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Abstract Eukaryotes produce a large number of cytochrome P450s that mediate the synthesis and degradation of diverse endogenous and exogenous metabolites. Yet, most of these P450s are uncharacterized and global tools to study these challenging, membrane-resident enzymes remain to be exploited. Here, we applied activity profiling of plant, mouse and fungal P450s with chemical probes that become reactive when oxidized by P450 enzymes. Identification by mass spectrometry revealed labeling of a wide range of active P450s, including six plant P450s, 40 mouse P450s and 13 P450s of the fungal wheat pathogen Zymoseptoria tritici. We next used transient expression of GFP-tagged P450s by agroinfiltration to show ER-targeting and NADPH-dependent, activity-based labeling of plant, mouse and fungal P450s. Both global profiling and transient expression can be used to detect a broad range of active P450s to study e.g. their regulation and discover selective inhibitors.

Surgical intervention is a common option for the treatment of wrist joint arthritis and traumatic wrist injury. Whether this surgery is arthrodesis or a motion preserving procedure such as arthroplasty, wrist joint biomechanics are inevitably altered. To evaluate effects of surgery on parameters such as range of motion, efficiency and carpal kinematics, repeatable and controlled motion of cadaveric specimens is required. This study describes the development of a device that enables cadaveric wrist motion to be simulated before and after motion preserving surgery in a highly controlled manner. The simulator achieves joint motion through the application of predetermined displacements to the five major tendons of the wrist, and records tendon forces. A pilot experiment using six wrists aimed to evaluate its accuracy and reproducibility. Biplanar X-ray videoradiography (BPVR) and X-Ray Reconstruction of Moving Morphology (XROMM) were used to measure overall wrist angles before and after total wrist arthroplasty. The simulator was able to produce flexion, extension, radioulnar deviation, dart thrower’s motion and circumduction within previously reported functional ranges of motion. Pre- and post-surgical wrist angles did not significantly differ. Intra-specimen motion trials were repeatable; root mean square errors between individual trials and average wrist angle and tendon force profiles were below 1° and 2 N respectively. Inter-specimen variation was higher, likely due to anatomical variation and lack of wrist position feedback. In conclusion, combining repeatable intra-specimen cadaveric motion simulation with BPVR and XROMM can be used to determine potential effects of motion preserving surgeries on wrist range of motion and biomechanics.

Management and conservation efforts that support the recovery and protection of large rivers are daunting, reflecting the complexity of the challenge and extent of effort (in terms of policy, economic investment, and spatial extent) needed to afford measurable change. These large systems have generally experienced intensive development and regulation, compromising their capacity to respond to disturbances such as climate change or wildfire. Functionally, large river and basin management require insights gained from social, ecological, geophysical, and hydrological sciences. This multi-disciplinary perspective can unveil the integrated relationship between a river network's biotic community and seasonally variable environmental conditions that are often influenced by human activities. Large rivers and their basins are constantly changing due to anthropogenic influences and as climate modifies patterns of temperature and precipitation. Because of these factors, the state of knowledge must advance to address changing conditions. The Willamette River, in western Oregon, USA, is a prime example of a basin that has experienced significant degradation and investment in rehabilitation in recent decades. Innovative science has facilitated development of fine-scale, spatially extensive datasets and models that can generate targeted conservation and rehabilitation actions that are prioritized across the entire river network. This prioritization allows investment decisions to be driven by site-specific conditions while simultaneously considering potentials for ecological improvement. Here, we review hydrologic, geomorphic, ecologic, and social conditions in the Willamette River basin through time—including pre-settlement, river development, and contemporary periods—and offer a future vision for consideration. Currently, detailed information about fish populations and habitat, hydrologic conditions, geomorphology, water quality, and land use can be leveraged to make informed decisions about protection, rehabilitation, and development. The time is ripe for strategic management and goal development for the entire Willamette River, and these efforts can be informed by comprehensive science realized through established institutions (e.g., public agencies, non-profit watershed groups, Tribes, and universities) focused on conservation and management. The approaches to science and social-network creation that were pioneered in the Willamette River basin offer insights into the development of comprehensive conservation-based planning that could be implemented in other large river systems globally.

