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Outdoors-based youth development programs demonstrate the efficacy to improve indicators of personal growth and mental health in a range of disadvantaged young people. However, the most marginalized young people in society, who stand to benefit the most from such initiatives, remain underrepresented in the research. My Strengths Training for Life (MST4Life) is a positive youth development (PYD) intervention for young people experiencing homelessness that incorporates a life skills program and an outdoor adventure education (OAE) course. The current study presents a qualitative investigation of the OAE course to understand its role in promoting positive changes for participants. Reflexive thematic analysis led to the development of inductively driven themes which were conceptualized based on relevant theories (e.g., relational developmental systems) and models (e.g., 5 Cs of PYD). Findings highlight the benefits of a preceding life skills program to psychologically prepare participants to thrive in the unfamiliar setting of the outdoors and related challenges. During the course, adaptive developmental regulations supported participants’ basic psychological needs and fostered personal growth. Improvements in social competence was a common theme across participants and played a pivotal role in facilitating balanced development across the 5 Cs. In addition, experiences during the course promoted indicators of mental health and intentions to make positive lifestyle changes. Implications of these findings are discussed in relation to making outdoors-based youth development courses more accessible for marginalized young people, as well as how OAE and PYD programs can add value to the youth homeless sector.

Traditionally, UK housing services have focused on providing temporary accommodation, identifying risk factors, and preventing negative outcomes to young people experiencing homelessness. However, deficit approaches may lead young people to becoming dependent on services and face greater marginalization and stigmatization. Meeting long-standing calls to focus more on young people's positive attributes and abilities, the My Strengths Training for Life™ (MST4Life™) program was developed as a community partnership with a large housing service. This paper describes the rationale, logic model, and content of the MST4Life™ program using the TIDieR (Template for Intervention Description and Replication) checklist. MST4Life™ is a strengths-based and experiential psychoeducation intervention for young people aged 16-24 years who are homeless or at risk. Grounded in positive youth development and basic psychological needs theory, its aim is to provide meaningful opportunities for participants to recognize, use, and further develop their mental skills and strengths. In turn, enhancing intentional self-regulation is expected to improve physical, mental, and social health and wellbeing, and support positive transitions to independent living. The potential long-term impacts include a reduction in the number of young people returning as homeless, lower rates of mental illness and mortality, and a cost saving to the public purse.

Individuals, particularly those considered "hard-to-reach," often engage well with assessment tools that involve active dialogue and the co-construction of knowledge. Strengths profiling is one such tool that enables a person-centered and autonomy supportive approach to the identification of character strengths. Strength profiling is an adaptation of performance profiling used in sport psychology, which has not yet been utilized in broader psychological research or clinical practice. Supporting an individual by raising awareness of their personal character strengths is an effective and growing mechanism for promoting psychological well-being. Strengths profiling involves several stages of exploring, defining, and assessing character strengths, leading to the identification of signature strengths and goals for future development. Informed by personal construct theory, the present study explored the experiences of homeless young people living in sheltered accommodation (N = 116), when using strengths profiling at the start and end of a 10-week, strengths-based intervention. Mixed-method data was obtained from the strengths profiles, questionnaires measuring resilience, self-worth, and well-being, and diary entries. Findings revealed a rich array of character strength terminology and individual meanings. Participants found strengths profiling to be highly engaging, particularly due to their active role in strength identification, which prompted interesting and meaningful reflections on character strengths that were pertinent to them. Participants felt their signature strengths were vital protective factors within their lives and strengths profiles were correlated with resilience, self-worth, and well-being. Character strengths and resilience were also significantly and meaningfully improved pre/post-intervention, providing support for the use of strengths profiling as a tool for monitoring change in character strength perceptions. Overall, this study demonstrates the utility and versatility of strengths profiling as a new method in the discipline of positive psychology and strengths-based research and applied practice.

Young people experiencing homelessness often have multiple and complex support needs, and subsequently face various health inequalities. In the United Kingdom, housing services recognise the need for more effective intervention strategies. In response to this issue, My Strengths Training for Life™ (MST4Life™) is a community- and outdoors-based, positive youth development programme that aims to promote meaningful change for young people experiencing homelessness (aged 16–24). Capturing the experiences of programme participants, housing service staff and outdoor instructors, a realist evaluation was conducted to understand how, why, and for whom the programme is effective. Findings indicate that MST4Life™ is an effective intervention for fostering psychosocial development, intentional self-regulation, and longer-term positive behavioural change. Central to the success of the programme is a consistent theory-informed approach, a strengths-based life skills programme, and an appropriate transfer setting. The societal, theoretical and programme specific implications of these findings are discussed.

// Anindita Dutta 1, 2, * , David N. Potier 1, * , Michael J. Walker 1 , Oliver J. Gray 3 , Catriona Parker 4 , Mark Holland 4 , Andrew J.K. Williamson 1 , Andrew Pierce 1 , Richard D. Unwin 1, 5 , Shekhar Krishnan 2 , Vaskar Saha 2, 4, * , Anthony D. Whetton 1, 3, * 1 Stem Cell and Leukaemia Proteomics Laboratory, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK 2 Tata Translational Cancer Research Centre, Kolkata, India 3 Stoller Biomarker Discovery Centre, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK 4 Children’s Cancer Group, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK 5 Current address: Centre for Advanced Discovery and Experimental Therapeutics, Central Manchester University Hospitals NHS Foundation Trust and Institute of Human Development, University of Manchester, Manchester, UK * These authors have contributed equally to this work Correspondence to: Anthony D. Whetton, email: tony.whetton@manchester.ac.uk Keywords: legumain, AEP, biomarker, SRM, protease Received: May 16, 2016 Accepted: September 15, 2016 Published: September 23, 2016 ABSTRACT Cancer Biomarkers have the capability to improve patient outcomes. They have potential applications in diagnosis, prognosis, monitoring of disease progression and measuring response to treatment. This type of information is particularly useful in the individualisation of treatment regimens. Biomarkers may take many forms but considerable effort has been made to identify and quantify proteins in biological fluids. However, a major challenge in measuring protein in biological fluids, such as plasma, is the sensitivity of the assay and the complex matrix of proteins present. Furthermore, determining the effect of proteases in disease requires measurement of their activity in biological fluids as quantification of the protein itself may not provide sufficient information. To date little progress has been made towards monitoring activity of proteases in plasma. The protease asparaginyl endopeptidase has been implicated in diseases such as breast cancer, leukaemia and dementia. Here we describe a new approach to sensitively and in a targeted fashion quantify asparaginyl endopeptidase activity in plasma using a synthetic substrate peptide protected from nonspecific hydrolysis using D-amino acids within the structure. Our selected reaction monitoring approach enabled asparaginyl endopeptidase activity to be measured in human plasma with both a high dynamic range and sensitivity. This manuscript describes a paradigm for future development of assays to measure protease activities in biological fluids as biomarkers of disease.

