Complex macrocycle exploration: parallel, heuristic, and constraint-based conformer generation using ForceGen.

ForceGen is a template-free, non-stochastic approach for 2D to 3D structure generation and conformational elaboration for small molecules, including both non-macrocycles and macrocycles. For conformational search of non-macrocycles, ForceGen is both faster and more accurate than the best of all tested methods on a very large, independently curated benchmark of 2859 PDB ligands. In this study, the primary results are on macrocycles, including results for 431 unique examples from four separate benchmarks. These include complex peptide and peptide-like cases that can form networks of internal hydrogen bonds. By making use of new physical movements ("flips" of near-linear sub-cycles and explicit formation of hydrogen bonds), ForceGen exhibited statistically significantly better performance for overall RMS deviation from experimental coordinates than all other approaches. The algorithmic approach offers natural parallelization across multiple computing-cores. On a modest multi-core workstation, for all but the most complex macrocycles, median wall-clock times were generally under a minute in fast search mode and under 2 min using thorough search. On the most complex cases (roughly cyclic decapeptides and larger) explicit exploration of likely hydrogen bonding networks yielded marked improvements, but with calculation times increasing to several minutes and in some cases to roughly an hour for fast search. In complex cases, utilization of NMR data to constrain conformational search produces accurate conformational ensembles representative of solution state macrocycle behavior. On macrocycles of typical complexity (up to 21 rotatable macrocyclic and exocyclic bonds), design-focused macrocycle optimization can be practically supported by computational chemistry at interactive time-scales, with conformational ensemble accuracy equaling what is seen with non-macrocyclic ligands. For more complex macrocycles, inclusion of sparse biophysical data is a helpful adjunct to computation

Rehabilitación de la voz después de la laringectomia total

Uno de los argumentos más empleados por los radioterapeutasen favor del tratamiento de las lesiones neoplásicas de la laringe por medio de los RX, es la pérdida de la voz que acarrea la cirugía. Sin embargo, esto no es completamente cierto ya que las intervenciones quirúrgicas como la laringofisura o la hemilaringectomía no dan lugar a pérdida de la voz sino más bien a modificaciones de ésta, las cuales en gran número de casos son poco manifiestas. Estas consideraciones son el fruto de una revisión de los trabajos presentados en este sentido por el doctor C. L. Jackson, cuyas conclusiones copio a continuación

Prospective Validation of Eight Different Adherence Measures for Use with Administrative Claims Data among Patients with Schizophrenia

ABSTRACTObjectiveThe aim of this study was to compare the predictive validity of eight different adherence measures by studying the variability explained between each measure and hospitalization episodes among Medicaid-eligible persons diagnosed with schizophrenia on antipsychotic monotherapy.MethodsThis study was a retrospective analysis of the Arkansas Medicaid administrative claims data. Continuously eligible adult schizophrenia (ICD-9-CM = 295.**) patients on antipsychotic monotherapy were identified in the recruitment period from July 2000 through April 2004. Adherence rates to antipsychotic therapy in year 1 were calculated using eight different measures identified from the literature. Univariate and multivariable logistic regression models were used to prospectively predict all-cause and mental health-related hospitalizations in the follow-up year.ResultsAdherence rates were computed for 3395 schizophrenic patients with a mean age of 42.9 years, of which 52.5% (n = 1782) were females, and 52.8% (n = 1793) were white. The proportion of days covered (PDC) and continuous measure of medication gaps measures of adherence had equal C-statistics of 0.571 in predicting both all-cause and mental health-related hospitalizations. The medication possession ratio (MPR) continuous multiple interval measure of oversupply were the second best measures with equal C-statistics of 0.568 and 0.567 for any-cause and mental health-related hospitalizations. The multivariate adjusted models had higher C-statistics but provided the same rank order results.ConclusionsMPR and PDC were among the best predictors of any-cause and mental health-related hospitalization, and are recommended as the preferred adherence measures when a single measure is sought for use with administrative claims data for patients not on polypharmacy

