Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

Autologous non-myeloablative haemopoietic stem cell transplantation in relapsing-remitting multiple sclerosis: a phase I/II study

Background Autologous non-myeloablative haemopoietic stem cell transplantation is a method to deliver intense immune suppression. We evaluated the safety and clinical outcome of autologous non-myeloablative haemopoietic stem cell transplantation in patients with retapsing-remitting multiple sclerosis (MS) who had not responded to treatment with interferon beta. Methods Eligible patients had relapsing-remitting MS, attended Northwestern Memorial Hospital, and despite treatment with interferon beta had had two corticosteroid-treated relapses within the previous 12 months, or one relapse and gadolinium-enhancing lesions seen on MRI and separate from the relapse. Peripheral blood haemopoietic stem cells were mobilised with 2 g per m(2) cyclophosphamide and 10 mu g per kg per day filgrastim. The conditioning regimen for the haemopoietic stem cells was 200 mg per kg cyclophosphamide and either 20 mg alemtuzumab or 6 mg per kg rabbit antithymocyte globulin. Primary outcomes were progression-free survival and reversal of neurological disability at 3 years post-transplantation. We also sought to investigate the safety and tolerability of autologous non-myeloablative haemopoietic stem cell transplantation. Findings Between January 2003, and February, 2005, 21 patients were treated. Engraftment of white blood cells and platelets was on median day 9 (range day 8-11) and patients were discharged from hospital on mean day 11 (range day 8-13). One patient had diarrhoea due to Clostridium difficile and two patients had dermatomal zoster. Two of the 17 patients receiving alemtuzumab developed late immune thrombocytopenic purpura that remitted with standard therapy. 17 of 21 patients (81%) improved by at least 1 point on the Kurtzke expanded disability status scale (EDSS), and five patients (24%) relapsed but achieved remission after further immunosuppression. After a mean of 37 months (range 24-48 months), all patients were free from progression (no deterioration in EDSS score), and 16 were free of relapses. Significant improvements were noted in neurological disability, as determined by EDSS score (p<0.0001), neurological rating scale score (p=0.0001), paced auditory serial addition test (p=0.014), 25-foot walk (p<0.0001), and quality of life, as measured with the short form-36 (SF-36) questionnaire (p<0.0001). Interpretation Non-myeloablative autologous haemopoietic stem cell transplantation in patients with relapsing-remitting MS reverses neurological deficits, but these results need to be confirmed in a randomised trial.

Nomenclature for congenital and paediatric cardiac disease: Historical perspectives and The International Pediatric and Congenital Cardiac Code

Clinicians working in the field of congenital and paediatric cardiology have long felt the need for a common diagnostic and therapeutic nomenclature and coding system with which to classify patients of all ages with congenital and acquired cardiac disease. A cohesive and comprehensive system of nomenclature, suitable for setting a global standard for multicentric analysis of outcomes and stratification of risk, has only recently emerged, namely, The International Paediatric and Congenital Cardiac Code. This review, will give an historical perspective on the development of systems of nomenclature in general, and specifically with respect to the diagnosis and treatment of patients with paediatric and congenital cardiac disease. Finally, current and future efforts to merge such systems into the paperless environment of the electronic health or patient record on a global scale are briefly explored. On October 6, 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. In January, 2005, the International Nomenclature Committee was constituted in Canada as The International Society for Nomenclature of Paediatric and Congenital Heart Disease. This International Society now has three working groups. The Nomenclature Working Group developed The International Paediatric and Congenital Cardiac Code and will continue to maintain, expand, update, and preserve this International Code. It will also provide ready access to the International Code for the global paediatric and congenital cardiology and cardiac surgery communities, related disciplines, the healthcare industry, and governmental agencies, both electronically and in published form. The Definitions Working Group will write definitions for the terms in the International Paediatric and Congenital Cardiac Code, building on the previously published definitions from the Nomenclature Working Group. The Archiving Working Group, also known as The Congenital Heart Archiving Research Team, will link images and videos to the International Paediatric and Congenital Cardiac Code. The images and videos will be acquired from cardiac morphologic specimens and imaging modalities such as echocardiography, angiography, computerized axial tomography and magnetic resonance imaging, as well as intraoperative images and videos. Efforts are ongoing to expand the usage of The International Paediatric and Congenital Cardiac Code to other areas of global healthcare. Collaborative efforts are under-way involving the leadership of The International Nomenclature Committee for Pediatric and Congenital Heart Disease and the representatives of the steering group responsible for the creation of the 11th revision of the International Classification of Diseases, administered by the World Health Organisation. Similar collaborative efforts are underway involving the leadership of The International Nomenclature Committee for Pediatric and Congenital Heart Disease and the International Health Terminology Standards Development Organisation, who are the owners of the Systematized Nomenclature of Medicine or ""SNOMED"". The International Paediatric and Congenital Cardiac Code was created by specialists in the field to name and classify paediatric and congenital cardiac disease and its treatment. It is a comprehensive code that can be freely downloaded from the internet (http://www.IPCCC.net) and is already in use worldwide, particularly for international comparisons of outcomes. The goal of this effort is to create strategies for stratification of risk and to improve healthcare for the individual patient. The collaboration with the World Heath Organization, the International Health Terminology Standards Development Organisation, and the healthcare Industry, will lead to further enhancement of the International Code, and to Its more universal use.

