Search

Abstract Cryptosporidium parvum and C. hominis are parasites that cause life-threatening diarrhea in children and immunocompromised people. There is only one approved treatment that is modestly effective for children and ineffective for AIDS patients. Here, screening 278 compounds from the Merck KGaA, Darmstadt, Germany collection and accelerated follow-up enabled by prior investigation of the compounds identifies a series of pyrazolopyrimidine human phosphodiesterase (PDE)-V (hPDE-V) inhibitors with potent anticryptosporidial activity and efficacy following oral administration in C. parvum-infected male mice. The lead compounds affect parasite host cell egress, inhibit both C. parvum and C. hominis, work rapidly, and have minimal off-target effects in a safety screening panel. Interestingly, the hPDE-V inhibitors sildenafil and the 4-aminoquinoline compound 7a do not affect Cryptosporidium. C. parvum expresses one PDE (CpPDE1) continuously during asexual growth, the inhibited life stage. According to homology modeling and docking, the lead compounds interact with CpPDE1. Bulkier amino acids (Val900 and His884) in the CpPDE1 active site replace alanines in hPDE-V and block sildenafil binding. Supporting this, sildenafil kills a CRISPR-engineered Cryptosporidium CpPDE1 V900A mutant. The CpPDE1 mutation also alters parasite susceptibility to pyrazolopyrimidines. CpPDE1 is therefore a validated pyrazolopyrimidine molecular target to exploit for target-based optimization for improved anticryptosporidial development.

This study explored stakeholder experiences and attitudes regarding the use of ID scanners in licensed venues in Queensland, Australia. In July 2017, the Queensland Government introduced mandatory, networked ID scanners in licensed venues within designated nightlife districts (SNPs). After 10pm, people seeking to enter late-night licensed venues must provide identification, which is verified by the scanner. The scanner also checks whether the patron has any recorded banning notice/s that may preclude entry into the venue. Semi-structured interviews were conducted with 66 key stakeholders and analysed using thematic analysis. Stakeholders reported that ID scanners support the enforcement of patron bans. Their mandated use within SNPs allows for accurate and timely identification of patrons, and may offer benefits with respect to reducing and solving crime, and improving patron behaviours. Some concerns were expressed regarding data privacy and the need to ensure procedural fairness and consistent use. Overall, the study highlighted the importance of ongoing monitoring and refining of ID scanner policy, particularly with respect to where and when scanners are used.

Abstract Objective To investigate the medium-term impacts of the COVID-19 pandemic on violence-related offences in Australia, and whether there was evidence of a ‘dual pandemic’ of family violence in addition to COVID-19. Methods Autoregressive Integrated Moving Average time series were conducted to analyse publicly available violent crime statistics data from January 2017 to November 2021. Population rates of homicide, sexual, domestic and non-domestic assault were assessed across each Australian state and territory, with the effects of COVID-19 being modelled using the average monthly World Health Organization COVID-19 stringency rating for each jurisdiction. Findings All jurisdictions in Australia showed increasing or stable domestic assault trends over the past decade, which were not significantly impacted by COVID-19, nor by the subsequent lockdowns. Non-domestic assaults demonstrated a significant, negative relationship with the stringency index for each jurisdiction, except Western Australia. There was no significant change in the rates of homicide or sexual assault across Australia in relation to COVID-19. Conclusion Overall, there was no evidence of a ‘dual pandemic’ in Australia, and whilst domestic assaults continue to increase across the country, non-domestic assaults showed a notable but brief decline. However, these have returned to levels at least as high as pre-COVID-19 and some states show a continuing upward trend. The findings also suggest that alcohol availability may have played a role in continuing high violence numbers. Given the ongoing increasing and high levels of family violence in Australia, revised conceptual frameworks and interventions are indicated.

