626 research outputs found
Effects of Australian Economic Activities on Waste Generation and Treatment
Understanding the relationships between the Australian economic system and waste generation from intermediate sectors and households is a prerequisite for planning and implementing waste management strategies at a national scale. Data of waste generation accounts link to those of national economic accounts. However, in Australia, some yearsâ data are absent and so these links cannot be made. To rectify this data gap, this paper interpolates and extrapolates the Australian input-output table (IOT) of 2010â2011. Waste input-output (WIO) analysis is then used to assess the effects of the Australian economy on waste generation and treatment between 2009â2010 and 2010â2011. Analysis indicated that the result of interpolation was more reasonable than that of extrapolation, and the interpolation of the Australian IOT of 2010â2011 can be applicable. This comparative analysis of the time series data in WIO model has identified that: (1) per million $AUD of output of the Construction sector generated the most amount of direct and total waste during the period; (2) the relationships between the development of Australian economy and waste generation illustrate that the Australian economy is currently a traditional linear economy; (3) the effectiveness of waste-related policies are shown by the growth of the sums of direct and total effects of intermediate sectors on the Recovery sector; and (4) the amount of waste generated by households increased sharply over the two years. The physical flows of waste footprint show details of waste generation and treatment in the Australian economic system. The information provided in this paper is beneficial to formulate tailor-made policies for waste management in Australia
Combining genomics and epidemiology to track mumps virus transmission in the United States.
Unusually large outbreaks of mumps across the United States in 2016 and 2017 raised questions about the extent of mumps circulation and the relationship between these and prior outbreaks. We paired epidemiological data from public health investigations with analysis of mumps virus whole genome sequences from 201 infected individuals, focusing on Massachusetts university communities. Our analysis suggests continuous, undetected circulation of mumps locally and nationally, including multiple independent introductions into Massachusetts and into individual communities. Despite the presence of these multiple mumps virus lineages, the genomic data show that one lineage has dominated in the US since at least 2006. Widespread transmission was surprising given high vaccination rates, but we found no genetic evidence that variants arising during this outbreak contributed to vaccine escape. Viral genomic data allowed us to reconstruct mumps transmission links not evident from epidemiological data or standard single-gene surveillance efforts and also revealed connections between apparently unrelated mumps outbreaks
Recruiting older people at nutritional risk for clinical trials: what have we learned?
BACKGROUND: The difficulty of recruiting older people to clinical trials is well described, but there is limited information about effective ways to screen and recruit older people into trials, and the reasons for their reluctance to enrol. This paper examines recruitment efforts for a community-based health intervention study that targeted older adults. METHODS: One year randomized control trial. Undernourished men and women, agedââ„â65Â years and living independently in the community were recruited in three Australian states. Participants were allocated to either oral testosterone undecanoate and high calorie oral nutritional supplement or placebo medication and low calorie oral nutritional supplementation. Hospital admissions, functional status, nutritional health, muscle strength, and other variables were assessed. RESULTS: 4023 potential participants were identified and 767 were screened by a variety of methods: hospital note screening, referrals from geriatric health services, advertising and media segments/appearances. 53 participants (7% of total screened) were recruited. The majority of potentially eligible participants declined participation in the trial after reading the information sheet. Media was the more successful method of recruiting, whereas contacting people identified by screening a large number of hospital records was not successful in recruiting any participants. CONCLUSION: Recruitment of frail and older participants is difficult and multiple strategies are required to facilitate participation. TRIAL REGISTRATION: Australian Clinical Trial Registry: ACTRN 12610000356066 date registered 4/5/2010.Cynthia Piantadosi, Ian M Chapman, Vasi Naganathan, Peter Hunter, Ian D Cameron, and Renuka Visvanatha
Desorption chemical ionization mass spectrometry of 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholines and analogues
Ammonia desorption chemical ionization of ether-linked phospholipids of the type 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (platelet-activating factors) and a series of analogues revealed a systematic fragmentation pattern that is characteristic for these compounds. The predominant ions included the protonated molecular ion and a series of fragments derived from the molecular ion having the following nominal mass losses: MH-14, MH-42, MH-59, and MH-183. Deuterated ammonia was used to elucidate the nature of several fragments. In addition, desorption chemical ionization was used to quantitate 1-O-hexadecyl-2-O-acetyl-sn-glycero-3-phosphocholine at the nanogram/sample level
dfpk : An R-package for Bayesian dose-finding designs using Pharmacokinetics (PK) for phase I clinical trials
Background and objective
Dose-finding, aiming at finding the maximum tolerated dose, and pharmacokinetics studies are the first in human studies in the development process of a new pharmacological treatment. In the literature, to date only few attempts have been made to combine pharmacokinetics and dose-finding and to our knowledge no software implementation is generally available. In previous papers, we proposed several Bayesian adaptive pharmacokinetics-based dose-finding designs in small populations. The objective of this work is to implement these dose-finding methods in an R package, called dfpk.
