The connection between Submarine Groundwater Discharge and seawater quality: The threat of treated wastewater injected into coastal aquifers.

Submarine Groundwater Discharge (SGD) delivers nutrients to the coastal sea triggering phytoplankton blooms, eutrophication, and can also serve as a pathway for contaminants. Wastewater treatment plants (WWTP) including injection wells in coastal areas influence coastal aquifers and might impact the composition and magnitude of SGD fluxes. In tourist areas, wastewater treatment may be less efficient and larger in volume during high seasons, potentially impacting nutrient fluxes from SGD and exacerbating environmental impacts. This study analyzes the nutrient transfer from treated wastewater injection in karstic aquifers to the coastal sea via SGD, considering the impacts of tourism seasonality. This study is conducted in Cala Deià, a small cove in the Balearic Islands, a Mediterranean tourist destination. The findings suggest that the seasonality of tourism, leading to variations in the volume of wastewater treated in the WWTP, influences the dynamics of the coastal aquifer. This leads to increased SGD water and nutrient fluxes to the sea in summer, i.e. the peak tourist season. The measured DIN, DIP, and DSi inventories in the cove are much larger in August than in April (3, 10, and 1.5 times higher, respectively) due to higher input of nutrients in summer due to SGD impacted by the WWTP. These elevated nutrient flows can support algal blooms in the cove, compromising water quality for local swimmers and tourists. Indeed, in August, shoreline stations exhibited eutrophic Chl-a concentrations, with peaks reaching approximately 4 mg Chl-a L-1. These elevated levels suggest the presence of an algal bloom during the survey. The anthropogenic origin of SGD-driven nutrients is traced in seawater and seagrass meadows, as evidenced by high ∂15N signatures indicative of polluted areas. Thus, the high pressure exerted on coastal areas by tourism activities increased the magnitude of SGD nutrient fluxes, thereby threatening coastal ecosystems and the services they provide.

Metastatic pulmonary dissemination as differential diagnosis of COVID-19 disease.

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks' duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing's sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.

Scalable Large-Margin Distance Metric Learning Using Stochastic Gradient Descent.

The key to success of many machine learning and pattern recognition algorithms is the way of computing distances between the input data. In this paper, we propose a large-margin-based approach, called the large-margin distance metric learning (LMDML), for learning a Mahalanobis distance metric. LMDML employs the principle of margin maximization to learn the distance metric with the goal of improving k -nearest-neighbor classification. The main challenge of distance metric learning is the positive semidefiniteness constraint on the Mahalanobis matrix. Semidefinite programming is commonly used to enforce this constraint, but it becomes computationally intractable on large-scale data sets. To overcome this limitation, we develop an efficient algorithm based on a stochastic gradient descent. Our algorithm can avoid the computations of the full gradient and ensure that the learned matrix remains within the positive semidefinite cone after each iteration. Extensive experiments show that the proposed algorithm is scalable to large data sets and outperforms other state-of-the-art distance metric learning approaches regarding classification accuracy and training time.

QuBiLS-MAS, open source multi-platform software for atom- and bond-based topological (2D) and chiral (2.5D) algebraic molecular descriptors computations.

BACKGROUND: In previous reports, Marrero-Ponce et al. proposed algebraic formalisms for characterizing topological (2D) and chiral (2.5D) molecular features through atom- and bond-based ToMoCoMD-CARDD (acronym for Topological Molecular Computational Design-Computer Aided Rational Drug Design) molecular descriptors. These MDs codify molecular information based on the bilinear, quadratic and linear algebraic forms and the graph-theoretical electronic-density and edge-adjacency matrices in order to consider atom- and bond-based relations, respectively. These MDs have been successfully applied in the screening of chemical compounds of different therapeutic applications ranging from antimalarials, antibacterials, tyrosinase inhibitors and so on. To compute these MDs, a computational program with the same name was initially developed. However, this in house software barely offered the functionalities required in contemporary molecular modeling tasks, in addition to the inherent limitations that made its usability impractical. Therefore, the present manuscript introduces the QuBiLS-MAS (acronym for Quadratic, Bilinear and N-Linear mapS based on graph-theoretic electronic-density Matrices and Atomic weightingS) software designed to compute topological (0-2.5D) molecular descriptors based on bilinear, quadratic and linear algebraic forms for atom- and bond-based relations. RESULTS: The QuBiLS-MAS module was designed as standalone software, in which extensions and generalizations of the former ToMoCoMD-CARDD 2D-algebraic indices are implemented, considering the following aspects: (a) two new matrix normalization approaches based on double-stochastic and mutual probability formalisms; (b) topological constraints (cut-offs) to take into account particular inter-atomic relations; (c) six additional atomic properties to be used as weighting schemes in the calculation of the molecular vectors; (d) four new local-fragments to consider molecular regions of interest; (e) number of lone-pair electrons in chemical structure defined by diagonal coefficients in matrix representations; and (f) several aggregation operators (invariants) applied over atom/bond-level descriptors in order to compute global indices. This software permits the parallel computation of the indices, contains a batch processing module and data curation functionalities. This program was developed in Java v1.7 using the Chemistry Development Kit library (version 1.4.19). The QuBiLS-MAS software consists of two components: a desktop interface (GUI) and an API library allowing for the easy integration of the latter in chemoinformatics applications. The relevance of the novel extensions and generalizations implemented in this software is demonstrated through three studies. Firstly, a comparative Shannon's entropy based variability study for the proposed QuBiLS-MAS and the DRAGON indices demonstrates superior performance for the former. A principal component analysis reveals that the QuBiLS-MAS approach captures chemical information orthogonal to that codified by the DRAGON descriptors. Lastly, a QSAR study for the binding affinity to the corticosteroid-binding globulin using Cramer's steroid dataset is carried out. CONCLUSIONS: From these analyses, it is revealed that the QuBiLS-MAS approach for atom-pair relations yields similar-to-superior performance with regard to other QSAR methodologies reported in the literature. Therefore, the QuBiLS-MAS approach constitutes a useful tool for the diversity analysis of chemical compound datasets and high-throughput screening of structure-activity data.

