bluuebunny/crossref_metadata_2025 huggingface dataset:
Human organisms begin to exist at fertilization
Authors: Miller Calum , Pruss Alexander
Published: August 2017

Eugene Mills has recently argued that human organisms cannot begin to exist at fertilization because the evidence suggests that egg cells persist through fertilization and simply turn into zygotes. He offers two main arguments for this conclusion: that ‘fertilized egg’ commits no conceptual fallacy, and that on the face of it, it looks as though egg cells survive fertilization when the process is watched through a microscope. We refute these arguments and offer several reasons of our own to think that egg cells do not survive fertilization, appealing to various forms of essentialism regarding persons, fission cases, and a detailed discussion of the biological facts relevant to fertilization and genetics. We conclude that it is plausible, therefore, that human organisms begin to exist at fertilization – or, at the very least, that there are grounds for thinking that they existed as zygotes which do not apply to the prior egg cells. While this does not entail that human persons begin to exist at this point, it nevertheless has considerable significance for this latter question.
A tale of two communication tools: Discussion‐forum and mobile instant‐messaging apps in collaborative learning
Authors: Sun Zhong , Lin Chin‐Hsi , Wu Minhua , Zhou Jianshe , Luo Liming
Published: August 2017

Computer‐supported collaborative learning (CSCL) has shown considerable promise, but thus far the literature has tended to focus on individual technological tools, without due regard for how the choice of one such tool over another impacts CSCL, either in outline or in detail. The present study, therefore, directly compared the learning‐related uses of an online discussion forum against such use of a mobile instant‐messaging app by the same group of 78 upper‐division undergraduate pre‐service teachers in China. The participants were asked to use one of the two communication tools during the first of three learning activities, then to switch to the other during the second, and to choose their preferred tool for the third. Based on the results of content analysis, social‐network analysis and a survey of the students' attitudes, it was found that while both tools facilitated collaborative learning, they appeared to have different affordances. Specifically, using the online discussion forum resulted in more communication aimed at knowledge construction, while using the mobile instant‐messaging app resulted in more social interactions.
Dexamethasone, rituximab and cyclophosphamide for relapsed and/or refractory and treatment‐naïve patients with Waldenstrom macroglobulinemia
Authors: Paludo Jonas , Abeykoon Jithma P. , Kumar Shaji , Shreders Amanda , Ailawadhi Sikander , Gertz Morie A. , Kourelis Taxiarchis , King Rebecca L. , Reeder Craig B. , Leung Nelson , Kyle Robert A. , Buadi Francis K. , Habermann Thomas M. , Dingli David , Witzig Thomas E. , Dispenzieri Angela , Lacy Martha Q. , Go Ronald S. , Lin Yi , Gonsalves Wilson I. , Warsame Rahma , Lust John A. , Rajkumar S. Vincent , Ansell Stephen M. , Kapoor Prashant
Published: August 2017

The management of Waldenström macroglobulinaemia (WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide (DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate (ORR) was 87%. The median progression‐free survival (PFS) and time‐to‐next‐therapy (TTNT) were 32 (95% confidence interval [CI]: 15–51) and 50 (95% CI: 35–60) months, respectively. In the previously untreated cohort (n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23–not reached [NR]) and NR (95% CI: 37–NR), respectively. Twenty‐five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well‐tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed‐duration option, with preliminary data suggesting efficacy independent of the patients’ MYD88 status.
Combination of anti‐CD4 antibody treatment and donor lymphocyte infusion ameliorates graft‐versus‐host disease while preserving graft‐versus‐tumor effects in murine allogeneic hematopoietic stem cell transplantation
Authors: Ueha Satoshi , Yokochi Shoji , Ishiwata Yoshiro , Kosugi‐Kanaya Mizuha , Shono Yusuke , Shibayama Shiro , Ito Satoru , Matsushima Kouji
Published: August 2017

Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is not only a well‐established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo‐HSCT to solid tumors is limited, despite the beneficial antitumor effects, by the risk of graft‐versus‐host disease (GVHD). CD4+ T cells have been implicated in several aspects of GVHD, and suppress antitumor CD8+ T‐cell responses. In the present study, we investigated clinically applicable allo‐HSCT protocols designed to maximize antitumor effects while reducing the risk of GVHD. We used a mouse model of allo‐HSCT with s.c. tumors. We found that myeloablative conditioning was associated with better inhibition of tumor growth but with severe acute GVHD. Early treatment with anti‐CD4 mAb substantially ameliorated GVHD while preserving antitumor effects, leading to improved survival in myeloablative allo‐HSCT. Late treatment with anti‐CD4 mAb also ameliorated GVHD to some extent. Donor lymphocyte infusion in GVHD mice treated with anti‐CD4 mAb further suppressed tumor growth without exacerbating GVHD. Collectively, our results suggest that myeloablative allo‐HSCT followed by anti‐CD4 mAb treatment and donor lymphocyte infusion could be a potent and safe immunotherapy for patients with cancers refractory to available therapies.
Specialist perioperative allergy clinic services in the UK 2016: Results from the Royal College of Anaesthetists Sixth National Audit Project
Authors: Egner W. , Cook T. , Harper N. , Garcez T. , Marinho S. , Kong K. L. , Nasser S. , Thomas M. , Warner A. , Hitchman J. , Floss K. ,   Sixth national audit project (NAP6) steering & Case Review panel, RCoA
Published: August 2017

Background

Guidelines for investigation of perioperative drug allergy exist, but the quality of services is unknown. Specialist perioperative anaphylaxis services were surveyed through the Royal College of Anaesthetists 6th National Audit Project.

