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Belief in powerful supernatural agents that enforce moral norms has been theoretically linked with cooperative altruism and prosociality. Correspondingly, prior research reveals an implicit association between atheism and extreme antisociality (e.g., serial murder). However, findings centered on associations between lack of faith and moral transgression do not directly address the hypothesized conceptual association between religious belief and prosociality. Accordingly, we conducted two pre-registered experiments depicting a “serial helper” to assess biases related to extraordinary helpfulness, mirroring designs depicting a serial killer used in prior cross-cultural work. In both a predominantly religious society (the U.S., Study 1) and a predominantly secular society (New Zealand, Study 2), we successfully replicated previous research linking atheism with transgression, and obtained evidence for a substantially stronger conceptual association between religiosity and virtue. The results suggest that stereotypes linking religiosity with prosociality are both real and global in scale. [ABSTRACT FROM AUTHOR]

Biosimilars have been available in the USA for over a decade, and in Europe for almost two decades. In that time, biosimilars have become established in the treatment landscape for a wide range of diseases, facilitating patient access and affordability of healthcare. However, patients can still struggle to access biological therapies in some markets. There is a need to streamline the process of developing biosimilars without compromising their quality, safety, or efficacy. This opinion piece considers the efficiencies that could be achieved within the biosimilar approval process. In clinical trials for biosimilars, clinical efficacy endpoints have been shown to be less sensitive measures of biosimilarity than biochemical, biophysical, and biological functional assays. Additional clinical efficacy studies comparing potential biosimilars and reference products do not add information that is useful for regulatory purposes. Large clinical studies of biosimilars with immunogenicity endpoints are of limited value, given the quality control processes in place for all biologics, including biosimilars. The expectation for multiple-switch studies for US interchangeability designation should be reconsidered immediately, and the category should be eliminated in the future. As biosimilars are typically approved globally based on a single set of clinical trials, and all subsequent manufacturing changes are already carefully monitored by regulatory authorities, comparative pharmacokinetic testing of EU and US reference products is unnecessary. Manufacturers and regulators could take greater advantage of existing real-world evidence. Streamlining biosimilar development would enable biosimilar development of more and a wider variety of biological drugs, accelerating biosimilar development without impacting patient safety or effectiveness. [ABSTRACT FROM AUTHOR]

A major focus in pastoralism studies has been on the socially porous or open-access nature of pastoral tenure systems that allow herd movements to respond to shifting availabilities of water and pasture without social constraints. We address the important question of whether herd movements in socially porous tenure regimes are influenced by the social identities of encampment host and visitor, reflecting other needs of mobile pastoralism requiring social cooperation. We assessed pastoral tenure characteristics and the social identities of encampment hosts and visitors at 1014 mapped encampment points in southeastern Chad. We found that under a socially porous tenure regime, visitation is biased toward co-membership of Arab clans. Informants point to the importance of social connections at encampments that facilitate actions to maintain resource access and reduce security risks. Together, these findings support multi-level institutional hybrid structures often found in customary pastoral organization as an important component in transhumance governance institutions. [ABSTRACT FROM AUTHOR]

Many species of pathogenic bacteria damage tissue cells by secreting toxins that form pores in plasma membranes. Here we show that glucocorticoids increase the intrinsic protection of tissue cells against pore-forming toxins. Dexamethasone protected several cell types against the cholesterol-dependent cytolysin, pyolysin, from Trueperella pyogenes. Dexamethasone treatment reduced pyolysin-induced leakage of potassium and lactate dehydrogenase, limited actin cytoskeleton alterations, reduced plasma membrane blebbing, and prevented cytolysis. Hydrocortisone and fluticasone also protected against pyolysin-induced cell damage. Furthermore, dexamethasone protected HeLa and A549 cells against the pore-forming toxins streptolysin O from Streptococcus pyogenes, and alpha-hemolysin from Staphylococcus aureus. Dexamethasone cytoprotection was not associated with changes in cellular cholesterol or activating mitogen-activated protein kinase (MAPK) cell stress responses. However, cytoprotection was dependent on the glucocorticoid receptor and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR). Collectively, our findings imply that glucocorticoids could be exploited to limit tissue damage caused by pathogens secreting pore-forming toxins. Treating cell lines with glucocorticoids offers protection against the damage caused by subsequent exposure to selected bacterial pore-forming toxins, and is dependent on the glucocorticoid receptor. [ABSTRACT FROM AUTHOR]

