Rapid tranquilization of severely agitated patients with schizophrenia spectrum disorders: a naturalistic, rater-blinded, randomized controlled study with oral haloperidol, risperidone, and olanzapine

Agitation is a major problem in acute schizophrenia. Still, only limited evidence exists on antipsychotic efficacy in severely agitated patients after the first 24 hours. We aimed to investigate the efficacy of oral haloperidol, risperidone, and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospective, randomized, rater-blinded, controlled design within a naturalistic treatment regimen. We enrolled 43 severely agitated patients at acute care psychiatric units. Participants were randomly assigned to receive either daily haloperidol 15 mg, olanzapine 20 mg, or risperidone 2 – 6 mg over 5 days. Positive and Negative Syndrome Scale psychotic agitation (PANSS-PAS) subscore was the primary outcome variable. A mixed model analyses was applied. All drugs were effective for rapid tranquillization within 2 hours. Over 5 days, the course differed between agents (p < 0.001) but none was superior. Dropouts occurred only in the risperidone and olanzapine groups. Men responded better to treatment than women during the initial 2 hours (p = 0.046) as well as over the 5 day course (p < 0.001). No difference between drug groups was observed regarding diazepam or biperiden use. Oral haloperidol, risperidone, and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders. We observed a gender effect with poorer outcome in women.

Highly pathogenic adapted HIV-1 strains limit host immunity and dictate rapid disease progression.

OBJECTIVE: The study of HIV-1 rapid progressors has been limited to specific case reports. Nevertheless, identification and characterization of the viral and host factors involved in rapid progression are crucial when attempting to uncover the correlates of rapid disease outcome. DESIGN: We carried out comparative functional analyses in rapid progressors (n = 46) and standard progressors (n = 46) early after HIV-1 seroconversion (≤1 year). The viral traits tested were viral replicative capacity, co-receptor usage, and genomic variation. Host CD8 T-cell responses, humoral activity, and HLA immunogenetic markers were also determined. RESULTS: Our data demonstrate an unusual convergence of highly pathogenic HIV-1 strains in rapid progressors. Compared with standard progressors, rapid progressor viral strains show higher in-vitro replicative capacity (81.5 vs. 67.9%; P = 0.025) and greater X4/DM co-receptor usage (26.3 vs. 2.8%; P = 0.006) in early infection. Limited or absent functional HIV-1 CD8 T-cell responses and neutralizing activity were measured in rapid progressors. Moreover, the increase in common HLA allele-restricted CD8 T-cell escape mutations in rapid progressors acts as a signature of uncontrolled HIV-1 replication and early impairment of adaptive cellular responses. CONCLUSION: Our data support a dominant role for viral factors in rapid progressors. Robust HIV-1 replication and intrinsic viral properties limit host adaptive immune responses, thus driving rapid disease progression.

Responses to rapid warming at Termination 1a at Gerzensee (Central Europe): Primary succession, albedo, soils, lake development, and ecological interactions

The transition from the Oldest Dryas to the Bølling around 14,685 cal yr BP was a period of extremely rapid climatic warming. From a single core of lake marl taken at Gerzensee (Switzerland) we studied the transition in stable isotopes of oxygen and carbon on bulk sediment and charophyte remains, as well as on monospecific samples of ostracods, after Pisidium a; in addition pollen, chironomids, and Cladocera were analyzed. The δ18O record serves as an estimate of mean air temperature, and by correlation to the one from NGRIP in Greenland it provides a timescale. The timing of responses: The statistically significant zone boundaries of the biostratigraphies are telescoped at the rapid increase of about 3‰ in δ18O at the onset of Bølling. Biotic responses may have occurred within sampling resolution (8 to 16 years), although younger zone boundaries are less synchronous. Gradual and longer-lasting responses include complex processes such as primary or secular succession. During the late-glacial interstadial of Bølling and Allerød, two stronger and two weaker cool phases were found. Biological processes involved in the responses occurred on levels of individuals (e.g. pollen productivity), of populations (increases or decreases, immigration, or extinction), and on the ecosystem level (species interactions such as facilitation or competition). Abiotic and biotic interactions include pedogenesis, nitrogen-fixation, nutrient cycling, catchment hydrology, water chemistry of the lake and albedo (controlled by the transition from tundra to forest). For the Swiss Plateau this major change in vegetation induced a change in the mammal fauna, which in turn led to changes in the tool-making by Paleolithic people.

