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The article focuses on the benefits if the trade relations between Cuba and the U.S. will normalize. According to the article, it would remove the embargo that has added to the suffering of the Cuban people. It is stated that it would also create a strong firewall against Russian and Chinese efforts to replace U.S. influence in the hemisphere.

Watershed managers often use physical geomorphic and habitat assessments in making decisions about the biological integrity of a stream, and to reduce the cost and time for identifying stream stressors and developing mitigation strategies. Such analysis is difficult since the complex linkages between reach-scale geomorphic and habitat conditions, and biological integrity are not fully understood. We evaluate the effectiveness of a generalized regression neural network ( GRNN) to predict biological integrity using physical (i.e., geomorphic and habitat) stream-reach assessment data. The method is first tested using geomorphic assessments to predict habitat condition for 1,292 stream reaches from the Vermont Agency of Natural Resources. The GRNN methodology outperforms linear regression (69% vs. 40% classified correctly) and improves slightly (70% correct) with additional data on channel evolution. Analysis of a subset of the reaches where physical assessments are used to predict biological integrity shows no significant linear correlation, however the GRNN predicted 48% of the fish health data and 23% of macroinvertebrate health. Although the GRNN is superior to linear regression, these results show linking physical and biological health remains challenging. Reasons for lack of agreement, including spatial and temporal scale differences, are discussed. We show the GRNN to be a data-driven tool that can assist watershed managers with large quantities of complex, nonlinear data. [ABSTRACT FROM AUTHOR]

Summary: Watershed managers and planners have long sought decision-making tools for forecasting changes in stream-channels over large spatial and temporal scales. In this research, we apply non-parametric, clustering and classification artificial neural networks to assimilate large amounts of disparate data types for use in fluvial hazard management decision-making. Two types of artificial neural networks (a counterpropagation algorithm and a Kohonen self-organizing map) are used in hierarchy to predict reach-scale stream geomorphic condition, inherent vulnerability and sensitivity to adjustments using expert knowledge in combination with a variety of geomorphic assessment field data. Seven hundred and eighty-nine Vermont stream reaches (+7500km) have been assessed by the Vermont Agency of Natural Resources’ geomorphic assessment protocols, and are used in the development of this work. More than 85% of the reach-scale stream geomorphic condition and inherent vulnerability predictions match expert evaluations. The method’s usefulness as a QA/QC tool is discussed. The Kohonen self-organizing map clusters the 789 reaches into groupings of stream sensitivity (or instability). By adjusting the weight of input variables, experts can fine-tune the classification system to better understand and document similarities/differences among expert opinions. The use of artificial neural networks allows for an adaptive watershed management approach, does not require the development of site-specific, physics-based, stream models (i.e., is data-driven), and provides a standardized approach for classifying river network sensitivity in various contexts. [Copyright &y& Elsevier]

Mitochondrial function is critical for energy homeostasis and should shape how genetic variation in metabolism is transmitted through levels of biological organization to generate stability in organismal performance. Mitochondrial function is encoded by genes in two distinct and separately inherited genomes—the mitochondrial genome and the nuclear genome—and selection is expected to maintain functional mito-nuclear interactions. The documented high levels of polymorphism in genes involved in these mito-nuclear interactions and wide variation for mitochondrial function demands an explanation for how and why variability in such a fundamental trait is maintained. Potamopyrgus antipodarum is a New Zealand freshwater snail with coexisting sexual and asexual individuals and, accordingly, contrasting systems of separate vs. co-inheritance of nuclear and mitochondrial genomes. As such, this snail provides a powerful means to dissect the evolutionary and functional consequences of mito-nuclear variation. The lakes inhabited by P. antipodarum span wide environmental gradients, with substantial across-lake genetic structure and mito-nuclear discordance. This situation allows us to use comparisons across reproductive modes and lakes to partition variation in cellular respiration across genetic and environmental axes. Here, we integrated cellular, physiological, and behavioral approaches to quantify variation in mitochondrial function across a diverse set of wild P. antipodarum lineages. We found extensive across-lake variation in organismal oxygen consumption and behavioral response to heat stress and differences across sexes in mitochondrial membrane potential but few global effects of reproductive mode. Taken together, our data set the stage for applying this important model system for sexual reproduction and polyploidy to dissecting the complex relationships between mito-nuclear variation, performance, plasticity, and fitness in natural populations. [ABSTRACT FROM AUTHOR]

