1. Longitudinal records of prey selection by 10 adult female sea otters on the Monterey Peninsula, California, from 1983 to 1990 demonstrate extreme inter-individual variation in diet. Variation in ...prey availability cannot explain these differences as the data were obtained from a common spatial-temporal area. 2. Individual dietary patterns persisted throughout our study, thus indicating that they are life-long characteristics. 3. Individual dietary patterns in sea otters appear to be transmitted along matrilines, probably by way of learning during the period of mother-young association. 4. Efficient utilization of different prey types probably requires radically different sensory/motor skills, each of which is difficult to acquire and all of which may exceed the learning and performance capacities of any single individual. This would explain the absence of generalists and inertia against switching, but not the existence of alternative specialists. 5. Such individual variation might arise in a constant environment from frequency-dependent effects, whereby the relative benefit of a given prey specialization depends on the number of other individuals utilizing that prey. Additionally, many of the sea otter's prey fluctuate substantially in abundance through time. This temporal variation, in conjunction with matrilineal transmission of foraging skills, may act to mediate the temporal dynamics of prey specializations. 6. Regardless of the exact cause, such extreme individual variation in diet has broad ramifications for population and community ecology. 7. The published literature indicates that similar patterns occur in many other species.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
The repair of focal cartilage defects remains one of the foremost issues in the field of orthopaedics. Chondral defects may arise from a variety of joint pathologies and left untreated, will likely ...progress to osteoarthritis. Current repair techniques, such as microfracture, result in short-term clinical improvements but have poor long-term outcomes. Emerging scaffold-based repair strategies have reported superior outcomes compared to microfracture and motivate the development of new biomaterials for this purpose. In this study, unique composite implants consisting of a base porous reinforcing component (woven poly(ε-caprolactone)) infiltrated with 1 of 2 hydrogels (self-assembling peptide or thermo-gelling hyaluronan) or bone marrow aspirate were evaluated. The objective was to evaluate cartilage repair with composite scaffold treatment compared to the current standard of care (microfracture) in a translationally relevant large animal model, the Yucatan minipig. While many cartilage-repair studies have shown some success in vivo, most are short term and not clinically relevant. Informed by promising 6-week findings, a 12-month study was carried out and those results are presented here. To aid in comparisons across platforms, several structural and functionally relevant outcome measures were performed. Despite positive early findings, the long-term results indicated less than optimal structural and mechanical results with respect to cartilage repair, with all treatment groups performing worse than the standard of care. This study is important in that it brings much needed attention to the importance of performing translationally relevant long-term studies in an appropriate animal model when developing new clinical cartilage repair approaches.
The primary human immunodeficiency virus (HIV) reservoir is composed of resting memory CD4
T cells, which often express the immune checkpoint receptors programmed cell death protein 1 (PD-1) and ...cytotoxic T lymphocyte-associated protein 4 (CTLA-4), which limit T cell activation via synergistic mechanisms. Using simian immunodeficiency virus (SIV)-infected, long-term antiretroviral therapy (ART)-treated rhesus macaques, we demonstrate that PD-1, CTLA-4 and dual CTLA-4/PD-1 immune checkpoint blockade using monoclonal antibodies is well tolerated, with evidence of bioactivity in blood and lymph nodes. Dual blockade was remarkably more effective than PD-1 blockade alone in enhancing T cell cycling and differentiation, expanding effector-memory T cells and inducing robust viral reactivation in plasma and peripheral blood mononuclear cells. In lymph nodes, dual CTLA-4/PD-1 blockade, but not PD-1 alone, decreased the total and intact SIV-DNA in CD4
T cells, and SIV-DNA and SIV-RNA in B cell follicles, a major site of viral persistence during ART. None of the tested interventions enhanced SIV-specific CD8
