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Understanding and mitigating consumer vulnerability is critical in an age of pervasive misinformation and deception. This research examines how technology dependence can heighten consumer vulnerability by elevating the risk of being deceived in the marketplace. Drawing from Human‐Computer Interaction (HCI) research and Media Systems Dependency Theory (MSD), we propose that high technology dependence depletes cognitive resources, reduces consumer skepticism, and increases susceptibility to deception, an essential element of consumer vulnerability. Through three empirical studies, we show that technology dependence heightens consumers' vulnerability to deceptive information, primarily through reduced skepticism. Furthermore, we found that consumers' moods moderate this relationship, with negative moods mitigating and positive moods amplifying the adverse effects of technology dependence on skepticism. Our findings reveal mechanisms driving consumer vulnerability in the digital age, offering valuable insights for marketers and policymakers to enhance consumer protection, as well as marketplace and digital literacy. [ABSTRACT FROM AUTHOR]

Molecular blood biomarkers are lacking for high‐grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN). To histologically distinguish between neuroendocrine carcinoma (NEC), neuroendocrine tumors G3 (NET G3), adenocarcinoma and MINEN is often challenging. The mRNA‐based NETest has diagnostic, prognostic and predictive value in neuroendocrine tumors G1‐2 but has not been studied in HG GEP‐NEN. Patients with advanced HG GEP‐NEN were prospectively included in an observational study. A blood sample was collected before the start of chemotherapy and pseudonymised before NETest was performed. NETest results are expressed as an activity index (NETest score) from 0 to 100. The normal score cut‐off is 20. Histological sections were pseudonymised before centralized pathological re‐evaluation. Samples from 60 patients were evaluable with the NETest. Main primary tumor sites were colon (14), rectum (12), pancreas (11) and esophagus (7). Re‐classification: 30 NEC, 12 NET G3, 3 HG‐NEN ambiguous morphology, 8 MiNEN, 3 adenocarcinomas with neuroendocrine differentiation (ADNE), 3 adenocarcinomas and 1 NET G2. Elevated NETest (>20) was seen in 38/45 (84%) HG GEP‐NEN, all 17 large‐cell NEC (100%), 11/13 (85%) small‐cell NEC, all ambiguous cases and 7/12 (64%) NET G3. NETest was elevated in 5/8 (63%) MiNEN, 2/3 ADNE, however not in 3 adenocarcinomas. Median survival was 10.2 months (9.6–10.8 95%CI) for evaluable HG GEP‐NEN treated with palliative chemotherapy (n = 39), and survival was significantly shorter in patients with NETest >60 with an OS of only 6.5 months. This is the first study to evaluate use of the NETest in advanced HG GEP‐NEN. The NETest was almost always elevated in GEP‐NEC and in all large‐cell NEC. The NETest was also frequently elevated in NET G3 and MiNEN, however cases were limited. Baseline NETest was not predictive for benefit of chemotherapy, however a NETest >60 was prognostic with a shorter survival for patients receiving chemotherapy. [ABSTRACT FROM AUTHOR]

