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This research seeks a clearer understanding of listener perspectives on issues of ethics in true crime podcasts (TCPs). To do so, the study first divides TCPs into three subgenres: Documentary, Recap and Expert. Then, it uses a mixed methods content analysis of listener reviews (n = 1200) of TCPs to ascertain listeners’ value systems and preferences when assessing podcasts, the role of ethics in audience evaluations of TCPs and the impact of subgenre on listener response. It finds that a large subsection of the reviewer audience (29.7 per cent) privileged ethics as a key criterion for evaluating and reviewing podcasts and that listeners’ level of engagement with issues of ethics is specific, careful and nuanced. It also finds that subgenre can play a role in shaping engagement with content, with Documentary and Recap formats more likely to result in listeners relating to content as entertainment.

The global temperature increase due to global change is predicted to be between 3.3 – 5.7°C by 2100 leading to changes at the base of the marine food web in species composition, abundance, and quality at the base of the marine food web leading to flow-on effects of higher trophic levels such as fish and humans. Changes in marine prey availability and nutritional quality can affect juvenile salmon conditions (i.e., growth, condition, and mortality) during the early marine phase. There is limited knowledge of the interplay between prey availability and prey quality and the importance of food quality under food-satiated conditions. Here, a three-phase feeding experiment measured the effects of nutritional quality (fatty acid composition and ratios) on juvenile Chinook salmon (Oncorhynchus tshawytscha) condition. Experimental diets represented the present three different climate scenarios with a present-day diet (Euphausia pacifica), a control diet (commercial aquaculture diet), and a predicted IPCC worst-case scenario diet with low essential fatty acid concentrations (IPCC SSP5-8.5). We tested how potential future low quality food affects growth rates, body condition, fatty acid composition and mortality rates in juvenile Chinook salmon compared to present-quality prey. Fatty acids were incorporated into the salmon muscle at varying rates but, on average, reflected dietary concentrations. High dietary concentrations of DHA, EPA and high DHA:EPA ratios resulted in increased fish growth and condition. In contrast, low concentrations of DHA and EPA and low DHA:EPA ratios in the diets were not compensated for by increased food quantity. This result highlights the importance of considering food quality when assessing fish response to changing ocean conditions.HighlightsClimate change may decrease the quality of salmon prey through changes in the fatty acid composition.Low dietary essential fatty acid levels reduce growth and condition and increase mortality rates in juvenile Chinook salmon.Food quality changes within zooplankton species but also by changes between species.Results suggest potential cascading effects on higher trophic levels when zooplankton species composition shifts to lower quality species.Higher food intake cannot compensate for low food quality.

Background: Coronavirus disease 2019 (COVID-19) is recognized as a multisystem disease affecting the whole body, with new complications from the disease being described on an almost-daily basis. Case Report: We report the case of a 50-year-old female with a medical history of diabetes and silicone breast implants who developed right-sided, multicentric breast masses after a prolonged hospitalization for COVID-19 infection complicated by renal failure requiring dialysis. The patient noted an onset of breast pain and masses, and subsequent imaging demonstrated multiple similar oval masses. She underwent biopsy and operative debridement of the lesions and recovered appropriately. Results were consistent with sterile abscesses that were considered secondary to a vasculitis-like process associated with COVID-19 infection. Conclusion: To our knowledge, this case is the first account of breast pathology associated with a diagnosis of COVID-19 in the medical literature and encourages systematic evaluations of patients with coronavirus infections, including breast examinations.

The North Pacific Marine Salmon Diet Database is an open-access relational database built to centralize and make accessible salmon diet data through a standardized database structure. The initial data contribution contains 21,862 observations of salmon diet, and associated salmon biological parameters, prey biological parameters, and environmental data from the North Pacific Ocean. The data come from 907 unique spatial areas and mostly fall within two time periods, 1959–1969 and 1987–1997, during which there are more data available compared to other time periods. Data were extracted from 62 sources identified through a systematic literature review, targeting peer-reviewed and gray literature. The purpose of this database is to consolidate data into a common format to address gaps in our ecological understanding of the North Pacific Ocean, particularly with respect to salmon. This database can be used to address a variety of questions regarding salmon foraging, productivity, and marine survival. The North Pacific Marine Salmon Diet Database will continue to grow in the future as more data are digitized and become available., Measurement(s) Gastric Content • diet Technology Type(s) digital curation • microscopy Factor Type(s) predator capture method • year of data collection • longitude • latitude • predator life stage • predator lowest taxonomic level • predator characteristics • predator replicates • type of diet data • prey life stage • prey lowest taxonomic level • prey characteristics Sample Characteristic - Organism Oncorhynchus mykiss • Oncorhynchus kisutch • Oncorhynchus tshawytscha • Oncorhynchus nerka • Oncorhynchus keta • Oncorhynchus gorbuscha Sample Characteristic - Environment ocean Sample Characteristic - Location North Pacific Ocean Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12981989

