The Impact of Market Factors on Meaningful Use of Electronic Health Records Among Primary Care Providers: Evidence From Florida Using Resource Dependence Theory and Information Uncertainty Perspective.

BACKGROUND: Using federal funds from the 2009 Health Information Technology for Economic and Clinical Health Act, the Centers for Medicare and Medicaid Services funded the 2011-2021 Medicaid electronic health record (EHR) incentive programs throughout the country. OBJECTIVE: Identify the market factors associated with Meaningful Use (MU) of EHRs after primary care providers (PCPs) enrolled in the Florida-EHR incentives program through Adopting, Improving, or Upgrading (AIU) an EHR technology. RESEARCH DESIGN: Retrospective cohort study using 2011-2018 program records for 8464 Medicaid providers. MAIN OUTCOME: MU achievement after first-year incentives. INDEPENDENT VARIABLES: The resource dependence theory and the information uncertainty perspective were used to generate key-independent variables, including the county's rurality, educational attainment, poverty, health maintenance organization penetration, and number of PCPs per capita. ANALYTICAL APPROACH: All the county rates were converted into 3 dichotomous measures corresponding to high, medium, and low terciles. Descriptive and bivariate statistics were calculated. A generalized hierarchical linear model was used because MU data were clustered at the county level (level 2) and measured at the practice level (level 1). RESULTS: Overall, 41.9% of Florida Medicaid providers achieved MU after receiving first-year incentives. Rurality was positively associated with MU ( P <0.001). Significant differences in MU achievements were obtained when we compared the "high" terciles with the "low" terciles for poverty rates ( P =0.002), health maintenance organization penetration rates ( P =0.02), and number of PCPs per capita ( P =0.01). These relationships were negative. CONCLUSIONS: Policy makers and health care managers should not ignore the contribution of market factors in EHR adoption.

The impact of county-level factors on meaningful use of electronic health records (EHRs) among primary care providers.

This study examines the impact of county-level factors on "meaningful use" (MU) of electronic health records (EHRs) for 8415 primary care providers (PCPs) that enrolled in the Florida Medicaid EHR Incentive Program through adopting, improving, or upgrading (AIU) a certified EHR technology. PCPs received incentive payments at enrollment and if they used their EHRs in meaningful ways; ways that benefit patients and providers alike they received additional payments. We conducted a retrospective cohort study of these providers over the 2011-2018 period while linking their records to other state data. We used the core constructs of the resource dependence theory (RDT), a well-established organization theory in business management, to operationalize the county-level variables. These variables were rurality, poverty, educational attainment, managed care penetration, changes in population, and number of PCPs per capita. The unit of analysis was provider-years. For practical and computational purposes, all the county variables were dichotomized. We used analysis of variance (ANOVA) to test for differences in MU attestation rates across each county variable. Odds ratios and corresponding 95% confidence intervals were derived from pooled logistic regressions using generalized estimated equations (GEE) with the binomial family and logit link functions. Clustered standard errors were used. Approximately 42% of these providers attested to MU after receiving first-year incentives. Rurality and poverty were significantly associated with MU. To some degree, managed care penetration, change in population size, and number of PCPs per capita were also associated with MU. Policy makers and healthcare managers should not ignore the contribution of county-level factors in the diffusion of EHRs among physician practices. These county-level findings provide important insights about EHR diffusion in places where traditionally underserved populations live. This county-perspective is particularly important because of the potential for health IT to enable public health monitoring and population health management that might benefit individuals beyond the patients treated by the Medicaid providers.

First-trimester cavum veli interpositi: prevalence and natural history.

