The Nestlé crash

On November 17, 1988, the board of directors of Nestlé AG decided to allow foreign investors to hold Nestlé registered stock, reversing a longstanding practice. This decision had a tremendous impact on the prices of the firm's three classes of common stock, as well as on the prices of several other corporations traded on the Zürich stock exchange. These price changes can be explained by the hypothesis that demand curves slope down.

Brain electric correlates of strong belief in paranormal phenomena: intracerebral EEG source and regional Omega complexity analyses

The neurocognitive processes underlying the formation and maintenance of paranormal beliefs are important for understanding schizotypal ideation. Behavioral studies indicated that both schizotypal and paranormal ideation are based on an overreliance on the right hemisphere, whose coarse rather than focussed semantic processing may favor the emergence of 'loose' and 'uncommon' associations. To elucidate the electrophysiological basis of these behavioral observations, 35-channel resting EEG was recorded in pre-screened female strong believers and disbelievers during resting baseline. EEG data were subjected to FFT-Dipole-Approximation analysis, a reference-free frequency-domain dipole source modeling, and Regional (hemispheric) Omega Complexity analysis, a linear approach estimating the complexity of the trajectories of momentary EEG map series in state space. Compared to disbelievers, believers showed: more right-located sources of the beta2 band (18.5-21 Hz, excitatory activity); reduced interhemispheric differences in Omega complexity values; higher scores on the Magical Ideation scale; more general negative affect; and more hypnagogic-like reveries after a 4-min eyes-closed resting period. Thus, subjects differing in their declared paranormal belief displayed different active, cerebral neural populations during resting, task-free conditions. As hypothesized, believers showed relatively higher right hemispheric activation and reduced hemispheric asymmetry of functional complexity. These markers may constitute the neurophysiological basis for paranormal and schizotypal ideation.

Face-elicited ERPs and affective attitude: brain electric microstate and tomography analyses

Objectives: Although behavioral studies have demonstrated that normative affective traits modulate the processing of facial and emotionally charged stimuli, direct electrophysiological evidence for this modulation is still lacking. Methods: Event-related potential (ERP) data associated with personal, traitlike approach- or withdrawal-related attitude (assessed post-recording and 14 months later) were investigated in 18 subjects during task-free (i.e. unrequested, spontaneous) emotional evaluation of faces. Temporal and spatial aspects of 27 channel ERP were analyzed with microstate analysis and low resolution electromagnetic tomography (LORETA), a new method to compute 3 dimensional cortical current density implemented in the Talairach brain atlas. Results: Microstate analysis showed group differences 132-196 and 196-272 ms poststimulus, with right-shifted electric gravity centers for subjects with negative affective attitude. During these (over subjects reliably identifiable) personality-modulated, face-elicited microstates, LORETA revealed activation of bilateral occipito-temporal regions, reportedly associated with facial configuration extraction processes. Negative compared to positive affective attitude showed higher activity right temporal; positive compared to negative attitude showed higher activity left temporo-parieto-occipital. Conclusions: These temporal and spatial aspects suggest that the subject groups differed in brain activity at early, automatic, stimulus-related face processing steps when structural face encoding (configuration extraction) occurs. In sum, the brain functional microstates associated with affect-related personality features modulate brain mechanisms during face processing already at early information processing stages.

Molecular phylogenetic analyses identify Alpine differentiation and dysploid chromosome number changes as major forces for the evolution of the European endemic Phyteuma (Campanulaceae)

Phyteuma is a chromosomally and ecologically diverse vascular plant genus and constitutes an excellent system for studying both the role of chromosomal change for species diversification and the evolution of high-mountain biota. This kind of research is, however, hampered by the lack of a sound phylogenetic framework exacerbated by the notoriously low predictive power of traditional taxonomy with respect to phylogenetic relationships in Campanulaceae. Based on a comprehensive taxon sampling and analyses of nuclear and plastid sequence and AFLP fingerprint data, Phyteuma is confirmed as a monophyletic group sister to the monotypic Physoplexis, which is in line with their peculiar flower morphologies. Within Phyteuma two clades, largely corresponding to previously recognized sections, are consistently found. The traditional circumscription of taxonomic series is largely rejected. Whereas distinctness of the currently recognized species is mostly corroborated, some interspecific relationships remain ambiguous due to incongruences between nuclear and plastid data. Major forces for diversification and evolution of Phyteuma are descending dysploidy (i.e., a decrease in chromosome base number) as well as allopatric and ecological differentiation within the Alps, the genus' center of species diversity. (C) 2013 Elsevier Inc. All rights reserved.

