bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paediatric Off‐Label Use of Melatonin – A Register Linkage Study between the Norwegian Prescription Database and Patient Register
Authors: Hartz Ingeborg , Handal Marte , Tverdal Aage , Skurtveit Svetlana 
Published: April 2015

AbstractThe aims were, for the entire Norwegian population aged 4–17 years, to study the prevalence of melatonin use during 2004–2012, recurrent use in incident users and psychiatric and neurological morbidity in recurrent users. Data on dispensed melatonin were retrieved from the Norwegian Prescription Database and linked to diagnostic data from the Norwegian Patient Register. Outcome measures were the following: 1‐year prevalence of use, proportion of recurrent use (use over three consecutive 365‐day periods among incident users in 2009) and annual number of milligrams and number of prescriptions dispensed in recurrent users. The prevalence of registered ICD‐10 diagnoses during the period of 2008–2012 was given for the recurrent users. The prevalence of melatonin use increased annually in both genders during 2004–2012 (boys: 3.4–11.0 per 1000; girls: 1.5–7.7 per 1000). Twenty‐nine per cent of boys and 23% of girls were recurrent melatonin users, with highest level of recurrent use among the youngest (aged 4–8 years; boys: 47%, girls: 42%). In the third year, the median annual amount of melatonin dispensed was 1080 (IQR 586–1800) milligrams in boys and 900 (IQR 402–1620) milligrams in girls. Among recurrent users, 91% had a diagnosis of either psychiatric (84%) or neurological (32%) disorder. Off‐label recurrent use of melatonin seems to have acquired a role mainly in treating secondary sleep problems in children and adolescents with psychiatric and neurological disorders. Once melatonin has been started, a large proportion of patients continue for at least 3 years, in doses corresponding to daily use in the majority.
A cost‐effectiveness analysis of real‐world treatment for elderly patients with multiple myeloma using a full disease model
Authors: Blommestein Hedwig M. , Verelst Silvia G. R. , de Groot Saskia , Huijgens Peter C. , Sonneveld Pieter , Uyl‐de Groot Carin A. 
Published: April 2015

AbstractObjectivesTo study the impact of novel treatments for elderly (≥66 yr) patients with multiple myeloma (MM) in daily practice by comparing real‐world effects [overall survival (OS) and quality‐adjusted life years (QALYs)] and costs over time. Also, we calculate cost‐effectiveness of treatment sequences commonly prescribed to predict effects and costs if patients had received a different treatment sequence.MethodsReal‐world data including patient and disease characteristics, treatment information and resource use were collected from 1054 elderly patients with MM. Patients received first‐line treatment during 2004–2007 (cohort 1) and 2008–2013 (cohort 2). The two cohorts were compared using a patient‐level simulation (PLS) model comprising regression models which used patient and disease characteristics to estimate time to next treatment and death. Effects and costs from cohort 2 were compared to 4 commonly prescribed real‐world sequences.ResultsUtilisation of novel agents was higher for cohort 2 compared to cohort 1. Modelled average OS for cohort 1 was 38 months (median 25) and total costs €44 200. OS for cohort 2 was 42 months (median 28) and total costs €69 017. The model identified potential OS gains if all patients were to be treated using combinations containing thalidomide, lenalidomide and bortezomib in that particular order. This sequence had, compared to real‐world treatment, the most favourable incremental cost‐effectiveness ratio, €24 618 per life year gained and €34 875 per QALY.ConclusionsOur patient‐level model enabled to study the effects and costs of entire treatment sequences and to compare real‐world treatment patterns over time. Increased utilisation of novel agents improved survival and increased costs for real‐world patients with MM in the Netherlands.
Differentiating neural systems mediating the acquisition vs. expression of goal‐directed and habitual behavioral control
Authors: Liljeholm Mimi , Dunne Simon , O'Doherty John P. 
Published: April 2015

