Influence of cell surface characteristics on adhesion of Saccharomyces cerevisiae to the biomaterial hydroxylapatite

The influence of the physicochemical properties of biomaterials on microbial cell adhesion is well known, with the extent of adhesion depending on hydrophobicity, surface charge, specific functional groups and acid–base properties. Regarding yeasts, the effect of cell surfaces is often overlooked, despite the fact that generalisations may not be made between closely related strains. The current investigation compared adhesion of three industrially relevant strains of Saccharomyces cerevisiae (M-type, NCYC 1681 and ALY, strains used in production of Scotch whisky, ale and lager, respectively) to the biomaterial hydroxylapatite (HAP). Adhesion of the whisky yeast was greatest, followed by the ale strain, while adhesion of the lager strain was approximately 10-times less. According to microbial adhesion to solvents (MATS) analysis, the ale strain was hydrophobic while the whisky and lager strains were moderately hydrophilic. This contrasted with analyses of water contact angles where all strains were characterised as hydrophilic. All yeast strains were electron donating, with low electron accepting potential, as indicated by both surface energy and MATS analysis. Overall, there was a linear correlation between adhesion to HAP and the overall surface free energy of the yeasts. This is the first time that the relationship between yeast cell surface energy and adherence to a biomaterial has been described

Why bean beer?

Beer can be a wholesome beverage, and the art of brewing beer has been intertwined with the development of civilised society for centuries. Today, the latest valuation of the economic value of beer (by accountants Ernst and Young in 2013), reported that Europe is the world’s biggest producer of beer with over 4,500 breweries delivering around 390 million hectolitres annually – which in plain English is 68,632,200,000 pints (since 1 hectolitre is a small spillage less than 176 imperial pints). The industry employs over 2 million people, and around 125,000 of these are employed in breweries themselves. It should also be no surprise then that sales generated 53 billion Euro, which is almost doubled again by the value added from the supply chain. Also, the EU brewing sector had a trade surplus (i.e. exports were greater than imports) to the value of 3 billion Euro in 2012. Beer is serious business

The HOME Study: study protocol for a randomised controlled trial comparing the addition of Proactive Psychological Medicine to usual care, with usual care alone, on the time spent in hospital by older acute hospital inpatients

Background: Prolonged acute hospital stays are a major problem for older people and for health services. Failure to effectively manage the psychological and social aspects of illness is an important cause of prolonged hospital stays. Proactive Psychological Medicine (PPM) is a new way of providing psychiatry services to medical wards. PPM is proactive, focussed, intensive and integrated with medical care. A major aim of PPM is to reduce the time older people spend in hospital because of unmanaged psychological and social problems. The HOME Study will test the effectiveness and cost-effectiveness of PPM. Methods/design: A two-arm parallel-group randomised controlled superiority trial, with a linked health economic analysis and an embedded process evaluation, will be conducted at three sites. A total of 3588 participants will be recruited and randomised to usual care or usual care plus PPM. The primary outcome is the number of days spent as an inpatient in a general hospital in the month (30 days) post-randomisation. Secondary outcomes for each participant (measured at 1 and 3 months) include quality of life, independent functioning, symptoms of anxiety and depression, cognitive function, and their experience of the hospital stay. Discussion: The trial has been designed to produce findings that are generalisable to all older medical inpatients (including those with cognitive impairment). It will provide information on the effectiveness and cost-effectiveness of PPM, which we hope will be of value to patients, clinicians, managers and service planners

Personalised randomised controlled trial designs—a new paradigm to define optimal treatments for carbapenem-resistant infections

Antimicrobial resistance is impacting treatment decisions for, and patient outcomes from, bacterial infections worldwide, with particular threats from infections with carbapenem-resistant Enterobacteriaceae, Acinetobacter baumanii, or Pseudomonas aeruginosa. Numerous areas of clinical uncertainty surround the treatment of these highly resistant infections, yet substantial obstacles exist to the design and conduct of treatment trials for carbapenem-resistant bacterial infections. These include the lack of a widely acceptable optimised standard of care and control regimens, varying antimicrobial susceptibilities and clinical contraindications making specific intervention regimens infeasible, and diagnostic and recruitment challenges. The current single comparator trials are not designed to answer the urgent public health question, identified as a high priority by WHO, of what are the best regimens out of the available options that will significantly reduce morbidity, costs, and mortality. This scenario has an analogy in network meta-analysis, which compares multiple treatments in an evidence synthesis to rank the best of a set of available treatments. To address these obstacles, we propose extending the network meta-analysis approach to individual randomisation of patients. We refer to this approach as a Personalised RAndomised Controlled Trial (PRACTical) design that compares multiple treatments in an evidence synthesis, to identify, overall, which is the best treatment out of a set of available treatments to recommend, or how these different treatments rank against each other. In this Personal View, we summarise the design principles of personalised randomised controlled trial designs. Specifically, of a network of different potential regimens for life-threatening carbapenem-resistant infections, each patient would be randomly assigned only to regimens considered clinically reasonable for that patient at that time, incorporating antimicrobial susceptibility, toxicity profile, pharmacometric properties, availability, and physician assessment. Analysis can use both direct and indirect comparisons across the network, analogous to network meta-analysis. This new trial design will maximise the relevance of the findings to each individual patient, and enable the top-ranked regimens from any personalised randomisation list to be identified, in terms of both efficacy and safety

