Targeting Hypercapnia in Chronic Lung Disease and Obesity Hypoventilation: Benefits and Challenges.

Hypoventilation is a complication that is not uncommon in chronic obstructive pulmonary disease and calls for both medical treatment of the underlying disease and, frequently, noninvasive ventilation either during exacerbations requiring hospitalization or in a chronic state in the patient at home. Obesity hypoventilation syndrome by definition is associated with ventilatory failure and hypercapnia. It may or may not be accompanied by obstructive sleep apnea, which when detected becomes an additional target for positive airway pressure treatment. Intensive research has not completely resolved the best choice of treatment, and the simplest modality, continuous positive airway pressure, may still be entertained.

Efficacy and pharmacodynamic effect of anti-CD73 and anti-PD-L1 monoclonal antibodies in combination with cytotoxic therapy: observations from mouse tumor models.

CD73 is a cell surface 5'nucleotidase (NT5E) and key node in the catabolic process generating immunosuppressive adenosine in cancer. Using a murine monoclonal antibody surrogate of Oleclumab, we investigated the effect of CD73 inhibition in concert with cytotoxic therapies (chemotherapies as well as fractionated radiotherapy) and PD-L1 blockade. Our results highlight improved survival in syngeneic tumor models of colorectal cancer (CT26 and MC38) and sarcoma (MCA205). This therapeutic outcome was in part driven by cytotoxic CD8 T-cells, as evidenced by the detrimental effect of CD8 depleting antibody treatment of MCA205 tumor bearing mice treated with anti-CD73, anti-PD-L1 and 5-Fluorouracil+Oxaliplatin (5FU+OHP). We hypothesize that the improved responses are tumor microenvironment (TME)-driven, as suggested by the lack of anti-CD73 enhanced cytopathic effects mediated by 5FU+OHP on cell lines in vitro. Pharmacodynamic analysis, using imaging mass cytometry and RNA-sequencing, revealed noteworthy changes in specific cell populations like cytotoxic T cells, B cells and NK cells in the CT26 TME. Transcriptomic analysis highlighted treatment-related modulation of gene profiles associated with an immune response, NK and T-cell activation, T cell receptor signaling and interferon (types 1 & 2) pathways. Inclusion of comparator groups representing the various components of the combination allowed deconvolution of contribution of the individual therapeutic elements; highlighting specific effects mediated by the anti-CD73 antibody with respect to immune-cell representation, chemotaxis and myeloid biology. These pre-clinical data reflect complementarity of adenosine blockade with cytotoxic therapy, and T-cell checkpoint inhibition, and provides new mechanistic insights in support of combination therapy.

Efficient Estimation of the Human Circadian Phase via Kalman Filtering.

Circadian rhythms play a vital role in maintaining a person's well-being but remain difficult to quantify accurately. Numerous approaches exist to measure these rhythms, but they often suffer from performance issues on the individual level. This work implements a Steady-State Kalman Filter as a method for estimating the circadian phase shifts from biometric signals. Our framework can automatically fit the filter's parameters to biometric data obtained for each individual, and we were able to consistently estimate the phase shift within 1 hour of melatonin estimates on 100% of all subjects in this study. The estimation method opens up the possibility of real-time control and assessment of the circadian system, as well as chronotherapeutic intervention.Clinical relevance- This establishes a near real-time alternative to melatonin measurements for the estimation of circadian phase shifts, with potential applications in feedback circadian control and chronotherapeutics.

Biological Invasions Affect Resource Processing in Aquatic Ecosystems: The Invasive Amphipod Dikerogammarus villosus Impacts Detritus Processing through High Abundance Rather than Differential Response to Temperature.

Anthropogenic stressors such as climate warming and invasive species and natural stressors such as parasites exert pressures that can interact to impact the function of ecosystems. This study investigated how these stressors interact to impact the vital ecosystem process of shredding by keystone species in temperate freshwater ecosystems. We compared metabolic rates and rates of shredding at a range of temperatures up to extreme levels, from 5 °C to 30 °C, between invasive and native amphipods that were unparasitised or parasitised by a common acanthocephalan, Echinorhynchus truttae. Shredding results were compared using the relative impact potential (RIP) metric to investigate how they impacted the scale with a numerical response. Although per capita shredding was higher for the native amphipod at all temperatures, the higher abundance of the invader led to higher relative impact scores; hence, the replacement of the native by the invasive amphipod is predicted to drive an increase in shredding. This could be interpreted as a positive effect on the ecosystem function, leading to a faster accumulation of amphipod biomass and a greater rate of fine particulate organic matter (FPOM) provisioning for the ecosystem. However, the high density of invaders compared with natives may lead to the exhaustion of the resource in sites with relatively low leaf detritus levels.