AbstractConsiderable behavioral data indicate that operant actions can become habitual, as demonstrated by insensitivity to changes in the action–outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with functional magnetic resonance imaging as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal‐directed encoding of the consequences of actions, or a habit‐like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also showed that the inferior parietal lobule (an area previously implicated in several aspects of goal‐directed action selection, including the attribution of intent and awareness of agency) predicted sensitivity to outcome devaluation. Finally, we revealed a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggested a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action–outcome and stimulus–response associations.
The effect of acute unilateral inflammation of the equine temporomandibular joint on the kinematics of mastication
Authors: Smyth T. T. , Carmalt J. L. , Treen T. T. , Lanovaz J. L. 
Published: April 2015

SummaryReasons for performing studyDiseases of the temporomandibular joint (TMJ) are well reported in man and some domestic animals other than the horse. The pathophysiology of equine TMJ disease and the effects of disease on the kinematics of mastication are unknown.ObjectivesTo determine whether transient unilateral inflammation of the equine TMJ results in alterations in the masticatory cycle.Study designAn experimental controlled study utilising 6 horses of various ages with normal dentition.MethodsEach horse was equipped with an optical motion tracking (kinematic) system. Horses were observed chewing grass hay over 3 min intervals. Regardless of the initial side of the power stroke in the masticatory cycle, lipopolysaccharide (LPS) was injected in the left TMJ in each horse and the horses were reassessed after 6 h.ResultsFour horses developed effusion of the injected TMJs; 2 of these also began quidding. All horses injected on the original side of the power stroke switched sides while the 2 injected on the contralateral side did not. All horses developed reduced vertical pitch (vertical opening) of the mandible. Overall, rostrocaudal movement of the mandible did not change; however, the timing of this movement relative to the phase of the masticatory cycle did. Injection with LPS did not affect the amount of lateral movement of the mandible.ConclusionsInjection of LPS into the TMJ significantly altered the masticatory cycle compared with baseline values representing avoidance behaviour due to inflammation of the joint, despite which the horses continued to eat using the contralateral mandible. Lipopolysaccharide administration also led to quidding and a loss of feed efficiency (in some individuals).
Early herniorrhaphy of large traumatic abdominal wounds in horses and mules
Authors: Azizi S. , Hashemi‐Asl S.‐M. , Torabi E. 
Published: April 2015

SummaryReasons for performing studySurgical treatment of traumatic abdominal hernias is usually delayed for 2–3 months following injury. The residual defects are then repaired by herniorrhaphy or mesh herniorrhaphy.ObjectiveTo describe the outcome following herniorrhaphy (without a mesh) within 21 days of initial injury to repair external traumatic lateral abdominal hernias in horses and mules.Study designDescriptive case series.MethodsTwenty‐two cases were included. Surgical treatment involved exposure of the hernia sac and closing of the abdominal wall defect with interrupted Mayo mattress or cruciate sutures after reduction of the herniated organ into the peritoneal cavity. Data collected included cause and site of the hernia, surgical findings, immediate and long‐term post operative complications, return to use, duration of convalescence and hernia recurrence.ResultsFalling while crossing impassable pathways was the most common initial cause of the hernia (9/11 horses and 10/11 mules). Adhesion formation to underlying viscera was found intraoperatively in 2 cases. Uncomplicated healing occurred in all animals except 3 with suture abscesses and one with a subcutaneous seroma. At the time of follow‐up (6–24 months after surgery), complete recovery without recurrence of herniation was achieved and animals had returned to their previous use.ConclusionHerniorrhaphy within 21 days using interrupted Mayo mattress or cruciate pattern sutures can be effective for treating external traumatic abdominal hernias in horses and mules.The Summary is available in Chinese – see Supporting Information.
Integrity testing and the prediction of counterproductive behaviours in the military
Authors: Fine Saul , Goldenberg Judith , Noam Yair 
Published: April 2015