Abstract Objective This study aimed to identify significant differences in cochlea microvessel size between a diabetic mouse model (db/db) and normal mice using three‐dimensional (3D) quantitative analysis. Methods Six control heterozygote db/+ as well as 18 male B6/BKS(D)‐Leprdb/J (db/db) mice aged 14 (n = 9) and 28 (n = 9) weeks were examined. After clearing the cochlea, we reconstructed the 3D volumes of the spiral modiolar artery (SMA) in the cochlea using light‐sheet microscopy and analyzed vessel wall thickness, cross‐sectional area, short and long diameter, and vessel height. Results The average SMA‐wall thickness in the db/db‐mouse group (3.418 ± 0.328 μm) was greater than that in the control group (2.388 ± 0.411 μm). The average cross‐sectional outer area, short diameter, and long diameter of the SMA in db/db mice were significantly larger than those in control mice (all p

Introduction The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was ‘Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?’ This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT.Methods and analysis We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress.Ethics and dissemination This study was approved by the Yorkshire and The Humber—Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group.Trial registration number ISRCTN41647111.

Comprender las causas que generan la variabilidad del reclutamiento en las poblaciones marinas constituye uno de los mayores desafíos de la ciencia pesquera. Nuestra capacidad predictiva para explicar estas variaciones es relativamente baja, debido a la interacción de factores exógenos y endógenos, que varían en el tiempo y el espacio dentro de las poblaciones. Con el fin de obtener información sobre las fluctuaciones en el reclutamiento de la merluza argentina (Merluccius hubbsi) del stock patagónico, revisamos los resultados obtenidos analizando la ecología reproductiva, la dinámica trófica y energética durante las diferentes etapas de desarrollo de esta especie y su relación con variables ambientales. Observamos que el potencial reproductivo está fuertemente influenciado por las características parentales, particularmente de las hembras, en cuanto a su tamaño, edad y condición. Esta característica, denominada “efecto materno”, sugiere que la biomasa de la población reproductora, comúnmente utilizada como índice de productividad en la evaluación de pesquerías, es un predictor deficiente del reclutamiento. También observamos que la supervivencia durante los primeros años de vida de la merluza se ve afectada por la coincidencia espacial con el Sistema Frontal Norpatagónico, caracterizado por una alta concentración de nutrientes, alta productividad y disponibilidad de alimento. Las condiciones físicas y la densidad larvaria en la zona de crianza afectaron el estado nutricional y la mortalidad de la merluza, principalmente por competencia por alimento o depredación. Se observó que la transición del hábitat pelágico al demersal en los juveniles se produce durante un período más extenso que el reconocido anteriormente para esta especie, lo que destaca la importancia de utilizar los registros acústicos para complementar la información de las redes de arrastre de fondo. Este es uno de los principales temas a desarrollar para estimar nuevos índices de reclutamiento de merluza argentina, junto con otras líneas de investigación propuestas para mejorar la evaluación del stock.

This brief article focuses upon Lady Emmeline Stuart-Wortley’s response to the Great Exhibition of 1851, both her celebration of luxury goods in her poetry and her poetry as such a consumer good.

Abstract Threatened ecosystem conservation requires an understanding of the effectiveness of management and the challenges hindering successful protection and recovery. Bringing together researchers, land managers and policymakers to identify key threats, management needs, and knowledge gaps provides a unified account of the evidence and tools needed to improve threatened ecosystem management. We undertook a research prioritization process for Australian alpine and subalpine peatlands with experts across policy, research, and management. Through individual interviews, structured group discussions, and voting, we generated 25 priority research questions that, if addressed, would enhance our capacity to conserve peatlands. Knowledge gaps spanned four topics: understanding peatland dynamics, impacts of threats, methods to manage these, and the effectiveness of management. Consistent monitoring standards, an open‐access knowledge platform and commitment to long‐term joint research and management were identified as vital. This collaboration enabled development of a shared agenda of research priorities to target knowledge gaps for informing policy and management of threatened alpine peatlands. Our findings substantiate the importance of stronger ongoing collaboration among researchers, land managers and policymakers across jurisdictions to support conservation.

