To draw informed conclusions from research studies, research consumers need full and accurate descriptions of study methods and procedures. Preregistration has been proposed as a means to clarify ...reporting of research methods and procedures, with the goal of reducing bias in research. However, preregistration has been applied primarily to research studies utilizing group designs. In this article, we discuss general issues in preregistration and consider the use of preregistration in single-case design research, particularly as it relates to differing applications of this methodology. We then provide a rationale and make specific recommendations for preregistering single-case design research, including guidelines for preregistering basic descriptive information, research questions, participant characteristics, baseline conditions, independent and dependent variables, hypotheses, and phase-change decisions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Schizophrenia is a chronic, complex and heterogeneous mental disorder, with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain. These ...pathological features manifest behaviorally as positive symptoms (including hallucinations, delusions and thought disorder), negative symptoms (such as social withdrawal, apathy and emotional blunting) and other psychopathological symptoms (such as psychomotor retardation, lack of insight, poor attention and impulse control). Altered glutamate neurotransmission has for decades been linked to schizophrenia, but all commonly prescribed antipsychotics act on dopamine receptors. LY404039 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors and has shown antipsychotic potential in animal studies. With data from rodents, we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine. To clinically test this mechanism, an oral prodrug of LY404039 (LY2140023) was evaluated in schizophrenic patients with olanzapine as an active control in a randomized, three-armed, double-blind, placebo-controlled study. Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P < 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
(-)-(1R,4S,5S,6S)-4-amino-2-sulfonylbicyclo3.1.0hexane-4,6-dicarboxylic acid (LY404039) is a potent and selective group II metabotropic glutamate (mGlu)2 and mGlu3 receptor agonist for which its ...prodrug LY2140023 (1R,4S,5S,6S)-2-thiabicyclo3.1.0-hexane-4,6-dicarboxylic acid,4-(2S)-2-amino-4-(methylthio)-1-oxobutylamino-, 2,2-dioxide monohydrate has recently been shown to have efficacy in the treatment of the positive and negative symptoms of schizophrenia. In this article, we use mGlu receptor-deficient mice to investigate the relative contribution of mGlu2 and mGlu3 receptors in mediating the antipsychotic profile of LY404039 in the phencyclidine (PCP) and d-amphetamine (AMP) models of psychosis. To further explore the mechanism of action of LY404039, we compared the drugs' ability to block PCP-induced hyperlocomotion to that of atypical antipsychotics in wild-type and mice lacking mGlu2/3 receptors. In wild-type animals, LY404039 (3-30 mg/kg i.p.) significantly reversed AMP (5 mg/kg, i.p.)-induced increases in ambulations, distance traveled, and reduced time spent at rest. LY404039 reversed PCP (7.5 mg/kg i.p.)-evoked behaviors at 10 mg/kg. The antipsychotic-like effects of LY404039 (10 mg/kg i.p.) on PCP and AMP-evoked behavioral activation were absent in mGlu2 and mGlu2/3 but not in mGlu3 receptor-deficient mice, indicating that the activation of mGlu2 and not mGlu3 receptors is responsible for the antipsychotic-like effects of the mGlu2/3 receptor agonist LY404039. In contrast, the atypical antipsychotic drugs clozapine and risperidone inhibited PCP-evoked behaviors in both wild-type and mGlu2/3 receptor-deficient mice. These data demonstrate that the antipsychotic-like effects of the mGlu2/3 receptor agonist LY404039 in psychostimulant models of psychosis are mechanistically distinct from those of atypical antipsychotic drugs and are dependent on functional mGlu2 and not mGlu3 receptors.
Herbicide-resistant weeds, especially Palmer amaranth (Amaranthus palmeri S. Watson), are problematic in row-crop producing areas of the United States. The objectives of this study were to determine ...if chlorimuron-ethyl, fomesafen, and glyphosate applied separately and in mixtures control A. palmeri and confirm the presence of various genotypes surviving two- and three-way herbicide mixtures. Fifteen percent of A. palmeri treated with the three-way herbicide mixture survived. Mixing fomesafen with chlorimuron-ethyl or fomesafen with glyphosate to create a two-way mixture reduced A. palmeri survival 22 to 24% and 60 to 62% more than glyphosate and chlorimuron-ethyl alone, respectively. Previously characterized mutations associated with A. palmeri survival to chlorimuron-ethyl, fomesafen, and glyphosate Trp574Leu, a missing glycine codon at position 210 of the PPX2L gene (ΔG210), and 5-enolpyruvylshikimate-3-phosphase synthase (EPSPS) gene amplification; respectively, were present in surviving plants. However, 37% of plants treated with chlorimuron-ethyl did not contain heterozygous or homozygous alleles for the Trp574Leu mutation, suggesting alternative genotypes contributed to plant survival. All surviving A. palmeri treated with fomesafen or glyphosate possessed genotypes previously documented to confer resistance. Indiana soybean Glycine max (L.) Merr fields infested with A. palmeri possessed diverse genotypes and herbicide surviving plants are likely to produce seed and spread if alternative control measures are not implemented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Patients with stable isolated injuries of the ankle syndesmosis can be treated conservatively, while unstable injuries require surgical stabilisation. Although evaluating syndesmotic injuries ...using ankle arthroscopy is becoming more popular, differentiating between stable and unstable syndesmoses remains a topic of on-going debate in the current literature. The purpose of this study was to quantify the degree of displacement of the ankle syndesmosis using arthroscopic measurements. The hypothesis was that ankle arthroscopy by measuring multiplanar fibular motion can determine syndesmotic instability.
