Simple Trial Research Articles

A simple greenhouse experiment to explore the effect of cryogenic water extraction for tracing plant source water

AbstractStable isotopes of water (2H and 18O) are useful tracers for determining root water uptake depths. In such studies, plant and soil water are extracted most commonly by cryogenic vacuum distillation. However, recent studies have suggested that cryogenic extraction conditions (extraction time, temperature, and vacuum) and soil physicochemical properties affect the isotopic composition of extracted soil water. Here, we perform a simple greenhouse trial with 2 plant species (Taraxacum officinale and Pelargonium spp.) in 2 soil types (clayey loam and sand) to test our ability to match plant water to its putative soil water source(s) by using different extraction conditions (30–240 min, 80–200 °C, 0.1 Pa). We irrigated plants with water of known isotopic composition, sampled root crowns and soils at 2 depths, and varied the cryogenic water extraction conditions.Our isotope results from the sandy soils were unaffected by cryogenic extraction conditions. In contrast, extraction parameters affected the isotope composition of waters recovered from clayey soil. This influenced the estimates of plant water sourcing, where δ2H and δ18O returned different results from each other. With higher extraction temperatures and longer extraction times, we gradually extracted more enriched soil water, which reflected the source water of both plant species. Our results imply that longer extraction times and temperatures for clayey soils are needed to reduce fractionation effects during the extraction procedure. Future studies should explore how these effects apply to natural clay‐rich soils as well as plant tissue isotope composition.

The Existence of Notary Honor Assemblies in the Criminal Justice Process

The aim of this study is to know and analyze the basic idea of the necessityfor the approval of the Notary Honor Assemblies to the Notary examination in thecriminal justice process and on the approval of the Notary Honor Assemblies to theNotary examination in the criminal justice process in relation to the principle fast,simple and low cost trial. This research uses doctrinal law research done or aimedat a concept that will be studied which is the concept or principle of fast, simpleand low cost trial in relation with the authority of Honorary Notary Assembly to thechecking of Notary in criminal justice process. The basic rationale of the existenceof this NHA is the effort to enforce the obligation to deny or deny notary rights(the obligation to conceal the contents of the deed). Thus, the NHA’s approval asa opening “key” to the obligation of Notaries public when facing the complicatedlegal process. Legal protection of notary as regulated in Article 66 paragraph (1)law of the Repulic of Indonesia concerning Position of Notary (LPN) is a legalprotection to notary public as a public official who is performing its task andobligation in carrying out government authority to keep the state documents in theform of authentic deed. The request for approval from NHA is not only done bythe investigator at the stage of investigation, but will also be requested again bythe prosecutor for the prosecution and by the judge for the court hearing not inaccordance with one of the principles in the criminal justice process that is fast,simple and low cost court principle. For the seizure of the copy of the minuta deedand the summon to the Notaries must first the investigator, the prosecutor and thejudge send the application for approval to NHA. It is said not to be in accordancewith the simple justice principle because according to Article 66 Law of Position ofNotary (LPN), the request for the approval of NHA is done at every stage of criminaljustice process.

THE EXISTENCE OF NOTARY HONOR ASSEMBLIES IN THE CRIMINAL JUSTICE PROCESS

The aim of this study is to know and analyze the basic idea of the necessity for the approval of the Notary Honor Assemblies to the Notary examination in the criminal justice process and on the approval of the Notary Honor Assemblies to the Notary examination in the criminal justice process in relation to the principle fast, simple and low cost trial. This research uses doctrinal law research done or aimed at a concept that will be studied which is the concept or principle of fast, simple and low cost trial in relation with the authority of Honorary Notary Assembly to the checking of Notary in criminal justice process. The basic rationale of the existence of this NHA is the effort to enforce the obligation to deny or deny notary rights (the obligation to conceal the contents of the deed). Thus, the NHA’s approval as a opening “key” to the obligation of Notaries public when facing the complicated legal process. Legal protection of notary as regulated in Article 66 paragraph (1) law of the Repulic of Indonesia concerning Position of Notary (LPN) is a legal protection to notary public as a public official who is performing its task and obligation in carrying out government authority to keep the state documents in the form of authentic deed. The request for approval from NHA is not only done by the investigator at the stage of investigation, but will also be requested again by the prosecutor for the prosecution and by the judge for the court hearing not in accordance with one of the principles in the criminal justice process that is fast, simple and low cost court principle. For the seizure of the copy of the minuta deed and the summon to the Notaries must first the investigator, the prosecutor and the judge send the application for approval to NHA. It is said not to be in accordance with the simple justice principle because according to Article 66 Law of Position of Notary (LPN), the request for the approval of NHA is done at every stage of criminal justice process.