BackgroundLiterature suggests limiting consumption of animal products is key to reducing emissions and adverse planetary impacts. However, influencing dietary behavior to achieve planetary health targets remains a formidable problem.ObjectiveWe investigated the effect of changing the default meal option at catered events–from meat to plant-based–on participants' meal choices using three parallel-group, balanced, randomized controlled trials (RCT), and use these experimental results to project differences in plant-based default vs. meat default events on greenhouse gas emissions (GHGEs) (kg CO2 − eq), land use (m2), nitrogen (g N), and phosphorus (g P) footprint.MethodsData collection was performed at three catered events (n = 280) across two college campuses. The selected experimental sites used convenience sampling. Events consisted of a graduate orientation, sorority dinner, and academic conference. Eligibility of individual participants included being 18 years or older and an invitation to RSVP for an enrolled event. Participants were randomly assigned to one of two groups: the control group received a RSVP form that presented a meat meal as the default catering option; whereas the intervention group received a form that presented a plant-based meal as the default. The primary outcome of interest in each group was the proportion of participants who selected plant-based meals. To explore environmental impacts, we modeled the footprints of four hypothetical meals. Using these meals and RCT results, the impact (GHGE, land use, nitrogen, phosphorus) of two hypothetical 100-person events was calculated and compared.ResultsIn all, participants assigned to the plant-based default were 3.52 (95% CI: [2.44, 5.09]) times more likely to select plant-based meals than those assigned to the meat default. Using these results, a comparison of hypothetical events serving modeled meat-based and plant-based meals showed a reduction of up to 42.3% in GHGEs as well as similar reductions in land use (41.8%), nitrogen (38.9%), and phosphorus (42.7%).ConclusionResults demonstrated plant-based default menu options are effective, providing a low-effort, high-impact way to decrease consumption of animal products in catered events. These interventions can reduce planetary impact while maintaining participant choice.

We tested the null hypothesis of equal likelihood of cigarette use among parents with a military connection and parents without a military connection, and independently compared risk factors for cigarette use. We obtained National Health Interview Survey (NHIS) data from 2015 to 2019 survey waves. We delimited analysis to 2-parent households who reported children aged

The mechanisms that shape the regulatory T cell repertoire in patients with cancer are not completely understood. Here, the authors observe that, in breast cancer patients, tumor-resident regulatory T cells do not show clonal relationship with their circulating counterpart, but share a common origin with intratumoral antigen-experienced conventional T cells.

Patagonian anchovy (Engraulis anchoita) and sprat (Sprattus fuegensis) constitute the two most important pelagic resources of the Argentine Patagonian shelf. Age and growth parameters of larvae and juveniles of both species were determined analyzing otoliths daily increments. A total of 404 anchovies (4.1-33 mm SL) and 157 sprats (5-41 mm SL) were analyzed. The Laird-Gompertz growth model was fitted to the length-at-age data of anchovies: L(t) = 4.2 exp (2.28 (1-(-0.034 t))). The parameters of the model were: L¥: 41.06 mm; the inflection point: 15.11 mm and 27 days; and the maximum growth rate: 0.51 mm day-1. The length-at-age data of sprat larvae and juveniles were represented in two linear models: L(t) = 0.32 t + 7.6; and L(t) = 0.22 t + 6.6. Slopes represented mean growth rates, 0.32 and 0.22 mm day-1 for larvae and juveniles, respectively. Variations in length-at-age between years were determined through the analysis of individual growth trajectories. Variations were found in sprats, not in anchovies.

