bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of intraperitoneal ropivacaine in laparoscopic appendicectomy: a prospective, double‐blinded randomized control Australian study
Authors: Huang Yang Y. , Suthananthan Arul E. , Hunt Victoria , Hruby Jan , Koek Sharnice , Rowcroft Alistair , Beh Han , Jayasundera Mohan
Published: January 2019

Background

Currently, intraoperative use of local anaesthetic is not routinely given in all laparoscopic appendicectomies. Although its use has been widely studied in laparoscopic hernia repairs, gynaecological laparoscopy and laparoscopic cholecystectomies, there are no published trials of the use of intraperitoneal local anaesthetic during laparoscopic appendicectomy in the Australasian setting. The aim of this study was to determine whether the use of intraperitoneal ropivacaine during laparoscopic appendicectomy will reduce the amount of post‐operative opiate analgesia used, abdominal pain, post‐operative nausea or vomiting, shoulder tip pain and length of hospital stay.

Methods

A randomized double‐blinded placebo versus control trial was conducted with patients with clinically diagnosed appendicitis undergoing laparoscopic appendicectomy. Primary outcomes measured were the number of times the patient‐controlled analgesia (PCA) button was pressed post‐operatively and the average and total amount of fentanyl from PCA consumed during the post‐operative period from 0 to 6 h and from 6 to 16 h.

Results

A total of 86 patients with 43 patients in the placebo normal saline group and 43 patients in the treatment ropivacaine group were included in the study. During the immediate post‐operative period (0–6 h), there was a statistically significant reduction in the number of times the PCA button was pressed in the ropivacaine group compared to the normal saline group (16 versus 24 times, P = 0.02).

Conclusion

Intraperitoneal ropivacaine has an analgesic effect for patients up to 6 h following emergency laparoscopic appendicectomy.
Modified laparoscopic keyhole plus repair to manage a parastomal hernia: A single‐center experience
Authors: Rajapandian Subbiah , Jankar Samrat V. , Kakkilaya Harish , Sabnis Sandeep , Ramkrishana Parathasarthi , Palanivelu Praveenraj , Chinnusamy Palanivelu
Published: January 2019

Introduction

Parastomal hernia (PH) is a common late complication of stoma formation for which laparoscopic repair is a well‐accepted modality of treatment. Keyhole repair has been frequently reported with recurrence, but our modification in surgical technique have lesser and acceptable recurrence rates. The present study aimed to assess the results of modified laparoscopic keyhole plus repair in the treatment of symptomatic PH.

Methods

We reviewed our prospectively maintained database to search for patients who had undergone laparoscopic modified keyhole repair between January 2008 and April 2018. All 23 symptomatic patients who had undergone this procedure were included in the present study.

Results

A total of 23 patients were studied. The median age was 37 years (range, 22‐54 years). Two patients with large PHs underwent open excision of the redundant skin and then laparoscopic modified keyhole repair. There was one conversion to open repair because of dense adhesions. The mean operative time was 112 ± 37 minutes. The mean postoperative hospital stay was 3 ± 2 days. There were no significant intraoperative or postoperative complications. During follow‐up, three patients had a seroma, which was managed conservatively. One morbidly obese patient who had an ileal conduit‐related stomal hernia had a symptomatic recurrence 3 years after surgery.

Conclusion

The modified laparoscopic keyhole plus repair is a safe, feasible, and effective technique for PH repair; it has an acceptable recurrence rate and offers good cosmesis and functional outcomes.
Physiologically‐based pharmacokinetics of ziprasidone in pregnant women
Authors: Biesdorf Carla , Martins Frederico S. , Sy Sherwin K.B. , Diniz Andrea
Published: January 2019

Aims

Pregnancy is associated with physiological changes that alter the pharmacokinetics (PK) of drugs. The aim of this study was to predict the PK of ziprasidone in pregnant women.

Methods

A full physiologically‐based pharmacokinetic (PBPK) model of ziprasidone was developed and validated for the non‐pregnant population (healthy adults, paediatrics, geriatrics), and this was extended to the pregnant state to assess the change in PK profile of ziprasidone throughout pregnancy.

Results

The PBPK model successfully predicted the ziprasidone disposition in healthy adult volunteers, wherein the predicted and observed AUC, Cmax and tmax were within the fold‐difference of 0.94–1.09, 0.89–1.40 and 0.80–1.08, respectively. The paediatric and geriatric population, also showed predicted AUC, Cmax and tmax within a two‐fold range of the observed values. The simulated exposure in pregnant women using a p‐PBPK model showed no significant difference when compared to non‐pregnant women.

Conclusions

The PBPK model predicted the impact of physiological changes during pregnancy on PK and exposure of ziprasidone, suggesting that dose adjustment is not necessary in this special population.
Population pharmacokinetics of lenalidomide in patients with B‐cell malignancies
Authors: Hughes Jim H. , Phelps Mitch A. , Upton Richard N. , Reuter Stephanie E. , Gao Yue , Byrd John C. , Grever Michael R. , Hofmeister Craig C. , Marcucci Guido , Blum William , Blum Kristie A. , Foster David J.R.
Published: January 2019

Aims

Lenalidomide is an immunomodulatory imide drug used broadly in the treatment of multiple myeloma and lymphoma. It continues to be evaluated in chronic lymphocytic leukaemia (CLL) at lower doses due to dose‐related toxicities including tumour flare and tumour lysis syndrome. This study aimed to develop a population pharmacokinetic model for lenalidomide in multiple cancers, including CLL, to identify any disease‐related differences in disposition.

