Geographic variation in responses of kelp forest communities of the California Current to recent climatic changes.

The changing global climate is having profound effects on coastal marine ecosystems around the world. Structure, functioning, and resilience, however, can vary geographically, depending on species composition, local oceanographic forcing, and other pressures from human activities and use. Understanding ecological responses to environmental change and predicting changes in the structure and functioning of whole ecosystems require large-scale, long-term studies, yet most studies trade spatial extent for temporal duration. We address this shortfall by integrating multiple long-term kelp forest monitoring datasets to evaluate biogeographic patterns and rates of change of key functional groups (FG) along the west coast of North America. Analysis of data from 469 sites spanning Alaska, USA, to Baja California, Mexico, and 373 species (assigned to 18 FG) reveals regional variation in responses to both long-term (2006-2016) change and a recent marine heatwave (2014-2016) associated with two atmospheric and oceanographic anomalies, the "Blob" and extreme El Niño Southern Oscillation (ENSO). Canopy-forming kelps appeared most sensitive to warming throughout their range. Other FGs varied in their responses among trophic levels, ecoregions, and in their sensitivity to heatwaves. Changes in community structure were most evident within the southern and northern California ecoregions, while communities in the center of the range were more resilient. We report a poleward shift in abundance of some key FGs. These results reveal major, ongoing region-wide changes in productive coastal marine ecosystems in response to large-scale climate variability, and the potential loss of foundation species. In particular, our results suggest that coastal communities that are dependent on kelp forests will be more impacted in the southern portion of the California Current region, highlighting the urgency of implementing adaptive strategies to sustain livelihoods and ensure food security. The results also highlight the value of multiregional integration and coordination of monitoring programs for improving our understanding of marine ecosystems, with the goal of informing policy and resource management in the future.

Prolonged acute care and post-acute care admission and recovery of physical function in survivors of acute respiratory failure: a secondary analysis of a randomized controlled trial.

BACKGROUND: The proportion of survivors of acute respiratory failure is growing; yet, many do not regain full function and require prolonged admission in an acute or post-acute care facility. Little is known about their trajectory of functional recovery. We sought to determine whether prolonged admission influenced the trajectory of physical function recovery and whether patient age modified the recuperation rate. METHODS: We performed a secondary analysis of a randomized clinical trial of intensive physical therapy for patients with acute respiratory failure requiring mechanical ventilation for ≥4 days. The primary outcome was Continuous Scale Physical Functional Performance, short form (CS-PFP-10), score. Predictor variables included prolonged admission in an acute or post-acute care facility at 1 month, time, and patient age. To determine whether the association between admission and functional outcome varied over time, a multivariable mixed effects linear regression model was fit using an interaction between prolonged admission and time with a primary outcome of total CS-PFP-10 score. RESULTS: Of the 89 patients included, 56% (50 of 89) required prolonged admission. At 1 month, patients who remained admitted had CS-PFP-10 scores that were 20.1 (CI 10.4-29.8) points lower (p < 0.0001) than patients who were discharged to home. However, there was no difference in the rate at which physical function improved from 3 to 6 months for patients who required prolonged admission compared with those who returned home (p = 0.24 for interaction between prolonged admission and time). Adjusted for age, Acute Physiology and Chronic Health Evaluation II score, and sex, both groups had CS-PFP-10 scores that were 8.2 (CI 4.5-12.0) points higher at 6 months than at 3 months (p < 0.0001). For each additional year in patient age, CS-PFP-10 recovered 0.36 points slower (95% CI 0.12-0.61; p = 0.004). CONCLUSIONS: Patients who require prolonged admission after acute respiratory failure have significantly lower physical functional performance than patients who return home. However, the rates of physical functional recovery between the two groups do not differ. The majority of survivors do not recover sufficiently to achieve functional independence by 6 months. Older age negatively influences the trajectory of functional recovery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01058421 . Registered on 26 January 2010.

A Randomized Trial of an Intensive Physical Therapy Program for Patients with Acute Respiratory Failure.