The FAIR principles, as applied to clinical and neuroimaging data, reflect the goal of making research products Findable, Accessible, Interoperable, and Reusable. The use of the Collaborative Informatics and Neuroimaging Suite Toolkit for Anonymized Computation (COINSTAC) platform in the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium combines the technological approach of decentralized analyses with the sociological approach of sharing data. In addition, ENIGMA + COINSTAC provides a platform to facilitate the use of machine-actionable data objects. We first present how ENIGMA and COINSTAC support the FAIR principles, and then showcase their integration with a decentralized meta-analysis of sex differences in negative symptom severity in schizophrenia, and finally present ongoing activities and plans to advance FAIR principles in ENIGMA + COINSTAC. ENIGMA and COINSTAC currently represent efforts toward improved Access, Interoperability, and Reusability. We highlight additional improvements needed in these areas, as well as future connections to other resources for expanded Findability. [ABSTRACT FROM AUTHOR]

The response of vegetation to variable flood regimes is an important research question for floodplains in semi-arid sub-Saharan Africa experiencing climate change. The Inland Niger Delta (IND), located within the Sahelian zone of Central Mali, is a large floodplain that has experienced a historically-significant period of recurrent drought from 1970 to 1994 followed by a recovery of floods since. Vegetation associations, as determined through 2014 fieldwork at 538 IND sites, were compared to the sites' vegetation associations as mapped in 1982. Site-specific flood histories were constructed through the analysis of Landsat imagery across the 1982–2014 period. In more deeply flooded portions of the floodplain, observations of vegetation associations in 2014 show remarkable consistency with those existing in 1982. In areas flooded infrequently and for the shortest duration, vegetation trajectories are more complicated with evidence for bush encroachment noted at 4.5% of all sites. Flood history explains only a portion of the few site-specific changes observed over the study period. Significant changes were more likely to be associated with more recent flood history (post 1999) rather than the flood history during the preceding abnormally dry period (1982–1991). These findings point to remarkable resiliency of IND vegetation to widely fluctuating levels of flooding that are driven not only by rainfall and run-off across the watershed but also by land use, water withdrawals and damming upstream. Given the low species diversity of IND vegetation, its resiliency derives from the combination of the seasonal plasticity of perennial grass growth in relation to rainfall and flood regimes and the efficiency of their vegetative and reproductive propagation in the context of highly seasonal grazing. The co-occurrence of interannual resiliency of the IND vegetation with annual vegetation production varying significantly with annual rainfall-flood conditions is consistent with non-equilibrium ecosystem dynamics. [ABSTRACT FROM AUTHOR]

This paper investigates the existence of localised axisymmetric (radial) patterns on the surface of a ferrofluid in the presence of a uniform vertical magnetic field. We formally investigate all possible small-amplitude solutions which remain bounded close to the pattern’s centre (the core region) and decay exponentially away from the pattern’s centre (the far-field region). The results are presented for a finite-depth, infinite expanse of ferrofluid equipped with a linear magnetisation law. These patterns bifurcate at the Rosensweig instability, where the applied magnetic field strength reaches a critical threshold. Techniques for finding localised solutions to a non-autonomous PDE system are established; solutions are decomposed onto a basis which is independent of the radius, reducing the problem to an infinite set of nonlinear, non-autonomous ODEs. Using radial centre manifold theory, local manifolds of small-amplitude solutions are constructed in the core and far-field regions, respectively. Finally, using geometric blow-up coordinates, we match the core and far-field manifolds; any solution that lies on this intersection is a localised radial pattern. Three distinct classes of stationary radial solutions are found: spot A and spot B solutions, which are equipped with two different amplitude scaling laws and achieve their maximum amplitudes at the core, and ring solutions, which achieve their maximum amplitudes away from the core. These solutions correspond exactly to the classes of localised radial solutions found for the Swift–Hohenberg equation. Different values of the linear magnetisation and depth of the ferrofluid are investigated and parameter regions in which the various localised radial solutions emerge are identified. The approach taken in this paper outlines a route to rigorously establish the existence of axisymmetric localised patterns in the future. [ABSTRACT FROM AUTHOR]