Malignant Cough Syncope from Idiopathic Vagal Inflammation.

We describe the case of a patient with malignant vasodepressive cough syncope. We demonstrated a vaso-vagal mechanism related to left vagal neuritis, by means of laryngoscopy and laryngeal electromyography. The condition resolved with steroid therapy.LEARNING POINTSLeft vagal neuritis should be considered in the differential diagnosis of recent onset repetitive loss of consciousness, in particular if cough related.Steroids were used to successfully treat recent onset cough-related syncope.Relatively simple trials of drug therapy can sometimes avoid intensive investigations; in our case, the use of a systemic steroid would probably have avoided many radiological and endoscopic examinations.

Alpha-gamma phase amplitude coupling subserves information transfer during perceptual sequence learning.

Cross-frequency coupling is suggested to serve transfer of information between wide-spread neuronal assemblies and has been shown to underlie many cognitive functions including learning and memory. In previous work, we found that alpha (8-13 Hz) - gamma (30-48 Hz) phase amplitude coupling (αγPAC) is decreased during sequence learning in bilateral frontal cortex and right parietal cortex. We interpreted this to reflect decreased demands for visuo-motor mapping once the sequence has been encoded. In the present study, we put this hypothesis to the test by adding a "simple" condition to the standard serial reaction time task (SRTT) with minimal needs for visuo-motor mapping. The standard SRTT in our paradigm entailed a perceptual sequence allowing for implicit learning of a sequence of colors with randomly assigned motor responses. Sequence learning in this case was thus not associated with reduced demands for visuo-motor mapping. Analysis of oscillatory power revealed a learning-related alpha decrease pointing to a stronger recruitment of occipito-parietal areas when encoding the perceptual sequence. Replicating our previous findings but in contrast to our hypothesis, αγPAC was decreased in sequence compared to random trials over right frontal and parietal cortex. It also tended to be smaller compared to trials requiring a simple motor sequence. We additionally analyzed αγPAC in resting-state data of a separate cohort. PAC in electrodes over right parietal cortex was significantly stronger compared to sequence trials and tended to be higher compared to simple and random trials of the SRTT data. We suggest that αγPAC in right parietal cortex reflects a "default-mode" brain state, which gets perturbed to allow for encoding of visual regularities into memory.

Assessment of Noninferiority (and Equivalence) for Simple Crossover Trials Using Bayesian Approach

To assess the noninferiority or equivalence of a general drug to a standard one, researchers generally use the odds ratio of patient response rates to evaluate the relative treatment efficacy. In this paper, we use a logistic random effects model to test noninferiority and equivalence based on the odds ratio of patient response rates for crossover trials with binary data. We use Bayesian sampling algorithm, data augmentation, and scaled mixture of normal representation to implement the approach and improve efficiency. The performance of the proposed approach is assessed via simulation and real data examples.

At the core of reasoning: Dissociating deductive and non-deductive load.

In recent years, neuroimaging methods have been used to investigate how the human mind carries out deductive reasoning. According to some, the neural substrate of language is integral to deductive reasoning. According to others, deductive reasoning is supported by a language-independent distributed network including left frontopolar and frontomedial cortices. However, it has been suggested that activity in these frontal regions might instead reflect non-deductive factors such as working memory load and general cognitive difficulty. To address this issue, 20 healthy volunteers participated in an fMRI experiment in which they evaluated matched simple and complex deductive and non-deductive arguments in a 2×2 design. The contrast of complex versus simple deductive trials resulted in a pattern of activation closely matching previous work, including frontopolar and frontomedial "core" areas of deduction as well as other "cognitive support" areas in frontoparietal cortices. Conversely, the contrast of complex and simple non-deductive trials resulted in a pattern of activation that does not include any of the aforementioned "core" areas. Direct comparison of the load effect across deductive and non-deductive trials further supports the view that activity in the regions previously interpreted as "core" to deductive reasoning cannot merely reflect non-deductive load, but instead might reflect processes specific to the deductive calculus. Finally, consistent with previous reports, the classical language areas in left inferior frontal gyrus and posterior temporal cortex do not appear to participate in deductive inference beyond their role in encoding stimuli presented in linguistic format.

Do drug release studies from SEDDS make any sense?

