Optical tweezers are a highly versatile tool for exploration of the mesoscopic world, permitting non-contact manipulation of nanoscale objects. However, direct illumination with intense lasers ...restricts their use with live biological specimens, and limits the types of materials that can be trapped. Here we demonstrate an indirect optical trapping platform which circumvents these limitations by using hydrodynamic forces to exert nanoscale-precision control over aqueous particles, without directly illuminating them. Our concept is based on optically actuated micro-robotics: closed-loop control enables highly localised flow-fields to be sculpted by precisely piloting the motion of optically-trapped micro-rotors. We demonstrate 2D trapping of absorbing particles which cannot be directly optically trapped, stabilise the position and orientation of yeast cells, and demonstrate independent control over multiple objects simultaneously. Our work expands the capabilities of optical tweezers platforms, and represents a new paradigm for manipulation of aqueous mesoscopic systems.
Osteoporosis is caused by an imbalance of osteoclasts and osteoblasts, occurring in close proximity to hematopoietic cells in the bone marrow. Recurrent somatic mutations that lead to an expanded ...population of mutant blood cells is termed clonal hematopoiesis of indeterminate potential (CHIP). Analyzing exome sequencing data from the UK Biobank, we found CHIP to be associated with increased incident osteoporosis diagnoses and decreased bone mineral density. In murine models, hematopoietic-specific mutations in Dnmt3a, the most commonly mutated gene in CHIP, decreased bone mass via increased osteoclastogenesis. Dnmt3a-/- demethylation opened chromatin and altered activity of inflammatory transcription factors. Bone loss was driven by proinflammatory cytokines, including Irf3-NF-κB-mediated IL-20 expression from Dnmt3a mutant macrophages. Increased osteoclastogenesis due to the Dnmt3a mutations was ameliorated by alendronate or IL-20 neutralization. These results demonstrate a novel source of osteoporosis-inducing inflammation.
Over the past 2 decades, chronic total occlusion (CTO) percutaneous coronary intervention has developed into its own subspecialty of interventional cardiology. Dedicated terminology, techniques, ...devices, courses, and training programs have enabled progressive advancements. However, only a few randomized trials have been performed to evaluate the safety and efficacy of CTO percutaneous coronary intervention. Moreover, several published observational studies have shown conflicting data. Part of the paucity of clinical data stems from the fact that prior studies have been suboptimally designed and performed. The absence of standardized end points and the discrepancy in definitions also prevent consistency and uniform interpretability of reported results in CTO intervention. To standardize the field, we therefore assembled a broad consortium comprising academicians, practicing physicians, researchers, medical society representatives, and regulators (US Food and Drug Administration) to develop methods, end points, biomarkers, parameters, data, materials, processes, procedures, evaluations, tools, and techniques for CTO interventions. This article summarizes the effort and is organized into 3 sections: key elements and procedural definitions, end point definitions, and clinical trial design principles. The Chronic Total Occlusion Academic Research Consortium is a first step toward improved comparability and interpretability of study results, supplying an increasingly growing body of CTO percutaneous coronary intervention evidence.
Adipose tissue (AT) regulatory T cells (T regs) control inflammation and metabolism. Diet-induced obesity causes hyperinsulinemia and diminishes visceral AT (VAT) T reg number and function, but ...whether these two phenomena were mechanistically linked was unknown. Using a T reg-specific insulin receptor (Insr) deletion model, we found that diet-induced T reg dysfunction is driven by T reg-intrinsic insulin signaling. Compared with Foxp3cre mice, after 13 wk of high-fat diet, Foxp3creInsrfl/fl mice exhibited improved glucose tolerance and insulin sensitivity, effects associated with lower AT inflammation and increased numbers of ST2+ T regs in brown AT, but not VAT. Similarly, Foxp3creInsrfl/fl mice were protected from the metabolic effects of aging, but surprisingly had reduced VAT T regs and increased VAT inflammation compared with Foxp3cre mice. Thus, in both diet- and aging-associated hyperinsulinemia, excessive Insr signaling in T regs leads to undesirable metabolic outcomes. Ablation of Insr signaling in T regs represents a novel approach to mitigate the detrimental effects of hyperinsulinemia on immunoregulation of metabolic syndrome.