OBJECTIVE: To confirm the identity and assess the prevalence and evolution of the fluid-filled interhemispheric midline structure, thought to be the cavum veli interpositi (CVI), in fetuses at 11-14 weeks' gestation. METHODS: This was a retrospective study of first-trimester ultrasound scans performed at a single center over 3 months. Inclusion criteria were singleton pregnancies at 11-14 weeks' gestation with known neonatal outcome. Five experts reviewed the images. Mixed-effects logistic regression and generalized estimating equations (GEE) were conducted to analyze the associations between the presence of the structure and variables including ultrasound approach (transabdominal vs transvaginal), maternal body mass index (BMI), gestational age, fetal crown-rump length (CRL) and biparietal diameter (BPD). Second-trimester ultrasound scans of the fetal central nervous system at 18-24 weeks' gestation were evaluated for the persistence of the CVI in fetuses in which the structure was observed in the first trimester. RESULTS: Of the 223 cases reviewed, 104 were included, among which the CVI was observed in 25 (24%) cases. There was no statistically significant difference in CVI visualization between transabdominal and transvaginal ultrasound examinations. GEE showed significant associations between the presence of the fetal structure and CRL (odds ratio (OR) per 10-unit increase, 1.32; P < 0.0001) and BPD (OR per 10-unit increase, 1.88; P = 0.0011). Maternal BMI and gestational age showed no significant effect on the presence of the CVI. At second-trimester follow-up of the 25 fetuses in which the CVI was observed initially, 44% still showed a CVI, 32% exhibited a cavum vergae, 4% had both structures and 20% had neither. CONCLUSIONS: Based on its anatomical location and, in some fetuses, its visualization as a distinct entity from the third ventricle, the identity of the interhemispheric midline structure in the suprathalamic region of the fetal brain between 11-14 weeks' gestation was confirmed as the CVI. The CVI and/or cavum vergae persisted into the second trimester in 80% of fetuses identified initially as having a CVI. Its presence is not linked to pathology, offering reassurance to practitioners and parents. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Optimized Methods for the Production of High-Purity 203Pb Using Electroplated Thallium Targets.

203Pb is a surrogate imaging match for 212Pb. This elementally matched pair is emerging as a suitable pair for imaging and targeted radionuclide therapy in cancer care. Because of the half-life (51.9 h) and low-energy γ-rays emitted, 203Pb is suitable for the development of diagnostic radiopharmaceuticals. The aim of this work was to optimize the production and separation of high-specific-activity 203Pb using electroplated thallium targets. We further investigated the radiochemistry optimization using a suitable chelator, tetraazacyclododecane-1,4,7-triacetic acid (DO3A), and targeting vector, VMT-α-NET (lead-specific chelator conjugated to tyr3-octreotide via a polyethylene glycol linker). Methods: Targets were prepared by electroplating of natural or enriched (205Tl) thallium metal. Scanning electron microscopy was performed to determine the structure and elemental composition of electroplated targets. Targets were irradiated with 24-MeV protons with varying current and beam time to investigate target durability. 203Pb was purified from the thallium target material using an extraction resin (lead resin) column followed by a second column using a weak cation-exchange resin to elute the lead isotope as [203Pb]PbCl2 Inductively coupled plasma mass spectrometry studies were used to further characterize the separation for trace metal contaminants. Radiolabeling efficiency was also investigated for DO3A chelator and VMT-α-NET (a peptide-based targeting conjugate). Results: Electroplated targets were prepared at a high plating density of 76-114 mg/cm2 using a plating time of 5 h. A reproducible separation method was established with a final elution in HCl (400 µL, 1 M) suitable for radiolabeling. Greater than 90% recovery yields were achieved, with an average specific activity of 37.7 ± 5.4 GBq/µmol (1.1 ± 0.1 Ci/µmol). Conclusion: An efficient electroplating method was developed to prepare thallium targets suitable for cyclotron irradiation. A simple and fast separation method was developed for routine 203Pb production with high recovery yields and purity.

Synchronization in a multilevel network using the Hamilton-Jacobi-Bellman (HJB) technique.

This paper presents the optimal control and synchronization problem of a multilevel network of Rössler chaotic oscillators. Using the Hamilton-Jacobi-Bellman technique, the optimal control law with a three-state variable feedback is designed such that the trajectories of all the Rössler oscillators in the network are optimally synchronized at each level. Furthermore, we provide numerical simulations to demonstrate the effectiveness of the proposed approach for the cases of one and three networks. A perfect correlation between the MATLAB and PSpice results was obtained, thus allowing the experimental validation of our designed controller and shows the effectiveness of the theoretical results.

Quantitative systems pharmacology modeling sheds light into the dose response relationship of a trispecific T cell engager in multiple myeloma.

