Automation of absolute protein-ligand binding free energy calculations for docking refinement and compound evaluation.

Absolute binding free energy calculations with explicit solvent molecular simulations can provide estimates of protein-ligand affinities, and thus reduce the time and costs needed to find new drug candidates. However, these calculations can be complex to implement and perform. Here, we introduce the software BAT.py, a Python tool that invokes the AMBER simulation package to automate the calculation of binding free energies for a protein with a series of ligands. The software supports the attach-pull-release (APR) and double decoupling (DD) binding free energy methods, as well as the simultaneous decoupling-recoupling (SDR) method, a variant of double decoupling that avoids numerical artifacts associated with charged ligands. We report encouraging initial test applications of this software both to re-rank docked poses and to estimate overall binding free energies. We also show that it is practical to carry out these calculations cheaply by using graphical processing units in common machines that can be built for this purpose. The combination of automation and low cost positions this procedure to be applied in a relatively high-throughput mode and thus stands to enable new applications in early-stage drug discovery.

Modelo computacional interactivo, semi-automatizado y de código abierto aplicado a la vigilancia de virus respiratorios / Interactive, semi-automatized and open source computational model applied to respiratory viruses surveillance

Resumen Las infecciones respiratorias agudas (IRA) causadas por virus son una importante causa de morbilidad y mortalidad en el mundo, afectando principalmente a niños y adultos mayores. Se asocian a un alto número de consultas y hospitalizaciones, a una significativa sobrecarga del sistema de salud y a un alto costo económico. La vigilancia de virus respiratorios tiene el potencial de ayudar a optimizar la respuesta sanitaria, garantizar la disponibilidad de recursos humanos, racionalizar los recursos y disminuir los costos asociados a la atención en salud. Con el objetivo de optimizar la recolección y visualización de los datos de nuestro actual sistema de vigilancia de virus respiratorios, se diseñó una plataforma basada en R y sus paquetes Shiny, que permite la creación de una interfase web interactiva y amigable para la recolección, análisis y publicación de los datos. Se ingresaron a esta plataforma los datos de la red de vigilancia metropolitana de virus respiratorios disponibles desde 2006. En esta plataforma, el investigador demora menos de un minuto en registrar los datos. El análisis y publicación es inmediato, llegando a cualquier usuario con un dispositivo conectado a Internet, quien puede elegir las variables a consultar. Con un costo muy bajo, en poco tiempo y utilizando el lenguaje de programación R, se logró crear un sistema simple e interactivo, disminuyendo el tiempo de carga y análisis de datos de forma considerable, posiblemente aumentando el impacto y la disponibilidad de esta vigilancia.

Abstract Acute respiratory infections (ARI) are an important cause of morbidity and mortality worldwide, affecting mainly children and the elderly. They are associated with a high economic burden, increased number of medical visits and hospitalizations. The surveillance of the circulation of respiratory viruses can reduce the health care associated costs, and to optimize the health response. A platform based on R and its package Shiny was designed, to create an interactive and friendly web interface for gathering, analysis and publication of the data. The data from the Chilean metropolitan respiratory viruses surveillance network, available since 2006, was uploaded into the platform. Using this platform, the researcher spends less than 1 minute to upload the data, and the analysis and publication is immediate, available to be seen by any user with a device connected to Internet, who can choose the variables to be displayed. With a very low cost, in a short time, and using the R programming language, it was possible to create a simple, and interactive platform, considerably decreasing the upload and analysis time, and increasing the impact and availability of this surveillance.

Should You Buy a Three-Dimensional Printer? A Study of an Orbital Fracture.

The use of three-dimensional (3D) printing has been growing significantly in medicine for the past 10 years, especially in maxillofacial surgery. A lot a different softwares and printers are available on the market, and it can be difficult to choose which one fits best one's needs. In the authors' institution, the authors regularly print orbits to prepare the reconstruction. The authors then compared the 3D printing of an orbital fracture between a professional and nonprofessional software and between a bottom of the range and a more elaborated printer. The results show that there is a wide variation between the quality of the printing, as well as the time used for the preparation. Costs between free or professional software must also be considered. In conclusion, an analysis of needs and what is available on the market must be studied before investing in 3D printing.

The Methodological Quality and Effectiveness of Technology-Based Smoking Cessation Interventions for Disadvantaged Groups: A Systematic Review and Meta-analysis.