Many factors interact to shape household food security and consumption and these must be analyzed together to build understandings of how they interact in particular contexts. In the Sahelian context, we report on a study investigating how productive resources (access to capital, land, labor), livelihood choices, food cultural norms and location together affect household food consumption by 120 rural households in the provinces of Yatenga and Seno in Burkina Faso. These two provinces have quite different cultural and socioeconomic conditions. Data was generated from an initial interview focused on household resource access followed by monitoring of household food consumption using 24-h and 7-day recall interviews over 11 months. Grain consumption was estimated along with the frequency of milk, meat, vegetable, oil/fats, and fruit consumption. Food security is shaped by the pathways through which households gain access to food. Surveyed household report low levels of self provisioning of grain (averaging around 50% of need) with different seasonal patterns of grain purchases based on cash sources. Principal components analysis finds significant degree of co-variation of food consumption parameters. Regression analysis finds that disposable wealth and cultural norms against milk consumption are positively and negatively associated with food consumption, controlling for land and labor access. Location (province) and ethnic identity (related or not to Mossi culture) are found to be important factors affecting household proclivity and ability to manage livestock which in turn leads to greater consumption of animal products (milk and meat) and greater savings to mobilize during times of grain deficit. [ABSTRACT FROM AUTHOR]

Purpose: Following prolonged stays on the International Space Station (ISS), some astronauts exhibit visual acuity changes, ophthalmological findings, and mildly elevated intracranial pressures as part of a novel process called spaceflight-associated neuro-ocular syndrome (SANS). To determine the pathophysiology of SANS, NASA conducted a multi-investigator study in which 11 healthy participants underwent head-down tilt bed rest, mimicking microgravity-induced cephalad fluid shifts, combined with elevated ambient CO2 levels similar to those on the ISS (HDT+CO2). As part of that study, we examined the effects of HDT+CO2 on cerebral perfusion. Methods: Using arterial spin labeling, we compared cerebral perfusion before, during, and after HDT+CO2 in participants who developed SANS (n = 5) with those who did not (n = 6). Results: All participants demonstrated a decrease in perfusion during HDT+CO2 (mean decrease of 25.1% at HDT7 and 16.2% at HDT29); however, the timing and degree of change varied between the groups. At day 7 of HDT+CO2, the SANS group experienced a greater reduction in perfusion than the non-SANS group (p =.05, 95% CI:-0.19 to 16.11, d=.94, large effect). Conversely, by day 29 of HDT+CO2, the SANS group had significantly higher perfusion (approaching their baseline) than the non-SANS group (p =.04, 95% CI:0.33 to 13.07, d=1.01, large effect). Conclusion: Compared with baseline and recovery, HDT+CO2 resulted in reduced cerebral perfusion which varied based on SANS status. Further studies are needed to unravel the relative role of HDT vs hypercapnia, to determine if these perfusion changes are clinically relevant, and whether perfusion changes contribute to the development of SANS during spaceflight. [ABSTRACT FROM AUTHOR]

In response to a growing need for STEM professionals, this study reports the results of the initial validation of a refined survey instrument that purports to measure the five constructs of the social cognitive career theory framework within the subjects of mathematics, science, engineering and technology. To investigate the instrument's reliability and psychometric properties, we administered this 45-item survey to students in grades 4–12. Reliability and validity (content and construct) were assessed using Cronbach's coefficient alphas and structural equation modeling. Path coefficients for the five constructs indicated weak to moderate influences on the subscales, and the goodness-of-fit indices demonstrated that the model is acceptable. Initial results indicate the survey has the potential to collect reliable and valid data and suggest the instrument may be helpful in measuring students' interests and choices in STEM careers for research, partnerships, and curricular development. Additionally, results highlight two areas for further investigation, which include the impact conscientious or random responders have on the survey's psychometric properties and what constitutes satisfactory Cronbach's alpha for results to be interpreted in a significant way. [ABSTRACT FROM AUTHOR]