Intravenous isotonic fluids induced a positive trend in natraemia in children admitted to a general paediatric ward.

AIM: Using hypotonic intravenous solutions for baseline fluid needs in paediatric patients on a nil by mouth diet may cause serious complications, including hyponatraemia, cerebral oedema and even death. We analysed the evolution of natraemia and explored any adverse effects on children treated with intravenous isotonic fluids. METHODS: This was a prospective study of 50 patients consecutively admitted to a general paediatric ward who were treated with isotonic intravenous fluids and on a nil by mouth diet. RESULTS: The most prevalent diagnosis was acute gastroenteritis (64%). Hyponatraemia, defined as sodium in plasma of <135 mEq/L, affected 22% of the subjects, but none displayed this during the first postadmission analysis at a median of eight hours. Sodium levels changed by an average of +0.64 mEq/L/hour. The subgroup analysis (0.91 versus 0.56 mEq/L/hour, p = 0.02) and multiple linear regression (R(2) = 0.756) showed a greater increase in sodium when patients had hyponatraemia on admission. Iatrogenic hyponatraemia was not detected, but two patients showed mild hypernatraemia and 35% developed clinically insignificant hyperchloraemia. CONCLUSION: Using intravenous isotonic fluids induced a positive trend in natraemia on a general paediatric ward, particularly if patients were hyponatraemic when admitted, and did not induce clinically relevant adverse effects.

Differences in prevalence of inflammatory bowel disease in Puerto Rico between commercial and government-sponsored managed health care insured individuals.

BACKGROUND: Evaluation of ethnic and racial patterns of Inflammatory Bowel Disease (IBD) has demonstrated a higher incidence of IBD in Jews, and lower rates in blacks and Hispanics when compared to whites. There is limited data describing incidence and prevalence among Hispanics, the fastest growing minority in the United States. METHODS: To estimate the prevalence of IBD computerized records of all physicians billing and hospital discharges classified with ICD-9-CM IBD related codes were searched. Prevalence was estimated by age group, sex, and type of insurance (commercial versus government-sponsored managed care). RESULTS: Of 1,248,993 insured individuals in 2005, 186 had a diagnosis of Crohn's disease and 291 of ulcerative colitis. The estimated prevalence per 100,000 was 14.9 for Crohn's disease, 23.3 for ulcerative colitis, and 38.2 cases for IBD. The most significant difference was found when comparing insurance type, with a total IBD prevalence rate of 61.75 cases among commercial versus 14.36 cases among government-sponsored insured. CONCLUSIONS: The prevalence of IBD in this insured population in Puerto Rico places it among the highest described in a Hispanic population. Given the continued rise in prevalence of IBD and the limited studies describing the epidemiology of IBD in Hispanics, further studies which may provide important clues to the etiology of the disease as well as valuable information for appropriate health care planning are important.

A Comparative Study of Nonlinear Machine Learning for the "In Silico" Depiction of Tyrosinase Inhibitory Activity from Molecular Structure.