Background: Several continuous monitoring solutions, including wireless wearable sensors, are available or being developed to improve patient surveillance on surgical wards. We designed a survey to understand the current perception and expectations of anaesthesiologists who, as perioperative physicians, are increasingly involved in postoperative care. Methods: The survey was shared in 40 university hospitals from Western Europe and the USA. Results: From 5744 anaesthesiologists who received the survey link, there were 1158 valid questionnaires available for analysis. Current postoperative surveillance was mainly based on intermittent spot-checks of vital signs every 4–6 h in the USA (72%) and every 8–12 h in Europe (53%). A majority of respondents (91%) considered that continuous monitoring of vital signs should be available on surgical wards and that wireless sensors are preferable to tethered systems (86%). Most respondents indicated that oxygen saturation (93%), heart rate (80%), and blood pressure (71%) should be continuously monitored with wrist devices (71%) or skin adhesive patches (54%). They believed it may help detect clinical deterioration earlier (90%), decrease rescue interventions (59%), and decrease hospital mortality (54%). Opinions diverged regarding the impact on nurse workload (increase 46%, decrease 39%), and most respondents considered that the biggest implementation challenges are economic (79%) and connectivity issues (64%). Conclusion: Continuous monitoring of vital signs with wireless sensors is wanted by most anaesthesiologists from university hospitals in Western Europe and in the USA. They believe it may improve patient safety and outcome, but may also be challenging to implement because of cost and connectivity issues.

A novel gliclazide-loaded elastomeric carbohydrate pharmaceutical vehicle was successfully developed. This new siliconized alginate platform showed pseudoplastic rheology with a zeta potential ranging from (−43.8 mV to −75.5 mV). A Buchi-B390 encapsulator was employed to formulate different types of silicone-grafted alginate microcapsules loaded with gliclazide relying on the vibrational ionic gelation technology. The use of tetraethyl orthosilicate (TEOS) to crosslink the silicone elastomer (hydroxy terminated polydimethylsiloxane) of this new platform had improved the gliclazide encapsulation (>92.13% ± 0.76) of the free-flowing composite microcapsules, which showed good mechanical durability (up to 12 h in PBS pH 6.8) and promising results to sustain the drug release.

Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be integrated with COVID-19 case data to inform timely pandemic response. However, more research is needed to apply and develop systematic methods to interpret the true SARS-CoV-2 signal from noise introduced in wastewater samples (e.g., from sewer conditions, sampling and extraction methods, etc.). In this study, raw wastewater was collected weekly from five sewersheds and one residential facility. The concentrations of SARS-CoV-2 in wastewater samples were compared to geocoded COVID-19 clinical testing data. SARS-CoV-2 was reliably detected (95% positivity) in frozen wastewater samples when reported daily new COVID-19 cases were 2.4 or more per 100,000 people. To adjust for variation in sample fecal content, four normalization biomarkers were evaluated: crAssphage, pepper mild mottle virus, Bacteroides ribosomal RNA (rRNA), and human 18S rRNA. Of these, crAssphage displayed the least spatial and temporal variability. Both unnormalized SARS-CoV-2 RNA signal and signal normalized to crAssphage had positive and significant correlation with clinical testing data (Kendall's Tau-b (τ)=0.43 and 0.38, respectively), but no normalization biomarker strengthened the correlation with clinical testing data. Locational dependencies and the date associated with testing data impacted the lead time of wastewater for clinical trends, and no lead time was observed when the sample collection date (versus the result date) was used for both wastewater and clinical testing data. This study supports that trends in wastewater surveillance data reflect trends in COVID-19 disease occurrence and presents tools that could be applied to make wastewater signal more interpretable and comparable across studies.

