The three-dimensional swimming tracks of motile microorganisms can be used to identify their species, which holds promise for the rapid identification of bacterial pathogens. The tracks also provide ...detailed information on the cells' responses to external stimuli such as chemical gradients and physical objects. Digital holographic microscopy (DHM) is a well-established, but computationally intensive method for obtaining three-dimensional cell tracks from video microscopy data. We demonstrate that a common neural network (NN) accelerates the analysis of holographic data by an order of magnitude, enabling its use on single-board computers and in real time. We establish a heuristic relationship between the distance of a cell from the focal plane and the size of the bounding box assigned to it by the NN, allowing us to rapidly localise cells in three dimensions as they swim. This technique opens the possibility of providing real-time feedback in experiments, for example by monitoring and adapting the supply of nutrients to a microbial bioreactor in response to changes in the swimming phenotype of microbes, or for rapid identification of bacterial pathogens in drinking water or clinical samples.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cities have become key players in climate change mitigation policy. To develop their climate policies, cities need good assessments of their current and future emissions. We use publically available ...national datasets to develop an integrated approach for estimating GHG emissions at the metropolitan level over time, between multiple locations, and across sectors. We estimate consistent production-based GHG emissions for the 100 most populated metropolitan areas in the United States in 2014. We find that total 2014 metropolitan CO2 emissions range from 4.1 million metric tons in Lancaster, Pennsylvania to nearly 170 million metric tons in the Houston, Texas; with an overall average of 27 million metric tons. The top 20 absolute emitters and top 20 per capita emitters only overlap for 9 locations. Per capita emissions also show a wide variation: from 5 metric tons per person in the Tucson, Arizona to 65 metric tons per person in the Baton Rouge, Louisiana; with an overall average of 14 metric tons per person. We also compute estimates for 2002 and 2011 and compare to our 2014 emission estimates. Across all locations analyzed, average total emissions increased by 3% and average per capita emissions decreased by 14%. Where possible, we also compare our emission estimates to those reported by the cities in their climate action plans and find an average absolute difference between our estimates and those reported by the cities of 5.6 metric tons CO2 per person, likely due to temporal and scope differences between the two estimates. Our integrated emission estimation approach complements bottom-up approaches typically employed by municipalities and helps practitioners divert their attention and resources away from continuous emission accounting toward more impactful emission mitigation efforts.
Resilience-based management is essential to protect ecosystems in the Anthropocene. Unlike large-scale climate threats to Great Barrier Reef (GBR) corals, outbreaks of coral-eating crown-of-thorns ...starfish (COTS; Acanthaster cf. solaris) can be directly managed through targeted culling. Here, we evaluate the outcomes of a decade of strategic COTS management in suppressing outbreaks and protecting corals during the 4th COTS outbreak wave at reef and regional scales (sectors). We compare COTS density and coral cover dynamics during the 3rd and 4th outbreak waves. During the 4th outbreak wave, sectors that received limited to no culling had sustained COTS outbreaks causing significant coral losses. In contrast, in sectors that received timely and sufficient cull effort, coral cover increased substantially, and outbreaks were suppressed with COTS densities up to six-fold lower than in the 3rd outbreak wave. In the Townsville sector for example, despite exposure to comparable disturbance regimes during the 4th outbreak wave, effective outbreak suppression coincided with relative increases in sector-wide coral cover (44%), versus significant coral cover declines (37%) during the 3rd outbreak wave. Importantly, these estimated increases span entire sectors, not just reefs with active COTS control. Outbreaking reefs with higher levels of culling had net increases in coral cover, while the rate of coral loss was more than halved on reefs with lower levels of