Evaluación de la sustentabilidad de agroecosistemas campesinos y su relación con la permanencia de familias rurales en la región central de Boyacá (Colombia)

Boyacá está situado en la región central de los Andes en Colombia. La mitad de su población es rural (49%) de la cual 68% está por debajo de la línea de pobreza (DPN, 2012). La investigación evalúa el nivel de sustentabilidad de los agroecosistemas familiares campesinos e identifica su posible relación con la permanencia de los integrantes del núcleo familiar rural en actividades agropecuarias. Se evalúan tres (3) agroecosistemas campesinos (fincas) para lo cual se usa como referente metodológico el Marco para la Evaluación de Sistemas de Manejo de Recursos Naturales Incorporando Indicadores de Sustentabilidad (MESMIS). Los resultados muestran que la sustentabilidad de los agroecosistemas está en función de las características bióticas y del manejo productivo, pero especialmente de la condición organizacional de la familia rural, y su mejor capacidad para incorporar prácticas agrícolas de bajo costo y poco riesgo. De los tres agroecosistemas campesinos evaluados se determinó que el agroecosistema Tocavita presenta el mejor nivel de sustentabilidad ya que presenta un menor nivel de dependencia de insumos externos, y la totalidad de los integrantes del núcleo familiar permanecen dedicados a actividades agropecuarias.Boyacá is located in the central region of the Andes in Colombia. Half of its population (49%) is rural, and 68% of this is below the poverty line. The research evaluates the level of sustainability of family farmers and identifies its possible relation to the permanence of rural household members in agricultural activities. Evaluate three farming systems are evaluated using as a methodological reference framework for assessing the management systems of natural resources (MESMIS) incorporating sustainability indicators. Results show that the sustainability of agro-ecosystems depends on biotic and management characteristics, but in particular of organizational conditions of rural families, and their ability to incorporate low cost and low risk agricultural practices. Of the three evaluated farming systems it was determined that the agroecosystem Tocavita presents the highest level of sustainability because it has a lower level of dependence on external inputs, and all the household members remain dedicated to agricultural activities.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos).Facultad de Ciencias Agrarias y Forestale

Evaluación de la sustentabilidad de agroecosistemas campesinos y su relación con la permanencia de familias rurales en la región central de Boyacá (Colombia)

Boyacá está situado en la región central de los Andes en Colombia. La mitad de su población es rural (49%) de la cual 68% está por debajo de la línea de pobreza (DPN, 2012). La investigación evalúa el nivel de sustentabilidad de los agroecosistemas familiares campesinos e identifica su posible relación con la permanencia de los integrantes del núcleo familiar rural en actividades agropecuarias. Se evalúan tres (3) agroecosistemas campesinos (fincas) para lo cual se usa como referente metodológico el Marco para la Evaluación de Sistemas de Manejo de Recursos Naturales Incorporando Indicadores de Sustentabilidad (MESMIS). Los resultados muestran que la sustentabilidad de los agroecosistemas está en función de las características bióticas y del manejo productivo, pero especialmente de la condición organizacional de la familia rural, y su mejor capacidad para incorporar prácticas agrícolas de bajo costo y poco riesgo. De los tres agroecosistemas campesinos evaluados se determinó que el agroecosistema Tocavita presenta el mejor nivel de sustentabilidad ya que presenta un menor nivel de dependencia de insumos externos, y la totalidad de los integrantes del núcleo familiar permanecen dedicados a actividades agropecuarias.Boyacá is located in the central region of the Andes in Colombia. Half of its population (49%) is rural, and 68% of this is below the poverty line. The research evaluates the level of sustainability of family farmers and identifies its possible relation to the permanence of rural household members in agricultural activities. Evaluate three farming systems are evaluated using as a methodological reference framework for assessing the management systems of natural resources (MESMIS) incorporating sustainability indicators. Results show that the sustainability of agro-ecosystems depends on biotic and management characteristics, but in particular of organizational conditions of rural families, and their ability to incorporate low cost and low risk agricultural practices. Of the three evaluated farming systems it was determined that the agroecosystem Tocavita presents the highest level of sustainability because it has a lower level of dependence on external inputs, and all the household members remain dedicated to agricultural activities.Eje: A1 Sistemas de producción de base agroecológica (Trabajos científicos).Facultad de Ciencias Agrarias y Forestale