Objectives

We compare self‐declared UK practice in specialist perioperative allergy services with national recommendations.

Methods

A SurveyMonkey™ questionnaire was distributed to providers of allergy services in the UK. Responses were assessed for adherence to the best practice recommendations of the British Society for Allergy and Clinical Immunology (BSACI), the Association of Anaesthetists of Great Britain and Ireland and the National Institute for Health and Care Excellence (NICE) Guidance on Drug Allergy—CG183.

Results

Over 1200 patients were evaluated in 44 centres annually. Variation in workload, waiting times, access, staffing and diagnostic approach was noted. Paediatric centres had the longest routine waiting times (most wait >13 weeks) in contrast to adult centres (most wait <12 weeks). Service leads are allergists/immunologists (91%) or anaesthetists (7%).

Potentially important differences were seen in: testing repertoire [10/44 (23%) lacked BSACI compliant neuromuscular blocking agent (NMBA) panels and 17/44 (39%) lacked a NAP6‐defined extended panel; many failed to screen all cases for chlorhexidine 19/44 (43%) or latex 21/44 (48%)], staffing [only 26/44 (59%) had specialist nurses and 18/44 (41%) an anaesthetist] and provision of information [18/44 (41%) gave immediate information in clinic and 5/44 (11%) sign‐posted support groups].

Most centres were able to provide diagnostic challenges to antibiotics [40/44 (91%]) and local anaesthetics [41/44 (93%)].

Conclusions and Clinical Relevance

Diagnostic testing is not harmonized, with marked variability in the NMBA panels used to identify safe alternatives. Chlorhexidine and latex are not part of routine testing in many centres.

Poor access to services and patient information provision require attention. Harmonization of diagnostic approach is desirable, particularly with regard to a minimum NMBA panel for identification of safe alternatives.
Allergic sensitization to laboratory animals is more associated with asthma, rhinitis, and skin symptoms than sensitization to common allergens
Authors: Simoneti C. S. , Ferraz E. , de Menezes M. B. , Bagatin E. , Arruda L. K. , Vianna E. O.
Published: August 2017

Background

Workers exposed to laboratory animals have a high risk of developing laboratory animal allergy (LAA). Atopy seems to be the main risk factor for LAA. We hypothesized that occupational sensitization is a better predictor for the development of asthma, rhinitis, and bronchial hyperresponsiveness (BHR) than common sensitization.

Objective

To investigate the association between occupational sensitization to laboratory animals and clinical outcomes.

Methods

This was a cross‐sectional study performed at two universities on students and employees dealing with small rodents. The subjects were allocated in groups: non‐sensitized, common sensitization, or occupational sensitization, according to the results of the skin prick test (SPT). All subjects answered a questionnaire about animal exposures, symptoms, allergic diseases, and underwent spirometry and bronchial challenge test with mannitol. Multivariate analysis was performed using Poisson regression to estimate the prevalence ratio (PR).

Results

Data from 453 volunteers were analysed. Non‐sensitized group comprised 237 subjects; common sensitization group, 142 subjects; and occupational sensitization group, 74 subjects. Occupational sensitization was associated with greater risk for all outcomes studied. When the common sensitization group was reference, skin symptoms had PR of 1.36, 95% confidence interval (CI): 1.01‐1.85; wheezing had PR of 1.75, CI 95%: 1.21‐2.53; rhinitis had PR of 1.25, 95%: 1.11‐1.40; nocturnal dyspnoea had PR of 2.40, 95% CI: 1.31‐4.40; bronchial hyperresponsiveness (BHR) had PR of 2.47, 95% CI: 1.50‐4.09; and confirmed asthma had PR of 2.65, 95% CI: 1.45‐4.85. In addition, the overlap of asthma, rhinitis, and skin symptoms in a same subject was significantly more prevalent in the occupational sensitization group, 16.2% versus 4.9% in the common sensitization group.

Conclusion and Clinical Relevance

Occupational sensitization is associated with allergic symptoms and respiratory diseases. SPT with occupational allergens along with other parameters may contribute to detection of risk for allergic and respiratory diseases associated with exposure to laboratory animals.
Coffin‐Siris syndrome and cardiac anomaly with a novel SOX11 mutation
Authors: Okamoto Nobuhiko , Ehara Eiji , Tsurusaki Yoshinori , Miyake Noriko , Matsumoto Naomichi
Published: August 2017

Coffin‐Siris syndrome (CSS) is characterized by growth deficiency, intellectual disability, microcephaly, dysmorphic features, and hypoplastic nails of the fifth fingers and/or toes. Variants in the genes encoding subunits of the BAF complex as well as in SOX11 encoding the transcriptional factor under the control of BAF complex are associated with CSS. We report a new patient with a novel SOX11 mutation. He showed the CSS phenotype and coarctation of the aorta. Sox11 is known to be associated with cardiac outflow development in mouse studies. Therefore, cardiac anomalies might be an important complication in patients with SOX11 mutations.
Angiogenesis on coronary angiography is a marker for accelerated cardiac allograft vasculopathy as assessed by intravascular ultrasound
Authors: Cheng Richard , Kransdorf Evan P. , Wei Janet , Patel Jignesh K. , Kobashigawa Jon A. , Azarbal Babak
Published: August 2017

Background

Errant neovascularization and coronary artery fistulae (CAF) are frequently observed after cardiac transplantation. The relationship between angiographic neovascularization/CAF and coronary plaque progression is unknown.