1,3-Bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene forms stable 1:1 adducts with tetrafluoroethylene (2), hexafluorocyclobutene (3), and octafluorocyclopentene (4). Adduct2shows properties typical for nonpolarized olefins, as indicated by NMR spectroscopy and X-ray crystallography. By contrast, adducts3and4are best described as ylides with a significant charge separation between the imidazoline ring and the perfluorocycloalkyl unit. Similarly, 1,3-di-1-adamantylimidazol-2-ylidene reacts with tetrakis(trifluoromethyl)allene to form a polarized trimethylenemethane derivative, and bis(trifluoromethyl)ketene to form an imidazolium enolate zwitterion. The synthesis and characterization of a number of fluorinated methyleneimidazolines are described herein. [ABSTRACT FROM AUTHOR]

Fitzgerald, Evan P., William B. Bowden, Samuel P. Parker, and Michael L. Kline, 2012. Urban Impacts on Streams Are Scale-Dependent with Nonlinear Influences on Their Physical and Biotic Recovery in Vermont, United States. Journal of the American Water Resources Association (JAWRA) 48(4): 679-697. DOI: 10.1111/j.1752-1688.2012.00639.x Abstract: The physical and biological conditions of stream reaches in 16 watersheds within the Lake Champlain Basin of Vermont, United States, were assessed and analyzed for a response to total impervious area (TIA) at multiple spatial scales. Natural gradients (e.g., channel slope) and human impacts to channel boundary conditions (e.g., bank armoring) were considered to ensure a robust test of the Impervious Cover Model for upslope TIA. The response of geomorphic stability and sensitive macroinvertebrates to TIA was nonlinear and significant ( p < 0.001), decreasing rapidly at 5% TIA. The effect of urbanization on stream condition was shown to interact significantly with drainage area and channel slope using the analysis of covariance (ANCOVA) ( p < 0.05). Hydraulic geometry regressions for urban and rural watersheds and ANCOVA were used to describe a significant watershed scale-dependent response of channel width to urbanization ( p = 0.001). The analysis of macroinvertebrate data from reaches in different stages of channel evolution indicated that stable reaches supported greater richness of pollution intolerant species ( p < 0.001) and overall taxa richness ( p < 0.01) than unstable reaches, and that biotic integrity improves as channels regain stability during their evolution into a state of quasi-equilibrium. We conclude that macroinvertebrate communities can respond positively to channel evolution processes leading to natural channel restabilization. [ABSTRACT FROM AUTHOR]

Background: Patients with gastroesophageal reflux disease (GERD) often complain of dysphagia and are frequently found to have intraepithelial eosinophils on esophageal biopsy.Aim: The aim of this study was to investigate the relationship between dysphagia and the number of intraepithelial eosinophils in patients with GERD.Methods: Review of all patients studied in our esophageal function laboratory from 1999 to 2007 identified 1,533 patients with increased esophageal acid exposure. Patients who complained of dysphagia without mechanical or motor causes were identified and divided into three groups based on whether dysphagia was their primary, secondary or tertiary symptom. A control group consisted of randomly selected GERD patients with no dysphagia. The highest number of intraepithelial eosinophils per high-power field (HPF) in biopsies from the squamocolumnar junction (SCJ) and esophageal body was compared across groups.Results: There were 71 patients with unexplained dysphagia. Dysphagia was the primary symptom in 13 (18%), secondary symptom in 34 (48%), and tertiary symptom in 24 (34%) patients. The number of eosinophils differed between the four groups, with the highest number in those with dysphagia as the primary symptom (P = 0.0007). This relationship persisted whether biopsies were from the SCJ (P = 0.0057) or esophageal body (P = 0.0096).Conclusion: An association exists between the number of intraepithelial eosinophils and dysphagia in GERD patients, with the highest number of eosinophils in those with the primary symptom of dysphagia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To conduct in vitro studies as well as a phase 2 clinical trial in patients with smoldering or Indolent multiple myeloma to determine if interleukin 1 (IL-1) inhibitors can delay or prevent active myeloma. PATIENTS AND METHODS: Stromal cells were cocultured with IL-Iβ-expressing myeloma cells In the presence of dexamethasone, IL-1 receptor antagonist (IL-1Ra), or both. Levels of lnterieukin 6 (IL-6) and of apoptosis were also quantified. Between November 19, 2002, and May 24, 2007, 47 patients were enrolled in the study and subsequently treated with IL-1Ra. in 25(53%) of the 47 study patients, low-dose dexamethasone (20 mg/wk) was added. The primary end point was progression-free survival (PFS). RESULTS: In vitro, IL-1Ra was superior to dexamethasone at Inhibiting IL-6 production; maximal IL-6 inhibition and apoptosis Induction were achieved by addition of both IL-1Ra and dexamethasone. In the clinical trial, 3 patients achieved a minor response to IL-1Ra alone; 5 patIents achieved a partial response and 4 patients a minor response after addition of dexamethasone. Seven patients showed a decrease In the plasma cell labeling Index that paralleled a decrease In high-sensitivity C-reactive protein (hs-CRP) levels. The median overall PFS was 37.5 months. The median PFS for patients without (n=12) or with (n=35) a greater than 15% decrease In 6-month vs baseline hs-CRP levels was 6 months and more than 3 years, respectively (P=.002). Disease stability was maintained in 8 patients who received therapy for more than 4 years. CONCLUSION: In patients with smoldering or indolent multiple myeloma who were at risk of progression to active myeloma, treatment with IL-1 inhibitors decreased the myeloma proliferative rate and hs-CRP levels in those who responded, leading to a chronic disease state and an Improved PFS. [ABSTRACT FROM AUTHOR]