While a great deal of research has been carried out on counterproductive work behaviours and integrity testing in civilian organizations, far less is known about these two areas in military settings. The present study developed a military‐oriented integrity test that successfully predicted future disciplinary infractions among a sample of 467 officer training school candidates (ρ = .26), while also discriminating between that sample and a comparable sample of soldiers serving time in military prisons (d = 2.24). In addition to its unique military setting, this study contributes to the integrity test literature by: (1) adopting both individual‐ and group‐level validity paradigms; (2) using a sample of actual job applicants; (3) measuring a reliable objective criterion in a predictive design; and (4) including comparative measures of cognitive ability, personality, and overall assessment centre ratings.Practitioner points

Military settings may uniquely facilitate the reliable and objective measurement of counterproductive work behaviours.

Integrity testing may be a valid and incremental predictor of counterproductive behaviours in military settings.
The integration of solid-form informatics into solid-form selection
Authors: Feeder Neil , Pidcock Elna , Reilly Anthony M , Sadiq Ghazala , Doherty Cheryl L , Back Kevin R , Meenan Paul , Docherty Robert 
Published: April 2015

Abstract

Objectives
To demonstrate how the use of structural informatics during drug development assists with the assessment of the risk of polymorphism and the selection of a commercial solid form.

Methods
The application of structural chemistry knowledge derived from the hundreds of thousands of crystal structures contained in the Cambridge Structural Database to drug candidates is described. Examples given show the comparison of intermolecular geometries to database-derived statistics, the use of Full Interaction Maps to assess polymorph stability and the calculation of hydrogen bond propensities to provide assurance of a stable solid form. The software tools used are included in the Cambridge Structural Database System and the Solid Form Module of Mercury.

Key findings
The early identification of an unusual supramolecular motif in the development phase of maraviroc led to further experimental work to find the most stable polymorph. Analyses of two polymorphs of a pain candidate drug demonstrated how consideration of molecular conformation and intermolecular interactions were used for the assessment of relative stability. Informatics analysis confirmed that the solid form of crizotinib, a monomorphic system, had a low risk of polymorphism.

Conclusions
The application of informatics-based assessment of new chemical entities complements experimental studies and provides a deeper understanding of the qualities of the structure. The information provided by structural analyses is incorporated into the assessment of risk. Informatics techniques are quick to apply and are straightforward to use, allowing an assessment of progressing drug candidates.
The impact PICU nursing expertise has on a child's unplanned extubation
Authors: Norridge Matthew , While Alison E 
Published: April 2015

ABSTRACTBackgroundUnplanned extubations in PICU are used as a measure of quality in clinical governance strategies. While many factors, such as sedation or unit activity, impact negatively on unplanned extubations, high nurse‐patient ratios reduce adverse patient events and improve patient safety. However, optimal nurse‐patient ratios and the impact of the level of nursing expertise on the quality of care are unknown.AimThe study aimed to examine the impact of PICU nursing expertise on the unplanned extubations of children.DesignAudit and analysis of existing adverse event patient and nurse workforce data.MethodThis single‐centre study examined unplanned extubations at a mixed general and cardiac tertiary PICU in the UK. Routinely collected data from nursing and adverse incident databases were examined. The dataset included over 74,477 nurse allocations between August 2006 and April 2011. Unplanned extubations were the adverse event of interest.ResultsA total of 78 unplanned extubations occurred between April 2006 and April 2011. The majority of unplanned extubations occurred when patients were looked after by junior nurses. The seniority of the nurse in‐charge and the qualifications of the patient's nurse were not related to unplanned extubations. However, more unplanned extubations occurred at times of higher patient occupancy.ConclusionsNursing expertise and nurse‐patient ratios were not related to unplanned extubations in this study. Further research is needed to explore the non‐workforce factors such as the securing of endotracheal tubes, sedation levels and unit activity and their relationship with adverse events.Relevance to Clinical PracticeIn paediatric intensive care units where nurse‐patient ratios are high, further investigation is needed to establish what impact non‐workforce factors have on unplanned extubations.
Dothistroma needle blight: an emerging epidemic caused by Dothistroma septosporum in Colombia
Authors: Rodas C. A. , Wingfield M. J. , Granados G. M. , Barnes I. 
Published: April 2015