Methods

Angiography and intravascular ultrasound were routinely performed at 4‐6 weeks and 1‐year post‐transplant. Pts were divided into three groups: no angiographic angiogenesis (Group 1), neovascularization only (Group 2), and CAF (Group 3). First‐year changes in maximal intimal thickness (MIT), maximal intimal area (MIA), and percent atheroma volume (PAV) were compared between groups.

Results

The 106 pts were included, 40/106 in Group 1, 42/106 in Group 2, and 24/106 in Group 3. Respectively, first‐year ΔMIT was 0.14 ± 0.13 mm, 0.32 ± 0.26 mm, and 0.50 ± 0.34 mm, P < .001. ΔMIA was 0.6 ± 0.6 mm2, 1.7 ± 1.8 mm2, and 3.0 ± 2.6 mm2, P < .001. ΔPAV was 2.3 ± 2.5%, 6.0 ± 5.1%, and 9.6 ± 9.0%, P < .001. Rapid plaque progression occurred in 1/40 (2.5%) pts in Group 1, 12/42 (28.6%) in Group 2, and 12/24 (50%) in Group 3, P < .001. Multivariate analysis identified both antithymocyte globulin and presence of CAF as independently associated with rapid plaque progression: OR 0.29 (P = .038) and 4.04 (P = .014).

Conclusion

Neovascularization and CAF are commonly present on surveillance angiography after cardiac transplantation and may signify amplified angiogenesis. Their presence is associated with accelerated coronary plaque progression by IVUS.
Cerebellar lesions are associated with TSC2 mutations in tuberous sclerosis complex: a retrospective record review study
Authors: Boronat Susana , Thiele Elizabeth Anne , Caruso Paul
Published: August 2017

Aim

Cerebellar lesions are present in approximately 30% of patients with tuberous sclerosis complex. Although several prior studies have characterized these lesions, our study provides the first description of the specific distribution of these lesions within the cerebellum and the first genotype–phenotype correlation yet to be published.

Method

We retrospectively reviewed magnetic resonance images from 220 paediatric and adult patients with tuberous sclerosis complex (95 males, 125 females; mean age 22.7y, range 9mo–81y). Sex, age, and genotype of patients with cerebellar lesions were recorded and specific characteristics, including signal intensity, number, shape, presence of enhancement, calcification or haemorrhage, and location within the cerebellar lobules were noted.

Results

Fifty‐eight patients (26.4%) had 106 cerebellar lesions (62 right, 44 left). The mean number of cerebellar lesions per patient was 1.8 (range 1–6). Enhancement was present in 42.4% of lesions and folial retraction in 84%. Calcification was detected in 86.8% of lesions. Patients with calcified lesions were older (mean age 21.6y) than patients without calcification (11.5y). TSC2 mutations were detected in 41/42 (97.6%) of patients with cerebellar tubers who had genetic testing and one patient had no mutation identified. None of the patients had TSC1 mutation.

Interpretation

We provide new information regarding cerebellar lesions in tuberous sclerosis complex: cerebellar lesions are significantly much more frequent in patients with TSC2 mutations than TSC1 mutations or patients with no mutation identified, and Crus II is the most frequent location of cerebellar lesions. New studies are needed to assess the clinical significance of these lesions.
Long‐term field study of transgenic hypovirulent strains of Cryphonectria parasitica in a forest setting
Authors: Double M. L. , Nuss D. L. , Rittenour W. R. , Holásková I. , Short D. P. G. , Kasson M. T. , MacDonald W. L.
Published: August 2017

Transgenic hypovirulent strains of Cryphonectria parasitica, the chestnut blight fungus, engineered to contain a chromosomally integrated full‐length infectious cDNA copy of virulence‐attenuating hypoviruses, differ from natural hypovirulent strains in the ability to transmit hypoviruses to ascospore progeny and with 100% efficiency through asexual spores. We report the results of a long‐term field study that examined whether these properties result in enhanced hypovirulence establishment, dissemination and persistence under field conditions. Informed by previous field results using a severe hypovirus, this study that employed 144 American chestnut trees was designed to provide improved inoculum formulation and delivery and to include the use of a mild hypovirus isolate (less debilitating) CHV‐1/Euro7 in an attempt to increase dissemination. Isogenic transgenic hypovirulent (TG), non‐transgenic cytoplasmic hypovirulent (CH) or virus‐free virulent (V) treatment strains were applied to artificially initiated and natural C. parasitica cankers three times each year for 7 years. Reservoirs of treatment inoculum also were initiated and refreshed annually for the first 6 years of the study. Sampling of 111,000 individual ascospores from 4,500 perithecia confirmed hypovirus‐containing spermatia successfully transmitted TG hypoviruses to ascospore progeny under field conditions. Surprisingly, TG ascospore progeny were recovered 3 years after the last annual application of treatment inoculum. Repeated sampling of over 440 cankers revealed dissemination of both CH and TG hypovirulent strains. However, no significance differences in establishment or dissemination were observed for the two hypovirulent strains. The results are discussed in terms of the contribution of ascospore progeny to infection, competition by endemic virulent C. parasitica, size of inoculated trees and the biological control potential of TG hypovirulent strains.
Orthodontically induced osteocyte apoptosis under different force magnitudes in rats: an immunohistochemical study
Authors: Kassem Hassan E. , Talaat Iman M. , El‐Sawa Afaf , Ismail Hanan , Zaher Abbas
Published: August 2017