Aims: To assess the methodological quality and effectiveness of technology-based smoking cessation interventions in disadvantaged groups. Method: Four databases (EMBASE, Cochrane, Medline, and PsycInfo) were searched for studies conducted from 1980 to May 2016. Randomized controlled trials that compared a behavioral smoking cessation intervention delivered primarily through a technology-based platform (eg, mobile phone) with a no-intervention comparison group among disadvantaged smokers were included. Three reviewers assessed all relevant studies for inclusion, and one reviewer extracted study, participant and intervention-level data, with a subset crosschecked by a second reviewer. Results: Thirteen studies targeting disadvantaged smokers (n =4820) were included. Only one study scored highly in terms of methodological rigor on EPOC criteria for judging risk of bias. Of the 13 studies using a technology-based platform, most utilized websites (n = 5) or computer programs (n = 5), and seven additionally offered nicotine replacement therapy. Technology-based interventions increased the odds of smoking cessation for disadvantaged groups at 1 month (odds ratio [OR] 1.70, 95% confidence interval [CI] 1.10, 2.63), 3 months (OR 1.30, 95% CI 1.07, 1.59), 6 months (OR 1.29, 95% CI 1.03, 1.62), and 18 months post-intervention (OR 1.83, 95% CI 1.11, 3.01). Conclusion: Few methodologically rigorous studies were identified. Mobile phone text-messaging, computer- and website-delivered quit support showed promise at increasing quit rates among Indigenous, psychiatric and inpatient substance use disorder patients. Further research is needed to address the role technology-based interventions have on overcoming health inequalities to meet the needs of disadvantaged groups. Implications: This review provides the first quantitative evidence of the effectiveness of a range of technology-based smoking cessation interventions among disadvantaged smokers, with separate estimates on the basis of intervention type, and cessation outcome measure. Providing cost-effective, easily accessible and real-time smoking cessation treatment is needed, and innovative technology-based platforms will help reach this endpoint. These interventions need to be tested in larger scale randomized controlled trial designs and target broader disadvantaged groups. Data collection beyond 6 months is also needed in order to establish the efficacy of these intervention approaches on long-term cessation rates among disadvantaged population groups.

Simulation training for medical emergencies in the dental setting using an inexpensive software application.

INTRODUCTION: Every dental provider needs to be educated about medical emergencies to provide safe dental care. Simulation training is available with simulators such as advanced life support manikins and robot patients. However, the purchase and development costs of these simulators are high. We have developed a simulation training course on medical emergencies using an inexpensive software application. The purpose of this study was to evaluate the educational effectiveness of this course. MATERIALS AND METHODS: Fifty-one dental providers participated in this study from December 2014 to March 2015. Medical simulation software was used to simulate a patient's vital signs. We evaluated participants' ability to diagnose and treat vasovagal syncope or anaphylaxis with an evaluation sheet and conducted a questionnaire before and after the scenario-based simulation training. RESULTS: The median evaluation sheet score for vasovagal syncope increased significantly from 7/9 before to 9/9 after simulation training. The median score for anaphylaxis also increased significantly from 8/12 to 12/12 (P < .01). For the item "I can treat vasovagal syncope/anaphylaxis adequately," the percentage responding "Strongly agree" or "Agree" increased from 14% to 56% for vasovagal syncope and from 6% to 42% for anaphylaxis with simulation training. CONCLUSIONS: This simulation course improved participants' ability to diagnose and treat medical emergencies and improved their confidence. This course can be offered inexpensively using a software application.

Does semi-automatic bone-fragment segmentation improve the reproducibility of the Letournel acetabular fracture classification?

BACKGROUND: The Letournel classification of acetabular fracture shows poor reproducibility in inexperienced observers, despite the introduction of 3D imaging. We therefore developed a method of semi-automatic segmentation based on CT data. The present prospective study aimed to assess: (1) whether semi-automatic bone-fragment segmentation increased the rate of correct classification; (2) if so, in which fracture types; and (3) feasibility using the open-source itksnap 3.0 software package without incurring extra cost for users. HYPOTHESIS: Semi-automatic segmentation of acetabular fractures significantly increases the rate of correct classification by orthopedic surgery residents. METHODS: Twelve orthopedic surgery residents classified 23 acetabular fractures. Six used conventional 3D reconstructions provided by the center's radiology department (conventional group) and 6 others used reconstructions obtained by semi-automatic segmentation using the open-source itksnap 3.0 software package (segmentation group). Bone fragments were identified by specific colors. Correct classification rates were compared between groups on Chi2 test. Assessment was repeated 2 weeks later, to determine intra-observer reproducibility. RESULTS: Correct classification rates were significantly higher in the "segmentation" group: 114/138 (83%) versus 71/138 (52%); P<0.0001. The difference was greater for simple (36/36 (100%) versus 17/36 (47%); P<0.0001) than complex fractures (79/102 (77%) versus 54/102 (53%); P=0.0004). Mean segmentation time per fracture was 27±3min [range, 21-35min]. The segmentation group showed excellent intra-observer correlation coefficients, overall (ICC=0.88), and for simple (ICC=0.92) and complex fractures (ICC=0.84). CONCLUSION: Semi-automatic segmentation, identifying the various bone fragments, was effective in increasing the rate of correct acetabular fracture classification on the Letournel system by orthopedic surgery residents. It may be considered for routine use in education and training. LEVEL OF EVIDENCE: III: prospective case-control study of a diagnostic procedure.

