bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety, Tolerability, and Pharmacokinetics of Therapeutic and Supratherapeutic Doses of Tramadol Hydrochloride in Healthy Adults: A Randomized, Double‐Blind, Placebo‐Controlled Multiple‐Ascending‐Dose Study
Authors: DeLemos Byron , Richards Henry M. , Vandenbossche Joris , Ariyawansa Jay , Natarajan Jaya , Alexander Binu , Ramakrishna Tage , Murtaugh Thomas , Stahlberg Hans‐Jürgen 
Published: September 2017

AbstractThis randomized, double‐blind, parallel‐group multiple‐ascending‐dose study evaluated the safety, tolerability, and pharmacokinetics of tramadol hydrochloride in healthy adults to inform dosage and design for a subsequent QT/QTc study. Healthy men and women, 18 to 45 years old (inclusive), were sequentially assigned to the tramadol 200, 400, or 600 mg/day treatment cohort and within each cohort, randomized (4:1) to either tramadol or placebo every 6 hours for 9 oral doses. Of the 24 participants randomized to tramadol (n = 8/cohort), 22 (91.7%) completed the study. The AUCtau,ss of tramadol increased approximately 2.2‐ and 3.6‐fold for the (+) enantiomer and 2.0‐ and 3.5‐fold for the (‐) enantiomer with increasing dose from 200 to 400 and 600 mg/day, whereas the Cmax,ss increased 2.1‐ and 3.3‐fold for the (+) enantiomer and 2.0‐ and 3.2‐fold for the (‐) enantiomer. Overall, 21 participants (87.5%) participants reported ≥1 treatment‐emergent adverse event; most frequent were nausea (17 of 24, 70.8%) and vomiting (7 of 24, 29.2%). Vomiting (affected participants and events) increased with increasing dose from 200 to 600 mg/day but was mild (5 of 24) or moderate (2 of 24) in severity. All tested dosage regimens of tramadol showed acceptable safety and tolerability profile for further investigation in a thorough QT/QTc study.
Population differentiation or species formation across the Indian and the Pacific Oceans? An example from the brooding marine hydrozoan Macrorhynchia phoenicea
Authors: Postaire Bautisse , Gélin Pauline , Bruggemann J. Henrich , Pratlong Marine , Magalon Hélène 
Published: September 2017

AbstractAssessing population connectivity is necessary to construct effective marine protected areas. This connectivity depends, among other parameters, inherently on species dispersal capacities. Isolation by distance (IBD) is one of the main modes of differentiation in marine species, above all in species presenting low dispersal abilities. This study reports the genetic structuring in the tropical hydrozoan Macrorhynchia phoenicea α (sensu Postaire et al., 2016a), a brooding species, from 30 sampling sites in the Western Indian Ocean and the Tropical Southwestern Pacific, using 15 microsatellite loci. At the local scale, genet dispersal relied on asexual propagation at short distance, which was not found at larger scales. Considering one representative per clone, significant positive FIS values (from −0.327*** to 0.411***) were found within almost all sites. Gene flow was extremely low at all spatial scales, among sites within islands (<10 km distance) and among islands (100 to >11,000 km distance), with significant pairwise FST values (from 0.035*** to 0.645***). A general pattern of IBD was found at the Indo‐Pacific scale, but also within ecoregions in the Western Indian Ocean province. Clustering and network analyses identified each island as a potential independent population, while analysis of molecular variance indicated that population genetic differentiation was significant at small (within island) and intermediate (among islands within province) spatial scales. As shown by this species, a brooding life cycle might be corollary of the high population differentiation found in some coastal marine species, thwarting regular dispersal at distances more than a few kilometers and probably leading to high cryptic diversity, each island housing independent evolutionary lineages.
Meeting in difference: Revisiting the therapeutic relationship based on patients′ and therapists′ experiences in several clinical contexts
Authors: Altimir Carolina , Capella Claudia , Núñez Lucía , Abarzúa Marianella , Krause Mariane 
Published: September 2017