Purpose – This paper aims to evaluate the perceived efficacy of outdoor groupwork skills programmes for the undergraduate and postgraduate students, and the factors that influence its success. It also illustrates the use of Kirkpatrick’s (1994) 4-level model of training evaluation as a framework for qualitative investigation of learning and transfer, from the perspective of key stakeholders. Design/methodology/approach – Over 24 hours of recorded data were collected using a video diary room, one-to-one interviews and focus group discussions. Participants were current students (n = 66), alumni (n = 12), outdoor education instructors (n = 6) and academic staff (n = 5). The data were transcribed, and then analysed by conducting conventional content analysis. Prolonged engagement, triangulation, peer debriefing and referential adequacy were used to establish the trustworthiness and reliability of the analyses. Findings – Outdoor groupwork skills programmes were widely viewed as being effective for developing interpersonal skills, attitudes and knowledge that were then further developed and applied during degree courses and later in the workplace. Four of the main perceived benefits were increased social integration amongst peers, academic success, personal development and employability. A range of psychological and environmental factors were reported to influence the extent of skill development and transfer, and are presented in the Model for Optimal Learning and Transfer. Practical implications – This study supports outdoor groupwork skills programmes as an effective method of groupwork skills training during higher education, and offers recommendations for promoting learning and transfer following training courses. Originality/value – This is the first study to systematically evaluate the long-term impact of outdoor groupwork skills programmes in higher education. A novel methodological approach is also demonstrated, which can be replicated in other contexts of training evaluation.

The aim of the present study was to develop and provide psychometric evidence in support of the groupwork skills questionnaire (GSQ) for measuring task and interpersonal groupwork skills. A 46-item version of the GSQ was initially completed by 672 university students. The number of items was reduced to 15 following exploratory factor analyses, and a two-factor model consisting of task and interpersonal groupwork skills was revealed. Confirmatory factor analyses with model re-specification on new data (n = 275 students) established that the best fitting model consisted of 10 items and the same two factors (task and interpersonal). Concurrent validity of the GSQ was then determined with 145 participants by demonstrating significant relationships (p

The purpose of this investigation was to evaluate the effectiveness of a mental skills training (MST) program for male youth elite rugby athletes. Three focus groups were held with 21 under-16 male rugby athletes and four male coaches involved in the MST program to examine the quality of service delivery, athlete responses to the MST program, the mental qualities used by athletes, and its perceived influence on athlete performance. Following inductive-deductive content analysis, 40 subcategories and 16 categories emerged. Participants believed the MST program to be an interactive, well-planned program that increased athlete understanding of MST methods and awareness of MST strategies to manage rugby performance. Athletes thought it important that their coaches develop a greater knowledge and understanding of MST methods. Finally, athletes perceived the MST skills and methods they learnt through the MST program were transferable to other sports and areas of their life outside of rugby (e.g., school).

Outdoor adventure education courses are used in higher education to develop transferable skills such as groupwork and problem-solving skills. There is a need for exploratory investigation into students’ perceptions of this experience. This study aimed to develop an innovative qualitative data collection method, and to use it to explore students’ perceived learning processes and developmental outcomes when taking part in an outdoor groupwork skills course. Participants (n = 40) were undergraduate engineering students who were taking part in the 3 day residential course as part of their degree course. Students’ experiences were captured whilst immersed in the course, using a semi-structured video diary room. Participants entered the diary room at different time points throughout the course and responded to openended questions. Following a thematic analysis, students were found to arrive on the course with mixed feelings towards groupwork and expected learning outcomes. Activities were enjoyable yet challenging, revealing students’ weaknesses and demanding a range of skills and coping methods. The outdoor environment added novelty, risk and natural consequences. Students reported developing a range of skills in groupwork, adaptability, persistence, planning, problem-solving, time-management, communication, leadership, cooperation, group reflection and team spirit, as well as benefits to physical activity, self-confidence, self-awareness, peer and staff relationships and internationalisation. These findings provide a base for future investigation into the long-term impact on student development and skill transfer. The semi-structured video diary room yielded rich data, contributing to the literature by offering a simple, yet effective, qualitative research method that can be implemented in a variety of contexts.

Drawing from the experiences of the authors in developing, conducting, and evaluating sport psychology interventions, several considerations are highlighted and recommendations offered for effective psychometric assessment. Using the Test of Performance Strategies (TOPS; Thomas, Murphy, & Hardy, 1999) as a working example, opportunities for bias to undermine a measure’s validity and reliability are discussed with reference to a respondent’s four cognitive processes: (a) comprehension, (b) retrieval, (c) decision-making, and (d) response generation. Further threats to an instrument’s psychometric properties are highlighted in the form of demand characteristics athletes perceive in the environment. With these concerns in mind, several recommendations are made relating to the process of questionnaire administration and how possible compromises to the psychometric soundness of measures used in applied interventions can be minimized.

The aim of the current study was to extend previous research by Holland and colleagues (2010) into the required psychological qualities of young talented rugby players by considering the perceptions and supportive role of influential others. Perceptions of players’ parents (n = 17), coaches (n = 7), and sport administration staff (SAS; n = 2) were explored through focus group discussions. Findings show that these influential others considered the same 11 higher order themes for psychological qualities previously identified as desirable by players. Their views on how they assisted in developing these player psychological qualities were classified into three higher-order themes, namely progressive development, professional environment, and performance environment. Specific behaviors contributing to each context and deemed helpful by influential others were discussed in terms of ecological systems theory (Bonfenbrenner, 1977). Recommendations for future research and applied implications for consultants are subsequently offered. At the highest level of sport, performance success is consistently differentiated by an athlete’s display of psychological qualities and effective use of mental techniques (Gould, Eklund, & Jackson, 1992). A number of in-depth qualitative studies have explored these psychological determinants of sporting success through interviews and questionnaires with performers at the pinnacle of their careers including Olympic and World Champions (Durand-Bush & Salmela, 2002; Gould, Dieffenbach, & Moffett, 2002; Orlick & Partington, 1988). Recollections made by elite athletes about the development of these psychological attributes and related mental techniques have furthered our understanding of the psychological dimensions of optimal performance. However, the accuracy of such self-reports are threatened by memory-decay over time. Current knowledge, beliefs, and expectations can distort memories and errors in retrieval can lead to biases in recall (Schacter, 1999). Although athletes have not indicated difficulties in recollecting meaningful

