Radioimmunotherapy confers long-term survival to lymphoma patients with acceptable toxicity: registry analysis by the international radioimmunotherapy network.

The Radioimmunotherapy Network (RIT-N) is a Web-based, international registry collecting long-term observational data about radioimmunotherapy-treated patients with malignant lymphoma outside randomized clinical studies. The RIT-N collects unbiased data on treatment indications, disease stages, patients' conditions, lymphoma subtypes, and hematologic side effects of radioimmunotherapy treatment. Methods: RIT-N is located at the University of Gottingen, Germany, and collected data from 14 countries. Data were entered by investigators into a Web-based central database managed by an independent clinical research organization. Results: Patients (1,075) were enrolled from December 2006 until November 2009, and 467 patients with an observation time of at least 12 mo were included in the following analysis. Diagnoses were as follows: 58% follicular lymphoma and 42% other B-cell lymphomas. The mean overall survival was 28 mo for follicular lymphoma and 26 mo for other lymphoma subtypes. Hematotoxicity was mild for hemoglobin (World Health Organization grade II), with a median nadir of 10 g/dL, but severe (World Health Organization grade III) for platelets and leukocytes, with a median nadir of 7,000/mu L and 2.2/mu L, respectively. Conclusion: Clinical usage of radioimmunotherapy differs from the labeled indications and can be assessed by this registry, enabling analyses of outcome and toxicity data beyond clinical trials. This analysis proves that radioimmunotherapy in follicular lymphoma and other lymphoma subtypes is a safe and efficient treatment option.

A regulatory network for the efficient control of transgene expression.

BACKGROUND: Expression of heterologous genes in mammalian cells or organisms for therapeutic or experimental purposes often requires tight control of transgene expression. Specifically, the following criteria should be met: no background gene activity in the off-state, high gene expression in the on-state, regulated expression over an extended period, and multiple switching between on- and off-states. METHODS: Here, we describe a genetic switch system for controlled transgene transcription using chimeric repressor and activator proteins functioning in a novel regulatory network. In the off-state, the target transgene is actively silenced by a chimeric protein consisting of multimerized eukaryotic transcriptional repression domains fused to the DNA-binding tetracycline repressor. In the on-state, the inducer drug doxycycline affects both the derepression of the target gene promoter and activation by the GAL4-VP16 transactivator, which in turn is under the control of an autoregulatory feedback loop. RESULTS: The hallmark of this new system is the efficient transgene silencing in the off-state, as demonstrated by the tightly controlled expression of the highly cytotoxic diphtheria toxin A gene. Addition of the inducer drug allows robust activation of transgene expression. In stably transfected cells, this control is still observed after months of repeated cycling between the repressed and activated states of the target genes. CONCLUSIONS: This system permits tight long-term regulation when stably introduced into cell lines. The underlying principles of this network system should have general applications in biotechnology and gene therapy.

Prévention quaternaire: agir est-il toujours justifié en médecine de famille [Quaternary prevention: is acting always justified in family medicine?].

Quaternary prevention aims to protect the patient or population against overmedicalisation. Quaternary prevention influences all the activities of family medicine by questioning the utility of primary prevention and early diagnosis, identifying the risks of creating new pathological entities and practicing a maximalist medicine. Family doctors can support quaternary prevention by focusing on their patients' priorities and the local resources of an efficient health system.

Soil infiltration based on bp neural network and grey relational analysis

Soil infiltration is a key link of the natural water cycle process. Studies on soil permeability are conducive for water resources assessment and estimation, runoff regulation and management, soil erosion modeling, nonpoint and point source pollution of farmland, among other aspects. The unequal influence of rainfall duration, rainfall intensity, antecedent soil moisture, vegetation cover, vegetation type, and slope gradient on soil cumulative infiltration was studied under simulated rainfall and different underlying surfaces. We established a six factor-model of soil cumulative infiltration by the improved back propagation (BP)-based artificial neural network algorithm with a momentum term and self-adjusting learning rate. Compared to the multiple nonlinear regression method, the stability and accuracy of the improved BP algorithm was better. Based on the improved BP model, the sensitive index of these six factors on soil cumulative infiltration was investigated. Secondly, the grey relational analysis method was used to individually study grey correlations among these six factors and soil cumulative infiltration. The results of the two methods were very similar. Rainfall duration was the most influential factor, followed by vegetation cover, vegetation type, rainfall intensity and antecedent soil moisture. The effect of slope gradient on soil cumulative infiltration was not significant.