Self-emulsifying drug delivery systems (SEDDS) are considered as a potential platform for mucosal drug delivery. The in vitro–in vivo correlation, however, is in particular for this type of delivery systems considerably poor resulting quite often in a simple trial and error approach in order to optimize formulations. One reason for this situation is certainly the lack of appropriate methods to determine the drug release from SEDDS in vitro, as the process is particularly troublesome. For quantification of the drug in the release medium the oily droplets need to be separated. In most studies this is achieved by utilizing a separating membrane such as dialysis membranes or filters having a huge impact on the obtained release profile. Moreover, sink conditions are very often not provided. As drug release from SEDDS is based on a simple diffusion process from a lipophilic liquid phase into an aqueous liquid phase, a likely more meaningful way to characterize the release behaviour might be just the determination of the distribution coefficient (log DSEDDS/RM) of the drug between the SEDDS pre-concentrate and the release medium (RM). As log D is simply the measure of the difference in solubility of a compound in two phases, it can be determined by measuring solubility of drug or drug complex in the SEDDS pre-concentrate and in the release medium in a separate manner. The impact of log DSEDDS/RM on the in vivo drug release behaviour is discussed including various case studies.

An Efficient, Clinically-Natural Electronic Medical Record System that Produces Computable Data.

Current commercially-available electronic medical record systems produce mainly text-based information focused on financial and regulatory performance. We combined an existing method for organizing complex computer systems—which we label activity-based design—with a proven approach for integrating clinical decision support into front-line care delivery—Care Process Models. The clinical decision support approach increased the structure of textual clinical documentation, to the point where established methods for converting text into computable data (natural language processing) worked efficiently. In a simple trial involving radiology reports for examinations performed to rule out pneumonia, more than 98 percent of all documentation generated was captured as computable data. Use cases across a broad range of other physician, nursing, and physical therapy clinical applications subjectively show similar effects. The resulting system is clinically natural, puts clinicians in direct, rapid control of clinical content without information technology intermediaries, and can generate complete clinical documentation. It supports embedded secondary functions such as the generation of granular activity-based costing data, and embedded generation of clinical coding (e.g., CPT, ICD-10 or SNOMED). Most important, widely-available computable data has the potential to greatly improve care delivery management and outcomes.

Influence of Sedimentation Length on the Convective Stability of a Colloidal Suspension

The сonvective stability of a colloidal suspension is studied in the case when the vertical dimension of the cavity is less than or comparable with the sedimentation length of nanoparticles. The analysis is carried out within the Boussinesq approximation on the basis of a modified model that takes into account the dependence of a thermodiffusion flow on the local value of impurity concentration. A new parameter of the problem is the ratio of the sedimentation length to the vertical dimension of the cavity. For a quiescent colloidal suspension, exact and approximate (in the case of small concentrations) solutions are obtained that describe the distributions of nanoparticles. A transformation is obtained that allows one to investigate the convective stability of a colloidal suspension stratified in the gravitational field by the Galerkin method with a set of simple trial functions. Instability boundaries and the characteristics of critical perturbations are determined. It is shown that, in the case of negative thermodiffusion, a decrease in the sedimentation length leads to a decrease in the convection threshold and the frequency of neutral oscillations.

Impact of fermented total mixed rations on intake, VFA and methane production of dairy heifers

The objective of this study was to determine the effect of feeding two fermented total mixed ration (FTMR) on methane production in dairy heifers. Four Holstein Friesian dairy heifers with mean body weight (BW) of 301.1 ± 42.2 kg were used in a simple cross-over design trial. Treatments consisted of 2 FTMR formulated to yield either low (LMD) or high CH4 production (HMD). No differences were observed in dry matter intake (DMI; 6.49 and 6.19 kg/d), BW change (-3.37 and -7.25 kg), or DM digestibility (50.64 and 46.99%) between diets. Ruminal pH, total volatile fatty acids (TVFA) and molar proportions of acetate, propionate and butyrate were not different among diets. Concentrations of blood glucose were higher (P=0.05) for HMD compared with LMD at 2 h post feeding; however, blood urea nitrogen was not different. Methane emissions were 236.32 L/d for LMD and 273.70 L/d for HMD and not different. Feeding the FTMR differing in CH4 potential did not affect DMI, digestibility, ruminal TVFA production or molar proportions of VFAs in dairy heifers.

Creating Affording Situations: Coaching through Animate Objects.

We explore the ways in which animate objects can be used to cue actions as part of coaching in Activities of Daily Living (ADL). In this case, changing the appearance or behavior of a physical object is intended to cue actions which are appropriate for a given context. The context is defined by the intention of the users, the state of the objects and the tasks for which these objects can be used. We present initial design prototypes and simple user trials which explore the impact of different cues on activity. It is shown that raising the handle of a jug, for example, not only cues the act of picking up the jug but also encourages use of the hand adjacent to the handle; that combinations of lights (on the objects) and auditory cues influence activity through reducing uncertainty; and that cueing can challenge pre-learned action sequences. We interpret these results in terms of the idea that the animate objects can be used to create affording situations, and discuss implications of this work to support relearning of ADL following brain damage or injury, such as might arise following a stroke.

