Concurrent SPECT/PET-CT imaging as a method for tracking adoptively transferred T-cells in vivo

BACKGROUND: The ability of T-cells to traffic to and penetrate tumors impacts the clinical efficacy of T-cell therapy therefore methods to track transferred T-cells in vivo are needed. In this preliminary report, we evaluated the use of concurrent SPECT/PET-CT imaging to monitor the egress of HER-2/neu specific T-cells in a breast cancer patient with extensive bone-only metastatic disease. FINDINGS: Indium (In-111) labeled T-cells demonstrated similar or greater viability than unlabeled T-cells at either a low or high dose of In-111 over a 24-h incubation period in vitro. The function of labeled or unlabeled T-cells was not significantly different (p > 0.05) at either dose. T-cells trafficked to all sites of metastatic disease and infiltrated the tumor as assessed by SPECT imaging. In-111 uptake at 24 h after infusion varied from 3.8 (right proximal humerus) to 6.3 (right sacrum) background corrected counts per pixel and remained elevated at 48 h. Concurrent PET-CT imaging demonstrated a fluorodeoxyglucose flare, measured by increase in tumor site uptake as high as 32 % and at most sites of disease at 48 h. This flare was associated with focal pain after T-cell infusion at metastatic sites. The patient had stable disease for 18 months after completion of T-cell therapy. CONCLUSION: Concurrent SPECT/PET-CT imaging, over a 48-h period after T-cell infusion, provided evidence of T-cell homing to all disease sites as well as a tumor metabolism flare response. This technique may be useful for monitoring T-cell trafficking after autologous as well as chimeric antigen receptor T-cell infusion. TRIAL REGISTRAION: Trial registered at ClinicalTrials.gov registration number NCT00791037, registered 13 November 2008

Functional diversity of marine ecosystems after the Late Permian mass extinction event

Article can be accessed from http://www.nature.com/ngeo/journal/v7/n3/full/ngeo2079.htmlThe Late Permian mass extinction event was the most severe such crisis of the past 500 million years and occurred during an episode of global warming. It is assumed to have had significant ecological impact, but its effects on marine ecosystem functioning are unknown and the patterns of marine recovery are debated. We analysed the fossil occurrences of all known Permian-Triassic benthic marine genera and assigned each to a functional group based on their inferred life habit. We show that despite the selective extinction of 62-74% of marine genera there was no significant loss of functional diversity at the global scale, and only one novel mode of life originated in the extinction aftermath. Early Triassic marine ecosystems were not as ecologically depauperate as widely assumed, which explains the absence of a Cambrian-style Triassic radiation in higher taxa. Functional diversity was, however, significantly reduced in particular regions and habitats, such as tropical reefs, and at these scales recovery varied spatially and temporally, probably driven by migration of surviving groups. Marine ecosystems did not return to their pre-extinction state, however, and radiation of previously subordinate groups such as motile, epifaunal grazers led to greater functional evenness by the Middle Triassic

Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement

Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source

Dynamic Fibrillar Assembly of αb-Crystallin Induced by Perturbation of the Conserved NT-IXI Motif Resolved by Cryo-Em

αB-crystallin is an archetypical member of the small heat-shock proteins (sHSPs) vital for cellular proteostasis and mitigating protein misfolding diseases. Gaining insights into the principles defining their molecular organization and chaperone function have been hindered by intrinsic dynamic properties and limited high-resolution structural analysis. To disentangle the mechanistic underpinnings of these dynamical properties, we mutated a conserved IXI-motif located within the N-terminal (NT) domain of human αB-crystallin. This resulted in a profound structural transformation, from highly polydispersed caged-like native assemblies into a comparatively well-ordered helical fibril state amenable to high-resolution cryo-EM analysis. The reversible nature of the induced fibrils facilitated interrogation of functional effects due to perturbation of the NT-IXI motif in both the native-like oligomer and fibril states. Together, our investigations unveiled several features thought to be key mechanistic attributes to sHSPs and point to a critical significance of the NT-IXI motif in αB-crystallin assembly, dynamics and chaperone activity

A descriptive study of International Special Olympic athletes\u27 vision care needs

Three hundred-seventy International Special Olympics participants and 115 staff members representing 39 countries participated . in a vision screening conducted by 32 members of the \u27 American Optometric Association\u27s Sports . Vision and/or Low Vision Sections during the 1991 International. Special Olympics, held in Minneapolis/St. Paul. The. program also included emergency eyecare services and educational· benefits relating to the role of vision in athletic and life performance. An age-matched population of normal nonathlete students were · compared on several measures of visual sensitivity and visual-motor performance. Results of the program substantiated the findings of the 1984-86 Oregon · State Special Olympics vision care program. An unmet need for comprehensive eyecare exists within the International Special Olympics population. Areas of greatest concern include the large number of competitors\u27 never having received vision care, nearly 113 of\u27 the athletes participate with uncompensated or. residual refractive error, and the increased risk of ocular trauma resulting from lack of · eye protection requirement