Optimal network topologies for local search with congestion

The problem of searchability in decentralized complex networks is of great importance in computer science, economy, and sociology. We present a formalism that is able to cope simultaneously with the problem of search and the congestion effects that arise when parallel searches are performed, and we obtain expressions for the average search cost both in the presence and the absence of congestion. This formalism is used to obtain optimal network structures for a system using a local search algorithm. It is found that only two classes of networks can be optimal: starlike configurations, when the number of parallel searches is small, and homogeneous-isotropic configurations, when it is large.

Hierarchical neural network with high storage capacity

A recent method used to optimize biased neural networks with low levels of activity is applied to a hierarchical model. As a consequence, the performance of the system is strongly enhanced. The steps to achieve optimization are analyzed in detail.

Offer and use of complementary and alternative medicine in hospitals of the French-speaking part of Switzerland.

BACKGROUND: In 2004, complementary and alternative medicine (CAM) was offered by physicians in one-third of Swiss hospitals. Since then, CAM health policy has changed considerably. This study aimed to describe the present supply and use of CAM in hospitals in the French-speaking part of Switzerland, and to explore qualitatively the characteristics of this offer. METHODS: Between June 2011 and March 2012, a short questionnaire was sent to the medical directors of hospitals (n = 46), asking them whether CAM was offered, where and by whom. Then, a semi-directive interview was conducted with ten CAM therapists. RESULTS: Among 37 responses (return rate 80%), 19 medical directors indicated that their hospital offered at least one CAM and 18 reported that they did not. Acupuncture was the most frequently available CAM, followed by manual therapies, osteopathy and aromatherapy. The disciplines that offered CAM most frequently were rehabilitation, gynaecology and obstetrics, palliative care, psychiatry, and anaesthetics. In eight out of ten interviews, it appeared that the procedures for introducing a CAM in the hospital were not tightly supervised by the hospital and were mainly based on the goodwill of the therapists, rather than clinical/scientific evidence. CONCLUSION: The number of hospitals offering CAM in the French-speaking part of Switzerland seemed to have risen since 2004. The selection of a CAM to be offered in a hospital should be based on the same procedure of evaluation and validation as conventional therapy, and if the safety and efficiency of the CAM is evidence-based, it should receive the same resources as a conventional therapy.

Diffusion Spectrum Imaging after stroke shows structural changes in the contra-lateral motor network correlating with functional recovery

There is growing interest in understanding the role of the non-injured contra-lateral hemisphere in stroke recovery. In the experimental field, histological evidence has been reported that structural changes occur in the contra-lateral connectivity and circuits during stroke recovery. In humans, some recent imaging studies indicated that contra-lateral sub-cortical pathways and functional and structural cortical networks are remodeling, after stroke. Structural changes in the contra-lateral networks, however, have never been correlated to clinical recovery in patients. To determine the importance of the contra-lateral structural changes in post-stroke recovery, we selected a population of patients with motor deficits after stroke affecting the motor cortex and/or sub-cortical motor white matter. We explored i) the presence of Generalized Fractional Anisotropy (GFA) changes indicating structural alterations in the motor network of patientsâeuro? contra-lateral hemisphere as well as their longitudinal evolution ii) the correlation of GFA changes with patientsâeuro? clinical scores, stroke size and demographics data iii) and a predictive model.

