Confounder-dependent Bayesian mixture model: Characterizing heterogeneity of causal effects in air pollution epidemiology.

Several epidemiological studies have provided evidence that long-term exposure to fine particulate matter (pm2.5) increases mortality rate. Furthermore, some population characteristics (e.g., age, race, and socioeconomic status) might play a crucial role in understanding vulnerability to air pollution. To inform policy, it is necessary to identify groups of the population that are more or less vulnerable to air pollution. In causal inference literature, the group average treatment effect (GATE) is a distinctive facet of the conditional average treatment effect. This widely employed metric serves to characterize the heterogeneity of a treatment effect based on some population characteristics. In this paper, we introduce a novel Confounder-Dependent Bayesian Mixture Model (CDBMM) to characterize causal effect heterogeneity. More specifically, our method leverages the flexibility of the dependent Dirichlet process to model the distribution of the potential outcomes conditionally to the covariates and the treatment levels, thus enabling us to: (i) identify heterogeneous and mutually exclusive population groups defined by similar GATEs in a data-driven way, and (ii) estimate and characterize the causal effects within each of the identified groups. Through simulations, we demonstrate the effectiveness of our method in uncovering key insights about treatment effects heterogeneity. We apply our method to claims data from Medicare enrollees in Texas. We found six mutually exclusive groups where the causal effects of pm2.5 on mortality rate are heterogeneous.

Predicting choice behaviour in economic games using gaze data encoded as scanpath images.

Eye movement data has been extensively utilized by researchers interested in studying decision-making within the strategic setting of economic games. In this paper, we demonstrate that both deep learning and support vector machine classification methods are able to accurately identify participants' decision strategies before they commit to action while playing games. Our approach focuses on creating scanpath images that best capture the dynamics of a participant's gaze behaviour in a way that is meaningful for predictions to the machine learning models. Our results demonstrate a higher classification accuracy by 18% points compared to a baseline logistic regression model, which is traditionally used to analyse gaze data recorded during economic games. In a broader context, we aim to illustrate the potential for eye-tracking data to create information asymmetries in strategic environments in favour of those who collect and process the data. These information asymmetries could become especially relevant as eye-tracking is expected to become more widespread in user applications, with the seemingly imminent mass adoption of virtual reality systems and the development of devices with the ability to record eye movement outside of a laboratory setting.

CRISPR-based oligo recombineering prioritizes apicomplexan cysteines for drug discovery.

Nucleophilic amino acids are important in covalent drug development yet underutilized as anti-microbial targets. Chemoproteomic technologies have been developed to mine chemically accessible residues via their intrinsic reactivity towards electrophilic probes but cannot discern which chemically reactive sites contribute to protein function and should therefore be prioritized for drug discovery. To address this, we have developed a CRISPR-based oligo recombineering (CORe) platform to support the rapid identification, functional prioritization and rational targeting of chemically reactive sites in haploid systems. Our approach couples protein sequence and function with biological fitness of live cells. Here we profile the electrophile sensitivity of proteinogenic cysteines in the eukaryotic pathogen Toxoplasma gondii and prioritize functional sites using CORe. Electrophile-sensitive cysteines decorating the ribosome were found to be critical for parasite growth, with target-based screening identifying a parasite-selective anti-malarial lead molecule and validating the apicomplexan translation machinery as a target for ongoing covalent ligand development.

Exposure to Unconventional Oil and Gas Development and All-cause Mortality in Medicare Beneficiaries.

Little is known about whether exposure to unconventional oil and gas development is associated with higher mortality risks in the elderly and whether related air pollutants are exposure pathways. We studied a cohort of 15,198,496 Medicare beneficiaries (136,215,059 person-years) in all major U.S. unconventional exploration regions from 2001 to 2015. We gathered data from records of more than 2.5 million oil and gas wells. For each beneficiary's ZIP code of residence and year in the cohort, we calculated a proximity-based and a downwind-based pollutant exposure. We analyzed the data using two methods: Cox proportional hazards model and Difference-in-Differences. We found evidence of statistically significant higher mortality risk associated with living in proximity to and downwind of unconventional oil and gas wells. Our results suggest that primary air pollutants sourced from unconventional oil and gas exploration can be a major exposure pathway with adverse health effects in the elderly.

