Adherence to prescribing restrictions for HER2-positive metastatic breast cancer in Australia: A national population-based observational study (2001-2016)

Background: Targeted cancer therapy is often complex, involving multiple agents and chemotherapeutic partners. In Australia, prescribing restrictions are put in place to reflect existing evidence of cost-effectiveness of these medicines. As therapeutic options continue to expand, these restrictions may not be perceived to align with best practice and it is not known if their use in the real-world clinic adheres to these restrictions. We examined the treatment of women receiving trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) to determine the extent to which treatment adhered to national prescribing restrictions. Patients and methods: Our population-based, retrospective cohort study used dispensing records for every Australian woman initiating publicly-subsidised trastuzumab for HER2+MBC between 2001±2013, followed through 2016. We used group-based trajectory models (GBTMs) to cluster patients, first on their patterns of trastuzumab exposure, and then on their patterns of lapatinib and chemotherapy exposure. We described the characteristics of patients within each cluster, and examined their treatments and combinations of treatments to determine restriction adherence. Results: Of 5,052 patients initiating trastuzumab, 1,795 (36%) received at least one non-adherent HER2-targeted treatment. The most common non-adherent treatments were trastuzumab combinations involving vinorelbine (24% of non-adherent treatments); capecitabine (24%); and anthracyclines (10%). Non-adherent lapatinib use was observed in 4% of patients. GBTM identified three trastuzumab exposure clusters, each containing three further subclusters. The largest proportions of non-adherent treatments were in sub-clusters with longer trastuzumab exposure and more non-taxane chemotherapy. Patients in these sub-clusters were younger than those in sub-clusters with less non-adherent treatment. Conclusions: Our study highlights that, even during the relatively simpler treatment era of our study period, a substantial amount of treatment did not adhere to prescribing restrictions. As more trials are conducted exploring pertuzumab and T-DM1 in combination with different chemotherapies and other HER2-targeted therapies, the regulation and funding of HER2-targeted treatment will become more challenging