Fish metamorphosis is an important ontogenetic process with a key role on early stages survival and on successful recruitment to adult populations. The whitemouth croaker (Micropogonias furnieri) is an important commercial resource for the coastal fisheries of Argentina and Uruguay. Metamorphosis was studied using morphometric and morphological analysis during larval development. Changes in morpho-meristic characters before and after metamorphosis were employed to determine the length interval of this transition by employing Principal Component Analysis. Individuals (n = 430) from 4 to 41 mm standard length (SL) were collected in the Río de la Plata estuary (35.45° S, 56.35° W) in March 2006. Length ranges of individual’s developmental stages were associated with the presence of key morphological characters. During early life stages, M. furnieri changes from a big-headed, robust shape larva to a slender and more elongated body form. Most of the morphometric variables showed an inflexion point at 15.2 mm SL, with a 95% confidence interval of 14.0-16.4 mm. The anterior part of the body grows faster during early stages, probably related to an intense feeding activity strategy. The completion of pectoral fin rays and the onset of squamation determine the beginning of metamorphosis at 11-12 mm SL. At around 18 mm SL, squamation ends, first barbels develop and the sagittae otoliths primordium is closed. The length-at-metamorphosis for M. furnieri was established between 9 to 18 mm SL, since all developmental characters studied highly overlapped at that interval. All those processes are indicative of the beginning of the juvenile period associated to the settlement and the start of a bottom-oriented life-style.

Bile acids (BA)s are known surfactants and well-documented to play a major role in food digestion and absorption. Recently, potential endocrinological and formulation-stabilisation effects of BAs have been explored and their pharmacological effects on supporting cell survival and functions have gained wide interest. Hence, this study aimed to explore the hyper-glycaemic dependent dose-effect of the BA chenodeoxycholic acid (CDCA) when encapsulated with pancreatic β-cells, allowing assessment of CDCA’s impacts when encapsulated. Four different concentrations of the BA were prepared, and viable cells were encapsulated and incubated for 2 days. Multiple analyses were carried out including confocal imaging, glucose-induced cellular mitochondrial viability indices, insulin production, inflammatory biomarker analyses and cellular bioenergetics measurements. There was a significant dose-effect with different concentrations of the BA, affecting cellular viability and antioxidant activities, cell functions and insulin release, inflammatory biomarkers, and cellular-bioenergetics at different oxidative stress levels. The results demonstrate that, when encapsulated, the BA CDCA exerts positive pharmacological effects at the cellular level, and such effects are concentration dependent.

Recent studies in our laboratories have shown promising effects of bile acids in ➀ drug encapsulation for oral targeted delivery (via capsule stabilization) particularly when encapsulated with Eudragit NM30D® and ➁ viable-cell encapsulation and delivery (via supporting cell viability and biological activities, postencapsulation). Accordingly, this study aimed to investigate applications of bile acid-Eudragit NM30D® capsules in viable-cell encapsulation ready for delivery. Mouse-cloned pancreatic β-cell line was cultured and cells encapsulated using bile acid-Eudragit NM30D® capsules, and capsules’ images, viability, inflammation, and bioenergetics of encapsulated cells assessed. The capsules’ thermal and chemical stability assays were also assessed to ascertain an association between capsules’ stability and cellular biological activities. Bile acid-Eudragit NM30D® capsules showed improved cell viability (e.g., F1 < F2 & F8; p < 0.05), insulin, inflammatory profile, and bioenergetics as well as thermal and chemical stability, compared with control. These effects were formulation-dependent and suggest, overall, that changes in ratios of bile acids to Eudragit NM30D® can change the microenvironment of the capsules and subsequent cellular biological activities.

Accumulation of aggregated α-synuclein into Lewy bodies is thought to contribute to the onset and progression of dopaminergic neuron degeneration in Parkinson's disease (PD) and related disorders. Although protein aggregation is associated with perturbation of proteostasis, how α-synuclein aggregation affects the brain proteome and signaling remains uncertain. In a mouse model of α-synuclein aggregation, 6% of 6215 proteins and 1.6% of 8183 phosphopeptides changed in abundance, indicating conservation of proteostasis and phosphorylation signaling. The proteomic analysis confirmed changes in abundance of proteins that regulate dopamine synthesis and transport, synaptic activity and integrity, and unearthed changes in mRNA binding, processing and protein translation. Phosphorylation signaling changes centered on axonal and synaptic cytoskeletal organization and structural integrity. Proteostatic responses included a significant increase in the levels of Lmp7, a component of the immunoproteasome. Increased Lmp7 levels and activity were also quantified in postmortem human brains with PD and dementia with Lewy bodies. Functionally, the immunoproteasome degrades α-synuclein aggregates and generates potentially antigenic peptides. Expression and activity of the immunoproteasome may represent testable targets to induce adaptive responses that maintain proteome integrity and modulate immune responses in protein aggregation disorders. Keywords: Neurodegeneration, Parkinson's disease, Dopaminergic neurons, Immunoproteasome, Proteostasis

