A systematic review of prescribing criteria to evaluate appropriateness of medications in frail older people

This study systematically reviews the published literature regarding inappropriate prescribing in frail individuals aged at least 65 years. Twenty-five of 466 identified studies met the inclusion criteria. All papers measured some surrogate indicators of frailty, such as performance-based tests, cognitive function and functional dependency. Beers criteria were used in 20 studies (74%) to evaluate inappropriate medication use and 36% (9/25) studies used more than one criterion. The prevalence of inappropriate medications ranged widely from 11 to 92%. Only a few studies reported the relationship between potentially inappropriate medication use and surrogate measures of frailty. These diverse findings indicate the need for a standardized measure for assessing appropriateness of medication in frail older individuals. Prescribing tools should address both medication and patient-related factors such as life expectancy and functional status to minimize inappropriate prescribing in frail individuals.

A strain-based failure criterion for pillar stability analysis

Strain-based failure criteria have several advantages over stress-based failure criteria: they can account for elastic and inelastic strains, they utilise direct, observables effects instead of inferred effects (strain gauges vs. stress estimates), and model complete stress-strain curves including pre-peak, non-linear elasticity and post-peak strain weakening. In this study, a strain-based failure criterion derived from thermodynamic first principles utilising the concepts of continuum damage mechanics is presented. Furthermore, implementation of this failure criterion into a finite-element simulation is demonstrated and applied to the stability of underground mining coal pillars. In numerical studies, pillar strength is usually expressed in terms of critical stresses or stress-based failure criteria where scaling with pillar width and height is common. Previous publications have employed the finite-element method for pillar stability analysis using stress-based failure criterion such as Mohr-Coulomb and Hoek-Brown or stress-based scalar damage models. A novel constitutive material model, which takes into consideration anisotropy as well as elastic strain and damage as state variables has been developed and is presented in this paper. The damage threshold and its evolution are strain-controlled, and coupling of the state variables is achieved through the damage-induced degradation of the elasticity tensor. This material model is implemented into the finite-element software ABAQUS and can be applied to 3D problems. Initial results show that this new material model is capable of describing the non-linear behaviour of geomaterials commonly observed before peak strength is reached as well as post-peak strain softening. Furthermore, it is demonstrated that the model can account for directional dependency of failure behaviour (i.e. anisotropy) and has the potential to be expanded to environmental controls like temperature or moisture.

Investigating how designers collaborate and respond to sustainable design criteria

This research provides a critical link to ensure designers remain at the forefront of developing safe, sustainable and innovative products and services in the future. The four key findings of this research contribute to the advancement of knowledge and provide an understanding of the relationships between designers' co-evolution approach and their use of analogy. The behavioural relationships between sketching and gesture were investigated. The outcome of this research is a Design Activity Framework. This framework demonstrates a novel understanding how designers design by concentrating on co-evolution, problem-framing and solution seeking.

Investigation of the effects of the fatty acid profile on fuel properties using a Multi-Criteria Decision Analysis

The structural features of fatty acids in biodiesel, including degree of unsaturation, percentage of saturated fatty acids and average chain length, influence important fuel properties such as cetane number, iodine value, density, kinematic viscosity, higher heating value and oxidation stability. The composition of fatty acid esters within the fuel should therefore be in the correct ratio to ensure fuel properties are within international biodiesel standards such as ASTM 6751 or EN 14214. This study scrutinises the influence of fatty acid composition and individual fatty acids on fuel properties. Fuel properties were estimated based on published equations, and measured according to standard procedure ASTM D6751 and EN 14214 to confirm the influences of the fatty acid profile. Based on fatty acid profile-derived calculations, the cetane number of the microalgal biodiesel was estimated to be 11.6, but measured 46.5, which emphasises the uncertainty of the method used for cetane number calculation. Multi-criteria decision analysis (MCDA), PROMETHEE-GAIA, was used to determine the influence of individual fatty acids on fuel properties in the GAIA plane. Polyunsaturated fatty acids increased the iodine value and had a negative influence on cetane number. Kinematic viscosity was negatively influenced by some long chain polyunsaturated fatty acids such as C20:5 and C22:6 and some of the more common saturated fatty acids C14:0 and C18:0. The positive impact of average chain length on higher heating value was also confirmed in the GAIA plane

Use ‘4Rs’ criteria to assess papers

We propose a '4R' approach to assessing reported research, underpinned by statistical rigour (see J. T. Leek and R. D. Peng Nature 520, 612; 2015). These 4Rs denote reproduction, replication, robustness and revelation...