We investigated the effect of different force magnitudes on osteocyte apoptosis in a model of orthodontic tooth movement. Forty‐nine male Sprague Dawley rats (7–9 wk of age) were divided into light‐ and heavy‐force groups (n = 21 each group) and a control group (n = 7). A coil spring delivered pressure (either 10–15 g or 20–25 g) to the left maxillary first molar. The rats were sacrificed 1, 3, or 5 d after placement of the appliance. Sections of the maxillary first molars were immunostained for caspase‐3. Upon force application, the number of apoptotic osteocytes significantly increased in the pressure side at 1 d and remained the same at 3 d and 5 d. However, there was no significant difference in the number of apoptotic osteocytes between the two force groups. We conclude that osteocyte apoptosis appears to increase under orthodontic loading, reaching a plateau after 1 d. However, osteocyte apoptosis seems to be independent of the magnitude of orthodontic forces tested.
Long‐term applicability of the new ILAE definition of epilepsy. Results from the PRO‐LONG study
Authors: Beretta Simone , Carone Davide , Zanchi Clara , Bianchi Elisa , Pirovano Marta , Trentini Claudia , Padovano Giada , Colombo Matteo , Cereda Diletta , Scanziani Sofia , Giussani Giorgia , Gasparini Sara , Bogliun Graziella , Ferrarese Carlo , Beghi Ettore ,   the PRO‐LONG Study Group
Published: August 2017

Objective

The new epilepsy definition adopted by the International League Against Epilepsy (ILAE) includes patients with one unprovoked seizure with a probability of further seizures, similar to the general recurrence risk after two unprovoked seizures, occurring in a 10‐year period. Long‐term follow‐up of patients diagnosed after a single seizure is needed to assess the applicability of the new epilepsy definition in clinical practice.

Methods

Patients with newly diagnosed epilepsy were recruited retrospectively with a minimum follow‐up of 10 years. Patients were stratified in two groups depending on the occurrence of one (new definition, ND) or two or more unprovoked seizures (traditional definition, TD) at the time of epilepsy diagnosis and compared for disease characteristics and factors predicting seizure recurrence. The primary outcome was the occurrence of a new unprovoked seizure during follow‐up in the ND group. The secondary outcome was the achievement of an early remission in both groups.

Results

Among 1,006 patients with newly diagnosed epilepsy, 152 (15.1%) were diagnosed after a single seizure. Compared to patients diagnosed using the TD, patients diagnosed according to the ND showed a higher proportion of subjects with an abnormal neurologic examination (19.9% vs. 13.7%, p = 0.0504) and with focal seizures (69.3% vs. 60.4%, p = 0.0021). The two samples differed in the presence of at least one of the factors predicting seizure recurrence (focal seizures or abnormal findings in at least one among the following: neurologic examination, electroencephalography [EEG], and neuroimaging) (94.6% vs. 89.1%, p = 0.0376). Long‐term recurrence in patients diagnosed with the new definition was 83.6% at 10 years and 89.1% at 15 years. The probability of early remission did not differ between the two groups.

Significance

Our results support the applicability of the new epilepsy definition in clinical practice. Individual patient characteristics and a personalized diagnostic approach can justify treatment after a single unprovoked seizure.
Failure of commercial extruded catalysts in simple compression and bulk thermal cycling
Authors: Young Alice , Henderson Sam , Buchanan Liam , Hall Daniel , Bishop Catherine
Published: August 2017

The mechanical performance of three commercial extruded catalyst pellets was characterized by single particle compression testing in five orientations and bulk crush testing during thermal cycles from 20°C to 900°C in a reformer tube. Failure loads were analyzed with Weibull statistics, and fragment shapes were cataloged. Maximum principal stresses from finite element simulations were consistent with the shapes of fragments from single pellet tests. In smaller scale bulk tests, excluding pellets in contact with the top and bottom plates, the most common location of damaged pellets was in contact with the reformer wall. In one large‐scale test (280 pellets), damage was most common in pellets at the reformer wall. The most common fragment shapes from ex‐service single pellet tests and bulk tests are similar, but differ from those from single pellet tests. Neither single pellet compression testing nor conventional bulk crush testing is a sufficient analog for the loading conditions on catalyst pellets in reformer tubes. This study demonstrates that catalyst pellet damage occurs in each full thermal cycle, and that using thermal cycling to reproduce the boundary conditions in service is essential for future studies.
A Clinical Evaluation of Large‐area Short‐time Haemodialysis
Authors: Ward R. A. , Farrell P. C. , Tiller D. J. , Horvath J. S. , Freeman J. M.
Published: August 2017

A large‐area short‐time (LAST) haemodialysis regimen (three hours by three times per week on a 2·5 M2 haemodialyser) has been compared with conventional haemodialysis (six hours by three times per week on a 1·3 M2 haemodialyser) on four patients over a period of eight months. Parameters monitored throughout the study included: Serum biochemistries, haematocrit, extracellular fluid space, platelet function, granulocyte kinetics, immunological status and neurological status.

