin, a synthetic vasopressin analogue, is a systemic vasoconstrictor used for the treatment of HRS-1, where it is available. Aim To compare the efficacy of terlipressin plus albumin vs. placebo plus albumin in patients with HRS-1. Methods Pooled patient-level data from two large phase 3, randomised, placebo-controlled studies were analysed for HRS reversal [serum creatinine (SCr) value ≤133 μmol/L], 90-day survival, need for renal replacement therapy and predictors of HRS reversal. Patients received intravenous terlipressin 1–2 mg every 6 hours plus albumin or placebo plus albumin up to 14 days. Results The pooled analysis comprised 308 patients (terlipressin: n = 153; placebo: n = 155). HRS reversal was significantly more frequent with terlipressin vs. placebo (27% vs. 14%; P = 0.004). Terlipressin was associated with a more significant improvement in renal function from baseline until end of treatment, with a mean between-group difference in SCr concentration of −53.0 μmol/L (P \u3c 0.0001). Lower SCr, lower mean arterial pressure and lower total bilirubin and absence of known precipitating factors for HRS were independent predictors of HRS reversal and longer survival in terlipressin-treated patients. Conclusions Terlipressin plus albumin resulted in a significantly higher rate of HRS reversal vs. albumin alone in patients with HRS-1. Terlipressin treatment is associated with improved renal function

Inferring statistics of planet populations by means of automated microlensing searches

(abridged) The study of other worlds is key to understanding our own, and not only provides clues to the origin of our civilization, but also looks into its future. Rather than in identifying nearby systems and learning about their individual properties, the main value of the technique of gravitational microlensing is in obtaining the statistics of planetary populations within the Milky Way and beyond. Only the complementarity of different techniques currently employed promises to yield a complete picture of planet formation that has sufficient predictive power to let us understand how habitable worlds like ours evolve, and how abundant such systems are in the Universe. A cooperative three-step strategy of survey, follow-up, and anomaly monitoring of microlensing targets, realized by means of an automated expert system and a network of ground-based telescopes is ready right now to be used to obtain a first census of cool planets with masses reaching even below that of Earth orbiting K and M dwarfs in two distinct stellar populations, namely the Galactic bulge and disk. The hunt for extra-solar planets acts as a principal science driver for time-domain astronomy with robotic-telescope networks adopting fully-automated strategies. Several initiatives, both into facilities as well as into advanced software and strategies, are supposed to see the capabilities of gravitational microlensing programmes step-wise increasing over the next 10 years. New opportunities will show up with high-precision astrometry becoming available and studying the abundance of planets around stars in neighbouring galaxies becoming possible. Finally, we should not miss out on sharing the vision with the general public, and make its realization to profit not only the scientists but all the wider society.Comment: 10 pages in PDF format. White paper submitted to ESA's Exo-Planet Roadmap Advisory Team (EPR-AT); typos corrected. The embedded figures are available from the author on request. See also "Towards A Census of Earth-mass Exo-planets with Gravitational Microlensing" by J.P. Beaulieu, E. Kerins, S. Mao et al. (arXiv:0808.0005

Review of rehabilitation and habilitation strategies for children and young people with homonymous visual field loss caused by cerebral vision impairment

Partial and homonymous visual field loss (HVFL) is a common consequence of post-chiasmatic injury to the primary visual pathway or injury to the primary visual cortex. Different approaches to rehabilitation have been reported for older adults with HVFL and there is evidence to support the use of compensatory training over other proposed therapies. We reviewed the literature to investigate the current state of the art of rehabilitation and habilitation strategies for children and young people with HVFL, and whether there is enough evidence to support the use of these strategies in the paediatric population. We have provided an overview of the existing literature on children and young people with HVFL, a brief overview of rehabilitation strategies for adults with HVFL, and evidence on whether these different interventions have been applied with children and young people effectively. We found that there have been very few studies to investigate these strategies with children and young people, and the quality of evidence is currently low. New research is required to evaluate which strategies are effective for children and young people with HVFL and whether new strategies need to be developed