Virtual Bronchoscopy Using OsiriX.

BACKGROUND: Although the utility of virtual bronchoscopy has been reported, the software for virtual bronchoscopy has not been popular because of the high cost. OsiriX is a reasonably priced software that is available to reconstruct virtual endoscopic images. Herein, we present the ability of OsiriX to enable virtual bronchoscopy. METHODS: Computed tomography of the chest was performed using a 16-row multidetector. Data in 2 mm slices from one lung were obtained from 10 patients with a lung nodule. Virtual bronchoscopic images were established by OsiriX version 5.5 (32-bit). To examine the ability to visualize small bronchi, we tried to visualize the distal bronchus if possible. We selected B and B for the right lung and B and B for the left lung. In addition, to predict whether a pathologic diagnosis can successfully be made by transbronchial lung biopsy, we reconstructed virtual bronchoscopic images toward the lung nodule. RESULTS: Bronchoscopic images were successfully reconstructed for all patients. The third to the seventh bronchi were visualized except in one patient whose right B was occluded by a tumor. In all patients, the virtual bronchoscopic path reached the lung nodule, and 5 lung nodules were successfully diagnosed by transbronchial biopsy. CONCLUSIONS: OsiriX is practicable for virtual bronchoscopy at a low cost.

REGSTATTOOLS: freeware statistical tools for the analysis of disease population databases used in health and social studies.

BACKGROUND: The repertoire of statistical methods dealing with the descriptive analysis of the burden of a disease has been expanded and implemented in statistical software packages during the last years. The purpose of this paper is to present a web-based tool, REGSTATTOOLShttp://regstattools.net intended to provide analysis for the burden of cancer, or other group of disease registry data. Three software applications are included in REGSTATTOOLS: SART (analysis of disease's rates and its time trends), RiskDiff (analysis of percent changes in the rates due to demographic factors and risk of developing or dying from a disease) and WAERS (relative survival analysis). RESULTS: We show a real-data application through the assessment of the burden of tobacco-related cancer incidence in two Spanish regions in the period 1995-2004. Making use of SART we show that lung cancer is the most common cancer among those cancers, with rising trends in incidence among women. We compared 2000-2004 data with that of 1995-1999 to assess percent changes in the number of cases as well as relative survival using RiskDiff and WAERS, respectively. We show that the net change increase in lung cancer cases among women was mainly attributable to an increased risk of developing lung cancer, whereas in men it is attributable to the increase in population size. Among men, lung cancer relative survival was higher in 2000-2004 than in 1995-1999, whereas it was similar among women when these time periods were compared. CONCLUSIONS: Unlike other similar applications, REGSTATTOOLS does not require local software installation and it is simple to use, fast and easy to interpret. It is a set of web-based statistical tools intended for automated calculation of population indicators that any professional in health or social sciences may require.

Interactive multicentre teleconferences using open source software in a team of thoracic surgeons.

Real-time consultation between a team of thoracic surgeons is important for the management of difficult cases. We established a system for interactive teleconsultation between multiple sites, based on open-source software. The graphical desktop-sharing system VNC (virtual network computing) was used for remotely controlling another computer. An image-processing package (OsiriX) was installed on the server to share the medical images. We set up a voice communication system using Voice Chatter, a free, cross-platform voice communication application. Four hospitals participated in the trials. One was connected by gigabit ethernet, one by WiMAX and one by ADSL. Surgeons at three of the sites found that it was comfortable to view images and consult with each other using the teleconferencing system. However, it was not comfortable using the client that connected via WiMAX, because of dropped frames. Apart from the WiMAX connection, the VNC-based screen-sharing system transferred the clinical images efficiently and in real time. We found the screen-sharing software VNC to be a good application for medical image interpretation, especially for a team of thoracic surgeons using multislice CT scans.