Vegetation responses to rapid warming and to minor climatic fluctuations during the Late-Glacial Interstadial (GI-1) at Gerzensee (Switzerland)

High-resolution pollen analyses made on the same samples on which the ratios of oxygen isotopes were measured that provided the time scale and a temperature proxy after correlation to NorthGRIP. (1) A primary succession: The vegetation responded to the rapid rise of temperatures around 14,685 yr BP, with a primary succession on a decadal to centennial time scale. The succession between ca 15,600 and 13,000 yr BP included: (1.1.) The replacement of shrub-tundra by woodland of Juniperus and tree birch (around 14,665 yr BP) (1.2.) The response of Juniperus pollen to the shift in oxygen isotopes in less than 20 yr, (1.3.) A sequence of population increases of Hippophaë rhamnoides (ca 14,600 yr BP), Salix spp. (ca 14,600 yr BP), Betula trees (ca.14,480 yr BP), Populus cf. tremula (ca. 14,300 yr BP), and Pinus cf. sylvestris (ca. 13,830 yr BP). (2) Biological processes: Plants responded to the rapid increase of summer temperatures on all organisational levels: (2.1) Individuals may have produced more pollen (e.g. Juniperus); (2.2) Populations increased or decreased (e.g. Juniperus, Betula, later Pinus), and (2.3) Populations changed their biogeographical range and may show migrational lags. (2.4) Plant communities changed in their composition because the species pools changed through immigration and (local) extinction. Some plant communities may have been without modern analogue.These mechanisms require increasing amounts of time. (2.5) Processes on the level of ecosystems, with species interactions, may involve various time scales. Besides competition and facilitation, nitrogen fixation is discussed. (3) The minor fluctuations of temperature during the Late-Glacial Interstadial, which are recorded in δ18O, resulted in only very minor changes in pollen during the Aegelsee Oscillation (Older Dryas biozone, GI-1d) and the Gerzensee Oscillation (GI-1b). (4) Biodiversity: The afforestation at the onset of Bølling coincided with a gradual increase of taxonomic diversity up to the time of the major Pinus expansion.

Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus.

Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus. Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear. Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes. In contrast, their acute silencing (eNpHR3.0, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration. In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes. Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.

Intrapartum detection of Group B streptococci colonization by rapid PCR-test on labor ward

OBJECTIVE Group B streptococci (GBS) may lead to early onset neonatal sepsis with severe morbidity and mortality of newborns. Intrapartum detection of GBS is needed. The objective was to compare a PCR-based test performed in the laboratory versus labor ward. STUDY DESIGN 300 patients were included prospectively. In phase I, swabs were analyzed by selective culture and rapid PCR in the laboratory. In phase II, swabs were analyzed accordingly, but the PCR test was conducted in labor ward. Test performances were analyzed and compared. RESULTS In phase I the rapid PCR test had a sensitivity of 85.71% and a specificity of 95.9%. The GBS colonization rate was 18.67%. Overall 8.5% of the PCR results were invalid. In phase II the PCR test showed a sensitivity of 85.71% and a specificity of 95.65%. The GBS colonization rate was 23.3%. Overall 23.5% of swabs tested with PCR were invalid. Initiation of specific, short 2-hour training for operating personnel in the labor ward reduced the invalid test rate to 13.4%. CONCLUSION The rapid PCR-based test yields adequate results to identify GBS colonization when performed in labor ward. In order to reduce the number of invalid tests a short training period is needed.

Eco-Evolutionary Spatial Dynamics. Rapid Evolution and Isolation Explain Food Web Persistence

One of the current challenges in evolutionary ecology is understanding the long-term persistence of contemporary-evolving predator–prey interactions across space and time. To address this, we developed an extension of a multi-locus, multi-trait eco-evolutionary individual-based model that incorporates several interacting species in explicit landscapes. We simulated eco-evolutionary dynamics of multiple species food webs with different degrees of connectance across soil-moisture islands. A broad set of parameter combinations led to the local extinction of species, but some species persisted, and this was associated with (1) high connectance and omnivory and (2) ongoing evolution, due to multi-trait genetic variability of the embedded species. Furthermore, persistence was highest at intermediate island distances, likely because of a balance between predation-induced extinction (strongest at short island distances) and the coupling of island diversity by top predators, which by travelling among islands exert global top-down control of biodiversity. In the simulations with high genetic variation, we also found widespread trait evolutionary changes indicative of eco-evolutionary dynamics. We discuss how the ever-increasing computing power and high-resolution data availability will soon allow researchers to start bridging the in vivo–in silico gap.

RADIX: a minimal-resources rapid-access drilling system

Determining the expected age at a potential ice-core drilling site on a polar ice sheet generally depends on a combination of information from remote-sensing methods, estimates of current accumulation and modelling. This poses irreducible uncertainties in retrieving an undisturbed ice core of the desired age. Although recently perfected radar techniques will improve the picture of the ice sheet below future drilling sites, rapid prospective drillings could further increase the success of deep drilling projects. Here we design and explore a drilling system for a minimum-size rapid-access hole. The advantages of a small hole are the low demand for drilling fluid, low overall weight of the equipment, fast installing and de-installing and low costs. We show that, in theory, drilling of a 20mm hole to a depth of 3000m is possible in ~4 days. First concepts have been realized and verified in the field. Both the drill cuttings and the hole itself can be used to characterize the properties of the ice sheet and its potential to provide a trustworthy palaeo-record. A candidate drilling site could be explored in ~2 weeks, which would enable the characterization of several sites in one summer season.