Plantation forestry in Colombia is based mainly on non‐native species of Pinus and Eucalyptus. Since 2008, a disease with symptoms similar to those of dothistroma needle blight (DNB) has been found affecting large areas planted to Pinus spp. The aim of this study was to identify the causal pathogen as well as to document the levels of disease incidence and severity. Isolates from each of three forestry zones, collected from different host species, were compared based on rDNA sequence of the ITS regions. These were conclusively identified as Dothistroma septosporum, one of two Dothistroma spp. known to cause DNB. Susceptibility was greatest on low elevation Pinus tecunumanii followed by Pinus kesiya and Pinus oocarpa. Pinus maximinoi and high elevation P. tecunumanii showed tolerance to D. septosporum. The disease incidence in the different zones varied significantly with the North zone being the most severely affected. This constitutes the first report of disease distribution and susceptibility of hosts, as well as the first consideration of the relative importance of D. septosporum in Colombia.
A Neoproterozoic ice advance sequence, Sperry Wash, California
Authors: Busfield Marie E. , Le Heron Daniel P. 
Published: April 2015

AbstractThe Kingston Peak Formation is an archetypal Cryogenian succession that crops out across the Death Valley region of eastern California. Above pre‐glacial strata (KP1), two distinct glacial phases have been recognized and are interpreted to be allied to the panglacial Sturtian (KP2 and KP3) and Marinoan (KP4) icehouse events. The thickest and most extensive unit, KP3, forms the entire exposed section at Sperry Wash. At this locality, ice‐distal turbidites are succeeded in turn by ice‐medial and ice‐proximal facies, comprising a spectrum of ice‐rafted debris‐bearing turbidites, debrites and shales. These are overlain by ice‐marginal grounding‐line fan deposits interbedded with glacitectonically deformed heterolithics, supporting local advance to an ice‐contact position. The succession records accumulation within a glacier‐fed subaqueous shelf, wherein the clear progradational signature is driven by ice advance towards the south‐east. Evolution of the subaqueous complex is five‐fold, comprising: (i) ice‐distal outwash; (ii) build‐out of ice‐medial depositional lobes; (iii) ice‐proximal deposition and increased calving; (iv) resumed ice‐margin advance; and (v) growth of ice‐contact grounding‐line fan. This sequence is unique in the Death Valley region for recording the first evidence of advance to ice‐marginal and ice‐contact settings, thereby enabling the location of the glacier terminus to be documented for the first time.
Bayesian network ensemble as a multivariate strategy to predict radiation pneumonitis risk
Authors: Lee Sangkyu , Ybarra Norma , Jeyaseelan Krishinima , Faria Sergio , Kopek Neil , Brisebois Pascale , Bradley Jeffrey D. , Robinson Clifford , Seuntjens Jan , El Naqa Issam 
Published: April 2015