SUMMARY A characteristic feature of Wegener's granulomatosis is the presence of antineutrophil cytoplasm antibodies (ANCA) to proteinase 3 (PR3). In vitro, ANCA activate neutrophils by co-ligating PR3 and FcγRIIa/IIIb receptors. ANCA are predominantly of the IgG isotype, and IgG1, IgG3 and IgG4 subclasses are particularly represented. To address the pathogenic role of individual ANCA-IgG subclass antibodies, patients’ sera were screened using indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA) and subclass PR3-ELISA to identify patients with high titres of PR3-ANCA within the IgG1, IgG3 or IgG4 subclasses. Unfractionated ANCA-IgG and subclass fractions were isolated by affinity chromatography and compared for their capacities to stimulate superoxide production by primed human neutrophils. Donor neutrophils were analysed for constitutive and induced FcγRI expression by flow cytometry. The IgG1, IgG3 and IgG4 subclass fractions, isolated from three different ANCA sera, each stimulated superoxide production from neutrophils derived from multiple donors. Subsequently, IgG4 subclass fractions isolated from a further four ANCA positive sera demonstrated varying abilities to stimulate release of superoxide; unrelated to PR3-ANCA titre, neutrophil donor, or neutrophil FcγRI expression. The stimulation of superoxide release by IgG1- and IgG3-ANCA subclass fractions is consistent with the proposed mechanism of co-ligation of PR3 antigen and FcγRIIa/IIIb receptors. However, the demonstration of similar activity for the IgG4-ANCA subclass fractions isolated from some sera was unexpected. This activity was independent of neutrophil donor and expression of FcγRI, suggesting it was capable of activating neutrophils via constitutively expressed FcγRIIa/IIIb or co-ligation of other, unidentified, cell surface molecules.

SUMMARYThe triad of small vessel vasculitides (SVV) comprise Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg–Strauss syndrome (CS). All three are associated with presence of circulating IgG antineutrophil cytoplasm antibodies (ANCA) which target autoantigens contained, primarily, within neutrophil azurophilic granules. The widely accepted model of pathogenesis suggests that ANCA activate cytokine-primed neutrophils within the microvasculature, leading to by-stander damage to endothelial cells, and rapid escalation of inflammation with recruitment of mononuclear cells. Activation may be initiated, in vitro, by the coligation of the PR3 or MPO antigen, translocated to the cell surface, and FcγRIIa/FcγRIIIb receptors. This suggests that the IgG subclass profile of ANCA and, possibly, its glycosylation status could influence the inflammatory mechanisms activated. The glycosylation status of total IgG isolated from the sera of patients with WG (13), MPA (6) and CSS (1) was determined by analysis of the released oligosaccharides. A deficit in IgG galactosylation is demonstrated for all patient samples, compared to controls. The mean percentage values for the agalactosylated (G0) oligosaccharides were 57% (SD ± 9·71), 47% (SD ± 4·25) and 28% (SD ± 4·09) for WG, MPO and control samples, respectively. The G0 levels for polyclonal IgG isolated from the sera of both WG and MPA patients were significantly increased compared to controls (P < 0·0001). The major glycoform present therefore is agalactosylated (G0) IgG. In previous studies the G0 glycoform of IgG has been shown to bind and activate mannan binding lectin, and hence to activate the complement cascade, and to facilitate mannose receptor binding and the uptake of IgG complexes by macrophages and dendritic cells. Both of these activities could impact on the processing and presentation of self-antigens in autoimmune disease.

There has been a profusion of studies related to the pathogenesis of antineutrophil cytoplasm antibody-associated small vessel vasculitis. Further definition of epitopes on the major antigens, proteinase-3 and myeloperoxidase, has been sought, and intracellular signal transduction pathways after antineutrophil cytoplasm antibody-neutrophil interactions are beginning to be explored. Antineutrophil cytoplasm antibody stimulation of neutrophils has highlighted the functional importance of the accelerated death that follows the initial activation. The consequences of neutrophil and monocyte activation for endothelium and tissue damage continue to point toward an inflammatory process that has become dysregulated. Factors that initiate vasculitis are being identified slowly. The most secure identifiable environmental trigger is the antithyroid drug propylthiouracil. It is likely that environmental factors operate against a background genetic susceptibility, and polymorphisms in genes for proteins associated with inflammation are being tested for possible links with small vessel vasculitides.

Abstract: The Northern Arran Granite has a sub-circular form in outcrop with a diameter of about 11 km. We have acquired six gravity profiles across the margin of the granite with an average station spacing of less than 250 m, two of which were extended to give an approximately diametric profile across the whole body. Simple modelling indicates that the granite ranges in thickness between 0.3 km and 1.2 km close to the margin, and that the base of the granite is approximately horizontal. Furthermore, the diametric profile shows no short-wavelength negative anomaly feature that could be associated with any abrupt increase in thickness of the granite. We concluded, therefore, that the granite probably has the form of a laccolith. More importantly, the shallow depth inferred for the base of the granite has a significant implication concerning its ascent mechanism. Intrusion of the granite led to the development of the Catacol synform in the Dalradian metasediments around its northwestern margin, and in 1992, England used structural analysis to demonstrate that the Dalradian rocks presently exposed at the margin were uplifted by 2–3 km during granite emplacement. Because gravity modelling shows that the granite is less than 1 km thick around its northwestern margin, the granite could not have uplifted beds from 2–3 km depth if it had been emplaced laterally following dyke ascent. Diapirism therefore appears to be the only ascent mechanism for the granite that is consistent both with its geometry and with the structures around its margin.

Flows from the Grande Ronde Basalt of the Columbia River Basalt Group include several with the chemical composition of ferro-andesites. These flows have SiO2 > 55%, MgO 206Pb/204Pb versus 207Pb/204Pb plot. Their Nd isotopic compositions lie between 143Nd/144Nd = 0.51252 and 0.51264, and their Sr isotopic compositions lie between 87Sr/86Sr = 0.7055 and 0.7060. These values define the enriched end of the Columbia River Basalt Group spectrum on a Sr–Nd epsilon diagram (excluding the Saddle Mountains Basalt). These ferro-andesite flows also form a compositional end member of the Columbia River Basalt Group and are sufficiently distinctive to warrant special consideration. We compare them with lavas from other tholeiitic provinces. Petrogenetically, they can be related to the Grande Ronde Basalt low-Mg basalts by plagioclase fractionation, or by clinopyroxene fractionation in partially melted eclogites. However, the situation may not be that simple, as their unique isotopic compositions are closely related to those of parental mantle materials, perhaps thus requiring separate reservoirs and (or) sources. Extending this argument to other parts of the Columbia River Basalt Group suggests that the origin of these basalts may be in a system of comparatively small magma chambers in the uppermost mantle, frequently replenished from a variety of sources.