AbstractDespite decades of research on the therapeutic relationship and the therapeutic alliance and their connection with therapeutic outcomes (Horvath, Del Re, Flückiger, & Symonds, 2011), only a handful of studies have examined how they are experienced by the therapy participants. The aim of the present study is to describe the therapeutic relationship from the subjective perspective of the patients and therapists involved in 3 clinical cases: (a) a 7‐year‐old child diagnosed with attention deficit hyperactivity disorder, (b) a 29‐year old woman diagnosed with a personality disorder, and (c) a 22‐year‐old man diagnosed with schizophrenia. We conducted semistructured interviews with patients and therapists that were later analyzed following grounded theory coding procedures (Corbin & Strauss, 2008). The results obtained reveal that the constitutive elements of the therapeutic relationship are linked to 2 dimensions of the patient–therapist meeting experience: the technical and role‐related dimension, characterized by relational asymmetry, and the affective exchange dimension, characterized by relational symmetry. The article discusses the possible association between the asymmetrical technical dimension, whose roles are defined by the organization of the helping relationship, and the notion of therapeutic alliance as commonly conceptualized and assessed; on the other hand, the experience of the bidirectional and symmetrical patient–therapist affective exchange is linked with concepts such as real relationship and intersubjectivity.
SECTION 61 OF THE TRUSTEE ACT 1925: A JUDICIOUS BREACH OF TRUST?
Authors: Haley Michael 
Published: September 2017

AbstractThis article is concerned with s. 61 of the Trustee Act 1925. It will analyse the origins, design and modern day operation of the jurisdiction to relieve a trustee from personal liability following a breach of trust. It will revisit the threshold conditions of honesty, reasonableness and fairness and, in the context of mortgage fraud, contend that this exculpatory jurisdiction ought not extend to the bare commercial trust that exists between the mortgagee and its solicitor. Defects, uncertainties and shortcomings associated with s. 61 will also be addressed.
Brain damage and behavioural disorders in fish induced by plastic nanoparticles delivered through the food chain
Authors: Mattsson Karin , Johnson Elyse V. , Malmendal Anders , Linse Sara , Hansson Lars-Anders , Cedervall Tommy 
Published: September 2017

AbstractThe tremendous increases in production of plastic materials has led to an accumulation of plastic pollution worldwide. Many studies have addressed the physical effects of large-sized plastics on organisms, whereas few have focused on plastic nanoparticles, despite their distinct chemical, physical and mechanical properties. Hence our understanding of their effects on ecosystem function, behaviour and metabolism of organisms remains elusive. Here we demonstrate that plastic nanoparticles reduce survival of aquatic zooplankton and penetrate the blood-to-brain barrier in fish and cause behavioural disorders. Hence, for the first time, we uncover direct interactions between plastic nanoparticles and brain tissue, which is the likely mechanism behind the observed behavioural disorders in the top consumer. In a broader perspective, our findings demonstrate that plastic nanoparticles are transferred up through a food chain, enter the brain of the top consumer and affect its behaviour, thereby severely disrupting the function of natural ecosystems.
Identification of Genetically Important Individuals of the Rediscovered Floreana Galápagos Giant Tortoise (Chelonoidis elephantopus) Provides Founders for Species Restoration Program
Authors: Miller Joshua M. , Quinzin Maud C. , Poulakakis Nikos , Gibbs James P. , Beheregaray Luciano B. , Garrick Ryan C. , Russello Michael A. , Ciofi Claudio , Edwards Danielle L. , Hunter Elizabeth A. , Tapia Washington , Rueda Danny , Carrión Jorge , Valdivieso Andrés A. , Caccone Adalgisa 
Published: September 2017

AbstractSpecies are being lost at an unprecedented rate due to human-driven environmental changes. The cases in which species declared extinct can be revived are rare. However, here we report that a remote volcano in the Galápagos Islands hosts many giant tortoises with high ancestry from a species previously declared as extinct: Chelonoidis elephantopus or the Floreana tortoise. Of 150 individuals with distinctive morphology sampled from the volcano, genetic analyses revealed that 65 had C. elephantopus ancestry and thirty-two were translocated from the volcano’s slopes to a captive breeding center. A genetically informed captive breeding program now being initiated will, over the next decades, return C. elephantopus tortoises to Floreana Island to serve as engineers of the island’s ecosystems. Ironically, it was the haphazard translocations by mariners killing tortoises for food centuries ago that created the unique opportunity to revive this “lost” species today.
Quantum interference in the presence of a resonant medium
Authors: Kalashnikov Dmitry A. , Melik-Gaykazyan Elizaveta V. , Kalachev Alexey A. , Yu Ye Feng , Kuznetsov Arseniy I. , Krivitsky Leonid A. 
Published: September 2017

