Use and outcomes of targeted therapies in early and metastatic HER2-positive breast cancer in Australia: Protocol detailing observations in a whole of population cohort

Background: The management of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) has changed dramatically with the introduction and widespread use of HER2-targeted therapies. However, there is relatively limited real-world information on patterns of use, effectiveness and safety in whole of population cohorts. The research programme detailed in this protocol will generate evidence on the prescribing patterns, safety monitoring and outcomes of patients with BC treated with HER2- targeted therapies in Australia. Methods/design: Our ongoing research programme will involve a series of retrospective cohort studies that include every patient accessing Commonwealth-funded HER2-targeted therapies for the treatment of early BC and advanced BC in Australia. At the time of writing, our cohorts consist of 11 406 patients with early BC and 5631 with advanced BC who accessed trastuzumab and lapatinib between 2001 and 2014. Pertuzumab and trastuzumab emtansine were publicly funded for metastatic BC in 2015, and future data updates will include patients accessing these medicines. We will use dispensing claims for cancer and other medicines, medical service claims and demographics data for each patient accessing HER2- targeted therapies to undertake this research. Ethics and dissemination: Ethics approval has been granted by the Population Health Service Research Ethics Committee and data access approval has been granted by the Australian Department of Human Services (DHS) External Review Evaluation Committee. Our findings will be reported in peer-reviewed publications, conference presentations and policy forums. By providing detailed information on the use and outcomes associated with HER2-targeted therapies in a national cohort treated in routine clinical care, our research programme will better inform clinicians and patients about the real-world use of these treatments and will assist third-party payers to better understand the use and economic costs of these treatments

What Determines the Depth of BALs? Keck HIRES Observations of BALQSO 1603+300

We find that the depth and shape of the broad absorption lines (BALs) in BALQSO 1603+3002 are determined largely by the fraction of the emitting source which is covered by the BAL flow. In addition, the observed depth of the BALs is poorly correlated with their real optical depth. The implication of this result is that abundance studies based on direct extraction of column densities from the depth of the absorption troughs are unreliable. Our conclusion is based on analysis of unblended absorption features of two lines from the same ion (in this case the Si IV doublet), which allows unambiguous separation of covering factor and optical depth effects. The complex morphology of the covering factor as a function of velocity suggests that the BALs are produced by several physically separated outflows. The covering factor is ion dependent in both depth and velocity width. We also find evidence that in BALQSO 1603+3002 the flow does not cover the broad emission line region.Comment: 13 pages, 2 figures, accepted for publication in Ap

Urban wastewater: A valuable resource for agriculture - A case study from Haroonabad, Pakistan

Waste waters / Irrigation water / Water reuse / Economic analysis / Soil properties / Households / Water availability / Water use / Water quality / Groundwater / Public health / Risks / Case studies

Tips for research recruitment: The views of sexual minority youth

Researchers often experience difficulties recruiting hard-to-reach populations. This is especially so for studies involving those who have been historically stigmatized, such as individuals who challenge heteronormative expectations or people who experience mental ill health. The authors aimed to obtain the views of sexual minority adolescents (n=25) about what encouraged their participation in a research project. The authors used a general inductive approach to analyze interview data. Feedback consisted of 2 main overarching themes: tips and suggestions for future research and appreciate participants’ motivation to get involved in research. Strategies for how recruitment can be optimized for studies involving sexual minority young people are discussed