RATIONALE: Early physical therapy (PT) interventions may benefit patients with acute respiratory failure by preventing or attenuating neuromuscular weakness. However, the optimal dosage of these interventions is currently unknown. OBJECTIVES: To determine whether an intensive PT program significantly improves long-term physical functional performance compared with a standard-of-care PT program. METHODS: Patients who required mechanical ventilation for at least 4 days were eligible. Enrolled patients were randomized to receive PT for up to 4 weeks delivered in an intensive or standard-of-care manner. Physical functional performance was assessed at 1, 3, and 6 months in survivors who were not currently in an acute or long-term care facility. The primary outcome was the Continuous Scale Physical Functional Performance Test short form (CS-PFP-10) score at 1 month. MEASUREMENTS AND MAIN RESULTS: A total of 120 patients were enrolled from five hospitals. Patients in the intensive PT group received 12.4 ± 6.5 sessions for a total of 408 ± 261 minutes compared with only 6.1 ± 3.8 sessions for 86 ± 63 minutes in the standard-of-care group (P < 0.001 for both analyses). Physical function assessments were available for 86% of patients at 1 month, for 76% at 3 months, and for 60% at 6 months. In both groups, physical function was reduced yet significantly improved over time between 1, 3, and 6 months. When we compared the two interventions, we found no differences in the total CS-PFP-10 scores at all three time points (P = 0.73, 0.29, and 0.43, respectively) or in the total CS-PFP-10 score trajectory (P = 0.71). CONCLUSIONS: An intensive PT program did not improve long-term physical functional performance compared with a standard-of-care program. Clinical trial registered with www.clinicaltrials.gov (NCT01058421).

Incorporating biogeography into evaluations of the Channel Islands marine reserve network.

Networks of marine reserves are increasingly a major component of many ecosystem-based management plans designed to conserve biodiversity, protect the structure and function of ecosystems, and rebuild and sustain fisheries. There is a growing need for scientific guidance in the design of network-wide monitoring programs to evaluate the efficacy of reserves at meeting their conservation and management goals. Here, we present an evaluation of the Channel Islands reserve network, which was established in 2003 off the coast of southern California. This reserve network spans a major environmental and biogeographic gradient, making it a challenge to assess network-wide responses of many species. Using fish community structure data from a long-term, large-scale monitoring program, we first identified persistent geographic patterns of community structure and the scale at which sites should be grouped for analysis. Fish communities differed most among islands with densities of individual species varying from 3- to 250-fold. Habitat structure differed among islands but not based on reserve status. Across the network, we found that, after 5 years, species targeted by fishing had higher densities (1.5×) and biomass (1.8×) inside reserves, whereas nontargeted species showed no significant differences. Examining trophic groups, piscivore and carnivore biomass was significantly greater inside reserves (1.8× and 1.3× more, respectively), whereas the biomass of planktivores and herbivores was similar inside and out. A framework for incorporating biogeographic variation into reserve network assessments is critical as we move from the evaluation of single reserves to networks of reserves.

Social Media Mining for Toxicovigilance: Automatic Monitoring of Prescription Medication Abuse from Twitter.

INTRODUCTION: Prescription medication overdose is the fastest growing drug-related problem in the USA. The growing nature of this problem necessitates the implementation of improved monitoring strategies for investigating the prevalence and patterns of abuse of specific medications. OBJECTIVES: Our primary aims were to assess the possibility of utilizing social media as a resource for automatic monitoring of prescription medication abuse and to devise an automatic classification technique that can identify potentially abuse-indicating user posts. METHODS: We collected Twitter user posts (tweets) associated with three commonly abused medications (Adderall(®), oxycodone, and quetiapine). We manually annotated 6400 tweets mentioning these three medications and a control medication (metformin) that is not the subject of abuse due to its mechanism of action. We performed quantitative and qualitative analyses of the annotated data to determine whether posts on Twitter contain signals of prescription medication abuse. Finally, we designed an automatic supervised classification technique to distinguish posts containing signals of medication abuse from those that do not and assessed the utility of Twitter in investigating patterns of abuse over time. RESULTS: Our analyses show that clear signals of medication abuse can be drawn from Twitter posts and the percentage of tweets containing abuse signals are significantly higher for the three case medications (Adderall(®): 23 %, quetiapine: 5.0 %, oxycodone: 12 %) than the proportion for the control medication (metformin: 0.3 %). Our automatic classification approach achieves 82 % accuracy overall (medication abuse class recall: 0.51, precision: 0.41, F measure: 0.46). To illustrate the utility of automatic classification, we show how the classification data can be used to analyze abuse patterns over time. CONCLUSION: Our study indicates that social media can be a crucial resource for obtaining abuse-related information for medications, and that automatic approaches involving supervised classification and natural language processing hold promises for essential future monitoring and intervention tasks.