Methods

Lenalidomide concentrations from 4 clinical trials were collated (1999 samples, 125 subjects), covering 4 cancers (multiple myeloma, CLL, acute myeloid leukaemia and acute lymphoblastic leukaemia) and a large dose range (2.5–75 mg). A population pharmacokinetic model was developed with NONMEM and patient demographics were tested as covariates.

Results

The data were best fitted by a 1‐compartment kinetic model with absorption described by 7 transit compartments. Clearance and volume of distribution were allometrically scaled for fat‐free mass. The population parameter estimates for apparent clearance, apparent volume of distribution and transit rate constant were 12 L/h (10.8–13.6), 68.8 L (61.8–76.3), and 13.5 h−1(11.9–36.8) respectively. Patients with impaired renal function (creatinine clearance <30 mL/min) exhibited a 22% reduction in lenalidomide clearance compared to patients with creatinine clearance of 90 mL/min. Cancer type had no discernible effect on lenalidomide disposition.

Conclusions

This is the first report of a lenalidomide population pharmacokinetic model to evaluate lenalidomide pharmacokinetics in patients with CLL and compare its pharmacokinetics with other B‐cell malignancies. As no differences in pharmacokinetics were found between the observed cancer‐types, the unique toxicities observed in CLL may be due to disease‐specific pharmacodynamics.
Bidirectional relationship of stress and affect with physical activity and healthy eating
Authors: Schultchen Dana , Reichenberger Julia , Mittl Theresa , Weh Tabea R. M. , Smyth Joshua M. , Blechert Jens , Pollatos Olga
Published: January 2019

Objectives

Physical activity and healthy eating seem to be protective against experiencing stress and negative affect as well as increase positive affect. At the same time, previous studies showed that people reduce salutogenic behaviours such as physical activity and healthy eating in the face of stress and negative affect while increasing such behaviours in the context of positive affect. Due to daily fluctuations of these behaviours, the present study examined these relationships in daily life using ecological momentary assessment (EMA).

Design and methods

Fifty‐one university students responded to six daily prompts during 7 days via smartphone‐based EMA. Items examined stress, emotional experience, physical activity duration, and healthy eating.

Results

Higher stress and negative affect, as well as lower positive affect, were related to a reduction in subsequent physical activity. Higher physical activity levels, in turn, were associated with less subsequent stress and negative affect, as well as more positive affect. No such effects for stress and affect on healthy eating or vice versa were found.

Conclusions

Engaging in physical activity is related to better mood and less stress/negative affect over the next several hours in daily life. Prevention efforts therefore may benefit by focusing on promoting physical activity, particularly when stress/negative affect is high to ‘break the cycle’ of inactivity, stress, and negative affect. Potential effects of healthy eating might be more subtle and characterized by interindividual differences or state effects.

Statement of contribution

What is already known on this subject?

Physical activity can reduce stress as well as negative emotions and can enhance positive emotions.

People tend to eat less healthy food during stressful times, and healthy eating can increase general health.

Physical activity and healthy eating have been mostly assessed separately and through retrospective methods.

What does this study add?

This is an EMA study investigating bidirectional effects of stress, emotions, and salutogenic behaviour.

After physical activity, people felt less stressed/negative and more positive; feeling better and less stressed resulted in more physical activity.

Healthy eating was not associated with stress or emotion level and vice versa.
Diagnosis and management in Pitt‐Hopkins syndrome: First international consensus statement
Authors: Zollino Marcella , Zweier Christiane , Van Balkom Ingrid D. , Sweetser David A. , Alaimo Joseph , Bijlsma Emilia K. , Cody Jannine , Elsea Sarah H. , Giurgea Irina , Macchiaiolo Marina , Smigiel Robert , Thibert Ronald L. , Benoist Ingrid , Clayton‐Smith Jill , De Winter Channa F. , Deckers Stijn , Gandhi Anusha , Huisman Sylvia , Kempink Dagmar , Kruisinga Frea , Lamacchia Vittoria , Marangi Giuseppe , Menke Leonie , Mulder Paul , Nordgren Ann , Renieri Alessandra , Routledge Sue , Saunders Carol J. , Stembalska Agnieszka , Van Balkom Hans , Whalen Sandra , Hennekam Raoul C.
Published: January 2019

Pitt‐Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices has prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care.
Baicalin mitigates cognitive impairment and protects neurons from microglia‐mediated neuroinflammation via suppressing NLRP3 inflammasomes and TLR4/NF‐κB signaling pathway
Authors: Jin Xin , Liu Ming‐Yan , Zhang Dong‐Fang , Zhong Xin , Du Ke , Qian Ping , Yao Wei‐Fan , Gao Hua , Wei Min‐Jie
Published: January 2019

Aims

Baicalin (BAI), a flavonoid compound isolated from the root of Scutellaria baicalensis Georgi, has been established to have potent anti‐inflammation and neuroprotective properties; however, its effects during Alzheimer's disease (AD) treatment have not been well studied. This study aimed to investigate the effects of BAI pretreatment on cognitive impairment and neuronal protection against microglia‐induced neuroinflammation and to explore the mechanisms underlying its anti‐inflammation effects.