The Tollie antiform occupies a tectonic break between an area to the north, where remnants of Archaean structures are preserved, and an area to the south, characterized by substantial Proterozoic reworking. The antiform produced in this tectonic boundary is a multistage structure containing three components Creag Mhor Thollaidh in the north, faulted against a central zone, which passes southwards into the highly sheared and attenuated Buanichean gneisses of the southwestern limb. The compositions of gneisses in the antiform assign them unambiguously to the Archaean gneisses of the Gruinard and Lochinver areas to the north. Gneisses of this extensive area were brought together within the narrow confines of the Tollie antiform. As the antiform evolved, the Buanichean gneisses acted as an anatectic source to a set of shear-refined potash-rich pegmatites, which penetrated north into the central zone of the developing antiformal structure. In this central zone, some of the pegmatites were deformed into open folds, whereas others were unmodified. The pegmatites thus form a point of reference within the evolution of the Tollie antiform. Rb–Sr isotopic data on the pegmatites give an age for their intrusion and crystallization of 1660 Ma. Downward shear of the southwestern limb of the antiform continued until about 1500 Ma. By the time this episode of structural restyling in the Lewisian had been completed, a deep-rooted wedge of Proterozoic cover sediments had become encased in an Archaean basement.

We present the first investigation into the utility of porous graphitic carbon (PGC) as a stationary phase in proteomic workflows involving complex samples. PGC offers chemical and physical robustness and is capable of withstanding extremes of pH and higher temperatures than traditional stationary phases, without the likelihood of catastrophic failure. In addition, unlike separations driven by ion exchange mechanisms, there is no requirement for high levels of non-volatile salts such as potassium chloride in the elution buffers, which must be removed prior to LC-MS analysis. Here we present data which demonstrate that PGC affords excellent peptide separation in a complex whole cell lysate digest sample, with good orthogonality to a typical low pH reversed-phase system. As strong cation exchange (SCX) is currently the most popular first dimension for 2D peptide separations, we chose to compare the performance of a PGC and SCX separation as the first dimension in a comprehensive 2D-LC-MS/MS workflow. A significant increase, in the region of 40%, in peptide identifications is reported with off-line PGC fractionation compared to SCX. Around 14,000 unique peptides were identified at an estimated false discovery rate of 1% (n=3 replicates) from starting material constituting only 100 μg of protein extract.

Research on the psychological characteristics of elite performers has primarily focused on Olympic and World champions; however, the mental attributes of young developing and talented athletes have received less attention. Addressing this, the current study had two aims: (a) to examine the perceptions held by youth athletes regarding the mental qualities they need to facilitate their development and (b) to investigate the mental techniques used by these athletes. Forty-three male youth rugby players participated in a series of focus groups. Inductive content analysis revealed 11 categories of psychological qualities, including enjoyment, responsibility, adaptability, squad spirit, self-aware learner, determination, confidence, optimal performance state, game sense, attentional focus, and mental toughness. Techniques employed included personal performance strategies, refection on action, taking advantage of a supportive climate, and team-based strategies. Findings are discussed in relation to their implications for mental skills training program development and evaluation in the case of youth elite team sport athletes.

l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as the primary AEP cleavage site. Sole modification at this site rendered ASNase resistant to AEP cleavage and suggested a key role for the flexible active loop in determining ASNase activity. We therefore propose what we believe to be a novel mechanism of drug resistance to ASNase. Our results may help to identify alternative therapeutic strategies with the potential of further improving outcome in childhood ALL.

Post-translational modifications (PTMs) of proteins produced in vivo may be tissue, developmentally and/or disease specific. PTMs impact on the stability and function of proteins and offer a challenge to the commercial production of protein biotherapeutics. We have previously reported a marked deficit in galactosylation of oligosaccharides released from polyclonal IgG isolated from sera of patients with the anti-neutrophil cytoplasmic antibodies (ANCA) associated vasculitides; Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Whilst normal polyclonal IgG molecules are glycosylated within the IgG-Fc region, approximately 20% of molecules also bear oligosaccharides attached to the variable regions of the light or heavy chain IgG-Fab. It is of interest, therefore to compare profiles of oligosaccharides released from the IgG-Fc and IgG-Fab of normal IgG with that isolated from the sera of patients with WG or MPA. This study shows that whilst the oligosaccharides released from ANCA IgG-Fc are hypogalactosylated those released from IgG-Fab are galactosylated and sialylated. These results show that hypogalactosylation of IgG-Fc is not due to a defect in the glycosylation or processing machinery. It rather suggests a subtle change in IgG-Fc conformation that influences the addition of galactose. Remarkably, this influence is exerted on all plasma cells. Interestingly, a licensed monoclonal antibody therapeutic, produced in Sp2/0 cells, is also shown to be hypogalactosylated in its IgG-Fc but fully galactosylated in its IgG-Fab.

The present investigation was undertaken to determine the incidence of alcohol, cocaine, and marijuana use among pregnant patients who suffered any type of physical trauma and to determine if the combination of substance use and physical trauma in pregnancy has extended perinatal implications.In this single institution, prospective patient series undertaken over 18 months, all pregnant patients who suffered any type of physical trauma were considered for study.Among 6828 live births over an 18-month period, there were 157 (2.3%) patients who reported physical trauma (insignificant = 153, minor = 2, severe = 2). Consent to screen for the presence of alcohol, marijuana, and cocaine was obtained from 85 (54%) patients with refusal by the remainder. Screening was positive in 11% for one or more substances. The perinatal morbidity and mortality for the 153 patients with insignificant trauma was 50:1000 and 20:1000, respectively, all associated with preterm labor and delivery which occurred in 21% of the patients. None of the four patients with minor or severe trauma either had a positive drug/alcohol screen or any perinatal morbidity or mortality. No maternal mortality occurred.An 11% incidence of positive drug screens was encountered in consenting pregnant trauma victims and a 21% incidence of preterm birth was encountered even in this patient population with so-called insignificant trauma.

