Decoding the identity of biomolecules from trace samples is a longstanding goal in the field of biotechnology. Advances in DNA analysis have substantially affected clinical practice and basic ...research, but corresponding developments for proteins face challenges due to their relative complexity and our inability to amplify them. Despite progress in methods such as mass spectrometry and mass cytometry, single-molecule protein identification remains a highly challenging objective. Towards this end, we combine DNA nanotechnology with single-molecule force spectroscopy to create a mechanically reconfigurable DNA nanoswitch caliper capable of measuring multiple coordinates on single biomolecules with atomic resolution. Using optical tweezers, we demonstrate absolute distance measurements with ångström-level precision for both DNA and peptides, and using multiplexed magnetic tweezers, we demonstrate quantification of relative abundance in mixed samples. Measuring distances between DNA-labelled residues, we perform single-molecule fingerprinting of synthetic and natural peptides, and show discrimination, within a heterogeneous population, between different posttranslational modifications. DNA nanoswitch calipers are a powerful and accessible tool for characterizing distances within nanoscale complexes that will enable new applications in fields such as single-molecule proteomics.
Tracking the Consolidation of U.S. Agriculture MacDonald, James M.
Applied economic perspectives and policy,
September 2020, 2020-09-00, 20200901, Letnik:
42, Številka:
3
Journal Article
Recenzirano
I assess farm sector consolidation in the United States from the 1980s through the most recent (2017) Census of Agriculture. Consolidation has been large, widespread across crop and livestock ...commodities, and persistent over time. Research on this topic benefits from access to farm‐level datasets, which provide more comprehensive insights into consolidation and alter what we thought we knew about farm consolidation in earlier studies using aggregated data. I close with a reflection on the applications and challenges that I have found in using firm‐, plant‐, and transactions‐level microdata through my career.
Racial disparities in healthcare utilization and outcomes have been reported and have wide-reaching implications for individual patient and healthcare system; as providers we bear an ethical burden ...to address this disparity and provide culturally competent care. This study will examine the influence of race on length of stay, discharge disposition, and complications requiring reoperation following total joint arthroplasty (TJA).
Single institution retrospective analysis of a consecutive series of 7208 primary TJA procedures performed between July 2013 and June 2017 was conducted. Chi-squared and t-tests were used to quantify differences between the groups and multiple logistic regression was used to identify race as an independent risk factor.
In total, 6182 (84.3%) white and 1026 (14.0%) African American (AA) patients were included. AA patients were younger (63.62 vs 66.84 years, P < .001), more likely female (68.8% vs 57.0%, P < .001), had a longer length of stay (2.19 vs 2.00 days, P < .001), more likely to experience septic complications (1.3% vs 0.5%, P = .002) and manipulation under anesthesia (3.9% vs 1.8%, P < .001), and less likely to discharge home (67.1% vs 81.1%, P < .001). Multiple logistic regression showed that AA patients were more likely to discharge to a facility (adjusted odds ratio 2.63, 95% confidence interval 2.19-3.16, P < .001) and experience a manipulation under anesthesia (adjusted odds ratio 1.90, 95% confidence interval 1.26-2.85, P = .002).
AA patients undergoing TJA were younger with longer length of stay and a higher rate of nonhome discharge; AA race was identified as an independent risk factor. Further study is required to understand the differences identified in this study. Targeted interventions should be developed to attempt to eliminate the disparity.
Elevated concentrations of CO2 in seawater can disrupt numerous sensory systems in marine fish. This is of particular concern for Pacific salmon because they rely on olfaction during all aspects of ...their life including during their homing migrations from the ocean back to their natal streams. We investigated the effects of elevated seawater CO2 on coho salmon (Oncorhynchus kisutch) olfactory‐mediated behavior, neural signaling, and gene expression within the peripheral and central olfactory system. Ocean‐phase coho salmon were exposed to three levels of CO2, ranging from those currently found in ambient marine water to projected future levels. Juvenile coho salmon exposed to elevated CO2 levels for 2 weeks no longer avoided a skin extract odor that elicited avoidance responses in coho salmon maintained in ambient CO2 seawater. Exposure to these elevated CO2 levels did not alter odor signaling in the olfactory epithelium, but did induce significant changes in signaling within the olfactory bulb. RNA‐Seq analysis of olfactory tissues revealed extensive disruption in expression of genes involved in neuronal signaling within the olfactory bulb of salmon exposed to elevated CO2, with lesser impacts on gene expression in the olfactory rosettes. The disruption in olfactory bulb gene pathways included genes associated with GABA signaling and maintenance of ion balance within bulbar neurons. Our results indicate that ocean‐phase coho salmon exposed to elevated CO2 can experience significant behavioral impairments likely driven by alteration in higher‐order neural signal processing within the olfactory bulb. Our study demonstrates that anadromous fish such as salmon may share a sensitivity to rising CO2 levels with obligate marine species suggesting a more wide‐scale ecological impact of ocean acidification.