This ENETS guidance paper for well‐differentiated nonfunctioning pancreatic neuroendocrine tumours (NF‐Pan‐NET) has been developed by a multidisciplinary working group, and provides up‐to‐date and practical advice on the management of these tumours. Using the extensive experience of centres treating patients with NF‐Pan‐NEN, the authors of this guidance paper discuss 10 troublesome questions in everyday clinical practice. Our many years of experience in this field are still being verified in the light of the results of new clinical, which set new ways of proceeding in NEN. The treatment of NF‐Pan‐NEN still requires a decision of a multidisciplinary team of specialists in the field of neuroendocrine neoplasms. This ENETS guidance paper provides up‐to‐date practical advice on the NF‐Pan‐NET diagnosis and treatment. Management of NF‐Pan‐NET patients requires a NET‐dedicated MDT decision. ENETS Centres of Excellence should be strongly considered to be involved in the diagnostic‐therapeutic strategy of these patients. Further studies are needed to fulfil the unmet needs in this field focusing on prognostic molecular markers, dilemmas concerning the selection of a therapeutic approach as well as the sequence of their use to achieve success in the management of NF‐Pan‐NETs patients. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to investigate factors associated with 30-day readmission in a multivariate model, including the CDC wound classes "clean," "clean/contaminated," "contaminated," and "dirty/infected." Methods: The 2017–2020 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for all patients undergoing total hip replacement, coronary artery bypass grafting, Ivor Lewis esophagectomy, pancreaticoduodenectomy, distal pancreatectomy, pneumonectomy, and colectomies. ACS-defined wound classes were concordant with CDC definitions. Multivariate linear mixed regression was used to determine risk factors for readmission while adjusting for type of surgery as a random intercept. Results: 477,964 cases were identified, with 38,734 (8.1%) patients having experienced readmission within 30 days of surgery. There were 181,243 (37.9%) cases classified as wound class "clean", 215,729 (45.1%) cases classified as "clean/contaminated", 40,684 cases (8.5%) classified as "contaminated", and 40,308 (8.4%) cases classified as "dirty/infected". In the multivariate generalized mixed linear model adjusting for type of surgery, sex, body mass index, race, American Society of Anesthesiologists class, presence of comorbidity, length of stay, urgency of surgery, and discharge destination, "clean/contaminated" (p <.001), "contaminated" (p <.001), and "dirty/infected" (p <.001) wound classes (when compared to "clean") were significantly associated with 30-day readmission. Organ/space surgical site infection and sepsis were among the most common reasons for readmission in all wound classes. Conclusions: Wound classification was strongly prognostic for readmission in multivariable models, suggesting that it may serve as a marker of readmissions. Surgical procedures that are "non-clean" are at significantly greater risk for 30-day readmission. Readmissions may be due to infectious complications; optimizing antibiotic use or source control to prevent readmission are areas of future study. [ABSTRACT FROM AUTHOR]

This ENETS guidance paper aims to provide practical advice to clinicians for the diagnosis, treatment and follow‐up of functioning syndromes in pancreatic neuroendocrine tumours (NET). A NET‐associated functioning syndrome is defined by the presence of a clinical syndrome combined with biochemical evidence of inappropriately elevated hormonal levels. Different hormonal syndromes can be encountered in pancreatic NET patients, including insulinoma, gastrinoma as well as the rare glucagonoma, VIPoma, ACTHoma, PTHrPoma, carcinoid syndrome, calcitoninoma, GHRHoma and somatostatinoma. The recommendations provided in this paper focus on the biochemical, genetic and imaging work‐up as well as therapeutic management of the individual hormonal syndromes in well‐differentiated, grade 1‐3, functioning NET with the primary tumour originating in the pancreas, and for specific subtypes also in the duodenum. [ABSTRACT FROM AUTHOR]