Improving Human Resource for Health in Rural Northern Nigeria

Inadequate number of health workers in rural areas is a major concern in many countries. It causes underutilization, prevents equitable access of health services, and is a barrier to universal health coverage. To increase the number and improve retention of health workers in rural areas, the World Health Organization (WHO) issued global recommendations to improve the rural retention of the health workforce. This paper presents the experiences of adopting and implementing the WHO recommendations in four states in Northern Nigeria. It highlights the results, challenges and lessons learnt with the implementation. We used an implementation research approach and evaluated the implementation at three stages: the pilot; full implementation; and immediate post exit. A total of 477 midwives were recruited and deployed to rural health facilities over a period of four years. Of these, 196 (41%) were in Jigawa, 126 (26.4%) in Yobe, 78 (16.4%) in Zamfara and 77 (16.1%) in Katsina. Midwives’ retention rates increased gradually over the four years. In three (Jigawa, Katsina and Zamfara) of the four states, midwives’ retention rates increased from 69.2% in Jigawa in 2013 to 98% in 2016; from 53.3% in Katsina in 2013 to 100% retention in 2016. Zamfara made the most progress with a poor retention rate of 42.8% in 2013 to 100% retention rate in 2016. In Yobe state, the retention rate of 47% in 2013 gradually increased to 100% in 2015. This however slightly dropped to 90% in 2016 as a result of the deteriorating security situation in 2015. Other effects of the initiative included: heightened determination of states to increase the production of indigenous midwives; reversal of policy directives that banned the recruitment of health workers including midwives; and to provide incentives such as safe and comfortable accommodation

Association between exposure to environmental tobacco smoke and biomarkers of oxidative stress among patients hospitalised with acute myocardial infarction

Objective To determine whether exposure to environmental tobacco smoke was associated with oxidative stress among patients hospitalised for acute myocardial infarction.<p></p> Design An existing cohort study of 1,261 patients hospitalised for acute myocardial infarction.<p></p> Setting Nine acute hospitals in Scotland.<p></p> Participants Sixty never smokers who had been exposed to environmental tobacco smoke (admission serum cotinine ≥3.0 ng/mL) were compared with 60 never smokers who had not (admission serum cotinine ≤0.1 ng/mL).<p></p> Intervention None.<p></p> Main outcome measures Three biomarkers of oxidative stress (protein carbonyl, malondialdehyde (MDA) and oxidised low-density lipoprotein (ox-LDL)) were measured on admission blood samples and adjusted for potential confounders.<p></p> Results After adjusting for baseline differences in age, sex and socioeconomic status, exposure to environmental tobacco smoke was associated with serum concentrations of both protein carbonyl (beta coefficient 7.96, 95% CI 0.76, 15.17, p = 0.031) and MDA (beta coefficient 10.57, 95% CI 4.32, 16.81, p = 0.001) but not ox-LDL (beta coefficient 2.14, 95% CI −8.94, 13.21, p = 0.703).<p></p> Conclusions Exposure to environmental tobacco smoke was associated with increased oxidative stress. Further studies are requires to explore the role of oxidative stress in the association between environmental tobacco smoke and myocardial infarction.<p></p&gt

LAMP for Human African Trypanosomiasis: A Comparative Study of Detection Formats

Loop-mediated isothermal amplification (LAMP) is at the forefront of the search for innovative diagnostics for human African trypanosomiasis (HAT). Several simple endpoint detection methods have been developed for LAMP and here we compare four of these: (i) visualization of turbidity; (ii) addition of hydroxynaphthol blue before incubation; (iii) addition of calcein with MnCl2 before incubation and (iv) addition of Quant-iT PicoGreen after incubation. These four methods were applied to four LAMP assays for the detection of human African trypanosomiasis, including two Trypanozoon specific and two Trypanosoma brucei rhodesiense specific reactions using DNA extracted from cryo-preserved procyclic form T. b. rhodesiense. A multi-observer study was performed to assess inter-observer reliability of two of these methods: hydroxynapthol blue and calcein with MnCl2, using DNA prepared from blood samples stored on Whatman FTA cards. Results showed that hydroxynaphthol blue was the best of the compared methods for easy, inexpensive, accurate and reliable interpretation of LAMP assays for HAT. Hydroxynapthol blue generates a violet to sky blue colour change that was easy to see and was consistently interpreted by independent observers. Visible turbidity detection is not possible for all currently available HAT LAMP reactions; Quant-iT PicoGreen is expensive and addition of calcein with MnCl2 adversely affects reaction sensitivity and was unpopular with several observers

The impact of CHIP premium increases on insurance outcomes among CHIP eligible children