Treatment of a Class II subdivision malocclusion with multiple congenitally missing teeth

This case report describes the treatment of a patient with a Class II Division 1 subdivision right malocclusion with 8 congenitally missing teeth, incompetent lips, and incisor protrusion. The treatment plan included extractions and space closure with retraction of the anterior teeth; symmetric mechanics were used in the mandibular arch and asymmetric mechanics in the maxillary arch. Because of the mechanics used, some midline deviations were expected. Knowledge of diagnosis and treatment planning of asymmetric malocclusions and dental esthetics are essential for success when correcting asymmetic problems, but, even so, small clinical compromises should be expected. (Am J Orthod Dentofacial Orthop 2009; 135: 663-70)

14-3-3 acts as an intramolecular bridge to regulate cdc25B localization and activity

One of the major regulators of mitosis in somatic cells is cdc25B. cdc25B is tightly regulated at multiple levels. The final activation step involves the regulated binding of 14-3-3 proteins. Previous studies have demonstrated that Ser-323 is a primary 14-3-3 binding site in cdc25B, which influences its activity and cellular localization. 14-3-3 binding to this site appeared to interact with the N-terminal domain of cdc25B to regulate its activity. The presence of consensus 14-3-3 binding sites in the N-terminal domain suggested that the interaction is through direct binding of the 14-3-3 dimer to sites in the N-terminal domain. We have identified Ser-151 and Ser-230 in the N-terminal domain as functional 14-3-3 binding sites utilized by cdc25B in vivo. These low affinity sites cooperate to bind the 14-3-3 dimer bound to the high affinity Ser-323 site, thus forming an intramolecular bridge that constrains cdc25B structure to prevent access of the catalytic site. Loss of 14-3-3 binding to either N-terminal site relaxes cdc25B structure sufficiently to permit access to the catalytic site, and the nuclear export sequence located in the N-terminal domain. Mutation of the Ser-323 site was functionally equivalent to the mutation of all three sites, resulting in the complete loss of 14-3-3 binding, increased access of the catalytic site, and access to nuclear localization sequence.

Non-selective optical wavelength-division multiplexing devices based on a-SiC:H multilayer heterostuctures

In this paper we present results on the optimization of multilayered a-SiC:H heterostructures for wavelength-division (de) multiplexing applications. The non selective WDM device is a double heterostructure in a glass/ITO/a-SiC:H (p-i-n) /a-SiC:H(-p) /a-Si:H(-i')/a-SiC:H (-n')/ITO configuration. The single or the multiple modulated wavelength channels are passed through the device, and absorbed accordingly to its wavelength, giving rise to a time dependent wavelength electrical field modulation across it. The effect of single or multiple input signals is converted to an electrical signal to regain the information (wavelength, intensity and frequency) of the incoming photogenerated carriers. Here, the (de) multiplexing of the channels is accomplished electronically, not optically. This approach offers advantages in terms of cost since several channels share the same optical components; and the electrical components are typically less expensive than the optical ones. An electrical model gives insight into the device operation.

