Systematics and Palynology of Picrodendron Further Evidence for Relationship with the Oldfieldioideae (Euphorbiaceae)

Although known to botanical science for 285 years, the genus Picrodendron Planchon has been poorly understood for most of this time. The most pervasive problem has been that of discerning familial relationships, and there have been additional difficulties in typifying the generic name (Hayden & Reveal, 1980) and in distinguishing its three nominate species. This paper provides a systematic treatment for Picrodendron and demonstrates its relationships with Euphorbiaceae subfam. Oldfieldioideae Kohler & Webster as evidenced by data on gross morphology, palynology, anatomy, and cytology

Rationality as the Rule of Reason

The demands of rationality are linked both to our subjective normative perspective (given that rationality is a person-level concept) and to objective reasons or favoring relations (given that rationality is non-contingently authoritative for us). In this paper, I propose a new way of reconciling the tension between these two aspects: roughly, what rationality requires of us is having the attitudes that correspond to our take on reasons in the light of our evidence, but only if it is competent. I show how this view can account for structural rationality on the assumption that intentions and beliefs as such involve competent perceptions of downstream reasons, and explore various implications of the account

Pre-exercise carbohydrate or protein ingestion influences substrate oxidation but not performance or hunger compared with cycling in the fasted state

Nutritional intake can influence exercise metabolism and performance, but there is a lack of research comparing protein-rich pre-exercise meals with endurance exercise performed both in the fasted state and following a carbohydrate-rich breakfast. The purpose of this study was to determine the effects of three pre-exercise nutrition strategies on metabolism and exercise capacity during cycling. On three occasions, seventeen trained male cyclists (VO2peak 62.2 ± 5.8 mL·kg−1·min−1, 31.2 ± 12.4 years, 74.8 ± 9.6 kg) performed twenty minutes of submaximal cycling (4 × 5 min stages at 60%, 80%, and 100% of ventilatory threshold (VT), and 20% of the difference between power at the VT and peak power), followed by 3 × 3 min intervals at 80% peak aerobic power and 3 × 3 min intervals at maximal effort, 30 min after consuming a carbohydrate-rich meal (CARB; 1 g/kg CHO), a protein-rich meal (PROTEIN; 0.45 g/kg protein + 0.24 g/kg fat), or water (FASTED), in a randomized and counter-balanced order. Fat oxidation was lower for CARB compared with FASTED at and below the VT, and compared with PROTEIN at 60% VT. There were no differences between trials for average power during high-intensity intervals (367 ± 51 W, p = 0.516). Oxidative stress (F2-Isoprostanes), perceived exertion, and hunger were not different between trials. Overall, exercising in the overnight-fasted state increased fat oxidation during submaximal exercise compared with exercise following a CHO-rich breakfast, and pre-exercise protein ingestion allowed similarly high levels of fat oxidation. There were no differences in perceived exertion, hunger, or performance, and we provide novel data showing no influence of pre-exercise nutrition ingestion on exercise-induced oxidative stress

Neural correlates of visuospatial working memory in the ‘at-risk mental state’

Background. Impaired spatial working memory (SWM) is a robust feature of schizophrenia and has been linked to the risk of developing psychosis in people with an at-risk mental state (ARMS). We used functional magnetic resonance imaging (fMRI) to examine the neural substrate of SWM in the ARMS and in patients who had just developed schizophrenia. Method. fMRI was used to study 17 patients with an ARMS, 10 patients with a first episode of psychosis and 15 agematched healthy comparison subjects. The blood oxygen level-dependent (BOLD) response was measured while subjects performed an object–location paired-associate memory task, with experimental manipulation of mnemonic load. Results. In all groups, increasing mnemonic load was associated with activation in the medial frontal and medial posterior parietal cortex. Significant between-group differences in activation were evident in a cluster spanning the medial frontal cortex and right precuneus, with the ARMS groups showing less activation than controls but greater activation than first-episode psychosis (FEP) patients. These group differences were more evident at the most demanding levels of the task than at the easy level. In all groups, task performance improved with repetition of the conditions. However, there was a significant group difference in the response of the right precuneus across repeated trials, with an attenuation of activation in controls but increased activation in FEP and little change in the ARMS. Conclusions. Abnormal neural activity in the medial frontal cortex and posterior parietal cortex during an SWM task may be a neural correlate of increased vulnerability to psychosis

Diphacinone and coumatetralyl persistence in deer and implications for wildlife management

Eason, C.T., Murphy, E., Ross, J.G., Hix, S., Arthur, D., MacMorran, D., Broome, K., Fairweather, A

Anti-GnRH antibodies can induce castrate levels of testosterone in patients with advanced prostate cancer