Abstract To assist intervention developers assess the likely effectiveness of messages designed to encourage greater use of protective behavioral strategies, this study developed and tested the Alcohol Message Perceived Effectiveness Scale (AMPES). Recommendations from the message effectiveness literature were used to guide AMPES development. The resulting scale was administered in online surveys at two time points to Australian drinkers aged 18–70 years (3001 at Time 1 and 1749 at Time 2). An exploratory factor analysis identified the presence of two factors (‘effect perceptions’ and ‘message perceptions’) that accounted for 71% of the variance in scores. Internal consistency of scores was good for the overall scale (ω = 0.83) and ‘effect perceptions’ factor (ω = 0.85), but suboptimal for the ‘message perceptions’ factor (α = 0.60). Scores on both factors significantly predicted enactment of protective behavioral strategies. The AMPES appears to be an appropriate tool to assess perceived message effectiveness and assist in the development of public health messages designed to reduce alcohol consumption.

Abstract Objectives: This study explores Australian public awareness and attitudes towards political donations from the alcohol industry and the ‘revolving door’ of politicians into industry or lobbyist positions. Methods: Data were collected via a nationwide online panel. Results: In total, n=1,044 participants completed the survey. More than half of the participants agreed that donations are made to influence government policy and to support the interests of the industry. More than half of the participants did not believe that it is appropriate for political parties to accept donations from the alcohol industry or for politicians to attend alcohol industry‐hosted events. One‐third of the participants agreed that public officials (including politicians) with a role in health policy should never be allowed to work or lobby for the alcohol industry (31.7%) and one‐third endorsed a waiting time of 4–5 years. Discussion: There were demographic differences in the views that participants held of the alcohol industry and the relationship between the government and the alcohol industry. The findings suggest that the laws and controls governing industry–government relationships should be reviewed to ensure they are in line with public expectations, accompanied by education programs including a focus on corporate political activity by the alcohol industry.

Abstract Objective: The Northern Territory (NT) Government introduced a minimum unit price (MUP) of $1.30 per standard drink (10g pure alcohol) explicitly aimed at reducing the consumption of cheap wine products from October 2018. We aimed to assess the impact of the NT MUP on estimates of beverage‐specific population‐adjusted alcohol consumption using wholesale alcohol supply data. Methods: Interrupted time series analyses were conducted to examine MUP effects on trends in estimated per capita alcohol consumption (PCAC) for cask wine, total wine and total alcohol, across the NT and in the Darwin/Palmerston region. Results: Significant step decreases were found for cask wine and total wine PCAC in Darwin/Palmerston and across the Northern Territory. PCAC of cask wine decreased by 50.6% in the NT, and by 48.8% in Darwin/Palmerston compared to the prior year. PCAC for other beverages (e.g. beer) were largely unaffected by MUP. Overall, PCAC across the Territory declined, but not in Darwin/Palmerston. Conclusion: With minimal implementation costs, the Northern Territory Government's MUP policy successfully targeted and reduced cask wine and total wine consumption. Cask wine, in particular, almost halved in Darwin/Palmerston where the impact of the MUP was able to be determined and considering other interventions. Implications for public health: Implementation of a minimum unit price for retail alcohol sales is a cost‐effective way to reduce the consumption of high alcohol content and high‐risk products, such as cheap cask wine.

Introduction The Banned Drinker Register (BDR) was reintroduced in the Northern Territory (NT) in September 2017. The BDR is a supply reduction measure and involves placing people who consume alcohol at harmful levels on a register prohibiting the purchase, possession and consumption of alcohol. The current study aims to evaluate the impacts of the reintroduction of the BDR, in the context of other major alcohol policy initiatives introduced across the NT such as Police Auxiliary Liquor Inspectors and a minimum unit price for alcohol of US$1.30 per standard drink.Methods and analyses The Learning from Alcohol (policy) Reforms in the Northern Territory project will use a mixed-methods approach and contain four major components: epidemiological analysis of trends over time (outcomes include health, justice and social welfare data); individual-level data linkage including those on the BDR (outcomes include health and justice data); qualitative interviews with key stakeholders in the NT (n≥50); and qualitative interviews among people who are, or were previously, on the BDR, as well as the families and communities connected to those on the BDR (n=150). The impacts of the BDR on epidemiological data will be examined using time series analysis. Linked data will use generalised mixed models to analyse the relationship between outcomes and exposures, utilising appropriate distributions. Qualitative data will be analysed using thematic analysis.Ethics and dissemination Ethics approvals have been obtained from NT Department of Health and Menzies School of Health Research Human Research Ethics Committee (HREC), Central Australia HREC and Deakin University HREC. In addition to peer-reviewed publications, we will report our findings to key organisational, policy, government and community stakeholders via conferences, briefings and lay summaries.