Pancreatic β-cell loss and failure with subsequent deficiency of insulin production is the hallmark of type 1 diabetes (T1D) and late-stage type 2 diabetes (T2D). Despite the availability of parental insulin, serious complications of both types are profound and endemic. One approach to therapy and a potential cure is the immunoisolation of β cells via artificial cell microencapsulation (ACM), with ongoing promising results in human and animal studies that do not depend on immunosuppressive regimens. However, significant challenges remain in the formulation and delivery platforms and potential immunogenicity issues. Additionally, the level of impact on key metabolic and disease biomarkers and long-term benefits from human and animal studies stemming from the encapsulation and delivery of these cells is a subject of continuing debate. The purpose of this review is to summarise key advances in this field of islet transplantation using ACM and to explore future strategies, limitations, and hurdles as well as upcoming developments utilising bioengineering and current clinical trials.

Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s disease, and hearing loss. Age-related hearing loss, also termed presbycusis, is one of the most common sensory impairments worldwide, affecting one in five people over 50 years of age, and this prevalence is growing annually. Associations have emerged between presbycusis and detrimental health outcomes, including social isolation and mental health. It remains largely untreatable apart from hearing aids, and with no globally established prevention strategies in the clinical setting. Hence, this review aims to explore the pathophysiology of presbycusis and potential therapies, based on a recent advancement in bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using the following keywords: presbycusis, drugs, hearing loss, bile acids, nanotechnology, and more than 150 publications were considered directly relevant. Evidence of the multifaceted oxidative stress and chronic inflammation involvement in cellular damage and apoptosis that is associated with a loss of hair cells, damaged and inflamed stria vascularis, and neuronal signalling loss and apoptosis continues to emerge. New robust and effective therapies require drug delivery deeper into the various layers of the cochlea. Bile acid-based nanotechnology has gained wide interest in its permeation-enhancing ability and potential for numerous applications in treating presbycusis.

Designing and controlling the collective behavior of a swarm often requires complex range, bearing sensors, and peer-to-peer communication strategies. Recent work studying swarm of robots that have no computational power has shown that complex behaviors such as aggregation and object clustering can be produced from extremely simple control policies and sensing capability. We extend previous work on computation-free swarm behaviors and show that it is possible to evolve simple control policies to form a perimeter around a target, rendezvous to a specific location, and perform foraging. We also demonstrate that simple manipulations of the environment can be used to control, these collective behaviors. The robustness and expressiveness of these behaviors, combined with the simple requirements for control and sensing, demonstrate the feasibility of implementing swarm behaviors at small scales or in extreme environments.

Se determinó el crecimiento y la condición nutricional de larvas de Engraulis anchoita en la Zona Común de Pesca Argentino-Uruguaya (ZCPAU). La condición se estimó a partir de la relación ARN/ADN estandarizada (RDs) del tronco muscular. El crecimiento se estudió calculando una tasa de crecimiento instantáneo sobre la base de un modelo que incluye RDs y temperatura. Se calculó, además, el crecimiento de los otolitos midiendo el espesor de los últimos tres incrementos completamente formados. Las muestras se obtuvieron en marzo de 2014. Los 12 lances oblicuos que se realizaron con red Bongo y malla de 300 µm mostraron presencia de larvas en seis de ellos. Se las separó a bordo y se fijaron en nitrógeno líquido. Posteriormente se las midió, se separaron las cabezas con un bisturí y se liofilizaron los troncos musculares en forma individual (N = 128). Se compararon dos secciones oceanográficas situadas sobre el margen sur y el margen norte de la ZCPAU (COSTAL I y II, respectivamente). La relación RDs de las larvas evidenció una buena condición nutricional. No se observaron diferencias significativas en la condición o el crecimiento entre ambas secciones. Se observó una correlación positiva entre el índice RDs y la talla, por lo que las comparaciones se realizaron considerando el estadio de desarrollo larval. El RDs para las larvas en preflexión en la COSTAL I fue 2,53 ± 1,29 (n = 53) y 2,92 ± 1,22 (n = 7) en la COSTAL II. Para las larvas en flexión fue 3,41 ± 1,07 (n = 22) y 2,91 ± 0,86 (n = 32) en las secciones I y II, respectivamente. La elevada condición nutricional de las larvas de anchoíta indica que las características ambientales que se observaron en marzo en el área de estudio serían apropiadas para su crecimiento y supervivencia.