Permanent vascular access in patients with end-stage renal disease, Brazil

OBJECTIVE: To assess factors associated with the establishment of permanent vascular access for patients with end-stage renal disease. METHODS: Cross-sectional study conducted in a nationally representative sample of Brazilian end-stage renal disease patients in dialysis and transplant centers during 2007. The sample comprised only patients who received hemodialysis as a primary therapy modality and reported the type of vascular access for their primary hemodialysis treatment (N=2,276). Data were from the TRS Project - "Economic and Epidemiologic Evaluation of Modalities of Renal Replacement Therapy in Brazil". Multiple logistic regression analysis was used to assess factors associated with the establishment of permanent vascular access in these patients. RESULTS: About 30% of the patients studied had an arteriovenous vascular access. The following factors were associated with a lower likelihood of having an arteriovenous vascular access as a primary type of access: time of hemodialysis start since the diagnosis of chronic renal failure < 1 year; shorter dialysis therapy; having no private health insurance; living in the central-western, northeastern and southeastern regions of Brazil; and living in the northern region plus having no private health insurance. In the final model there was found a positive association between the outcome and pre-dialysis care and no were association with socioeconomic and comorbidity variables. CONCLUSIONS: The study results showed that the focus should on pre-dialysis care to increase the establishment of an arteriovenous vascular access before starting hemodialysis in Brazil.

Internet based VRS Code Positioning

Absolute positioning – the real time satellite based positioning technique that relies solely on global navigation satellite systems – lacks accuracy for several real time application domains. To provide increased positioning quality, ground or satellite based augmentation systems can be devised, depending on the extent of the area to cover. The underlying technique – multiple reference station differential positioning – can, in the case of ground systems, be further enhanced through the implementation of the virtual reference station concept. Our approach is a ground based system made of a small-sized network of three stations where the concept of virtual reference station was implemented. The stations provide code pseudorange corrections, which are combined using a measurement domain approach inversely proportional to the distance from source station to rover. All data links are established trough the Internet.

TDBS: a time division beacon scheduling mechanism for ZigBee cluster-tree wireless sensor networks

Synchronization is a challenging and important issue for time-sensitive Wireless Sensor Networks (WSN) since it requires a mutual spatiotemporal coordination between the nodes. In that concern, the IEEE 802.15.4/ZigBee protocols embody promising technologies for WSNs, but are still ambiguous on how to efficiently build synchronized multiple-cluster networks, specifically for the case of cluster-tree topologies. In fact, the current IEEE 802.15.4/ZigBee specifications restrict the synchronization to beacon-enabled (by the generation of periodic beacon frames) star networks, while they support multi-hop networking in mesh topologies, but with no synchronization. Even though both specifications mention the possible use of cluster-tree topologies, which combine multi-hop and synchronization features, the description on how to effectively construct such a network topology is missing. This paper tackles this issue by unveiling the ambiguities regarding the use of the cluster-tree topology and proposing a synchronization mechanism based on Time Division Beacon Scheduling (TDBS) to build cluster-tree WSNs. In addition, we propose a methodology for efficiently managing duty-cycles in every cluster, ensuring the fairest use of bandwidth resources. The feasibility of the TDBS mechanism is clearly demonstrated through an experimental test-bed based on our open-source implementation of the IEEE 802.15.4/ZigBee protocols.

Static-priority scheduling over wireless networks with multiple broadcast domains

We propose a wireless medium access control (MAC) protocol that provides static-priority scheduling of messages in a guaranteed collision-free manner. Our protocol supports multiple broadcast domains, resolves the wireless hidden terminal problem and allows for parallel transmissions across a mesh network. Arbitration of messages is achieved without the notion of a master coordinating node, global clock synchronization or out-of-band signaling. The protocol relies on bit-dominance similar to what is used in the CAN bus except that in order to operate on a wireless physical layer, nodes are not required to receive incoming bits while transmitting. The use of bit-dominance efficiently allows for a much larger number of priorities than would be possible using existing wireless solutions. A MAC protocol with these properties enables schedulability analysis of sporadic message streams in wireless multihop networks.