Clinical and laboratory studies in childhood acute lymphoblastic leukemia (ALL) suggest that the bone marrow microenvironment protects blast cells, thus influencing disease relapse. This study was designed to identify the mechanisms by which bone marrow stromal cells could mediate chemoresistance in ALL cells. An in vitro organotypic extracellular matrix-bone marrow stromal cells (ECM-BMSC) culture system, that sustained primary cells without the addition of exogenous factors, was created. ECM-BMSC derived conditioned medium (CM) conferred broad-spectrum chemoprotection to ALL and other cancer cells. Multi drug resistant sub-clones (MDRS), derived by exposing ALL cells in CM to Mitoxantrone, retained chemoresistance even beyond 50 passages in normal medium. Chemoprotective effect was retained in the Proteinase K, RNase and heat resistant, < 3kDa fraction of CM; transmission electron microscopy demonstrated the presence of stromal cell derived exosomes in this fraction. Confocal microscopy confirmed the uptake of ultra-centrifuged fluorescently labelled (PKH 67) stromal exosomes by ALL cells which then developed a resistant phenotype. Stromal derived exosomes and MDRS were enriched in miRNA expression (TaqMan Human miRNA array V3), compared to parent cells, with 92% concordance. Ingenuity™ pathway-based analysis of the unique miRNA pattern predicted dysregulation of mitochondrial function and oxidative phosphorylation. SILAC based phosphoproteomics and U133A V2 gene expression array analysis revealed aberrant PI3K/AKT and oxidative phosphorylation activity. A kinase inhibitor screen showed that PI3K/AKT inhibitors were most potent in reversing CM mediated chemoresistance. Exposure to CM initially (24 hours), pAKT activity and ROS level decreased to lower than the basal level, with upregulation of CDKN1B and MCL-1, and a decreased mitochondrial membrane potential. shRNA knockdown of CDKN1B restored normal growth rate but not chemosensitivity. MDRS that were resistant to exogenous H2O2 induced apoptosis, regained sensitivity after MCL-1 knockdown. Upregulation of ROS and downregulation of MCL-1 using PEITC lead to cell death in chemo sensitive and resistant cells. Our study identifies that the microenvironment produces soluble factors that induces a redox adaptation in ALL cells leading to chemoresistance. This can be overcome by the simultaneous inhibition of the antioxidant system (to increase ROS) and suppressing antiapoptic proteins (to eliminate the mitochondrial membrane safeguard). Tumour protection by the microenvironment is likely to be common to other cancers. Future therapeutic strategies need to consider targeting the host-tumor interactions in adjunct to conventional chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1506. doi:1538-7445.AM2012-1506

We sought to determine the extent to which vaginal birth after cesarean delivery was attempted since 1987 or 1988 in a representative sample of three regional level II hospitals in Mississippi.The medical record department in each hospital identified all potential study subjects for this retrospective case series. One author abstracted relevant information from each medical record and entered it into a relational data base.Among 18,703 live births, 1574 patients had previous abdominal delivery (8.4%). Trial of labor was undertaken in 286 patients (18%), with an overall successful vaginal delivery rate of 71%. Although success rates for the three level II hospitals were similar (63-81%), utilization rates varied considerably (7-40%). One uterine dehiscence led to hysterectomy; otherwise, there were no serious perinatal complications or differences in measures of maternal morbidity, except for a higher incidence of endomyometritis with failed trial of labor (13 versus 3%). The only consistent differences observed between successful and unsuccessful trials in all groups were length of hospitalization and rate of cervical dilatation in active labor (1.4 versus 0.5 cm/hour).Although each regional level II hospital successfully conducted trials of labor in patients with previous cesarean birth, there was considerable variation among sites regarding frequency of utilization, suggesting a strong influence of nonclinical patient-physician factors upon the decision-making process.

The efficacy of the key anti-leukaemic agent E.coli L-Asparaginase (L-Asp) is limited by variable therapeutic activity and development of antibodies/hypersensitivity. Observing more frequent clinical hypersensitivity in children with high risk acute lymphoblastic leukaemia (ALL), we speculated that L-Asp was proteolytically degraded by lymphoblasts, generating immunogenic fragments. On incubation with whole cell lysate from a lymphoblastic cell line, L-Asp was cleaved into at least three fragments. This cleavage was blocked only by MV026630, a specific inhibitor of the cysteine protease Asparaginyl Endopeptidase (AEP). Incubation of L-Asp with purified recombinant AEP produced an identical cleavage pattern at the carboxy termini of specific asparagine and aspartate residues. The level of AEP expression at diagnosis in 148 childhood ALL patients was measured using U133A, Exon 1.0 ST arrays and quantitative PCR. High levels of expression were detected in 38 patients (25%), including all 6 patients with clinical hypersensitivity. Elevated AEP expression was more commonly observed in high-risk disease (42% v 21%). Molecular modelling of AEP cleavage sites predicts that the N-terminal cleavage site (C1) provides tetramer stability while the highly-conserved second cleavage site (C2) is critical for tetramer formation and enzyme activity. This model was confirmed by analyses of recombinant L-Asp variants mutated to resist AEP cleavage. Cleavage is sequential from the N terminus. A product resistant to cleavage at C1 is not degraded by AEP, forms a tetramer and retains enzymatic activity comparable to the wild-type. The C2 mutated product shows little activity and is rapidly degraded by AEP. Known antigenic epitopes of L-Asp are retained within AEP-cleaved fragments. The contribution of AEP to antigenic processing of L-Asp is being investigated by T-cell activation assays using a synthetic peptide library and T cells from patients with known hypersensitivity. Thus patients with AEP-overexpressing lymphoblasts may not benefit from L-Asp therapy either due to inactivation, the development of antibodies or both. Replacement of a single amino acid of L-Asp can prevent this process without loss of activity. This product potentially has a longer half-life and less antigenicity. Our investigations have identified a hitherto unknown pathway for L-Asp degradation and a novel mechanism of drug resistance in childhood ALL. These observations require further validation by correlation of AEP expression with asparaginase activity and antibody formation in children receiving L-Asp during treatment for ALL. Further potential improvements in therapy could include screening for AEP expression at diagnosis and the use of non E Coli asparaginase or preferably a modified recombinant L-Asp and/or AEP inhibitors for those with high levels of expression.

IgA nephropathy (IgAN) and Henoch-Schönlein purpura (HSP) are both characterized by IgA-mediated tissue injury, including mesangial proliferative glomerulonephritis. Abnormalities of IgA1 glycosylation are described in IgA nephropathy and HSP nephritis. IgA-antineutrophil cytoplasmic antibodies (ANCA) have been inconsistently described in the serum of patients with HSP. In IgA myeloma, the paraprotein-mediated renal lesion is typically cast nephropathy; IgAN or HSP have only rarely been reported in myeloma even when an IgA paraprotein is circulating in large concentrations. We report the case of a 50-year-old man with IgA myeloma who presented with HSP including nephritis and rapidly progressive renal failure. His IgA1 had altered O-glycosylation in the pattern seen in IgAN and also contained an IgA-ANCA. This case adds further weight to the evidence that IgA1 O-glycosylation abnormalities predispose to mesangial IgA deposition and also that IgA-ANCA may have a pathogenic role in the development of HSP.