Methods

To determine whether BAI plays a positive role in ameliorating the memory and cognition deficits in APP (amyloid beta precursor protein)/PS1 (presenilin‐1) mice, behavioral experiments were conducted. We assessed the effects of BAI on microglial activation, the production of proinflammatory cytokines, and neuroinflammation‐mediated neuron apoptosis in vivo and in vitro using Western blot, RT‐PCR, ELISA, immunohistochemistry, and immunofluorescence. Finally, to elucidate the anti‐inflammation mechanisms underlying the effects of BAI, the protein expression of NLRP3 inflammasomes and the expression of proteins involved in the TLR4/NF‐κB signaling pathway were measured using Western blot and immunofluorescence.

Results

The results indicated that BAI treatment attenuated spatial memory dysfunction in APP/PS1 mice, as assessed by the passive avoidance test and the Morris water maze test. Additionally, BAI administration effectively decreased the number of activated microglia and proinflammatory cytokines, as well as neuroinflammation‐mediated neuron apoptosis, in APP/PS1 mice and LPS (lipopolysaccharides)/Aβ‐stimulated BV2 microglial cells. Lastly, the molecular mechanistic study revealed that BAI inhibited microglia‐induced neuroinflammation via suppression of the activation of NLRP3 inflammasomes and the TLR4/NF‐κB signaling pathway.

Conclusion

Overall, the results of the present study indicated that BAI is a promising neuroprotective compound for use in the prevention and treatment of microglia‐mediated neuroinflammation during AD progression.
Comparing Gelfoam vs fat as a sealing material in stapedotomy: A prospective double‐blind randomised clinical trial
Authors: Faramarzi Mohammad , Roosta Sareh , Aminpour Safoura
Published: January 2019

Objectives

One research aspect of stapes surgery is various materials that are used to seal the oval window. Several materials are used to seal the oval window, for example adipose tissue, perichondrium, vein graft, gelatin sponge (Gelfoam), blood clot and soft connective tissue. Up to now, there has been no randomised clinical trial that has evaluated the effects of different types of sealing material on hearing outcomes after stapedotomy. Hence, the present study aimed to find out which of these materials; fat or Gelfoam was associated with better hearing outcome, when used as a sealing material.

Design

This prospective, double‐blind, randomised clinical trial was carried out on ears that had undergone stapedotomy.

Setting

Dastgheib Hospital affiliated to Shiraz University of Medical Sciences, a referral otology centre in southern Iran.

Participants

A total of 176 primary stapedotomies were analysed. Fat harvested from the ear lobule was used in 86 ears and Gelfoam in 90 ears.

Main outcome measures

Preoperative and postoperative pure tone audiometric data and incidence of sensorineural hearing loss were evaluated.

Results

Total of 90.7% of all ears in the fat group and 87.8% of ears in Gelfoam group achieved postoperative air‐bone gap (ABG) within 20 dB, and this difference was not significant. There was no case of sensorineural hearing loss (defined as 10 dB or more reduction in BC threshold) in both groups in mean frequencies of 0.5‐3 kHz. There were 9 cases of sensorineural hearing loss at 4 kHz in the fat group vs 4 in the Gelfoam group. The occurrence of sensorineural hearing loss in different frequencies was not significant between the two groups (P > 0.05). In addition, there was no case of dead ear in either group.

Conclusions

We found similarity between hearing outcome in the Gelfoam and fat as sealing materials in stapedotomy. We believe that the first limitation of this study was the short‐term follow‐up in stapedotomy. The other issue is that one has to be cautious when using our result, which might not be applicable in larger fenestra stapedectomy.
Bias at the intersection of race and gender: Evidence from preschool‐aged children
Authors: Perszyk Danielle R. , Lei Ryan F. , Bodenhausen Galen V. , Richeson Jennifer A. , Waxman Sandra R.
Published: January 2019

There is ample evidence of racial and gender bias in young children, but thus far this evidence comes almost exclusively from children's responses to a single social category (either race or gender). Yet we are each simultaneously members of many social categories (including our race and gender). Among adults, racial and gender biases intersect: negative racial biases are expressed more strongly against males than females. Here, we consider the developmental origin of bias at the intersection of race and gender. Relying on both implicit and explicit measures, we assessed 4‐year‐old children's responses to target images of children who varied systematically in both race (Black and White) and gender (male and female). Children revealed a strong and consistent pro‐White bias. This racial bias was expressed more strongly for males than females: children's responses to Black boys were less positive than to Black girls, White boys or White girls. This outcome, which constitutes the earliest evidence of bias at the intersection of race and gender, underscores the importance of addressing bias in the first years of life.
A mental number line in human newborns
Authors: Di Giorgio Elisa , Lunghi Marco , Rugani Rosa , Regolin Lucia , Dalla Barba Beatrice , Vallortigara Giorgio , Simion Francesca
Published: January 2019