Effectiveness and cost-effectiveness of computer and other electronic aids for smoking cessation: a systematic review and network meta-analysis.

BACKGROUND: Smoking is harmful to health. On average, lifelong smokers lose 10 years of life, and about half of all lifelong smokers have their lives shortened by smoking. Stopping smoking reverses or prevents many of these harms. However, cessation services in the NHS achieve variable success rates with smokers who want to quit. Approaches to behaviour change can be supplemented with electronic aids, and this may significantly increase quit rates and prevent a proportion of cases that relapse. OBJECTIVE: The primary research question we sought to answer was: What is the effectiveness and cost-effectiveness of internet, pc and other electronic aids to help people stop smoking? We addressed the following three questions: (1) What is the effectiveness of internet sites, computer programs, mobile telephone text messages and other electronic aids for smoking cessation and/or reducing relapse? (2) What is the cost-effectiveness of incorporating internet sites, computer programs, mobile telephone text messages and other electronic aids into current nhs smoking cessation programmes? and (3) What are the current gaps in research into the effectiveness of internet sites, computer programs, mobile telephone text messages and other electronic aids to help people stop smoking? DATA SOURCES: For the effectiveness review, relevant primary studies were sought from The Cochrane Library [Cochrane Central Register of Controlled Trials (CENTRAL)] 2009, Issue 4, and MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Health Management Information Consortium (HMIC) (Ovid) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost) from 1980 to December 2009. In addition, NHS Economic Evaluation Database (NHS EED) and Database of Abstracts of Reviews of Effects (DARE) were searched for information on cost-effectiveness and modelling for the same period. Reference lists of included studies and of relevant systematic reviews were examined to identify further potentially relevant studies. Research registries of ongoing studies including National Institute for Health Research (NIHR) Clinical Research Network Portfolio Database, Current Controlled Trials and ClinicalTrials.gov were also searched, and further information was sought from contacts with experts. REVIEW METHODS: Randomised controlled trials (RCTs) and quasi-RCTs evaluating smoking cessation programmes that utilise computer, internet, mobile telephone or other electronic aids in adult smokers were included in the effectiveness review. Relevant studies of other design were included in the cost-effectiveness review and supplementary review. Pair-wise meta-analyses using both random- and fixed-effects models were carried out. Bayesian mixed-treatment comparisons (MTCs) were also performed. A de novo decision-analytical model was constructed for estimating the cost-effectiveness of interventions. Expected value of perfect information (EVPI) was calculated. Narrative synthesis of key themes and issues that may influence the acceptability and usability of electronic aids was provided in the supplementary review. RESULTS: This effectiveness review included 60 RCTs/quasi-RCTs reported in 77 publications. Pooled estimate for prolonged abstinence [relative risk (RR) = 1.32, 95% confidence interval (CI) 1.21 to 1.45] and point prevalence abstinence (RR = 1.14, 95% CI 1.07 to 1.22) suggested that computer and other electronic aids increase the likelihood of cessation compared with no intervention or generic self-help materials. There was no significant difference in effect sizes between aid to cessation studies (which provide support to smokers who are ready to quit) and cessation induction studies (which attempt to encourage a cessation attempt in smokers who are not yet ready to quit). Results from MTC also showed small but significant intervention effect (time to relapse, mean hazard ratio 0.87, 95% credible interval 0.83 to 0.92). Cost-threshold analyses indicated some form of electronic intervention is likely to be cost-effective when added to non-electronic behavioural support, but there is substantial uncertainty with regard to what the most effective (thus most cost-effective) type of electronic intervention is, which warrants further research. EVPI calculations suggested the upper limit for the benefit of this research is around £ 2000-3000 per person. LIMITATIONS: The review focuses on smoking cessation programmes in the adult population, but does not cover smoking cessation in adolescents. Most available evidence relates to interventions with a single tailored component, while evidence for different modes of delivery (e.g. e-mail, text messaging) is limited. Therefore, the findings of lack of sufficient evidence for proving or refuting effectiveness should not be regarded as evidence of ineffectiveness. We have examined only a small number of factors that could potentially influence the effectiveness of the interventions. A comprehensive evaluation of potential effect modifiers at study level in a systematic review of complex interventions remains challenging. Information presented in published papers is often insufficient to allow accurate coding of each intervention or comparator. A limitation of the cost-effectiveness analysis, shared with several previous cost-effectiveness analyses of smoking cessation interventions, is that intervention benefit is restricted to the first quit attempt. Exploring the impact of interventions on subsequent attempts requires more detailed information on patient event histories than is available from current evidence. CONCLUSIONS: Our effectiveness review concluded that computer and other electronic aids increase the likelihood of cessation compared with no intervention or generic self-help materials, but the effect is small. The effectiveness does not appear to vary with respect to mode of delivery and concurrent non-electronic co-interventions. Our cost-effectiveness review suggests that making some form of electronic support available to smokers actively seeking to quit is highly likely to be cost-effective. This is true whether the electronic intervention is delivered alongside brief advice or more intensive counselling. The key source of uncertainty is that around the comparative effectiveness of different types of electronic interventions. Our review suggests that further research is needed on the relative benefits of different forms of delivery for electronic aids, the content of delivery, and the acceptability of these technologies for smoking cessation with subpopulations of smokers, particularly disadvantaged groups. More evidence is also required on the relationship between involving users in the design of interventions and the impact this has on effectiveness, and finally on how electronic aids developed and tested in research settings are applied in routine practice and in the community.