In the preset report, for the first time, support vector machine (SVM), artificial neural network (ANN), Bayesian networks (BNs), k-nearest neighbor (k-NN) are applied and compared on two "in-house" datasets to describe the tyrosinase inhibitory activity from the molecular structure. The data set Data I is used for the identification of tyrosinase inhibitors (TIs) including 701 active and 728 inactive compounds. Data II consists of active chemicals for potency estimation of TIs. The 2D TOMOCOMD-CARDD atom-based quadratic indices are used as molecular descriptors. The derived models show rather encouraging results with the areas under the Receiver Operating Characteristic (AURC) curve in the test set above 0.943 and 0.846 for the Data I and Data II, respectively. Multiple comparison tests are carried out to compare the performance of the models and reveal the improvement of machine learning (ML) techniques with respect to statistical ones (see Chemometr. Intell. Lab. Syst. 2010, 104, 249). In some cases, these ameliorations are statistically significant. The tests also demostrate that k-NN, despite being a rather simple approach, presents the best behavior in both data. The obtained results suggest that the ML-based models could help to improve the virtual screening procedures and the confluence of these different techniques can increase the practicality of data mining procedures of chemical databases for the discovery of novel TIs as possible depigmenting agents.

Desirability-based methods of multiobjective optimization and ranking for global QSAR studies. Filtering safe and potent drug candidates from combinatorial libraries.

Up to now, very few applications of multiobjective optimization (MOOP) techniques to quantitative structure-activity relationship (QSAR) studies have been reported in the literature. However, none of them report the optimization of objectives related directly to the final pharmaceutical profile of a drug. In this paper, a MOOP method based on Derringer's desirability function that allows conducting global QSAR studies, simultaneously considering the potency, bioavailability, and safety of a set of drug candidates, is introduced. The results of the desirability-based MOOP (the levels of the predictor variables concurrently producing the best possible compromise between the properties determining an optimal drug candidate) are used for the implementation of a ranking method that is also based on the application of desirability functions. This method allows ranking drug candidates with unknown pharmaceutical properties from combinatorial libraries according to the degree of similarity with the previously determined optimal candidate. Application of this method will make it possible to filter the most promising drug candidates of a library (the best-ranked candidates), which should have the best pharmaceutical profile (the best compromise between potency, safety and bioavailability). In addition, a validation method of the ranking process, as well as a quantitative measure of the quality of a ranking, the ranking quality index (Psi), is proposed. The usefulness of the desirability-based methods of MOOP and ranking is demonstrated by its application to a library of 95 fluoroquinolones, reporting their gram-negative antibacterial activity and mammalian cell cytotoxicity. Finally, the combined use of the desirability-based methods of MOOP and ranking proposed here seems to be a valuable tool for rational drug discovery and development.

Utilization of health services and prescription patterns among lupus patients followed by primary care physicians and rheumatologists in Puerto Rico.

OBJECTIVE: To examine the utilization of health services and prescription patterns among patients with systemic lupus erythematosus (SLE) followed by primary care physicians and rheumatologists in Puerto Rico. METHODS: The insurance claims submitted by physicians to a health insurance company of Puerto Rico in 2003 were examined. The diagnosis of lupus was determined by using the International Classification of Diseases, Ninth Revision, code for SLE (710.0). Of 552,733 insured people, 665 SLE patients were seen by rheumatologists, and 92 were followed by primary care physicians. Demographic features, selected co-morbidities, healthcare utilization parameters, and prescription patterns were examined. Fisher exact test, chi2 test, and analysis of variances were used to evaluate differences between the study groups. RESULTS: SLE patients followed by rheumatologists had osteopenia/osteoporosis diagnosed more frequently than did patients followed by primary care physicians. The frequency of high blood pressure, diabetes mellitus, hypercholesterolemia, coronary artery disease, and renal disease was similar for both groups. Rheumatologists were more likely to order erythrocyte sedimentation rate, anti-dsDNA antibodies, and serum complements. No differences were observed for office or emergency room visits, hospitalizations, and utilization of routine laboratory tests. Rheumatologists prescribed hydroxychloroquine more frequently than did primary care physicians. The use of nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, glucocorticoids, azathioprine, cyclophosphamide, and methotrexate was similar for both groups. CONCLUSION: Overall, the utilization of health services and prescription patterns among SLE patients followed by primary care physicians and rheumatologists in Puerto Rico are similar. However, rheumatologists ordered SLE biomarkers of disease activity and prescribed hydroxychloroquine more frequently than did primary care physicians.

Prevalence of systemic lupus erythematosus and associated comorbidities in Puerto Rico.