P3 event-related brain potential reflects allocation and use of central processing capacity in language production

Allocation and use of central processing capacity have been associated with the P3 event-related brain potential amplitude in a large variety of non-linguistic tasks. However, little is known about the P3 in spoken language production. Moreover, the few studies that are available report opposing P3 effects when task complexity is manipulated. We investigated allocation and use of central processing capacity in a spoken phrase production task: Participants switched every second trial between describing pictures using noun phrases with one adjective (size only; simple condition, e.g., “the big desk”) or two adjectives (size and color; complex condition, e.g., “the big red desk”). Capacity allocation was manipulated by complexity, and capacity use by switching. Response time (RT) was longer for complex than for simple trials. Moreover, complexity and switching interacted: RTs were longer on switch than on repeat trials for simple phrases but shorter on switch than on repeat trials for complex phrases. P3 amplitude increased with complexity. Moreover, complexity and switching interacted: The complexity effect was larger on the switch trials than on the repeat trials. These results provide evidence that the allocation and use of central processing capacity in language production are differentially reflected in the P3 amplitude.

Noninvasive high-frequency ventilation and the errors from the past: designing simple trials neglecting complex respiratory physiology.

Noninvasive high-frequency ventilation and the errors from the past: designing simple trials neglecting complex respiratory physiology

Response to 'Non-invasive high frequency ventilation and the errors from the past: designing simple trials neglecting complex respiratory physiology'.

Response to ‘Non-invasive high frequency ventilation and the errors from the past: designing simple trials neglecting complex respiratory physiology’

A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age

ObjectiveTo evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. MethodsForty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). ResultsOverall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed. ConclusionThis pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment.

Application of PI Current Controller in Single Phase Inverter System Connected to Non Linear Load

This study is concerned with the problem of network power quality when inverter systems are connected to a nonlinear load. Nonlinear loads are well known as one of the biggest source of harmonics in the power system. Besides that, inverter systems also have their nonlinearity characteristic because of the electronic components. As the inverter system is connected to nonlinear load, it resulting in harmonic distortion-related problem and draw non-sinusoidal currents in the system, thus reducing the power quality in the system. The application of Proportional Integral controller in this system is the main interest of this study. This current controller capable of reducing total harmonic distortion and improve the state of current waveform. This paper focuses on application of simple manual trial and error tuning technique to produce the optimum value for the gains. The result of study verifies the trial and error manual tuning of PI current controller in compensating harmonic distortions. Simulation and modelling of the system are successfully developed using Matlab/Simulink.

Involving seldom-heard groups in a PPI process to inform the design of a proposed trial on the use of probiotics to prevent preterm birth: a case study

Plain English summaryWhen designing clinical trials it is important to involve members of the public, who can provide a view on what may encourage or prevent people participating and on what matters to them. This is known as Public and Patient Involvement (PPI). People from minority ethnic groups are often less likely to take part in clinical trials, but it is important to ensure they are able to participate fully so that health research and its findings are relevant to a wide population. We are preparing to conduct a randomised controlled trial (RCT) to test whether taking probiotic capsules can play a role in preventing preterm birth. Women from some minority ethnic groups, for example women from West Africa, and those who are from low-income groups are more likely to suffer preterm births. Preterm birth can lead to extra costs to health services and psychosocial costs for families. In this article we describe how we engaged women in discussion about the design of the planned trial, and how we aim to use our findings to ensure the trial is workable and beneficial to women, as well as to further engage service users in the future development of the trial. Four socially and ethnically diverse groups of women in East London took part in discussions about the trial and contributed their ideas and concerns. These discussions have helped to inform and improve the design of a small practice or ‘pilot’ trial to test the recruitment in a ‘real life’ setting, as well as encourage further PPI involvement for the future full-scale trial.Background Patient and public involvement (PPI) is an important tool in approaching research challenges. However, involvement of socially and ethnically diverse populations remains limited and practitioners need effective methods of involving a broad section of the population in planning and designing research.Methods In preparation for the development of a pilot randomised controlled trial (RCT) on the use of probiotics to prevent preterm birth, we conducted a public consultation exercise in a socially disadvantaged and ethnically diverse community. The consultation aimed to meet and engage local service users in considering the acceptability of the proposed protocol, and to encourage their participation in future and ongoing patient and public involvement activities. Four discussion groups were held in the community with mothers of young children within the proposed trial region, using an inclusive approach that incorporated a modified version of the Nominal Group Technique (NGT). Bringing the consultation to the community supported the involvement of often seldom-heard participants, such as those from minority ethnic groups.Results The women involved expressed a number of concerns about the proposed protocol, including adherence to the probiotic supplement regimen and randomisation. The proposal for the RCT in itself was perceived as confirmation that probiotic supplements had potentially beneficial effects, but also that they had potentially harmful side-effects. The complexity of the women’s responses provided greater insights into the challenges of even quite simple trial designs and enabled the research team to take these concerns into account while planning the pilot trial.Conclusions The use of the NGT method allowed for a consultation of a population traditionally less likely to participate in medical research. A carefully facilitated PPI exercise can allow members to express unanticipated concerns that may not have been elicited by a survey method. Findings from such exercises can be utilised to improve clinical trial design, provide insight into the feasibility of trials, and enable engagement of often excluded population groups.