[This corrects the article DOI: 10.1371/journal.pone.0225650.].

Despite considerable research, it remains controversial as to whether viral-infections are associated with Meniere's Disease (MD), a clinically heterogeneous set of chronic inner-ear disorders strongly associated with endolymphatic hydrops. Here, we investigated whether viral-infections are associated with MD through a systematic review and meta-analysis of observational clinical studies using molecular-diagnostics. Eligible for inclusion were case-controlled studies which ascertained molecular-determinants of past or present viral-infection through either viral nucleic acids or host serological marker in MD cases and non-MD controls. Across online databases and grey literature, we identified 210 potentially relevant articles in the English language, from which a total of 14 articles fully satisfied our eligibility criteria such that meta-groups of 611 MD-cases and 373 controls resulted. The aggregate quality of the modest-sized (14 studies) body of evidence was limited and varied considerably with regards to participant selection, matching, and ascertainment(s) and determinant(s) of viral-infection. Most data identified concerned the human cytomegalovirus (CMV), and meta-analysis of eligible studies revealed that evidence of CMV-infection was associated approximately three-fold with MD compared to controls, however the timing of the infections was indeterminate as the pooled analyses combined antiviral serological markers with viral nucleic acid markers. No association was found for any of HSV-1, -2, VZV, or EBV. Associative analyses of any viral species not aforementioned were precluded by limited data, and thus potential associations between other viral species and MD, especially other than Herpesviridae, are yet to be characterised. Overall, we have found a small association between CMV-infection and MD, however it is to be determined for what sub-groups of MD this finding may be relevant, and ideally the reported association remains would be reproduced by a greater volume of higher quality evidence.

The Great Lakes Integrated Sciences and Assessments program (GLISA) has led the co-development of usable climate information for decision-making in several case study projects. Although each case study is with a unique partnering organization made up of different stakeholders with varying information needs and capabilities, several patterns have emerged that GLISA has identified and overcome to advance the practice of applied climate information. There are three main barriers that GLISA encounters at the onset of many of the case studies: (1) mismatched terminology used by scientists and stakeholders to describe the types of information that are available and needed for problem solving (translation); (2) unrealistic expectations regarding the development of climate information products for problem solving; and (3) disordered integration of when stakeholders want to bring climate information into decision-making processes. Although some or all of these barriers are likely to exist at the onset of any new climate information partnership, GLISA has developed methods for overcoming them more quickly so that the process of co-developing usable climate information is more efficient and effective. In this paper we describe in detail GLISA’s experiences that have led to the realization of these barriers and the steps GLISA has taken to overcome them. We also relate these barriers to literature on the “usability gap” between climate science and information use in decision-making as well as uncertainty cascades in climate change adaptation. These experiences demonstrate that climate scientists performing outreach experience similar struggles as the stakeholders they interact with. However, they also reveal the potential for climate-centered boundary organizations to cultivate their own capacities to overcome these challenges in their partnerships.