Antegrade endoscopic dilatation as an alternative approach to primary obstructive megaureter. / Dilatación endoscópica anterograda como abordaje alternativo del megauréter obstructivo primario.

OBJECTIVES: Congenital primary obstructive megaureter (POM) is caused by ureterovesical junction stenosis, reduced peristalsis, and the resulting dilatation. Even though ureteral re-implantation remains the current gold standard technique, retrograde dilatation is considered as an effective therapeutic alternative with good results and growing proponents - to the extent it has become the technique of choice in some healthcare facilities. The objective was to present an alternative approach for treatment purposes. MATERIALS AND METHODS: This is the case of a 5-month-old infant with POM and pyonephrosis requiring nephrostomy and intravenous antibiotic therapy. Endoscopic dilatation was carried out by means of a percutaneous drainage in an antegrade fashion and did not require cystoscopy. RESULTS: The procedure was uneventful. During follow-up, ureterohydronephrosis decreased, while ureteral dilatation persisted to a lesser extent with an adequate peristalsis and absence of secondary VUR. The patient has had no symptoms after an 11-month follow-up. CONCLUSIONS: POM antegrade dilatation is an effective alternative in selected patients as it makes the pathology disappear.

OBJETIVOS: El megauréter obstructivo primario congénito (MOP) se produce por la estenosis de la unión ureterovesical, disminución en la peristalsis y su consecuente dilatación. Aunque actualmente el gold standard para el tratamiento de esta entidad sigue siendo el reimplante ureteral, la dilatación retrógrada se considera una alternativa terapéutica eficaz con buenos resultados y que está ganando cada vez más adeptos, siendo en algunos centros la técnica de elección. El objetivo es presentar una alternativa de abordaje para su tratamiento. MATERIAL Y METODOS: Se presenta el caso de un lactante de 5 meses con MOP afecto de pionefrosis que precisa nefrostomía y antibioterapia endovenosa. La dilatación endoscópica se realizó a través del drenaje percutáneo de manera anterógrada sin necesidad de cistoscopia. RESULTADOS: El procedimiento se llevó a cabo sin incidencias. En el seguimiento se apreció una disminución de la ureterohidronefrosis, persistiendo la dilatación del uréter en menor grado con adecuada peristalsis y la ausencia de RVU secundario. Tras 11 meses de seguimiento, permanece asintomático. CONCLUSIONES: La dilatación anterógrada del MOP es una alternativa efectiva en pacientes seleccionados que permite la resolución de la patología.

Long-term outcomes of colonic stent as a "bridge to surgery"for left-sided malignant large-bowel obstruction.

BACKGROUND: The role of self-expandable metallic stents (SEMS) as a bridge to surgery in left-sided malignant colonic obstruction is still debated. Here we assess the morbidity, mortality and long-term oncological outcomes as a bridge to surgery for patients with left-sided malignant colonic obstruction. METHOD: Prospective observational study with retrospective analysis of patients with left-sided malignant colonic obstruction undergoing stenting. April 2006-April 2018. We assessed all patients with intent-to treat and per protocol analyses and long-term follow-up variables. RESULTS: Colonic stent was performed in 117 patients. Technical and clinical success of SEMS placement: 94.4% (111/117), only 4.3% perforation. Elective surgery resection following the strategy of SEMS was performed in 83.8% (98/117). A laparoscopic approach was: 25.6% (30/117); 76.9% in the last two years. Primary anastomosis rate: 92.8% (91/98), without protective stoma in any patients. Anastomotic leakage rate: 8.2% (8/97). Median follow-up: 44.5 months (range 0-109). The intent-to-treat analysis showed overall and disease-free survival rates of 63.3% (74/117) and 58.1% (68/117), and local and distant recurrence rates: 9.4% (11/117) and 58.1% (68/117). In the per protocol analysis, overall and disease-free survival rates: 63.2% (62/98) and 60.2% (58/98), and local and distant recurrence rates: 10.2% (10/98) and 36.7% (36/98). Disease progression was predominantly observed during the first 5 years' follow-up as disease recurrence; after five years' follow-up, 60% of the patients were disease-free. CONCLUSIONS: According to the results of the study SEMS as a bridge to surgery achieves perioperative results comparable to non-occlusive colonic cancer surgery and does not adversely affect long-term oncological outcomes. Further investigations are needed.