Humans represent numbers on a mental number line with smaller numbers on the left and larger numbers on the right side. A left‐to‐right oriented spatial–numerical association, (SNA), has been demonstrated in animals and infants. However, the possibility that SNA is learnt by early exposure to caregivers’ directional biases is still open. We conducted two experiments: in Experiment 1, we tested whether SNA is present at birth and in Experiment 2, we studied whether it depends on the relative rather than the absolute magnitude of numerousness. Fifty‐five‐hour‐old newborns, once habituated to a number (12), spontaneously associated a smaller number (4) with the left and a larger number (36) with the right side (Experiment 1). SNA in neonates is not absolute but relative. The same number (12) was associated with the left side rather than the right side whenever the previously experienced number was larger (36) rather than smaller (4) (Experiment 2). Control on continuous physical variables showed that the effect is specific of discrete magnitudes. These results constitute strong evidence that in our species SNA originates from pre‐linguistic and biological precursors in the brain.
School Grants and Education Quality: Experimental Evidence from Senegal
Authors: Carneiro Pedro , Koussihouèdé Oswald , Lahire Nathalie , Meghir Costas , Mommaerts Corina
Published: January 2019

The effect of increasing school resources on educational outcomes is a central issue in the debate on improving school quality. In this paper we use a randomized experiment to analyse the impact of a school grants programme in Senegal, which allowed schools to apply for funding for pedagogic improvements of their choice. We find positive effects on test scores at lower grades that persist for at least two years. These effects are concentrated among schools that focused funds on human resources improvements rather than school materials, reinforcing that teachers and principals are a central determinant of school quality.
Understanding the implementation of coordinated specialty Care for Early Psychosis in New York state: A guide using the RE‐AIM framework
Authors: Mascayano Franco , Nossel Ilana , Bello Iruma , Smith Thomas , Ngo Hong , Piscitelli Sarah , Malinovsky Igor , Susser Ezra , Dixon Lisa
Published: January 2019

Aim

Consistent evidence shows that early interventions for individuals with psychosis lead to improvements in symptoms, social functioning and treatment satisfaction. These results, combined with the allocation of specific funds for early psychosis services, have contributed to the emergence and dissemination of coordinated specialty care for early psychosis in the United States. Despite the rapid growth of such services across the country over the last 5 years, implementation processes are not yet well understood. We employ the RE‐AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance) framework to describe processes, achievements and challenges of an early psychosis program called OnTrackNY that has been implemented in New York State.

Methods

OnTrackNY is a coordinated specialty care program that delivers early intervention services that include both medications and psychosocial interventions to youths experiencing a first episode of non‐affective psychosis. By drawing on outcome and care process data that are collected quarterly from all OnTrackNY sites, we describe the status of each RE‐AIM dimension regarding OnTrackNY implementation followed by an evaluation of both achievements and shortcomings.

Results

In general terms, OnTrackNY has shown to be a scalable and sustainable model for addressing early psychosis, reaching and providing recovery‐oriented services to a large population in need.

Conclusion

Despite its advancements, a series of limitations pose challenges to the implementation and maintenance of the model including, but not to, the lack of incentives for coordination of services, the fragmentation of child and adult services, and concerns about financial sustainability.
Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system
Authors: Härönen Heli , Zainul Zarin , Naumenko Nikolay , Sormunen Raija , Miinalainen Ilkka , Shakirzyanova Anastasia , Santoleri Sabrina , Kemppainen Antti V. , Giniatullin Rashid , Pihlajaniemi Taina , Heikkinen Anne
Published: January 2019

Transmembrane collagen XIII has been linked to maturation of the musculoskeletal system. Its absence in mice (Col13a1−/−) results in impaired neuromuscular junction (NMJ) differentiation and function, while transgenic overexpression (Col13a1oe) leads to abnormally high bone mass. Similarly, loss‐of‐function mutations in COL13A1 in humans produce muscle weakness, decreased motor synapse function and mild dysmorphic skeletal features. Here, analysis of the exogenous overexpression of collagen XIII in various muscles revealed highly increased transcript and protein levels, especially in the diaphragm. Unexpectedly, the main location of exogenous collagen XIII in the muscle was extrasynaptic, in fibroblast‐like cells, while some motor synapses were devoid of collagen XIII, possibly due to a dominant negative effect. Concomitantly, phenotypical changes in the NMJs of the Col13a1oe mice partly resembled those previously observed in Col13a1−/− mice. Namely, the overall increase in collagen XIII expression in the muscle produced both pre‐ and postsynaptic abnormalities at the NMJ, especially in the diaphragm. We discovered delayed and compromised acetylcholine receptor (AChR) clustering, axonal neurofilament aggregation, patchy acetylcholine vesicle (AChV) accumulation, disrupted adhesion of the nerve and muscle, Schwann cell invagination and altered evoked synaptic function. Furthermore, the patterns of the nerve trunks and AChR clusters in the diaphragm were broader in the adult muscles, and already prenatally in the Col13a1oe mice, suggesting collagen XIII involvement in the development of the neuromuscular system. Overall, these results confirm the role of collagen XIII at the neuromuscular synapses and highlight the importance of its correct expression and localization for motor synapse formation and function.
Caffeine and cannabinoid receptors modulate impulsive behavior in an animal model of attentional deficit and hyperactivity disorder
Authors: Leffa Douglas T. , Ferreira Samira G. , Machado Nuno J. , Souza Carolina M. , Rosa Fernanda da , de Carvalho Cristiane , Kincheski Grasielle C. , Takahashi Reinaldo N. , Porciúncula Lisiane O. , Souza Diogo O. , Cunha Rodrigo A. , Pandolfo Pablo
Published: January 2019