New analyses of 1518 rocks for major and certain trace elements are used to examine chemical variations between the 15 larger volcanic islands of the Lesser Antilles island arc. The depth to the top of the subduction zone dipping westward at about 40° lies about 100km below all the volcanoes of the arc. Most of the sampled eruptions are post-Miocene (5-1 m.y.) although south of Martinique, the Oligocene-Miocene and the younger arc are superimposed. There is a chemical variation along the arc axis, from alkalic (southern) through calc-alkalic (central) to tholeiitic (northern) volcanic suites. Three islands are examined in detail as type examples of this variation, i.e. Grenada (south), Dominica (centre), and St. Kitts (north). The Grenada suite includes basanites, alkalic basalts, and subalkalic basalts, andesites and dacites. The subalkalic basalts, andesites and dacites each fall into three chemical groupings along the axis of the arc, distinguished especially by K, Zr, Ni and Cr abundances. The whole Lesser Antilles assemblage is characterised by low K abundances and low K/Rb ratios, compared with other island arcs. The magmas are believed to have evolved through processes of partial melting and crystal fractionation. Partial melting of garnet Iherzolite at about 100km depth in a relatively ‘fertile’ zone of upper mantle in the southern sector, above the subducted slab of basaltic ocean crust, could have produced the undersaturated alkalic magmas. In the central and northern sectors, where the crustal structures are more complex, partial melting may have occurred within more ‘barren’ upper mantle, to produce tholeiitic and calc-alkalic magmas depleted in certain trace elements. In either case, water was probably added to the melted zone from the subducted and hydrated oceanic crust, since the whole arc assemblage was erupted explosively and the rocks are rich in A12O3, plagioclase is very calcic, and amphibole is an important phase. The second process was crystal fractionation at low pressure, as evidenced by the abundance of cumulate xenoliths. Separating phases for the southern volcanoes were olivine, calcic augite and Cr-spinel, followed by hornblende, anorthite and Ti-magnetite at lower temperatures. There is little evidence of the higher-temperature fractionation controls for the central and northern volcanoes.

Hornblendic and felsic groups of Archean age and each of broadly similar geochemical composition across the Malton Gneiss Complex southeast of Valemount, Bristish Columbia, show detailed mineralogical and chemical variations from one geographical district to another. The complex appears to be composed of meta-igneous rocks which were originally developed as petrologically discrete units on a roughly 10-km scale, but which all belonged to one similar petrographic province. Overall they are characterized by rather high immobile trace and alkali element abundances. Their nearest geochemical equivalent appear to be found in the grey gneiss complexes of the North Atlantic Craton rather than in the granite-greenstone complexes of the Canadian Shield, but no other Archean complex possesses their overall characteristics. Some similarities in A-F-M and Q-Ab-Or content of these gneisses and those of the Laramie Range, Wyoming, are noted.

Synopsis Comparison of chemical analyses of the principal units of the Morar Division suggest that the inter-relationship between psammites and pelitic rocks is dominated by mechanical rather than chemical processes. This conclusion is drawn from similar ratios of Fe 2 O 3 /MgO, K/Rb, K/Ba and Ca/Y, and dissimilar ratios of Ti, Nb and Zr to Fe. Rocks of the Glenfinnan Division differ from comparable members of the Morar Division in having higher Nb/P 2 O 2 and Nb/Y for any given Sr or Fe 2 O 3 /Ni ratio, and higher Sr/Y for any given SiO 2 level. These distinctions may reflect consistent differences in the ratios of quartz and feldspar, ferromagnesians, and accessory minerals. Samples from the Loch Eil Division tend to have higher Zr/P 2 O 5 , Y/P 2 O 5 , CaO/P 2 O 5 , Rb/Sr and lower Ca/Y and K/Rb than their counterparts in the Morar and Glenfinnan Divisions. The Morar Basal Pelite has an immature chemistry showing affinity with the Lewisian basement upon which it rests. It can be distinguished from other Moinian pelitic units by its high Sr/Y. Certain individual psammitic horizons can be distinguished by their contents of P, Ti, Nb and Zr, and sometimes by Cr/Fe. The Morar Division has a chemistry consistent with deposition in a basin close to its supposed Lewisian source. In contrast, the Loch Eil Division may have been partly derived from a (post-Lewisian) sedimentary source, and may rest unconformably upon the underlying Moinian rocks.

SUMMARY: Within the Ordovician sequence of the Southern Uplands of Scotland numerous basaltic units occur, forming local basement to sequences of chert, graptolitic mudstone and greywacke. The basalts are fault-bounded at their base. Although they have suffered secondary alteration to varying degrees, the least mobile elements, Ti, Zr, Y and Nb, show a correlation between relative chemical abundances and supposed tectonic level. The most northern tectonic slice contains alkali basalts; the central slice contains 11 examples of what are apparently ocean-floor tholeiites and 4 mildly alkaline basalts; a third slice, found at one locality only, also contains tholeiites whose chemistry is comparable with the most primitive basalts. Samples of Ordovician extrusives from Bail Hill have calc-alkaline to alkaline affinities, while extrusives from Wrae Hill are quartz-keratophyres. The geochemical pattern is consistent with a model of an opening Iapetus Ocean in which rifting pre-dated spreading such that the basement to the Lower Palaeozoic sequence of the Southern Uplands was oceanic.

SummaryComparison is made between the semipelitic and psammitic schists of the Morar and Glenfinnan Division in their type areas and the succession in the Fannich district of Northern Ross-shire. The tentative lithological correlation of the Morar Pelite with the Sgurr Mor Pelite is confirmed, while the Meall an t-Sithe Pelite and the semipelites of the Glenfinnan Division likewise have a similar geochemistry. In establishing these similarities, ratios involving Sr, Nb, Y, Zr and P2O5 have been found to be most useful, particularly Sr/Y. Other ratios (Ca/Y, K/Rb, K2O/(Na2O+CaO) and K/Ba) can also yield useful information regarding correlation and sedimentary history. Sr/Y decreases stratigraphically upwards in these successions and also towards the north east, suggesting a palaeogeography for the Morar Division involving increasing remoteness from the source area with time and in a northeasterly direction.

A suite of lavas from Great Ararat is described. Analyses are reported for Si, Al, Fe, Mg, Ca, Na, K, Ti, Mn, S, P, Ba, Nb, Zr, Y, Sr, Rb, Zn, Cu, and Ni. Two distinct series can be recognized, each consisting of andesite, dacite, and rhyodacite (designated Low-Y and high-Y series), they are distinguished by significantly different K. Mn, P, Nb, Zr, Y, Rb, Cu, and normative feldspar contents-The high-Y series corresponds closely to a normal calc-alkali series, but the low-Y series is relatively deficient in K, Mn, P, Nb, Zr, Y, and Rb. $$^{87}Sr/^{86}Sr$$ from both series is $$0.7050 \pm 0.0005$$. Petrographi-cally, both series are characterized by three generations of feldspar, all rock types containing labradorite together with more sodic phenocrysts and groundmass plagioclase: orthopyroxene, clinopyroxene, magnetite and ilmenite are present. Quartz and K-feldspar phenocrysts are absent. Suggestions of the former presence of garnet and brown hornblende, together with relevant experimental and geo-chemic...