Supply & value chain analysis of onions in Ethiopia

Ethiopia is a developing country situated on Africa’s horn. Ethiopia ranks 173rd on United Nations human development index where the least developed country ranks 186. About 85% of all Ethiopians are employed in agriculture. Onion is one of the basic ingredients in the Ethiopian cuisine and thus an important crop. Previous studies on fruits and vegetables in Ethiopia points at post-harvest losses between 15% and 70%. To estimate the losses for onions in Ethiopia a supply and value chain analysis has been made. A literature review on supply chain management, value chain analysis, onion cultivation, and agricultural and logistical conditions in Ethiopia has been made in order to acquire a holistic view of the topic. Interviews with aid from interpreters have been made to gather the necessary information from the chain actors. The chain actors have been identified and the losses at each level of the chain quantified and analyzed. The value chain for onions in Ethiopia has been researched to identify the different actors and their activities carried out when the onions move from producer to consumer. All expenses related to the activities in each step has been studied to find the value added and to calculate the profit for each actor. The complete chain consists of six actors; farmer, broker, transporter, wholesaler, retailer and consumer. The onions can reach the end-consumer without passing through all steps; broker, transporter and retailer are not always involved. The conclusions from the supply chain analysis were: - The total amount of losses in the chain is about 13% and most of these losses occur at the end of the chain at consumer level. - The supply chain of onions is fragmented and thus not an integrated logistic system. - The fragmentation of the chain causes a non-collaborative system, which in turn results in higher losses at the end of the chain. The conclusions of the value chain analysis were: - The use of fertilizers and pesticides has a major impact in the value chain but differs widely between the farmers. A more controlled and effective use can have positive effect on both the economy and the environment for the farmer. - The actor making the biggest profit is the wholesaler. The farmers have a higher profit per kg of onions, but the fact that they only get three harvests per year makes the annual profit low. The wholesalers have (by far) the highest sale rate and the second highest profit per kg. - The wholesalers are not following the tax-regulations. None of the wholesalers include 15% VAT as a standard procedure, which they should. VAT is only added when the customers want a receipt. Only three of the nine wholesalers pay tax on their profit. - Wastes from onion production at farmer level can be used to produce electricity corresponding to 5.7% of the total electricity consumption in Meki and Ziway.Etiopien är ett utvecklingsland som ligger på Afrikas horn i nordöstra Afrika, Etiopien rankas på 173:e platsen i FN:s index för mänsklig utveckling, där det minst utvecklade landet rankas som nummer 186. Cirka 85 % av alla etiopier arbetar inom jordbruket. Lök är en basingrediens i det etiopiska köket och är därför en viktig gröda för bönderna och befolkningen. Tidigare studier på frukt och grönt i Etiopien pekar på fysiska förluster mellan 15 % och 70 %. För att uppskatta de förluster som finns för lök i Etiopien har en analys på Supply Chain och värdekedjan gjorts. En litteraturstudie om Supply Chain Mangement, värdekedjeanalys, lökodling, samt jordbruksförhållanden och logistiska förutsättningar i Etiopien har gjorts för att erhålla en helhetssyn på ämnet. Intervjuer med hjälp av tolkar har gjorts för att samla in den nödvändiga informationen från aktörerna i kedjan. Värdekedjan för lök i Etiopien har undersökts för att identifiera de olika aktörerna och deras aktiviteter som utförs för att löken ska komma från producent till konsument. Alla utgifter kopplade till de olika aktiviteterna i varje steg har undersökts för att hitta värdeförändringen och för att beräkna vinsten för varje aktör. De aktörer som finns i kedjan har identifierats och förlusterna på varje nivå i kedjan kvantifierats och analyserats. Hela kedjan består av sex aktörer; jordbrukare, mäklare, transportör, grossist, återförsäljare och konsument. Löken kan nå konsumenten utan att passera genom alla steg; mäklare, transportör och återförsäljare används inte alltid. Slutsatserna från Supply Chain Management analysen är: - Den totala mängden fysiska förluster i kedjan är ca 13 % och de flesta av dessa förluster uppstår i slutet av kedjan på konsumentnivå. - Leveranskedjan av lök är fragmenterad och är inte ett integrerat logistiksystem. - Uppdelningen av kedjan medför ett icke - samverkande system, vilket i sin tur leder till högre förluster i slutet av kedjan. Slutsatserna av analysen av värdekedjan är: - Användningen av gödningsmedel och bekämpningsmedel har stor inverkan i värdekedjan men skiljer sig stort mellan bönderna. En mer kontrollerad och effektiv användning kan ge positiva effekter på både ekonomin och miljön för jordbrukarna. - Den aktör som gör störst vinst på löken är grossiten. Jordbrukarna får den högsta vinsten per kilo producerad lök, men det faktum att de bara får tre skördar per år gör den årliga vinsten låg. Grossisterna har överlägset störst försäljningsgrad och näst högst vinst per kg - Grossisterna följer inte skattereglerna. Ingen av grossisterna inkluderade 15 % i mervärdesskatt som standardförfarande, vilket de borde. Mervärdesskatt läggs bara på när kunderna kräver kvitto. Endast tre av de nio grossisterna betalar vinstskatt. - Restprodukter från lökproduktionen hos jordbrukarna kan användas till att producera el motsvarande 5,7 % av den totala elanvändningen i Meki och Ziway

Standardizing and Scaling up Quality Adolescent Friendly Health Services in Tanzania.

Adolescents in Tanzania require health services that respond to their sexual and reproductive health - and other - needs and are delivered in a friendly and nonjudgemental manner. Systematizing and expanding the reach of quality adolescent friendly health service provision is part of the Tanzanian Ministry of Health and Social Welfare's (MOHSW) multi-component strategy to promote and safeguard the health of adolescents. We set out to identify the progress made by the MOHSW in achieving the objective it had set in its National Adolescent Health and Development Strategy: 2002-2006, to systematize and extend the reach of Adolescent Friendly Health Services (AFHS) in the country. We reviewed plans and reports from the MOHSW and journal articles on AFHS. This was supplemented with several of the authors' experiences of working to make health services in Tanzania adolescent friendly. The MOHSW identified four key problems with what was being done to make health services adolescent friendly in the country - firstly, it was not fully aware of the various efforts under way; secondly, there was no standardized definition of AFHS; thirdly, it had received reports that the quality of the AFHS being provided by some organizations was poor; and fourthly, only small numbers of adolescents were being reached by the efforts that were under way. The MOHSW responded to these problems by mapping existing services, developing a standardized definition of AFHS, charting out what needed to be done to improve their quality and expand their coverage, and integrating AFHS within wider policy and strategy documents and programmatic measurement instruments. It has also taken important preparatory steps to stimulate and support implementation. The MOHSW is aware that the focus of the effort must now shift from the national to the regional, council and local levels. The onus is on regional and council health management teams as well as health facility managers to take the steps needed to ensure that all adolescents in the country obtain the sexual and reproductive health (SRH) services they need, delivered in a friendly and non-judgemental manner. But they cannot do this without substantial and ongoing support

Genetic inactivation of the vesicular glutamate transporter 2 (VGLUT2) in the mouse: What have we learnt about functional glutamatergic neurotransmission?