Attention deficit and hyperactivity disorder (ADHD) is characterized by impaired levels of hyperactivity, impulsivity, and inattention. Adenosine and endocannabinoid systems tightly interact in the modulation of dopamine signaling, involved in the neurobiology of ADHD. In this study, we evaluated the modulating effects of the cannabinoid and adenosine systems in a tolerance to delay of reward task using the most widely used animal model of ADHD. Spontaneous Hypertensive Rats (SHR) and Wistar–Kyoto rats were treated chronically or acutely with caffeine, a non‐selective adenosine receptor antagonist, or acutely with a cannabinoid agonist (WIN55212‐2, WIN) or antagonist (AM251). Subsequently, animals were tested in the tolerance to delay of reward task, in which they had to choose between a small, but immediate, or a large, but delayed, reward. Treatment with WIN decreased, whereas treatment with AM251 increased the choices of the large reward, selectively in SHR rats, indicating a CB1 receptor‐mediated increase in impulsive behavior. An acute pre‐treatment with caffeine blocked WIN effects. Conversely, a chronic treatment with caffeine increased the impulsive phenotype and potentiated the WIN effects. The results indicate that both cannabinoid and adenosine receptors modulate impulsive behavior in SHR: the antagonism of cannabinoid receptors might be effective in reducing impulsive symptoms present in ADHD; in addition, caffeine showed the opposite effects on impulsive behavior depending on the length of treatment. These observations are of particular importance to consider when therapeutic manipulation of CB1 receptors is applied to ADHD patients who consume coffee.
Uncontrolled eating: a unifying heritable trait linked with obesity, overeating, personality and the brain
Authors: Vainik Uku , García‐García Isabel , Dagher Alain
Published: January 2019

Many eating‐related psychological constructs have been proposed to explain obesity and overeating. However, these constructs, including food addiction, disinhibition, hedonic hunger, emotional eating, binge eating and the like all have similar definitions, emphasizing loss of control over intake. As questionnaires measuring the constructs correlate strongly (r > 0.5) with each other, we propose that these constructs should be reconsidered to be part of a single broad phenotype: uncontrolled eating. Such an approach enables reviewing and meta‐analysing evidence obtained with each individual questionnaire. Here, we describe robust associations between uncontrolled eating, body mass index (BMI), food intake, personality traits and brain systems. Reviewing cross‐sectional and longitudinal data, we show that uncontrolled eating is phenotypically and genetically intertwined with BMI and food intake. We also review evidence on how three psychological constructs are linked with uncontrolled eating: lower cognitive control, higher negative affect and a curvilinear association with reward sensitivity. Uncontrolled eating mediates all three constructs’ associations with BMI and food intake. Finally, we review and meta‐analyse brain systems possibly subserving uncontrolled eating: namely, (i) the dopamine mesolimbic circuit associated with reward sensitivity, (ii) frontal cognitive networks sustaining dietary self‐control and (iii) the hypothalamus‐pituitary‐adrenal axis, amygdala and hippocampus supporting stress reactivity. While there are limits to the explanatory and predictive power of the uncontrolled eating phenotype, we conclude that treating different eating‐related constructs as a single concept, uncontrolled eating, enables drawing robust conclusions on the relationship between food intake and BMI, psychological variables and brain structure and function.
Plato and the Theodosian Code
Authors: Schmidt‐Hofner Sebastian
Published: January 2019

The codification project initiated in 429 ad that resulted in the Theodosian Code was originally designed to integrate three types of law: one, imperial constitutions since Constantine; two, the legal material collected in the tetrarchic Codices Gregorianus and Hermogenianus; and three, a florilegium of juristic writings and responsa. The ultimate aim was to condense all this in a single comprehensive law book that would govern the entire life of the empire and its subjects. As this paper shows, such a project had no precedent in Roman legal history and in fact ran counter to the traditional multiplicity of legal sources in Rome. This prompts a question: from where did the intellectual fathers of the codification project drew inspiration for such a revolutionary idea? In the paper's second part, I argue that one important model for the codification project of 429 could have been the legal code Plato designed for the ideal state of the Laws.
Microplastic Contamination in Karst Groundwater Systems
Authors: Panno Samuel V. , Kelly Walton R. , Scott John , Zheng Wei , McNeish Rachel E. , Holm Nancy , Hoellein Timothy J. , Baranski Elizabeth L.
Published: January 2019

Groundwater in karst aquifers constitutes about 25% of drinking water sources globally. Karst aquifers are open systems, susceptible to contamination by surface‐borne pollutants. In this study, springs and wells from two karst aquifers in Illinois, USA, were found to contain microplastics and other anthropogenic contaminants. All microplastics were fibers, with a maximum concentration of 15.2 particles/L. The presence of microplastic was consistent with other parameters, including phosphate, chloride and triclosan, suggesting septic effluent as a source. More studies are needed on microplastic sources, abundance, and impacts on karst ecosystems.
Do European trade unions foster social solidarity? Evidence from multilevel data in 18 countries
Authors: Rosetti Nicolo
Published: January 2019