T cell responses during ART or viral control after ART interruption. Thus, despite CTLA-4/PD-1 blockade inducing robust latency reversal and reducing total levels of integrated virus, the degree of reservoir clearance was still insufficient to achieve viral control. These results suggest that immune checkpoint blockade regimens targeting PD-1 and/or CTLA-4, if performed in people living with HIV with sustained aviremia, are unlikely to induce HIV remission in the absence of additional interventions.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Environmental monitoring plays a central role in diagnosing climate and management impacts on natural and agricultural systems; enhancing the understanding of hydrological processes; optimizing the ...allocation and distribution of water resources; and assessing, forecasting, and even preventing natural disasters. Nowadays, most monitoring and data collection systems are based upon a combination of ground-based measurements, manned airborne sensors, and satellite observations. These data are utilized in describing both small- and large-scale processes, but have spatiotemporal constraints inherent to each respective collection system. Bridging the unique spatial and temporal divides that limit current monitoring platforms is key to improving our understanding of environmental systems. In this context, Unmanned Aerial Systems (UAS) have considerable potential to radically improve environmental monitoring. UAS-mounted sensors offer an extraordinary opportunity to bridge the existing gap between field observations and traditional air- and space-borne remote sensing, by providing high spatial detail over relatively large areas in a cost-effective way and an entirely new capacity for enhanced temporal retrieval. As well as showcasing recent advances in the field, there is also a need to identify and understand the potential limitations of UAS technology. For these platforms to reach their monitoring potential, a wide spectrum of unresolved issues and application-specific challenges require focused community attention. Indeed, to leverage the full potential of UAS-based approaches, sensing technologies, measurement protocols, postprocessing techniques, retrieval algorithms, and evaluation techniques need to be harmonized. The aim of this paper is to provide an overview of the existing research and applications of UAS in natural and agricultural ecosystem monitoring in order to identify future directions, applications, developments, and challenges.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Bioadhesion and surface wettability are influenced by microscale topography. In the present study, engineered pillars, ridges and biomimetic topography inspired by the skin of fast moving sharks ...(Sharklet AF™) were replicated in polydimethylsiloxane elastomer. Sessile drop contact angle changes on the surfaces correlated well (R
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= 0.89) with Wenzel and Cassie and Baxter's relationships for wettability. Two separate biological responses, i.e. settlement of Ulva linza zoospores and alignment of porcine cardiovascular endothelial cells, were inversely proportional to the width (between 5 and 20 μm) of the engineered channels. Zoospore settlement was reduced by ∼85% on the finer (ca 2 μm) and more complex Sharklet AF™ topographies. The response of both cell types suggests their responses are governed by the same underlying thermodynamic principles as wettability.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Infections with group A rotaviruses are common among infants and young children worldwide.
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The outcome ranges from asymptomatic infection to severe, life-threatening diarrhea.
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Rotavirus ...is the leading cause of severe diarrhea among children and causes an estimated 870,000 deaths annually in developing countries.
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The disease burden of rotavirus is so great that development of a vaccine is a global priority for public health.
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Epidemiologic studies of rotavirus have suggested that natural immunity is acquired after early exposure to the virus and that many children acquire immunity only after several infections.
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However, observations . . .
OBJECTIVES
The goal of this study was to compare T-wave alternans (TWA), signal-averaged electrocardiography (SAECG) and programmed ventricular stimulation (EPS) for arrhythmia risk stratification in ...patients undergoing electrophysiology study.
BACKGROUND
Accurate identification of patients at increased risk for sustained ventricular arrhythmias is critical to prevent sudden cardiac death. T-wave alternans is a heart rate dependent measure of repolarization that correlates with arrhythmia vulnerability in animal and human studies. Signal-averaged electrocardiography and EPS are more established tests used for risk stratification.
METHODS
This was a prospective, multicenter trial of 313 patients in sinus rhythm who were undergoing electrophysiologic study. T-wave alternans, assessed with bicycle ergometry, and SAECG were measured before EPS. The primary end point was sudden cardiac death, sustained ventricular tachycardia, ventricular fibrillation or appropriate implantable defibrillator (ICD) therapy, and the secondary end point was any of these arrhythmias or all-cause mortality.
RESULTS
Kaplan-Meier survival analysis of the primary end point showed that TWA predicted events with a relative risk of 10.9, EPS had a relative risk of 7.1 and SAECG had a relative risk of 4.5. The relative risks for the secondary end point were 13.9, 4.7 and 3.3, respectively (p < 0.05). Multivariate analysis of 11 clinical parameters identified only TWA and EPS as independent predictors of events. In the prespecified subgroup with known or suspected ventricular arrhythmias, TWA predicted primary end points with a relative risk of 6.1 and secondary end points with a relative risk of 8.0.