ObjectiveMost current cardiovascular disease (CVD) risk stratification tools are for people without CVD, but very few are for prevalent CVD. In this study, we developed and validated a CVD severity score in people with coronary heart disease (CHD) and evaluated the association between severity and adverse outcomes.MethodsPrimary and secondary care data for 213 088 people with CHD in 398 practices in England between 2007 and 2017 were used. The cohort was randomly divided into training and validation datasets (80%/20%) for the severity model. Using 20 clinical severity indicators (each assigned a weight=1), baseline and longitudinal CVD severity scores were calculated as the sum of indicators. Adjusted Cox and competing-risk regression models were used to estimate risks for all-cause and cause-specific hospitalisation and mortality.ResultsMean age was 64.5±12.7 years, 46% women, 16% from deprived areas, baseline severity score 1.5±1.2, with higher scores indicating a higher burden of disease. In the training dataset, 138 510 (81%) patients were hospitalised at least once, and 39 944 (23%) patients died. Each 1-unit increase in baseline severity was associated with 41% (95% CI 37% to 45%, area under the receiver operating characteristics (AUROC) curve=0.79) risk for 1 year for all-cause mortality; 59% (95% CI 52% to 67%, AUROC=0.80) for cardiovascular (CV)/diabetes mortality; 27% (95% CI 26% to 28%) for any-cause hospitalisation and 37% (95% CI 36% to 38%) for CV/diabetes hospitalisation. Findings were consistent in the validation dataset.ConclusionsHigher CVD severity score is associated with higher risks for any-cause and cause-specific hospital admissions and mortality in people with CHD. Our reproducible score based on routinely collected data can help practitioners better prioritise management of people with CHD in primary care.

This commentary considers the changing nature of feature writing within the contexts of: multimedia tools, the online publishing landscape, shrinking newsrooms, changing revenue models, freelance markets, audience and story analytics and journalism education.

We examined spatial patterns in diet, trophic niche width and niche overlap for chum, pink and sockeye salmon across the North Pacific during 1959–1969. This is a baseline period before major hatchery enhancement occurred coinciding with a negative phase of the Pacific Decadal Oscillation. Large-scale (between regions) and fine-scale (within regions) spatial and interspecies differences were apparent. In the Western Subarctic, all species tended to consume zooplankton. In the Bering Sea, chum consumed zooplankton, while sockeye and pink alternated between zooplankton and micronekton. In the Gulf of Alaska/Eastern Subarctic, chum and sockeye specialized on gelatinous zooplankton and cephalopod prey, respectively, while pink consumed a mixture of zooplankton and micronekton. The highest diet overlap across the North Pacific was between pink and sockeye (46.6%), followed by chum and pink (31.8%), and chum and sockeye (30.9%). Greater diet specialization was evident in the Gulf of Alaska/Eastern Subarctic compared to the Western Pacific. Generally, species had higher niche width and overlap in areas of high prey availability, and this was particularly evident for chum salmon. In addition to the large-scale trophic patterns, our data revealed novel fine-scale spatial patterns, including latitudinal, onshore-offshore, and cross-gyre gradients. Our results showed that pink tended to be more generalist consumers, and their diets may be a better reflection of overall prey presence and abundance in the environment. Conversely, chum and sockeye tended to be more specialist consumers, and their diets may provide a better reflection of interspecies dynamics or prey availability. This study provides a baseline for comparison with current and future changes in salmon marine ecology and North Pacific ecosystems. Finally, we identify two important data gaps that need addressing, that of improved taxonomic resolution diet data for Pacific salmon and focused research on sub-mesoscale oceanographic features that may play an important role in salmon health and productivity.

In December of 2017, the Craft Beverage and Modernization Tax Reform Act (CBMTRA) initially lowered Federal beer excise taxes for a period of two years. At the end of 2019, Congress extended the legislation through December 31, 2020. The Taxpayer Certainty and Disaster Tax Act of 2020 made the reduction permanent. The intent of the CBMTRA was to encourage investment in the craft (micro) brewing industry. We evaluate the ramifications of the CBMTRA on producers, consumers, and tax receipts, as well as quantify potential differential effects between the micro, regional, and macro brewing sectors. We also quantify the impact of excise tax reductions on input suppliers including barley, labor, non-labor, and equity capital providers. Although the per barrel excise tax reduction was supposed to primarily support the micro brewing sector, we find that the CBMTRA actually provided a larger benefit to the regional and macro brewing sectors.

This chapter examines the relationships between three complimentary paradigms: food experiences, food well-being, and design thinking. All three are holistic approaches to improving individual and community well-being – herein, food well-being is the goal, food experiences are the mechanism, and design thinking is the tool. This chapter first defines each concept, which are all relatively new to academic inquiry. Next, it traces the history of design thinking from its roots in 20th century mechanical and industrial engineering, to its modern incarnation of rethinking our approach to effective problem-solving. The chapter simultaneously examines the evolution of food design during the same timeframe, noting when and how food experiences have received greater and less attention from designers and consumers. Next, the chapter examines how a design thinking approach can be used to examine and improve food experiences, and to increase food well-being. Finally, because food experiences and food well-being are, to date, underrepresented in the portfolio of design thinking contexts, we conclude by emphasizing how food-related research can and should be put into practice by applying design thinking, thus increasing our understanding of the utility of all three concepts.