Combining follow-up and change data is valid in meta-analyses of continuous outcomes: a meta-epidemiological study

OBJECTIVE To investigate whether it is valid to combine follow-up and change data when conducting meta-analyses of continuous outcomes. STUDY DESIGN AND SETTING Meta-epidemiological study of randomized controlled trials in patients with osteoarthritis of the knee/hip, which assessed patient-reported pain. We calculated standardized mean differences (SMDs) based on follow-up and change data, and pooled within-trial differences in SMDs. We also derived pooled SMDs indicating the largest treatment effect within a trial (optimistic selection of SMDs) and derived pooled SMDs from the estimate indicating the smallest treatment effect within a trial (pessimistic selection of SMDs). RESULTS A total of 21 meta-analyses with 189 trials with 292 randomized comparisons in 41,256 patients were included. On average, SMDs were 0.04 standard deviation units more beneficial when follow-up values were used (difference in SMDs: -0.04; 95% confidence interval: -0.13, 0.06; P=0.44). In 13 meta-analyses (62%), there was a relevant difference in clinical and/or significance level between optimistic and pessimistic pooled SMDs. CONCLUSION On average, there is no relevant difference between follow-up and change data SMDs, and combining these estimates in meta-analysis is generally valid. Decision on which type of data to use when both follow-up and change data are available should be prespecified in the meta-analysis protocol.

Patient-reported outcomes in meta-analyses - part 2: methods for improving interpretability for decision-makers

Systematic reviews and meta-analyses of randomized trials that include patient-reported outcomes (PROs) often provide crucial information for patients, clinicians and policy-makers facing challenging health care decisions. Based on emerging methods, guidance on improving the interpretability of meta-analysis of patient-reported outcomes, typically continuous in nature, is likely to enhance decision-making. The objective of this paper is to summarize approaches to enhancing the interpretability of pooled estimates of PROs in meta-analyses. When differences in PROs between groups are statistically significant, decision-makers must be able to interpret the magnitude of effect. This is challenging when, as is often the case, clinical trial investigators use different measurement instruments for the same construct within and between individual randomized trials. For such cases, in addition to pooling results as a standardized mean difference, we recommend that systematic review authors use other methods to present results such as relative (relative risk, odds ratio) or absolute (risk difference) dichotomized treatment effects, complimented by presentation in either: natural units (e.g. overall depression reduced by 2.4 points when measured on a 50-point Hamilton Rating Scale for Depression); minimal important difference units (e.g. where 1.0 unit represents the smallest difference in depression that patients, on average, perceive as important the depression score was 0.38 (95%CI 0.30 to 0.47) units less than the control group); or a ratio of means (e.g. where the mean in the treatment group is divided by the mean in the control group, the ratio of means is 1.27, representing a 27%relative reduction in the mean depression score).

Biochemical, single-channel, whole-cell patch clamp, and pharmacological analyses of endogenous TRPM4 channels in HEK293 cells