D17DT consists of the GnRH decapeptide linked to diphtheria toxoid. The aim of this pilot study was to assess the tolerance of D17DT and the production of anti-GnRH antibodies from two doses, 30 and 100 μg, in patients with locally advanced prostate cancer. Twelve patients with histologically proven prostate cancer in whom hormonal therapy was indicated were recruited. Patients received either 30 or 100 μg given intramuscularly on three separate occasions over six weeks. Patients were followed up and blood was taken for estimation of serum testosterone, PSA and anti-GnRH antibody titre. Overall the drug was well tolerated. In 5 patients a significant reduction in serum testosterone and PSA was seen. Castrate levels of testosterone were achieved in 4 and maintained for up to 9 months. Patients with the highest antibody titre had the best response in terms of testosterone suppression. This study shows that it is possible to immunize a patient with prostate cancer against GnRH to induce castrate levels of testosterone. This state appears to be reversible. This novel form of immunotherapy may have advantages over conventional forms of hormonal therapy and further studies are warranted in order to try and increase the proportion of responders. © 2000 Cancer Research Campaig

CYP2D6 drug-gene and drug-drug-gene interactions among patients prescribed pharmacogenetically actionable opioids

Purpose When codeine and tramadol are used for pain management, it is imperative that nurses are able to assess for potential drug-gene and drug-drug-gene interactions that could adversely impact drug metabolism and ultimately pain relief. Both drugs are metabolized through the CYP2D6 metabolic pathway which can be affected by medications as well the patient's own pharmacogenotype. The purpose of this brief report is to identify drug-gene and drug-drug-gene interactions in 30 adult patients prescribed codeine or tramadol for pain. Methods We used three data sources: (1) six months of electronic health record data on the number and types of medications prescribed to each patient; (2) each patient's CYP2D6 pharmacogenotype, and (3) published data on known CYP2D6 gene-drug and drug-drug-gene interactions. Results Ten patients (33%) had possible drug-gene or drug-drug-gene interactions. Five patients had CYP2D6 drug-gene interactions indicating they were not good candidates for codeine or tramadol. In addition, five patients had potential CYP2D6 drug-drug-gene interactions with either codeine or tramadol. Conclusion Our findings from this exploratory study underscores the importance of assessing and accounting for drug-gene and drug-drug-gene interactions in patients prescribed codeine or tramadol

Global Governance Behind Closed Doors : The IMF Boardroom, the Enhanced Structural Adjustment Facility, and the Intersection of Material Power and Norm Change in Global Politics

Up on the 12th floor of its 19th Street Headquarters, the IMF Board sits in active session for an average of 7 hours per week. Although key matters of policy are decided on in the venue, the rules governing Boardroom interactions remain opaque, resting on an uneasy combination of consensual decision-making and weighted voting. Through a detailed analysis of IMF Board discussions surrounding the Enhanced Structural Adjustment Facility (ESAF), this article sheds light on the mechanics of power in this often overlooked venue of global economic governance. By exploring the key issues of default liability and loan conditionality, I demonstrate that whilst the Boardroom is a more active site of contestation than has hitherto been recognized, material power is a prime determinant of both Executive Directors’ preferences and outcomes reached from discussions. And as the decisions reached form the backbone of the ‘instruction sheet’ used by Fund staff to guide their everyday operational decisions, these outcomes—and the processes through which they were reached—were factors of primary importance in stabilizing the operational norms at the heart of a controversial phase in the contemporary history of IMF concessional lending

Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome

Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P = .041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis

Wnt5a induces ROR1 to complex with HS1 to enhance migration of chronic lymphocytic leukemia cells.

ROR1 (receptor tyrosine kinase-like orphan receptor 1) is a conserved, oncoembryonic surface antigen expressed in chronic lymphocytic leukemia (CLL). We found that ROR1 associates with hematopoietic-lineage-cell-specific protein 1 (HS1) in freshly isolated CLL cells or in CLL cells cultured with exogenous Wnt5a. Wnt5a also induced HS1 tyrosine phosphorylation, recruitment of ARHGEF1, activation of RhoA and enhanced chemokine-directed migration; such effects could be inhibited by cirmtuzumab, a humanized anti-ROR1 mAb. We generated truncated forms of ROR1 and found its extracellular cysteine-rich domain or kringle domain was necessary for Wnt5a-induced HS1 phosphorylation. Moreover, the cytoplamic, and more specifically the proline-rich domain (PRD), of ROR1 was required for it to associate with HS1 and allow for F-actin polymerization in response to Wnt5a. Accordingly, we introduced single amino acid substitutions of proline (P) to alanine (A) in the ROR1 PRD at positions 784, 808, 826, 841 or 850 in potential SH3-binding motifs. In contrast to wild-type ROR1, or other ROR1P→︀A mutants, ROR1P(841)A had impaired capacity to recruit HS1 and ARHGEF1 to ROR1 in response to Wnt5a. Moreover, Wnt5a could not induce cells expressing ROR1P(841)A to phosphorylate HS1 or activate ARHGEF1, and was unable to enhance CLL-cell motility. Collectively, these studies indicate HS1 plays an important role in ROR1-dependent Wnt5a-enhanced chemokine-directed leukemia-cell migration