Location, location, location: the evolutionary history of CD1 genes and the NKR-P1/ligand systems

This is the final version. Available on open access from Springer Verlag via the DOI in this recordCD1 genes encode cell surface molecules that present lipid antigens to various kinds of T lymphocytes of the immune system. The structures of CD1 genes and molecules are like the major histocompatibility complex (MHC) class I system, the loading of antigen and the tissue distribution for CD1 molecules are like those in the class II system, and phylogenetic analyses place CD1 between class I and class II sequences, altogether leading to the notion that CD1 is a third ancient system of antigen presentation molecules. However, thus far, CD1 genes have only been described in mammals, birds and reptiles, leaving major questions as to their origin and evolution. In this review, we recount a little history of the field so far and then consider what has been learned about the structure and functional attributes of CD1 genes and molecules in marsupials, birds and reptiles. We describe the central conundrum of CD1 evolution, the genomic location of CD1 genes in the MHC and/or MHC paralogous regions in different animals, considering the three models of evolutionary history that have been proposed. We describe the natural killer (NK) receptors NKR-P1 and ligands, also found in different genomic locations for different animals. We discuss the consequence of these three models, one of which includes the repudiation of a guiding principle for the last 20 years, that two rounds of genome-wide duplication at the base of the vertebrates provided the extra MHC genes necessary for the emergence of adaptive immune system of jawed vertebrates

An international comparative study of blood pressure in populations of European vs. African descent

Background: The consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue. Methods: Using a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants). Results: The range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks. Conclusions: These data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated

Society for immunotherapy of cancer (SITC) statement on the proposed changes to the common rule

The Common Rule is a set of ethical principles that provide guidance on the management of human subjects taking part in biomedical and behavioral research in the United States. The elements of the Common Rule were initially developed in 1981 following a revision of the Declaration of Helsinki in 1975. Most academic facilities follow the Common Rule in the regulation of clinical trials research. Recently, the government has suggested a revision of the Common Rule to include more contemporary and streamlined oversight of clinical research. In this commentary, the leadership of the Society for Immunotherapy of Cancer (SITC) provides their opinion on this plan. While the Society recognizes the considerable contribution of clinical research in supporting progress in tumor immunotherapy and supports the need for revisions to the Common Rule, there is also some concern over certain elements which may restrict access to biospecimens and clinical data at a time when high throughput technologies, computational biology and assay standardization is allowing major advances in understanding cancer biology and providing potential predictive biomarkers of immunotherapy response. The Society values its professional commitment to patients for improving clinical outcomes with tumor immunotherapy and supports continued discussion with all stakeholders before implementing changes to the Common Rule in order to ensure maximal patient protections while promoting continued clinical research at this historic time in cancer research

Studies of lifetimes in an ion storage ring using laser technique

The laser-probing method for lifetime measurements of metastable levels, performed by applying the Fast Ion Beam Laser (FIBLAS) method to ions stored in a storage ring, has been developed by the Stockholm group. Recently, we have applied this method to lifetime measurements of close lying metastable levels. In this paper we discuss experimental studies of ions with complex structure and present the first experimentally obtained lifetimes of selected metastable levels in complex systems as Fe+, Eu+ and La+

Successful Internalization of a Chronic Biliary Cutaneous Fistula After Liver Transplantation: Deepithelializing the Fistula Tract

Biliary cutaneous fistulas are uncommon sequelae after biliary surgery and can be a source of significant morbidity. We describe a liver recipient who developed a biliary cutaneous fistula secondary to hepatic artery thrombosis; this subsequently drained for over 7 years. Through a novel approach, using the transabdominal fistula tract as a conduit, the fistula skin opening was deepithelialized and anastomosed to a jejunal loop, internally draining the tract. For over 7 years postoperatively, this internal drainage procedure has continued to function effectively. This approach may have value in internalizing longstanding biliary cutaneous fistulas in well-selected patients in whom there is no existing biliary ductal system or the existing system anatomically does not lend itself to restoration of functional internal drainage through conventional approaches

Trichotillometry: the reliability and practicality of hair pluckability as a method of nutritional assessment

<p>Abstract</p> <p>Background</p> <p>A nutritional assessment method that is quick and easy to conduct would be extremely useful in a complex emergency, where currently there is no agreed practical and acceptable method. Hair pluckability has been suggested to be a useful method of assessing protein nutritional status. The aim was to investigate the reliability of the trichotillometer and to explore the effects of patient characteristics on hair epilation force.</p> <p>Methods</p> <p>Three observers plucked hair from twelve participants to investigate the within- and between-observer reliability. To investigate the effect of patient characteristics on hair pluckability, 12 black African and 12 white volunteers were recruited. Participants completed a short questionnaire to provide basic information on their characteristics and hair.</p> <p>Results</p> <p>Mean hair pluckability measurements for the 12 participants obtained by the three observers (39.5 g, 41.2 g and 32.7 g) were significantly different (p < 0.001). Significant variation between patients was also found (p < 0.001). None of the patient characteristics significantly affected hair pluckability, with the exception of age, although this relationship was not consistent.</p> <p>Conclusion</p> <p>Due to significant variation in measurements, hair pluckability does not appear to be a reliable method for assessing adult nutritional status. Hair pluckability could be a useful method of nutritional assessment in complex humanitarian emergencies but only if the reliability was improved.</p

