To test or to treat? an analysis of influenza testing and Antiviral treatment strategies using economic computer modeling

Background: Due to the unpredictable burden of pandemic influenza, the best strategy to manage testing, such as rapid or polymerase chain reaction (PCR), and antiviral medications for patients who present with influenza-like illness (ILI) is unknown. Methodology/Principal Findings: We developed a set of computer simulation models to evaluate the potential economic value of seven strategies under seasonal and pandemic influenza conditions: (1) using clinical judgment alone to guide antiviral use, (2) using PCR to determine whether to initiate antivirals, (3) using a rapid (point-of-care) test to determine antiviral use, (4) using a combination of a point-of-care test and clinical judgment, (5) using clinical judgment and confirming the diagnosis with PCR testing, (6) treating all with antivirals, and (7) not treating anyone with antivirals. For healthy younger adults (<65 years old) presenting with ILI in a seasonal influenza scenario, strategies were only cost-effective from the societal perspective. Clinical judgment, followed by PCR and point-of-care testing, was found to be cost-effective given a high influenza probability. Doubling hospitalization risk and mortality (representing either higher risk individuals or more virulent strains) made using clinical judgment to guide antiviral decision-making cost-effective, as well as PCR testing, point-of-care testing, and point-of-care testing used in conjunction with clinical judgment. For older adults (≥65 years old), in both seasonal and pandemic influenza scenarios, employing PCR was the most cost-effective option, with the closest competitor being clinical judgment (when judgment accuracy ≥50%). Point-of-care testing plus clinical judgment was cost-effective with higher probabilities of influenza. Treating all symptomatic ILI patients with antivirals was cost-effective only in older adults. Conclusions/Significance: Our study delineated the conditions under which different testing and antiviral strategies may be cost-effective, showing the importance of accuracy, as seen with PCR or highly sensitive clinical judgment. © 2010 Lee et al

Public health responses to influenza in care homes: a questionnaire-based study of local Health Protection Units.

BACKGROUND: Influenza virus infection poses a major threat to the elderly people in residential care. We sought to describe the extent to which local public health services in England were positioned to detect and respond effectively to influenza-like illness (ILI) in nursing homes. METHODS: A questionnaire-based survey was conducted in all 34 Health Protection Units (HPUs) regarding the 2004-05 influenza season. RESULTS: Of the 20 responses, half reported 24 outbreaks of ILI in care homes. The mean resident population attack rate was 41% (range 15-79) with 31 deaths. Staff ILI occurred in 23 of 24 outbreaks. Seven of 20 HPUs stated that a local policy for the management of ILI in nursing homes was in place, with only four specifying the use of neuraminidase inhibitors (NI) for treatment of cases and prophylaxis of residents. In the outbreaks reported, NIs were used for treatment and prophylaxis, respectively, in only 46 and 54% of instances. CONCLUSIONS: Given the availability of effective interventions for treatment and prophylaxis, there is potential to prevent substantial morbidity and mortality from influenza in at-risk populations. This study suggests that challenges remain in the effective response to influenza outbreaks in care homes and that there are wide variations in practice at local level

Diversity of Melissococcus plutonius from Honeybee Larvae in Japan and Experimental Reproduction of European Foulbrood with Cultured Atypical Isolates

European foulbrood (EFB) is an important infectious disease of honeybee larvae, but its pathogenic mechanisms are still poorly understood. The causative agent, Melissococcus plutonius, is a fastidious organism, and microaerophilic to anaerobic conditions and the addition of potassium phosphate to culture media are required for growth. Although M. plutonius is believed to be remarkably homologous, in addition to M. plutonius isolates with typical cultural characteristics, M. plutonius-like organisms, with characteristics seemingly different from those of typical M. plutonius, have often been isolated from diseased larvae with clinical signs of EFB in Japan. Cultural and biochemical characterization of 14 M. plutonius and 19 M. plutonius-like strain/isolates revealed that, unlike typical M. plutonius strain/isolates, M. plutonius-like isolates were not fastidious, and the addition of potassium phosphate was not required for normal growth. Moreover, only M. plutonius-like isolates, but not typical M. plutonius strain/isolates, grew anaerobically on sodium phosphate-supplemented medium and aerobically on some potassium salt-supplemented media, were positive for β-glucosidase activity, hydrolyzed esculin, and produced acid from L-arabinose, D-cellobiose, and salicin. Despite the phenotypic differences, 16S rRNA gene sequence analysis and DNA-DNA hybridization demonstrated that M. plutonius-like organisms were taxonomically identical to M. plutonius. However, by pulsed-field gel electrophoresis analysis, these typical and atypical (M. plutonius-like) isolates were separately grouped into two genetically distinct clusters. Although M. plutonius is known to lose virulence quickly when cultured artificially, experimental infection of representative isolates showed that atypical M. plutonius maintained the ability to cause EFB in honeybee larvae even after cultured in vitro in laboratory media. Because the rapid decrease of virulence in cultured M. plutonius was a major impediment to elucidation of the pathogenesis of EFB, atypical M. plutonius discovered in this study will be a breakthrough in EFB research