Trade unions have been analysed quantitatively primarily in their role as vested interest organisations, attempting to quantify the excludable benefits they provide to members rather than examine their wider impact in an institutional context. Power resource theory acknowledges unions as social agents but assumes the willingness to oppose neoliberalism is constant, limited only by scarce power resources. Whilst true in general terms, this fails to explain trends of increasing labour market dualism in resource‐rich industrial relations regimes. This article examines social solidarity as a union power resource, measuring the impact of trade union membership on social attitudes of solidarity. Data were collected from the 2016 European Social Survey for 18 countries, grouped into five distinct industrial relations regimes. The findings suggest that, at European level, union membership still has a significant effect on all dimensions of social solidarity, but these relationships vary significantly across industrial relations regimes.
Laser‐quality Tm:(Lu0.8Sc0.2)2O3 mixed sesquioxide ceramics shaped by gelcasting of well‐dispersed nanopowders
Authors: Wu Huajun , Pan Guo‐Hui , Hao Zhendong , Zhang Liangliang , Zhang Xia , Zhang Ligong , Zhao Haifeng , Zhang Jiahua
Published: January 2019

Tm3+‐doped mixed sesquioxide transparent ceramics are attractive candidates for the generation of robust ~2.1 μm lasers. In this paper, laser‐quality Tm:(Lu0.8Sc0.2)2O3 mixed sesquioxide ceramics were shaped for the first time by gelcasting of well‐dispersed nanopowders, which were obtained using a modified coprecipitation method. The dispersibility of starting nanopowders was largely improved using alcohol‐water solvent. The rheological properties of slurries were optimized for gelcasting. We also investigated the densification behavior of the gel‐casted green compacts. In contrast to the dry‐pressing route, it was found that gelcasting could yield more homogeneous and transparent ceramics. The optical in‐line transmittance of the ceramic rod 12 mm in length was as high as 80.3% at 2090 nm. Upon pumping the ceramic rod by 796 nm diode laser, a 1.88 W CW laser at 2090 nm was acquired with a slope efficiency of 24.6% (with respect to the input pump power).
PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms
Authors: Jiang Xuan , Li Xiaoying , Li Weihua , Bai Huimin , Zhang Zhenyu
Published: January 2019

Poly (ADP‐ribose) polymerase (PARP) inhibitors have provided great clinical benefits to ovarian cancer patients. To date, three PARP inhibitors, namely, olaparib, rucaparib and niraparib have been approved for the treatment of ovarian cancer in the United States. Homologous recombination deficiency (HRD) and platinum sensitivity are prospective biomarkers for predicting the response to PARP inhibitors in ovarian cancers. Preclinical data have focused on identifying the gene aberrations that might generate HRD and induce sensitivity to PARP inhibitors in vitro in cancer cell lines or in vivo in patient‐derived xenografts. Clinical trials have focused on genomic scar analysis to identify biomarkers for predicting the response to PARP inhibitors. Additionally, researchers have aimed to investigate mechanisms of resistance to PARP inhibitors and strategies to overcome this resistance. Combining PARP inhibitors with HR pathway inhibitors to extend the utility of PARP inhibitors to BRCA‐proficient tumours is increasingly foreseeable. Identifying the population of patients with the greatest potential benefit from PARP inhibitor therapy and the circumstances under which patients are no longer suited for PARP inhibitor therapy are important. Further studies are required in order to propose better strategies for overcoming resistance to PARP inhibitor therapy in ovarian cancers.
Efficacy of reconstructive surgical therapy at peri‐implantitis‐related bone defects. A systematic review and meta‐analysis
Authors: Tomasi Cristiano , Regidor Erik , Ortiz‐Vigón Alberto , Derks Jan
Published: January 2019

Objectives

The present systematic review aimed at evaluating the efficacy of reconstructive surgical therapy at peri‐implantitis‐related bone defects.

Methods

Studies reporting on outcomes of reconstructive surgery at peri‐implantitis‐related bone defects at 12 months were identified through an electronic search. Following data extraction, two different sets of meta‐analyses were performed. Primarily, controlled studies were used to evaluate the potential benefit of reconstructive surgical therapy over controls. Secondly, overall outcome of reconstructive surgical therapy was assessed by comparing baseline values with outcomes at 12 months. Results were expressed as weighted mean differences (WMD) or risk ratios (RR). Heterogeneity was described by I2 and prediction intervals.

Results

The potential benefit of reconstructive techniques over control procedures was evaluated in three studies, representing a total of 116 implants. Altogether, 16 studies reported on the outcome of reconstructive measures at 12 months after surgery. The meta‐analyses identified a larger improvement in marginal bone levels (MBL, WMD = 1.7 mm) and in defect fill (WMD = 57%) for test procedures, but found no differences for clinical measures (reduction of probing depth (PD) and bleeding on probing (BOP). Changes of clinical attachment and soft tissue levels were not considered. In terms of overall outcome, therapy resulted in improved MBL (WMD = 2.0 mm) and CAL (WMD = 1.8 mm), in recession (WMD = 0.7 mm), in reduced PD (WMD = 2.8 mm) and in reduced BOP (Implants: RR = 0.4/Sites: RR = 0.2). None of the included studies addressed patient‐reported outcome measures.