Cryptosporidium infection can cause severe diarrhea with limited treatment options available. Here, Lunde et al. perform a drug repositioning screen with a library of benzoxaboroles and identify AN7973 as potent inhibitor of intracellular parasite development with good efficacy in murine and neonatal dairy calf disease models.

Though often perceived as static, Amish identity is subject to change. The mid-twentieth century was a period of notable change. The recent experience of World War II, American religious revival movements, and economic pressures all placed pressure upon Amish communities to adapt. This paper highlights the experience of the Amish community of Partridge, Kansas, where these pressures and widespread interest in mission work eventually led to a church division in the 1950s. This paper explores the contributing factors to that split and examines the reactions on both sides to the division.

Here, the authors provide a panel of medium-throughput assays to test potential drug candidates against different life cycle stages of Cryptosporidium with the goal to support a drug development pipeline that contains compounds with diverse molecular mechanisms of action.

Political redistricting is the redrawing of electoral district boundaries. It is normally undertaken to reflect population changes. The process can be abused, in what is called gerrymandering, to favor one party or interest group over another, resulting thereby in broadly undemocratic outcomes that misrepresent the views of the voters. Gerrymandering is especially vexing in the United States. This paper introduces an algorithm, with an implementation, for creating districting plans (whether for political redistricting or for other districting applications). The algorithm, Seed-Fill-Shift-Repair (SFSR), is demonstrated for Congressional redistricting in American states. SFSR is able to create thousands of valid redistricting plans, which may then be used as points of departure for public deliberation regarding how best to redistrict a given polity. The main objectives of this paper are: (i) to present SFSR in a broadly accessible form, including code that implements it and test data, so that it may be used for both civic deliberations by the public and for research purposes. (ii) to make the case for what SFSR essays to do, which is to approach redistricting, and districting generally, from a constraint satisfaction perspective and from the perspective of producing a plurality of feasible solutions that may then serve in subsequent deliberations. To further these goals, we make the code publicly available. The paper presents, for illustration purposes, a corpus of 11,206 valid redistricting plans for the Commonwealth of Pennsylvania (produced by SFSR), using the 2017 American Community Survey, along with descriptive statistics. Also, the paper presents 1,000 plans for each of the states of Arizona, Michigan, North Carolina, Pennsylvania, and Wisconsin, using the 2018 American Community Survey, along with descriptive statistics on these plans and the computations involved in their creation.

Abstract Background This study aims to explore short-term changes following the introduction of alcohol restrictions (most notably 2 am to 3 am last drinks). We examined patterns of nightlife attendance, intoxication, and alcohol use among patrons shortly before and after restrictions were introduced in Fortitude Valley, Brisbane: the largest night-time entertainment precinct of Queensland. Methods Street-intercept patron interviews were conducted in Fortitude Valley in June (n = 497) and July (n = 562) 2016. A pre-post design was used to assess changes in time spent out drinking/partying prior to the interview, time of arrival in the precinct, pre-drinking, and blood alcohol concentration (BAC). Results Regression models indicated that after the policy introduction, the proportion of people arriving at Fortitude Valley before 10:00 pm increased (OR = 1.38; 95% CI = 1.04, 1.82). Participants reported going out, on average, one hour earlier after the intervention (β = − 0.17; 95% CI = 0.11, 0.22). There was a decrease (RRR = 0.58; 95% CI = 0.43, 0.79) in the proportion of participants who had a high level of intoxication (BAC ≥0.10 g/dL) post-intervention. No other significant differences were found. Conclusions Earlier cessation of alcohol sales and stopping the sale of rapid intoxication drinks after midnight was associated with people arriving in Fortitude Valley earlier. Though legislative loopholes allowed some venues to continue trading to 5 am, the proportion of people in the precinct who were highly intoxicated decreased after the restriction. Further measurement will be required to determine whether the reduction has persisted.