CONCLUSIONS
T-wave alternans is a strong independent predictor of spontaneous ventricular arrhythmias or death. It performed as well as programmed stimulation and better than SAECG in risk stratifying patients for life-threatening arrhythmias.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gut-homing lymphocytes that express the integrin α4β7 and CCR9 might contribute to development of primary sclerosing cholangitis (PSC). Vedolizumab, which blocks the integrin α4β7, is used to treat ...patients with inflammatory bowel diseases (IBD), but there are few data on its efficacy in patients with PSC. We investigated the effects of vedolizumab in a large international cohort of patients with PSC and IBD.
We collected data from European and North American centers participating in the International PSC Study Group from patients with PSC and IBD who received at least 3 doses of vedolizumab (n = 102; median vedolizumab treatment duration, 412 days). Demographic and clinical data were collected from baseline and during the follow-up period (until liver transplantation, death, or 56 days after the final vedolizumab infusion). We analyzed overall changes in biochemical features of liver and proportions of patients with reductions in serum levels of alkaline phosphatase (ALP) of 20% or more, from baseline through last follow-up evaluation. Other endpoints included response of IBD to treatment (improved, unchanged, or worsened, judged by the treating clinician, as well as endoscopic score) and liver-related outcomes.
In the entire cohort, the median serum level of ALP increased from 1.54-fold the upper limit of normal at baseline to 1.64-fold the upper limit of normal at the last follow-up examination (P = .018); serum levels of transaminases and bilirubin also increased by a small amount between baseline and the last follow-up examination. Serum levels of ALP decreased by 20% or more in 21 patients (20.6%); only the presence of cirrhosis (odds ratio, 4.48; P = .019) was independently associated with this outcome. Of patients with available endoscopic data, 56.8% had a response of IBD to treatment. Liver-related events occurred in 21 patients (20.6%), including bacterial cholangitis, cirrhosis decompensation, or transplantation.
In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
Differences in diet composition among conspecifics (dietary specialization) have been documented across a broad range of taxonomic groups and habitats, and such variation at the individual level is ...increasingly recognized as an important component of diversity in trophic interactions. Accurate identification of individual dietary specialization, however, requires longitudinal dietary records that are labor-intensive and cost-prohibitive to obtain for many species. Here we explore the use of stable isotopes (δ¹³C and δ¹⁵N) as a promising technique for detecting and quantifying patterns of individual dietary specialization. Southern sea otters (Enhydra lutris nereis) offer a unique opportunity for testing this approach because (1) they consume a wide variety of prey that span multiple trophic levels, habitats, and ecologically defined functional groups; and (2) individual diet specialization can be validated with existing observational data. We analyzed the isotopic composition of sea otter vibrissae (n = 31) in order to characterize inter- and intra-individual variation in sea otter diets at Monterey Bay, California, USA. At the population level, sea otters showed substantial variation in both δ¹³C and δ¹⁵N values, occupying nearly all of the "isotopic space" created by the diversity of isotopic signatures of potential prey taxa. Most of the variation in sea otter vibrissae was accounted for by differences between individuals, with much less contributed by within-individual variation. A majority of sea otters (∼80%) showed relatively little temporal variability in isotopic composition, suggesting that the proportional composition of most individuals' diets is relatively constant over time; a few individuals (∼20%) exhibited a high degree of intra-vibrissa isotopic variability, suggesting seasonal shifts in diet composition. These results and our interpretation of them were supported by long-term observational data on the diets of radio-tagged sea otters from the same population (n = 23). Our results demonstrate that stable isotopes can provide an efficient tool for measuring individual- and population-level dietary breadth and may be useful for studying populations where longitudinal data on individuals would otherwise be impossible to acquire. This will be critical for examining the causes and consequences of dietary variation within and among consumer populations, thereby improving our understanding of these important ecological and evolutionary processes at the community level.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
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