Predicting promoters in phage genomes using machine learning models

The renewed interest in phages as antibacterial agents has led to the exponentially growing number of sequenced phage genomes. Therefore, the development of novel bioinformatics methods to automate and facilitate phage genome annotation is of utmost importance. The most difficult step of phage genome annotation is the identification of promoters. As the existing methods for predicting promoters are not well suited for phages, we used machine learning models for locating promoters in phage genomes. Several models were created, using different algorithms and datasets, which consisted of known phage promoter and non-promoter sequences. All models showed good performance, but the ANN model provided better results for the smaller dataset (92% of accuracy, 89% of precision and 87% of recall) and the SVM model returned better results for the larger dataset (93% of accuracy, 91% of precision and 80% of recall). Both models were applied to the genome of Pseudomonas phage phiPsa17 and were able to identify both types of promoters, host and phage, found in phage genomes.This study was supported by the Portuguese Foundation for Science andTechnology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and theProject POCI-01-0145-FEDER-029628. This work was also supported by BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fundunder the scope of Norte2020 - Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersio

Mobilizing management knowledge in healthcare : institutional imperatives and professional and organizational mediating effects

Recent changes within UK healthcare have had dramatic consequences for management and put managerial capabilities firmly under the spotlight. Yet, despite extensive research on managers, comparatively little is known about how they acquire and apply their management knowledge and how this is influenced by their professional background and organizational context. Drawing upon work that distinguishes between different forms of knowledge, managers’ mobilization of management knowledge is examined in the light of recent changes in healthcare. Case study evidence is presented from diverse managerial groups across three types of hospital trust (acute, care and specialist). The analysis demonstrates the mediating effects of interactions between professional background and organizational context on knowledge mobilization and highlights how current pressures on public services are reinforcing a reliance on existing management practices, creating enormous challenges for management learning in this sector

Understanding the threats posed by non-native species: public vs. conservation managers.

Public perception is a key factor influencing current conservation policy. Therefore, it is important to determine the influence of the public, end-users and scientists on the prioritisation of conservation issues and the direct implications for policy makers. Here, we assessed public attitudes and the perception of conservation managers to five non-native species in the UK, with these supplemented by those of an ecosystem user, freshwater anglers. We found that threat perception was not influenced by the volume of scientific research or by the actual threats posed by the specific non-native species. Media interest also reflected public perception and vice versa. Anglers were most concerned with perceived threats to their recreational activities but their concerns did not correspond to the greatest demonstrated ecological threat. The perception of conservation managers was an amalgamation of public and angler opinions but was mismatched to quantified ecological risks of the species. As this suggests that invasive species management in the UK is vulnerable to a knowledge gap, researchers must consider the intrinsic characteristics of their study species to determine whether raising public perception will be effective. The case study of the topmouth gudgeon Pseudorasbora parva reveals that media pressure and political debate has greater capacity to ignite policy changes and impact studies on non-native species than scientific evidence alone

Core Depressive Symptoms In Depressed Cancer OutpatientsB

Objective: This study aimed to estimate the prevalence of core depressive symptoms among cancer outpatients diagnosed with depressive or adjustment disorders with depressed mood. We also aimed to detect potential differences between patient self-assessment and psychiatrist evaluation in classifying the severity of depression. Methods: Fifty-two outpatients diagnosed with solid tumor malignancy and depressive or adjustment disorder with depressed mood were assessed using the Hamilton Depression Rating Scale (HAMD-17) (and its shortened version the HAMD-7) and the Zung Self-Rating Depression Scale (ZSDS) (and its shortened version BZSDS). Results: Based on HAMD-7 results, the prevalence of moderate depression was low (7.7%); using the BZSDS moderate depression was absent. Mild depression was identified in 82.3% and 73% of our subjects using the HAMD-7 and the BZSDS, respectively. The strength of agreement between psychiatrist and patients' self-evaluation for mild depression was "slight", employing the original and the abbreviated versions of both scales. Conclusion: Our findings suggest that the prevalence of core depressive symptoms is very low in cancer patients diagnosed with depressive disorder. The lack of a strong agreement between psychiatrist and patient in classifying the severity of depression highlights the importance of factors such as well-being and functional status among depressed cancer patients in their self assessment of depression. © Massimo et al

Effect of P2X4 and P2X7 receptor antagonism on the pressure diuresis relationship in rats.