The standardized preanalytical code (SPREC) aggregates warm ischemia (WIT), cold ischemia (CIT), and fixation times (FIT) in a precise format. Despite its growing importance underpinned by the European in vitro diagnostics regulation or broad preanalytical programs by the National Institutes of Health, little is known about its empirical occurrence in biobanked surgical specimen. In several steps, the Tissue Bank Bern achieved a fully informative SPREC code with insights from 10,555 CIT, 4,740 WIT, and 3,121 FIT values. During process optimization according to LEAN six sigma principles, we identified a dual role of the SPREC code as a sample characteristic and a traceable process parameter. With this preanalytical study, we outlined real‐life data in a variety of organs with specific differences in WIT, CIT, and FIT values. Furthermore, our FIT data indicate the potential to adapt the SPREC fixation toward concrete paraffin‐embedding time points and to extend its categories beyond 72 h due to weekend delays. Additionally, we identified dependencies of preanalytical variables from workload, daytime, and clinics that were actionable with LEAN process management. Thus, streamlined biobanking workflows during the day were significantly resilient to workload peaks, diminishing the turnaround times of native tissue processing (i.e. CIT) from 74.6 to 46.1 min under heavily stressed conditions. In conclusion, there are surgery‐specific preanalytics that are surgico‐pathologically limited even under process optimization, which might affect biomarker transfer from one entity to another. Beyond sample characteristics, SPREC coding is highly beneficial for tissue banks and Institutes of Pathology to track WIT, CIT, and FIT for process optimization and monitoring measurements. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms (NENs) present with advanced disease at diagnosis in up to 28% of cases, precluding the possibility of curative‐intent surgery. Histopathological heterogeneity of this disease can be observed inter‐individually as well as intra‐individually during disease course. The present study aimed to assess the frequency of Ki‐67 change after radical surgery, in a series of patients with radically resected entero‐pancreatic neuroendocrine tumors (EP‐NETs). We present the analysis of a multicenter, retrospective, series of EP‐NETs G1–G2 recurring after radical resection and with histological re‐evaluation at disease recurrence (DR). The primary endpoint was the description of Ki‐67 change at DR compared to time of surgery. The secondary endpoint was assessment of recurrence‐free survival (RFS) rates. In total, 47 patients had a second histological evaluation and could be included in the present study. Median Ki‐67 at surgery was 3% (range 1–15%) but, at DR, a significant increase in the value was observed (7%, range 1–30%; p <.01) and involved 66.0% of cases, with a corresponding increase in tumor grading in 34.0% (p =.05). Median RFS of the overall population was 40 months, and was worse when Ki‐67 increased at DR vs. stable Ki‐67 value (36 vs. 61 months, respectively; p =.02). In conclusion, in more than half of the cases with relapse after radical surgery, a higher proliferative index with a potentially more aggressive potential was observed. Therefore, histological reassessment should be considered on DR because tailored therapeutic strategies may be required for these patients. [ABSTRACT FROM AUTHOR]

In recent years the WHO classification of neuroendocrine neoplasms (NEN) has evolved. Nomenclature as well as thresholds for grading have changed leading to potential confusion and lack of comparability of tumour reports. Therefore, the European Neuroendocrine Tumour Society (ENETS) has set‐up an interdisciplinary working group to develop templates for a pathology data set for standardised reporting of NEN. Experts of various disciplines, members of the ENETS Advisory Board, formed a taskforce that discussed and decided on the structure, content and the number of templates needed for reporting the most common NEN. The selection of the required items was based on the WHO classification of digestive system tumours, the WHO classification of tumours of the lung and mediastinum and on "ENETS standard of care" reports. The final proposal of the working group was approved by the ENETS Advisory Board. Templates for synoptic reporting were created for the seven most common NEN primary sites, that is, stomach, duodenum, jejunum‐ileum, appendix, colon‐rectum, pancreas, lung and mediastinum. In addition, a general template for reporting biopsies was designed. The templates allow the recording of the essential items on differentiation, proliferation (Ki‐67 and mitosis), neuroendocrine features (positivity for chromogranin A and synaptophysin) and stage as well as several optional markers especially helpful for the distinction of neuroendocrine tumours (NET) from neuroendocrine carcinomas (NEC). In summary, this paper presents the content and development of synoptic reports for most sites of NEN by a multidisciplinary team of international experts in the field, which could help to improve unambiguous reporting of NEN. [ABSTRACT FROM AUTHOR]

We investigate the relationship between adolescents' construction of a transgression relating to a hypothetical temptation and bystander behaviour and bullying (offline and online). A total of 331 Swiss eighth graders completed an electronic questionnaire on bystanding, bullying, moral disengagement, and empathy. Moral functioning was assessed in a hypothetical scenario, using different moral judgements (deontic and self‐judgement, judging the transgression; paper‐and‐pencil measure). Cluster analyses were used to identify patterns of moral functioning. For the open situation (deontic and self‐judgement), happy transgressors, happy moralists, ashamed moralists, and indifferent moralists were differentiated, and for the transgression (accomplished deed) moralists and happy opportunists. The analyses yielded significant differences between the different cluster groups. Happy transgressors (open situation) reported higher levels of assisting the bullying than unconcerned moralists. Happy transgressors also reported lower levels of helping than ashamed and happy moralists. Opportunists (accomplished deed) reported higher levels of assisting the bullying, offline bullying, and lower levels of helping the victim. The multivariate GEE analyses showed that happy transgressors reported higher levels of assisting the bully and online bullying than the moralist groups (open situation). The study shows that adolescents who construct a favourable interpretation of yielding to temptation in a hypothetical scenario displayed higher levels of both assisting the bully and online bullying, emphasizing the need for incorporating targeted moral education in bullying prevention. [ABSTRACT FROM AUTHOR]