Human embryonic kidney cells 293 (HEK293) are widely used as cellular heterologous expression systems to study transfected ion channels. This work characterizes the endogenous expression of TRPM4 channels in HEK293 cells. TRPM4 is an intracellular Ca(2+)-activated non-selective cationic channel expressed in many cell types. Western blot analyses have revealed the endogenous expression of TRPM4. Single channel 22pS conductance with a linear current-voltage relationship was observed using the inside-out patch clamp configuration in the presence of intracellular Ca(2+). The channels were permeable to the monovalent cations Na(+) and K(+), but not to Ca(2+). The open probability was voltage-dependent, being higher at positive potentials. Using the whole-cell patch clamp "ruptured patch" configuration, the amplitude of the intracellular Ca(2+)-activated macroscopic current was dependent on time after patch rupture. Initial transient activation followed by a steady-increase reaching a plateau phase was observed. Biophysical analyses of the macroscopic current showed common properties with those from HEK293 cells stably transfected with human TRPM4b, with the exception of current time course and Ca(2+) sensitivity. The endogenous macroscopic current reached the plateau faster and required 61.9±3.5μM Ca(2+) to be half-maximally activated versus 84.2±1.5μM for the transfected current. The pharmacological properties, however, were similar in both conditions. One hundred μM of flufenamic acid and 9-phenanthrol strongly inhibited the endogenous current. Altogether, the data demonstrate the expression of endogenous TRMP4 channels in HEK293 cells. This observation should be taken into account when using this cell line to study TRPM4 or other types of Ca(2+)-activated channels.

Chronology of Lake El'gygytgyn sediments – a combined magnetostratigraphic, palaeoclimatic and orbital tuning study based on multi-parameter analyses

A 318-metre-long sedimentary profile drilled by the International Continental Scientific Drilling Program (ICDP) at Site 5011-1 in Lake El’gygytgyn, Far East Russian Arctic, has been analysed for its sedimentologic response to global climate modes by chronostratigraphic methods. The 12 km wide lake is sited off-centre in an 18 km large crater that was created by the impact of a meteorite 3.58 Ma ago. Since then sediments have been continuously deposited. For establishing their chronology, major reversals of the earth’s magnetic field provided initial tie points for the age model, confirming that the impact occurred in the earliest geomagnetic Gauss chron. Various stratigraphic parameters, reflecting redox conditions at the lake floor and climatic conditions in the catchment were tuned synchronously to Northern Hemisphere insolation variations and the marine oxygen isotope stack, respectively. Thus, a robust age model comprising more than 600 tie points could be defined. It could be shown that deposition of sediments in Lake El’gygytgyn occurred in concert with global climatic cycles. The upper �160m of sediments represent the past 3.3 Ma, equivalent to sedimentation rates of 4 to 5 cm ka−1, whereas the lower 160m represent just the first 0.3 Ma after the impact, equivalent to sedimentation rates in the order of 45 cm ka−1. This study also provides orbitally tuned ages for a total of 8 tephras deposited in Lake El’gygytgyn.

[Sense and nonsense of toxicological analyses in the daily clinical routine]

Screening tests for drugs of abuse are regularly used in the clinical routine. These tests identify the targeted substances very differently if tests from different manufacturers are used and sometimes also react positive after the intake of drugs which are not intended to be detected. Therefore, implausible results have to be questioned. A test result can be falsely negative, if a patient has taken a compound which is not detected by the antibody used in the test system. Chromatographic confirmation and screening assays are more laborious to perform and more demanding for the interpretation and are therefore only offered by several specialized clinical laboratories. However, their specificity is excellent and many different compounds can be detected depending on the number of compounds which are part of the mass spectra library used. If the clinical evaluation results in the differential diagnosis of an acute intoxication, screening tests for drugs of abuse can help to identify a single compound or a group of substances. The clinical picture, however, can usually not been explained by a qualitative test result. In addition, there are no published data demonstrating that these tests meaningfully influence triage, treatment, diagnosis or further therapy of a poisoned patient. The quantitative determination of specific compounds in the blood allows for example an appraisal of the prognosis and helps to indicate a specific therapy after intake of acetaminophen or methanol. New designer drugs can not at all be detected by the classic screening tests for drugs of abuse. The have to be identified by chromatographic methods.