Postactivation Potentiation for Muay Thai Kicking Performance.

ABSTRACT: Brown, L, Doyle, G, Bruce-Low, S, Domingos, S, Anthony, K, Rowan, F, and Galbraith, A. Postactivation potentiation for Muay Thai kicking performance. J Strength Cond Res 37(10): 2032-2037, 2023-The purpose of this study was to investigate the effects of postactivation potentiation (PAP) on Muay Thai kicking performance based on 3 different rest intervals. Aiming to quantify and indicate timing protocols for conditioning coaches when training athletes using PAP. 17 male (25.3 ± 3.6 years old; 179.3 ± 2.3 cm; 78.0 ± 5.2 kg), experienced Muay Thai fighters completed a standardized warm-up, including a 10-minute cycle on the Wattbike at 60 watts and 30 body mass squats for a dynamic stretch. Subjects then completed a baseline test by striking a PowerKube using the roundhouse and Teep kick techniques. PAP exercise consisted of 4 squat repetitions to maximum effort, followed by a rest period of 2, 5, or 8 minutes. Subjects then struck the PowerKube again using the roundhouse and Teep kick techniques. Rest periods were presented in a randomized order on separate days, with 72 hours between conditions. The level of significance was set at α = 0.05. Significant increases in both roundhouse (χ 2 (3) = 38.51, p < 0.05) and Teep kick (χ 2 (3) = 26.33, p < 0.05) striking power were observed when compared with baseline. For the roundhouse kick, significant differences and large effect sizes were present between all conditions except baseline and 2-minute rest. For the Teep kick, significant differences and large effect sizes were present between baseline and 5-minute rest and baseline and 8-minute rest. This indicates that PAP with 5- or 8-minute rest increased roundhouse and Teep kick power. This research reports that a PAP stimulus from a 4RM squat exercise, followed by a 5- or 8-minute rest period, enhances kick power in trained Muay Thai fighters. This technique provides a readily available, time-efficient method to enhance performance that can be built into the warm-up procedure of athletes before training or competition.

Climate-driven spatial and temporal patterns in peatland pool biogeochemistry.

Peatland pools are freshwater bodies that are highly dynamic aquatic ecosystems because of their small size and their development in organic-rich sediments. However, our ability to understand and predict their contribution to both local and global biogeochemical cycles under rapidly occurring environmental change is limited because the spatiotemporal drivers of their biogeochemical patterns and processes are poorly understood. We used (1) pool biogeochemical data from 20 peatlands in eastern Canada, the United Kingdom, and southern Patagonia and (2) multi-year data from an undisturbed peatland of eastern Canada, to determine how climate and terrain features drive the production, delivering and processing of carbon (C), nitrogen (N), and phosphorus (P) in peatland pools. Across sites, climate (24%) and terrain (13%) explained distinct portions of the variation in pool biogeochemistry, with climate driving spatial differences in pool dissolved organic C (DOC) concentration and aromaticity. Within the multi-year dataset, DOC, carbon dioxide (CO2 ), total N concentrations, and DOC aromaticity were highest in the shallowest pools and at the end of the growing seasons, and increased gradually from 2016 to 2021 in relation to a combination of increases in summer precipitation, mean air temperature for the previous fall, and number of extreme summer heat days. Given the contrasting effects of terrain and climate, broad-scale terrain characteristics may offer a baseline for the prediction of small-scale pool biogeochemistry, while broad-scale climate gradients and relatively small year-to-year variations in local climate induce a noticeable response in pool biogeochemistry. These findings emphasize the reactivity of peatland pools to both local and global environmental change and highlight their potential to act as widely distributed climate sentinels within historically relatively stable peatland ecosystems.

A meta-analysis of environmental responses to freshwater ecosystem restoration in China (1987-2018).