Feasibility study of a randomised controlled trial to investigate the effectiveness of using a humanoid robot to improve the social skills of children with an Autism Spectrum Disorder (Kaspar RCT): A Study Protocol

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http:// creativecommons. org/licenses/ by/ 4.0/Introduction: Interventions using robot-assisted therapy may be beneficial for the social skills development of children with autism spectrum disorder (ASD), however randomised controlled trials (RCTs) are lacking. The present research aims to assess the feasibility of conducting a RCT evaluating the effectiveness of a social skills intervention using the robot ‘Kaspar’ with children with ASD. Methods and analysis: Forty children will be recruited. Inclusion criteria are: aged 5-10 years, confirmed ASD diagnosis, IQ over 70, English language comprehension, a carer who can complete questionnaires in English, and no current participation in a private social communication intervention. Children will be randomised to receive an intervention with a therapist and Kaspar, or with the therapist only. They will receive two familiarisation sessions and six treatment sessions over eight weeks. They will be assessed at baseline, and at 10-weeks and 22-weeks after baseline. The primary outcome of this study is to evaluate whether the pre-determined feasibility criteria for a full-scale trial are met. The potential primary outcome measures for a full-scale trial are the Social Communication Questionnaire (SCQ) and the Social Skills Improvement System (SSIS). We will conduct a preliminary economic analysis. After the study has ended, a sample of twenty participants and their families will be invited to participate in semi-structured interviews to explore the feasibility and acceptability of the study’s methods and intervention. Ethics and dissemination: Parents/carers will provide informed consent, and children will give assent, where appropriate. Care will be taken to avoid pressure or coercion to participate. Aftercare is available from the recruiting NHS Trust and a phased withdrawal protocol will be followed if children become excessively attached to the robot. The results of the study will be disseminated to academic audiences and non-academic stakeholders, e.g. families of children with ASD, support groups, clinicians and charities. Registration details: ISRCTN14156001.Peer reviewe

Challenging the knowledge-transfer orthodoxy: Knowledge co-construction in technology-enhanced learning for children with autism

Experimental intervention studies constitute the current dominant research designs in the autism education field. Such designs are based on a ‘knowledge-transfer’ model of evidence-based practice in which research is conducted by researchers, and is then ‘transferred’ to practitioners to enable them to implement evidence-based interventions. While these research designs contribute important knowledge, they lead to a gap between what the research evidence may prescribe and what happens in practice, with a concomitant disparity between the priorities of researchers and practitioners. This paper discusses findings from the ESRC-funded ‘SHAPE’ project, which adopted a different model of evidence-based practice, focusing on knowledge co-construction. Pupils (N = 8), teachers (N = 10), a speech and language therapist and a parent in three different school communities investigated creative ways in which children's social communication skills could be enhanced through technology use. Through a participatory methodology, digital stories were used as a method to enable engagement with the practical realities of the classroom and empower practitioners to construct and share their own authentic narratives. Participants articulated precise knowledge about the learning opportunities afforded to them and their pupils through quality interactions that were mediated by the technologies, as evidenced through digital stories. The SHAPE project shows that it is feasible to develop methodologies that enable genuine knowledge co-construction with school practitioners, parents and pupils. Such co-construction could offer realistic opportunities for pedagogical emancipation and innovation in evidence-based practice as an alternative to the currently dominant and narrow model of knowledge transfer

Comparative study of the blind spot locations between right and left eyes

A study of the blind spots of 42 college students revealed no clinically significant difference in their location when comparing the right eye to the left eye. The mean difference at the nerve head is zero, with an absolute standard deviation of the difference equal to 0.46. This finding demonstrates the high degree of symmetry in the location of the blind spots for individual subjects

A barreira costeira holocênica e suas relações com a morfodinâmica praial no Estado do Rio Grande do Sul, Brasil