Temperate Forage Grass-Legume Mixtures: Advances And Perspectives

The paper summarises some of the advances which have been made a) in increasing understanding of the grass-legume association, especially grass-white clover, so that the association can be more predictably exploited and b) in overcoming limitations in the use of such mixtures. The contribution which forage legumes make to the N economy of mixtures is reviewed with estimates approaching 400 kg N ha-1 for some. Uptake by grass of legume- derived N (N transfer) reduces soil mineral N levels and increases the proportion of fixed N in the total legume N relative to legume monoculture. Although N transfer also causes inconsistent contribution of legume to mixed swards, models of the effect of legume derived N on the interaction between grass and legume are helping to predict likely grass-legume balance, even when grazed. The higher nutritive value and intake of legumes relative to grass is due to a range of factors including faster rate of particle breakdown, faster digestion in the rumen, more non- ammonium N reaching the small intestine and higher efficiency of energy utilization although efficiency of N utilization is lower. Poor utilization is not an issue with birdsfoot trefoil and sainfoin due to their herbage having a high content of condensed tannins which protect protein from degradation in the rumen. Breeding programmes using conventional and biotechnological methods are aiming to improve nutritive value such as increasing protein quality and introducing condensed tannins into clovers and lucerne. Breeding of legumes to reduce antiquality factors, such as bloat, is underway. Breeding to reduce oestrogenic effects has been successful in red clover and subclover. Advances are leading to improved legume consistency in mixture including improvement in tolerance to biotic and environmental stress by breeding and increased understanding of the role of companion grasses. Research which underpins management techniques to improve predictability of grass-legume balance is also discussed, including the positive and negative role of the grazing animal. The potential and limitations of grass-legume swards to reduce N loss, including NO3 leaching, in whole farm systems is evaluated where grass/white clover can reduce leaching by 50% compared with a high fertilizer N system at only 20% reduction in output. Other factors which may result in increased reliance on forage legumes, in addition to the improvements in forage legumes resulting from research, include de-intensification policy decisions to reduce stocking rates, increased uptake of organic farming, increased cost of N fertilizer relative to commodity prices. Shared research effort between countries is advocated to supply adequate resources to solve some of the remaining problems in grass/legume associations and effective technology transfer should include development of decision support systems due to the complexity of the association

Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial

AIMS/HYPOTHESIS: The aim was to evaluate the efficacy and safety of transcutaneous frequency-modulated electromagnetic neural stimulation (frequency rhythmic electrical modulation system, FREMS) as a treatment for symptomatic peripheral neuropathy in patients with diabetes mellitus. METHODS: This was a double-blind, randomised, multicentre, parallel-group study of three series, each of ten treatment sessions of FREMS or placebo administered within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The primary endpoint was the change in nerve conduction velocity (NCV) of deep peroneal, tibial and sural nerves. Secondary endpoints included the effects of treatment on pain, tactile, thermal and vibration sensations. Patients eligible to participate were aged 18-75 years with diabetes for ≥ 1 year, HbA(1c) <11.0% (97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities (i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural nerve, but with an evocable potential and measurable NCV of the sural nerve), a Michigan Diabetes Neuropathy Score ≥ 7 and on a stable dose of medications for diabetic neuropathy in the month prior to enrolment. Data were collected in an outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1 ratio) according to a sequence generated by a computer random number generator, without block or stratification factors. Investigators digitised patients' date of birth and site number into an interactive voice recording system to obtain the assigned treatment. Participants, investigators conducting the trial, or people assessing the outcomes were blinded to group assignment. RESULTS: Patients (n = 110) with symptomatic neuropathy were randomised to FREMS (n = 54) or placebo (n = 56). In the intention-to-treat population (50 FREMS, 51 placebo), changes in NCV of the three examined nerves were not different between FREMS and placebo (deep peroneal [means ± SE]: 0.74 ± 0.71 vs 0.06 ± 1.38 m/s; tibial: 2.08 ± 0.84 vs 0.61 ± 0.43 m/s; and sural: 0.80 ± 1.08 vs -0.91 ± 1.13 m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in day and night pain as measured by a visual analogue scale immediately after each treatment session, although this beneficial effect was no longer measurable 3 months after treatment. Compared with the placebo group, in the FREMS group the cold sensation threshold was significantly improved, while non-significant differences were observed in the vibration and warm sensation thresholds. No relevant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS proved to be a safe treatment for symptomatic diabetic neuropathy, with immediate, although transient, reduction in pain, and no effect on NCV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01628627. FUNDING: The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy), lately Lorenz Lifetech (Ozzano dell'Emilia, Italy)