The European Lead Factory: Results from a decade of collaborative, public-private, drug discovery programs.

The European Lead Factory (ELF) is a consortium of universities and small and medium-sized enterprises (SMEs) dedicated to drug discovery, and the pharmaceutical industry. This unprecedented consortium provides high-throughput screening, triage, and hit validation, including to non-consortium members. The ELF library was created through a novel compound-sharing model between nine pharmaceutical companies and expanded through library synthesis by chemistry-specialized SMEs.

The development of the O-sensing system in an amphibious fish: consequences of variation in environmental O levels.

Proper development of the O-sensing system is essential for survival. Here, we characterized the development of the O-sensing system in the mangrove rivulus (Kryptolebias marmoratus), an amphibious fish that transitions between hypoxic aquatic environments and O-rich terrestrial environments. We found that NECs formed in the gills and skin of K.

Fluctuating environments during early development can limit adult phenotypic flexibility: insights from an amphibious fish.

The interaction between developmental plasticity and the capacity for reversible acclimation (phenotypic flexibility) is poorly understood, particularly in organisms exposed to fluctuating environments. We used an amphibious killifish () to test the hypotheses that organisms reared in fluctuating environments (i) will make no developmental changes to suit any one environment because fixing traits to suit one environment could be maladaptive for another, and (ii) will be highly phenotypically flexible as adults because their early life experiences predict high environmental variability in the future. We reared fish under constant (water) or fluctuating (water-air) environments until adulthood and assessed a suite of traits along the oxygen cascade (e.

Ageing impacts phenotypic flexibility in an air-acclimated amphibious fish.

The ability to tolerate environmental change may decline as fishes age. We tested the hypothesis that ageing influences the scope for phenotypic flexibility in the mangrove rivulus (Kryptolebias marmoratus), an amphibious fish that transitions between two vastly different environments, water and land. We found that older fish (4-6 years old) exhibited marked signs of ageing; older fish were reproductively senescent, had reduced fin regenerative capacity and body condition, and exhibited atrophy of both oxidative and glycolytic muscle fibers relative to younger adult fish (1-2 years old).

Hydrogen sulphide toxicity and the importance of amphibious behaviour in a mangrove fish inhabiting sulphide-rich habitats.

We investigated amphibious behaviour, hydrogen sulphide (HS) tolerance, and the mechanism of HS toxicity in the amphibious mangrove rivulus (Kryptolebias marmoratus). We found that fish emersed (left water) in response to acutely elevated [HS] (~ 130-200 µmol l). The emersion response to HS may be influenced by prior acclimation history due to acclimation-induced alterations in gill morphology and/or the density and size of neuroepithelial cells (NECs) on the gills and skin.

Bundling Care for Cardiac Surgery Patients.

Patients returning to the community after surgery often experience a disconnect when transitioning from hospital to community home care. Many receive little organized/planned care following discharge sometimes resulting in unplanned expensive care in hospital emergency departments and inpatient readmissions. Trillium Health Partners, a large community/teaching hospital, in partnership with community care provider Saint Elizabeth Health Care, designed and implemented a seamless "bundled care program" for cardiac surgery patients extending from hospitalization to 30 days after discharge.

The ELF Honest Data Broker: informatics enabling public-private collaboration in a precompetitive arena.

New precompetitive ways of working in the pharmaceutical industry are driving the development of new informatics systems to enable their execution and management. The European Lead Factory (ELF) is a precompetitive, 30-partner collaboration between academic groups, small-medium enterprises and pharmaceutical companies created to discover small molecule hits against novel biological targets. A unique HTS screening and triage workflow has been developed to balance the intellectual property and scientific requirements of all the partners.

Fifty years of infection control and healthcare design.

The examination of 1962 perspectives on healthcare provided by Ross Graham and Shannon Sibbald in their article "Looking Back 50 Years in Hospital Administration" provides an opportunity to see not only what happened 50 years ago, but how modern attitudes and concerns both match and differ from those of the past. Focusing on infection prevention and hospital design, this commentary explores the changes in procedure, policy and attitudes since 1962, and how they are affecting healthcare today.

Uniting board to bedside: the use of driver diagrams in quality monitoring and improvement at Trillium Health Centre.