The L‐type Ca2+ channel CaV1.2 governs gene expression, cardiac contraction, and neuronal activity. Binding of α‐actinin to the IQ motif of CaV1.2 supports its surface localization and postsynaptic targeting in neurons. We report a bi‐functional mechanism that restricts CaV1.2 activity to its target sites. We solved separate NMR structures of the IQ motif (residues 1,646–1,664) bound to α‐actinin‐1 and to apo‐calmodulin (apoCaM). The CaV1.2 K1647A and Y1649A mutations, which impair α‐actinin‐1 but not apoCaM binding, but not the F1658A and K1662E mutations, which impair apoCaM but not α‐actinin‐1 binding, decreased single‐channel open probability, gating charge movement, and its coupling to channel opening. Thus, α‐actinin recruits CaV1.2 to defined surface regions and simultaneously boosts its open probability so that CaV1.2 is mostly active when appropriately localized. Synopsis: Regulation of the L‐type voltage‐gated Ca2+ channel CaV1.2 by the EF hand proteins apo‐calmodulin (apoCaM) and α‐actinin remains debated. Here, structure‐function analyses report a dual role for α‐actinin‐1 in both instructing CaV1.2 cell surface localisation and increasing channel activity. NMR structures of ‐actinin‐1 and apoCaM EF3/4 hands bound to the CaV1.2 IQ motif identify distinct residues critical for binding.CaV1.2 IQ mutations impairing α‐actinin‐1 binding decrease channel open probability.CaV1.2 IQ mutations impairing apoCaM binding do not alter channel activity.α‐Actinin‐1 binding increases coupling of CaV1.2 gating charge movement to channel opening. [ABSTRACT FROM AUTHOR]

Untargeted metabolite profiling of biological samples is a challenge for analytical science due to the high degree of complexity of biofluids. Isobaric species may also not be resolved using mass spectrometry alone. As a result of these factors, many potential biomarkers may not be detected or are masked by co-eluting interferences in conventional LC-MS metabolomic analyses. In this study, a comprehensive liquid chromatography-mass spectrometry workflow incorporating a fast-scanning miniaturised high-field asymmetric waveform ion mobility spectrometry separation (LC-FAIMS-MS) is applied to the untargeted metabolomic analysis of human urine. The time-of-flight mass spectrometer used in the study was scanned at a rate of 20 scans s−1 enabling a FAIMS CF spectrum to be acquired within a 1-s scan time, maintaining an adequate number of data points across each LC peak. The developed method is demonstrated to be able to resolve co-eluting isomeric species and shows good reproducibility (%RSD < 4.9%). The nested datasets obtained for fresh, aged, and QC urine samples were submitted for multivariate statistical analysis. Seventy unique biomarker ions showing a statistically significant difference between fresh and aged urine were identified with optimal transmission CF values obtained across the full CF spectrum. The potential of using FAIMS to select ions for in-source collision-induced dissociation is demonstrated for FAIMS-selected methylxanthine ions yielding characteristic fragment ion species indicative of the precursor. [ABSTRACT FROM AUTHOR]

A method combining field asymmetric waveform ion mobility spectrometry with liquid chromatography-mass spectrometry (LC-FAIMS-MS) has been developed for the analysis of the oxypurine compounds hypoxanthine (HX) and xanthine (XA) in saliva. Separation of the oxypurines from interfering matrix components was investigated using FAIMS-MS. The selected FAIMS parameters were then applied to the rapid LC-FAIMS-MS analysis of HX and XA using a short chromatographic separation method (7 min). A comparison of the LC-MS method with and without FAIMS applied, resulted in improved discrimination from saliva matrix interferences and improved chromatographic peak integration for both HX and XA using a FAIMS separation. A quantitative evaluation of the LC-FAIMS-MS method was performed giving limits of detection of 2.0 ng mL−1 for HX and 1.8 ng mL−1 for XA, and limits of quantification of 6.6 ng mL−1 for HX and 6.0 ng mL−1 for XA. The developed LC-FAIMS-MS method was applied to the targeted analysis of the oxypurine metabolites in saliva collected from healthy male athletes (n = 11) before and after exercise designed to induce oxidative stress; post-exercise collection time-points included immediately after exercise, one hour and twenty-four hours’ post-exercise. The salivary concentrations of both HX and XA were lower after physical exercise, compared to the pre-exercise (rest) concentrations and returned to approximately pre-exercise levels after twenty-four hours. The method reported has the potential for monitoring the salivary oxypurines, HX and XA, as biomarkers of oxidative stress and in other clinical applications. [ABSTRACT FROM AUTHOR]

The Stat6VT mouse model of atopic dermatitis (AD) is induced by T-cell-specific expression of a constitutively active form of the protein signal transducer and activator of transcription 6 (STAT6). Although AD-like lesions are known to develop in Stat6VT mice, this study was designed to determine if these mice develop acute and chronic phases of disease similar to humans. To address this, AD-like lesions from Stat6VT mice were harvested at two different timepoints relative to their onset. Lesions harvested within 1 week after development were defined as acute lesions, and those present for 1 month or more were defined as chronic lesions. Acute and chronic AD-like lesions from Stat6VT mice exhibited histologic findings and cytokine expression patterns similar to acute and chronic AD lesions in humans. Further analysis revealed increased levels of interleukin (IL)-33 transcripts in AD-like lesions compared to Stat6VT nonlesional and wild-type skin controls. Immunofluorescence also revealed increased numbers of IL-33+ keratinocytes in Stat6VT lesional skin and localized IL-33+ keratinocytes to a keratin 5+ subset. Furthermore, AD-like disease was more severe in IL-33-deficient Stat6VT mice compared to IL-33-sufficient Stat6VT mice. These studies suggest that Stat6VT mice can serve as a model of acute and chronic AD and that IL-33 may attenuate inflammation in this system. [ABSTRACT FROM AUTHOR]