During the past decade, three proteins that possess the capability of packaging glutamate into presynaptic vesicles have been identified and characterized. These three vesicular glutamate transporters, VGLUT1–3, are encoded by solute carrier genes Slc17a6–8. VGLUT1 (Slc17a7) and VGLUT2 (Slc17a6) are expressed in glutamatergic neurons, while VGLUT3 (Slc17a8) is expressed in neurons classically defined by their use of another transmitter, such as acetylcholine and serotonin. As glutamate is both a ubiquitous amino acid and the most abundant neurotransmitter in the adult central nervous system, the discovery of the VGLUTs made it possible for the first time to identify and specifically target glutamatergic neurons. By molecular cloning techniques, different VGLUT isoforms have been genetically targeted in mice, creating models with alterations in their glutamatergic signalling. Glutamate signalling is essential for life, and its excitatory function is involved in almost every neuronal circuit. The importance of glutamatergic signalling was very obvious when studying full knockout models of both VGLUT1 and VGLUT2, none of which were compatible with normal life. While VGLUT1 full knockout mice die after weaning, VGLUT2 full knockout mice die immediately after birth. Many neurological diseases have been associated with altered glutamatergic signalling in different brain regions, which is why conditional knockout mice with abolished VGLUT-mediated signalling only in specific circuits may prove helpful in understanding molecular mechanisms behind such pathologies. We review the recent studies in which mouse genetics have been used to characterize the functional role of VGLUT2 in the central nervous system

Allergy education and training for physicians.

The increasing prevalence of allergic diseases has placed a significant burden on global healthcare and society as whole. This has necessitated a rapid development of "allergy" as a specialist area. However, as allergy is so common and, for most, relatively easy to diagnose and control, all clinicians need to have basic knowledge and competence  to manage  mild disease and recognize when referral is required. The allergology specialty has not yet been recognized in many countries and even where allergy is fully recognized as a specialty, the approach to training in allergy differs significantly. In the light of recent developments in allergy diagnosis and management, there is an urgent need to harmonize core competences for physicians, as well as the standardization of core principles for medical education and post-graduate training in allergy. All physicians and allied health professionals must appreciate the multidisciplinary team (MDT) approach to allergy, which is key to achieving the highest standards in holistic care. Due to worldwide variation in resources and personnel, some MDT roles will need to be absorbed by the treating physician or other healthcare professionals. We draw particular attention to the role of psychological input for all allergy patients, dietetic input in the case of food allergy and patient education to support all patients in the supported self-management of their condition on a daily basis. A strong appreciation of these multidisciplinary aspects will help physicians provide quality patient-centered care. We consider that harmonization of allergy components within undergraduate curricula is crucial to ensure all physicians develop the appropriate allergy-related knowledge and skills, particularly in light of inconsistencies seen in the primary care management of allergy. This review from the World Allergy Organization (WAO) Education and Training Committee also outlines allergy-related competences required of physicians working with allergic patients and provides recommendations to promote harmonization of allergy training and practice worldwide

Fit to father? Online accounts of lifestyle changes and help-seeking on a male infertility board

The reproductive realm is routinely viewed as a feminised space requiring women’s commitment and labour. By contrast, men’s procreative contributions and ‘reproductive masculinity’ is represented as unproblematic, with men assumed to be fertile across the lifespan. Recent scientific research has, however, cast doubt over these longstanding assumptions, suggesting that a link does exist between ‘lifestyle’ factors and male fertility. The notion that fertility can be improved with effort (for both women and men) can be located within wider cultural and political shifts which construct individuals as increasingly responsible for acting on health messages and engaging in self-disciplining body projects. Through an exploration of ‘lifestyle changes’ within a men’s online infertility discussion forum board, this paper examines how discourses of individualisation healthism and masculinity are reproduced and interlinked. Our thematic analysis indicates that ‘lifestyle work’ is construed as crucial for achieving conception - and as a means to demonstrate men’s commitment to the dyadic goal of parenthood, which in turn may challenge and extend previous notions of ‘reproductive masculinity’

Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management

This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. The pattern of infection in the population was investigated using a serial cross-sectional serological study over a 25-month period, with blood sampled from 521 individuals over six sampling sessions. Antibody titres to the virus were determined by virus neutralisation test. In contrast to the expected episodic infection pattern, we observed that seroprevalence gradually increased over the two years suggesting infection was endemic in the population over the study period. Our results suggested age, pregnancy and lactation were significant risk factors for a detectable neutralizing antibody response. Antibody titres were significantly higher in females than males, with the highest titres occurring in pregnant animals. Temporal variation in antibody titres suggests that herd immunity to the virus may wax and wane on a seasonal basis. These findings support an endemic infection pattern of henipaviruses in bat populations suggesting their infection dynamics may differ significantly from the acute, self limiting episodic pattern observed with related viruses (e.g. measles virus, phocine distemper virus, rinderpest virus) hence requiring a much smaller critical host population size to sustain the virus. These findings help inform predictive modelling of henipavirus infection in bat populations, and indicate that the life cycle of the reservoir species should be taken into account when developing risk management strategies for henipaviruses

Evidence of Endemic Hendra Virus Infection in Flying-Foxes (Pteropus conspicillatus)—Implications for Disease Risk Management

This study investigated the seroepidemiology of Hendra virus in a spectacled flying-fox (Pteropus conspicillatus) population in northern Australia, near the location of an equine and associated human Hendra virus infection in late 2004. The pattern of infection in the population was investigated using a serial cross-sectional serological study over a 25-month period, with blood sampled from 521 individuals over six sampling sessions. Antibody titres to the virus were determined by virus neutralisation test. In contrast to the expected episodic infection pattern, we observed that seroprevalence gradually increased over the two years suggesting infection was endemic in the population over the study period. Our results suggested age, pregnancy and lactation were significant risk factors for a detectable neutralizing antibody response. Antibody titres were significantly higher in females than males, with the highest titres occurring in pregnant animals. Temporal variation in antibody titres suggests that herd immunity to the virus may wax and wane on a seasonal basis. These findings support an endemic infection pattern of henipaviruses in bat populations suggesting their infection dynamics may differ significantly from the acute, self limiting episodic pattern observed with related viruses (e.g. measles virus, phocine distemper virus, rinderpest virus) hence requiring a much smaller critical host population size to sustain the virus. These findings help inform predictive modelling of henipavirus infection in bat populations, and indicate that the life cycle of the reservoir species should be taken into account when developing risk management strategies for henipaviruses

Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the $\gamma p$ centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil

Algal MIPs, high diversity and conserved motifs

<p>Abstract</p> <p>Background</p> <p>Major intrinsic proteins (MIPs) also named aquaporins form channels facilitating the passive transport of water and other small polar molecules across membranes. MIPs are particularly abundant and diverse in terrestrial plants but little is known about their evolutionary history. In an attempt to investigate the origin of the plant MIP subfamilies, genomes of chlorophyte algae, the sister group of charophyte algae and land plants, were searched for MIP encoding genes.</p> <p>Results</p> <p>A total of 22 MIPs were identified in the nine analysed genomes and phylogenetic analyses classified them into seven subfamilies. Two of these, Plasma membrane Intrinsic Proteins (PIPs) and GlpF-like Intrinsic Proteins (GIPs), are also present in land plants and divergence dating support a common origin of these algal and land plant MIPs, predating the evolution of terrestrial plants. The subfamilies unique to algae were named MIPA to MIPE to facilitate the use of a common nomenclature for plant MIPs reflecting phylogenetically stable groups. All of the investigated genomes contained at least one <it>MIP </it>gene but only a few species encoded MIPs belonging to more than one subfamily.</p> <p>Conclusions</p> <p>Our results suggest that at least two of the seven subfamilies found in land plants were present already in an algal ancestor. The total variation of MIPs and the number of different subfamilies in chlorophyte algae is likely to be even higher than that found in land plants. Our analyses indicate that genetic exchanges between several of the algal subfamilies have occurred. The PIP1 and PIP2 groups and the Ca²⁺gating appear to be specific to land plants whereas the pH gating is a more ancient characteristic shared by all PIPs. Further studies are needed to discern the function of the algal specific subfamilies MIPA-E and to fully understand the evolutionary relationship of algal and terrestrial plant MIPs.</p