Effects of exercise on anxiety and depression disorders: Review of meta-analyses and neurobiological mechanisms

Anxiety and depression are the most frequently diagnosed psychological diseases showing a high co-morbidity. They have a severe impact on the lives of the persons concerned. Many meta-analytical studies suggested a positive anxiolytic and depression reducing effect of exercise programs. The aim of the present article is to synthesize metaanalyses on the effects of exercise on anxiety and depression and to describe average effect sizes. For this purpose 37 meta-analyses were included reporting 50 effect sizes for anxiety scores of 42,264 participants and depression scores of 48,207 persons. The average documented anxiolytic effect of exercise in these reviews was small, 0.34. In contrast, the effect of exercise on depression was significantly higher and at a moderate level, 0.56. Data of randomized controlled trials suggest higher sizes for the effect of exercise on anxiety and depression leading to increases up to moderate and large effects, respectively. Additionally, exercise seems to be more beneficial for patients compared to participants within a nonclinical, normal range of psychological disease. Especially for the effect of exercise on anxiety, more high quality meta-analyses of randomized controlled trials are needed. Finally, possible neurobiological explanations are suggested for the positive effect of exercise on psychological disorders like anxiety and depression.

Effects of erythropoiesis-stimulating agents on fatigue- and anaemia-related symptoms in cancer patients: systematic review and meta-analyses of published and unpublished data.

Background:Erythropoiesis-stimulating agents (ESAs) reduce the need for red blood cell transfusions; however, they increase the risk of thromboembolic events and mortality. The impact of ESAs on quality of life (QoL) is controversial and led to different recommendations of medical societies and authorities in the USA and Europe. We aimed to critically evaluate and quantify the effects of ESAs on QoL in cancer patients.Methods:We included data from randomised controlled trials (RCTs) on the effects of ESAs on QoL in cancer patients. Randomised controlled trials were identified by searching electronic data bases and other sources up to January 2011. To reduce publication and outcome reporting biases, we included unreported results from clinical study reports. We conducted meta-analyses on fatigue- and anaemia-related symptoms measured with the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and FACT-Anaemia (FACT-An) subscales (primary outcomes) or other validated instruments.Results:We identified 58 eligible RCTs. Clinical study reports were available for 27% (4 out of 15) of the investigator-initiated trials and 95% (41 out of 43) of the industry-initiated trials. We excluded 21 RTCs as we could not use their QoL data for meta-analyses, either because of incomplete reporting (17 RCTs) or because of premature closure of the trial (4 RCTs). We included 37 RCTs with 10 581 patients; 21 RCTs were placebo controlled. Chemotherapy was given in 27 of the 37 RCTs. The median baseline haemoglobin (Hb) level was 10.1 g dl(-1); in 8 studies ESAs were stopped at Hb levels below 13 g dl(-1) and in 27 above 13 g dl(-1). For FACT-F, the mean difference (MD) was 2.41 (95% confidence interval (95% CI) 1.39-3.43; P<0.0001; 23 studies, n=6108) in all cancer patients and 2.81 (95% CI 1.73-3.90; P<0.0001; 19 RCTs, n=4697) in patients receiving chemotherapy, which was below the threshold (⩾3) for a clinically important difference (CID). Erythropoiesis-stimulating agents had a positive effect on anaemia-related symptoms (MD 4.09; 95% CI 2.37-5.80; P=0.001; 14 studies, n=2765) in all cancer patients and 4.50 (95% CI 2.55-6.45; P<0.0001; 11 RCTs, n=2436) in patients receiving chemotherapy, which was above the threshold (⩾4) for a CID. Of note, this effect persisted when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy. There was some evidence that the MDs for FACT-F were above the threshold for a CID in RCTs including cancer patients receiving chemotherapy with Hb levels below 12 g dl(-1) at baseline and in RCTs stopping ESAs at Hb levels above 13 g dl(-1). However, these findings for FACT-F were not confirmed when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy.Conclusions:In cancer patients, particularly those receiving chemotherapy, we found that ESAs provide a small but clinically important improvement in anaemia-related symptoms (FACT-An). For fatigue-related symptoms (FACT-F), the overall effect did not reach the threshold for a CID.British Journal of Cancer advance online publication, 17 April 2014; doi:10.1038/bjc.2014.171 www.bjcancer.com.