Compelling empirical evidence suggests that people move in response changes in pollution and that firms move in response to regulation. We investigate the problem of benefit estimation and transfer in the context of a simple model where firms and people can move in response to regulation and pollution. Including these margins of adjustment changes the problem of benefit-transfer. It requires the evaluation of policies that affect more than one region at a time. This suggests an important role for evaluation strategies based on easily observable indicators of local welfare like total population, real income net of real estate, or the use of elementary standardized models of spatial equilibrium. [ABSTRACT FROM AUTHOR]

Postsynaptic density protein-95 ( PSD-95) localizes AMPA-type glutamate receptors ( AMPARs) to postsynaptic sites of glutamatergic synapses. Its postsynaptic displacement is necessary for loss of AMPARs during homeostatic scaling down of synapses. Here, we demonstrate that upon Ca2+ influx, Ca2+/calmodulin (Ca2+/CaM) binding to the N-terminus of PSD-95 mediates postsynaptic loss of PSD-95 and AMPARs during homeostatic scaling down. Our NMR structural analysis identified E17 within the PSD-95 N-terminus as important for binding to Ca2+/CaM by interacting with R126 on CaM. Mutating E17 to R prevented homeostatic scaling down in primary hippocampal neurons, which is rescued via charge inversion by ectopic expression of Ca MR126E, as determined by analysis of miniature excitatory postsynaptic currents. Accordingly, increased binding of Ca2+/CaM to PSD-95 induced by a chronic increase in Ca2+ influx is a critical molecular event in homeostatic downscaling of glutamatergic synaptic transmission. [ABSTRACT FROM AUTHOR]

N-methyl-pyrrolidine (NMP) a potential impurity in the cephalosporin antibiotic cefepime is analysed using a rapid thermal desorption - ion mobility spectrometry (TD-IMS) method. The thermal desorption approach is shown to be capable of rapidly extracting NMP from the cefepime at 80 °C without causing thermal degradation of the cefepime. The ion mobility method has an analysis time of 1 min and demonstrates good linearity over a range from 0.3-3.0 μg ml of NMP, with limits of detection and quantification of 0.056 and 0.1875 μg ml respectively. The developed method was applied to the analysis of a cefepime sample and determined that NMP was present in a cefepime sample at a level of 0.0376 % with a percentage relative standard deviation ( n = 6) of 3.2 %. This was compared with a LC-UV method which was in close agreement measuring NMP at 0.0384 % in the cefepime sample with a percentage RSD ( n = 6) of 5.7 %. These results show that the TD-IMS method gives comparable data to the established LC methods and demonstrates the potential of TD-IMS for rapid measurement of volatile compounds in pharmaceutical matrices. [ABSTRACT FROM AUTHOR]