Petrological and geochemical analyses of gneisses from the Malton Gneiss Complex (199°W 52°30′N, south of Valemount, B.C. and west of the Rocky Mountain trench) reveal four distinct mineralogical and geochemical groups, based on their petrology, Y and Nb contents and Fe Mg ratios. The Complex appears to be an Archean meta-igneous complex, which has been chemically modified, with alkali enrichment, during an Upper Proterozoic igneous event. Group 1, the most common rock type in the Complex, consists of mafic biotite—hornblende gneisses and amphibolites. They have low Y contents and the lowest Fe Mg ratios in the Complex. (Na2O + K2O) averages about 5%, K Rb ratios are between 200 and 400, K/Ba between 200 and 100 and Sr Ba ratios vary widely. The group 2 rocks are granitic and tonalitic gneisses characteristically garnetiferous and preserving their Archean age. They have Y Nb ratios of about 2 and low Y and Nb contents. Rb values are also low, but not exceptionally so, the range being 70–180 ppm. K Rb ratios lie between 20 and 400, K/Ba between 20 and 50 and Sr/Ba between 0.1 and 0.5. Groups 3 and 4 are alkali granitic gneisses generally occurring as intrusive sheets. Group 3 gneisses have Y Nb ratios of approximately 0.5 and have higher Nb contents than groups 1 or 2. Group 4 gneisses have Y Nb ratios of apporoximately 1 and both Y and Nb contents are higher than in groups 1 and 2. Parameters indicating an increase in differentiation are higher in groups 3 and 4 than in groups 1 and 2, but group 3 gneisses include some rocks with very high K Rb ratios, the range being 200–800 and the average above 400. The Malton Gneiss has no obvious analogues in the nearest surface Canadian Shield. It has geochemical similarities with the Grey Gneiss of the North Atlantic Craton and may be similar to the Archean of Western Montana.

Suites of samples from the type area of the Leven Schist and from localities within the Monadhliath Schists of the Central Highlands have been analysed for major and trace elements and for their Sr isotopes. Petrologically the two schist groups are consistently different: the Leven Schists are muscovite-rich, plagioclase-poor semipelites to pelites, whereas the Monadhliath Schists are a typical ‘Moinian’ semipelite, consisting almost entirely of biotite, sodic andesine and quartz. Equally, consistent geochemical differences between the two include more Nb, Zr, Y and Rb, and less Ca, Sr and Ni in the Leven than the Monadhliath Schists. Ratios of Rb: Sr and of Y to P 2 ,O 5 , Sr and CaO discriminate the Leven from the Monadhliath schists. Factor analyses of the chemical data also serve to distinguish the two suites Rb-Sr isochron studies give 655±f2.5Ma, initial 87 Sr/ 86 Sr = 0.7232±f10, for the Leven Schists, and 486±9Ma, initial "Sr 87 /"Sr 86 = 0.7190±1, for the Monadhliath Schists and also separate the two formations from one another. The 655 Ma age for the Leven Schists is thought to record sedimentation and diagenesis, whereas the 486±9 age for the Monadhliath Schists is probably related to the cessation of Rb and Sr migration at or after the peak of the Grampian orogeny. Their Sr isotopic compositions were also completely different hack to 1300 Ma ago and serve to confirm the lack of any continuity between the Leven and Monadhliath schists. Sets of schists located between the main outcrop areas were also analysed and can be assigned without ambiguity either to the Leven or the Monadhliath schists on the basis of their chemistry. The results of this study imply that the Lower Dalradian Appin Group rests on the Grampian Division unconformably and that the latter is closely related, through its geochemistry, to the Moinian NW of the Great Glen.

All geochemical data for basalts from holes 332A. 332B. 333. 334, and 335 drilled into the west flank of the Mid-Atlantic Ridge near 37° N, are reviewed. The 785 samples analyzed, providing some 14 000 data items, are grouped into 50 units of distinct geochemical character. Holes 332A, 332B, 333, and 334 penetrated basalt piles containing 32 normal oceanic tholeiite units. 2 tholeiites with low Zr. 7 units with low Zr and high Ca, and 8 units with low Zr and high Mg. Hole 335 penetrated tholeiite s rich in heavy rare earths and Y, and with many other distinct geochemical characteristics. The tholeiites of 335 were exceptionally uniform over a depth of 102 m, and the top and bottom halves of this sequence are geochemically indistinguishable. Oxygen, strontium, and lead isotope evidence combines with the geochemical data to indicate little post-extrusion metasomatism.A marked positive correlation exists between all of the elements Ti, Mn, Nb, Zr, Y, Rb, Zn, K, U, and Ba, and in turn these all correlate positively with Fe and Fe/Fe + Mg). Sc also shows a significant linear correlation with Fe. In all subsets among the elements listed so far, the 'low-Zr' (≤ 50 ppm) and the 'normal' basalts form two distinct groups. Other element pairs or groups clearly show the existence of the three sets, normal, low-Zr/high-Ca. and low-Zr/high-Mg in the form of tri-linear or Y-shaped plots. The interrelationships of Mg, Fe, Ca, Sr. Cr, V, Ni, Co, Y, and the REE fall into this category. The trace elements in this set are those that proxy for major elements in the principal silicates or spinels, whereas most of the previous set (Ti, etc.) may be dominantly in minor phases. The trace-element abundances in the low-Zr units, the negative correlation of Cr with V, a positive correlation of Cr with Ca and Cr with Mg, positive correlation of most Y and REE with Ca, and the details of REE distribution (La-rich) are used to argue that partial melting of garnel-free lherzolite is the dominant cause of the composition of the tholeiites in 332A to 334. Basalts from 335 are of different origin and were produced either from La-impoverished. heavy REE-rich mantle, or from a multi-stage partial melting process involving a garnet-lherzolite source. The high-Ca and high-Mg basalts both of which are Cr-rich and picotite-bearing and are respectively bytownite- and olivine-phyric, are considered to be the products of high percentage partial melting. It is argued that the normal tholeiites were produced at a liquid–olivine–labradorite–pytoxene perilectic at early stages of partial melting and that the low-Zr varieties by higher percentage melting at and beyond a liquid–olivine–bytownite–Cr–spinel peritectic, almost to an ultrabasic level of melting.The lead isotope and geochemical data for DSDP 37 and various Atlantic basalt suites indicate a heterogeneous mantle. We believe that this heterogeneity is due to a large-scale gneissic mantle structure, consisting of layers or slabs created and fractionated much earlier in geological history. On arriving at accreting plate margins these slabs give the margins distinctive geochemical and isotopic characteristics over distances on the 500–1000 km scale, within which various degrees of partial melting of material derived from various types of 'barren mantle' (plus former crust?) operate to produce individual basalt horizons.