This project is contextualized in Shijing Xu and Michael Connelly’s (2013-2020) SSHRC Partnership Grant Project, Canada-China Reciprocal Learning in Teacher Education and School Education. The goal of the SSHRC Partnership Grant Project is to compare Canadian and Chinese education in such a way that the cultural narratives of each provide frameworks for understanding and appreciating educational similarities and differences (Xu & Connelly, 2017). The overall goal centers on reciprocal learning in teacher education between Canada and China. Xu and Connelly (2017) emphasize research that focuses on centering the voices of teachers in both Canada and China. This work seeks to help the project by providing data about China’s politics curriculum to create a better understanding of China’s education system, and to gain some insight into the hopes and dreams of Chinese politics teachers.

Objectives: Despite continued health concerns associated with the practice of consuming alcohol mixed with energy drinks (AmED), few Australian studies have examined the popularity of this combination or attempted to characterise AmED consumers. The purpose of this paper is to replicate two previously used survey approaches to consolidate a national picture of AmED consumption in Australia. Methods: The survey approaches used were: an online survey with a convenience sample of New South Wales (NSW), Australia, residents (n = 1931; 63.7% female; median age 23.0 years); and street intercept surveys in regional and metropolitan entertainment precincts in NSW (n = 1265; 58.2% male; median age 21.0 years). Analyses explored the rates and frequency of AmED use across both samples, and the sociodemographic and substance use predictors of AmED consumption in the past 12 months. Results: More than 90% of participants in both samples reported alcohol consumption in the past 12 months, with approximately 40% of current drinkers also reporting AmED use in the past 12 months. Three-quarters of participants interviewed in entertainment precincts reported alcohol consumption in the previous 12 hours, with one in six of these also reporting AmED consumption in the past 12 hours. AmED users across both samples were more likely than alcohol-only consumers to be younger and male, and to report riskier substance use practices. Conclusions: Health promotion activities are warranted to promote awareness of energy drink guidelines, and the potential harms of exceeding these guidelines, among alcohol consumers. In addition, health workers should consider enquiring about AmED use as an indicator of risk related to substance use.

Cryptosporidiosis causes life-threatening diarrhea in infants, but the best available treatment is only modestly efficacious. Rodents infected with relevant Cryptosporidium species do not develop diarrhea, which complicates drug development. Cryptosporidium parvum infection of dairy calves, however, causes an illness like that seen in infants. Here, the clinical and microbiologic anti-Cryptosporidium efficacy of the piperazine-based compound MMV665917 was demonstrated in neonatal calves. Oral administration of MMV665917 (22 mg/kg once daily) was begun two days after the onset of severe diarrhea and continued for seven days. Treatment resulted in prompt resolution of diarrhea, and reduced total fecal oocyst shedding by ~94%. MMV665917 was useful for treatment, rather than just prophylaxis, since it was safe and effective when administered well after the onset of diarrhea. Furthermore, even though all animals received intensive supportive care, there was a strong trend towards improved secondary health outcomes, including general health, appetite, and dehydration measures amongst treated animals. These data establish MMV665917 as an outstanding lead compound for Cryptosporidium drug development.

Abstract Objective: To investigate alcohol consumption, substance use and risky and harmful behaviour among young people attending ‘schoolies’ week in Victoria. Methods: Breathalyser tests and brief surveys (n=558) measuring alcohol, energy drink and illicit drug use, and experience of aggressive incidents, alcohol‐related injury and unprotected sex, were undertaken with young people attending schoolies week in Lorne and Torquay. Results: Schoolies reported consuming a mean of 8.8 drinks in the current session, with a mean blood alcohol count (BAC) of 0.05; 18.3% recorded a BAC of greater than 0.08. One in six participants had consumed alcohol with energy drinks; 7.7% reported using illicit substances. Participants who co‐consumed alcohol and energy drinks recorded a higher BAC than alcohol‐only users. One in five participants had experienced alcohol‐related harm at schoolies week, including aggressive incidents, alcohol‐related injury and engagement in unprotected sex. Each alcoholic drink consumed increased the potential for involvement in aggressive incidents by 8% and alcohol‐related accidents/injuries by 5%; illicit drug use was associated with six times the likelihood of engaging in unprotected sex with a non‐partner. Conclusions and implications: Excessive alcohol consumption and experience of related harms are common among young people attending schoolies week. Harm reduction initiatives targeting schoolies week should focus on the consequences of excessive alcohol consumption, illicit drugs and the co‐consumption of alcohol and energy drinks.