In relapsed and refractory multiple myeloma (RRMM), there are few treatment options once patients progress from the established standard of care. Several bispecific T-cell engagers (TCE) are in clinical development for multiple myeloma (MM), designed to promote T-cell activation and tumor killing by binding a T-cell receptor and a myeloma target. In this study we employ both computational and experimental tools to investigate how a novel trispecific TCE improves activation, proliferation, and cytolytic activity of T-cells against MM cells. In addition to binding CD3 on T-cells and CD38 on tumor cells, the trispecific binds CD28, which serves as both co-stimulation for T-cell activation and an additional tumor target. We have established a robust rule-based quantitative systems pharmacology (QSP) model trained against T-cell activation, cytotoxicity, and cytokine data, and used it to gain insight into the complex dose response of this drug. We predict that CD3-CD28-CD38 killing capacity increases rapidly in low dose levels, and with higher doses, killing plateaus rather than following the bell-shaped curve typical of bispecific TCEs. We further predict that dose-response curves are driven by the ability of tumor cells to form synapses with activated T-cells. When competition between cells limits tumor engagement with active T-cells, response to therapy may be diminished. We finally suggest a metric related to drug efficacy in our analysis-"effective" receptor occupancy, or the proportion of receptors engaged in synapses. Overall, this study predicts that the CD28 arm on the trispecific antibody improves efficacy, and identifies metrics to inform potency of novel TCEs.

Long-read genome sequencing resolves a complex 13q structural variant associated with syndromic anophthalmia.

Microphthalmia, anophthalmia, and coloboma (MAC) are a heterogeneous spectrum of anomalous eye development and degeneration with genetic and environmental etiologies. Structural and copy number variants of chromosome 13 have been implicated in MAC; however, the specific loci involved in disease pathogenesis have not been well-defined. Herein we report a newborn with syndromic degenerative anophthalmia and a complex de novo rearrangement of chromosome 13q. Long-read genome sequencing improved the resolution and clinical interpretation of a duplication-triplication/inversion-duplication (DUP-TRP/INV-DUP) and terminal deletion. Sequence features at the breakpoint junctions suggested microhomology-mediated break-induced replication (MMBIR) of the maternal chromosome as the origin. Comparing this rearrangement to previously reported copy number alterations in 13q, we refine a putative dosage-sensitive critical region for MAC that might provide new insights into its molecular etiology.

The Effect of Exoskeletal-Assisted Walking on Spinal Cord Injury Bowel Function: Results from a Randomized Trial and Comparison to Other Physical Interventions.

Bowel function after spinal cord injury (SCI) is compromised because of a lack of voluntary control and reduction in bowel motility, often leading to incontinence and constipation not easily managed. Physical activity and upright posture may play a role in dealing with these issues. We performed a three-center, randomized, controlled, crossover clinical trial of exoskeletal-assisted walking (EAW) compared to usual activity (UA) in people with chronic SCI. As a secondary outcome measure, the effect of this intervention on bowel function was assessed using a 10-question bowel function survey, the Bristol Stool Form Scale (BSS) and the Spinal Cord Injury Quality of Life (SCI-QOL) Bowel Management Difficulties instrument. Fifty participants completed the study, with bowel data available for 49. The amount of time needed for the bowel program on average was reduced in 24% of the participants after EAW. A trend toward normalization of stool form was noted. There were no significant effects on patient-reported outcomes for bowel function for the SCI-QOL components, although the time since injury may have played a role. Subset analysis suggested that EAW produces a greater positive effect in men than women and may be more effective in motor-complete individuals with respect to stool consistency. EAW, along with other physical interventions previously investigated, may be able to play a previously underappreciated role in assisting with SCI-related bowel dysfunction.

Provider participation in the Florida Medicaid Promoting Interoperability program: Practice characteristics, meaning use attestations, and incentive payments.