Juvenile coho salmon exposed to elevated CO2 levels for 2 weeks showed a compromised ability to detect a predator alarm odor relative to coho salmon maintained in ambient CO2 seawater. Electrophysiological and gene expression analysis of coho salmon olfactory tissues indicated that the behavioral impairments experienced by salmon exposed to elevated CO2 may be associated with alterations in higher‐order neural signal processing within the olfactory bulb. Our study demonstrates that anadromous fish such as salmon may share a sensitivity to rising CO2 levels with obligate marine species, suggesting potential wide‐scale ecological impacts of ocean acidification on fish.
Vaccines are critical cost-effective tools to control the coronavirus disease 2019 (COVID-19) pandemic. However, the emergence of variants of the severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2) may threaten the global impact of mass vaccination campaigns.
The objective of this study was to provide an up-to-date comparative analysis of the characteristics, adverse events, efficacy, effectiveness and impact of the variants of concern for 19 COVID-19 vaccines.
References for this review were identified through searches of PubMed, Google Scholar, BioRxiv, MedRxiv, regulatory drug agencies and pharmaceutical companies' websites up to 22nd September 2021.
Overall, all COVID-19 vaccines had a high efficacy against the original strain and the variants of concern, and were well tolerated. BNT162b2, mRNA-1273 and Sputnik V after two doses had the highest efficacy (>90%) in preventing symptomatic cases in phase III trials. mRNA vaccines, AZD1222, and CoronaVac were effective in preventing symptomatic COVID-19 and severe infections against Alpha, Beta, Gamma or Delta variants. Regarding observational real-life data, full immunization with mRNA vaccines and AZD1222 seems to effectively prevent SARS-CoV-2 infection against the original strain and Alpha and Beta variants but with reduced effectiveness against the Delta strain. A decline in infection protection was observed at 6 months for BNT162b2 and AZD1222. Serious adverse event rates were rare for mRNA vaccines—anaphylaxis 2.5–4.7 cases per million doses, myocarditis 3.5 cases per million doses—and were similarly rare for all other vaccines. Prices for the different vaccines varied from $2.15 to $29.75 per dose.
All vaccines appear to be safe and effective tools to prevent severe COVID-19, hospitalization, and death against all variants of concern, but the quality of evidence greatly varies depending on the vaccines considered. Questions remain regarding a booster dose and waning immunity, the duration of immunity, and heterologous vaccination. The benefits of COVID-19 vaccination outweigh the risks, despite rare serious adverse effects.
Background.
Oral antineoplastic therapies not only improve survival but also reduce the burden of care for patients. Yet patients and clinicians face new challenges in managing adherence to these ...oral therapies. We conducted a systematic literature review to assess rates and correlates of adherence to oral antineoplastic therapies and interventions aimed at improving adherence.
Methods.
Following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, we conducted a comprehensive literature search of the Ovid MEDLINE database from January 1, 2003 to June 30, 2015, using relevant terminology for oral antineoplastic agents. We included observational, database, and intervention studies. At least two researchers evaluated each paper to ensure accuracy of results and determine risk of bias.
Results.
We identified 927 records from the search and screened 214 s. After conducting a full‐text review of 167 papers, we included in the final sample 51 papers on rates/correlates of adherence to oral antineoplastic therapy and 12 papers on intervention studies to improve adherence. Rates of adherence varied widely, from 46% to 100%, depending on patient sample, medication type, follow‐up period, assessment measure, and calculation of adherence. Of the intervention studies, only 1 of the randomized trials and 2 of the cohort studies showed benefit regarding adherence, with the majority suffering high risk of bias.
Conclusions.
Although no reliable estimate of adherence to oral antineoplastic therapies can be gleaned from the literature, a substantial proportion of patients struggle to adhere to these medications as prescribed. The few intervention studies for adherence have notable methodological concerns, thereby limiting the evidence to guide practice in promoting medication adherence among patients with cancer.
Implications for Practice:
Given the tremendous growth and development of oral antineoplastic therapies in the last decade, significant gaps have emerged in oncology practice with respect to standardized procedures for safe administration, monitoring, and management of these medications. Although rates of adherence to oral antineoplastic therapies vary widely depending on population, cancer type, and method of measurement, a substantial proportion of patients struggle to take their oral antineoplastic medications as prescribed. On the basis of current evidence and national recommendations, oncology practices should develop standard procedures for educating patients, reviewing and documenting treatment plans, and routinely monitoring patient adherence to oral antineoplastic therapies.
