Mountain pine beetles and Colorado forests : findings from a re-survey of Colorado community residents

North Central Colorado has experienced an extensive mountain pine beetle outbreak over the last 20 years. We conducted a survey of Colorado residents about their response to forest disturbance by mountain pine beetles in 2007. A survey questionnaire was sent to randomly selected households in Breckenridge, Dillon, Frisco, Granby, Kremmling, Silverthorne, Steamboat Springs, Vail, and Walden, Colorado. In 2018, we did a follow-up mail survey to see how local communities and residents have experienced and reacted to the mountain pine beetle outbreak and the accompanying changes in Colorado forests over time. These reports describe major findings of the 2018 re-survey for the whole study area and for individual study communities.This research was supported by the Decision, Risk and Management Sciences Program of the National Science Foundation (Award #1733990).This research was supported by the Decision, Risk and Management Sciences Program of the National Science Foundation (Award #1733990).Hua Qin, Elizabeth Prentice, Christine Sanders (University of Missouri-Columbia), Hannah Brenkert-Smith, Jamie Vickery (University of Colorado Boulder)Colorado re-survey report (20 pages : illustration) -- Breckenridge community survey report (13 pages : illustration) -- Dillon community survey report (13 pages : illustration) -- Frisco community survey report (13 pages : illustration) -- Granby community survey report (13 pages : illustration) -- Kremmling community survey report (13 pages : illustration) -- Silverthorne community survey report (13 pages : illustration) -- Steamboat Spring community survey report (13 pages : illustration) -- Vait community survey report (13 pages : illustration) -- Walden community survey report (13 pages : illustration

Fulfilling the Promise of Personalized Medicine? Systematic Review and Field Synopsis of Pharmacogenetic Studies

BACKGROUND: Studies of the genetic basis of drug response could help clarify mechanisms of drug action/metabolism, and facilitate development of genotype-based predictive tests of efficacy or toxicity (pharmacogenetics). OBJECTIVES: We conducted a systematic review and field synopsis of pharmacogenetic studies to quantify the scope and quality of available evidence in this field in order to inform future research. DATA SOURCES: Original research articles were identified in Medline, reference lists from 24 meta-analyses/systematic reviews/review articles and U.S. Food and Drug Administration website of approved pharmacogenetic tests. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTION CRITERIA: We included any study in which either intended or adverse response to drug therapy was examined in relation to genetic variation in the germline or cancer cells in humans. STUDY APPRAISAL AND SYNTHESIS METHODS: Study characteristics and data reported in abstracts were recorded. We further analysed full text from a random 10% subset of articles spanning the different subclasses of study. RESULTS: From 102,264 Medline hits and 1,641 articles from other sources, we identified 1,668 primary research articles (1987 to 2007, inclusive). A high proportion of remaining articles were reviews/commentaries (ratio of reviews to primary research approximately 25 ratio 1). The majority of studies (81.8%) were set in Europe and North America focussing on cancer, cardiovascular disease and neurology/psychiatry. There was predominantly a candidate gene approach using common alleles, which despite small sample sizes (median 93 [IQR 40-222]) with no trend to an increase over time, generated a high proportion (74.5%) of nominally significant (por=4 studies, only 31 meta-analyses were identified. The majority (69.4%) of end-points were continuous and likely surrogate rather than hard (binary) clinical end-points. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The high expectation but limited translation of pharmacogenetic research thus far may be explained by the preponderance of reviews over primary research, small sample sizes, a mainly candidate gene approach, surrogate markers, an excess of nominally positive to truly positive associations and paucity of meta-analyses. Recommendations based on these findings should inform future study design to help realise the goal of personalised medicines. SYSTEMATIC REVIEW REGISTRATION NUMBER: Not Registered