A Survey of Patients with Inflatable Penile Prostheses: Assessment of Timing and Frequency of Intercourse and Analysis of Implant Durability

Introduction.  This study was conducted to determine how long after inflatable penile prosthesis (IPP) surgery patients attempt sexual intercourse and the frequency of subsequent relations. We also examined survival‐related factors for the AMS 700 CX, Mentor Alpha 1, and Mentor Alpha Narrow Base. Aims.  The aim was to survey men who received IPPs and collect information about their return to sexual function and frequency of use, and to assess the resilience of their devices. Methods.  Phase I involved retrospective chart review of 1,298 virgin IPP surgeries performed by one surgical team from January 1992 to December 1998. Phase II included 330 subjects selected by stratified, systematic, random sampling from phase I patients. Data were collected by computer‐assisted telephone interview, using a 27‐question survey. All patients had been instructed to wait 4 weeks before using the implant and were taught how to inflate/deflate their prostheses at the 4‐week postsurgical visits. Main Outcome Measures.  The survey examines the length of time after surgery for men to resume sexual function. In the same study, information was garnered about mechanical durability of the device. Results.  Among phase I subjects, the 5‐year survival rate was 83% (N = 1,069) for IPP revision for any reason. Of the 330 phase II subjects, 248 (75%) were successfully contacted; 199 (80%) responded to the full survey and 49 (20%) responded to selected parts of the survey. Sexual intercourse was resumed postoperatively at 1–4 weeks for 41% (78/190), at 5–6 weeks for 31% (59/190), at 7–8 weeks for 16% (30/190), and at >8 weeks for 12% (23/190) of the patients. More than 60% of patients reported using their IPP at least once weekly. Conclusion.  The three‐piece IPP has excellent 5‐year survival rates. Most patients return to sexual activity relatively quickly, with high frequency of usage of their prostheses. Henry GD, Brinkman MJ, Mead SF, Delk JR II, Cleves MA, Jennermann C, Wilson SK, and Kramer AC. A survey of patients with inflatable penile prostheses: Assessment of timing and frequency of intercourse and analysis of implant durability. J Sex Med 2012;9:1715–1721.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92055/1/j.1743-6109.2012.02729.x.pd

Stock market investors' use of stop losses and the disposition effect

The disposition effect is an investment bias where investors hold stocks at a loss longer than stocks at a gain. This bias is associated with poorer investment performance and exhibited to a greater extent by investors with less experience and less sophistication. A method of managing susceptibility to the bias is through use of stop losses. Using the trading records of UK stock market individual investors from 2006 to 2009, this paper shows that stop losses used as part of investment decisions are an effective tool for inoculating against the disposition effect. We also show that investors who use stop losses have less experience and that, when not using stop losses, these investors are more reluctant to realise losses than other investors

Subarachnoid versus General Anesthesia in Penile Prosthetic Implantation: Outcomes Analyses

The leading patient complaint during the perioperative period for penile prosthesis implantation is postoperative pain, while emesis and urticaria also affect the procedure’s perceived success. In analyzing surgical outcomes, assessment of the anesthetic for postoperative pain and side effects should be included. This paper retrospectively reviews 90 consecutive, primary inflatable penile prosthetic operations performed by a single surgeon at one private medical center. Fifty-seven patients were included in final analysis. Patients who had more than one procedure that day or who used chronic pain medication were excluded. The type and amount of each drug used for each respective side effect (within the first 24 hours after procedure) were compared to determine relative benefit. Twenty patients received general anesthesia (denoted herein as “GA”) and 37 received spinal (or also known as subarachnoid) anesthesia (denoted herein as “SA”). Patients receiving GA had significantly greater (P<0.0001) occurrence and amount of intravenous pain treatment than those receiving SA. Patients with SA required less intravenous pain medication and less treatment for nausea/emesis