Previous studies have shown nonpartisan direct mail interventions have a small turnout effect. It is less clear, however, what effect these interventions have with regard to cognitive mobilization of young voters. We report the results of a large ( N =52,324) experiment conducted during the February 2015 mayoral election in Chicago. A random sample of 22,179 registrants between 18 and 30 were sent a voter guide containing two sets of orienting political information for the five candidates: a list of their endorsements and their policy positions on five issues in the campaign. We find turnout among the treated group was 0.9 points higher than the control group which did not receive a guide (33.6% compared with 32.7%; SE is 0.003). We find, however, that treated registrants in above-median household income census tracts are significantly more likely to vote than treated registrants in lower-income census tracts.

Estimate the amount of alcohol advertising in sport vs. non-sport programming in Australian free-to-air TV and identify children's viewing audience composition at different times of the day. Alcohol advertising and TV viewing audience data were purchased for free-to-air sport and non-sport TV in Australia for 2012. We counted alcohol advertisements in sport and non-sport TV in daytime (6 am-8.29 pm) and evening periods (8.30 pm-11.59 pm) and estimated viewing audiences for children and young adults (0-4 years, 5-13 years, 14-17 years, 18-29 years). During the daytime, most of the alcohol advertising (87%) was on sport TV. In the evening, most alcohol advertising (86%) was in non-sport TV. There was little difference in the mean number of children (0-17 years) viewing TV in the evening (N = 273,989), compared with the daytime (N = 235,233). In programs containing alcohol advertising, sport TV had a greater mean number of alcohol adverts per hour (mean 1.74, SD = 1.1) than non-sport TV (mean 1.35, SD = .94). Alcohol advertising during the daytime, when large numbers of children are watching TV, is predominantly in free-to-air sport TV. By permitting day-time advertising in sport programs and in any programs from 8.30 pm when many children are still watching TV, current regulations are not protecting children from exposure to alcohol advertising.

On the French continental shelf of the Bay of Biscay the variability of the surface salinity distribution has been mainly investigated at the seasonal and inter-annual scales. Here, new mesoscale features such as lower-salinity lenses observed in model results are investigated by hydrological measurements acquired during 8 cruises (1997-2000). These lenses are 50-80 km wide and ~30 m thick and occur during westerly to northerly wind events that push offshore the less saline water of river plumes. These water masses detached from the coast are replaced with upwelled saltier water at the coast, so coastal upwelling is often observed at the same time along Landes and southern Brittany coasts. We show that in addition to the influence of seasonal and inter-annual variability of the wind and river outflows, short term meteorological variability may drive mesoscale structures on this continental shelf.

Individual Carbon Nanotubes (CNTs) have a great mechanical strength that needs to be transferred into macroscopic fiber assemblies. One approach to improve the mechanical strength of the CNT assemblies is by creating covalent bonding among their individual CNT building blocks. Chemical cross-linking of multiwall CNTs (MWCNTs) within the fiber has significantly improved the strength of MWCNT thread. Results reported in this work show that the cross-linked thread had a tensile strength six times greater than the strength of its control counterpart, a pristine MWCNT thread (1192 MPa and 194 MPa, respectively). Additionally, electrical conductivity changes were observed, revealing 2123.40 S·cm−1 for cross-linked thread, and 3984.26 S·cm−1 for pristine CNT thread. Characterization suggests that the obtained high tensile strength is due to the cross-linking reaction of amine groups from ethylenediamine plasma-functionalized CNT with the epoxy groups of the cross-linking agent, 4,4-methylenebis(N,N-diglycidylaniline).

This essay aims to introduce readers to the social studies of accounting, attending in particular to the roles and relevance of Foucault’s works for this field. We provide a brief overview of social studies of accounting, discuss recent developments in Foucault oriented accounting scholarship, and position the articles that appear in this special issue in the context of these developments. In the concluding section, we argue that accounting is an inherently territorializing activity. The calculative instruments of accountancy transform not only the possibilities for personhood, they also construct the physical and abstract calculable spaces that individuals inhabit. A focus on territorializing shifts attention to the links between calculating and governing.