Shoe-stiffening inserts for first metatarsophalangeal joint osteoarthritis (the SIMPLE trial): study protocol for a randomised controlled trial

BackgroundThis article describes the design of a parallel-group, participant- and assessor-blinded randomised controlled trial comparing the effectiveness of shoe-stiffening inserts versus sham shoe insert(s) for reducing pain associated with first metatarsophalangeal joint (MTPJ) osteoarthritis (OA).MethodsNinety participants with first MTPJ OA will be randomised to receive full-length shoe-stiffening insert(s) (Carbon Fibre Spring Plate, Paris Orthotics, Vancouver, BC, Canada) plus rehabilitation therapy or sham shoe insert(s) plus rehabilitation therapy. Outcome measures will be obtained at baseline, 4, 12, 24 and 52 weeks; the primary endpoint for assessing effectiveness being 12 weeks. The primary outcome measure will be the foot pain domain of the Foot Health Status Questionnaire (FHSQ). Secondary outcome measures will include the function domain of the FHSQ, severity of first MTPJ pain (using a 100-mm Visual Analogue Scale), global change in symptoms (using a 15-point Likert scale), health status (using the Short-Form-12® Version 2.0 and EuroQol (EQ-5D-5L™) questionnaires), use of rescue medication and co-interventions, self-reported adverse events and physical activity levels (using the Incidental and Planned Activity Questionnaire). Data will be analysed using the intention-to-treat principle. Economic analysis (cost-effectiveness and cost-utility) will also be performed. In addition, the kinematic effects of the interventions will be examined at 1 week using a three-dimensional motion analysis system and multisegment foot model.DiscussionThis study will determine whether shoe-stiffening inserts are a cost-effective intervention for relieving pain associated with first MTPJ OA. The biomechanical analysis will provide useful insights into the mechanism of action of the shoe-stiffening inserts.Trial registrationAustralian New Zealand Clinical Trials Registry, identifier: ACTRN12616000552482. Registered on 28 April 2016.

Incorporating Site-less Clinical Trials Into Drug Development: A Framework for Action

PurposeOptions for leveraging available telemedicine technologies, ranging from simple webcams and telephones to smartphone apps and medical-grade wearable sensors, are evolving faster than the culture of clinical research. Until recently, most clinical trials relied on paper-based processes and technology. This cost- and labor-intensive system, while slowly changing, remains an obstacle to new drug development. Alternatives that use existing tools and processes for collecting real-world data in home settings warrant closer examination. MethodsThe site-less clinical research organization (CRO) model, whereby pharmacists or other health care professionals provide useful and timely counseling for protocol compliance by regular phone and videoconferencing sessions, is a flexible approach to managing clinical trial participants directly from their homes. An expert panel, including clinical specialists in metabolic or neurodegenerative diseases, health information technology and CRO innovators, and the pharmaceutical industry, met in Dallas, Texas, December 2016, to discuss advancing avenues for site-less CRO and other remote clinical trial practices, taking into account investigator, sponsor, and regulatory perspectives. FindingsReal-time “site-less” management of clinical trials can augment traditional research and development methods by providing data from a broader, more diverse group of patients in real-world practice settings. This methodology also helps to proactively identify safety profile and operational issues. Current use of site-less CRO practices constitutes an important bridge to alternative trial models, including “large simple trials” that strive to answer one or two questions using data derived from representative patient populations treated in typical clinical settings. ImplicationsSite-less CROs offer a working example of how remote technologies and in-home monitoring methods can address shortcomings of conventional drug development. This model maximizes time and cost, as well as potentially earlier identification of adverse events. Coordinated communication among investigators, sponsors, regulators, and patients will be needed to develop standardized strategies for incorporating site-less CROs into current and future study design.