The need to maintain or increase livestock mobility in arid Africa has been widely embraced by ecologists, social scientists, and more recently regional governments. These movements are seen to sustain livestock production under a highly variable and changing climate. At the same time, livestock mobility is threatened by the expansion of agriculture onto rangelands. A major conundrum raised in the pastoral development literature is the potential contradiction of the need for spatially-fixed, exclusionary forms of tenure to protect key pastoral resources with the need for socially-porous open systems of resource tenure that ensure flexible access. This has been called the 'paradox of pastoral land tenure.' By adopting a transhumance corridor network approach, this paper demonstrates that there is a middle ground where flexible access can be maintained within a fixed network of corridors. A transhumance network includes not only the physical paths or corridors followed by livestock herds but also the encampment sites where livestock pass the night while moving along corridors and the water sources linked to encampment site. This study mapped and characterized 5000 km of corridors, 744 encampments, and 1010 water points in eastern Senegal. These pastoral features form a network of interconnected resources providing alternative options for travel, water, and forage as herds move along a north-south trajectory. The research analyzes spatial variation in the network's ability to provide these services (water, quality forage, and travel) as influenced by rainfall variability, cropping pressure, and social institutions. Four distinct zones within the study area were compared with analyses showing variation among them in the importance of different factors shaping access. More broadly, the study demonstrates that extant transhumance networks accommodate the competing needs of pastoral tenure security by facilitating herd movements in response to changing resource availabilities through a series of spatially-fixed components (encampment sites, water points, and corridors) that can be recognized and protected through legislation. Thus, the demands for tenure security and flexible patterns of resource use can both be potentially accommodated. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the real-world treatment patterns and outcomes of chemotherapy-induced (febrile) neutropenia (chemotherapy-induced (CIN)/febrile neutropenia (FN)) prophylaxis with biosimilar filgrastim (Zarzio®).Methods: MONITOR-GCSF is an international (12 countries), multi-center (140), prospective (max. six cycles), observational, open-label, pharmaco-epidemiologic study of cancer patients (n = 1447) treated with myelosuppressive chemotherapy across a total of 6,213 cycles and receiving prophylaxis with Zarzio®. Data were analyzed using both the patient and cycle as unit of analysis.Results: Most (72.3 %) received primary prophylaxis; dosed mainly (53.2 %) at 30 MIU but differentiated by weight, chemotoxicity, and tumor type; and mainly (53.2 %) initiated in the 24-72h post-chemotherapy window but differentiated by prophylaxis type, tumor type, and chemotoxicity and for modal/median duration of 5 days. Relative to European Organisation for Research and Treatment of Cancer (EORTC) guidelines, 56.6 % were correctly prophylacted, 17.4 % under-prophylacted, and 26.0 % over-prophylacted. The following incidence rates were recorded: CIN grade 4 13.2 % of patients and 3.9 % of cycles, FN 5.9 % of patients and 1.4 % of cycles, CIN/FN-related hospitalizations 6.1 % of patients and 1.5 % of cycles, CIN/FN-related chemotherapy disturbances 9.5 % of patients and 2.8 % of cycles, and composite outcomes index 22.3 % of patients and 6.7 % of cycles. Rates varied by type of prophylaxis and tumor, chemotoxicity, initiation day, and prophylaxis duration. There were 1834 musculoskeletal events with 24.7 % of patients reporting bone pain of any grade (mostly mild to moderate), and 148 adverse drug reactions, including 4 serious, were recorded in 76 patients.Conclusions: The clinical and safety outcomes are well within the range of historically reported data for originator filgrastim underscoring the clinical effectiveness and safety of biosimilar filgrastim in daily clinical practice. [ABSTRACT FROM AUTHOR]

The homeobox gene (Hoxd13) codes for a transcription factor protein that binds to AT-rich DNA sequences and controls expression of proteins that control embryonic morphogenesis. We report NMR chemical shift assignments of mouse Hoxd13 DNA binding domain bound to an 11-residue DNA duplex (BMRB No. 25133). [ABSTRACT FROM AUTHOR]

Purpose: Data from an ongoing European pharmacoepidemiological study (MONITOR-CKD5) were used to examine congruence between physician-reported risk-based individualisation of target haemoglobin (Hb) and the actual Hb targets set by these physicians for their patients, as well as actual Hb levels in their patients. Methods: Physician investigators participating in the study completed a questionnaire about their anaemia practice patterns and attitudes post-TREAT at the start of the study (T1) and in summer 2013 (T2). These data were compared with the Hb targets identified at baseline for actual patients ( n = 1197) enrolled in the study. Risk groups included presence/absence of hypertension, diabetes, cardiovascular complications, history of stroke, history of cancer, and age/activity level (elderly/inactive or young/active). Results: At each time point, more than three quarters of physicians responded that results from the TREAT study, in patients not on dialysis, have influenced their use of erythropoiesis-stimulating agents in patients on haemodialysis. At T1, there was a clear difference in physician-reported (theoretical) target Hb levels for patients across the different risk groups, but there was no difference in patients' actual Hb levels across the risk groups. A similar disparity was noted at T2. Conclusions: Physicians' theoretical attitudes to anaemia management in patients on haemodialysis appear to have been influenced by the results of the TREAT study, which involved patients not on dialysis. Physicians claim to use risk-based target Hb levels to guide renal anaemia care. However, there is discrepancy between these declared risk-based target Hb levels and actual target Hb levels for patients with variable risk factors. [ABSTRACT FROM AUTHOR]