Mobile applications for dermatology.

The number of available mobile applications has increased by 500% over the past 3 years. Searching for useful dermatology applications may be overwhelming. The following summary may help both advanced and budding dermatologists select useful programs.

Environmental causes of breast cancer and radiation from medical imaging: findings from the Institute of Medicine report.

Susan G. Komen for the Cure asked the Institute of Medicine (IOM) to perform a comprehensive review of environmental causes and risk factors for breast cancer. Interestingly, none of the consumer products (ie, bisphenol A, phthalates), industrial chemicals (ie, benzene, ethylene oxide), or pesticides (ie, DDT/DDE) considered could be conclusively linked to an increased risk of breast cancer, although the IOM acknowledged that the available evidence was insufficient to draw firm conclusions for many of these exposures, calling for more research in these areas. The IOM found sufficient evidence to conclude that the 2 environmental factors most strongly associated with breast cancer were exposure to ionizing radiation and to combined postmenopausal hormone therapy. The IOM's conclusion of a causal relation between radiation exposure and cancer is consistent with a large and varied literature showing that exposure to radiation in the same range as used for computed tomography will increase the risk of cancer. It is the responsibility of individual health care providers who order medical imaging to understand and weigh the risk of any medical procedures against the expected benefit.

Implementation of a configurable laboratory information management system for use in cellular process development and manufacturing.

BACKGROUND AIMS: Regulatory requirements for the manufacturing of cell products for clinical investigation require a significant level of record-keeping, starting early in process development and continuing through to the execution and requisite follow-up of patients on clinical trials. Central to record-keeping is the management of documentation related to patients, raw materials, processes, assays and facilities. METHODS: To support these requirements, we evaluated several laboratory information management systems (LIMS), including their cost, flexibility, regulatory compliance, ongoing programming requirements and ability to integrate with laboratory equipment. After selecting a system, we performed a pilot study to develop a user-configurable LIMS for our laboratory in support of our pre-clinical and clinical cell-production activities. We report here on the design and utilization of this system to manage accrual with a healthy blood-donor protocol, as well as manufacturing operations for the production of a master cell bank and several patient-specific stem cell products. RESULTS: The system was used successfully to manage blood donor eligibility, recruiting, appointments, billing and serology, and to provide annual accrual reports. Quality management reporting features of the system were used to capture, report and investigate process and equipment deviations that occurred during the production of a master cell bank and patient products. CONCLUSIONS: Overall the system has served to support the compliance requirements of process development and phase I/II clinical trial activities for our laboratory and can be easily modified to meet the needs of similar laboratories.

Medical teleconference about thoracic surgery using free Internet software.

Surgical teleconferences using advanced academic networks are becoming common; however, reports regarding Internet teleconferencing using free software packages such as Skype, USTREAM, and Dropbox are very rare. Teleconferences concerning mainly surgical techniques were held five times between Fukuoka University Hospital and other institutions from April to September 2010. These teleconferences used Skype and USTREAM as videophones to establish communication. Both PowerPoint presentations and surgical videos were made. These presentation files were previously sent to all stations via mail, e-mail, or Dropbox, and shared. A slide-show was simultaneously performed following the presenter's cue in each station. All teleconferences were successfully completed, even though there were minor instances of the Skype link being broken for unknown reasons during the telecommunication. Internet surgical teleconferences using ordinary software are therefore considered to be sufficiently feasible. This method will become more convenient and common as the Internet environments advance.