Access to high cost medicines in Australia: ethical perspectives

Access to "high cost medicines" through Australia's Pharmaceutical Benefits Scheme (PBS) is tightly regulated. It is inherently difficult to apply any criteria-based system of control in a way that provides a fair balance between efficient use of limited resources for community needs and equitable individual access to care. We suggest, in relation to very high cost medicines, that the present arrangements be re-considered in order to overcome potential inequities. The biological agents for the treatment of rheumatoid arthritis are used as an example by which to discuss the ethical issues associated with the current scheme. Consideration of ethical aspects of the PBS and similar programs is important in order to achieve the fairest outcomes for individual patients, as well as for the community

On the use of AI for generation of functional music to improve mental health

Increasingly music has been shown to have both physical and mental health benefits including improvements in cardiovascular health, a link to reduction of cases of dementia in elderly populations, and improvements in markers of general mental well-being such as stress reduction. Here, we describe short case studies addressing general mental well-being (anxiety, stress-reduction) through AI-driven music generation. Engaging in active listening and music-making activities (especially for at risk age groups) can be particularly beneficial, and the practice of music therapy has been shown to be helpful in a range of use cases across a wide age range. However, access to music-making can be prohibitive in terms of access to expertise, materials, and cost. Furthermore the use of existing music for functional outcomes (such as targeted improvement in physical and mental health markers suggested above) can be hindered by issues of repetition and subsequent over-familiarity with existing material. In this paper, we describe machine learning (ML) approaches which create functional music informed by biophysiological measurement across two case studies, with target emotional states at opposing ends of a Cartesian affective space (a dimensional emotion space with points ranging from descriptors from relaxation, to fear). We use Galvanic skin response (GSR) as a marker of psychological arousal and as an estimate of emotional state to be used as a control signal in the training of the ML algorithm. This algorithm creates a non-linear time series of musical features for sound synthesis ‘on-the-fly’, using a perceptually informed musical feature similarity model. We find an interaction between familiarity (or more generally, the featureset model we have implemented) and perceived emotional response so focus on generating new, emotionally-congruent pieces. We also report on subsequent psychometric evaluation of the generated material, and consider how these - and similar techniques -might be useful for a range of functional music generation tasks, for example in nonlinear sound-tracking such as that found in interactive media or video games

Bacterial Attachment to Polymeric Materials Correlates with Molecular Flexibility and Hydrophilicity

A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials\u27 pendant groups. This correlation is applicable to 86% of the hydrocarbon pendant moieties surveyed, quantitatively supporting the previous qualitative observation that bacteria are repelled from poly(meth)acrylates containing a hydrophilic ester group when the pendant group is both rigid and hydrophobic. This insight will help inform and predict the further development of polymers resistant to bacterial attachment

Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to areas of highest pressure: cohort observations at baseline and twelve months

BackgroundPlantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA.Methods A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson’s correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures.ResultsAt baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially.Conclusions We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures

An improved competitive inhibition enzymatic immunoassay method for tetrodotoxin quantification

Quantifying tetrodotoxin (TTX) has been a challenge in both ecological and medical research due to the cost, time and training required of most quantification techniques. Here we present a modified Competitive Inhibition Enzymatic Immunoassay for the quantification of TTX, and to aid researchers in the optimization of this technique for widespread use with a high degree of accuracy and repeatability

The response of perennial and temporary headwater stream invertebrate communities to hydrological extremes

The headwaters of karst rivers experience considerable hydrological variability, including spates and streambed drying. Extreme summer flooding on the River Lathkill (Derbyshire, UK) provided the opportunity to examine the invertebrate community response to unseasonal spate flows, flow recession and, at temporary sites, streambed drying. Invertebrates were sampled at sites with differing flow permanence regimes during and after the spates. Following streambed drying at temporary sites, dewatered surface sediments were investigated as a refugium for aquatic invertebrates. Experimental rehydration of these dewatered sediments was conducted to promote development of desiccation-tolerant life stages. At perennial sites, spate flows reduced invertebrate abundance and diversity, whilst at temporary sites, flow reactivation facilitated rapid colonisation of the surface channel by a limited number of invertebrate taxa. Following streambed drying, 38 taxa were recorded from the dewatered and rehydrated sediments, with Oligochaeta being the most abundant taxon and Chironomidae (Diptera) the most diverse. Experimental rehydration of dewatered sediments revealed the presence of additional taxa, including Stenophylax sp. (Trichoptera: Limnephilidae) and Nemoura sp. (Plecoptera: Nemouridae). The influence of flow permanence on invertebrate community composition was apparent despite the aseasonal high-magnitude flood events

Natural coagulates for wastewater treatment; a review for application and mechanism

The increase of water demand and wastewater generation is among the global concerns in the world. The less effective management of water sources leads to serious consequences, the direct disposal of untreated wastewater is associated with the environmental pollution, elimination of aquatic life and the spread of deadly epidemics. The flocculation process is one of the most important stages in water and wastewater treatment plants, wherein this phase the plankton, colloidal particles, and pollutants are precipitated and removed. Two major types of coagulants are used in the flocculation process included the chemical and natural coagulants. Many studies have been performed to optimize the flocculation process while most of these studies have confirmed the hazardous effects of chemical coagulants utilization on the ecosystem. This chapter reviews a summary of the coagulation/flocculation processes using natural coagulants as well as reviews one of the most effective natural methods of water and wastewater treatment

Health related quality of life of obese adolescents in Kuwait

Obesity impairs health related quality of life (HRQL) in adolescents, but most evidence in this area has mostly come from western societies. We wanted to test the hypothesis that obesity impairs HRQL in Kuwaiti adolescents, and to test for differences in HRQL assessed by self-report and parent-proxy report. In 500 Kuwaiti 10-14 year olds HRQL was assessed using the Peds QL (TM) with both adolescent self-reports (n = 500) and parent-proxy reports (n = 374). Obesity was not significantly associated with HRQL in regression analysis. In a paired comparison of 98 pairs of obese adolescents vs. 98 healthy weight peers, impairment of HRQL reached significance only for physical score (95% CI = -1.5, -9.4), not for psychosocial score or total score. In a paired comparison of parent-proxy vs. self-reports for the obese adolescents, total score (95% CI = -4.9, -10.9), physical score (95% CI = -3.2, -11.0), and psychosocial score (95% CI = -4.2, -10.8) were all significantly lower in the parent reports. Obesity is not associated with marked impairment of HRQL in adolescents in Kuwait, in contrast to studies in western societies. This may reflect cultural differences in attitudes towards obesity