This paper focuses on a conundrum that has dominated the literature on pastoral mobility and institutions in dryland regions of the world, where livestock production is the main livelihood system. High spatiotemporal variability of rainfall and forage resources are seen to require flexible rules and porous social boundaries to facilitate pastoral mobility-characteristics that run counter to conventional views of the requirements for effective common property institutions. We seek to explore this paradox by investigating the spatiotemporal variability of forage availability (using satellite derived vegetation indices as a proxy for green forage) in four transhumance zones ('transhumance sheds') in Mali, West Africa. For each transhumance shed, three characteristics with important institutional implications are evaluated over an eleven-year period between 2000 and 2010: the inter-annual variability of forage phenology, seasonal changes in connectivity of green forage patches, and the degree to which key forage locations exist in the form of consistently early green-up and/or late senescence. Periods of vegetation green-up and senescence, which determine the timing of transhumant livestock movements, are found to be sufficiently regular from year to year to be governed by conventional institutions. Seasonal changes in the north-south connectivity of green patches are sufficiently rapid for customary systems of sharing of pasture information to be effective (rather than more technologically sophisticated systems of pasture information). Moreover, transhumance sheds contain key pastoral forage sites, which because of their consistently early greening or late senescence, are strong candidates for territorial protection from alternative land uses such as agriculture. These findings support local herders' views of transhumance as composed of regular patterns of herd movements along prescribed corridors between key pastoral sites. The seasonal regularity of key pastoral resources has been obscured by an overemphasis on environmental unpredictability that characterizes dryland systems at certain spatial and temporal scales. This paper suggests that policies directed at improving pastoral resource governance must focus instead on securing pastoralists' access rights to movement corridors, specific pastures and water points. [ABSTRACT FROM AUTHOR]

Over the past 10 years, mobility of livestock has been portrayed as increasing the resilience of rural households in semi-arid Africa to climate change and variability. With this recognition, there has been important work characterizing livestock mobility and the barriers to it. This paper adds to this work by addressing two gaps in the literature: 1. An understanding in the variation of livestock mobility practices among communities; and 2. An understanding of rural peoples' views of the advantages and disadvantages of livestock mobility as well as the factors affecting their decisions about herd movements. A mixed-methods approach was adopted to analyze data collected by household survey and group interviews conducted in 32 multi-ethnic villages in Mali and Niger spanning the 12.5° N to 16.5° N latitudinal range. The results of regression and qualitative analyses show that: 1. A large fraction of rural households rely on livestock as part of their livelihood strategies; 2. Grazing management of a large majority of village livestock depends on movements outside of the village territory, especially during the rainy season; 3. The mobility of village livestock is not strongly influenced by the village's sociprofessional composition (farmer, herder, fisher, artisan..etc.); and 4. The prevalence of extra-village movements of village livestock (sheep and cattle) is higher in areas of higher population density. Despite the advantages of livestock mobility cited by informants, longer-distance movements are inhibited by risks associated with climatic, land-use, and sociopolitical change. Herd managers make decisions using diverse information about potential destinations with greater trust of information gathered by themselves or close kin. The implications of these findings for livestock management and policy in the region are discussed. [ABSTRACT FROM AUTHOR]

A method has been developed for metabolite profiling of the salivary metabolome based on protein precipitation and ultra-high performance liquid chromatography coupled with ion mobility-mass spectrometry (UHPLC–IM–MS). The developed method requires 0.5 mL of human saliva, which is easily obtainable by passive drool. Standard protocols have been established for the collection, storage and pre-treatment of saliva. The use of UHPLC allows rapid global metabolic profiling for biomarker discovery with a cycle time of 15 min. Mass spectrometry imparts the ability to analyse a diverse number of species reproducibly over a wide dynamic range, which is essential for profiling of biofluids. The combination of UHPLC with IM–MS provides an added dimension enabling complex metabolic samples to be separated on the basis of retention time, ion mobility and mass-to-charge ratio in a single chromatographic run. The developed method has been applied to targeted metabolite identification and untargeted metabolite profiling of saliva samples collected before and after exercise-induced physiological stress. δ-Valerolactam has been identified as a potential biomarker on the basis of retention time, MS/MS spectrum and ion mobility drift time. [ABSTRACT FROM AUTHOR]