Criteria for interpreting kimberlite as coherent: Insights from the Muskox and Jericho kimberlites (Nunavut, Canada)

The Jurassic Muskox and Jericho kimberlites (Northern Slave Province, Nunavut, Canada) contain a variety of facies exhibiting different geometries, contact relationships, internal organisation, country rock abundance and olivine shapes, although many have similar matrix/groundmass mineralogies and textures. Five facies are examined that either have characteristics consistent with coherent rocks in general (i.e. intrusive and extrusive non-fragmental rocks) or are mineralogically and texturally similar to kimberlite described as coherent (or apparent coherent). Three facies are interpreted as coherent on the basis of: (1) geological setting, (2) apparent-porphyritic texture, (3) sharp contacts with fragmental kimberlite, (4) relative abundance of elongate and unbroken olivine crystals and (5) paucity of country rock xenoliths, while the remaining two facies are interpreted as fragmental on the basis of: (1) the gradational contacts with demonstrably fragmental kimberlite, (2) relative abundance and range of sizes of country rock lithic clasts and (3) numerous broken olivine crystals. Comparisons are made with coherent and apparent-coherent kimberlite from the literature. Our three coherent facies are similar to literature reported coherent kimberlite dykes hosted in country rock (CKd) in terms of internal organisation, low abundance of country rock xenoliths, and apparent-porphyritic texture. Conversely, our two fragmental facies share attributes with previously described pipe-filling coherent and apparent-coherent kimberlite (CKpf) in terms of geometry, internal organisation and abundance of country rock xenoliths. We conclude that CKd and most CKpf, although similar in matrix/groundmass mineralogy and texture, can be distinguished on the basis of internal organisation, country rock lithic clast abundance, texture (e.g. apparent-porphyritic texture) and possibly olivine crystal shapes and suggest that fragmental kimberlite is more common than reported.

Selection criteria in the search for a sperm donor: Behavioural traits versus physical appearance

Despite extensive literature on female mate choice, empirical evidence on women’s mating preferences in the search for a sperm donor is scarce, even though this search, by isolating a male’s genetic impact on offspring from other factors like paternal investment, offers a naturally ”controlled” research setting. In this paper, we work to fill this void by examining the rapidly growing online sperm donor market, which is raising new challenges by offering women novel ways to seek out donor sperm. We not only identify individual factors that influence women’s mating preferences but find strong support for the proposition that behavioural traits (inner values) are more important in these choices than physical appearance (exterior values). We also report evidence that physical factors matter more than resources or other external cues of material success, perhaps because the relevance of good character in donor selection is part of a female psychological adaptation throughout evolutionary history. The lack of evidence on a preference for material resources, on the other hand, may indicate the ability of peer socialization and better access to resources to rapidly shape the female decision process. Overall, the paper makes useful contributions to both the literature on human behaviour and that on decision-making in extreme and highly important situations.

After the gold rush: Patent law and biological inventions

In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. ’For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: ’There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as ’novelty', ’inventive step', and ’utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the ’Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.

Scoring rules and abnormally low bids criteria in construction tenders: A taxonomic review

In the global construction context, the Best Value or Most Economically Advantageous Tender is becoming a widespread approach for contractor selection, as an alternative to other traditional awarding criteria such as the Lowest Price. In these multi-attribute tenders, the owner or auctioneer solicits proposals containing both a price bid and additional technical features. Once the proposals are received, each bidder's price bid is given an economic score according to a scoring rule, generally called an Economic Scoring Formula (ESF) and a technical score according to pre-specified criteria. Eventually, the contract is awarded to the bidder with the highest weighted overall score (economic + technical). However, Economic Scoring Formula selection by auctioneers is invariably and paradoxically a highly intuitive process in practice, involving few theoretical or empirical considerations, despite having being considered traditionally and mistakenly as objective, due to its mathematical nature. This paper provides a taxonomic classification of a wide variety of ESF and Abnormally Low Bid Criteria (ALBC) gathered in several countries with different tendering approaches. Practical implications concern the optimal design of price scoring rules in construction contract tenders, as well as future analyses of the effects of ESF and ALBC on competitive bidding behaviour.

