Discovery of O-linked carbohydrate on HIV-1 envelope and its role in shielding against one category of broadly neutralizing antibodies

Approximately 50% of the mass of the Envelope (Env) glycoprotein surface subunit (gp120) of human immunodeficiency virus type 1 (HIV-1) is composed of N-linked carbohydrate. Until now, the dogma has been that HIV-1 lacks O-linked carbohydrate on Env. Here we show that a subset of patient-derived HIV-1 isolates contain O-linked carbohydrate on the variable 1 (V1) domain of Env gp120. We demonstrate the presence of this O-glycosylation both on virions and on gp120 expressed as a secreted protein. Further, we establish that these O-linked glycans can confer a more than 1,000-fold decrease in neutralization sensitivity (IC50) to V3-glycan broadly neutralizing antibodies. These findings uncover a structural modification to the HIV-1 Env and suggest a functional role in promoting viral escape from one category of broadly neutralizing antibodies

Effects of tutor-related behaviours on the process of problem-based learning

Tutors in a Problem-Based Learning (PBL) curriculum are thought to play active roles in guiding students to develop frameworks for use in the construction of knowledge. This implies that both subject-matter expertise and the ability of tutors to facilitate the learning process must be important in helping students learn. This study examines the behavioural effects of tutors in terms of subject-matter expertise, social congruence and cognitive congruence on students’ learning process and on their final achievement. The extent of students’ learning at each PBL phase was estimated by tracking the number of relevant concepts recalled at the end of each learning phase, while student achievement was based on students’ ability to describe and elaborate upon the relationship between relevant concepts learned. By using Analysis of Covariance, social congruence of the tutor was found to have a significant influence on learning in each PBL phase while all of the tutor-related behaviours had a significant impact on student achievement. The results suggest that the ability of tutors to communicate informally with students and hence create a less threatening learning environment that promotes a free flow exchange of ideas, has a greater impact on learning at each of the PBL phases as compared to tutors’ subject-matter expertise and their ability to explain concepts in a way that is easily understood by students. The data presented indicates that these tutor-related behaviours are determinants of learning in a PBL curriculum, with social congruence having a greater influence on learning in the different PBL phases

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Symptoms associated with victimization in patients with schizophrenia and related disorders

Background: Patients with psychoses have an increased risk of becoming victims of violence. Previous studies have suggested that higher symptom levels are associated with a raised risk of becoming a victim of physical violence. There has been, however, no evidence on the type of symptoms that are linked with an increased risk of recent victimization. Methods: Data was taken from two studies on involuntarily admitted patients, one national study in England and an international one in six other European countries. In the week following admission, trained interviewers asked patients whether they had been victims of physical violence in the year prior to admission, and assessed symptoms on the Brief Psychiatric Rating Scale (BPRS). Only patients with a diagnosis of schizophrenia or related disorders (ICD-10 F20–29) were included in the analysis which was conducted separately for the two samples. Symptom levels assessed on the BPRS subscales were tested as predictors of victimization. Univariable and multivariable logistic regression models were fitted to estimate adjusted odds ratios. Results: Data from 383 patients in the English sample and 543 patients in the European sample was analysed. Rates of victimization were 37.8% and 28.0% respectively. In multivariable models, the BPRS manic subscale was significantly associated with victimization in both samples. Conclusions: Higher levels of manic symptoms indicate a raised risk of being a victim of violence in involuntary patients with schizophrenia and related disorders. This might be explained by higher activity levels, impaired judgement or poorer self-control in patients with manic symptoms. Such symptoms should be specifically considered in risk assessments

Quality and Safety Aspects of Infant Nutrition

Quality and safety aspects of infant nutrition are of key importance for child health, but oftentimes they do not get much attention by health care professionals whose interest tends to focus on functional benefits of early nutrition. Unbalanced diets and harmful food components induce particularly high risks for untoward effects in infants because of their rapid growth, high nutrient needs, and their typical dependence on only one or few foods during the first months of life. The concepts, standards and practices that relate to infant food quality and safety were discussed at a scientific workshop organized by the Child Health Foundation and the Early Nutrition Academy jointly with the European Society for Paediatric Gastroenterology, Hepatology and Nutrition, and a summary is provided here. The participants reviewed past and current issues on quality and safety, the role of different stakeholders, and recommendations to avert future issues. It was concluded that a high level of quality and safety is currently achieved, but this is no reason for complacency. The food industry carries the primary responsibility for the safety and suitability of their products, including the quality of composition, raw materials and production processes. Introduction of new or modified products should be preceded by a thorough science based review of suitability and safety by an independent authority. Food safety events should be managed on an international basis. Global collaboration of food producers, food-safety authorities, paediatricians and scientists is needed to efficiently exchange information and to best protect public health. Copyright (C) 2012 S. Karger AG, Base