Variation in responses of fishes across multiple reserves within a network of marine protected areas in temperate waters.

Meta-analyses of field studies have shown that biomass, density, species richness, and size of organisms protected by no-take marine reserves generally increase over time. The magnitude and timing of changes in these response variables, however, vary greatly and depend upon the taxonomic groups protected, size and type of reserve, oceanographic regime, and time since the reserve was implemented. We conducted collaborative, fishery-independent surveys of fishes for seven years in and near newly created marine protected areas (MPAs) in central California, USA. Results showed that initially most MPAs contained more and larger fishes than associated reference sites, likely due to differences in habitat quality. The differences between MPAs and reference sites did not greatly change over the seven years of our study, indicating that reserve benefits will be slow to accumulate in California's temperate eastern boundary current. Fishes in an older reserve that has been closed to fishing since 1973, however, were significantly more abundant and larger than those in associated reference sites. This indicates that reserve benefits are likely to accrue in the California Current ecosystem, but that 20 years or more may be needed to detect significant changes in response variables that are due to MPA implementation. Because of the high spatial and temporal variability of fish recruitment patterns, long-term monitoring is needed to identify positive responses of fishes to protection in the diverse set of habitats in a dynamic eastern boundary current. Qualitative estimates of response variables, such as would be obtained from an expert opinion process, are unlikely to provide an accurate description of MPA performance. Similarly, using one species or one MPA as an indicator is unlikely to provide sufficient resolution to accurately describe the performance of multiple MPAs.

An online database for informing ecological network models: http://kelpforest.ucsc.edu.

Ecological network models and analyses are recognized as valuable tools for understanding the dynamics and resiliency of ecosystems, and for informing ecosystem-based approaches to management. However, few databases exist that can provide the life history, demographic and species interaction information necessary to parameterize ecological network models. Faced with the difficulty of synthesizing the information required to construct models for kelp forest ecosystems along the West Coast of North America, we developed an online database (http://kelpforest.ucsc.edu/) to facilitate the collation and dissemination of such information. Many of the database's attributes are novel yet the structure is applicable and adaptable to other ecosystem modeling efforts. Information for each taxonomic unit includes stage-specific life history, demography, and body-size allometries. Species interactions include trophic, competitive, facilitative, and parasitic forms. Each data entry is temporally and spatially explicit. The online data entry interface allows researchers anywhere to contribute and access information. Quality control is facilitated by attributing each entry to unique contributor identities and source citations. The database has proven useful as an archive of species and ecosystem-specific information in the development of several ecological network models, for informing management actions, and for education purposes (e.g., undergraduate and graduate training). To facilitate adaptation of the database by other researches for other ecosystems, the code and technical details on how to customize this database and apply it to other ecosystems are freely available and located at the following link (https://github.com/kelpforest-cameo/databaseui).

Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for prevention of upper gastrointestinal ulcers in patients with osteoarthritis and/or rheumatoid arthritis.

BACKGROUND: Single-tablet ibuprofen/famotidine is approved by the US Food and Drug Administration for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcers in patients taking ibuprofen for those indications. Currently, little is known about the cost impact of gastroprotective therapies, and an estimate of the financial consequences of adopting these therapies will be helpful to decision makers. OBJECTIVES: The goal of this study was to review a model that evaluates the expected financial impact to US health care plans from the introduction of single-tablet ibuprofen/famotidine into the chronic NSAID user population. METHODS: A budget impact model, considering a typical health plan of 1 million enrollees, was used to compare patients receiving: (1) single-tablet ibuprofen/famotidine; (2) chronic NSAID treatment plus any GI-protective agent; and (3) chronic NSAID treatment without a GI-protective agent. RESULTS: The expected medication cost for single-tablet ibuprofen/famotidine was $734,192 ($81,577 in year 1, $244,731 in year 2, and $407,884 in year 3), corresponding to a total per-member per-month cost of $0.020 ($0.007 in year 1, $0.020 in year 2, and $0.034 in year 3). Considering anticipated decreases in the use of other NSAIDs, the use of GI-protective agents, and GI complications, the total expected 3-year drug cost for single-tablet ibuprofen/famotidine was offset by 50%, representing an estimated total budget impact of $364,396 or $0.010 per member per month. Sensitivity analyses of cost and market share variables and clinical and drug characteristics identified the most influential variables to be the cost of the drug and persistence to the ibuprofen/famotidine formulation, respectively. CONCLUSIONS: The expected decrease in treatment costs for less serious GI-related complications illustrates the benefits of single-tablet ibuprofen/famotidine as a gastroprotective therapy in patients receiving chronic NSAID treatment, with a modest financial impact on total health care costs.