All patients showed weight increases (3–12%) during the LAST dialysis period. These increases were related to problems of intradialytic hypotension which resulted from the increased rate of fluid removal required during the LAST dialysis period. Hypotension was not a problem during routine treatment over six hours. During LAST dialysis all patients showed an increase of 10–20% (P < 0.05) in predialysis serum urea and creatinine and a moderate decrease in predialysis serum bicarbonate (from 24·8 ± 2·2 to 21·4 ± 2·6 mM/I, P < 0.005).

This study indicates that, providing fluid balance can be controlled, a LAST dialysis regimen provides comparable therapy to conventional haemodialysis. However, recent studies have suggested that short‐time dialysis may be possible with conventional 1.0 to 1.3 M2 haemodialysers, indicating that short‐time haemodialysis may not need to involve more costly large‐area haemodialysers.
Clinical Evaluation of a Dialysate Regeneration System for Maintenance Haemodialysis
Authors: Farrell P. C. , Mahony J. F. , Jones B. F. , Mathew T. H. , Dawborn J. K. , Disney A. P.
Published: August 2017

A commercially available sorbent‐based dialysate regeneration system has been compared to conventional single‐pass dialysate delivery systems for treatment periods of six weeks in 13 patients on maintenance dialysis. The results of treatment were virtually identical in comparing sorbent and conventional systems except that seven of the eight patients using 2·5 M2 dialysers for 3–4 hours thrice per week developed asymptomatic metabolic acidosis with the dialysate regeneration system. This complication was not seen in the five patients using 1·3 M2 dialysers and having a 6–7 hour treatment thrice weekly.

Dialysate regeneration systems are particularly suited for use when water supplies are limited or of insufficient purity for single‐pass dialysis, and when a portable artificial kidney is required. To avoid metabolic acidosis with this system, using currently available disposable cartridges, each dialysis treatment should be of at least 4·5 hours duration.
Goitre Survey in Armidale and the New England Region
Authors: Barbato M. P.
Published: August 2017

The results of a goitre survey in school children in the New England Region are presented and compared with previous studies. Goitre incidence has fallen significantly in Tamworth but has remained unchanged in Armidale. Analyses of blood and urine showed no differences in thyroid hormone levels, TSH, and urinary iodide in goitre and non‐goitre subjects. In one group of goitre subjects prolactin levels were found to be significantly higher than those in a non‐goitre group matched for sex, age and years in the district. The estimated iodine intake was well above normal requirements in all age groups studied. Sources of dietary iodine in the New England Region are outlined with special reference to milk and water.

A brief review of clinical thyroid disease in Armidale is presented and reveals an unusually high incidence of both hyper‐ and hypo‐thyroidism.
Diabetes Mellitus and Tropical Form of Chronic Calcific Pancreatitis in Thailand
Authors: Chandraprasert S. , Samranvej P. , Arthachinta S. , Isarasena S.
Published: August 2017

Six cases of chronic calcific pancreatitis in Thailand occurring in patients aged 13 to 22 years are reported. Protein malnutrition was a possible aetiologic factor. Abdominal pain was mild to moderate and intermittent and not a presenting feature. Severe diabetes mellitus was present in all. Extensive pancreatic calcification was seen on abdominal X‐ray.
Metastatic Hepatoma in the Stomach Masquerading as a Leiomyoma
Authors: Green P. H. R. , Fevre D. I. , Barratt P. J.
Published: August 2017

Metastatic hepatoma in the stomach is rare. A case is described in which a gastric tumour appeared to be a leiomyoma, but after laparotomy proved to be an isolated secondary deposit from a hepatoma.
Preparing master‐level mental health nurses to work within a wellness paradigm: Findings from the eMenthe project
Authors: Doyle Louise , Ellilä Heikki , Jormfeldt Henrika , Lahti Mari , Higgins Agnes , Keogh Brian , Meade Oonagh , Sitvast Jan , Skärsäter Ingela , Stickley Theo , Kilkku Nina
Published: August 2017

Mental health promotion remains an important component of mental health nursing practice. Supporting wellness at both the individual and societal levels has been identified as one of the key tenets of mental health promotion. However, the prevailing biomedical paradigm of mental health education and practice has meant that many nurses have not been equipped to incorporate a wellness perspective into their mental health practice. In the present study, we report on an exploratory study which details the knowledge, skills, and attitudes required by master‐level mental health nurses to practice within a wellness paradigm from the perspective of three groups of key stakeholders: (i) service users and family members (n = 23); (ii) experienced mental health nurses (n = 49); and (iii) master‐level mental health nursing students (n = 37). The findings, which were reported from individual and focus group interviews across five European countries, suggested a need to reorientate mental health nursing education to include a focus on wellness and resilience to equip mental health nurses with the skills to work within a strengths‐based, rather than a deficits‐based, model of mental health practice. Key challenges to working within a wellness paradigm were identified as the prevailing dominance of the biomedical model of cause and treatment of mental health problems, which focusses on symptoms, rather than the holistic functioning of the individual, and positions the person as passive in the nurse–service user relationship.
Shaping Discourse and Setting Examples: Normative Power Europe can Work in the Israeli–Palestinian Conflict
Authors: Persson Anders
Published: August 2017