R0 Resection Margin, A New Quality Measure in the Era of National Bowel Screening?

Aims To determine the completeness of polyp resection (i.e. achieving an R0 margin) and its relation with Endoscopists, histopathologist, size, location and technique of polypectomy in an NSS cohort. The definition of R0 margin is complete macroscopic resection with a negative microscopic margin at polypectomy. Method NCCS (National Colon Cancer Screening) colonoscopies are offered to bowel cancer screening patients after a positive faecal immunochemical test (FIT) test in a Joint Advisory Group (JAG) accredited Gastrointestinal Endoscopy centre. We histologically evaluated the polyp margins for complete resection, which was defined as the absence of adenomatous or hyperplastic tissue in the resected polyp margins in a cohort of faecal immunochemical test positive patients. Results A total of 186 consecutive NCCS colonoscopies out of a total of 542 performed between 2013 and 2017 were included in this study. Of the polyps excised 152(27%) had a R0 margin histologically, and 30(5%) had involvement of the margin. Surprisingly in 373(67%) of polyps pathologists were unable to assess the margin. Conclusion Achieving an R0 margin should be a key performance indicator for endoscopists performing polypectomy. At the same time more studies on polyp margins are recommended.

PrediCTC, liquid biopsy in precision oncology: a technology transfer experience in the Spanish health system.

PURPOSE: Management of metastatic disease in oncology includes monitoring of therapy response principally by imaging techniques like CT scan. In addition to some limitations, the irruption of liquid biopsy and its application in personalized medicine has encouraged the development of more efficient technologies for prognosis and follow-up of patients in advanced disease. METHODS: PrediCTC constitutes a panel of genes for the assessment of circulating tumor cells (CTC) in metastatic colorectal cancer patients, with demonstrated improved efficiency compared to CT scan for the evaluation of early therapy response in a multicenter prospective study. In this work, we designed and developed a technology transfer strategy to define the market opportunity for an eventual implementation of PrediCTC in the clinical practice. RESULTS: This included the definition of the regulatory framework, the analysis of the regulatory roadmap needed for CE mark, a benchmarking study, the design of a product development strategy, a revision of intellectual property, a cost-effectiveness study and an expert panel consultation. CONCLUSION: The definition and analysis of an appropriate technology transfer strategy and the correct balance among regulatory, financial and technical determinants are critical for the transformation of a promising technology into a viable technology, and for the decision of implementing liquid biopsy in the monitoring of therapy response in advanced disease.

Percutaneous radiofrequency ablation of renal tumors in high-risk patients: 10 years' experience. / Ablación percutánea mediante radiofrecuencia de tumores renales en pacientes de alto riesgo: 10 años de experiencia.

OBJECTIVE: To retrospectively evaluate the efficacy and safety of percutaneous radiofrequency ablation (RFA) done to treat renal tumors in patients with high surgical risk or with the risk of developing multiple renal tumors in the medium term at our center over a period of 10 years. MATERIAL AND METHODS: Between 2005 and 2015, we used RFA to treat 89 T1a or T1b tumors in 87 patients (mean age, 73.7±10.87 years) with high surgical risk. We excluded patients treated with radiofrequency and embolization or microwave ablation. The tumors treated were clear cell carcinomas (43.6%), papillary renal carcinomas (17.2%), chromophobe renal cell carcinomas (10.3%), cystic tumors (2.2%), and an angiomyolipoma (1.1%). The mean size of the tumors was 2.6cm. Computed tomography and/or ultrasonography were used to guide the procedure. We analyzed the relation between the efficacy of the procedure and patients' age, the type of needle, the source of the patients, the size and location of the tumor, and the number of sessions required to achieve ablation. We recorded all complications. RESULTS: The RFA procedure was completed in all patients. The mean follow-up period was 32.1 months. The efficacy was 93.7%. A single session was sufficient in 87.5% of patients; 8% required two sessions and 4.5% required three sessions. The only factor associated with worse efficacy was the size of the tumor (p=0.03). The rate of complications was 5.6%. CONCLUSIONS: RFA is efficacious and safe, with results comparable to those reported in the literature.