OBJECTIVE: The objective of this study was to quantify the rate of provider participation beyond year 1 incentive in the Florida Medicaid Promoting Interoperability (PI) program, formerly the Electronic Health Record Incentive program, and identify the provider and practice characteristics associated with Meaningful Use attestations. METHODS AND MATERIALS: We conducted a retrospective cohort study using the 2011-2018 records from the PI program, Provider Participation Database. Bivariate associations between Meaningful Use and categorical and ordinal variables were tested using Chi-square and Mantel-Haenszel Chi-square, respectively, with results informing logistic regressions. Adjusted odds ratios and 95 % confidence intervals are reported. RESULTS: We found that 42.56 % of Florida Medicaid providers achieved Meaningful Use after receiving first-year incentives. Logistic regression showed that pediatricians represented the largest percentage of providers who achieved Meaningful Use (65.06 %) while dentists had the lowest Meaningful Use (7.78 %). We also found that certain geographic areas and various EHR vendors were associated with higher rates of providers Meaningful Use attestation. DISCUSSION: Although the PI program successfully influenced the adoption of a basic EHR system, low Meaningful Use attestations have inadvertently created a digital "advanced use" divide among providers who serve large numbers of Medicaid patients. This is concerning because advanced EHR functions are necessary precursors to address unmet socioeconomic needs to reduce health disparities. CONCLUSION: Florida has distributed over $100 million to Medicaid providers who ultimately did not achieve Meaningful Use after collecting their first-year incentive. Policy interventions that can promote advanced EHR use functions are necessary to optimize technology in low-resourced practice settings where the potential benefits are greater.

Exoskeletal-assisted walking may improve seated balance in persons with chronic spinal cord injury: a pilot study.

STUDY DESIGN: Pre-post intervention. OBJECTIVE: To explore the potential effect of exoskeletal-assisted walking (EAW) on seated balance for persons with chronic motor complete spinal cord injury (SCI). SETTING: A SCI research center. METHODS: Eight participants who were over 18 years of age with chronic SCI and used a wheelchair for mobility were enrolled. Seven able-bodied participants were used for normal seated balance comparative values. Participants with chronic SCI received supervised EAW training using a powered exoskeleton (ReWalkTM) for a median 30 sessions (range from 7 to 90 sessions). Before and after EAW training, seated balance testing outcomes were collected using computerized dynamic posturography, providing measurements of endpoint excursion (EPE), maximal excursion (MXE), and directional control (DCL). Modified functional reach test (MFRT) and the sub-scales of physical functioning and role limitations due to physical health from the Short Form (36) Health Survey (SF-36) were used to identify changes in functional activities. RESULTS: After EAW training, seated balance significantly improved in total-direction EPE and MXE (P < 0.01 and P < 0.017 respectively). The results of MFRT and sub-scales of physical functioning and role limitations due to physical health improved after EAW training but were not statistically significant. CONCLUSIONS: EAW training may have the potential to improve seated balance for persons with chronic motor complete SCI. Due to the limitations of the study, such as small sample size and lack of a control group, further studies are needed to clarify the effect of improving seated balance through EAW training.

Oxygen Uptake During Exoskeletal-Assisted Walking in Persons With Paraplegia.

OBJECTIVE: To determine the cardiometabolic demands associated with exoskeletal-assisted walking (EAW) in persons with paraplegia. This study will further examine if training in the device for 60 sessions modifies cost of transport (CT). DESIGN: Prospective cohort study. Measurements over the course of a 60-session training program, approximately 20 sessions apart. SETTING: James J. Peters Bronx Veterans Affairs Medical Center, Center for the Medical Consequences of Spinal Cord Injury Research Center. PARTICIPANTS: The participants' demographics (N=5) were 37-61 years old, body mass index (calculated as weight in kilograms divided by height in meters squared) of 22.7-28.6, level of injury from T1-T11, and 2-14 years since injury. INTERVENTIONS: Powered EAW. MAIN OUTCOME MEASURES: Oxygen consumption per unit time (V˙O2, mL/min/kg), velocity (m/min), cost of transport (V˙O2/velocity), and rating of perceived exertion (RPE). RESULTS: With training: EAW velocity significantly improved (Pre: 51±51m; 0.14±0.14m/s vs Post: 99±42m; 0.28±0.12m/s, P=.023), RPE significantly decreased (Pre: 13±6 vs Post: 7±4, P=.001), V˙O2 significantly improved (Pre: 9.76±1.23 mL/kg/m vs Post: 12.73±2.30 mL/kg/m, P=.04), and CT was reduced from the early to the later stages of training (3.66±5.2 vs 0.87±0.85 mL/kg/m). CONCLUSIONS: The current study suggests that EAW training improves oxygen uptake efficiency and walking velocities, with a lower perception of exertion.

Dynamics of multilayer networks with amplification.