cull effort. Our results also indicate that outbreak wave progression to adjoining sectors has been delayed, probably via suppression of COTS larval supply. Our findings provide compelling evidence that proactive, targeted, and sustained COTS management can effectively suppress COTS outbreaks and deliver coral growth and recovery benefits at reef and sector-wide scales. The clear coral protection outcomes demonstrate the value of targeted manual culling as both a scalable intervention to mitigate COTS outbreaks, and a potent resilience-based management tool to "buy time" for coral reefs, protecting reef ecosystem functions and biodiversity as the climate changes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This data compilation synthesizes 36 static environmental and spatial variables, and temporally explicit modeled estimates of three major disturbances to coral cover on the Great Barrier Reef (GBR): ...(1) coral bleaching, (2) tropical cyclones, and (3) outbreaks of the coral-eating crown-of-thorns starfish Acanthaster cf. solaris. Data are provided on a standardized grid (0.01° × 0.01° ∼ 1 × 1 km) for reef locations along the GBR, containing 15,928 pixels and excluding the northernmost sections (<12° S) where empirical data were sparse. This compilation provides a consistent and high-resolution characterization of the abiotic environment and disturbance regimes for GBR reef locations at a fine spatial scale to be used in the development of complex ecosystem models. Static estimates of environmental variables (e.g., depth, bed shear stress, average temperature, temperature variation) originally developed by the Commonwealth of Australia’s Environment Research Facility (CERF) Marine Biodiversity Hub were provided by Geoscience Australia. Annual (1985–2017) disturbance estimates were either interpolated from empirical data (A. cf. solaris), predicted from proxy indicators (e.g., degree heating weeks DHW as a proxy for bleaching severity), or explicitly modeled (e.g., wave height model for each cyclone). This data set synthesizes some of the most recent advances in remote sensing and modeling of environmental conditions on the GBR; yet it is not exhaustive and we highlight areas that should be expanded through future research. The characterization of abiotic and disturbance regimes presented here represent an essential tool for the development of complex regional scale models of the GBR; preventing redundancy between working groups and promoting collaboration, innovation, and consistency. When using the data set, we kindly request that you cite this article and/or the articles cited in the reference section, recognizing the work that went into compiling the data together and the original authors’ willingness to make it publicly available.
In recent years, cities across the United States have devoted considerable attention and resources to developing greenhouse gas (GHG) inventories and climate action plans (CAPs). Using integrated ...metropolitan-level GHG estimates from publicly available national datasets, we explore the implications of inventory scope and boundary choices for 41 metropolitan areas across the United States. We quantify emissions from 'under-reported' activities (i.e. emissions from industrial processes and from transportation between urban and suburban areas) and 'under-reported' geographies (i.e. emissions from all activities occurring within the metropolitan area, but outside the city limits), and find that, in most cases, these 'under-reported' emissions constitute a considerable portion of total metropolitan emissions. Given the important role local CAPs continue to play in national-level GHG reduction efforts, there appears to be much to gain from continuing to expand the scope and boundaries of local-level GHG accounting and reduction actions. This analysis helps illustrate why transitions toward policies at the regional (as opposed to the city level) may be warranted, as well as highlights some key issues that may arise as local-level GHG policies continue to evolve and expand. For example, if local decision-makers choose to expand the scope and/or scale of their policies, GHG reduction plans may warrant substantial alterations to baseline emission levels, targeted annual emission reduction rates, overall emission target levels, or the number of years needed to achieve a desired emission reduction. Ultimately, the manner in which these policies evolve will determine their overall contribution to national and international climate mitigation efforts.