Association of cardiometabolic risk factors and prevalent cardiovascular events.

BACKGROUND: Although cardiovascular disease causes substantial morbidity and mortality, how individual and groups of risk factors contribute to cardiovascular outcomes is incompletely understood. This study evaluated cardiometabolic risk factors and their relationship to prevalent diagnosis of acute myocardial infarction (AMI) and stroke. METHODS: We used retrospective data from 3 integrated health-care systems that systematically collect and store detailed patient-level data. Adult enrollees were eligible for inclusion if they had all of the following clinical measurements: weight, height, blood pressure, high density lipoproteins, triglycerides, and fasting blood glucose or evidence of diabetes from July 1, 2003, to June 30, 2005. We used National Cholesterol Education Program Adult Treatment Panel III guidelines to determine qualifying levels for cardiometabolic risk factors. RESULTS: A total of 170,648 persons met the inclusion/exclusion criteria; 11,757 had no qualifying risk factors, 25,684 had 1, 38,176 had 2, and 95,031 had 3 or more risk factors. Compared to those without risk factors, persons with any 1 risk factor were 2.21 (95% confidence interval [CI], 1.78-2.74) times more likely to have had a diagnosis of AMI or stroke. The risk increased to 2.79 (95% CI, 2.26-3.42) for persons with 2, 3.45 (95% CI, 2.80-4.24) for persons with 3, 4.35 (95% CI, 3.54-5.35) for persons with 4, and 5.73 (95% CI, 4.65-7.07) for persons with 5 risk factors. The highest risk was conferred by having the combination of risk factors of diabetes, hypertension, and dyslipidemia, with or without weight risk. CONCLUSIONS: This study demonstrates a direct association between an increasing number of cardiometabolic risk factors and prevalent diagnosis of AMI and stroke. The combination of risk factors conferring the highest risk was diabetes, hypertension, and dyslipidemia.

Investigation of traumatic brain injuries using the next generation of simulated injury monitor (SIMon) finite element head model.

The objective of this study was to investigate potential for traumatic brain injuries (TBI) using a newly developed, geometrically detailed, finite element head model (FEHM) within the concept of a simulated injury monitor (SIMon). The new FEHM is comprised of several parts: cerebrum, cerebellum, falx, tentorium, combined pia-arachnoid complex (PAC) with cerebro-spinal fluid (CSF), ventricles, brainstem, and parasagittal blood vessels. The model's topology was derived from human computer tomography (CT) scans and then uniformly scaled such that the mass of the brain represents the mass of a 50th percentile male's brain (1.5 kg) with the total head mass of 4.5 kg. The topology of the model was then compared to the preliminary data on the average topology derived from Procrustes shape analysis of 59 individuals. Material properties of the various parts were assigned based on the latest experimental data. After rigorous validation of the model using neutral density targets (NDT) and pressure data, the stability of FEHM was tested by loading it simultaneously with translational (up to 400 g) combined with rotational (up to 24,000 rad/s2) acceleration pulses in both sagittal and coronal planes. Injury criteria were established in the manner shown in Takhounts et al. (2003a). After thorough validation and injury criteria establishment (cumulative strain damage measure--CSDM for diffuse axonal injuries (DAI), relative motion damage measure--RMDM for acute subdural hematoma (ASDH), and dilatational damage measure--DDM for contusions and focal lesions), the model was used in investigation of mild TBI cases in living humans based on a set of head impact data taken from American football players at the collegiate level. It was found that CSDM and especially RMDM correlated well with angular acceleration and angular velocity. DDM was close to zero for most impacts due to their mild severity implying that cavitational pressure anywhere in the brain was not reached. Maximum principal strain was found to correlate well with RMDM and angular head kinematic measures. Maximum principal stress didn't correlate with any kinematic measure or injury metric. The model was then used in the investigation of brain injury potential in NHTSA conducted side impact tests. It was also used in parametric investigations of various "what if" scenarios, such as side versus frontal impact, to establish a potential link between head kinematics and injury outcomes. The new SIMon FEHM offers an advantage over the previous version because it is geometrically more representative of the human head. This advantage, however, is made possible at the expense of additional computational time.