Deported Mexican migrants: health status and access to care

OBJECTIVE To describe the health status and access to care of forced-return Mexican migrants deported through the Mexico-United States border and to compare it with the situation of voluntary-return migrants. METHODS Secondary data analysis from the Survey on Migration in Mexico’s Northern Border from 2012. This is a continuous survey, designed to describe migration flows between Mexico and the United States, with a mobile-population sampling design. We analyzed indicators of health and access to care among deported migrants, and compare them with voluntary-return migrants. Our analysis sample included 2,680 voluntary-return migrants, and 6,862 deportees. We employ an ordinal multiple logistic regression model, to compare the adjusted odds of having worst self-reported health between the studied groups. RESULTS As compared to voluntary-return migrants, deportees were less likely to have medical insurance in the United States (OR = 0.05; 95%CI 0.04;0.06). In the regression model a poorer self-perceived health was found to be associated with having been deported (OR = 1.71, 95%CI 1.52;1.92), as well as age (OR = 1.03, 95%CI 1.02;1.03) and years of education (OR = 0.94 95%CI 0.93;0.95). CONCLUSIONS According to our results, deportees had less access to care while in the United States, as compared with voluntary-return migrants. Our results also showed an independent and statistically significant association between deportation and having poorer self-perceived health. To promote the health and access to care of deported Mexican migrants coming back from the United States, new health and social policies are required.

Collision-free prioritized medium access in the presence of hidden nodes without relying on out-of-band signaling

Consider the problem of sharing a wireless channel between a set of computer nodes. Hidden nodes exist and there is no base station. Each computer node hosts a set of sporadic message streams where a message stream releases messages with real-time deadlines. We propose a collision-free wireless medium access control (MAC) protocol which implements staticpriority scheduling. The MAC protocol allows multiple masters and is fully distributed. It neither relies on synchronized clocks nor out-of-band signaling; it is an adaptation to a wireless channel of the dominance protocol used in the CAN bus. But unlike that protocol, our protocol does not require a node having the ability to receive an incoming bit from the channel while transmitting to the channel. Our protocol has the key feature of not only being prioritized and collision-free but also dealing successfully with hidden nodes. This key feature enables schedulability analysis of sporadic message streams in multihop networks.

Collision-free prioritized medium access control in wireless networks with hidden nodes

We propose a collision-free medium access control (MAC) protocol, which implements static-priority scheduling and works in the presence of hidden nodes. The MAC protocol allows multiple masters and is fully distributed; it is an adaptation to a wireless channel of the dominance protocol used in the CAN bus. But unlike that protocol, our protocol does not require a node having the ability to sense the channel while transmitting to the channel. Our protocol is collision-free even in the presence of hidden nodes and it achieves this without synchronized clocks or out-of-band busy tones. In addition, the protocol is designed to ensure that many non-interfering nodes can transmit in parallel and it functions for both broadcast and unicast transmissions.

Enabling Global Experiments With Interactive Reconfiguration And Steering By Multiple Users

In global scientific experiments with collaborative scenarios involving multinational teams there are big challenges related to data access, namely data movements are precluded to other regions or Clouds due to the constraints on latency costs, data privacy and data ownership. Furthermore, each site is processing local data sets using specialized algorithms and producing intermediate results that are helpful as inputs to applications running on remote sites. This paper shows how to model such collaborative scenarios as a scientific workflow implemented with AWARD (Autonomic Workflow Activities Reconfigurable and Dynamic), a decentralized framework offering a feasible solution to run the workflow activities on distributed data centers in different regions without the need of large data movements. The AWARD workflow activities are independently monitored and dynamically reconfigured and steering by different users, namely by hot-swapping the algorithms to enhance the computation results or by changing the workflow structure to support feedback dependencies where an activity receives feedback output from a successor activity. A real implementation of one practical scenario and its execution on multiple data centers of the Amazon Cloud is presented including experimental results with steering by multiple users.

Access to continued-use medication among older adults, Brazil

OBJECTIVE To determine the prevalence and associated access factors for all continued-use prescription drugs and the ways in which they can be obtained.METHODS Data was obtained from the 2008 Household National Survey. The sample comprised 27,333 individuals above 60 years who reported that they used continued-use prescription drugs. A descriptive analysis and binary and multiple multinomial logistic regressions were performed.RESULTS 86.0% of the older adults had access to all the medication they needed, and among them, 50.7% purchased said medication. Those who obtained medication from the public health system were younger (60-64 years), did not have health insurance plans, and belonged to the lower income groups. It is remarkable that 14.0% of the subjects still had no access to any continued-use medication, and for those with more than four chronic diseases, this amount reached 22.0%. Those with a greater number of chronic diseases ran a higher risk of not having access to all the medication they needed.CONCLUSIONS There are some groups of older adults with an increased risk of not obtaining all the medication they need and of purchasing it. The results of this study are expected to contribute to guide programs and plans for access to medication in Brazil.