Hwyneeds: Methodology, Analysis and Evaluation, March 2001

The quadrennial need study was developed to assist in identifying county highway financial needs (construction, rehabilitation, maintenance, and administration) and in the distribution of the road use tax fund (RUTF) among the counties in the state. During the period since the need study was first conducted using HWYNEEDS software, between 1982 and 1998, there have been large fluctuations in the level of funds distributed to individual counties. A recent study performed by Jim Cable (HR-363, 1993), found that one of the major factors affecting the volatility in the level of fluctuations is the quality of the pavement condition data collected and the accuracy of these data. In 1998, the Center for Transportation Research and Education researchers (Maze and Smadi) completed a project to study the feasibility of using automated pavement condition data collected for the Iowa Pavement Management Program (IPMP) for the paved county roads to be used in the HWYNEEDS software (TR-418). The automated condition data are objective and also more current since they are collected in a two year cycle compared to the 10-year cycle used by HWYNEEDS right now. The study proved the use of the automated condition data in HWYNEEDS would be feasible and beneficial in educing fluctuations when applied to a pilot study area. In another recommendation from TR-418, the researchers recommended a full analysis and investigation of HWYNEEDS methodology and parameters (for more information on the project, please review the TR-418 project report). The study reported in this document builds on the previous study on using the automated condition data in HWYNEEDS and covers the analysis and investigation of the HWYNEEDS computer program methodology and parameters. The underlying hypothesis for this study is thatalong with the IPMP automated condition data, some changes need to be made to HWYNEEDS parameters to accommodate the use of the new data, which will stabilize the process of allocating resources and reduce fluctuations from one quadrennial need study to another. Another objective of this research is to investigate the gravel roads needs and study the feasibility of developing a more objective approach to determining needs on the counties gravel road network. This study identifies new procedures by which the HWYNEEDS computer program is used to conduct the quadrennial needs study on paved roads. Also, a new procedure will be developed to determine gravel roads needs outside of the HWYNEED program. Recommendations are identified for the new procedures and also in terms of making changes to the current quadrennial need study. Future research areas are also identified.

Online teaching of inflammatory skin pathology by a French-speaking international university network

Introduction: Developments in technology, webbased teaching and whole slide imaging have broadened the teaching horizon in anatomic pathology. Creating online learning material including many types of media like radiologic images, videos, clinical and macroscopic photographs and whole slides imaging is now accessible to almost every university. Unfortunately, a major limiting factor to maintain and update the learning material is the amount of work, time and resources needed. In this perspective, a French national university network was initiated in 2011 to build mutualised online teaching pathology modules with clinical cases and tests. This network has been extended to an international level in 2012-2014 (Quebec, Switzerland and Ivory Coast). Method: One of the first steps of the international project was to build a learning module on inflammatory skin pathology intended for interns and residents of pathology and dermatology. A pathology resident from Quebec spent 6 weeks in France and Switzerland to develop the contents and build the module on an e-learning Moodle platform (http: //moodle.sorbonne-paris-cite.fr) under the supervision of two dermatopathologists (BV, MB). The learning module contains text, interactive clinical cases, tests with feedback, whole slides images (WSI), images and clinical photographs. For that module, the virtual slides are decentralized in 2 universities (Bordeaux and Paris 7). Each university is responsible of its own slide scanning, image storage and online display with virtual slide viewers. Results: The module on inflammatory skin pathology includes more than 50 web pages with French original content, tests and clinical cases, links to over 45 WSI and more than 50 micro and clinical photographs. The whole learning module is currently being revised by four dermatopathologists and two senior pathologists. It will be accessible to interns and residents in spring 2014. The experience and knowledge gained from that work will be transferred to the next international fellowship intern whose work will be aimed at creating lung and breast pathology learning modules. Conclusion: The challenges of sustaining a project of this scope are numerous. The technical aspect of whole-slide imaging and storage needs to be developed by each university or group. The content needs to be regularly updated, completed and its use and existence needs to be promoted by the different actors in pathology. Of the great benefits of that kind of project are the international partnerships and connections that have been established between numerous Frenchspeaking universities and pathologists with the common goals of promoting education in pathology and the use of technology including whole slide imaging. * The Moodle website is hosted by PRES Sorbonne Paris Cité, and financial supports for hardware have been obtained from UNF3S (http://www.unf3s.org/) and PRES Sorbonne Paris Cité. Financial support for international fellowships has been obtained from CFQCU (http://www.cfqcu.org/).