We study the dynamics of a multilayer network of chaotic oscillators subject to amplification. Previous studies have proven that multilayer networks present phenomena such as synchronization, cluster, and chimera states. Here, we consider a network with two layers of Rössler chaotic oscillators as well as applications to multilayer networks of the chaotic jerk and Liénard oscillators. Intra-layer coupling is considered to be all to all in the case of Rössler oscillators, a ring for jerk oscillators and global mean field coupling in the case of Liénard, inter-layer coupling is unidirectional in all these three cases. The second layer has an amplification coefficient. An in-depth study on the case of a network of Rössler oscillators using a master stability function and order parameter leads to several phenomena such as complete synchronization, generalized, cluster, and phase synchronization with amplification. For the case of Rössler oscillators, we note that there are also certain values of coupling parameters and amplification where the synchronization does not exist or the synchronization can exist but without amplification. Using other systems with different topologies, we obtain some interesting results such as chimera state with amplification, cluster state with amplification, and complete synchronization with amplification.

The design of a randomized control trial of exoskeletal-assisted walking in the home and community on quality of life in persons with chronic spinal cord injury.

There are more than 300,000 estimated cases of spinal cord injury (SCI) in the United States, and approximately 27,000 of these are Veterans. Immobilization from SCI results in adverse secondary medical conditions and reduced quality of life. Veterans with SCI who have completed rehabilitation after injury and are unable to ambulate receive a wheelchair as standard of care. Powered exoskeletons are a technology that offers an alternative form of limited mobility by enabling over-ground walking through an external framework for support and computer-controlled motorized hip and knee joints. Few studies have reported the safety and efficacy for use of these devices in the home and community environments, and none evaluated their impact on patient-centered outcomes through a randomized clinical trial (RCT). Absence of reported RCTs for powered exoskeletons may be due to a range of challenges, including designing, statistically powering, and conducting such a trial within an appropriate experimental framework. An RCT for the study of exoskeletal-assisted walking in the home and community environments also requires the need to address key factors such as: avoiding selection bias, participant recruitment and retention, training, and safety concerns, particularly in the home environment. These points are described here in the context of a national, multisite Department of Veterans Affairs Cooperative Studies Program-sponsored trial. The rationale and methods for the study design were focused on providing a template for future studies that use powered exoskeletons or other strategies for walking and mobility in people with immobilization due to SCI.

Changing the Culture: Improving Helmet Utilization to Prevent Traumatic Brain Injury.

BACKGROUND: Several groups have instituted helmet initiatives with varying success across the world. Helmet use has been well documented to prevent traumatic brain injury. Despite the known benefits, many people, including university students, refuse to utilize helmets when riding bikes, mopeds, or motorcycles. We recognized a need within our community regarding the lack of helmet use at University of Florida and developed a program to institute change. METHODOLOGY: We identified community champions and hosted weekly round table discussion initiatives. Through these round table discussions we identified events already going on within the community and developed new opportunities to promote helmet use. We had stories from survivors and parents, utilized school administration support, and partnered with local bike shops. RESULTS: The pilot initiative was successful in increasing awareness across the city and got stakeholders excited in the process. It also spearheaded more data driven initiatives that will look at reduction of traumatic brain injuries in the clinical setting. CONCLUSION: This project highlights the University of Florida Helmet Initiative that has already generated renewed interest in safety and traumatic brain injury prevention. The school of nursing has implemented safety protocols and further support is being garnered by the administration across campus. Most importantly we have identified community champions that will carry the work forward.

Mobility Skills With Exoskeletal-Assisted Walking in Persons With SCI: Results From a Three Center Randomized Clinical Trial.