Critical electrolyte concentration of silk gland chromatin of the sugarcane borer Diatraea saccharalis, induced using agrochemicals.

The sugarcane borer Diatraea saccharalis is widely known as the main pest of sugarcane crop, causing increased damage to the entire fields. Measures to control this pest involve the use of chemicals and biological control with Cotesia flavipes wasps. In this study, we evaluated the insecticides fipronil (Frontline; 0.0025%), malathion (Malatol Bio Carb; 0.4%), cipermetrina (Galgotrin; 10%), and neem oil (Natuneem; 100%) and the herbicide nicosulfuron (Sanson 40 SC; 100%) in the posterior region silk glands of 3rd- and 5th-instar D. saccharalis by studying the variation in the critical electrolyte concentration (CEC). Observations of 3rd-instar larvae indicated that malathion, cipermetrina, and neem oil induced increased chromatin condensation that may consequently disable genes. Tests with fipronil showed no alteration in chromatin condensation. With the use of nicosulfuron, there was chromatin and probable gene decompaction. In the 5th-instar larvae, the larval CEC values indicated that malathion and neem oil induced increased chromatin condensation. The CEC values for 5th-instar larvae using cipermetrina, fipronil, and nicosulfuron indicated chromatin unpacking. These observations led us to conclude that the quantity of the pesticide does not affect the mortality of these pests, can change the conformation of complexes of DNA, RNA, and protein from the posterior region of silk gland cells of D. saccharalis, activating or repressing the expression of genes related to the defense mechanism of the insect and contributing to the selection and survival of resistant individuals.

Prospective, controlled, randomized study of intraoperative colonic lavage versus stent placement in obstructive left-sided colonic cancer.

BACKGROUND: The main aim of this study was to compare short-term results and long-term outcomes of patients who underwent intraoperative colonic lavage (IOCL) with primary anastomosis with those who had stent placement prior to scheduled surgery for obstructive left-sided colonic cancer (OLCC). METHODS: We conducted a prospective, controlled, randomized study of patients diagnosed with OLCC. Patients were divided into two groups: stent and deferred surgery (group 1) and emergency IOCL (group 2). Demographic variables, risk prediction models, postoperative morbidity and mortality, staging, complications due to stent placement, surgical time, clinical follow-up, health costs, and follow-up of survival were recorded. RESULTS: Twenty-eight patients (15 group 1 and 13 group 1) were enrolled. The study was suspended upon detecting excess morbidity in group 2. The two groups were homogeneous in clinical and demographic terms. Overall morbidity in group 1 was 2/15 (13.3%) compared with 7/13 (53.8%) in group 2 (p = 0.042). None of the 15 patients in group 1 presented anastomotic dehiscence compared with 4/13 (30.7%) in group 2 (p = 0.035). Surgical site infection was detected in 2 (13.3%) patients in group 1 and in 6 (46.1%) in group 2 (p = 0.096). Postoperative stay was 8 days (IQR 3, group 1) and 10 days (IQR 10, group 2) (p = 0.05). The mean follow-up period was 37.6 months (SD = 16.08) with no differences in survival between the groups. CONCLUSION: In our setting, the use of a stent and scheduled surgery is safer than IOCL and is associated with lower morbidity, shorter hospital stay, and equally good long-term survival.