Understanding how abiotic and biotic components respond to aquatic ecosystem restoration is pivotal for sustainable development in the face of economic development and global environmental change. However, the post-restoration monitoring and evaluation of aquatic ecosystems across large spatial and temporal scales is underfunded or not well documented, especially outside of Europe and North America. We present a meta-analysis of abiotic and biotic indices to quantify post-restoration (2 months-13 years) effects from reported aquatic restoration projects throughout the China-mainland, incorporating 39 lentic and 36 lotic ecosystems. Decreases in dissolved nutrients (total nitrogen, ammonia nitrogen and total phosphorus) post-restoration were rapid, but tended to slow down after about 9.3 years. Response ratios summarizing biodiversity responses (incorporating phytoplankton, invertebrates, vascular plants, fish and birds) typically lagged behind abiotic changes, suggesting longer timescales are needed for biotic indices to recover. Time since restoration interacted with lentic project size showing that, even with the same proportional efforts of restoration, larger lentic ecosystems responded much more slowly than smaller ones. Spatial heterogeneity, reflecting the effects of different restoration approaches (e.g., sewage interception, polluted sediment dredging, artificial wetlands, etc.), had a significantly stronger effect on biotic than abiotic indices, particularly in rivers compared to standing waters. This reflects the complexity of fluvial ecosystem dynamics and hints at a limitation in the reinstatement of ecological processes in these systems to overcome issues such as dispersal limitations. Overall, the different timelines and processes by which abiotic and biotic indices recover after restoration should be taken into account when defining restoration targets and monitoring programs. Our study illustrates the value of long-term aquatic ecosystem monitoring, especially in China given the scale and magnitude of ongoing restoration investments in the country.

Workplace Violence in Imaging Departments.

PURPOSE: To investigate the types and frequency of workplace violence experienced by radiologic technologists and to identify which technologists using specific imaging modalities are at increased risk. METHODS: A mixed-methods approach was employed using a research electronic data capture (REDCap; Vanderbilt University) survey designed to establish information on radiologic technologists' self-reported experiences with workplace violence. The survey was distributed to a random sample of 10 000 radiologic technologists working with various imaging disciplines. Participants (N = 193) were asked questions regarding personal and employment demographics, experiences with violence, and reporting and education practices. RESULTS: Radiologic technologists were shown to have experienced most workplace violence from patients or visitors. Among those surveyed, 50% or more reported being hit, bitten, called names, harassed, threatened, or having hair pulled by a patient. Verbal intimidation by patients, visitors, and others also was reported, with more than 50% experienced from visitors and more than 40% from patients, coworkers, radiologists, other physicians, or other health care providers. Statistical tests to evaluate a relationship between types of workplace violence and imaging modalities showed an association between name-calling by visitors and modality (P < .001). Results indicated that technologists performing computed tomography imaging, adult diagnostic imaging in the emergency department, and magnetic resonance imaging experienced the most frequent occurrences of name-calling by visitors. DISCUSSION: Workplace violence, which can affect a person mentally, physically, and emotionally, might occur in any work environment. In the health care setting, radiologic technologists might experience workplace violence originating from coworkers, other health care professionals, patients, visitors, or a combination of these sources. Therefore, a health care organization's acknowledgment of workplace violence and their resolve to prevent or reduce its occurrence is important. Providing sufficient human resources and adequate workplace violence education courses might be the first steps in eliminating workplace violence in the health care environment. CONCLUSION: Workplace violence creates an undesirable working environment, leading to negative implications for the health care worker and the patient. Education that details possible types of workplace violence and best practices for handling each type is key to protecting employees. This study provides a foundation for future quality improvement studies aimed at protecting the mental and physical health of imaging professionals.

Radiologic Sciences Student Perceptions of Advisement.

PURPOSE: To investigate student perceptions of a structured advisement program. METHODS: Using a mixed-methods approach, 24 radiologic sciences students were surveyed in the initial and final semesters of the program to capture their perceptions of advisement practices. Quantitative data were analyzed for percentages and descriptive statistics, and qualitative responses were analyzed for emergent themes. RESULTS: Qualitative data analyses identified 3 themes: building relationships, strengthening student performance, and determining best practices for advisement. Quantitative data demonstrated that students appreciated the advisement process and acknowledged improvements in communication skills and the feedback loop. DISCUSSION: Advisement sessions can serve an important role in identifying areas where students can improve their performance. To grow and develop, students must understand their own strengths and weaknesses. Structured forms of advisement can serve as important tools to guide advisement conversations toward specific topics. CONCLUSION: The results of this study indicate that student advising is a vital component of radiologic sciences programs. Participants indicated that the advisement process helped them build relationships with faculty members and improved their overall performance.

High concentrations of pharmaceuticals emerging as a threat to Himalayan water sustainability.

The sixth UN Sustainable Development Goal, Clean Water and Sanitation, directly underpins other goals of Health, Life in Water and Sustainable Cities. We highlight that poor sanitation, exemplified through some of the highest concentrations of pharmaceuticals ever detected in rivers, will amplify societal and environmental stress where climate-induced reductions in flow are predicted. Rapidly growing urban centres with inadequate water treatment works will need to prioritise water quality improvement before supply reductions become a reality. For 23 river locations within Kathmandu City and the Annapurna region, Nepal, we show the presence of 28 of 35 monitored human-use pharmaceuticals. Concentrations of antibiotics measured in this sampling campaign in both Kathmandu City (sulfamethazine, metronidazole and ciprofloxacin) and rural locations (ciprofloxacin) are in excess of predicted no effect concentrations, suggesting these sites are at risk of proliferating antimicrobial resistance as well as affecting other ecotoxicological endpoints. It is anticipated that climate-induced reductions in flow combined with contaminated river systems will amplify future societal and environmental stress.