AbstractInteraction of light with media often occurs with a femtosecond response time. Its measurement by conventional techniques requires the use of femtosecond lasers and sophisticated time-gated optical detection. Here we demonstrate that by exploiting quantum interference of entangled photons it is possible to measure the dephasing time of a resonant media on the femtosecond time scale (down to 100 fs) using accessible continuous wave laser and single-photon counting. We insert a sample in the Hong-Ou-Mandel interferometer and observe the modification of the two-photon interference pattern, which is driven by the coherent response of the medium, determined by the dephasing time. The dephasing time is then inferred from the observed pattern. This effect is distinctively different from the basic effect of spectral filtering, which was studied in earlier works. In addition to its ease of use, our technique does not require compensation of group velocity dispersion and does not induce photo-damage of the samples. Our technique will be useful for characterization of ultrafast phase relaxation processes in material science, chemistry, and biology.
Balintgruppenarbeit, Supervision und Selbsterfahrung
Authors: Petzold E. R. 
Published: September 2017

ZusammenfassungDieser Beitrag summiert psychoanalytische Kernsätze der Balintarbeit in
England und Erfahrungen aus einer Supervisionsgruppe in Deutschland. Der Akzent
lieg auf dem Umgang der Ärzte mit dem eigenen Erleben in der
Arzt-Patient Beziehung.
Vaccinations and Malaria Chemoprophylaxis of Adolescents Traveling From Greece to International Destinations
Authors: Maltezou Helena C. , Pavli Androula , Theodoridou Kalliopi , Katerelos Panos , Spilioti Athina , Tedoma Anastasia , Lymperi Ioanna , Theodoridou Maria 
Published: September 2017

Background:
There are few publications focusing on vaccination and malaria chemoprophylaxis in adolescent travelers. We assessed pretravel vaccinations and malaria chemoprophylaxis of adolescents 12–18 years old traveling from Greece to international destinations.

Methods:
We prospectively studied 239 adolescents 12–18 years old during 2008–2016. A standard questionnaire was used to collect data.

Results:
Adolescents sought pretravel services at a mean of 24.1 days before departure. Their main destinations were sub-Saharan Africa (79 adolescents; 33.1%), Latin America (56; 23.5%) and North America (26; 10.9%). Almost half (46.1%) of them planned to stay abroad for at least 3 months. Sixteen (7.4%) adolescents planned to visit friends and relatives. The yellow fever vaccine and the typhoid vaccine were the most frequently administered vaccines (74.1% and 20.5%, respectively), while the hepatitis A vaccine and the tetanus–diphtheria vaccine accounted for most routine vaccinations (18% and 14.2%, respectively). The rabies and the typhoid fever vaccines were administered inadequately to adolescents traveling to endemic areas. Malaria chemoprophylaxis should have been prescribed in many cases traveling to sub-Saharan Africa and the Indian subcontinent.

Conclusions:
Only a small number of adolescents from Greece traveling abroad seek pretravel counseling. We found significant gaps in typhoid fever and rabies vaccinations of adolescents traveling to endemic areas. We also found gaps in prescription of malaria chemoprophylaxis for those traveling to high-risk areas. There is a need to develop communication strategies to access adolescent travelers and improve appropriate vaccination and use of malaria chemoprophylaxis.
Advanced vascular exams improve the accuracy of conventional parameters in distinguishing normal tension from primary open angle glaucoma
Authors: Barbosa Breda J. , Van Keer K. , Abegão Pinto L. , Nassiri V. , Willekens K. , Vandewalle E. , Rocha Sousa A. , Stalmans I. 
Published: September 2017

PurposeThe role vascular factors play in glaucoma is still not fully understood. We aim to understand if advanced vascular exams can improve our ability to distinguish primary open angle glaucoma (POAG) from normal tension glaucoma (NTG) patients.MethodsWe applied multivariate logistic regression on the Leuven Eye Study data (182 NTG and 202 POAG patients), and created three prediction models. One with conventional parameters, one with parameters from advanced vascular exams [colour Doppler imaging (CDI), retinal oximetry, ocular pulse amplitude and choroidal thickness] and one where both kinds of parameters were allowed in (mixed). The area under the curve (AUC) was calculated and compared between them. Intra‐ocular pressure (IOP) and IOP‐related variables were excluded.ResultsThe conventional model included Raynaud phenomenon, mean arterial pressure (MAP), central corneal thickness, migraine, visual field mean deviation (VF MD), cup‐disc (C/D) ratio, visual acuity and mean retinal nerve fiber layer (mRNFL) thickness (in decreasing order of importance). The advanced vascular model included parameters from CDI and retinal oximetry. The mixed model included Raynaud phenomenon, MAP, arterio‐venous retinal oxygen saturation difference, acceleration (acc) of central retinal artery (CRA), end‐diastolic velocity of CRA, resistive index of ophthalmic artery, VF MD, C/D ratio, mRNFL thickness, acc of temporal posterior ciliary artery and migraine (in decreasing order of importance). The AUCs were 0.687, 0.677 and 0.743, respectively. The mixed model was able to significantly increase the prediction ability of the conventional model (p = 0.049).ConclusionsAdding advanced vascular exams increased the accuracy of the conventional model to distinguish between groups. These results show how important vascular factors can be in the pathogenesis of glaucoma.
Reproducibility of angle metrics in children using hand‐held spectral domain optical coherence tomography: intra‐observer and inter‐observer variability
Authors: Edawaji B. , Shah S. , Proudlock F. , Gottlob I. 
Published: September 2017