Background: Clinical exoskeletal-assisted walking (EAW) programs for individuals with spinal cord injury (SCI) have been established, but many unknown variables remain. These include addressing staffing needs, determining the number of sessions needed to achieve a successful walking velocity milestone for ambulation, distinguishing potential achievement goals according to level of injury, and deciding the number of sessions participants need to perform in order to meet the Food and Drug Administration (FDA) criteria for personal use prescription in the home and community. The primary aim of this study was to determine the number of sessions necessary to achieve adequate EAW skills and velocity milestones, and the percentage of participants able to achieve these skills by 12 sessions and to determine the skill progression over the course of 36 sessions. Methods: A randomized clinical trial (RCT) was conducted across three sites, in persons with chronic (≥6 months) non-ambulatory SCI. Eligible participants were randomized (within site) to either the EAW arm first (Group 1), three times per week for 36 sessions, striving to be completed in 12 weeks or the usual activity arm (UA) first (Group 2), followed by a crossover to the other arm for both groups. The 10-meter walk test seconds (s) (10MWT), 6-min walk test meters (m) (6MWT), and the Timed-Up-and-Go (s) (TUG) were performed at 12, 24, and 36 sessions. To test walking performance in the exoskeletal devices, nominal velocities and distance milestones were chosen prior to study initiation, and were used for the 10MWT (≤ 40s), 6MWT (≥80m), and TUG (≤ 90s). All walking tests were performed with the exoskeletons. Results: A total of 50 participants completed 36 sessions of EAW training. At 12 sessions, 31 (62%), 35 (70%), and 36 (72%) participants achieved the 10MWT, 6MWT, and TUG milestones, respectively. By 36 sessions, 40 (80%), 41 (82%), and 42 (84%) achieved the 10MWT, 6MWT, and TUG criteria, respectively. Conclusions: It is feasible to train chronic non-ambulatory individuals with SCI in performance of EAW sufficiently to achieve reasonable mobility skill outcome milestones.

Changes in bowel function following exoskeletal-assisted walking in persons with spinal cord injury: an observational pilot study.

STUDY DESIGN: Prospective, observational study. OBJECTIVE: To explore the effects of exoskeletal-assisted walking (EAW) on bowel function in persons with spinal cord injury (SCI). SETTING: Ambulatory research facility located in a tertiary care hospital. METHODS: Individuals 18-65 years of age, with thoracic vertebrae one (T1) to T11 motor-complete paraplegia of at least 12 months duration were enrolled. Pre- and post-EAW training, participants were asked to report on various aspects of their bowel function as well as on their overall quality of life (QOL) as related to their bowel function. RESULTS: Ten participants completed 25-63 sessions of EAW over a period of 12-14 weeks, one participant was lost to follow up due to early withdrawal after ten sessions. Due to the small sample size, each participant's results were presented descriptively in a case series format. At least 5/10 participants reported improvements with frequency of bowel evacuations, less time spent on bowel management per bowel day, fewer bowel accidents per month, reduced laxative and/or stool softener use, and improved overall satisfaction with their bowel program post-EAW training. Furthermore, 8/10 reported improved stool consistency and 7/10 reported improved bowel function related QOL. One participant reported worsening of bowel function post-EAW. CONCLUSION: Between 50 and 80% of the participants studied reported improvements in bowel function and/or management post-EAW training. EAW training appeared to mitigate SCI-related bowel dysfunction and the potential benefits of EAW on bowel function after SCI is worthy or further study.

More salt, please: global patterns, responses and impacts of foliar sodium in grasslands.

Sodium is unique among abundant elemental nutrients, because most plant species do not require it for growth or development, whereas animals physiologically require sodium. Foliar sodium influences consumption rates by animals and can structure herbivores across landscapes. We quantified foliar sodium in 201 locally abundant, herbaceous species representing 32 families and, at 26 sites on four continents, experimentally manipulated vertebrate herbivores and elemental nutrients to determine their effect on foliar sodium. Foliar sodium varied taxonomically and geographically, spanning five orders of magnitude. Site-level foliar sodium increased most strongly with site aridity and soil sodium; nutrient addition weakened the relationship between aridity and mean foliar sodium. Within sites, high sodium plants declined in abundance with fertilisation, whereas low sodium plants increased. Herbivory provided an explanation: herbivores selectively reduced high nutrient, high sodium plants. Thus, interactions among climate, nutrients and the resulting nutritional value for herbivores determine foliar sodium biogeography in herbaceous-dominated systems.

Contemporary limnology of the rapidly changing glacierized watershed of the world's largest High Arctic lake.