Methods
Arthroscopic assessment of the ankle syndesmosis was performed on 22 fresh above knee cadaveric specimens, first with all syndesmotic and ankle ligaments intact and subsequently with sequential sectioning of the anterior inferior tibiofibular ligament, the interosseous ligament, the posterior inferior tibiofibular ligament, and deltoid ligaments. In all scenarios, four loading conditions were considered under 100N of direct force: (1) unstressed, (2) a lateral hook test, (3) anterior to posterior (AP) translation test, and (4) posterior to anterior (PA) translation test. Anterior and posterior coronal plane tibiofibular translation, as well as AP and PA sagittal plane translation, were arthroscopically measured.
Results
As additional ligaments of the syndesmosis were transected, all arthroscopic multiplanar translation measurements increased (p values ranging from
p
< 0.001 to
p
= 0.007). The following equation of multiplanar fibular motion relative to the tibia measured in millimeters: 0.76*AP sagittal translation + 0.82*PA sagittal translation + 1.17*anterior third coronal plane translation—0.20*posterior third coronal plane translation, referred to as the Arthroscopic Syndesmotic Assessment tool, was generated from our data. According to our results, an Arthroscopic Syndesmotic Assessment value equal or greater than 3.1 mm indicated an unstable syndesmosis.
Conclusions
This tool provides a more reliable opportunity in determining the presence of syndesmotic instability and can help providers decide whether syndesmosis injuries should be treated conservatively or operatively stabilized. The long-term usefulness of the tool will rest on whether an unstable syndesmosis correlates with acute or chronic clinical symptoms.
Summary
The geochemical dynamics and composition of microbial communities within a low‐temperature (∼8.5°C), long‐abandoned (> 90 years) underground pyrite mine (Cae Coch, located in north Wales) ...were investigated. Surface water percolating through fractures in the residual pyrite ore body that forms the roof of the mine becomes extremely acidic and iron‐enriched due to microbially accelerated oxidative dissolution of the sulfide mineral. Water droplets on the mine roof were found to host a very limited diversity of exclusively autotrophic microorganisms, dominated by the recently described psychrotolerant iron/sulfur‐oxidizing acidophile Acidithiobacillus ferrivorans, and smaller numbers of iron‐oxidizing Leptospirillum ferrooxidans. In contrast, flowing water within the mine chamber was colonized with vast macroscopic microbial growths, in the form of acid streamers and microbial stalactites, where the dominant microorganisms were Betaproteobacteria (autotrophic iron oxidizers such as ‘Ferrovum myxofaciens’ and a bacterium related to Gallionella ferruginea). An isolated pool within the mine showed some similarity (although greater biodiversity) to the roof droplets, and was the only site where archaea were relatively abundant. Bacteria not previously associated with extremely acidic, metal‐rich environments (a Sphingomonas sp. and Ralstonia pickettii) were found within the abandoned mine. Data supported the hypothesis that the Cae Coch ecosystem is underpinned by acidophilic, mostly autotrophic, bacteria that use ferrous iron present in the pyrite ore body as their source of energy, with a limited role for sulfur‐based autotrophy. Results of this study highlight the importance of novel bacterial species (At. ferrivorans and acidophilic iron‐oxidizing Betaproteobacteria) in mediating mineral oxidation and redox transformations of iron in acidic, low‐temperature environments.