Adapting to climate change requires the production and use of climate information to inform adaptation decisions. By facilitating sustained interaction between science producers, boundary organizations narrow the gap between science and decision-making and foster the co-production of actionable knowledge. While traditional boundary organization approaches focused on intense one-on-one interactions between producers and users increases usability, this approach requires significant time and resources. Forming “boundary chains”, linking complimentary boundary organizations together, may reduce those costs. In this paper, we use longitudinal observations of a boundary chain, interviews and surveys to explore: (1) how producer-user interactions increase understanding and information usability and (2) if and how efficiencies in climate information production, dissemination and use arise as a result of the boundary chain. We find that forming and sustaining an effective boundary chain requires not only interest, commitment and investment from every link in the chain but also a level of non-overlapping mutual dependency and complementary skill sets. In this case, GLISA’s strength in producing scientific information and their credibility as climate scientists and HRWC’s strengths in facilitation, connection with potential information users, and their recognition and reputation in the watershed add value to the boundary chain enabling the boundary chain to accomplish more with greater efficiency than if each organization in the chain tried to work independently. Finally, data show how the boundary chain increased efficiencies in educating potential users about the strengths and limitations of climate science and improving the production, dissemination, and use of climate information.

Imperfect and internal rhymes are two important features in rap music previously ignored in the music information retrieval literature. We developed a method of scoring potential rhymes using a probabilistic model based on phoneme frequencies in rap lyrics. We used this scoring scheme to automatically identify internal and line-final rhymes in song lyrics and demonstrated the performance of this method compared to rules-based models. We then calculated higher-level rhyme features and used them to compare rhyming styles in song lyrics from different genres, and for different rap artists. We found that these detected features corresponded to real- world descriptions of rhyming style and were strongly characteristic of different rappers, resulting in potential applications to style-based comparison, music recommendation, and authorship identification.

Type 2 diabetes (T2D) occurs when there is insufficient insulin release to control blood glucose, due to insulin resistance and impaired β-cell function. The GPR39 receptor is expressed in metabolic tissues including pancreatic β-cells and has been proposed as a T2D target. Specifically, GPR39 agonists might improve β-cell function leading to more adequate and sustained insulin release and glucose control. The present study aimed to test the hypothesis that GPR39 agonism would improve glucose stimulated insulin secretion in vivo. A high throughput screen, followed by a medicinal chemistry program, identified three novel potent Zn2+ modulated GPR39 agonists. These agonists were evaluated in acute rodent glucose tolerance tests. The results showed a lack of glucose lowering and insulinotropic effects not only in lean mice, but also in diet-induced obese (DIO) mice and Zucker fatty rats. It is concluded that Zn2+ modulated GPR39 agonists do not acutely stimulate insulin release in rodents.

Vancomycin trough concentrations should be measured within 30 min of the next dose, but studies have shown that troughs are often measured too early, producing erroneous results that could lead to dosing errors. The purpose of this study was to identify the frequency of early trough measurements and to evaluate whether pharmacokinetically extrapolating mistimed concentrations may locate sub-therapeutic concentrations. Vancomycin troughs were retrospectively reviewed. For troughs ≥10 mg/L and measured >0.5 h early, the true trough was estimated using pharmacokinetic extrapolation methods to identify sub-therapeutic outcomes. Differences ≥2 mg/L between the measured and estimated true trough level was considered to have potential clinical significance. Of 143 troughs evaluated, 62 (43%) were measured too early and 48 of those troughs were ≥10 mg/L. 25% of those 48 troughs were sub-therapeutic. The potential for a difference ≥2 mg/L between the measured and estimated true trough was found to be greatest when the measured trough was ≥10 mg/L, the patient’s creatinine clearance (CrCl) was ≥60 mL/min, and the timing error was ≥2 h. To increase the therapeutic utility of early vancomycin trough concentrations, estimated true troughs can be determined by extrapolating measured values based on the time difference and CrCl.

This brief forum contribution reflects upon some historical factors in the formation of nineteenth century science and of the literature and science discipline that has since arisen to study its literary receptions. Noting the preponderance of studies focusing upon forms of scientific developmentalism, principally Darwinian biology, and of novels and other prose, and more broadly, on literary figures, rather than the writings of scientists, the paper introduces some poetry on science by scientists. It concentrates principally on those working and writing in the fields of physics and mathematics, areas that have been neglected in literature and science studies.