Here, we report the genome sequence of Arthrobacter sp. strain RT-1, isolated from a cocktail of termite gut and rumen fluid. Strain RT-1 degrades a variety of lignin monomers and dimers as the growth substrates. The genome annotation predicted the genes necessary for the catabolism of lignin-derived aromatic compounds.

Salmon migrate thousands of kilometers through dynamic ecosystems of the North Pacific Ocean, however, their open ocean life phase is poorly understood with limited research comparing salmon trophic ecology across the entire basin. Understanding the marine trophic ecology of salmon has the potential to reveal information about ocean conditions, competition, prey abundance, as well as salmon health and survival. The first goal of this research was to build an open-access database to centralize Pacific salmon diet data using a standardized format (‘North Pacific Marine Salmon Diet Database’). This database was then populated with an initial data set that came from 62 sources identified through a systematic literature review, targeting peer reviewed and gray literature from time periods with high research activity: 1959–1969 and 1987–1997. The second goal was to examine spatial and interspecies differences in diet and trophic niche for chum, pink and sockeye salmon across the North Pacific between 1959 and 1969, a period during a negative phase of the Pacific Decadal Oscillation and prior to significant hatchery enhancement. In the Western Subarctic, all species tended to consume zooplankton and prey availability was higher than the Eastern Subarctic. In the Gulf of Alaska and Eastern Subarctic, interspecies differences in diet were most apparent with chum and sockeye specializing on zooplankton and micronekton, respectively, while pink ate a mixture of zooplankton and micronekton. In the Bering Sea chum ate zooplankton while sockeye and pink alternated between zooplankton and micronekton. In addition to the large-scale trophic patterns, these data revealed novel fine-scale spatial trophic patterns, including latitudinal, onshore-offshore, and cross-gyre gradients. These results showed that pink were more generalist consumers, and their diets may be a better reflection of overall prey presence and abundance in the environment. Conversely, chum and sockeye were more specialist consumers, and their diets may be a better reflection of interspecies dynamics and/or specific prey presence and abundance of zooplankton and micronekton, respectively. Overall, this research provides an open-access database that can help address gaps in ecological understanding of the North Pacific, as well as complementary data analyses to further understanding of salmon marine ecology.

As a case study, this article will illustrate how a project-based approach has addressed some of the challenges of embedding data journalism content into courses at a small Australian university. I...

Introduction Obesity during pregnancy is associated with meta-inflammation and an increased likelihood of clinical complications. Surgery results in intense, acute inflammatory responses in any individual. Because obese individuals exhibit constitutive inflammatory responses and high rates of Caesarian section, it is important to understand the impact of surgery in such populations. Whether more pronounced pro-inflammatory cytokine responses and/or counterbalancing changes in anti-inflammatory immune modulators occurs is unknown. Here we investigated innate immune capacity in vivo and in vitro in non-obese, term-pregnant controls versus healthy, term-pregnant obese women (Class II, BMI 35–40). Methods Systemic in vivo induction of eleven pro- and anti-inflammatory biomarkers and acute phase proteins was assessed in plasma immediately prior to and again following Caesarian section surgery. Independently, innate immune capacity was examined by stimulating freshly isolated PBMC in vitro with a panel of defined PRR-ligands for TLR4, TLR8, TLR3, and RLR 24 h post-surgery. Results The kinetics and magnitude of the in vivo inflammatory responses examined were indistinguishable in the two populations across the broad range of biomarkers examined, despite the fact that obese women had higher baseline inflammatory status. Deliberate in vitro stimulation with a range of PRR ligands also elicited pro- and anti-inflammatory cytokine responses that were indistinguishable between control and obese mothers. Conclusions Acute in vivo innate immune responses to C-section, as well as subsequent in vitro stimulation with a panel of microbial mimics, are not detectably altered in Class II obese women. The data argue that while Class II obesity is undesirable, it has minimal impact on the in vivo inflammatory response, or innate immunomodulatory capacity, in women selecting C-section.