Given the limited resources available for managing erosion hazards and addressing water quality impairment along rivers, stakeholders engaged in water resource management would benefit from tools to identify those river reaches most prone to adjustment and which disproportionately load sediment to receiving waters. The extent and rate of vertical and lateral channel adjustments in response to natural and human disturbances vary considerably across space and time; and this complexity and nonlinearity introduce challenges for classification or modeling of river reaches using conventional statistical techniques. The Self-Organizing Map (SOM) is a data-driven computational tool with advantages for clustering or classifying multivariate observations and for exploratory data analysis and visualization of complex, nonlinear systems. We applied a SOM to cluster multivariate stream geomorphic assessment data into reach-scale sediment process domains for 193 river reaches in glacially-conditioned catchments of northeastern US using field- and GIS-derived hydraulic and geomorphic parameters. The reaches comprised a range of channel types from confined to unconfined, steep- to shallow-gradient, mid-to-high order, and bedrock to alluvial channels. Fifteen variables were identified that meaningfully separated reaches into seven sediment regimes, following a two-stage application of the SOM. A coarse-tune SOM identified sediment regime classes at the supply-limited and transport-limited extremes of a continuum, including bedrock channels and confined, steep-gradient reaches as well as braided, depositional channels at alluvial fan or delta settings. A second-stage, fine-tune SOM nuanced differences in sediment production and transport for unconfined reaches with varying degrees of floodplain disconnection resulting from natural or human stressors. This classification framework is transferable to other hydroclimatic regions, with consideration of additional or alternate independent variables unique to those regions, and can provide valuable insights for river management to promote flood resiliency, restore water quality and improve instream and riparian habitats. • Classified reach-scale sediment process domains using a Self-Organizing Map (SOM) • Identified 15 variables that explained 7 classes for 193 reaches in northeast US • Improved previous classifications by including degree of floodplain disconnection • SOM visualization tools provided insight into channel evolution processes. • Sediment regime classification framework supports adaptive river management. [ABSTRACT FROM AUTHOR]

Despite the advancements in analytical techniques, there are still great challenges and difficulties in accurately and effectively quantifying and characterizing dissolved organic carbon (DOC) in environmental samples. The objectives of this review paper are (a) to understand the roles and variability of DOC along the water continuum; (b) to identify the constraints, inconsistences, limitations, and artifacts in DOC characterization; and (c) to provide recommendations and remarks to improve the analytical accuracy. For the first objective, we summarize the four ecological and engineering roles of DOC along the water continuum from source water to municipal utility, including nutrients and energy sources, controlling the fates of micropollutants, buffering capacity, and treatability and precursors of disinfection byproducts. We also discuss three major challenges in DOC analysis, including spatial and temporal variations, degradability and stability, and unknown structures and formulas. For the second objective, we review the procedures and steps in DOC analysis, including sampling in diverse environmental matrices, isolation of DOC fraction, storage and preservation techniques, and analyses on bulk chemical characteristics. We list and discuss the available options and evaluate the advantages and disadvantages of each choice. Last, we provide recommendations and remarks for each stage: sampling, isolation, storage, and analysis., (© 2022 The Authors. Journal of Environmental Quality published by Wiley Periodicals LLC on behalf of American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America.)