Patent law and biological inventions

In response to scientific breakthroughs in biotechnology, the development of new technologies, and the demands of a hungry capitalist marketplace, patent law has expanded to accommodate a range of biological inventions. There has been much academic and public debate as to whether gene patents have a positive impact upon research and development, health-care, and the protection of the environment. In a satire of prevailing patenting practices, the English poet and part-time casino waitress, Donna MacLean, sought a patent application - GB0000180.0 - in respect of herself. She explained that she had satisfied the usual patent criteria - in that she was novel, inventive, and useful: It has taken 30 years of hard labor for me to discover and invent myself, and now I wish to protect my invention from unauthorized exploitation, genetic or otherwise. I am new: I have led a private existence and I have not made the invention of myself public. I am not obvious (2000: 18). MacLean said she had many industrial applications. 'For example, my genes can be used in medical research to extremely profitable ends - I therefore wish to have sole control of my own genetic material' (2000: 18). She observed in an interview: 'There's a kind of unpleasant, grasping, greedy atmosphere at the moment around the mapping of the human genome ... I wanted to see if a human being could protect their own genes in law' (Meek, 2000). This special issue of Law in Context charts a new era in the long-standing debate over biological inventions. In the wake of the expansion of patentable subject matter, there has been great strain placed upon patent criteria - such as 'novelty', 'inventive step', and 'utility'. Furthermore, there has been a new focus upon legal doctrines which facilitate access to patented inventions - like the defence of experimental use, the 'Bolar' exception, patent pooling, and compulsory licensing. There has been a concerted effort to renew patent law with an infusion of ethical principles dealing with informed consent and benefit sharing. There has also been a backlash against the commercialisation of biological inventions, and a call by some activists for the abolition of patents on genetic inventions. This collection considers a wide range of biological inventions - ranging from micro-organisms, plants and flowers and transgenic animals to genes, express sequence tags, and research tools, as well as genetic diagnostic tests and pharmaceutical drugs. It is thus an important corrective to much policy work, which has been limited in its purview to merely gene patents and biomedical research. This collection compares and contrasts the various approaches of a number of jurisdictions to the legal problems in respect of biological inventions. In particular, it looks at the complexities of the 1998 European Union Directive on the Legal Protection of Biotechnological Inventions, as well as decisions of member states, such as the Netherlands, and peripheral states, like Iceland. The edition considers US jurisprudence on patent law and policy, as well as recent developments in Canada. It also focuses upon recent developments in Australia - especially in the wake of parallel policy inquiries into gene patents and access to genetic resources.

A multi-criteria analysis approach for ranking and selection of microorganisms for the production of oils for biodiesel production

Oleaginous microorganisms have potential to be used to produce oils as alternative feedstock for biodiesel production. Microalgae (Chlorella protothecoides and Chlorella zofingiensis), yeasts (Cryptococcus albidus and Rhodotorula mucilaginosa), and fungi (Aspergillus oryzae and Mucor plumbeus) were investigated for their ability to produce oil from glucose, xylose and glycerol. Multi-criteria analysis (MCA) using analytic hierarchy process (AHP) and preference ranking organization method for the enrichment of evaluations (PROMETHEE) with graphical analysis for interactive aid (GAIA), was used to rank and select the preferred microorganisms for oil production for biodiesel application. This was based on a number of criteria viz., oil concentration, content, production rate and yield, substrate consumption rate, fatty acids composition, biomass harvesting and nutrient costs. PROMETHEE selected A. oryzae, M. plumbeus and R. mucilaginosa as the most prospective species for oil production. However, further analysis by GAIA Webs identified A. oryzae and M. plumbeus as the best performing microorganisms.