Extreme prematurity and intra uterine growth restriction effects in brain network topology at school age

Higher risk for long-term behavioral and emotional sequelae, with attentional problems (with or without hyperactivity) is now becoming one of the hallmarks of extreme premature (EP) birth and birth after pregancy conditions leading to poor intra uterine growth restriction (IUGR) [1,2]. However, little is know so far about the neurostructural basis of these complexe brain functional abnormalities that seem to have their origins in early critical periods of brain development. The development of cortical axonal pathways happens in a series of sequential events. The preterm phase (24-36 post conecptional weeks PCW) is known for being crucial for growth of the thalamocortical fiber bundles as well as for the development of long projectional, commisural and projectional fibers [3]. Is it logical to expect, thus, that being exposed to altered intrauterine environment (altered nutrition) or to extrauterine environment earlier that expected, lead to alterations in the structural organization and, consequently, alter the underlying white matter (WM) structure. Understanding rate and variability of normal brain development, and detect differences from typical development may offer insight into the neurodevelopmental anomalies that can be imaged at later stages. Due to its unique ability to non-invasively visualize and quantify in vivo white matter tracts in the brain, in this study we used diffusion MRI (dMRI) tractography to derive brain graphs [4,5,6]. This relatively simple way of modeling the brain enable us to use graph theory to study topological properties of brain graphs in order to study the effects of EP and IUGR on childrens brain connectivity at age 6 years old.

Traumatic Brain Injury in Iowa: Iowa Brain Injury Resource Network Outcome Evaluation 2007-2009, August 2011

Termed the “silent epidemic,” traumatic brain injury (TBI) is the most debilitating outcome of injury, and is characterized by the irreversibility of its damages, long-term effects on quality of life and healthcare costs. The latest data available from the CDC estimate that nationally, 52,000 people die each year from TBI2. In Iowa, TBI is a major public health problem. The numbers and rates of hospitalizations and emergency department (ED) visits due to TBIs are steadily increasing. From 2006 to 2008, there were on average 545 injury deaths per year. Among the injured Iowans, TBI constituted nearly 30 percent (545) of all injury deaths, ten percent (1,591) of people hospitalized and seven percent (17,696) of ED visitors. 3 The state of Iowa has been supporting secondary prevention services to TBI survivors for several years. An Iowa organization that has made a significant effort in assisting TBI survivors is the Brain Injury Association of Iowa (BIAIA). The BIAIA administers the IBIRN program in cooperation with the Iowa Department of Public Health (IDPH) through HRSA TBI Implementation grant funding and state appropriations.

Social network architecture and the maintenance of deleterious cultural traits.

How have changes in communications technology affected the way that misinformation spreads through a population and persists? To what extent do differences in the architecture of social networks affect the spread of misinformation, relative to the rates and rules by which individuals transmit or eliminate different pieces of information (cultural traits)? Here, we use analytical models and individual-based simulations to study how a 'cultural load' of misinformation can be maintained in a population under a balance between social transmission and selective elimination of cultural traits with low intrinsic value. While considerable research has explored how network architecture affects percolation processes, we find that the relative rates at which individuals transmit or eliminate traits can have much more profound impacts on the cultural load than differences in network architecture. In particular, the cultural load is insensitive to correlations between an individual's network degree and rate of elimination when these quantities vary among individuals. Taken together, these results suggest that changes in communications technology may have influenced cultural evolution more strongly through changes in the amount of information flow, rather than the details of who is connected to whom.

Light intensity modulates the regulatory network of the shade avoidance response in Arabidopsis.

Plants such as Arabidopsis thaliana respond to foliar shade and neighbors who may become competitors for light resources by elongation growth to secure access to unfiltered sunlight. Challenges faced during this shade avoidance response (SAR) are different under a light-absorbing canopy and during neighbor detection where light remains abundant. In both situations, elongation growth depends on auxin and transcription factors of the phytochrome interacting factor (PIF) class. Using a computational modeling approach to study the SAR regulatory network, we identify and experimentally validate a previously unidentified role for long hypocotyl in far red 1, a negative regulator of the PIFs. Moreover, we find that during neighbor detection, growth is promoted primarily by the production of auxin. In contrast, in true shade, the system operates with less auxin but with an increased sensitivity to the hormonal signal. Our data suggest that this latter signal is less robust, which may reflect a cost-to-robustness tradeoff, a system trait long recognized by engineers and forming the basis of information theory.