Boards of directors of healthcare organizations are increasingly being urged to extend their governance activities beyond financial matters to include the quality of patient care. Recently, Trillium Health Centre identified four big dot indicators and generated corollary driver diagrams aimed at helping its board understand and measure the organization's quality improvement plans, efforts and results. In addition to keeping board members up to date on these developments, the driver diagrams have supported quality improvements in their own right--for example, with hospital-acquired pressure ulcers--and have helped staff to focus and become more deeply engaged in Trillium's patient-centred quality improvement initiatives.

Long-term outcomes of stereotactic breast biopsies.

Stereotactic core needle biopsies (SCNBs) are accurate and relatively convenient for the patient; however, the long-term follow-up of benign results has not been reported. All patients between 1993 and 1998 undergoing SCNB at a community-based hospital were entered into a registry. Follow-up was obtained by a retrospective analysis of the charts.

Analysis of cathepsin D in human breast cancer: usefulness of the processed 31 kDa active form of the enzyme as a prognostic indicator in node-negative and node-positive patients.

The relative amounts of the precursor (52 kDa) and processed (31,27 kDa) forms of cathepsin D have been analyzed by Western blotting in biopsied breast tissue cytosols from 134 lesions from invasive breast cancer patients, 24 lesions from patients with ductal carcinoma in situ (DCIS), 227 lesions from benign breast disease patients, and 28 lesions from normal control subjects. The mean relative percentage amount of the 31 kDa form was significantly increased (p < 0.001) in the invasive breast cancer group compared to the other three groups.

Laparoscopic procedures in pregnancy.

As the applications of laparoscopy for general surgical procedures expanded in the 1990s, pregnancy was initially considered a contraindication. Several case reports have suggested the safety of laparoscopy in pregnancy. Previous clinical studies indicate a higher fetal mortality may exist and advised caution.

"How are the Egyptians behaving?" Herbert Brookes, British-Australian.

Herbert Brookes was a wealthy businessman, a distinguished patron of high culture in Melbourne society, an anti-Labor eminence who moved comfortably in the highest of imperial circles. The richness of his papers in the National Library provides the opportunity to examine the life of a leading British-Australian, to analyse issues of conscience and purpose that do not figure much in current historiography and perhaps to throw new light on the concerns of the generation that saw its world disrupted after 1914. Using the notion of Protestant stewardship, I have suggested that Brookes' life offers one way into the dynamics of liberalism before the Great War and of loyalism after it.

Water relations of Eucalyptus pauciflora near the alpine tree line in winter.

Water potential measurements were made, over three winter seasons, on Eucalyptus pauciflora Sieb. ex Spreng. at four elevations extending up to 200 m above the natural tree line in the Snowy Mountains area of southeastern Australia.

Factors influencing germination and establishment of Eucalyptus pauciflora near the alpine tree line.

Factors affecting seed germination, seedling establishment and growth to reproductive maturity in Eucalyptus pauciflora Sieb. ex Spreng. at the tree line in southeastern Australia were investigated.

Hazards of 'deleading' homes of children with lead poisoning.

"Deleading" the homes of children with lead poisoning is a necessary step to terminate the child's exposure to lead. Lead poisoning as a result of lead exposure during the process of deleading has occurred in deleading workers but has not been well documented among children whose homes are deleaded. We treated four children with classes I through III lead poisoning (range of blood lead [Pb-B] level, 1.

Stomatal responses and water relations of Eucalyptus pauciflora in summer along an elevational gradient.

The spatial and temporal variation of lead conductance (g) in Eucalyptus pauciflora was analysed with respect to photon flux area density (I), temperature (T), water vapour concentration deficit (Δw), and leaf water potential (Ψ) at four different sites between 940 m and 2,040 m altitude in the Snowy Mountains of south-eastern Australia. Along this altitudinal gradient the precipitation/evaporation ratio increases from 1 to 4. The results show that gas diffusion in this tree species is primarily controlled by I and Δw at all sites, independently of the specific soil moisture regime.

Gastrointestinal bleeding in patients with acute spinal injuries.

Twenty out of 365 patients (5.5 per cent) with acute spinal cord injuries referred to a spinal ward over a 91/2-year period bled from the gastrointestinal tract. A cause of the haemorrhage was found in 15 patients.