Corneal cross-linking in keratoconus using the standard and rapid treatment protocol: differences in demarcation line and 12-month outcomes.

PURPOSE To compare the occurrence rate and depth of the demarcation line and topographical outcome after corneal cross-linking (CXL) for keratoconus using two different treatment protocols. METHODS A retrospective analysis of 131 eyes with progressive keratoconus treated with CXL using riboflavin and UV-A was performed. Eyes were treated either with the standard Dresden protocol (30 minutes irradiation, 3 mW/cm(2), UV-XTM 1000) or a rapid protocol (10 minutes irradiation, 9 mW/cm(2), UV-XTM 2000). The presence and depth of the corneal demarcation line was assessed with an anterior segment optical coherence tomography device 1 month after CXL by a masked observer. Corneal topography and tomography was performed at baseline and at 12-month follow-up with Pentacam and the TMS (Topographic Modeling System) device. RESULTS In the standard protocol group, 76.5% (62/81) of treated corneas revealed a demarcation line 1 month after CXL, whereas such a demarcation line was observed in only 22% (11/50) of eyes treated with the rapid protocol (P < 0.0001). The demarcation line was significantly more superficial in the rapid protocol group (P = 0.004). Corneal topography values between baseline and 12 months after CXL showed a mean change of -0.76 diopters (D) in Kmax (SD ± 2.7) in the standard protocol group versus a mean change of +0.72 D in Kmax (SD ± 1.5) in the rapid protocol (P = 0.007). CONCLUSIONS The rapid CXL protocol negatively influences the occurrence and depth of the demarcation line 1 month after CXL. Our results show a negative effect on the topographical outcome 1 year after CXL.

A novel universal DNA labeling and amplification system for rapid microarray-based detection of 117 antibiotic resistance genes in Gram-positive bacteria.

A rapid and simple DNA labeling system has been developed for disposable microarrays and has been validated for the detection of 117 antibiotic resistance genes abundant in Gram-positive bacteria. The DNA was fragmented and amplified using phi-29 polymerase and random primers with linkers. Labeling and further amplification were then performed by classic PCR amplification using biotinylated primers specific for the linkers. The microarray developed by Perreten et al. (Perreten, V., Vorlet-Fawer, L., Slickers, P., Ehricht, R., Kuhnert, P., Frey, J., 2005. Microarray-based detection of 90 antibiotic resistance genes of gram-positive bacteria. J.Clin.Microbiol. 43, 2291-2302.) was improved by additional oligonucleotides. A total of 244 oligonucleotides (26 to 37 nucleotide length and with similar melting temperatures) were spotted on the microarray, including genes conferring resistance to clinically important antibiotic classes like β-lactams, macrolides, aminoglycosides, glycopeptides and tetracyclines. Each antibiotic resistance gene is represented by at least 2 oligonucleotides designed from consensus sequences of gene families. The specificity of the oligonucleotides and the quality of the amplification and labeling were verified by analysis of a collection of 65 strains belonging to 24 species. Association between genotype and phenotype was verified for 6 antibiotics using 77 Staphylococcus strains belonging to different species and revealed 95% test specificity and a 93% predictive value of a positive test. The DNA labeling and amplification is independent of the species and of the target genes and could be used for different types of microarrays. This system has also the advantage to detect several genes within one bacterium at once, like in Staphylococcus aureus strain BM3318, in which up to 15 genes were detected. This new microarray-based detection system offers a large potential for applications in clinical diagnostic, basic research, food safety and surveillance programs for antimicrobial resistance.

Rapid and accurate identification of Escherichia coli K-12 strains

A specific PCR for the identification of K-12 strains, based on the genetic structure of the O-antigen gene cluster (rfb) of Escherichia coli K-12, is described. The assay clearly differentiates E. coli K-12-derived strains from other E. coli strains used in the laboratory or isolated from human and animal clinical specimens, from food, or from environmental samples. Moreover, lineages of K-12 strains can be distinguished with a second PCR based on the same gene cluster. The method presents a useful tool in identifying K-12 for monitoring strains which are used as biologically safe vehicles in biotechnological research, development, and production processes.

Avian area vasculosa and CAM as rapid in vivo pro-angiogenic and antiangiogenic models.

Angiogenesis, the development of new blood vessels from preexisting ones, is driven by coordinated signaling pathways governed by specific molecules, hemodynamic forces, and endothelial and periendothelial cells. The processes involve adhesion, migration, and survival machinery within the target endothelial and periendothelial cells. Factors that interfere with any of these processes may therefore influence angiogenesis either positively (pro-angiogenesis) or negatively (antiangiogenesis). The avian area vasculosa (AV) and the avian chorioallantoic membrane (CAM) are two useful tools for studying both angiogenesis and antiangiogenesis since they are amenable to both intravascular and topical administration of target, agents, are relatively rapid assays, and can be adapted very easily to study angiogenesis-dependent processes, such as tumor growth. Both models provide a physiological setting that permits investigation of pro-angiogenic and antiangiogenic agent interactions in vivo.