Background: Spiral enteroscopy is rapidly emerging, along with double- and single-balloon enteroscopy, as a paramount method to evaluate lesions in the deep small bowel. While the latter two methods have been used to manage patients with surgically altered anatomy, there are few reports on the role of spiral enteroscopy in this group. Our principal aim was to characterize the therapeutic uses of spiral enteroscopy in patients with surgically altered anatomy., Methods and Results: Patients with surgically altered anatomy who failed management with conventional endoscopic methods for therapeutic indications were included in this prospective series at our tertiary referral center. The spiral technique was used to control variceal bleeding, dilate enteral anastomotic narrowing, and perform pancreaticobiliary interventions in seven patients. The cases were performed quickly and effectively and the need for surgery was obviated in all cases., Conclusion: The spiral enteroscopy system has significant therapeutic potential in patients with surgically altered anatomy.

Background & Aims: Fifty percent of patients with gastroesophageal reflux disease-like symptoms and negative endoscopy have negative 24-hour pH testing, suggesting that symptoms are not caused by abnormal esophageal acid exposure. Multichannel intraluminal impedance (MII)-24-hour pH allows the recognition of major acid, minor acid, nonacid, and gas reflux. Recorded symptoms can be correlated with all reflux events (eg, acid, minor acid, nonacid, and gas) and a symptom score can be generated. We aimed to determine whether the Symptom Index (SI) obtained using MII-pH identified an association of symptoms with reflux events in nonclassic acid-reflux disease., Methods: Thirty-seven patients with heartburn or regurgitation, negative endoscopy, and 24-hour pH were enlisted. Acid suppression was stopped, a 24-hour MII-pH test was performed, and an SI was calculated for major acid reflux alone and for all reflux episodes including major, minor, and nonacid. On this basis patients were divided into 4 groups: (1) standard acid reflux: positive standard pH test; (2) acid sensitive: positive SI for major acid but normal pH test; (3) general reflux: positive SI for major, minor, and nonacid combined, but not for major acid alone; and (4) no reflux: negative SI., Results: Six patients (16%) had standard reflux, 10 patients (27%) had acid-sensitive esophagus, 14 patients (38%) had general reflux, and 7 patients (19%) had a negative SI., Conclusions: Fifty-seven percent of patients received a diagnosis unachievable with standard pH testing (38% had symptoms associated with general reflux and 19% had no reflux symptom associations). These findings support a potential role for MII-pH testing in this difficult group.

Objective: Bcl-2 family proteins play a critical role in malignancies by regulating the balance between cell survival and apoptosis. R-(-)-gossypol (AT-101) is a small molecule that mimics the BH3 domain of cellular Bcl-2 inhibitors and interferes with the function of prosurvival Bcl-2 proteins. We examined the cytotoxicity of AT-101 in the context of multiple myeloma, a fatal hematological malignancy., Materials and Methods: Multiple myeloma cell lines and primary cells obtained from multiple myeloma patients were used to investigate the effects of AT-101. Cell viability, apoptosis, and apoptosis pathways were examined using conventional viability assays, flow cytometry, and immunoblots., Results: AT-101 was not only cytotoxic to conventional multiple myeloma cell lines, but was also effective against drug-resistant cell lines and primary multiple myeloma patient cells. Furthermore, AT-101 decreased proliferation of multiple myeloma cell lines in the presence of marrow stromal cells, indicating that this drug may overcome the protective effect of the microenvironment that is important for multiple myeloma cell proliferation and survival. Apoptosis was activated via the mitochondrial pathway in multiple myeloma cell lines treated with AT-101 as demonstrated by an increased Bax to Bcl-2 ratio, mitochondrial membrane depolarization, and caspase activation. Finally, our studies demonstrated that AT-101 exhibits potent synergy with dexamethasone, a valuable therapeutic for multiple myeloma., Conclusion: These data suggest that the activity of AT-101 may be highly relevant to multiple myeloma disease biology and may represent an option for treatment of patients with this disease.

Multiple myeloma (MM) is a product of interactions between tumor plasma cells and multiple cell types native to the bone marrow (BM). We have used antibody array technology to examine the proteins produced by BM stromal cells in response to stimulation by BM taken from patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and MM. We observed increased production of the chemokine IL-8 by stromal cells co-cultured with supernatants from bone marrow cells of patients with active myeloma. IL-8 production is correlated with active disease and is dependent upon IL-1beta and NF-kappaB signaling. Consistent with the pro-angiogenic activity of IL-8, increased BM microvessel density (MVD) correlated with stimulation of stromal cell IL-8 production. In addition, the majority of MM cell lines and MM patient plasma cells were found to express IL-8 receptors CXCR1 and CXCR2. We conclude that stromal cell IL-8 production parallels MM disease activity, is IL-1beta induced, and correlates with bone marrow angiogenesis.