Increasing demand for river water now conflicts with an increasing desire to maintain riparian ecosystems. Efficiently managing river flows for riparian vegetation requires an understanding of the ...time scale of flow effects, but this information is limited by the absence of long‐term studies of vegetation change in response to flow variation. To investigate the influence of short‐ and long‐term flow variability and dam operation on riparian vegetation, we determined the occurrence of 107 plant species in 133 permanent plots of known inundating discharge along the Gunnison River in Colorado on five different occasions between 1990 and 2013. Individual species moved up and down the gradient of inundating discharge coincident with increases and decreases in mean annual flow, and the correlations between flow and species occurrence were strongest when flows were weighted by time before vegetation sampling with a median half‐life of 1.5 years. Some tall, rhizomatous, perennial species, however, responded to flows on a longer time scale. Logistic regression of species occurrence showed a significant relation with inundation duration for 70 out of 107 species. Plot species richness and total vegetative cover decreased in association with desiccation at low inundation durations and with fluvial disturbance at high inundation durations. Within‐plot similarity in species occurrence between years decreased strongly with increasing inundation duration. Moderate inundation durations were dominated by tall, rhizomatous, perennial herbs, including invasive Phalaris arundinacea (reed canary grass). Over the 23‐year study period, species richness declined, and the proportion of rhizomatous perennials increased, consistent with the hypothesis that decreases in flow peaks and increases in low flows caused by flow regulation have decreased establishment opportunities for disturbance‐dependent species. In summary, annual‐scale changes in vegetation were strongly influenced by flow variation, and decadal‐scale changes were influenced by decreases in fluvial disturbance from upstream flow regulation beginning decades prior to the onset of this study.
To investigate whether modification of liver complement factor H (CFH) production, by alteration of liver CFH Y402H genotype through liver transplantation (LT), influences the development of ...age-related macular degeneration (AMD).
Multicenter, cross-sectional study.
We recruited 223 Western European patients ≥ 55 years old who had undergone LT ≥ 5 years previously.
We determined AMD status using a standard grading system. Recipient CFH Y402H genotype was obtained from DNA extracted from recipient blood samples. Donor CFH Y402H genotype was inferred from recipient plasma CFH Y402H protein allotype, measured using enzyme-linked immunosorbent assays. This approach was verified by genotyping donor tissue from a subgroup of patients. Systemic complement activity was ascertained by measuring levels of plasma complement proteins using an enzyme-linked immunosorbent assay, including substrates (C3, C4), activation products (C3a, C4a, and terminal complement complex), and regulators (total CFH, C1 inhibitor).
We evaluated AMD status and recipient and donor CFH Y402H genotype.
In LT patients, AMD was associated with recipient CFH Y402H genotype (P = 0.036; odds ratio OR, 1.6; 95% confidence interval CI, 1.0-2.4) but not with donor CFH Y402H genotype (P = 0.626), after controlling for age, sex, smoking status, and body mass index. Recipient plasma CFH Y402H protein allotype predicted donor CFH Y402H genotype with 100% accuracy (n = 49). Plasma complement protein or activation product levels were similar in LT patients with and without AMD. Compared with previously reported prevalence figures (Rotterdam Study), LT patients demonstrated a high prevalence of both AMD (64.6% vs 37.1%; OR, 3.09; P<0.001) and the CFH Y402H sequence variation (41.9% vs 36.2%; OR, 1.27; P = 0.014).
Presence of AMD is not associated with modification of hepatic CFH production. In addition, AMD is not associated with systemic complement activity in LT patients. These findings suggest that local intraocular complement activity is of greater importance in AMD pathogenesis. The high AMD prevalence observed in LT patients may be associated with the increased frequency of the CFH Y402H sequence variation.
The authors have no proprietary or commercial interest in any materials discussed in this article.
In contrast to conventional multipixel cameras, single-pixel cameras capture images using a single detector that measures the correlations between the scene and a set of patterns. However, these ...systems typically exhibit low frame rates, because to fully sample a scene in this way requires at least the same number of correlation measurements as the number of pixels in the reconstructed image. To mitigate this, a range of compressive sensing techniques have been developed which use a priori knowledge to reconstruct images from an undersampled measurement set. Here, we take a different approach and adopt a strategy inspired by the foveated vision found in the animal kingdom-a framework that exploits the spatiotemporal redundancy of many dynamic scenes. In our system, a high-resolution foveal region tracks motion within the scene, yet unlike a simple zoom, every frame delivers new spatial information from across the entire field of view. This strategy rapidly records the detail of quickly changing features in the scene while simultaneously accumulating detail of more slowly evolving regions over several consecutive frames. This architecture provides video streams in which both the resolution and exposure time spatially vary and adapt dynamically in response to the evolution of the scene. The degree of local frame rate enhancement is scene-dependent, but here, we demonstrate a factor of 4, thereby helping to mitigate one of the main drawbacks of single-pixel imaging techniques. The methods described here complement existing compressive sensing approaches and may be applied to enhance computational imagers that rely on sequential correlation measurements.