Myriad automated interventions have been designed to help consumers set and achieve behavioral goals. Firms and governments are making significant investments in applications that help consumers manage their behavior. However, scant evidence demonstrates their effectiveness. Are such interventions effective? Are they worth our time and money? Might they do more harm than good? This study presents the results of an exploratory experiment using Self Determination Theory to test the efficacy of one type of motivational aid used in many apps--the automated prompt. We examine how effective this approach is at helping people make long-term behavioral changes. We also test whether providing people with motivational wisdom--i.e., "it takes three weeks to form a habit"--has an effect on behavioral change. In addition to practical implications for consumers' health, productivity, and happiness, and policy implications, our project contributes to the literature on consumers' motivation and goal pursuit. It is no secret that despite our best intentions, most people's New Year's resolutions are resolutely broken by February 1, books on our "must read" lists gather dust, and dissertations remain unpublished. Despite steady progress surrounding the intention-behavior gap (Gollwitzer 1993, 1999; Lally and Gardner 2013; Orbell, Hodgkins, and Sheeran 1997), people still struggle to attain simple behavioral goals, such as flossing their teeth regularly (Sniehotta, Soares, and Dombrowski 2007). Naturally, then, goal-setting and motivation are ripe targets for self-help innovations. As such, corporations and governments are making significant investments in apps to help people improve their behaviors and lifestyles (Sifferlin 2013). However, while myriad websites and apps promise to help people achieve their goals, there are critical questions that must be answered: Are these programs effective? Are they worth our time and money? Might they do more harm than good? As Forbes asks, "Will an App a Day Keep the Doctor Away?" (Tilenius 2013). Despite the emergence of internet-based and mobile interventions to help consumers achieve behavioral goals, scant nonanecdotal evidence demonstrates their effectiveness. Even evidence-based programs such as stickK (Ashraf, Karlan, and Yin 2006) provide no empirical evidence of their efficacy. Nonetheless, tech bloggers (e.g., Newman 2013), lifestyle gurus (e.g., Ferriss 2010), and academics (e.g., Rutledge et al. 2011) promote them. Motivational apps are appealing because they confirm people's instinct that "an ounce of prevention is worth a pound of cure." Paradoxically, the proliferation of information online may make it harder for consumers to determine how to improve their well-being (Austin et al. 2012; Cline and Haynes 2001; Eysenbach and Kohler 2002). Thus, we are concerned about potential harms, ranging from wasting money to experiencing negative unintended effects (Moller, Ryan, and Deci 2006). Research that demonstrates which types of programs enhance people's health, productivity, and happiness--and why--would be invaluable. The benefits of such a project are meaningful in terms of time, money, effort, and policy recommendations. This article reports the results of an exploratory study. Using Self Determination Theory (SDT, Deci and Ryan 1985), we examine the efficacy of two popular tools--automated daily reminders (i.e., electronic periodic prompts, Fry and Neff 2009), and promoting an oft-repeated canard as fact (i.e., "It takes 21 days to form a habit")--for making positive behavioral changes. Our experiment does not test for genuine habit formation, rather, we test how effective extrinsic motivators are for helping people achieve behavioral goals. The results are counterintuitive (cf. Loibl and Scharff 2010). SDT can help guide a comprehensive effort toward understanding the mechanisms underlying motivational apps. We agree with other researchers (e. …

Myotonic Dystrophy is the most common form of muscular dystrophy in adults, affecting an estimated 10 per 100,000 people. It is a multisystemic disorder affecting multiple generations with increasing severity. There are currently no licenced therapies to reverse, slow down or cure its symptoms. In 2009 TREAT-NMD (a global alliance with the mission of improving trial readiness for neuromuscular diseases) and the Marigold Foundation held a workshop of key opinion leaders to agree a minimal dataset for patient registries in myotonic dystrophy. Eight years after this workshop, we surveyed 22 registries collecting information on myotonic dystrophy patients to assess the proliferation and utility the dataset agreed in 2009. These registries represent over 10,000 myotonic dystrophy patients worldwide (Europe, North America, Asia and Oceania).The registries use a variety of data collection methods (e.g. online patient surveys or clinician led) and have a variety of budgets (from being run by volunteers to annual budgets over €200,000). All registries collect at least some of the originally agreed data items, and a number of additional items have been suggested in particular items on cognitive impact.The community should consider how to maximise this collective resource in future therapeutic programmes.

ELISAs and similar immunoassays are a backbone of biomedical research and clinical practice. Here we review the major factors to consider in the development and application of ultrasensitive ELISAs for analysis of human immune responses in plasma, serum, urine, or tissue culture supernatants. We focus on cytokine and chemokine biomarkers of health and chronic inflammatory diseases including allergy, asthma, autoimmunity, and cardiovascular disease. Detailed protocols for ELISA and Meso Scale Discovery assays (an improved variant of ELISA) are provided for 15 cytokines and 11 chemokines that play immune-regulatory roles in human innate and adaptive immunity. Protocols have been individually optimized to yield ultrasensitive limits of detection and quantification. Major factors enhancing immunoassay sensitivity, precision, and reproducibility, as well as key pitfalls in assay design and execution, are critically reviewed.

