A spatial-temporal analysis of section 404 wetland permitting in Texas and Florida: Thirteen years of impact along the coast

Over the past 200 years, an estimated 53% (about 47 million ha) of the original wetlands in the conterminous United States have been lost, mainly as a result of various human activities. Despite the importance of wetlands (particularly along the coast), and a longstanding federal policy framework meant to protect their integrity, the cumulative impact on these natural systems over large areas is poorly understood. We address this lack of research by mapping and conducting descriptive spatial analyses of federal wetland alteration permits (pursuant to section 404 of the Clean Water Act) across 85 watersheds in Florida and coastal Texas from 1991 to 2003. Results show that more than half of the permits issued in both states (60%) fell under the Nationwide permitting category. Permits issued in Texas were typically located outside of urban areas (78%) and outside 100-year floodplains (61%). More than half of permits issued in Florida were within urban areas (57%) and outside of 100-year floodplains (51%). The most affected wetlands types were estuarine in Texas (47%) and palustrine in Florida (55%). We expect that an additional outcome of this work will be an increased awareness of the cumulative depletion of wetlands and loss of ecological services in these urbanized areas, perhaps leading to increased conservation efforts

Incidence of and predictors for antiseizure medication gaps in Medicare beneficiaries with epilepsy: a retrospective cohort study.

BACKGROUND For the two-thirds of patients with epilepsy who achieve seizure remission on antiseizure medications (ASMs), patients and clinicians must weigh the pros and cons of long-term ASM treatment. However, little work has evaluated how often ASM discontinuation occurs in practice. We describe the incidence of and predictors for sustained ASM fill gaps to measure discontinuation in individuals potentially eligible for ASM withdrawal. METHODS This was a retrospective cohort of Medicare beneficiaries. We included patients with epilepsy by requiring International Classification of Diseases codes for epilepsy/convulsions plus at least one ASM prescription each year 2014-2016, and no acute visit for epilepsy 2014-2015 (i.e., potentially eligible for ASM discontinuation). The main outcome was the first day of a gap in ASM supply (30, 90, 180, or 360 days with no pills) in 2016-2018. We displayed cumulative incidence functions and identified predictors using Cox regressions. RESULTS Among 21,819 beneficiaries, 5191 (24%) had a 30-day gap, 1753 (8%) had a 90-day gap, 803 (4%) had a 180-day gap, and 381 (2%) had a 360-day gap. Predictors increasing the chance of a 180-day gap included number of unique medications in 2015 (hazard ratio [HR] 1.03 per medication, 95% confidence interval [CI] 1.01-1.05) and epileptologist prescribing physician (≥25% of that physician's visits for epilepsy; HR 2.37, 95% CI 1.39-4.03). Predictors decreasing the chance of a 180-day gap included Medicaid dual eligibility (HR 0.75, 95% CI 0.60-0.95), number of unique ASMs in 2015 (e.g., 2 versus 1: HR 0.37, 95% CI 0.30-0.45), and greater baseline adherence (> 80% versus ≤80% of days in 2015 with ASM pill supply: HR 0.38, 95% CI 0.32-0.44). CONCLUSIONS Sustained ASM gaps were rarer than current guidelines may suggest. Future work should further explore barriers and enablers of ASM discontinuation to understand the optimal discontinuation rate

Antiseizure medication withdrawal risk estimation and recommendations: A survey of American Academy of Neurology and EpiCARE members