PurposeTo evaluate intraobserver and interobserver agreements of anterior chamber angle measurements in children using hand‐held spectral domain optical coherence tomography (HH‐SDOCT).MethodsHH‐SDOCT (Leica Microsystems Ltd) was used to scan the anterior chamber of 30 normal children (mean age = 5.12 ± 3.5 years, range: 2 days to 12 years). Two independent observers analysed the same B‐scan showing both clear nasal and temporal angles using ImageJ. They identified iridocorneal angle landmarks: scleral spur (SS), Schwalbe`s line (SL) and angle recess (AR) and used them to calculate parameters such as trabecular meshwork length (TML), SS angle opening distance (SSAOD), SL angle opening distance (SLAOD), SL angle (SLA), SS limbal distance (SSLD), SL limbal distance (SLLD), trabecular iris surface area (TISA500), nasal to temporal SS distance (SS‐SSD) and pupil diameter (PD). The reproducibility of measurements were assessed using interclass correlation coefficients (ICC) and Bland‐Altman plots.ResultsRepeated measurements of anterior chamber were calculated in 141 images. Both intra‐observer and inter‐observer agreements of most measurements ranged from fair to excellent (0.66 to 0.97). Intra‐observer and inter‐observer ICC for SSAOD, SLAOD, SLA, SSLD, SLLD, TISA500, SS‐SSD and PD were 0.74, 0.78, 0.81, 0.72, 0.80, 0.76, 0.96, 0.96 and 0.83, 0.85, 0.77, 0.91, 0.89, 0.83, 0.84, 0.97, respectively. TML reproducibility was poor, ICC were 0.42 and 0.33, respectively. Bland Altman plots showed no significant difference between repeated measurements (p value were >0.05) for parameters with ICC reproducibility ≥0.7.ConclusionsReproducible quantitative measurements in children using HH‐SDOCT was possible with ICC of up to 0.97. Anterior segment OCT could be a potential method in understanding the normal and abnormal ocular development of children.
Using biomarkers in clinical trials in ophthalmology
Authors: Beuerman R. 
Published: September 2017

SummaryDetailed investigations of the composition and changes in the composition of the tears of the ocular surface have provided new ways of evaluating patient outcomes. This intimate knowledge comes from the ability to very accurately quantify proteins found in the tears. As such proteomics as a method is rather similar to performing hundreds or thousands of ELISA assays (which would be an impossible task as the tear volume is insufficient). Moreover, the results using only a few microliters of tears are reproducible so that patients can be statistically evaluated for examining outcomes. Tear proteins can be evaluated in some cases according to their source: for example, lacritin, and lysozyme are secreted from the lacrimal gland while the pro‐inflammatory proteins S100A8 and S100A9 are secreted by PMNs and ocular surface epithelial cells. The ability to indicate which proteins support ocular surface and which are inflammatory can reveal how a therapeutic treatment is changing or has not changed the basic pathology.
Practical examples of proteomic studies
Authors: Uusitalo H. 
Published: September 2017

SummaryProteomics, along with other omics, is a potentially valuable tool of personalized medicine and thus helping in selecting the most cost‐effective diagnostic and therapeutic options for each patients. This type of personalized approach is becoming more common in the future, since new diagnostic and therapeutic methods are constantly being developed. On the other hand, processing and analyzing of the proteomic samples is becoming easier, more accurate and also cheaper. Tear fluid and ocular surfaces are important and easily available source of samples reflecting not only the state of the anterior segment of the eye but also eye and even human body in general. This presentation is based on the previous ones describing methods of sample processing and mass spectrometric analysis methods of this type of samples as well as on aspects of bioinformatics analysis of proteomic data. It is aimed to provide basic scientists and clinicians an overview of the aspects that are important by using practical examples of this type of research. These examples are covering clinical studies on dry eye, glaucoma medication, glaucoma surgery and refractive surgery.
Neural retina identity is specified by lens‐derived BMP signals
Authors: Gunhaga L. , Pandit T. , Patthey C. , Jidigam V. 
Published: September 2017