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

The therapist as victim: a preliminary discussion

p. 155-158Increasingly reports are being received from colleagues, supervisees, and consultees from around the country that patients who were severely abused as children and are pathologically dissociated as adults may be increasingly prone to victimize their therapists intentionally. Actions taken by such patients have included the filing of frivolous or malicious complaints or lawsuits, the spreading of rumors about the therapist, harassment of other patients of the therapist, and violation of the therapist's privacy and personal space, among many others. Such behaviors may be in response to patients' own internal distress, to unrecognized complexities within the therapeutic process, to re-enactments, and/or to patients' resistance against focusing on their own issues. The authors contend that although some therapists have behaved inappropriately with their patients, there are identifiable dynamics within the patients and within the therapeutic relationship that could alert the therapist to the potential of destructive acting-out towards the therapist. The purpose of this paper is to acknowledge the phenomenon of therapist victimization, to discuss some of the underlying dynamics, and to begin to address possible preventive measures

E-journals at the British Library: from selection to access

The British Library is embracing e-technology across all aspects of its work and this article concentrates on e-journals. The Library is facing some real challenges in use of the medium from licensing issues to the question of legal deposit of electronic material, both of which are outlined in the article. A code of practice for the voluntary deposit of non-print publications is in place between publishers and legal deposit libraries, covering offline electronic media, but deposit of print serial issues is still rising. E-journals are purchased for both reading room reference and remote document supply and statistics show that reading room use of e-journals is increasing. The Library is increasingly working with others and sees partnerships with similar institutions as the best way forward

Expression, purification and characterisation of GIGANTEA: A circadian clock-controlled regulator of photoperiodic flowering in plants

The Arabidopsis thaliana (Arabidopsis) GIGANTEA (GI) gene is a central component of the photoperiodic flowering pathway. While it has been 40 years since the first mutant alleles of GI were described much is still unknown about the molecular mechanism of GI action. To investigate the biochemistry and domain organisation (and ultimately to give a greater understanding of the role of GI in floral induction), it is first necessary to produce significant quantities of purified protein. Soluble affinity-tagged full-length GI was expressed in Escherichia coli (E. coli) and was stabilised by the addition of the detergent n-dodecyl-β-d-maltoside (DDM) to storage and purification buffers. Stabilised GI was purified using a variety of chromatographic methods, and characterised using a selection of biochemical techniques including circular dichroism, and dynamic light scattering. This showed that purified GI contained secondary structure, but was polydisperse in solution. Electron microscopy suggests a possible tetramer arrangement of GI. Limited proteolytic digests and mass spectrometry were used to identify potential GI domains. This led to the identification of a predicted 46 kDa amino-terminal GI domain. GI was also expressed in Sf9 insect cells using the baculovirus expression system. GI produced via this route gave insoluble protein

RelB NF-κB Represses Estrogen Receptor α Expression via Induction of the Zinc Finger Protein Blimp1▿ ‡

Aberrant constitutive expression of NF-κB subunits, reported in more than 90% of breast cancers and multiple other malignancies, plays pivotal roles in tumorigenesis. Higher RelB subunit expression was demonstrated in estrogen receptor alpha (ERα)-negative breast cancers versus ERα-positive ones, due in part to repression of RelB synthesis by ERα signaling. Notably, RelB promoted a more invasive phenotype in ERα-negative cancers via induction of the BCL2 gene. We report here that RelB reciprocally inhibits ERα synthesis in breast cancer cells, which contributes to a more migratory phenotype. Specifically, RelB is shown for the first time to induce expression of the zinc finger repressor protein Blimp1 (B-lymphocyte-induced maturation protein), the critical mediator of B- and T-cell development, which is transcribed from the PRDM1 gene. Blimp1 protein repressed ERα (ESR1) gene transcription. Commensurately higher Blimp1/PRDM1 expression was detected in ERα-negative breast cancer cells and primary breast tumors. Induction of PRDM1 gene expression was mediated by interaction of Bcl-2, localized in the mitochondria, with Ras. Thus, the induction of Blimp1 represents a novel mechanism whereby the RelB NF-κB subunit mediates repression, specifically of ERα, thereby promoting a more migratory phenotype