High Concentrations of Pharmaceuticals in a Nigerian River Catchment.

Pharmaceutical contamination of the environment is recognized as a global problem although most research has focused on Europe and North America to date, and there remains a dearth of information for developing countries, including those in Africa. To address this data gap, the occurrence of 37 pharmaceuticals belonging to 19 therapeutic classes was monitored in surface water and effluents in Lagos State, Southwest Nigeria. Samples were collected quarterly between April 2017 and March 2018 from 22 sites, and 26 compounds were detected at least once, many in the µg/L range. Maximum concentrations for those compounds detected ranged from 75 to 129 µg L-1 , and even mean concentrations for 13 compounds were in the order of µg L-1 . These values are among the highest ever measured globally. Sewage effluent was more important than drug manufacturing waste in polluting rivers, although there are likely to be numerous unregulated sources of effluent being discharged to rivers that require further study, including urban waste collection areas and vacuum trucks that collect effluent. Seasonal trends in the data were complex, with some compounds being found at higher concentrations in the dry season and, conversely, others being greater during the wet period; this variation potentially relates to the variety of pollution sources in the catchment. Pharmaceuticals are indispensable to human health, although their usage and discharge into the aquatic environment may lead to ecological problems and antibiotic resistance. The data we present indicate that pharmaceutical pollution of freshwaters is a serious issue in Nigeria, and management efforts are needed to improve this problem. Environ Toxicol Chem 2022;41:551-558. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

A global agenda for advancing freshwater biodiversity research.

Global freshwater biodiversity is declining dramatically, and meeting the challenges of this crisis requires bold goals and the mobilisation of substantial resources. While the reasons are varied, investments in both research and conservation of freshwater biodiversity lag far behind those in the terrestrial and marine realms. Inspired by a global consultation, we identify 15 pressing priority needs, grouped into five research areas, in an effort to support informed stewardship of freshwater biodiversity. The proposed agenda aims to advance freshwater biodiversity research globally as a critical step in improving coordinated actions towards its sustainable management and conservation.

Fast tuning of observer-based circadian phase estimator using biometric data.

Circadian rhythms play a vital role in maintaining an individual's well-being, and they have been shown to be the product of the master oscillator in the suprachiasmatic nuclei (SCN) located in the brain. The SCN however, is inaccessible for assessment, so existing standards for circadian phase estimation often focus on the use of indirect measurements as proxies for the circadian state. These methods often suffer from severe delays due to invasive methods of sample collection, making online estimation impossible. In this paper, we propose a linear state observer as an elegant solution for continuous phase estimation. This observer-based filter is used in isolating the frequency components of input biometric signals, which are then taken to be the circadian state. We start the design process by fixing the observer's oscillatory frequency at 24 hours, and then we tune its gains using an evolutionary optimization algorithm to extract the target components from individuals' data. The resulting filter was able to provide phase estimates with an average absolute error within 1.5 hours on all test subjects, given their minute-to-minute actigraphy data collected in ambulatory conditions.

Accelerated mass loss of Himalayan glaciers since the Little Ice Age.

Himalayan glaciers are undergoing rapid mass loss but rates of contemporary change lack long-term (centennial-scale) context. Here, we reconstruct the extent and surfaces of 14,798 Himalayan glaciers during the Little Ice Age (LIA), 400 to 700 years ago. We show that they have lost at least 40 % of their LIA area and between 390 and 586 km3 of ice; 0.92 to 1.38 mm Sea Level Equivalent. The long-term rate of ice mass loss since the LIA has been between - 0.011 and - 0.020 m w.e./year, which is an order of magnitude lower than contemporary rates reported in the literature. Rates of mass loss depend on monsoon influence and orographic effects, with the fastest losses measured in East Nepal and in Bhutan north of the main divide. Locally, rates of loss were enhanced with the presence of surface debris cover (by 2 times vs clean-ice) and/or a proglacial lake (by 2.5 times vs land-terminating). The ten-fold acceleration in ice loss we have observed across the Himalaya far exceeds any centennial-scale rates of change that have been recorded elsewhere in the world.

Mitigation of urbanization effects on aquatic ecosystems by synchronous ecological restoration.