Reduced glomerular filtration, hypertension and renal microvascular injury are hallmarks of chronic kidney disease, which has a global prevalence of ~10%. We have shown previously that the Fischer (F344) rat has lower GFR than the Lewis rat, and is more susceptible to renal injury induced by hypertension. In the early stages this injury is limited to the pre-glomerular vasculature. We hypothesized that poor renal hemodynamic function and vulnerability to vascular injury are causally linked and genetically determined. In the present study, normotensive F344 rats had a blunted pressure diuresis relationship, compared with Lewis rats. A kidney microarray was then interrogated using the Endeavour enrichment tool to rank candidate genes for impaired blood pressure control. Two novel candidate genes, P2rx7 and P2rx4, were identified, having a 7- and 3- fold increased expression in F344 rats. Immunohistochemistry localized P2X4 and P2X7 receptor expression to the endothelium of the pre-glomerular vasculature. Expression of both receptors was also found in the renal tubule; however there was no difference in expression profile between strains. Brilliant Blue G (BBG), a relatively selective P2X7 antagonist suitable for use in vivo, was administered to both rat strains. In Lewis rats, BBG had no effect on blood pressure, but increased renal vascular resistance, consistent with inhibition of some basal vasodilatory tone. In F344 rats BBG caused a significant reduction in blood pressure and a decrease in renal vascular resistance, suggesting that P2X7 receptor activation may enhance vasoconstrictor tone in this rat strain. BBG also reduced the pressure diuresis threshold in F344 rats, but did not alter its slope. These preliminary findings suggest a physiological and potential pathophysiological role for P2X7 in controlling renal and/or systemic vascular function, which could in turn affect susceptibility to hypertension-related kidney damage

Prospects for radical emissions reduction through behaviour and lifestyle change

Over the past two decades, scholars and practitioners across the social sciences, in policy and beyond have proposed, trialled and developed a wide range of theoretical and practical approaches designed to bring about changes in behaviours and lifestyles that contribute to climate change. With the exception of the establishment of a small number of iconic behaviours such as recycling, it has however proved extremely difficult to bring about meaningful transformations in personal greenhouse gas emissions at either the individual or societal level, with multiple reviews now pointing to the limited efficacy of current approaches. We argue that the majority of approaches designed to achieve mitigation have been constrained by the need to operate within prevailing social scientific, economic and political orthodoxies which have precluded the possibility of non-marginal change. In this paper we ask what a truly radical approach to reducing personal emissions would look like from social science perspectives which challenge the unstated assumptions severely limiting action to date, and which explore new alternatives for change. We emphasise the difficulties likely to impede the instituting of genuinely radical societal change regarding climate change mitigation, whilst proposing ways that the ground could be prepared for such a transformation to take place

Luminescence Dating in Fluvial Settings: Overcoming the Challenge of Partial Bleaching

Optically stimulated luminescence (OSL) dating is a versatile technique that utilises the two most ubiquitous minerals on Earth (quartz or K-feldspar) for constraining the timing of sediment deposition. It has provided accurate ages in agreement with independent age control in many fluvial settings, but is often characterised by partial bleaching of individual grains. Partial bleaching can occur where sunlight exposure is limited and so only a portion of the grains in the sample was exposed to sunlight prior to burial, especially in sediment-laden, turbulent or deep water columns. OSL analysis on multiple grains can provide accurate ages for partially bleached sediments where the OSL signal intensity is dominated by a single brighter grain, but will overestimate the age where the OSL signal intensity is equally as bright (often typical of K-feldspar) or as dim (sometimes typical of quartz). In such settings, it is important to identify partial bleaching and the minimum dose population, preferably by analysing single grains, and applying the appropriate statistical age model to the dose population obtained for each sample. To determine accurate OSL ages using these age models, it is important to quantify the amount of scatter (or overdispersion) in the well-bleached part of the partially bleached dose distribution, which can vary between sediment samples depending upon the bedrock sources and transport histories of grains. Here, we discuss how the effects of partial bleaching can be easily identified and overcome to determine accurate ages. This discussion will therefore focus entirely on the burial dose determination for OSL dating, rather than the dose-rate, as only the burial doses are impacted by the effects of partial bleaching