The Torridon Inlier of the Lewisian of Scotland contains ~30 sq. km of granodioritic gneisses. A coordinated study of this inlier, including detailed mapping, geochemical analyses and geochronological work, has indicated that Rb-Sr whole rock analyses yield “ages” that are functions of the local structural setting and of the chemistry and mineralogy of the rock, as well as of the overall geological history of the region. This Archean region has been invaded by a swarm of northwest striking dykes of Inverian (2400 to 2240 Ma) age, accompanied by new foliations and major structures. However, several structurally distinct areas, termed “pips”, 1–2 km2 in extent, are free of Inverian foliation and largely free of Inverian dykes. The 38 samples analysed for Rb and Sr scatter widely about a 2.66 Ma isochron; but give meaningful results only when subdivided according to their structural setting and lithology. A subset of silicic gneiss samples from the area most strongly overprinted by Inverian structures yields an age of 2240 ± 70 Ma with an initial 87Sr86Sr of 0.7098 ± 18. A subset of samples from “pips” further north yields an age of2790± 100 Ma (initial 87Sr86Sr = 0.7020± 10), identical to the 2780± 70 Ma U-Pb age obtained from zircon fractions separated from two of the samples. Samples from this northern district, located outside the “pips” in areas showing weak Inverian foliation, or within 50 m of Inverian dykes, or both, have grossly disturbed Rb-Sr systematics. The apparent ages of the felsic gneisses have been increased, while those of their mafic enclaves have been decreased (to as low as 1380 Ma). Field and geochemical evidence relate the increase directly to Rb loss and/or radiogenic Sr gain in the immediate vicinity of major dykes, which themselves have gained Rb and K by comparison with dykes elsewhere in the Lewisian. In terms of Rb-Sr work on complex terranes, these results must caution against direct interpretation of such data, especially in the absence of detailed field knowledge.

SummaryPelitic schists from the Appin Group of the Dalradian Supergroup are all chemically distinct from pelitic schists in the older Moinian Supergroup. In addition, trace-element geochemistry can also discriminate between the individual pelitic schists within the Appin Group, especially those within the Lochaber Subgroup. These differences apparently relate mainly to differences in provenance rather than differences of sedimentary environment, and are sufficiently consistent to offer a means for correlation or identification of pelitic units in areas of the Central Highlands where the stratigraphy is still in dispute.

Petrographic, geochemical, and geochronological data are presented on the gneisses of the Bulldog Creek block, the Mount Blackman block, and the Hugh Allan Creek block, which lie to the east of the Southern Rocky Mountain Trench (SRMT) south of Valemount, British Columbia. Petrographical and geochemical data, especially immobile-trace-element ratios (Nb: Y, Ti: Zr), and CaO versus Y and AFM plots are used to deduce the probable origins and protoliths of the gneisses. The Mount Blackman block consists of a psammitic paragneiss, probably derived from an immature arkosic sedimentary protolith, intruded by sills of tholeiitic basalt, now amphibolites. The Bulldog Creek block consists of felsic orthogneisses of calc-alkaline affinity, which are structurally concordant with mafic orthogneisses of possible tholeiitic basalt parentage. The Hugh Allan Creek block consists of a felsic orthogneiss with a probable alkaline granite protolith. Rb-Sr, and some U-Pb analyses show that each block has experienced a separate geological history. The Mount Blackman block psammitic paragneisses are the only analysed gneisses east of SRMT with a probable Archean Rb-Sr model crustal residence age. U-Pb analyses on zircons from these gneisses give a 1950 Ma minimum source rock age, and Rb-Sr whole-rock analyses suggest a 1860 * 50 Ma age for amphibolite-facies metamorphism of both paragneisses and amphibolites. The Bulldog Creek block gneisses have a metamorphic age of at least 640 Ma, but their Rb-Sr systematics have been extensively disturbed, possibly during Mesozoic retrogressive metamorphism. The Hugh Allan Creek block gneisses have a Rb-Sr model crustal residence age of -900 Ma and a metamorphic age of 805 11 Ma. It is not possible to correlate any of these lithologies or events across the SRMT with the Malton block, and it is concluded that the SRMT is the site of a major fault or faults at this latitude. Nous prksentons les donnkes pktrographiques, gkochimiques et gkochronologiques sur les gneiss des blocs Bulldog Creek, Mount Blackman et Hugh Allan Creek, lesquels sont situks i I'est du sillon des Rocheuses du Sud, au sud de Valemount en Colombie-Britannique.

The replication of vaccinia virus in human hematopoietic cell lines was studied, to ascertain whether the cell type and the stage of differentiation can influence the outcome of the infection. Lymphocytic NB104 cells and myelogenous leukemic K562 cells can be productively infected with vaccinia. Whereas NB104 cells were readily lysed, cells from the K562 line stayed persistently infected. Infection of promyelocytic leukemia HL60 cells results in an abortive infection in which the virus is uncoated, does not replicate, remains latent and can be rescued by cocultivation with permissive cells. Upon addition of phorbol esters to HL60 cell cultures, viral replication resumed. These results suggests that, although vaccinia virus replication is almost independent of host-specific functions, the outcome of the infection may depend on the cell type and its stage of differentiation.

Rare-earth elements and other trace elements have been determined by activation analysis and X-ray fluorescence for representative samples from each of the four blocks of basement gneisses near Valemount, eastern British Columbia. Patterns in mafic and tonalitic gneisses are generally as expected, but the granite–gneisses have very large negative europium anomalies, up to Eu*/Eu = 18, indicating multistage histories involving plagioclase fractionation. Modelling shows that plagioclase fractionation alone is insufficient to account for these anomalies without intervention of other phases: apatite control is suggested, among other possibilities. The granite–gneisses also contain exceptionally low magnesium (0.1–0.2%), phosphorus (

Synopsis The chemical composition of 63 samples of non-calcareous semipelitic schists from the Lewisian Loch Maree Group at Gairloch, Wester Ross is compared with that of 83 samples of the adjacent acid gneisses. The semipelitic metasediments can be clearly distinguished from the gneisses by their significantly higher Fe 2 O 3 (total), MgO, TiC 2 , Nb, Y, Zr, Zn, Cu, Cr and Ni contents, and lower concentrations of Al 2 O 3 , Na 2 O, Ba and Sr. These chemical differences can be used to distinguish sheared gneisses from sheared metasediments in certain transitional schist belts where the origin was formerly in doubt. Previous views that the semipelitic schists represented predominantly non-volcanogenic, greywacke-type sediments are confirmed, and the presence of two chemically distinct types representing different stratigraphic units is established. These metasediments are distinct from other Lewisian metasediments described in Assynt and Harris.