The Deuteron Confronts Big Bang Nucleosynthesis

Recent determinations of the deuterium abundance, $^2$H/H, in high redshift Lyman limit hydrogen clouds challenge the usual picture of primordial nucleosynthesis based on \lq\lq concordance\rq\rq\ of the calculated light element ($^2$H, $^3$He, $^4$He, $^7$Li) nucleosynthesis yields with the observationally-inferred abundances of these species. Concordance implies that all light element yields can be made to agree with the observationally-inferred abundances (within errors) for single global specifications of the baryon-to-photon ratio, $\eta$; lepton number; neutron lifetime; and expansion rate (or equivalently, effective number of light neutrino degrees of freedom $N_{\nu}$). Though one group studying Lyman limit systems obtains a high value of $^2$H/H ($\sim 2\times {10}^{-4}$), another group finds consistently low values ($\sim 2\times {10}^{-5}$). In the former case, concordance for $N_{\nu} =3$ is readily attained for the current observationally-inferred abundances of $^4$He and $^7$Li. But if the latter case represents the primordial deuterium abundance, then concordance for {\it any} $N_{\nu}$ is impossible unless the primordial value of $^7$Li/H is considerably larger than the abundance of lithium as measured in old, hot Pop II halo stars. Furthermore, concordance with $N_{\nu}=3$ is possible for low $^2$H/H only if either (1) the primordial $^4$He abundance has been significantly underestimated, or (2) new neutrino sector physics is invoked. We argue that systematic underestimation of both the $^7$Li and $^4$He primordial abundances is the likely resolution of this problem, a conclusion which is strengthened by new results on $^4$He.Comment: To be published in Nucl. Phys. B (Proc. Suppl.), in the proceedings of "Sources and Detection of Dark Matter in the Universe", held in Santa Monica, Feb. 14-16 1996. 5 pages. Replaced version has a TeX command removed that apparently caused some latex compilers to fai

The Personalised Randomized Controlled Trial: Evaluation of a new trial design

In some clinical scenarios, for example, severe sepsis caused by extensively drug resistant bacteria, there is uncertainty between many common treatments, but a conventional multiarm randomized trial is not possible because individual participants may not be eligible to receive certain treatments. The Personalised Randomized Controlled Trial design allows each participant to be randomized between a “personalised randomization list” of treatments that are suitable for them. The primary aim is to produce treatment rankings that can guide choice of treatment, rather than focusing on the estimates of relative treatment effects. Here we use simulation to assess several novel analysis approaches for this innovative trial design. One of the approaches is like a network meta-analysis, where participants with the same personalised randomization list are like a trial, and both direct and indirect evidence are used. We evaluate this proposed analysis and compare it with analyses making less use of indirect evidence. We also propose new performance measures including the expected improvement in outcome if the trial's rankings are used to inform future treatment rather than random choice. We conclude that analysis of a personalized randomized controlled trial can be performed by pooling data from different types of participants and is robust to moderate subgroup-by-intervention interactions based on the parameters of our simulation. The proposed approach performs well with respect to estimation bias and coverage. It provides an overall treatment ranking list with reasonable precision, and is likely to improve outcome on average if used to determine intervention policies and guide individual clinical decisions

Optimised processing of faba bean (<i>Vicia faba L.</i>) kernels as a brewing adjunct

Pulse (Fabaceae) grains, such as peas and beans, are derived from crops that are usually cultivated in the absence of mineral nitrogen fertiliser as these crops can obtain their nitrogen requirement naturally from the air via biological nitrogen fixation. Therefore, pulses present a significantly lower greenhouse gas (GHG) footprint than crops demanding nitrogen fertiliser, whilst also offering significant quantities of starch for the brewing and distilling industries. Mitigation of agriculture derived GHG emissions through utilisation of pulses can have a positive environmental impact. To this end, the potential of exploiting dry, dehulled faba bean (Vicia faba L.) kernel flour as an adjunct for beer production was evaluated. The impact of different temperature regimes and commercial enzymes were assessed for their effect on wort: viscosity; run-off rate; primary amino nitrogen content and, fermentability. Faba beans demonstrated insufficient endogenous enzyme capacity for starch conversion and generated a viscous wort. However, using a stepped temperature mashing regime and exogenous enzyme additions, the faba bean wort was comparable in processability and fermentability to that of 100% malted barley wort. The faba based beer and co-product qualities demonstrate the environmental, nutritional and commercial potential of pulses in brewing.</p

Tumour cells surviving in vivo cisplatin chemotherapy display elevated c-myc expression.

The c-myc oncogene has been extensively implicated in cell proliferation, cell differentiation and programmed cell death. Aberrant expression of the c-myc gene product has been observed in a range of tumours and has also been implicated in cisplatin (cis-dichlorodiammineplatinum)-mediated chemoresistance. A solid transplantable tumour model in syngeneic DA rats was subjected to treatment with cisplatin to determine the impact of such therapy on endogenous c-myc gene expression. Serially transplanted tumours were intravenously treated with a single cisplatin dose (1 mg/kg) and c-myc expression analysed 2 and 7 days after treatment. The surviving tumour cells display a significant 2-fold elevation in c-myc expression at 48 h and 7 days after treatment. Primary cell cultures have been derived from untreated in vivo tumours of the same model and subjected to treatment with a c-myc phosphorothioate antisense oligomer. Administration of 5 microM c-myc antisense oligomer directed at the initiation codon and first four codons of c-myc mRNA results in total inhibition of c-myc expression and coincident suspension of cell growth for a period of 4 days in culture. Antisense therapies directed at the c-myc gene may well prove an effective tool for treating tumours in conjunction with cisplatin as these findings show that tumour cells surviving cisplatin chemotherapy display elevated c-myc expression