The conventional wisdom in the literature on EU–Israel/Palestine relations is that the EU has only displayed very limited, if any, normative power in the Israeli–Palestinian conflict. Previous studies have focused on the ability, or rather inability, of the EU to diffuse any of the core norms behind Ian Manners' concept of ‘Normative Power Europe’ (NPE) into the Israeli–Palestinian conflict, while tending to ignore the ability of the EU to shape what is considered normal in many aspects of the conflict – either by making others adopt its policies, or by contributing to creating consensus around an issue. By using Tuomas Forsberg's framework of four different mechanisms of normative power: persuasion, invoking norms, shaping the discourse and the power of example on three important case studies from the conflict (EC/EU's declaratory diplomacy on the need for a just peace in the conflict, the Palestinians' bid for statehood at the UN in 2011 and the emerging ‘differentiation strategy’), this article concludes that the EU has much more normative power in the Israeli–Palestinian conflict than the literature has previously acknowledged.
Understanding European Union Science Diplomacy
Authors: López de San Román Alea , Schunz Simon
Published: August 2017

Science diplomacy represents a relatively novel field of EU external action. This contribution provides a better understanding of the under‐researched development of this policy domain, asking how and why the EU has extended the scope of its external activities in the scientific area. To answer these questions, it conducts an analysis of EU policy‐makers' discourses on external science policies inspired by role theory. It finds that EU role conceptions in this domain take the forms of ‘science for diplomacy’ or ‘diplomacy for science’, and that they correspond either to an image of normative or market power Europe. These findings are confirmed by a study of the EU's recent external science policies. The article argues that the ambiguity of rationales invoked for introducing a genuine science diplomacy in the EU helps to appeal to different constituencies. This, in turn, enhances the Union's chances for successfully expanding the scope of its activities.
The role of nutrition as risk factor for polyneuropathy: a case‐control study
Authors: Visser Nora A. , Notermans Nicolette C. , de Vries Jeanne H. M. , van den Berg Leonard H. , Vrancken Alexander F. J. E.
Published: August 2017

The aim of this case–control study is to investigate the role of nutrition as risk factor for polyneuropathy. Three hundred eighteen patients with chronic idiopathic axonal polyneuropathy and 636 matched controls completed a validated food frequency questionnaire that covered nutrient intake and alcohol consumption. As risk estimates, we calculated adjusted odds ratios for the intake of energy and nutrients. Energy and nutrient intake did not differ between patients and controls, regardless of moderate alcohol consumption. Nutrition is not a risk factor for chronic idiopathic axonal polyneuropathy.
The fate of the vitelline and umbilical veins during the development of the human liver
Authors: Hikspoors Jill P. J. M. , Peeters Mathijs M. J. P. , Mekonen Hayelom K. , Kruepunga Nutmethee , Mommen Greet M. C. , Cornillie Pieter , Köhler S. Eleonore , Lamers Wouter H.
Published: August 2017

Differentiation of endodermal cells into hepatoblasts is well studied, but the remodeling of the vitelline and umbilical veins during liver development is less well understood. We compared human embryos between 3 and 10 weeks of development with pig and mouse embryos at comparable stages, and used Amira 3D reconstruction and Cinema 4D remodeling software for visualization. The vitelline and umbilical veins enter the systemic venous sinus on each side via a common entrance, the hepatocardiac channel. During expansion into the transverse septum at Carnegie Stage (CS)12 the liver bud develops as two dorsolateral lobes or ‘wings’ and a single ventromedial lobe, with the liver hilum at the intersection of these lobes. The dorsolateral lobes each engulf a vitelline vein during CS13 and the ventromedial lobe both umbilical veins during CS14, but both venous systems remain temporarily identifiable inside the liver. The dominance of the left‐sided umbilical vein and the rightward repositioning of the sinuatrial junction cause de novo development of left‐to‐right shunts between the left umbilical vein in the liver hilum and the right hepatocardiac channel (venous duct) and the right vitelline vein (portal sinus), respectively. Once these shunts have formed, portal branches develop from the intrahepatic portions of the portal vein on the right side and the umbilical vein on the left side. The gall bladder is a reliable marker for this hepatic vascular midline. We found no evidence for large‐scale fragmentation of embryonic veins as claimed by the ‘vestigial’ theory. Instead and in agreement with the ‘lineage’ theory, the vitelline and umbilical veins remained temporally identifiable inside the liver after being engulfed by hepatoblasts. In agreement with the ‘hemodynamic’ theory, the left–right shunts develop de novo.
Morphological and histological features of the vomeronasal organ in the brown bear
Authors: Tomiyasu Jumpei , Kondoh Daisuke , Sakamoto Hideyuki , Matsumoto Naoya , Sasaki Motoki , Kitamura Nobuo , Haneda Shingo , Matsui Motozumi
Published: August 2017