Age Related Macular Degeneration (AMD) is the leading cause of registerable blindness with a high medical and societal cost burden. Much of the research examining experiences of living with AMD has ...been conducted independently with small sample sizes and has failed to impact on practice. Meta-synthesis of qualitative research can improve the understanding of the experience of living with AMD by drawing together findings of qualitative studies. This article presents a systematic review and meta-synthesis of qualitative studies investigating the experience of AMD (literature searched up to April 2012; published studies identified range from 1996 to 2009). The review highlights themes relating to: functional limitations, adaptation and independence; feelings about the future with vision impairment; interaction with the health service; social engagement; disclosure; and the emotional impacts of living with AMD. Attention to the experience of living with AMD can help us to better understand the needs of patients. This meta-synthesis aimed to bring together the findings of qualitative research studies and highlights important areas for consideration when caring for patients with AMD. Our findings suggest that a holistic approach to service provision and support for AMD is needed which takes into account individuals' needs and experiences when coping with and adjusting to living with AMD. This support should aim to reduce stigma, increase social engagement, and develop the psychological resources of patients with AMD.
► Draws together the qualitative research conducted with patients with age-related macular degeneration (AMD). ► Highlights knowledge about the experience of living with AMD which can help to better understand the needs of patients. ► Provides support for holistic approaches to service provision which acknowledge unique experiences of older patients. ► Advises developing services to reduce stigma, increase social engagement, and develop psychological resources of patients.
Acellular dermal matrices (ADMs) are commonly used in prepectoral breast reconstruction. However, ADM is associated with high cost and potentially infection and seroma. Comparative studies on ...prepectoral reconstruction with and without ADM are limited to small, single-institution series. The purpose of this study was to perform a meta-analysis of prepectoral reconstruction with and without ADM. A systematic literature review was performed to identify studies comparing prepectoral reconstruction with and without ADM using PubMed, EMBASE, and Cochrane databases. Pooled rates of patient demographics and outcomes were analyzed. Meta-analytic effect size estimates were calculated for reconstructive complications in studies comparing reconstruction with and without ADM. In total, 515 reconstructions from four studies were included. Most cases were nipple-sparing mastectomies and utilized tissue-expander reconstructions. Meta-analysis demonstrated no significant difference in the rate of complications between cohorts with and without ADM. Short-term complications included reconstructive failure (1.2% in ADM cohort and 2.8% in no-ADM), seroma (1.2% and 8.3%, respectively), hematoma (1.2% and 2.1%), infection (4.7% and 4.2%), and mastectomy flap ischemia and/or necrosis (2.4% and 5.2%). Long-term complications included rippling (3.3% in ADM and 5.1% in no-ADM cohorts) and capsular contracture (6.8% and 3.4%, respectively). This meta-analysis demonstrated no difference in the rate of complications between cases with and without ADM. However, the outcomes data from no-ADM reconstruction mostly reflect robust mastectomy flaps. Surgeon discretion as informed by specific clinical scenarios should guide decisions regarding the use of ADM in prepectoral breast reconstruction.
Abstract
In the current era of Big Data, existing synthesis tools such as formal meta-analyses are critical means to handle the deluge of information. However, there is a need for complementary tools ...that help to (a) organize evidence, (b) organize theory, and (c) closely connect evidence to theory. We present the hierarchy-of-hypotheses (HoH) approach to address these issues. In an HoH, hypotheses are conceptually and visually structured in a hierarchically nested way where the lower branches can be directly connected to empirical results. Used for organizing evidence, this tool allows researchers to conceptually connect empirical results derived through diverse approaches and to reveal under which circumstances hypotheses are applicable. Used for organizing theory, it allows researchers to uncover mechanistic components of hypotheses and previously neglected conceptual connections. In the present article, we offer guidance on how to build an HoH, provide examples from population and evolutionary biology and propose terminological clarifications.
PDF