ELISAs and similar immunoassays are a backbone of biomedical research and clinical practice. Here we review the major factors to consider in the development and application of ultrasensitive ELISAs for analysis of human immune responses in plasma, serum, urine, or tissue culture supernatants. We focus on cytokine and chemokine biomarkers of health and chronic inflammatory diseases including allergy, asthma, autoimmunity, and cardiovascular disease. Detailed protocols for ELISA and Meso Scale Discovery assays (an improved variant of ELISA) are provided for 15 cytokines and 11 chemokines that play immune-regulatory roles in human innate and adaptive immunity. Protocols have been individually optimized to yield ultrasensitive limits of detection and quantification. Major factors enhancing immunoassay sensitivity, precision, and reproducibility, as well as key pitfalls in assay design and execution, are critically reviewed.

Since 2011, unusually large quantities of pelagic Sargassum fluitans and S. natans (sargasso) have been washing ashore along the coasts of some African countries and the Greater Caribbean, impacting ecosystems and economies. We estimated biomass and composition of sargasso arriving to a Mexican Caribbean coast from September 2016 until May 2020. In 2016, the beached masses comprised S. natans VIII and S. fluitans III. S. fluitans III was the predominant form throughout the study period, comprising on average >60 % of total wet biomass. The relative abundance of S. natans VIII decreased in time from 2016 to 2019 (41 to 3 %), although it became prevalent again in the first months of 2020. The third morphological form, S. natans I, was not registered until February 2018, and its relative abundance increased from 23 % in 2018 to 31 % in 2019. The initial composition of Sargassum species and morphotypes of the beached sargasso in Mexico differed from that commonly reported in the Sargasso Sea. The total biomass of beached sargasso varied considerably among years and seasons, with peaks during the summer months of 2018 and 2019. Seasonal variations in biomass were explained by 1) presence of sargasso in the Yucatan Current and 2) prevailing trade winds. This study is the first report on biomass and species composition of beached sargasso in the Western Caribbean and may help to understand patterns of the massive influxes; which will aid in the management of this new phenomenon.

Background Adolescent girls involved with the juvenile justice system have higher rates of sexually transmitted infections and pregnancy than their nondetained peers. Although they may receive reproductive health care while detained, following clinician recommendations and accessing services in the community can be challenging. Objectives This study aimed to determine the barriers this population faces 1) accessing reproductive health care and 2) following the recommendations they receive when they are in the community. Methods Adolescent girls at a juvenile detention facility completed online surveys about their demographics and sexual health behaviors. A subsequent semistructured interview assessed their experiences with reproductive health care services. Results Twenty-seven girls aged 14 to 19 were interviewed. The majority (86%) self-reported as Latina or Hispanic. The average age of sexual debut was 13.8 years. The major interview themes were 1) personal priorities and motivations affect decision making, 2) powerful external voices influence reproductive health choices, 3) accessing services “on the run” is particularly challenging, and 4) detention represents an opportunity for intervention and change. Conclusion Adolescent girls who are detained within the juvenile justice system face reproductive health challenges that vary with their life circumstances. They frequently have priorities, external voices, and situations that influence their decisions. Clinicians who care for these young women are in a unique position to address their health needs. Eliciting girls' goals, beliefs, and influences through motivational interviewing, as well as developing targeted interventions based on their unique experiences, may be particularly helpful for this population.

Worldwide, journalism students—under the supervision of lecturers, and backed by the resources of universities—have begun to distinguish themselves as important creators of public interest reporting. The industry shift towards collaborative, multi-directional news-gathering processes places these students, as networked journalists, in a favoured position within emerging information spaces. However, despite widespread interest within the industry and academe in the roles non-traditional participants can play in creating media content, literature outlining the frameworks and processes for networked journalism initiatives is scarce. Using a data-driven political investigation by Bond University students as a case study, this article contributes to the creation of such frameworks. The ‘Order in the House’ project (published by Crikey in June 2013 ) mined publicly available Australian parliamentary records to assess 150 politicians’ engagement and efficiency in the lead-up to a federal election. This article outlines the scope and limitations of the project, and the research design, teaching techniques and technology used to facilitate data collection and presentation.