Purpose:Prediction of radiation pneumonitis (RP) has been shown to be challenging due to the involvement of a variety of factors including dose–volume metrics and radiosensitivity biomarkers. Some of these factors are highly correlated and might affect prediction results when combined. Bayesian network (BN) provides a probabilistic framework to represent variable dependencies in a directed acyclic graph. The aim of this study is to integrate the BN framework and a systems’ biology approach to detect possible interactions among RP risk factors and exploit these relationships to enhance both the understanding and prediction of RP.Methods:The authors studied 54 nonsmall‐cell lung cancer patients who received curative 3D‐conformal radiotherapy. Nineteen RP events were observed (common toxicity criteria for adverse events grade 2 or higher). Serum concentration of the following four candidate biomarkers were measured at baseline and midtreatment: alpha‐2‐macroglobulin, angiotensin converting enzyme (ACE), transforming growth factor, interleukin‐6. Dose‐volumetric and clinical parameters were also included as covariates. Feature selection was performed using a Markov blanket approach based on the Koller–Sahami filter. The Markov chain Monte Carlo technique estimated the posterior distribution of BN graphs built from the observed data of the selected variables and causality constraints. RP probability was estimated using a limited number of high posterior graphs (ensemble) and was averaged for the final RP estimate using Bayes’ rule. A resampling method based on bootstrapping was applied to model training and validation in order to control under‐ and overfit pitfalls.Results:RP prediction power of the BN ensemble approach reached its optimum at a size of 200. The optimized performance of the BN model recorded an area under the receiver operating characteristic curve (AUC) of 0.83, which was significantly higher than multivariate logistic regression (0.77), mean heart dose (0.69), and a pre‐to‐midtreatment change in ACE (0.66). When RP prediction was made only with pretreatment information, the AUC ranged from 0.76 to 0.81 depending on the ensemble size. Bootstrap validation of graph features in the ensemble quantified confidence of association between variables in the graphs where ten interactions were statistically significant.Conclusions:The presented BN methodology provides the flexibility to model hierarchical interactions between RP covariates, which is applied to probabilistic inference on RP. The authors’ preliminary results demonstrate that such framework combined with an ensemble method can possibly improve prediction of RP under real‐life clinical circumstances such as missing data or treatment plan adaptation.
A Monte Carlo simulation framework for electron beam dose calculations using Varian phase space files for TrueBeam Linacs
Authors: Rodrigues Anna , Sawkey Daren , Yin Fang‐Fang , Wu Qiuwen 
Published: April 2015

Purpose:To develop a framework for accurate electron Monte Carlo dose calculation. In this study, comprehensive validations of vendor provided electron beam phase space files for Varian TrueBeam Linacs against measurement data are presented.Methods:In this framework, the Monte Carlo generated phase space files were provided by the vendor and used as input to the downstream plan‐specific simulations including jaws, electron applicators, and water phantom computed in the EGSnrc environment. The phase space files were generated based on open field commissioning data. A subset of electron energies of 6, 9, 12, 16, and 20 MeV and open and collimated field sizes 3 × 3, 4 × 4, 5 × 5, 6 × 6, 10 × 10, 15 × 15, 20 × 20, and 25 × 25 cm2 were evaluated. Measurements acquired with a CC13 cylindrical ionization chamber and electron diode detector and simulations from this framework were compared for a water phantom geometry. The evaluation metrics include percent depth dose, orthogonal and diagonal profiles at depths R100, R50, Rp, and Rp+ for standard and extended source‐to‐surface distances (SSD), as well as cone and cut‐out output factors.Results:Agreement for the percent depth dose and orthogonal profiles between measurement and Monte Carlo was generally within 2% or 1 mm. The largest discrepancies were observed within depths of 5 mm from phantom surface. Differences in field size, penumbra, and flatness for the orthogonal profiles at depths R100, R50, and Rp were within 1 mm, 1 mm, and 2%, respectively. Orthogonal profiles at SSDs of 100 and 120 cm showed the same level of agreement. Cone and cut‐out output factors agreed well with maximum differences within 2.5% for 6 MeV and 1% for all other energies. Cone output factors at extended SSDs of 105, 110, 115, and 120 cm exhibited similar levels of agreement.Conclusions:We have presented a Monte Carlo simulation framework for electron beam dose calculations for Varian TrueBeam Linacs. Electron beam energies of 6 to 20 MeV for open and collimated field sizes from 3 × 3 to 25 × 25 cm2 were studied and results were compared to the measurement data with excellent agreement. Application of this framework can thus be used as the platform for treatment planning of dynamic electron arc radiotherapy and other advanced dynamic techniques with electron beams.