Ecosystem degradation and biodiversity loss have been caused by economic booms in developing countries over recent decades. In response, ecosystem restoration projects have been advanced in some countries but the effectiveness of different approaches and indicators at large spatio-temporal scales (i.e., whole catchments) remains poorly understood. This study assessed the effectiveness of a diverse array of 440 aquatic restoration projects including wastewater treatment, constructed wetlands, plant/algae salvage and dredging of contaminated sediments implemented and maintained from 2007 to 2017 across more than 2000 km2 of the northwest Taihu basin (Yixing, China). Synchronized investigations of water quality and invertebrate communities were conducted before and after restoration. Our analysis showed that even though there was rapid urbanization at this time, nutrient concentrations (NH4+-N, TN, TP) and biological indices of benthic invertebrate (taxonomic richness, Shannon diversity, sensitive taxon density) improved significantly across most of the study area. Improvements were associated with the type of restoration project, with projects targeting pollution-sources leading to the clearest ecosystem responses compared with those remediating pollution sinks. However, in some locations, the recovery of biotic communities appears to lag behind nutrients (e.g., nitrogen and phosphorus), likely reflecting long-distance re-colonization routes for invertebrates given the level of pre-restoration degradation of the catchment. Overall, the study suggests that ecological damage caused by recent rapid economic development in China could potentially be mitigated by massive restoration investments synchronized across whole catchments, although these effects could be expected to be enhanced if urbanization rates were reduced at the same time.

Multiparametric MRI of early tumor response to immune checkpoint blockade in metastatic melanoma.

BACKGROUND: Immune checkpoint inhibitors are now standard of care treatment for many cancers. Treatment failure in metastatic melanoma is often due to tumor heterogeneity, which is not easily captured by conventional CT or tumor biopsy. The aim of this prospective study was to investigate early microstructural and functional changes within melanoma metastases following immune checkpoint blockade using multiparametric MRI. METHODS: Fifteen treatment-naïve metastatic melanoma patients (total 27 measurable target lesions) were imaged at baseline and following 3 and 12 weeks of treatment on immune checkpoint inhibitors using: T2-weighted imaging, diffusion kurtosis imaging, and dynamic contrast-enhanced MRI. Treatment timepoint changes in tumor cellularity, vascularity, and heterogeneity within individual metastases were evaluated and correlated to the clinical outcome in each patient based on Response Evaluation Criteria in Solid Tumors V.1.1 at 1 year. RESULTS: Differential tumor growth kinetics in response to immune checkpoint blockade were measured in individual metastases within the same patient, demonstrating significant intertumoral heterogeneity in some patients. Early detection of tumor cell death or cell loss measured by a significant increase in the apparent diffusivity (Dapp) (p<0.05) was observed in both responding and pseudoprogressive lesions after 3 weeks of treatment. Tumor heterogeneity, as measured by apparent diffusional kurtosis (Kapp), was consistently higher in the pseudoprogressive and true progressive lesions, compared with the responding lesions throughout the first 12 weeks of treatment. These preceded tumor regression and significant tumor vascularity changes (Ktrans, ve, and vp) detected after 12 weeks of immunotherapy (p<0.05). CONCLUSIONS: Multiparametric MRI demonstrated potential for early detection of successful response to immune checkpoint inhibitors in metastatic melanoma.

Extreme flood disturbance effects on multiple dimensions of river invertebrate community stability.

Multidimensional analysis of community stability has recently emerged as an overarching approach to evaluating ecosystem response to disturbance. However, the approach has previously been applied only in experimental and modelling studies. We applied this concept to an 18-year time series (2000-2017) of macroinvertebrate community dynamics from a southeast Alaskan river to further develop and test the approach in relation to the effects of two extreme flood events occurring in 2005 (event 1) and 2014 (event 2). Five components of stability were calculated for pairs of pre- or post-event years. Individual components were tested for differences between pre- and post-event time periods. Stability components' pairwise correlations were assessed and ellipsoids of stability were developed for each time period and compared to a null model derived from the permuted dataset. Only one stability component demonstrated a significant difference between time periods. In contrast, 80% of moderate and significant correlations between stability components were degraded post-disturbance and significant changes to the form of stability ellipsoids were observed. Ellipsoids of stability for all periods after the initial disturbance (2005) were not different to the null model. Our results illustrate that the dimensionality of stability approach can be applied to natural ecosystem time-series data. The major increase in dimensionality of stability observed following disturbance potentially indicates significant shifts in the processes which drive stability following disturbance. This evidence improves our understanding of community response beyond what is possible through analysis of individual stability components.