Conclusions

The available evidence on reconstructive therapy at peri‐implantitis‐related defects is limited by (a) the low number of controlled studies, (b) the lack of controlled studies for commonly used procedures, (c) the heterogeneity between studies and (d) the choice of outcome measures. A high variability for predicted outcomes at 12 months was noted. The interpretation of the demonstrated larger MBL gain for test procedures is difficult as graft material may not be distinguishable from newly formed bone. Potential aesthetic and patient‐reported advantages remain to be demonstrated.
Mirogabalin for the treatment of diabetic peripheral neuropathic pain: A randomized, double‐blind, placebo‐controlled phase III study in Asian patients
Authors: Baba Masayuki , Matsui Norimitsu , Kuroha Masanori , Wasaki Yosuke , Ohwada Shoichi
Published: January 2019

Aims/Introduction

This study evaluated the efficacy and safety of mirogabalin, a novel, potent, selective ligand of the α2δ subunit of voltage‐dependent Ca2+ channels, for the treatment of diabetic peripheral neuropathic pain (DPNP).

Materials and Methods

During this double‐blind, multisite, placebo‐controlled phase III study, Asian patients aged ≥20 years with type 1 or 2 diabetes and DPNP were randomized 2:1:1:1 to a placebo, mirogabalin 15, 20 or 30 mg/day for up to 14 weeks, with a 1‐ to 2‐week titration (NCT02318706). The primary endpoint was the change from baseline in average daily pain score (ADPS) at week 14, defined as a weekly average of daily pain (0 = no pain to 10 = worst possible pain, for the past 24 h).

Results

Of 834 randomized patients, 330, 164, 165 and 165 received placebo, mirogabalin 15, 20 or 30 mg/day, respectively, and were included in analyses (modified intention‐to‐treat population, n = 824); 755 (90.5%) completed the study. At week 14, the least squares mean average daily pain score change from baseline was −1.31, −1.34, −1.47 and −1.81, respectively, showing statistical significance for mirogabalin 30 mg/day versus placebo (P = 0.0027). The treatment‐emergent adverse events observed were mostly mild‐to‐moderate in all mirogabalin doses, and the most frequent treatment‐emergent adverse events were nasopharyngitis, somnolence, dizziness, peripheral edema and weight increase.

Conclusions

Mirogabalin relieved DPNP in a dose‐dependent manner; mirogabalin 30 mg/day showed statistically significant pain relief (vs placebo) in Asian DPNP patients. All doses of mirogabalin tested were well tolerated.
Two new species of Heptapterus (Siluriformes: Heptapteridae) from the Uruguay River basin, Brazil
Authors: Faustino‐Fuster Dario R. , Bockmann Flávio A. , Malabarba Luiz R.
Published: January 2019

As part of an ongoing taxonomic revision of the genus Heptapterus from the Laguna dos Patos and Uruguay River drainages and Atlantic coastal streams of southern Brazil and Uruguay, two new species closely related to Heptapterus mustelinus were identified. Both species are endemic to small tributaries of the Uruguay River. The two new species are distinguished from each other and from other species of Heptapterus by arrangement of cephalic and trunk laterosensory systems, number of vertebrae and number of dorsal, pectoral and anal‐fin rays. Phylogenetic analyses of mitochondrial DNA (coI and cytb) sequence data further supports distinctiveness of the two new species.
Patients' and physicians' interpretation of chemotherapy‐induced peripheral neurotoxicity
Authors: Cavaletti Guido , Cornblath David R. , Merkies Ingemar S.J. , Postma Tjeerd J. , Rossi Emanela , Alberti Paola , Bruna Jordi , Argyriou Andreas A. , Briani Chiara , Velasco Roser , Kalofonos Haralabos P. , Psimaras Dimitri , Ricard Damien , Pace Andrea , Faber Catharina G. , Lalisang Roy I. , Brandsma Dieta , Koeppen Susanne , Kerrigan Simon , Schenone Angelo , Grisold Wolfgang , Mazzeo Anna , Padua Luca , Dorsey Susan G. , Penas‐Prado Marta , Valsecchi Maria G. ,   the CI‐PeriNomS Group
Published: January 2019

To test if and how chemotherapy‐induced peripheral neurotoxicity (CIPN) is perceived differently by patients and physicians, making assessment and interpretation challenging. We performed a secondary analysis of the CI‐PeriNomS study which included 281 patients with stable CIPN. We tested: (a) the association between patients' perception of activity limitation in performing eight common tasks and neurological impairment and (b) how the responses to questions related to these daily activities are interpreted by the treating oncologist. To achieve this, we compared patients' perception of their activity limitation with neurological assessment and the oncologists' blind interpretation. Distribution of the scores attributed by oncologists to each daily life maximum limitation (“impossible”) generated three groups: Group 1 included limitations oncologists attributed mainly to motor impairment; Group 2 ones mainly attributed to sensory impairment and Group 3 ones with uncertain motor and sensory impairment. Only a subset of questions showed a significant trend between severity in subjective limitation, reported by patients, and neurological impairment. In Group 1, neurological examination confirmed motor impairment in only 51%‐65% of patients; 76%‐78% of them also had vibration perception impairment. In Group 2, sensory impairment ranged from 84% to 100%; some degree of motor impairment occurred in 43%‐56% of them. In Group 3 strength reduction was observed in 49%‐50% and sensory perception was altered in up to 82%. Interpretation provided by the panel of experienced oncologists was inconsistent with the neurological impairment. These observations highlight the need of a core set of outcome measures for future CIPN trials.
Children’s views on postsurgical pain in recovery units in Norway: A qualitative study
Authors: Smeland Anja Hetland , Rustøen Tone , Næss Torgun , Nybro Lill , Lundeberg Stefan , Reinertsen Hanne , Diseth Trond H. , Twycross Alison
Published: January 2019

Aims and objectives

To explore children's postsurgical experiences with pain and pain management in the recovery unit.