We conducted a 16-week randomized controlled trial in psychiatric outpatients with a lifetime diagnosis of a mood and/or anxiety disorder to measure the impact of a first-of-its-kind precision ...digital intervention software solution based on social rhythm regulation principles. The full intent-to-treat (ITT) sample consisted of 133 individuals, aged 18-65. An exploratory sub-sample of interest was those individuals who presented with moderately severe to severe depression at study entry (baseline PHQ-8 score ≥15;
= 28). Cue is a novel digital intervention platform that capitalizes on the smartphone's ability to continuously monitor depression-relevant behavior patterns and use each patient's behavioral data to provide timely, personalized "micro-interventions," making this the first example of a precision digital intervention of which we are aware. Participants were randomly allocated to receive Cue plus care-as-usual or digital monitoring only plus care as usual. Within the full study and depressed-at-entry samples, we fit a mixed effects model to test for group differences in the slope of depressive symptoms over 16 weeks. To account for the non-linear trajectory with more flexibility, we also fit a mixed effects model considering week as a categorical variable and used the resulting estimates to test the group difference in PHQ change from baseline to 16 weeks. In the full sample, the group difference in the slope of PHQ-8 was negligible (Cohen's
= -0.10); however, the Cue group demonstrated significantly greater improvement from baseline to 16 weeks (
= 0.040). In the depressed-at-entry sample, we found evidence for benefit of Cue. The group difference in the slope of PHQ-8 (Cohen's
= -0.72) indicated a meaningfully more rapid rate of improvement in the intervention group than in the control group. The Cue group also demonstrated significantly greater improvement in PHQ-8 from baseline to 16 weeks (
= 0.009). We are encouraged by the size of the intervention effect in those who were acutely ill at baseline, and by the finding that across all participants, 80% of whom were receiving pharmacotherapy, we observed significant benefit of Cue at 16 weeks of treatment. These findings suggest that a social rhythm-focused digital intervention platform may represent a useful and accessible adjunct to antidepressant treatment (https://clinicaltrials.gov/ct2/show/NCT03152864?term=ellen+frank&draw=2&rank=3).
Lay Summary The ability to successfully resolve conflict is an important means of enhancing fitness and reproductive success within social groups. In the Eastern mosquitofish, we show that in ...response to increased temperatures, subordinate group members regulate their growth to resolve potential conflict with dominant individuals within their hierarchy. This is the first demonstration of a link between the abiotic environment and conflict resolution in a social species.In social groups, hierarchies are the fundamental organizational unit and integral to the structure of social groups. For many social fishes, rank is determined by body size and conflict over rank is resolved via aggressive threats from dominants and growth restraint by subordinates. However, this balance may be offset by an alteration of abiotic factors, such as elevated temperature expected from climate change, which could thereby disrupt the usual mechanisms of conflict resolution. Here, we determined the effect of elevated temperature on hierarchy structure, stability, and conflict resolution in the Eastern mosquitofish, Gambusia holbrooki. Body size was significantly related to dominance rank, and aggression was more commonly directed toward subordinates and was heightened between individuals of adjacent rank, demonstrating that conflict over rank occurs in size-based hierarchies. Temperature did not affect overall levels or directionality/adjacency of aggression but substantially altered subordinate growth patterns. In only the high-temperature groups, growth rates of subordinates decreased as the size ratio between themselves and their immediate dominant approached 1.0, whereas growth rates of dominants were unaffected. This unique finding suggests that only under high temperatures, subordinates may adopt growth regulation to resolve conflict, when the costs of conflict with dominants are greater. This provides the first causal link between abiotic stressors and changes to hierarchical structure and functioning, providing a springboard for further research into implications of temperature-dependent subordinate growth alteration at higher levels of ecological organization.
Summary
Background and Aims
Current guidelines recommend long‐term nucleot(s)ide analogue (NA) therapy for patients with HBeAg‐negative chronic hepatitis B (CHB). However, disease remission has been ...described after stopping NA therapy, as well as HBsAg loss.
Methods
We performed a prospective multi‐centre cohort study of stopping NA therapy. Inclusion criteria were HBeAg‐negative CHB, the absence of cirrhosis and HBVDNA<lower limit of quantification for ≥18 months. We assessed virological and biochemical outcomes including HBsAg loss, as well as NA restart rates, over 96 weeks.
Results
In total, 110 patients 62% entecavir (ETV); 28% tenofovir (TDF), 10% other were enrolled. Median age was 56 years, 57% were male, 85% were Asian, median baseline HBsAg level was 705 (214–2325) IU/ml. Virological reactivation occurred in 109/110 patients, median time to detection was 8 (4–12) weeks, and occurred earlier after stopping TDF versus ETV (median 4 vs. 12 weeks p < 0.001). At week 96, 77 (70%) remained off‐treatment, 65 (59%) had ALT <2× ULN, 31 (28%) patients were in disease remission with HBVDNA <2000 IU/ml plus ALT <2× ULN and 7 (6%) patients had lost HBsAg. Baseline HBsAg ≤10 IU/ml was associated with HBsAg loss (6/9 vs. 1/101 p < 0.001). ALT >5× ULN occurred in 35 (32%); ALT flares were not associated with HBsAg loss. There were no unexpected safety issues.