Glacial runoff is predicted to increase in many parts of the Arctic with climate change, yet little is known about the biogeochemical impacts of meltwaters on downstream freshwater ecosystems. Here we document the contemporary limnology of the rapidly changing glacierized watershed of the world's largest High Arctic lake (Lake Hazen), where warming since 2007 has increased delivery of glacial meltwaters to the lake by up to 10-times. Annually, glacial meltwaters accounted for 62-98% of dissolved nutrient inputs to the lake, depending on the chemical species and year. Lake Hazen was a strong sink for NO3--NO2-, NH4+ and DOC, but a source of DIC to its outflow the Ruggles River. Most nutrients entering Lake Hazen were, however, particle-bound and directly transported well below the photic zone via dense turbidity currents, thus reinforcing ultraoligotrophy in the lake rather than overcoming it. For the first time, we apply the land-to-ocean aquatic continuum framework in a large glacierized Arctic watershed, and provide a detailed and holistic description of the physical, chemical and biological limnology of the rapidly changing Lake Hazen watershed. Our findings highlight the sensitivity of freshwater ecosystems to the changing cryosphere, with implications for future water quality and productivity at high latitudes.

Drivers of Mercury Cycling in the Rapidly Changing Glacierized Watershed of the High Arctic's Largest Lake by Volume (Lake Hazen, Nunavut, Canada).

Across the Arctic, glaciers are melting and permafrost is thawing at unprecedented rates, releasing not only water to downstream aquatic systems, but also contaminants like mercury, archived in ice over centuries. Using concentrations from samples collected over 4 years and calibrated modeled hydrology, we calculated methylmercury (MeHg) and total mercury (THg) mass balances for Lake Hazen, the world's largest High Arctic lake by volume, for 2015 and 2016. Glacial rivers were the most important source of MeHg and THg to Lake Hazen, accounting for up to 53% and 94% of the inputs, respectively. However, due to the MeHg and THg being primarily particle-bound, Lake Hazen was an annual MeHg and THg sink. Exports of MeHg and THg out the Ruggles River outflow were consequently very low, but erosion and permafrost slumping downstream of the lake increased river MeHg and THg concentrations significantly before entering coastal waters in Chandler Fjord. Since 2001, glacial MeHg and THg inputs to Lake Hazen have increased by 0.01 and 0.400 kg yr-1, respectively, in step with dramatic increases in glacial melt. This study highlights the potential for increases in mercury inputs to arctic ecosystems downstream of glaciers despite recent reductions in global mercury emissions.

Carbonic anhydrase inhibitors in patients with respiratory failure and metabolic alkalosis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Metabolic alkalosis is common in patients with respiratory failure and may delay weaning in mechanically ventilated patients. Carbonic anhydrase inhibitors block renal bicarbonate reabsorption, and thus reverse metabolic alkalosis. The objective of this systematic review is to assess the benefits and harms of carbonic anhydrase inhibitor therapy in patients with respiratory failure and metabolic alkalosis. METHODS: We searched the following electronic sources from inception to August 2017: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and SCOPUS. Randomized clinical trials were included if they assessed at least one of the following outcomes: mortality, duration of hospital stay, duration of mechanical ventilation, adverse events, and blood gas parameters. Teams of two review authors worked in an independent and duplicate manner to select eligible trials, extract data, and assess risk of bias of the included trials. We used meta-analysis to synthesize statistical data and then assessed the certainty of evidence using the GRADE methodology. RESULTS: Six eligible studies were identified with a total of 564 participants. The synthesized data did not exclude a reduction or an increase in mortality (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.57 to 1.56) or in duration of hospital stay (mean difference (MD) 0.42 days, 95% CI -4.82 to 5.66) with the use of carbonic anhydrase inhibitors. Carbonic anhydrase inhibitor therapy resulted in a decrease in the duration of mechanical ventilation of 27 h (95% CI -50 to -4). Also, it resulted in an increase in PaO2 (MD 11.37 mmHg, 95% CI 4.18 to 18.56) and a decrease in PaCO2 (MD -4.98 mmHg, 95% CI -9.66, -0.3), serum bicarbonate (MD -5.03 meq/L, 95% CI -6.52 to -3.54), and pH (MD -0.04, 95% CI -0.07 to -0.01). There was an increased risk of adverse events in the carbonic anhydrase inhibitor group (RR 1.71, 95% CI 0.98 to 2.99). Certainty of evidence was judged to be low for most outcomes. CONCLUSION: In patients with respiratory failure and metabolic alkalosis, carbonic anhydrase inhibitor therapy may have favorable effects on blood gas parameters. In mechanically ventilated patients, carbonic anhydrase inhibitor therapy may decrease the duration of mechanical ventilation. A major limitation of this finding was that only two trials assessed this clinically important outcome.