SummaryDuring early development of the CNS, the anterior neural domain becomes restricted into different regions as: the telencephalon, the optic cup and the diencephalon. Simultaneously, lens progenitors are specified in the neural plate border. The molecular mechanisms that regulate the induction and maintenance of eye‐field cells, and the specification of neural retina cells in relation to other forebrain domains have been poorly defined. If prospective lens cells affect the early development of retinal progenitors have been debated. We have analysed these issues in intact chick embryos and explant assays. Our results show that BMP signals emanating from the lens ectoderm maintain eye‐field identity, inhibit telencephalic character and induce neural retinal cells. This highlights a novel role for BMP signals during the early development of the retina that is distinct from previously described roles in dorso‐ventral patterning and fate choice between neural versus RPE cells. Our findings link the requirement of the lens ectoderm for neural retina specification with the molecular mechanism by which cells in the forebrain become specified as neural retina by BMP activity.
Choroidal thickness assessed by swept‐source optical coherence tomography in patients with diabetes
Authors: Horváth H. , Kovács I. , Sándor G. , Czakó C. , Récsán Z. , Somogyi A. , Zoltán Nagy Z. , Ecsedy M. 
Published: September 2017

PurposeTo measure choroidal thickness (CT) in diabetic subjects and to correlate it to the severity of diabetic retinopathy (DR) and diabetic macular edema (DME).MethodsProspective study using swept‐source optical coherence tomography. Choroidal thickness maps of 117 eyes of 60 diabetic patients were compared to 45 eyes of 24 healthy controls. The type of DR (no retinopathy: n = 18 eyes; non proliferative DR – NPDR: n = 62 eyes, proliferative DR – PDR: n = 37 eyes), the type of DME (no DME: n = 39 eyes, diffuse: n = 36 eyes, cystoid: n = 36 eyes, mixed: n = 6 eyes), the duration of diabetes, blood hemoglobin A1C (HbA1C) level and hypertension (HT) were recorded, and their relation to CT was evaluated using multiple regression models.ResultsNo significant difference in central subfoveal and mean overall CT was observed between diabetic patients and controls (p > 0.05). A significantly thinner choroid was measured in PDR eyes compared to NPDR group (p < 0.01). CT did not show any correlation with type of DME (p > 0.05). Analysing the whole cohort, the decrease of CT was assessed in subjects with HT (p < 0.05). Aging showed significant correlation with choroidal thinning (30 μm/10 years; p < 0.001) after adjustment for HbA1C level and HT. In diabetic patients the duration of the disease significantly correlated with choroidal thinning (15 μm/10 years; p < 0.05) after adjusting for the effect of age, HbA1C level and HT.ConclusionsThe thinning of the choroid is affected more significantly by the age and HT, than the presence of diabetes. In diabetic patients the duration of the disease is an independent predictor of choroidal thinning.
Infectious posterior uveitis
Authors: Markomichelakis N. 
Published: September 2017

SummarySeveral infectious agents (parasites, bacteria, fungi, and viruses) can invade the eye and lead to ocular inflammation. Infectious causes should always be considered and ruled out in all patients with posterior uveitis. Toxoplasma gondii is by far the most common cause of infectious posterior uveitis in all ages, while Toxocara canis infects typically children. Onchocerciasis and other parasitic diseases may also cause posterior uveitis, more commonly in developing countries. Nowadays, old bacterial diseases, tuberculosis and syphilis, emerged as common causes of posterior uveitis. Bartonella henselae and Borrelia burgdorferi are other bacteria that can also cause posterior uveitis.Fungal posterior uveitis usually occurs in immunosuppressed patients or in intravenous drug users. Herpes viruses (HSV, VZV, CMV) are also associated with infectious retinitis, in immunocompromised as well as immunocompetent patients, with quite destructive clinical course. Recently, more viruses (such as West Nile virus, Rift valley fever, dengue fever, and chikungunya) have been recognized as etiologic factors of posterior infectious uveitis. A rapid and accurate diagnosis is of high importance for the successful treatment and visual outcome of infectious uveitis. Techniques and methods, such PCR and detection of specific antibodies in the intraocular fluids (Goldmann‐Witmer coefficient), play a key role towards the detection of the pathogen of posterior infectious uveitis.