Background

Children's pain is underestimated and undertreated. Untreated pain can cause unnecessary suffering, increased complication risks and may lead to chronic pain. Research exploring children's experiences with postoperative pain and pain management is limited.

Design

A qualitative, exploratory study. The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ).

Methods

Children (N = 20), 8–16 years old, took part in semi‐structured interviews about their experiences with pain and postoperative pain management while they were in a recovery unit. Data were collected at two university hospitals in Norway. Content analysis was used to analyse the data.

Results

Three themes emerged from the interviews: “children's experiences of what felt unpleasant and painful,” “children's experiences with pain management” and “children's recommendations for future pain management”. About half of the children reported moderate to severe pain while in the recovery unit and they did not always tell their nurses when they had pain. They also reported experiencing pain in places other than their surgical wounds and stated that nausea and vomiting felt unpleasant and painful. The children indicated that pain medications and the use of nonpharmacological methods helped them cope with their pain and provided several recommendations about how to improve pain management.

Conclusion

Paediatric postoperative pain management remains suboptimal. The children in our study provided useful information about their pain experiences, how to improve pain management and explained why they did not tell their nurses when they were in pain.

Relevance to clinical practice

These findings should direct further improvements in paediatric postoperative pain management, such as increased use of pain assessment tools and preparatory information, as well as more appropriate administration of pain medications.
Factors associated with glycaemic control in patients with diabetes mellitus: A systematic literature review
Authors: Cheng Ling Jie , Wang Wenru , Lim Suan Tee , Wu Vivien Xi
Published: January 2019

Objectives

To perform a systematic review search and critically review the empirical evidence concerning the factors affecting glycaemic control in patients with type 1 or 2 diabetes mellitus.

Background

Previous primary studies have investigated the factors associated with glycaemic control among patients with type 1 or 2 diabetes, but attempts to amalgamate these evidences have been methodologically limited. Hence, a robust review of the evidence is essential to explore factors that can be addressed to promote good glycaemic control in patients with diabetes.

Design

Mixed‐method systematic review using the Preferred Reporting Items for Systematic review and Meta‐Analysis 2009 flow diagram, integrating evidence from qualitative and quantitative studies (see Supporting Information File S1).

Methods

A systematic review of the literature published between 2006–2017 was conducted in seven electronic databases (CINAHL, MEDLINE, Scopus, EMBASE, PsycINFO, PubMed and ScienceDirect) using the search terms “diabetes mellitus,” “glycemic control,” “self‐concept,” “knowledge,” “self‐efficacy,” “empowerment,” “race,” “ethnicity,” “duration,” “medication,” “obesity” and “comorbidity.”

Results

A total of 1,582 articles were initially retrieved, and 24 of these articles were included in this systematic literature review. The overall empirical evidence suggested that higher socio‐economic status, greater dietary knowledge, and higher self‐efficacy and empowerment improve glycaemic control among patients with diabetes mellitus.

Conclusions

This review presented the factors associated with glycaemic control that may pose significant socio‐economic problems to most nations worldwide and impede development nationally, regionally and even globally. Greater emphasis needs to be placed on implementing lifestyle changes on a societal level to stem the tide of the epidemic.

Relevance to Clinical Practice

There is a need to implement self‐management initiatives, that incorporate dietary knowledge, to empower patients with diabetes in their own care. Future public health policy must be geared towards increasing the capability of dealing with the rising incidence of diabetes and implementing primary prevention.
Introducing early‐phase medical students to clinical paediatrics using simulation and a flipped‐classroom
Authors: Uther Penelope , Van Munster Kerri‐Anne , Briggs Nancy , O'Neill Susan , Kennedy Sean
Published: January 2019

Aim

Both simulation and the flipped‐classroom improve learning outcomes in medical education, with evidence emerging that they are effective in combination (‘flipped‐simulation’). Previous studies evaluating simulation in paediatrics have assessed efficacy for senior students. This study aimed to assess whether using flipped‐simulation in early‐phase medical student education would show similar benefits.

Methods

A flipped‐simulation session was introduced into the earliest phase of the University of New South Wales Sydney's undergraduate medical program. A pre‐test‐post‐test study design was used to assess short‐term knowledge gains with an eight‐item quiz administered before and after students attended the session. A retrospective cohort design was used to assess long‐term knowledge retention, with student scores from a 10‐item quiz administered at the second‐phase paediatric course orientation, compared between a group that completed the flipped‐simulation course and a group that attended an alternative play‐based session. Additional survey data regarding student satisfaction were gathered.

Results

Students demonstrated short‐term knowledge gains: mean test scores improved from the pre‐test to post‐test (3.4 ± 1.5 vs. 6.0 ± 1.3, P < 0.001). Students attending the flipped‐simulation course retained knowledge more effectively in the longer term: mean test scores of students who completed the flipped‐simulation session were significantly higher than those who attended the alternative play‐based session (4.4 ± 1.9 vs. 3.4 ± 1.8, P < 0.001). Survey data demonstrated high student confidence in practical skills.

Conclusion

Combining simulation and the flipped‐classroom is effective for early‐phase medical students, with improved knowledge over the short and long term, and high student satisfaction.