Patterns of Clinical Response with Talimogene Laherparepvec (T-VEC) in Patients with Melanoma Treated in the OPTiM Phase III Clinical Trial

PURPOSE: Talimogene laherparepvec (T-VEC) is an oncolytic immunotherapy designed to induce tumor regression of injected lesions through direct lytic effects, and of uninjected lesions through induction of systemic antitumor immunity. In this study, we describe the patterns and time course of response to T-VEC from the phase III OPTiM trial of 436 patients with unresected stages IIIB–IV melanoma. METHODS: Lesion-level response analyses were performed based on the type of lesion (injected or uninjected cutaneous, subcutaneous, or nodal lesions; or visceral lesions [uninjected]), and the best percentage change from baseline of the sum of products of the longest diameters was calculated. Patients randomized to T-VEC (n = 295) who experienced a durable response (continuous partial or complete response for ≥6 months) were evaluated for progression prior to response (PPR), defined as the appearance of a new lesion or >25 % increase in total baseline tumor area. RESULTS: T-VEC resulted in a decrease in size by ≥50 % in 64 % of injected lesions (N = 2116), 34 % of uninjected non-visceral lesions (N = 981), and 15 % of visceral lesions (N = 177). Complete resolution of lesions occurred in 47 % of injected lesions, 22 % of uninjected non-visceral lesions, and 9 % of visceral lesions. Of 48 patients with durable responses, 23 (48 %) experienced PPR, including 14 who developed new lesions only. No difference in overall survival was observed, and median duration of response was not reached in patients with PPR versus those without PPR. CONCLUSIONS: Responses in uninjected lesions provide validation of T-VEC-induced systemic immunotherapeutic effects against melanoma. PPR did not negatively impact the clinical effectiveness of T-VEC. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1245/s10434-016-5286-0) contains supplementary material, which is available to authorized users

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in Williams syndrome

There is increasing evidence that Williams syndrome (WS) is associated with elevated anxiety that is non-social in nature, including generalised anxiety and fears. To date very little research has examined the cognitive processes associated with this anxiety. In the present research, attentional bias for non-social threatening images in WS was examined using a dot-probe paradigm. Participants were 16 individuals with WS aged between 13 and 34 years and two groups of typically developing controls matched to the WS group on chronological age and attentional control ability respectively. The WS group exhibited a significant attention bias towards threatening images. In contrast, no bias was found for group matched on attentional control and a slight bias away from threat was found in the chronological age matched group. The results are contrasted with recent findings suggesting that individuals with WS do not show an attention bias for threatening faces and discussed in relation to neuroimaging research showing elevated amygdala activation in response to threatening non-social scenes in WS

Virtual interactive musculoskeletal system (VIMS) in orthopaedic research, education and clinical patient care

The ability to combine physiology and engineering analyses with computer sciences has opened the door to the possibility of creating the "Virtual Human" reality. This paper presents a broad foundation for a full-featured biomechanical simulator for the human musculoskeletal system physiology. This simulation technology unites the expertise in biomechanical analysis and graphic modeling to investigate joint and connective tissue mechanics at the structural level and to visualize the results in both static and animated forms together with the model. Adaptable anatomical models including prosthetic implants and fracture fixation devices and a robust computational infrastructure for static, kinematic, kinetic, and stress analyses under varying boundary and loading conditions are incorporated on a common platform, the VIMS (Virtual Interactive Musculoskeletal System). Within this software system, a manageable database containing long bone dimensions, connective tissue material properties and a library of skeletal joint system functional activities and loading conditions are also available and they can easily be modified, updated and expanded. Application software is also available to allow end-users to perform biomechanical analyses interactively. Examples using these models and the computational algorithms in a virtual laboratory environment are used to demonstrate the utility of these unique database and simulation technology. This integrated system, model library and database will impact on orthopaedic education, basic research, device development and application, and clinical patient care related to musculoskeletal joint system reconstruction, trauma management, and rehabilitation

Identifying discrete behavioural types: A re-analysis of public goods game contributions by hierarchical clustering

We propose a framework for identifying discrete behavioural types in experimental data. We re-analyse data from six previous studies of public goods voluntary contributions games. Using hierarchical clustering analysis, we construct a typology of behaviour based on a simi- larity measure between strategies. We identify four types with distinct sterotypical behaviours, which together account for about 90% of participants. Compared to previous approaches, our method produces a classification in which different types are more clearly distinguished in terms of strategic behaviour and the resulting economic implications