Conclusion
Virological reactivation was very common after stopping NA therapy and occurred earlier after stopping TDF versus ETV. The majority of patients had ALT <2× ULN at week 96, but only one‐third achieved disease remission and HBsAg loss was rare. Very low HBsAg levels at baseline were uncommon but predicted for HBsAg loss and disease remission.
Clinical outcomes over time—Intention to treat analysis of clinical outcomes in 110 patients who stopped NA therapy. Patients were classified into the following groups: HBsAg loss, Biochemical Remission (ALT <2× ULN), Virological Remission (HBV DNA <2000), or NA treatment restarted (Figure 1); Low baseline HBsAg levels were associated with higher likelihood of HBsAg loss and lower rates of Virological and Biochemical Relapse—(A) Baseline HBsAg level ≤10 IU/ml was associated with HBsAg loss – 6 of 7 patients who lost HBsAg had a baseline HBsAg level ≤10 IU/ml HBsAg ≤10 IU/ml, HBsAg loss = 6/9 (67%) versus HBsAg >10 IU/ml, HBsAg loss = 1/101 (1%), p < 0.001, Figure 5. Low baseline HBsAg levels were also associated with a lower rate of (B) virological relapse HBsAg level ≤10 IU/ml, 3/9 vs. HBsAg level >10, 95/101, HR 0.15 (0.05, 0.47) p = 0.001 and (C) biochemical relapse HBsAg level ≤10 IU/ml, 1/9 vs. HBsAg level >10, 54/101, HR 0.16 (0.02, 1.13) p = 0.066 through 96 weeks of follow‐up (Figure 2).
Platinum resistance is a common occurrence in high-grade serous ovarian cancer and a major cause of ovarian cancer deaths. Platinum agents form DNA cross-links, which activate nucleotide excision ...repair (NER), Fanconi anemia, and homologous recombination repair (HRR) pathways. Chromatin modifications occur in the vicinity of DNA damage and play an integral role in the DNA damage response (DDR). Chromatin modifiers, including polycomb repressive complex 1 (PRC1) members, and chromatin structure are frequently dysregulated in ovarian cancer and can potentially contribute to platinum resistance. However, the role of chromatin modifiers in the repair of platinum DNA damage in ovarian cancer is not well understood. We demonstrate that the PRC1 complex member RING1A mediates monoubiquitination of lysine 119 of phosphorylated H2AX (γH2AXub1) at sites of platinum DNA damage in ovarian cancer cells. After platinum treatment, our results reveal that NER and HRR both contribute to RING1A localization and γH2AX monoubiquitination. Importantly, replication protein A, involved in both NER and HRR, mediates RING1A localization to sites of damage. Furthermore, RING1A deficiency impairs the activation of the G
-M DNA damage checkpoint, reduces the ability of ovarian cancer cells to repair platinum DNA damage, and increases sensitivity to platinum. IMPLICATIONS: Elucidating the role of RING1A in the DDR to platinum agents will allow for the identification of therapeutic targets to improve the response of ovarian cancer to standard chemotherapy regimens.
There is growing evidence that pre-exposure prophylaxis (PrEP) prevents HIV acquisition. However, in the United States, approximately only 4% of people who could benefit from PrEP are currently ...receiving it, and it is estimated only 1 in 5 physicians has ever prescribed PrEP. We conducted a scoping review to gain an understanding of physician-identified barriers to PrEP provision. Four overarching barriers presented in the literature: Purview Paradox, Patient Financial Constraints, Risk Compensation, and Concern for ART Resistance. Considering the physician-identified barriers, we make recommendations for how physicians and students may work to increase PrEP knowledge and competence along each stage of the PrEP cascade. We recommend adopting HIV risk assessment as a standard of care, improving physician ability to identify PrEP candidates, improving physician interest and ability in encouraging PrEP uptake, and increasing utilization of continuous care management to ensure retention and adherence to PrEP.
PDF