OBJECTIVE: To examine the prevalence of systemic lupus erythematosus (SLE) and its associated comorbidities in patients from Puerto Rico using a database from a health insurance company. METHODS: The insurance claims submitted by physicians in 2003 to a health insurance company of Puerto Rico were examined. Of 552,733 insured people, 877 had a diagnosis of SLE (code 710.0) per the International Classification of Diseases, Ninth Revision (ICD-9). Demographic parameters and selected comorbidities were determined. The diagnosis of comorbities was ascertained using the ICD-9 code, the Current Procedural Terminology-4 code (for disease-specific procedures) and/or the Medi-Span Therapeutic Classification System (for disease-specific pharmacologic treatment). Fisher exact test and chi were used to evaluate differences between SLE patients groups. RESULTS: The mean age was 42.0 +/- 13.5, and the female-to-male ratio was 12.5:1. The overall prevalence of SLE was 159 per 100,000 individuals. The prevalence for females was 277 per 100,000 women and for males it was 25 per 100,000 men. The most common comorbidities were high blood pressure (33.7%), osteopenia/osteoporosis (22.2%), hypothyroidism (19.0%), diabetes mellitus (11.6%), and hypercholesterolemia (11.6%). Overall, high blood pressure, diabetes mellitus, hypercholesterolemia, and coronary artery disease were more prevalent in SLE patients older than 54 years. Osteopenia/osteoporosis was more prevalent in women than in men. CONCLUSIONS: The prevalence of SLE in Puerto Rico is very high. High blood pressure, diabetes mellitus and hypercholesterolemia, hypothyroidism, and osteopenia/osteoporosis are common comorbidities in these patients. Identification and management of these comorbidities are critical for optimal medical care to this population.

Prevalence of inflammatory bowel disease in an insured population in Puerto Rico during 1996.

OBJECTIVES: Limited data exists about Inflammatory Bowel Disease (IBD) in Hispanic populations. The aims of the present study were to estimate overall and specific prevalence of IBD (Crohn's disease and ulcerative colitis) and to describe the characteristics of a group of patients from the University of Puerto Rico's IBD Registry. METHODS: To estimate the prevalence of IBD, computerized records of all physician billing and hospital discharges from a major health insurer in Puerto Rico and classified with ICD-9-CM codes 555.0-555.9 (Crohn's disease) and 556.0-556.9 (ulcerative colitis) during 1996 were searched. Prevalence was estimated by age group, sex, and type of insurance. To describe demographic and selected clinical information from patients with IBD, data gathered in the University of Puerto Rico's IBD Registry from 1995 through 2000 was analyzed. RESULTS: Out of 802,726 insured individuals, 332 had a diagnosis of Crohn's disease, 499 of ulcerative colitis and 21 had both diagnoses. The estimated prevalence per 100,000 was 41.4 for Crohn's disease, 62.2 for ulcerative colitis, and 106.1 cases per 100,000 for IBD. Peak prevalence of Crohn's disease occurred among the age groups 50-59 years and > or = 60 years, and the overall female:male prevalence ratio of Crohn's disease was 1.13 (95% CI: 0.91-1.42). Ulcerative colitis was most prevalent among insured individuals aged 50-59 years and 40-49 years. The prevalence of ulcerative colitis was significantly higher among females than among males, with an overall prevalence ratio of 1.42 (95% CI: 1.18-1.71). Of 342 patients participating in the IBD Registry, 155 (45.3%) had Crohn's disease and 187 (54.7%) had ulcerative colitis. Among patients diagnosed with Crohn's disease, 51.6% were females, the mean age was 35.2 +/- 18.3 years, and 18.1% had a family history of IBD. More than half (57.8%) of patients with ulcerative colitis were females, the mean age was 42.6 +/- 17 years, and 17.1% had a family history of IBD. CONCLUSIONS: The estimated prevalence of IBD in this insured population in Puerto Rico places it among the middle-range of that reported for other countries. Additional studies must be conducted in Puerto Rico in order to confirm the observed findings. Population-based epidemiologic studies aimed at estimating the burden of IBD in Hispanic populations in the United States and Latin America are essential for health care planning.

Descriptive epidemiology of head and neck squamous cell carcinoma in Puerto Ricans

This study comprised 134 patients who had developed head and neck squamous carcinoma (HNSCC), and attended the cancer clinics of the Otolaryngology Department at the Isaac González Martínez Oncologic Hospital between August 1993 and November 1995. In-person interviews, and medical record review of the HNSCC patients provided data on demography, family history of cancer, history of a second primary cancer, history of environmental, tobacco and ethanol exposure, and current disease status. The average age at the time of diagnosis was 62.3 (range 18-94), and eighty percent of the subjects were male. Most (59 per cent) of the patients had moderately differentiated tumors and 14 per cent had a recurrence of the carcinoma. The most frequent primary site in males was the laryngeal area, and the oral cavity in females. Exposure to alcohol and smoking were identified as predisposing factors in 95 per cent of the patients.

El laser de CO2 en dermatología / CO2 laser in dermatology

Presentamos 74 pacientes con diferentes patologías que fueron tratadas con laser de CO2. Describimos la técnica usada en cada patología. los resultados y evolución