Methods
All methods were developed in a sequential Bayesian setting and Bayesian parameter estimation is carried out using the rstan package. All available pharmacokinetics and toxicity data are used to suggest the dose of the next cohort with a constraint regarding the probability of toxicity. Stopping rules are also considered for each method. The ggplot2 package is used to create summary plots of toxicities or concentration curves.
Results
For all implemented methods, dfpk provides a function (nextDose) to estimate the probability of efficacy and to suggest the dose to give to the next cohort, and a function to run trial simulations to design a trial (nsim). The sim.data function generates at each dose the toxicity value related to a pharmacokinetic measure of exposure, the AUC, with an underlying pharmacokinetic one compartmental model with linear absorption. It is included as an example since similar data-frames can be generated directly by the user and passed to nsim.
Conclusion
The developed user-friendly R package dfpk, available on the CRAN repository, supports the design of innovative dose-finding studies using PK information
Binding and metabolism of platelet-activating factor by human neutrophils.
Human polymorphonuclear neutrophils rapidly incorporated radiolabeled platelet-activating factor, 1-O-[hexadecyl-9, 10-3H2]-2-acetyl-sn-glycero-3-phosphocholine ([3H]PAF), and then metabolized it into its sn-2-fatty acyl derivative. Fractionation of radiolabel-pretreated cells over Percoll gradients revealed that virtually all of the intact [3H]PAF was located in nongranule membranes that were enriched with alkaline phosphatase and cell surface glycoproteins. While still membrane associated, the ligand was rapidly converted to its acyl derivative and then more slowly transferred to specific granules and, to a lesser extent, azurophilic granules. In contrast, neutrophils did not metabolize [3H]PAF at 4 degrees C but rather gradually accumulated it in their alkaline phosphatase-enriched membrane subfractions. These same subfractions contained receptors for the ligand, as determined by their capacity to bind [3H]PAF specifically. Binding was readily saturated, partially reversible, and fit a two receptor model; dissociation constant (Kd) values for high and low affinity sites were 0.2 and 500 nM, respectively. Receptors with similar affinities were detected in whole cells. Furthermore, the potencies of several structural analogues in inhibiting binding of [3H]PAF to membranes correlated closely with their respective potencies in stimulating degranulation responses. Finally, quantitative studies suggested all or most of the cell's receptors were membrane associated. We conclude that PAF rapidly enters cellular membranes to bind with specific receptors that trigger function. The intramembranous ligand is also deacetylated, acylated, and then transferred to granules. This metabolism may be sufficiently rapid to limit ligand-receptor binding and distort quantitative analyses of receptors
Patient-centric trials for therapeutic development in precision oncology
An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine
Prospective SPECT-CT organ dosimetry-driven radiation-absorbed dose escalation using the In-111 (111In)/yttrium 90 (90Y) ibritumomab tiuxetan (Zevalin Âź) theranostic pair in patients with lymphoma at myeloablative dose levels
PURPOSE: We prospectively evaluated the feasibility of SPECT-CT/planar organ dosimetry-based radiation dose escalation radioimmunotherapy in patients with recurrent non-Hodgkin\u27s lymphoma using the theranostic pair of
METHODS: 24 patients with CD20-positive relapsed or refractory rituximab-sensitive, low-grade, mantle cell, or diffuse large-cell NHL, with normal organ function, platelet counts \u3e 75,000/mm
RESULTS: Patient-specific hybrid SPECT/CT + planar organ dosimetry was feasible in all 18 cases and used to determine the patient-specific therapeutic dose and guide dose escalation (26.8 ± 7.3 MBq/kg (mean), 26.3 MBq/kg (median) of
CONCLUSIONS: Patient-specific outpatien
Changes in monthly unemployment rates may predict changes in the number of psychiatric presentations to emergency services in South Australia
BACKGROUND To determine the extent to which variations in monthly Mental Health Emergency Department (MHED) presentations in South Australian Public Hospitals are associated with the Australian Bureau of Statistics (ABS) monthly unemployment rates. METHODS Times series modelling of relationships between monthly MHED presentations to South Australian Public Hospitals derived from the Integrated South Australian Activity Collection (ISAAC) data base and the ABS monthly unemployment rates in South Australia between January 2004âJune 2011. RESULTS Time series modelling using monthly unemployment rates from ABS as a predictor variable explains 69 % of the variation in monthly MHED presentations across public hospitals in South Australia. Thirty-two percent of the variation in current monthâs male MHED presentations can be predicted by using the 2 monthsâ prior male unemployment rate. Over 63 % of the variation in monthly female MHED presentations can be predicted by either male or female prior monthly unemployment rates. CONCLUSIONS The findings of this study highlight that even with the relatively favourable economic conditions, small shifts in monthly unemployment rates can predict variations in monthly MHED presentations, particularly for women. Monthly ABS unemployment rates may be a useful metric for predicting demand for emergency mental health services.Niranjan Bidargaddi, Tarun Bastiampillai, Geoffrey Schrader, Robert Adams, Cynthia Piantadosi, Jörg Strobel, Graeme Tucker, and Stephen Alliso
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