Although no reliable estimate of adherence to oral antineoplastic therapies can be gleaned from the literature, a substantial proportion of patients struggle to adhere to these medications as prescribed. The few intervention studies for adherence have notable methodological concerns, thereby limiting the evidence to guide practice in promoting medication adherence among patients with cancer.
Our perception of time varies considerably from moment to moment, but how this variability relates to endogenous fluctuations in attentional states has been neglected. Here, we tested the hypothesis ...that perceptual decoupling during spontaneous mind wandering episodes distorts interval timing. In two studies with different visual subsecond interval timing paradigms, participants judged their attentional state on a trial-by-trial basis. Mind wandering states were characterized by underestimation of temporal intervals and a decline in temporal discrimination. Further analyses suggested that temporal contraction during mind wandering, but not the decline in temporal discrimination, could be attributed in part to attentional lapses. By contrast, we did not find any robust evidence that metacognition pertaining to interval timing was altered during mind wandering states. These results highlight the role of transient fluctuations in attentional states in intraindividual variability in time perception and have implications for the perceptual consequences, behavioral markers, and costs and benefits, of mind wandering.
Public Significance Statement
The way we experience time changes from one moment to the next: We may underestimate or overestimate time or we may perceive it as uniform or fragmented. Previous research has identified factors that influence our perception of time but the variables that underlie spontaneous fluctuations in time perception have been neglected. Here, we examined whether changes in our tendency to mind wander (to think about things other than the task at hand) might explain some of the variability in our time perception. In 2 studies, we show that participants underestimate time and are poorer at discriminating different temporal intervals when they are mind wandering. Temporal contraction seems to be attributable, in part, to lapses in our attention, whereas poorer temporal discrimination may be attributable to impaired perception when mind wandering. These results help to clarify the role of spontaneous changes in attentional states to variations in our perception of time.
Attentional sampling of multiple wagon wheels Macdonald, James S. P.; Cavanagh, Patrick; VanRullen, Rufin
Attention, perception & psychophysics,
2014/1, Letnik:
76, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Attending to a periodic motion stimulus can induce illusory reversals of the direction of motion. This continuous wagon wheel illusion (c-WWI) has been taken to reflect discrete sampling of motion ...information by visual attention. An alternative view is that it is caused by adaptation. Here, we attempt to discriminate between these two interpretations by asking participants to attend to multiple periodic motion stimuli: The discrete attentional sampling account, but not the adaptation account, predicts a decrease of c-WWI temporal-frequency tuning with set size (with a single periodic motion stimulus the c-WWI is tuned to a temporal frequency of 10 Hz). We presented one to four rotating gratings that occasionally reversed direction while participants counted reversals. We considered reversal overestimations as manifestations of the c-WWI and determined the temporal-frequency tuning of the illusion for each set size. Optimal temporal frequency decreased with increasing set size. This outcome favors the discrete attentional sampling interpretation of the c-WWI, with a sampling rate for each individual stimulus dependent on the number of stimuli attended.
Background Shorter length of stay (LOS) for total hip arthroplasty (THA) is becoming standard, yet variables identifying candidates for a 1-day discharge in an enhanced recovery after surgery (ERAS) ...program are not well defined. With growing emphasis on cost-efficiency and bundled care for THA, this study looked to identify variables that correlated with LOS. Methods A retrospective chart review was performed for 273 primary THAs, from April 2014 to January 2015. Clinical measures differentiating a 1-day LOS cohort from that of a LOS longer than one day were identified. Direct medical costs were calculated for services billed during hospitalization. Results Logistic regression identified the following preoperative patient characteristics to correlate with a LOS longer than one day: older age (1.06 OR, p<0.001), increased BMI (1.06 OR, p=0.005), female gender (1.76 OR, p=0.031), ASA 3 or 4 (1.84 OR, p=0.029), and coronary artery disease (3.90 OR, p=0.013). After adjusting for age, BMI, and gender, the following perioperative variables led to a LOS≥2 days: general anesthesia (2.24 OR, p=0.007), longer operative time (1.04 OR, p<0.001), and increased blood loss (1.01 OR, p=0.001). Postoperatively, not ambulating on the day of surgery strongly correlated with a LOS≥2 days (3.9 OR, p<0.001). Hospital costs were approximately $2,900 higher for a 2-day LOS. Conclusion With growing emphasis on cost-efficiency, studying the association of clinical factors with LOS is necessary to develop a preoperative and perioperative predictive risk stratification model that may be used to help optimize discharge protocols for patients in an ERAS program.
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