The ASAS criteria for axial spondyloarthritis: Strengths, weaknesses, and proposals for a way forward

Classification criteria should facilitate selection of similar patients for clinical and epidemiologic studies, therapeutic trials, and research on etiopathogenesis to enable comparison of results across studies from different centers. We critically appraise the validity and performance of the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA). It is still debatable whether all patients fulfilling these criteria should be considered as having true axSpA. Patients with radiographically evident disease by the ASAS criteria are not necessarily identical with ankylosing spondylitis (AS) as classified by the modified New York criteria. The complex multi-arm selection design of the ASAS criteria induces considerable heterogeneity among patients so classified, and applying them in settings with a low prevalence of axial spondyloarthritis (SpA) greatly increases the proportion of subjects falsely classified as suffering from axial SpA. One of the unmet needs in non-radiographic form of axial SpA is to have reliable markers that can identify individuals at risk for progression to AS and thereby facilitate early intervention trials designed to prevent such progression. We suggest needed improvements of the ASAS criteria for axSpA, as all criteria sets should be regarded as dynamic concepts open to modifications or updates as our knowledge advances.

Manufacturing and use of human placenta-derived mesenchymal stromal cells for phase I clinical trials: Establishment and evaluation of a protocol

Background/Aim. Mesenchymal stromal cells (MSCs) have been utilised in many clinical trials as an experimental treatment in numerous clinical settings. Bone marrow remains the traditional source tissue for MSCs but is relatively hard to access in large volumes. Alternatively, MSCs may be derived from other tissues including the placenta and adipose tissue. In an initial study no obvious differences in parameters such as cell surface phenotype, chemokine receptor display, mesodermal differentiation capacity or immunosuppressive ability, were detected when we compared human marrow derived- MSCs to human placenta-derived MSCs. The aim of this study was to establish and evaluate a protocol and related processes for preparation placenta-derived MSCs for early phase clinical trials. Methods. A full-term placenta was taken after delivery of the baby as a source of MSCs. Isolation, seeding, incubation, cryopreservation of human placentaderived MSCs and used production release criteria were in accordance with the complex regulatory requirements applicable to Code of Good Manufacturing Practice manufacturing of ex vivo expanded cells. Results. We established and evaluated instructions for MSCs preparation protocol and gave an overview of the three clinical areas application. In the first trial, MSCs were co-transplanted iv to patient receiving an allogeneic cord blood transplant as therapy for treatmentrefractory acute myeloid leukemia. In the second trial, MSCs were administered iv in the treatment of idiopathic pulmonary fibrosis and without serious adverse effects. In the third trial, MSCs were injected directly into the site of tendon damage using ultrasound guidance in the treatment of chronic refractory tendinopathy. Conclusion. Clinical trials using both allogeneic and autologous cells demonstrated MSCs to be safe. A described protocol for human placenta-derived MSCs is appropriate for use in a clinical setting, relatively inexpensive and can be relatively easily adjusted to a different set of regulatory requirements, as applicable to early phase clinical trials.

Australian data do not support current pharmaceutical benefits scheme criteria for use of tumour necrosis factor-α inhibitors in ankylosing spondylitis

On the basis of local data, we write in support of the conclusions of Smith and Ahern that current Pharmaceu- tical Benefits Scheme (PBS) criteria for tumour necrosis factor (TNF)-a inhibitors in ankylosing spondylitis (AS) are not evidence-based. 1 As a prerequisite to the appropriate use of biological therapy in AS, three aspects of the disease need to be defined: (i) diagnosis, (ii) activity and (iii) therapeutic failure (Table 1)....

Intra-cluster correlation structure in longitudinal data analysis: Selection criteria and misspecification tests

Selection criteria and misspecification tests for the intra-cluster correlation structure (ICS) in longitudinal data analysis are considered. In particular, the asymptotical distribution of the correlation information criterion (CIC) is derived and a new method for selecting a working ICS is proposed by standardizing the selection criterion as the p-value. The CIC test is found to be powerful in detecting misspecification of the working ICS structures, while with respect to the working ICS selection, the standardized CIC test is also shown to have satisfactory performance. Some simulation studies and applications to two real longitudinal datasets are made to illustrate how these criteria and tests might be useful.