Improving community ambulation after stroke: the AMBULATE trial

<p>Abstract</p> <p>Background</p> <p>It has been reported that following rehabilitation, only 7% of stroke survivors are able to walk at a level commensurate with community participation. Previous research indicates that treadmill and overground walking training can improve walking capacity in people living in the community after stroke. The main objectives of the AMBULATE trial are to determine (i) whether a 4-month treadmill walking program is more effective than a 2-month program, compared to control, in improving walking capacity, health and community participation and (ii) the "threshold" walking speed that results in sufficient walking capacity that makes walking self-sustaining.</p> <p>Methods/Design</p> <p>A prospective randomised controlled trial of unsupported treadmill training with a 12 month follow-up with concealed allocation and blinded assessment will be conducted. 210 community-dwelling people after stroke who are able to walk independently but slowly will be recruited and randomly allocated to either a 4 month training group, 2 month training group or the control (no intervention) group. Intervention for the two training groups will occur 3 days per week for 30 minutes each session. Measurements of walking, health and community participation will be taken at baseline, 2 months, 4 months, 6 months and 12 months. This study has obtained ethical approval from the relevant Human Research Ethics Committees.</p> <p>Discussion</p> <p>By improving stroke survivors' walking ability, it is likely also to improve their general wellbeing by promoting better health and greater community participation. Furthermore, if stroke survivors can reach a point where their walking and community participation is self-sustaining, this will reduce the burden of care on family and friends as well as the economic burden on the health system. Given the major demographic shift in developed nations involving significant growth in the aged population, this research will make an important evidence-based contribution to the promotion of healthy ageing.</p> <p>Trial registration</p> <p>This trial is registered with the Australian New Zealand Clinical Trials Registry, (ACTRN012607000227493)</p

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

The influence of foot geometry on the calcaneal osteotomy angle based on two-dimensional static force analyses

Background: Malalignment of the hindfoot can be corrected with a calcaneal osteotomy (CO). A well-selected osteotomy angle in the sagittal plane will reduce the shear force in the osteotomy plane while walking. The purpose was to determine the presence of a relationship between the foot geometry and loading of the calcaneus, which influences the choice of the preferred CO angle. Methods A static free body force analysis was made of the posterior calcaneal fragment in the second half of the stance phase to determine the main loads: the plantar apeunorosis (PA) and Achilles tendon (AT). The third load is on the osteotomy surface which should be oriented such that the shear component of the force is zero. The force direction of the PA and AT was measured on 58 MRIs of the foot, and the force ratio between both structures was taken from the literature. In addition the PA-to-AT force ratio was estimated for different foot geometries to identify the relationship. Results: Based on the wish to minimize the shear force during walking, a mean CO angle was determined to be 33º (SD8) relative to the foot sole. In pes planus foot geometry, the angle should be higher than the mean. In pes cavus foot geometry, the angle should be smaller. Conclusion: Foot geometry, in particular the relative foot heights is a determinant for the individual angle in performing the sliding calcaneal osteotomy. It is recommended to take into account the foot geometry (arch) when deciding on the CO angle for hindfoot correction.Biomechanical EngineeringMechanical, Maritime and Materials Engineerin

Non-invasive Predictors of Human Cortical Bone Mechanical Properties: T2-Discriminated 1H NMR Compared with High Resolution X-ray

Recent advancements in magnetic resonance imaging (MRI) have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. To this end, 1H nuclear magnetic resonance (NMR) and high-resolution X-ray signals from human cortical bone samples were correlated with mechanical properties of bone. Results showed that 1H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These 1H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk

The AIDS and Cancer Specimen Resource: Role in HIV/AIDS scientific discovery

The AIDS Cancer and Specimen Resource (ACSR) supports scientific discovery in the area of HIV/AIDS-associated malignancies. The ACSR was established as a cooperative agreement between the NCI (Office of the Director, Division of Cancer Treatment and Diagnosis) and regional consortia, University of California, San Francisco (West Coast), George Washington University (East Coast) and Ohio State University (Mid-Region) to collect, preserve and disperse HIV-related tissues and biologic fluids and controls along with clinical data to qualified investigators. The available biological samples with clinical data and the application process are described on the ACSR web site. The ACSR tissue bank has more than 100,000 human HIV positive specimens that represent different processing (43), specimen (15), and anatomical site (50) types. The ACSR provides special biospecimen collections and prepares speciality items, e.g., tissue microarrays (TMA), DNA libraries. Requests have been greatest for Kaposi's sarcoma (32%) and non-Hodgkin's lymphoma (26%). Dispersed requests include 83% tissue (frozen and paraffin embedded), 18% plasma/serum and 9% other. ACSR also provides tissue microarrays of, e.g., Kaposi's sarcoma and non-Hodgkin's lymphoma, for biomarker assays and has developed collaborations with other groups that provide access to additional AIDS-related malignancy specimens. ACSR members and associates have completed 63 podium and poster presentations. Investigators have submitted 125 letters of intent requests. Discoveries using ACSR have been reported in 61 scientific publications in notable journals with an average impact factor of 7. The ACSR promotes the scientific exploration of the relationship between HIV/AIDS and malignancy by participation at national and international scientific meetings, contact with investigators who have productive research in this area and identifying, collecting, preserving, enhancing, and dispersing HIV/AIDS-related malignancy specimens to funded, approved researchers at no fee. Scientific discovery has been advanced by this unique biorepository. Investigators are encouraged to browse the ACSR Internet site for materials to enhance their own scientific initiatives