A análise dos parâmetros morfométricos publicados buscou relacionar o comportamento morfodinâmico praial com o da barreira costeira holocênica no estado do Rio Grande do Sul (RS), para estabelecer de que maneira estes ambientes estão relacionados. Foram analisados os dados de 31 praias, de Torres ao Chuí, possibilitando uma revisão e reavaliação dos estágios morfodinâmicos, com a compartimentação destes locais em cinco grupos, baseados em sua morfodinâmica e mobilidade praial. O grupo 1 é composto pelas praias intermediárias de mobilidade moderada à alta, que estão em sua maioria localizadas no litoral médio do RS correspondente a barreira agradacional, com alto desenvolvimento de campos de dunas transgressivas e dunas frontais, e estão também associadas às praias com característica retrogradante da barreira, porção sul da barreira agradacional. O grupo 2 compõe as praias dissipativas, com estágio intermediário ocorrendo de maneira secundária, de moderada à alta mobilidade, associadas a barreira progradante do litoral norte. Este setor apesar de apresentar alto potencial de transporte sedimentar por ventos e por ondas não apresenta campos de dunas bem desenvolvidos, onde o aporte sedimentar favorece a progradação costeira. O grupo 3 é formado por praias intermediárias de baixa mobilidade, associadas à porção norte da barreira agradacional e às praias do litoral sul que representam a transição entre a barreira progradante e retrogradante. No litoral médio a associação da baixa mobilidade praial com a alta capacidade de transporte e disponibilidade sedimentar, resultante do transporte sedimentar pelo vento no sentido continental, permitiu o desenvolvimento de grandes campos de dunas transgressivos e de dunas frontais. O grupo 4 é constituído por praias dissipativas e secundariamente intermediárias, de baixa mobilidade, da barreira progradante do litoral sul, que não desenvolveu vastos campos de dunas, semelhante ao que ocorre na barreira progradante ao norte. O grupo 5 é formado por duas praias diferenciadas, onde o estágio intermediário predomina e o refletivo ocorre eventualmente no verão, e estão localizadas em barreiras retrogradantes. As praias dissipativas são responsáveis por remobilizar o maior volume sedimentar da antepraia ao ambiente praial, onde integra o processo de progradação costeira. A porção da barreira agradacional, responsável pelas maiores dunas frontais, apresenta a menor mobilidade, sendo que conforme sua mobilidade é aumentada em direção ao sul, os maiores campos de dunas transgressivas ocorrem. Os estágios intermediários possuem energia suficiente para transportar sedimentos da antepraia para a praia, enquanto que a formação ou não das dunas é influenciada pelo potencial de transporte do vento NE e pela orientação da linha de costa com relação a este vento. As barreiras retrogradantes estão associadas a estágios intermediários de mobilidade variável, sendo que os dois focos erosivos do estado estão associados à alta mobilidade, o qual deixa estes ambientes susceptíveis aos episódios de erosão durante a passagem de eventos de tempestades. Assim, o caráter erosivo da barreira pode estar associado tanto com a energia de ondas, quanto com uma antepraia irregular e um déficit sedimentar, que acarreta em variações na morfodinâmica praial.The analysis of the morphometric parameters of the published works about beach morphodynamics in the State of Rio Grande do Sul had the objective to relate the morphodynamic behavior of the beach with the holocene coastal barrier, in order to establish how these environments are related. The data of 31 beaches were analyzed, allowing a review and reevaluation of the morphodynamic stages, with the compartmentalization of these sites in five groups, based on their morphodynamics and beach mobility. Group 1 is composed of intermediate beaches with moderate to high mobility, which are located in the middle coast corresponding to the aggradational barrier, with high development of transgressive dunes and foredunes, and, associated too with the beaches with retrogradational characteristics of the barrier. Group 2 consists of dissipative beaches, with intermediate stage occurring in a secondary way, being these from moderate to high mobility, associated with the progradational barrier of the north coast. This sector, despite to present a high potential for sediment transport by winds and waves, does not have well development dunefields, where the sediment budget supports coastal progradation. Group 3 is formed by intermediate beaches of low mobility, associated with the northern portion of the aggradational barrier and the beaches of the south coast that represent the transition between the prograded and retrograded barrier. In the middle coast, the association of low beach mobility with high transport capacity and sedimentary availability, and the resulting of the sedimentary transport by wind onshore, allowed the development of large transgressive dunefields and foredunes. Group 4 consists of dissipative and secondarily intermediate beaches, with low mobility, of the progradational barrier of the south coast, which, similar to what occurs in the progradational barrier of the north, did not develop largest dune fields. Group 5 is formed by two beaches with peculiar characteristics, where the intermediate stage predominates and the reflective occurs eventually in the summer, associated with the retrograded barrier. The dissipative beaches are responsible for remobilizing highs sediments volumes of the shoreface and provide to the beach environment, where, in this case, it is converted into coastal progradation. The portion of the aggradational barrier responsible for the largest frontal dunes presents the smaller mobility, and as its mobility is increased towards the south, the largest transgressive dunefields in the state occurs. The intermediate stages have enough energy to carry sediments from the shoreface to the beach, while the formation of the dunes is influenced by the transport potential of the NE wind and by the orientation of the coastline in relation to this wind. Retrograded barriers are associated to intermediary stages of variable mobility, and the two erosive hotspots of the state are associated with high mobility, which turns these environments susceptible to erosion episodes during the passing of storm events. Thus, the erosive character of the barrier may be associated with both wave energy and an irregular shoreface and a negative sediment budget, which leads to variations in beach morphodynamics

Gegenwärtige Wanderungsbewegungen und Prognosen für Deutschland.

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