Objective Choosing candidates for antiseizure medication (ASM) withdrawal in well‐controlled epilepsy is challenging. We evaluated (a) the correlation between neurologists' seizure risk estimation (“clinician predictions”) vs calculated predictions, (b) how viewing calculated predictions influenced recommendations, and (c) barriers to using risk calculation.MethodsWe asked US and European neurologists to predict 2‐year seizure risk after ASM withdrawal for hypothetical vignettes. We compared ASM withdrawal recommendations before vs after viewing calculated predictions, using generalized linear models. Results Three‐hundred and forty‐six neurologists responded. There was moderate correlation between clinician and calculated predictions (Spearman coefficient 0.42). Clinician predictions varied widely, for example, predictions ranged 5%‐100% for a 2‐year seizure‐free adult without epileptiform abnormalities. Mean clinician predictions exceeded calculated predictions for vignettes with epileptiform abnormalities (eg, childhood absence epilepsy: clinician 65%, 95% confidence interval [CI] 57%‐74%; calculated 46%) and surgical vignettes (eg, focal cortical dysplasia 6‐month seizure‐free mean clinician 56%, 95% CI 52%‐60%; calculated 28%). Clinicians overestimated the influence of epileptiform EEG findings on withdrawal risk (26%, 95% CI 24%‐28%) compared with calculators (14%, 95% 13%‐14%). Viewing calculated predictions slightly reduced willingness to withdraw (−0.8/10 change, 95% CI −1.0 to −0.7), particularly for vignettes without epileptiform abnormalities. The greatest barrier to calculator use was doubting its accuracy (44%). Significance Clinicians overestimated the influence of abnormal EEGs particularly for low‐risk patients and overestimated risk and the influence of seizure‐free duration for surgical patients, compared with calculators. These data may question widespread ordering of EEGs or time‐based seizure‐free thresholds for surgical patients. Viewing calculated predictions reduced willingness to withdraw particularly without epileptiform abnormalities

Vertical integration and firm boundaries : the evidence

Since Ronald H. Coase's (1937) seminal paper, a rich set of theories has been developed that deal with firm boundaries in vertical or input–output structures. In the last twenty-five years, empirical evidence that can shed light on those theories also has been accumulating. We review the findings of empirical studies that have addressed two main interrelated questions: First, what types of transactions are best brought within the firm and, second, what are the consequences of vertical integration decisions for economic outcomes such as prices, quantities, investment, and profits. Throughout, we highlight areas of potential cross-fertilization and promising areas for future work

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

Pharmacokinetics and pharmacodynamics of clofazimine for treatment of cryptosporidiosis

Infection with Cryptosporidium spp. can cause severe diarrhea leading to long-term adverse impacts and even death in malnourished children and immunocompromised patients. The only FDA-approved drug for treating cryptosporidiosis, nitazoxanide, has limited efficacy in the populations impacted the most by the diarrheal disease, and safe, effective treatment options are urgently needed. Initially identified by a large-scale phenotypic screening campaign, the antimycobacterial therapeutic clofazimine demonstrated great promise in both in vitro and in vivo preclinical models of Cryptosporidium infection. Unfortunately, a Phase 2a clinical trial in HIV infected adults with cryptosporidiosis did not identify any clofazimine treatment effect on Cryptosporidium infection burden or clinical outcomes. To explore whether clofazimine's lack of efficacy in the Phase 2a trial may have been due to subtherapeutic clofazimine concentrations, a pharmacokinetic/pharmacodynamic modeling approach was undertaken to determine the relationship between clofazimine in vivo concentrations and treatment effects in multiple preclinical infection models. Exposure-response relationships were characterized using Emax and logistic models which allowed predictions of efficacious clofazimine concentrations for the control and reduction of disease burden. After establishing exposure-response relationships for clofazimine treatment of Cryptosporidium infection in our preclinical model studies, it was unmistakable that the clofazimine levels observed in the Phase 2a study participants were well below concentrations associated with anti-Cryptosporidium efficacy. Thus, despite a dosing regimen above the highest doses recommended for mycobacterial therapy, it is very likely the lack of treatment effect in the Phase 2a trial was at least partially due to clofazimine concentrations below those required for efficacy against cryptosporidiosis. It is unlikely that clofazimine will provide a remedy for the large number of cryptosporidiosis patients currently without a viable treatment option unless alternative, safe clofazimine formulations with improved oral absorption are developed