Synthetic auxin herbicides such as 2,4-D and dicamba are often utilized to control broadleaf weeds in preplant burndown applications to soybean. Halauxifen-methyl is a new synthetic auxin herbicide ...for broadleaf weed control in preplant burndown applications to corn, cotton, and soybean at low use rates (5 g ae ha-1). Field experiments were conducted to evaluate efficacy and weed control spectrum of halauxifen-methyl applied alone and in mixtures with 2,4-D (560 g ae ha-1), dicamba (280 g ae ha-1), and glyphosate (560 g ae ha-1). Glyphosate-resistant (GR) horseweed was controlled with halauxifen-methyl applied alone (90% control) and in mixtures (87% to 97% control) 35 d after treatment (DAT). Common ragweed was controlled 93% with halauxifen-methyl applied alone and 91% to 97% in mixtures 35 DAT. Halauxifenmethyl applied alone resulted in poor giant ragweed control 21 DAT (73% control); however, mixtures of halauxifen-methyl with 2,4-D, dicamba, or glyphosate controlled giant ragweed (86% to 98% control). Halauxifen-methyl alone resulted in poor redroot pigweed control (62% control) 21 DAT; however, mixtures of halauxifen-methyl with dicamba, 2,4-D, or glyphosate controlled redroot pigweed (89% to 98% control). Halauxifen-methyl controls GR horseweed and common ragweed applied alone and in mixtures with other synthetic auxin herbicides and glyphosate. Furthermore, mixing 2,4-D or dicamba with halauxifen-methyl can increase the weed control spectrum in preplant burndown applications. Nomenclature: 2,4-D; dicamba; glyphosate; halauxifenmethyl; common ragweed, Ambrosia artemisiifolia L. AMBEL; giant ragweed, Ambrosia trifida L. AMBTR; horseweed, Conyza canadensis (L.) Cronq. ERICA; redroot pigweed, Amaranthus retroflexus L. AMARE; corn, Zea mays L.; cotton, Gossypium hirsutum L.; soybean, Glycine max (L.) Merr
Group II metabotropic glutamate (mGlu) receptor agonists were efficacious in randomized clinical research trials for schizophrenia and generalized anxiety disorder. The regional quantification of ...mGlu2 and mGlu3 receptors remains unknown. A selective and structurally novel mGlu2/3 receptor agonist, 2-amino-4-fluorobicyclo3.1.0hexane-2,6-dicarboxylic acid (LY459477) was tritiated and the distribution of mGlu2 and mGlu3 receptors was studied in transgenic mice lacking either mGlu2, mGlu3 or both receptors. LY459477 is an agonist with 1–2 nM potency for rodent and human mGlu2 and mGlu3 receptors. The functional selectivity of LY459477 was demonstrated by over 640-fold selectivity and the displacement binding selectivity was greater than 320-fold for all glutamate receptors except mGlu6 (∼230-fold). More than 1000-fold selectivity was demonstrated for all non-glutamate receptors known to be targeted by antipsychotic drugs. Like atypical antipsychotic drugs, LY459477 reversed in vitro electrophysiological effects of a serotonergic hallucinogen and behavioral effects of phencyclidine or amphetamine. There was virtually no binding of 3HLY459477 to any brain region in mice with a deletion of both mGlu2 and mGlu3 receptors. Regions enriched in mGlu2 receptors included the medial prefrontal cortex, select hippocampal regions, the medial mammillary nucleus, the medial habenula, and the cerebellar granular cell layer. Regions enriched in mGlu3 receptors were the dorsolateral entorhinal cortex, the hippocampal CA1 field, the piriform cortex, the substantia nigra, the thalamic reticular nucleus, and primary sensory thalamic nuclei. These findings suggest 3HLY459477 should be a useful tool to further define the role of mGlu2 and mGlu3 receptors throughout the brain with respect to major neuropsychiatric syndromes.
This article is part of a Special Issue entitled ‘Metabotropic Glutamate Receptors’.
► LY459477 is a selective agonist for mGlu2 and mGlu3 receptors. ► There is no binding of 3HLY459477 in mice without both mGlu2 and mGlu3 receptors. ► In mGlu3−/− mice, 3HLY459477 binds in same brain areas as mGlu2 receptor antibodies. ► In mGlu2−/− mice, 3HLY459477 binds in same brain areas as mGlu3 receptor antibodies. ► mGlu2 receptors are distributed in brain areas associated with psychosis and anxiety.
The use of soil residual herbicides, along with other practices that diversify weed management strategies, have been recommended to improve weed management and deter the progression of herbicide ...resistance. Although soil characteristics influence recommended application rates for these herbicides, the common practice is to apply a uniform dose of soil residual herbicides across fields with variable soil characteristics. Mapping fields for soil characteristics that dictate the optimal dose of soil residual herbicides could improve the efficiency and effectiveness of these herbicides, as well as improve environmental stewardship. The objectives of this research were to develop and quantify the accuracy of management zone classifications for variable-rate residual herbicide applications using multiple soil data sources and soil sampling intensities. The maps were created from soil data that included (i) Soil Survey Geographic database (SSURGO), (ii) soil samples (SS), (iii) soil samples regressed onto soil electrical conductivity (EC) measurements (SSEC), (iv) soil samples with organic matter (OM) data from SmartFirmer® (SF) sensors (SSSF), and (v) soil samples regressed onto EC measurements plus OM data from SmartFirmer® sensor (SSECSF). A modified Monte Carlo cross validation method was used on ten commercial Indiana fields to generate 36,000 maps across all sources of spatial soil data, sampling density, and three representative herbicides (pyroxasulfone, s-metolachlor, and metribuzin). Maps developed from SSEC data were most frequently ranked with the highest management zone classification accuracy compared to maps developed from SS data. However, SS and SSEC maps concurrently had the highest management zone classification accuracy of 34% among maps developed across all fields, herbicides, and sampling intensities. One soil sample per hectare was the most reliable sampling intensity to generate herbicide application management zones compared to one soil sample for every 2 or 4 hectares. In conclusion, soil sampling with EC
a
data should be used for defining the management zones for variable-rate (VR) residual herbicide applications.
PDF