Background: Within the United States, public insurance premiums are used both to discourage private health policy holders from dropping coverage and to reduce state budget costs. Prior research suggests that the odds of having private coverage and being uninsured increase with increases in public insurance premiums. The aim of this paper is to test effects of Children's Health Insurance Program (CHIP) premium increases on public insurance, private insurance, and uninsurance rates. Methods: The fact that families just below and above a state-specific income cut-off are likely very similar in terms of observable and unobservable characteristics except the premium contribution provides a natural experiment for estimating the effect of premium increases. Using 2003 Medical Expenditure Panel Survey (MEPS) merged with CHIP premiums, we compare health insurance outcomes for CHIP eligible children as of January 2003 in states with a two-tier premium structure using a cross-sectional regression discontinuity methodology. We use difference-in-differences analysis to compare longitudinal insurance outcomes by December 2003. Results: Higher CHIP premiums are associated with higher likelihood of private insurance. Disenrollment from CHIP in response to premium increases over time does not increase the uninsurance rate. Conclusions: When faced with higher CHIP premiums, private health insurance may be a preferable alternative for CHIP eligible families with higher incomes. Therefore, competition in the insurance exchanges being formed under the Affordable Care Act could enhance choice

\u3ci\u3eAquastella gen. nov.\u3c/i\u3e: A new genus of saprolegniaceous oomycete rotifer parasites related to \u3ci\u3eAphanomyces\u3c/i\u3e, with unique sporangial outgrowths

The oomycete genus Aquastella is described to accommodate two new species of parasites of rotifers observed in Brooktrout Lake, New York State, USA. Three rotifer species – Keratella taurocephala,Polyarthra vulgaris, and Ploesoma truncatum – were infected, and this is the first report of oomycete infection in these species. Aquastella attenuata was specific to K. taurocephala and Aquastella aciculariswas specific to P. vulgaris and P. truncatum. The occurrence of infections correlated with peak host population densities and rotifers were infected in the upper layers of the water column. Sequencing of 18S rRNA and phylogenetic analysis of both species placed them within the order Saprolegniales, in a clade closely related to Aphanomyces. The Aquastella species were morphologically distinct from other rotifer parasites as the developing sporangia penetrated out through the host body following its death to produce unique tapered outgrowths. Aquastella attenuata produced long, narrow, tapering, finger-like outgrowths, whilst A. acicularis produced shorter, spike-like outgrowths. We hypothesize that the outgrowths serve to deter predation and slow descent in the water column. Spore cleavage was intrasporangial with spore release through exit tubes. Aquastella attenuata produced primary zoospores, whereas A. acicularisreleased spherical primary aplanospores, more typical of other genera in the Aphanomyces clade

Modulation of the Cellular Expression of Circulating Advanced Glycation End-Product Receptors in Type 2 Diabetic Nephropathy

Background. Advanced glycation end-products (AGEs) and their receptors are prominent contributors to diabetic kidney disease. Methods. Flow cytometry was used to measure the predictive capacity for kidney impairment of the AGE receptors RAGE, AGE-R1, and AGE-R3 on peripheral blood mononuclear cells (PBMCs) in experimental models of type 2 diabetes (T2DM) fed varied AGE containing diets and in obese type 2 diabetic and control human subjects. Results. Diets high in AGE content fed to diabetic mice decreased cell surface RAGE on PBMCs and in type 2 diabetic patients with renal impairment (RI). All diabetic mice had elevated Albumin excretion rates (AERs), and high AGE fed dbdb mice had declining Glomerular filtration rate (GFR). Cell surface AGE-R1 expression was also decreased by high AGE diets and with diabetes in dbdb mice and in humans with RI. PBMC expression of AGE R3 was decreased in diabetic dbdb mice or with a low AGE diet. Conclusions. The most predictive PBMC profile for renal disease associated with T2DM was an increase in the cell surface expression of AGE-R1, in the context of a decrease in membranous RAGE expression in humans, which warrants further investigation as a biomarker for progressive DN in larger patient cohorts