Background and Objectives: Bone marrow angiogenesis is increased in patients with multiple myeloma (MM) and correlates with disease stage., Design and Methods: Previous studies of quantifying vascular endothelial growth factor (VEGF) and VEGF receptors (VEGFR) in plasma cells from patients at different stages of MM found no significant difference in expression between overt MM and earlier pre-malignant stages of the disease namely, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM)., Results: In this report we used quantitative flow cytometry to study cytoplasmic VEGF (cyVEGF) expression (measured as antibody binding capacity) in plasma cells from patients with MM (n = 22), MGUS/SMM (n = 12), and AL-amyloidosis (AL) (n = 9). CyVEGF expression was higher in MM (169,591) than in MGUS/SMM (144,858), or AL (106,011) although these differences were not statistically significant. Using an indirect VEGFR assay that measures VEGF binding, we found VEGF receptors on plasma cells from all groups of patients, with the lowest expression on plasma cells from normal individuals. We detected VEGF R1, VEGF R2, and VEGF R3 on plasma cells from all groups of patients and found receptor expression predominantly in the subset of CD45-positive plasma cells., Interpretation and Conclusions: This study supports the concept that VEGF is involved in the pathogenesis of MM, and suggests that VEGF may differentially affect a subset of plasma cells.

Purpose: Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease., Patients and Methods: Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis., Results: We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004)., Conclusion: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.

Background & Aims: Gastroesophageal reflux disease is a prevalent disorder that often requires long-term medical therapy or surgery. The United States Food and Drug Administration recently cleared new endoluminal gastroesophageal reflux disease treatments; however, no controlled trials exist., Methods: We randomly assigned 64 gastroesophageal reflux disease patients to radiofrequency energy delivery to the gastroesophageal junction (35 patients) or to a sham procedure (29 patients). Principal outcomes were reflux symptoms and quality of life. Secondary outcomes were medication use and esophageal acid exposure. After 6 months, interested sham patients crossed over to active treatment., Results: At 6 months, active treatment significantly and substantially improved patients' heartburn symptoms and quality of life. More active vs. sham patients were without daily heartburn symptoms (n = 19 [61%] vs. n = 7 [33%]; P = 0.05), and more had a >50% improvement in their gastroesophageal reflux disease quality of life score (n = 19 [61%] vs. n = 6 [30%]; P = 0.03). Symptom improvements persisted at 12 months after treatment. At 6 months, there were no differences in daily medication use after a medication withdrawal protocol (n = 17 [55%] vs. n = 14 [61%]; P = 0.67) or in esophageal acid exposure times. There were no perforations or deaths., Conclusions: Radiofrequency energy delivery significantly improved gastroesophageal reflux disease symptoms and quality of life compared with a sham procedure, but it did not decrease esophageal acid exposure or medication use at 6 months. This procedure represents a new option for selected symptomatic gastroesophageal reflux disease patients who are intolerant of, or desire an alternative to, traditional medical therapies.

The origin and biologic significance of cardiac gastric mucosa are controversial. Traditionally, it has been considered native mucosa and part of normal foregut development. It has been recently suggested that cardiac mucosa is present only as a metaplastic response to gastroesophageal reflux disease and therefore always abnormal. We evaluated the esophagogastric junction in 100 pediatric autopsy samples to determine the existence, characteristics, and length of pure cardiac mucosa at different ages. No patient had a history of gastroesophageal reflux disease. Cardiac mucosa immediately distal and contiguous to the esophageal squamous mucosa was identified in all 100 samples, varying in length from 0.1 to 3 mm; the mean length was 1 mm. There was an inverse correlation between patient age and length of cardiac mucosa; gender had no influence on measured length. Three patients had mild to moderate histologic esophagitis; two had gastritis. No metaplastic features or Helicobacter pylori were identified. These findings support the concept that there is a normal, variably narrow developmental zone at the esophagogastric junction covered by cardiac mucosa and is present at birth. When cardiac type mucosa is found in biopsy material, it does not necessarily represent evidence of a mucosal metaplastic response to gastroesophageal reflux disease.