The loss and dysfunction of selected populations of synapses is characteristic of mammalian brain ageing and alterations in these receptive compartments are considered to underpin age-related cognitive decline. Discrete neuro-anatomical regions of the cortical architecture harbour disparate populations of synapses that demonstrate significant heterogeneity with regards to advancing age. Of particular interest is the hippocampus, which is selectively vulnerable during ageing. The hippocampal synaptic architecture exhibits subtle structural and biophysical alterations, which are considered to promote the manifestation of cognitive symptoms in aged patients. This notion of “selective synaptic vulnerability” has been the focal point of a multitude of morphological studies investigating age-related cognitive decline, which have often provided tentative conclusions as to how this phenomenon may be regulated. The molecular correlates bolstering the reported age-dependent morphological and functional shift remain elusive and studies are only now beginning to unravel how discrete organelles, proteins and signalling cascades may hierarchically or synergistically attenuate synaptic function. Until there is considerable comprehension of how functional mediators drive the biochemical substrates regulating age-related cognitive decline, there are limited strategic avenues for the development of efficacious therapeutic interventions that promote successful ageing. To address the phenomenon of selective synaptic vulnerability, we have utilised an unbiased combinatorial approach, including quantitative proteomic analyses coupled with in vivo candidate assessments in lower order animals (Drosophila), to temporally profile regional synapse and synaptic mitochondrial biochemistry during normal healthy ageing. We begin by demonstrating that cortical mitochondria located at the synaptic terminal are morphologically distinct from non-synaptic mitochondria in adult rodents and human patients. Biochemical isolation and purification of discrete mitochondrial subpopulations from control adult rat fore-brain enabled generation of synaptic and non-synaptic mitochondrial molecular fingerprints using quantitative proteomics, which revealed that expression of the mitochondrial proteome is highly dependent on subcellular localisation. We subsequently demonstrate that the molecular differences observed between mitochondrial sub-populations are capable of selectively influencing synaptic morphology in-vivo. Next, we sought to examine how the synaptic mitochondrial proteome was dynamically and temporally regulated throughout ageing to determine whether protein expression changes within the mitochondrial milieu are actively regulating the age-dependent vulnerability of the synaptic compartment. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo. Although we had comprehensively characterised the temporal regulation of rodent cortical mitochondrial subpopulations, providing a number of novel candidates that may be mediating synaptic vulnerability during ageing, we sought to establish whether similar alterations were occurring in the primate brain. Using synaptic isolates from neuroanatomically distinct age-resistant (occipital cortex) and age-vulnerable (hippocampus) regions, we demonstrate that synaptic ageing is brainregion dependent and that discrete populations of synapses significantly differ at a biochemical level in the healthy human and non-human primate brain. Recapitulation of aged hippocampal protein expression with genetic manipulation in vivo revealed numerous novel candidates that have the propensity to significantly modulate multiple morphological parameters at the synapse. Furthermore, we demonstrate that several of these candidates sit downstream of TGFβ1 and activation of the TGFβ1 signalling cascade in hippocampal synaptic populations drives the aberrant expression of selected candidates during ageing. Finally, we show that selective pharmacological inhibition of this pathway rescues synaptic phenotypes in multiple candidate lines. The data affirmed that activation of the TGFβ1 transduction pathway modulates synaptic stability and thus may contribute to the selective vulnerability of hippocampal synapses during ageing.

Survey to capture details about the registry, database or mailing list. (PDF 270 kb)

One third of adults have taken an illicit drug at some point during their lifetime ( Home Office, 2014 ). This article aims to aid understanding of the implications substance misuse may have on oral health and dental care and how to treat patients who misuse substances

In some insects, eusociality has evolved independently more than once, such that closely related species differ in the presence or absence of altruistic traits. Such groups offer opportunities to study the ecological and evolutionary drivers of transitions to sociality. In Pemphigus aphids, for example, eusociality has evolved independently multiple times, but most species are assumed to be nonsocial. Eusocial aphids thus typically have close relatives that are nonsocial, indicating a rapid and distinct transition to sociality. However, there has been only limited study of the behaviour of nonsocial species that permit direct comparisons with eusocial species. In this study, we characterized three aphid species along two axes of social behaviour: housekeeping and defence. Previous evidence suggested that these three species differ in the presence or absence of social traits. We found that for the ecological and behavioural traits we tested, there were quantifiable differences between social and nonsocial species. However, there was no clear threshold that differentiated social from nonsocial species, meaning that definitions of sociality in aphids depend in part on the traits that are measured. If sociality is measured by defence, for example, the eusocial species, Pemphigus obesinymphae clearly expressed the greatest degree of aggressive and effective defence. However, some defensive behaviour was also present in the species traditionally defined as nonsocial. Conversely, if sociality in aphids is measured by traits related to homeostasis and housekeeping, then the species traditionally considered nonsocial expressed nearly the same behaviours as the eusocial species. These results imply that sociality in aphids evolves as a collection of uncorrelated traits. Clear analogues or antecedents of more derived social characters can be identified in species that are nominally nonsocial.

Introduction Obesity during pregnancy is associated with meta‐inflammation and an increased likelihood of clinical complications. Surgery results in intense, acute inflammatory responses in any individual. Because obese individuals exhibit constitutive inflammatory responses and high rates of Caesarian section, it is important to understand the impact of surgery in such populations. Whether more pronounced pro‐inflammatory cytokine responses and/or counterbalancing changes in anti‐inflammatory immune modulators occurs is unknown. Here we investigated innate immune capacity in vivo and in vitro in non‐obese, term‐pregnant controls versus healthy, term‐pregnant obese women (Class II, BMI 35–40). Methods Systemic in vivo induction of eleven pro‐ and anti‐inflammatory biomarkers and acute phase proteins was assessed in plasma immediately prior to and again following Caesarian section surgery. Independently, innate immune capacity was examined by stimulating freshly isolated PBMC in vitro with a panel of defined PRR‐ligands for TLR4, TLR8, TLR3, and RLR 24 h post‐surgery. Results The kinetics and magnitude of the in vivo inflammatory responses examined were indistinguishable in the two populations across the broad range of biomarkers examined, despite the fact that obese women had higher baseline inflammatory status. Deliberate in vitro stimulation with a range of PRR ligands also elicited pro‐ and anti‐inflammatory cytokine responses that were indistinguishable between control and obese mothers. Conclusions Acute in vivo innate immune responses to C‐section, as well as subsequent in vitro stimulation with a panel of microbial mimics, are not detectably altered in Class II obese women. The data argue that while Class II obesity is undesirable, it has minimal impact on the in vivo inflammatory response, or innate immunomodulatory capacity, in women selecting C‐section.