Biosimilars are similar, but non-identical, versions of existing biological drugs for which patents have expired. Despite the rigorous approval process for biosimilars, concerns have been expressed about the efficacy and safety of these products in clinical practice. Biosimilars of filgrastim, based on the originator product Neupogen®, have been available since 2008 and are now in widespread clinical use in Europe and elsewhere. Three biosimilar G-CSFs have been approved based on a combination of physicochemical and biological protein characterisation, pharmacokinetic and pharmacodynamic assessment in healthy volunteers and efficacy and safety data in patients with cancer. To assess whether biosimilars are effective in the real-world clinical practice setting, a pooled analysis of five post-approval studies of biosimilar G-CSF (Zarzio®) that included 1,302 adult patients who received at least one cycle of chemotherapy with G-CSF support for the prevention of neutropenia was conducted. A total of 36 % of patients had a febrile neutropenia risk of >20 %, while 39.6 % had a risk of 10-20 % based on chemotherapy regimen. The occurrence of severe or febrile neutropenia was within the range of that observed in previous studies of originator G-CSF. In addition, the safety profile of Zarzio® was consistent with that reported for originator G-CSF and the known safety profile of G-CSF. Initial concerns about the use of biosimilars, at least with regard to biosimilar G-CSFs, appear to be unfounded. Adoption of cost-effective biosimilars should help reduce healthcare costs and improve patient access to biological treatments. [ABSTRACT FROM AUTHOR]

Prior longitudinal observational studies have examined the practice patterns and outcomes of anaemia management, including the use of erythropoiesis-stimulating agents (ESAs). Several dimensions of effectiveness remain unaddressed; especially considering the revised ESA label (target Hb levels between 10 and 12 g/dL), the recently published TREAT study, and the European approval of the first ESA biosimilar (HX575). Anecdotal evidence suggests that patient outcomes are influenced by physician-related variables and whether anaemia management is congruent with practice guidelines, but this has not been studied systematically. MONITOR-CKD5 is an international, prospective, observational, pharmacoepidemiological study evaluating the multi-level factors and outcomes of treatment with HX575 for renal anaemia in haemodialysis patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates an advocated statistical methodology here to fore used mainly in the social and behavioural sciences; assesses factors potentially predictive of a poor treatment response; and evaluates the extent to which treatment is congruent with evidence-based guidelines, good practice evidence, and the revised ESA label. This pan-European study will recruit at least 1,000 patients from a minimum of 75 centres, and follow them for up to 24 months following initiation of anaemia management with biosimilar epoetin alfa. MONITOR-CKD5 will not only study the core issues addressed by prior observational studies but also aims to take knowledge discovery a step further by assessing outcomes across varying cohorts of patients, and examining the impact of evidence-based practice on clinical outcomes, differentiating, in the process, between physician-level and patient-level determinants. [ABSTRACT FROM AUTHOR]

Goal Of Work: The goal of this study is to test the validity of RESPOND, a web-based decision support system to assess and manage anemia in cancer patients as per the European Organisation for Research and Treatment of Cancer (EORTC) guidelines. The intraclass correlation metrics for the algorithmic definitions were reported previously. Reported here are the concurrent validity, the extent to which clinicians' anemia management is guidelines-congruent when using the system; and discriminant validity, the extent to which clinicians practice in congruence with guidelines when vs. when not using the system.Patients and Methods: Hybrid matched design with precohort (retrospective; clinicians not using RESPOND) and postcohort (prospective; clinicians using RESPOND) of anemic patients matched on cancer type and chemotherapy regimen and followed up over 4 months after treatment initiation with erythropoietic proteins (34 patients per cohort; total N = 68). Congruence scores quantified the extent to which anemia management was congruent with the EORTC guidelines (range 0-10).Main Results: Hemoglobin (Hb) increased significantly for both cohorts, but the postcohort group showed more rapid rate of Hb increase over time (p < 0.006), higher Hb by visit 4 (p = 0.007), and greater Hb increase by visit 4 (p = 0.006). Concurrent validity was high with mean postcohort congruence scores of 8.18 +/- 1.38. Discriminant validity was inferred from statistically significant differences in mean congruence scores between cohorts (p < 0.001) and from the postcohort having odds ratios of 3.64 for patients to reach Hb >or= 11 g/dL and 2.91 to achieve Hb >or= 12 g/dL.Conclusions: RESPOND, a validated computerized clinical guidance system with an incremental effect beyond the pharmacotherapeutic effect of erythropoietic proteins, offers clinicians accurate and safe guidance in managing anemia in cancer patients. [ABSTRACT FROM AUTHOR]