The vomeronasal organ (VNO) is a peripheral receptor structure that is involved in reproductive behavior and is part of the vomeronasal system. Male bears exhibit flehmen behavior that is regarded as the uptake of pheromones into the VNO to detect estrus in females. However, the morphological and histological features of the VNO in bears have not been comprehensively studied. The present study investigated the properties and degree of development of the VNO of the brown bear by histological, histochemical and ultrastructural methods. The VNO of bears was located at the same position as that of many other mammals, and it opened to the mouth like the VNO of most carnivores. The shape of the vomeronasal cartilages and the histological features of the sensory epithelium in the bear VNO were essentially similar to those of dogs. Receptor cells in the VNO of the bear possessed both cilia and microvilli like those of dogs. The dendritic knobs of receptor cells were positive for anti‐G protein alpha‐i2 subunit (Gαi2) but negative for anti‐G protein alpha‐o subunit, indicating preferential use of the V1R‐Gαi2 pathway in the vomeronasal system of bears, as in other carnivores. The VNO of the bear possessed three types of secretory cells (secretory cells of the vomeronasal gland, multicellular intraepithelial gland cells and goblet cells), and the present findings showed that the secretory granules in these cells also had various properties. The vomeronasal lumen at the middle region of the VNO invaginated toward the ventral region, and this invagination contained tightly packed multicellular intraepithelial gland cells. To our knowledge, this invagination and intraepithelial gland masses in the VNO are unique features of brown bears. The VNO in the brown bear, especially the secretory system, is morphologically well‐developed, suggesting that this organ is significant for information transmission in this species.
Lipid‐body containing interstitial cells (lipofibroblasts) in the lungs of various mouse strains
Authors: Opitz Luka , Kling Katharina Maria , Brandenberger Christina , Mühlfeld Christian
Published: August 2017

Pulmonary alveolar septa are thought to contain at least two types of fibroblasts that are termed myofibroblasts and lipofibroblasts based on their morphological characteristics. Lipofibroblasts possess cytoplasmic lipid inclusions (lipid bodies or droplets) and are involved in several important functions, such as surfactant synthesis, development, vitamin A storage and presumably regeneration. As vitamin A was shown to reduce pulmonary emphysema in several but not all mouse and rat strains, we hypothesized that these strain differences might be explained by a differential occurrence of lipofibroblasts and their lipid bodies in various mouse strains. Therefore, mouse lungs of six strains (NMRI, BALB/c, C3H/HeJ, C57BL/6J, C57BL/6N and FVB/N) were investigated by light and electron microscopic stereology to quantify the amount of lipid bodies and the composition of alveolar septa. Lipofibroblasts were observed qualitatively by transmission electron microscopy in every investigated mouse strain. The total volume and the volume‐weighted mean volume of lipid bodies were similar in all mouse strains. The results on the composition of the interalveolar septa did not show major differences between the groups. The only mouse strain that differed significantly from the other strains was the NMRI strain because the lungs had a higher volume and consequently many of the morphological parameters were also larger than in the other groups. In conclusion, the present study showed that lipofibroblasts are a common cell type in the mouse lung across various strains. Therefore, the mere presence or absence of lipofibroblasts does not explain differences in the pulmonary regenerative potential among mouse strains.
The notochord in Atlantic salmon (Salmo salarL.) undergoes profound morphological and mechanical changes during development
Authors: Kryvi Harald , Rusten Iselin , Fjelldal Per Gunnar , Nordvik Kari , Totland Geir K. , Karlsen Tine , Wiig Helge , Long John H.
Published: August 2017

We present the development of the notochord of the Atlantic salmon (Salmo salarL.), from early embryo to sexually mature fish. Over the salmon's lifespan, profound morphological changes occur. Cells and gross structures of the notochord reorganize twice. In the embryo, the volume of the notochord is dominated by large, vacuolated chordocytes; each cell can be modeled as a hydrostat organized into a larger cellular‐hydrostat network, structurally bound together with desmosomes. After the embryo hatches and grows into a fry, vacuolated chordocytes disappear, replaced by extracellular lacunae. The formation of mineralized, segmental chordacentra stiffens the notochord and creates intervertebral joints, where tissue strain during lateral bending is now focused. As development proceeds towards the parr stage, a process of devacuolization and intracellular filament accumulation occur, forming highly dense, non‐vacuolated chordocytes. As extracellular lacunae enlarge, they are enclosed by dense filamentous chordocytes that form transverse intervertebral septa, which are connected to the intervertebral ligaments, and a longitudinal notochordal strand. In the vertebral column of pelagic adults, large vacuolated chordocytes reappear; cells of this secondary population have a volume up to 19 000 times larger than the primary vacuolated chordocytes of the early notochord. In adults the lacunae have diminished in relative size. Hydrostatic pressure within the notochord increases significantly during growth, from 525 Pa in the alevins to 11 500 Pa in adults, at a rate of increase with total body length greater than that expected by static stress similarity. Pressure and morphometric measurements were combined to estimate the stress in the extracellular material of the notochordal sheath and intervertebral ligaments and the flexural stiffness of the axial skeleton. The functional significance of the morphological changes in the axial skeleton is discussed in relation to the different developmental stages and locomotor behavior changes over the lifespan of the fish.
Bioresorbable vascular scaffold to treat in‐stent restenosis: Single‐center experience
Authors: Picard Fabien , Avram Robert , Marquis‐Gravel Guillaume , Tadros Victor‐Xavier , Ly Hung Q. , de Hemptinne Quentin , Dorval Jean‐François , L'allier Philippe L. , Tanguay Jean‐François
Published: August 2017

Aims

The management of patients with in‐stent restenosis (ISR) is still a major clinical challenge even in the era of drug‐eluting stents (DES). Recent studies have demonstrated acceptable clinical outcomes for the everolimus‐eluting bioresorbable vascular scaffold (BVS) ABSORB™ in patients with stable coronary artery disease but data are scarce on its use in patients with ISR. We report the long‐term results of our preliminary experience with this novel approach at our institution.