[Natural history of hepatocellular carcinoma in a cohort of pacients from a county hospital]. / Historia natural del carcinoma hepatocelular en una cohorte de pacientes de un hospital comarcal.

BACKGROUND: hepatocellular carcinoma (HCC) is a cancer with high incidence and mortality. OBJECTIVE: our aim was to describe the natural history of a patient cohort with HCC, and to identify the factors associated with survival. PATIENTS AND METHODS: a retrospective and descriptive study of patients diagnosed with HCC between 1995 and 2002. Qualitative variables were expressed as frequencies and percentages. Quantitative variables were expressed as medians and standard deviations. Survival was calculated using the Kaplan-Meier method and log rank. RESULTS: a total of 154 patients were analyzed. The men-to-women ratio was 2.9/1. Mean age was 68 +/- 9 years. 82% of patients died during a median follow-up of 28 months. Median survival was 21.5 months (95% CI: 16.98-26.04). Curative treatment was done in 40.3% of diagnosed patients, and 59.7% of patients received palliative treatment. Factors associated with survival were: ascites, number of lesions at diagnosis, and curative treatment. No statistical differences were found for the next factors: age, sex, etiology of cirrhosis, and Child-Pugh stage at diagnosis. CONCLUSIONS: factors associated with low survival in patients with HCC were ascites and number of lesions. Curative treatment is associated with a higher survival when compared to palliative treatment.

Colorectal stenting as an effective therapy for preoperative and palliative treatment of large bowel obstruction: 9 years' experience.

BACKGROUND: Since their introduction, selfextending metal stents (SEMS) have established themselves as an option in the treatment of obstructive colorectal cancer. Thanks to stenting, patients traditionally treated with emergency surgery can now be converted to scheduled surgery with mechanical preparation of the colon and primary anastomosis. Stenting represents a valid one-step surgical alternative for intestinal obstruction of the colon. METHODS: We performed a prospective study of 95 patients (mean age, 68 years; range 48-94) with large bowel obstruction due to colorectal cancer treated with SEMS placed under fluoroscopic guidance, some as a bridge to surgery (group A) and others with palliative intent (group B). Computed tomography was performed for diagnostic purposes and to study the extent of disease. RESULTS: Treatment was palliative in 28 cases (group B) and as a bridge to surgery in 67 (group A). The latter group underwent mechanical preparation of the colon and elective surgery. No patients died as a result of the procedure. In 90 cases (95%), treatment was effective and the obstruction resolved. Complications were 4 cases of perforation, 1 of tenesmus, 4 obstructions and 4 migrations. In 7 cases, a second stent was inserted to allow subsequent scheduled surgery. CONCLUSIONS: Self-extending stents resolve colorectal cancer obstruction and allow optimal patient staging and scheduled surgical treatment. Stenting is also a useful option in advanced or irresectable tumors, avoiding the need for surgery and offering good palliation.

[Arterial hypertension and stenosis of the accessory renal artery]. / Hipertensión arterial y estenosis de la arteria renal accesoria.

We present the case of a 45 year old patient with severe hypertension refractory to medical treatment who was diagnosed a significant stenosis of an accessory renal artery whilst the main renal arteries were normal. The arterial dilatation through angioplasty of the accessory artery improved dramatically the control of his hypertension.

[Carotid stenosis: appropriate diagnosis and treatment]. / Estenosis carotídea: cómo se diagnostica y se trata adecuadamente.

Ischemic cerebral infarcts represent a serious health problem with important social and economic repercussions in the western world. The presence of carotid stenosis is one of the main risk factors for the appearance of cerebral infarcts. Carotid stenosis represents a challenge for the medical community, both because of the enormous amount of scientific information available and because of the constant advances in diagnostic procedures and especially in revascularization techniques for treatment. General radiologists as well as those specializing in vascular pathology need to have ample knowledge of how to reach the diagnosis and of the different treatment options for this pathology if they are to play a successful role in multidisciplinary teams dealing with carotid stenosis. This update aims to present the basic information that we consider to be essential in a simple way to enable radiologists to meet this challenge.