Objective: The objective of this article is to assess the readability of leaflets about urological procedures provided by the British Association of Urological Surgeons (BAUS) to evaluate their suitability for providing information. Methods: Information leaflets were assessed using three measures of readability: Flesch Reading Ease, Flesch-Kincaid and Simple Measure of Gobbledygook (SMOG) grade formulae. The scores were compared with national literacy statistics. Results: Relatively good readability was demonstrated using the Flesch Reading Ease (53.4–60.1) and Flesch-Kincaid Grade Level (6.5–7.6) methods. However, the average SMOG index (14.0–15.0) for each category suggests that the majority of the leaflets are written above the reading level of an 18-year-old. Using national literacy statistics, at least 43% of the population will have significant difficultly understanding the majority of these leaflets. Conclusions: The results suggest that comprehension of the leaflets provided by the BAUS is likely to be poor. These leaflets may be used as an adjunct to discussion but it is essential to ensure that all the information necessary to make an informed decision has been conveyed in a way that can be understood by the patient.

While there is a significant literature on the rise of narrative journalism in daily newspapers, mostly from the United States, few studies have investigated the breakdown of newswriting styles in the front end of the newspaper, with a specific focus on the use of narrative techniques. This study investigates the writing styles of two daily metropolitan print newspapers in order to provide some concrete data on narrative news reporting in Australia. In a sense, it responds to Mark Kramer's comment in 2000 that “no one has added up the reallocated column inches to quantify this change.” The research analyses 5000 articles from the news sections of broadsheets The Australian and The Sydney Morning Herald in 2007 and 2009 to determine a breakdown of writing styles. It found that narrative writing styles had decreased over the two-year period, claiming almost one-fifth of stories in 2007 but less than one-sixth in 2009. It also brings to the discussion in-depth interviews with leading newspaper editors and jo...

The Rare and Undiagnosed Diseases Diagnostic Service (RUDDS) is a Clinical Genomic Diagnostic Pipeline operating within the clinical service at Genetic Services of Western Australia (GSWA). GSWA has provided a state-wide service for clinical genetic care for more than 25 years and it serves a population of 2.5 million people. It includes paediatric, adult, prenatal and familial cancer services in metropolitan and regional WA. Within this framework, and in partnership with the Office of Population Health Genomics, Diagnostic Genomics at PathWest and others, it is delivering a clinically integrated pipeline. This service is aligned to the WA Rare Diseases Strategic Framework 2015-2018 to address the unmet need of the diagnostic odyssey of those living with rare and undiagnosed diseases. It is: (I) delivered in a patient-centric manner that is resonant with the patient journey; (II) offers multiple options including non-genetic testing; monogenic and genomic (targeted and whole exome) analysis, and matchmaking; (III) is synchronous with precision phenotyping methods, including 3D facial analysis, and phenotype-enabled decision support; (IV) captures new knowledge, including multiple expert review; (V) has multiple points for entry, exit and re-entry to allow people access to information they can use, when they want to receive it; (VI) draws on the clarity gained from the extremity of rare diseases to provide insights for more common diseases; (VII) is integrated with current translational genomic research activities; and (VIII) is designed for flexibility for integrative generation of, and integration with, further clinical research including for diagnostics, community engagement, policy and models of care.

Clinical decisions rely on expert knowledge that draws on quality patient phenotypic and physiological data. In this regard, systems that can support patient-centric care are essential. Patient registries are a key component of patient-centre care and can come in many forms such as disease-specific, recruitment, clinical, contact, post market and surveillance. There are, however, a number of significant challenges to overcome in order to maximise the utility of these information management systems to facilitate improved patient-centred care. Registries need to be harmonised regionally, nationally and internationally. However, the majority are implemented as standalone systems without consideration for data standards or system interoperability. Hence the task of harmonisation can become daunting. Fortunately, there are strategies to address this. In this paper, a disease registry framework is outlined that enables efficient deployment of national and international registries that can be modified dynamically as registry requirements evolve. This framework provides a basis for the development and implementation of data standards and enables patients to seamlessly belong to multiple registries. Other significant advances include the ability for registry curators to create and manage registries themselves without the need to contract software developers, and the concept of a registry description language for ease of registry template sharing.

Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of diabetic retinopathy. We investigated whether transgenic mice with moderate VEGF expression in photoreceptors (trVEGF029) developed changes similar to diabetic retinopathy and whether retinopathy progressed with time.Human VEGF(165) (hVEGF(165)) expression was analysed using ELISA and quantitative RT-PCR; serum glucose levels were also measured. Fundus fluorescein angiography (FA) was used to screen the degree of retinopathy from 6 weeks. Dynamic changes in the density of retinal microvasculature, as well as other changes similar to diabetic retinopathy, including retinal leucostasis, capillary endothelial cell and pericyte loss, and numbers of acellular capillaries, were quantified.trVEGF029 mice were normoglycaemic and showed a moderate, short-term hVEGF(165) upregulation for up to 3 weeks. Changes in the retinal microvasculature not only mimicked those seen in diabetic retinopathy, but also showed similar pathological progression with time. FA at 6 weeks identified two phenotypes, mild and moderate, which were distinguished by the extent of vascular leakage. Quantitative analysis of diabetic retinopathy-like changes revealed that these parameters were tightly correlated with the initial degree of vascular leakage; low levels reflected slow and limited retinal microvascular changes in mild cases and high levels reflected more rapid and extensive changes in moderate cases.The data suggest that even an early short-term elevation in hVEGF(165) expression might set a train of events that lead to progressive retinopathy. Induction of many features characteristic of diabetic retinopathy in trVEGF029 enables mechanisms leading to the disease state to be examined, and provides a relevant animal model for testing novel therapeutics.

Activation loop phosphorylation plays critical regulatory roles for many kinases. Unlike other protein kinase Cs (PKC), PKC-δ does not require phosphorylation of its activation loop (Thr-507) for in vitro activity. We investigated the structural basis for this unusual capacity and its relevance to PKC-δ function in intact cells. Mutational analysis demonstrated that activity without Thr-507 phosphorylation depends on 20 residues N-terminal to the kinase domain and a pair of phenylalanines (Phe-500/Phe-527) unique to PKC-δ in/near the activation loop. Molecular modeling demonstrated that these elements stabilize the activation loop by forming a hydrophobic chain of interactions from the C-lobe to activation loop to N-terminal (helical) extension. In cells PKC-δ mediates both apoptosis and transcription regulation. We found that the T507A mutant of the PKC-δ kinase domain resembled the corresponding wild type in mediating apoptosis in transfected HEK293T cells. But the T507A mutant was completely defective in AP-1 and NF-κB reporter assays. A novel assay in which the kinase domain of PKC-δ and its substrate (a fusion protein of PKC substrate peptide with green fluorescent protein) were co-targeted to lipid rafts revealed a major substrate-selective defect of the T507A mutant in phosphorylating the substrate in cells. In vitro analysis showed strong product inhibition on the T507A mutant with particular substrates whose characteristics suggest it contributes to the substrate selective defect of the PKC-δ T507A mutant in cells. Thus, activation loop phosphorylation of PKC-δ may regulate its function in cells in a novel way.

Background People with neuromuscular disorders (NMD) exhibit weak coughs and are susceptible to recurrent chest infections and acute respiratory complications, the most frequent reasons for their unplanned hospital admissions. Mechanical insufflation-exsufflation (MI-E) devices are a non-invasive method of increasing peak cough flow, improving cough efficacy, the clearance of secretion and overcoming atelectasis. There is limited published evidence on the impact of home use MI-E devices on health service utilisation. The aims of the study were: to assess the self-reported health and lifestyle benefits experienced as a result of home use of MI-E devices; and evaluate the effects of in-home use of MI-E devices on Emergency Department (ED) presentations, hospital admissions and inpatient length of stay (LOS). Methods Individuals with NMD who were accessing a home MI-E device provided through Muscular Dystrophy Western Australia were invited to participate in a quantitative survey to obtain information on their experiences and self-assessed changes in respiratory health. An ad-hoc record linkage was performed to extract hospital, ED and mortality data from the Western Australian Department of Health (DOHWA). The main outcome measures were ED presentations, hospital separations and LOS, before and after commencement of home use of an MI-E device. Results Thirty seven individuals with NMD using a MI-E device at home consented to participate in this study. The majority (73%) of participants reported using the MI-E device daily or weekly at home without medical assistance and 32% had used the machine to resolve a choking episode. The survey highlighted benefits to respiratory function maintenance and the ability to manage increased health care needs at home. Not using a home MI-E device was associated with an increased risk of ED presentations (RR = 1.76, 95% CI 1.1-2.84). The number of hospital separations and LOS reduced after the use of MI-E device, but not significantly. No deaths were observed in participants using the MI-E device at home. Conclusions Home use of a MI-E device by people living with NMD may have a potential impact on reducing their health service utilisation and risk of death. Future research with greater subject numbers and longer follow-up periods is recommended to enhance this field of study. Electronic supplementary material The online version of this article (doi:10.1186/s13023-015-0267-0) contains supplementary material, which is available to authorized users.