Methods and Results

We investigated the safety and efficacy of BVS implantation to treat ISR. 34 consecutive patients (37 lesions) underwent PCI for ISR with BVS implantation between May 2013 and June 2015 at our institution and were included in the current analysis. Follow‐up was available in 91.9% of the patients. Mean follow‐up period was 801.9 ± 179 days. One patient had definite scaffold thrombosis (ScT) 2 months after stent implantation which was treated with DES. Five patients (six lesions) experienced target lesion revascularization (TLR). The composite endpoint rate of TLR, ScT, myocardial infarction, and death occured in 6/37 lesions at follow‐up (16.2%).

Conclusions

These real‐world data using BVS in patients with ISR demonstrates that ISR treatment with ABSORB™ BVS is feasible but could have slightly higher target lesion failure rates as compared to DES. This proof of concept could be hypothesis‐generating for larger randomized controlled studies.
Masculinization of the Native Bay Snook, Petenia splendida, Using Oral Administration of the Synthetic Steroid 17α‐methyltestosterone
Authors: Contreras‐García María de J. , Contreras‐Sánchez Wilfrido M. , Mcdonal‐Vera Alejandro , Hernández‐Vidal Ulises
Published: August 2017

The possibility of inducing sex reversal in bay snook, Petenia splendida, was evaluated to generate a protocol aimed at producing single‐sex populations (100% males) and improving farming conditions for this species. This popular staple food is a cichlid fish native to Central America, with aquaculture potential. We evaluated oral administration of the synthetic steroid 17α‐methyltestosterone (MT) to determine optimal dosage (30, 45, and 60 mg/kg of food) and days of feeding (30, 45, and 60) to attain efficient masculinization. The statistical analysis indicates a highly significant effect of both factors as well as for the interaction (P < 0.01). We registered significant differences in growth at the end of the experiment; fish fed with 60 mg of MT for 60 d reached the largest size, while fish fed with no MT were smaller. No significant differences were observed for survival (P > 0.05), ranging from 55.7 to 75.3% in the treatments. We recommend the use of 60 mg/kg of MT for 30 d for achieving successful sex reversal. This study provides valuable information supporting the inclusion of new species in aquaculture, reducing time and costs associated with sex reversal previously proposed for the species.
Dosing of indocyanine green for intraoperative laser fluorescence angiography in kidney transplantation
Authors: Rother Ulrich , Gerken Andreas L. H. , Karampinis Ioannis , Klumpp Madeline , Regus Susanne , Meyer Alexander , Apel Hendrik , Krämer Bernhard K. , Hilgers Karl , Lang Werner , Nowak Kai
Published: August 2017

Objective

Sufficient blood supply is a crucial factor determining postoperative allograft function in kidney transplantation. Therefore, besides the surgeon's individual impression, a method for evaluating the quality of the organ's microperfusion is required. Laser fluorescence angiography with indocyanine green (ICG) is an emerging tool for this purpose. However, no reproducible quantification of ICG fluorescence has been performed in transplantation so far.

Methods

This retrospective two‐center study was designed to evaluate the dosing of ICG for intraoperative laser fluorescence angiography in kidney transplantation.

The Spy Elite® system (NOVADAQ, Canada) was employed for quantitative assessment of allograft microperfusion. ICG was administered systemically 5 minutes after reperfusion applying doses between 0.25 and 0.01 mg ICG per kg body weight. Quantitative assessment was performed with the implemented SPY‐Q Software.

Results

A total of 57 kidney recipients were included in two centers. The generated curves showing ICG IN and EgR were not evaluable due to oversensing when doses exceeded 0.02 mg per kg body weight.

Conclusions

Fluorescence angiography with ICG is an emerging tool for the intraoperative quality control and evaluation of microperfusion in kidney transplantation. A dose of 0.02 mg ICG per kg body weight is recommended to ensure the quantitative assessment with SPY‐Q.
Major gene‐regulatory mechanisms operating in ribosomally synthesized and post‐translationally modified peptide (RiPP) biosynthesis
Authors: Bartholomae Maike , Buivydas Andrius , Viel Jakob H. , Montalbán‐López Manuel , Kuipers Oscar P.
Published: August 2017

Post‐translationally modified peptides commonly display antimicrobial activity, but can also aid the development of bacterial colonies, giving a competitive advantage in the ecological niche. The production of post‐translationally modified peptides by bacteria is a complex and energetically costly process that is strictly orchestrated in the cell. The onset of peptide production is linked to the different enzymes that take part during maturation, the transporters and the immunity determinants (if required). Thus, the population can make optimal use of available resources and obtain the benefits of production at an advantageous moment during growth, avoiding toxicity to itself. The timing and level of expression of the different operons is controlled by diverse (complex) regulatory pathways in response to environmental changes, stress or master regulators during specific growth transition phases. In this review, we highlight the basic principles and mechanisms of regulation of expression of post‐translationally modified peptides and the relationship with the overall culture developmental processes and/or cellular differentiation. We also discuss the biotechnological consequences derived from the understanding of regulatory networks involved in the biosynthesis of these natural products.