The quality of social pretend play may have a positive impact on children's development. This study investigated to what degree this quality is a characteristic of a child versus a function of the play partner or the specific pairing of two children. For this purpose, preschool children's general pretend play quality (actor effect), their general influence on their play partner's pretend play quality (partner effect) and the role of the specific constellation between two children (relationship effect) were examined in a dyadic setting. Potential associations of the effects with children's age, gender, social cognitive and social competencies, as well as the dyadic composition of these variables and their friendship were examined. Children completed two to four dyadic pretend play situations with different peers. They were tested for their language ability, theory of mind and emotion understanding. Educators rated children's social competence (cooperation and sociability) and evaluated their friendship with one another. A social relations model analysis was conducted. The results indicated that children's pretend play quality was determined to the same degree by the child and by the specific pairing of two children. Positive associations were found between children's pretend play quality and age, emotion understanding and sociability on the individual level. Further, the quality of children's social pretend play benefited from having older and more advanced play partners. [ABSTRACT FROM AUTHOR]

Aims: Nested variant of urothelial carcinoma (NVUC) is rare, and only a few small series exist. Molecular characteristics and the classifying marker profile as well as therapeutic targets of this specific variant are mostly unknown. The aim of this study was to characterise NVUC at the molecular level in one of the largest cohorts to date. In addition, we applied an immunohistochemical marker panel in order to define the molecular subtype. Methods and results: Sixty NVUC cases were collected from different departments. TERT promoter mutation analysis was carried out in all samples using SNaPshot analysis. Targeted sequencing of 48 cancer‐related genes by next‐generation sequencing (NGS) analysis was performed in a subset of 26 cases. Immunohistochemical markers CD44, CK5, CK14, EGFR, p63, FOXA1, GATA3, CD24 and CK20 were used to elucidate the molecular subtype. A total of 62.5% of NVUC cases harboured a mutation of the TERT promoter. Additionally, TP53, JAK3 and CTNNB1 were among the most frequently mutated genes identified by NGS analysis. Subtyping revealed that all NVUC express luminal markers such as CD24, FOXA1, GATA3 and CK20. Conclusions: In summary, NVUC belong to the luminal molecular subtype. Moreover, a subset of NVUC seems to be characterised by mutations of the Wnt and inflammatory pathways, including JAK3 mutations, indicating a different biological background compared to conventional urothelial bladder cancer. [ABSTRACT FROM AUTHOR]

Background: Approximately half of high-grade serous ovarian carcinomas (HGSOCs) demonstrate homologous recombination repair (HR) pathway defects, resulting in a distinct clinical phenotype comprising hypersensitivity to platinum, superior clinical outcome, and greater sensitivity to poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. EMSY, which is known to be amplified in breast and ovarian cancers, encodes a protein reported to bind and inactivate BRCA2. Thus, EMSY overexpression may mimic BRCA2 mutation, resulting in HR deficiency. However, to our knowledge, the phenotypic consequences of EMSY overexpression in HGSOC patients has not been explored.Methods: Here we investigate the impact of EMSY expression on clinical outcome and sensitivity to platinum-based chemotherapy using available data from transcriptomically characterized HGSOC cohorts.Results: High EMSY expression was associated with better clinical outcome in a cohort of 265 patients with HGSOC from Edinburgh (overall survival multivariable hazard ratio, 0.58 [95% CI, 0.38-0.88; P = .011] and progression-free survival multivariable hazard ratio, 0.62 [95% CI, 0.40-0.96; P = .030]). Superior outcome also was demonstrated in the Medical Research Council ICON7 clinical trial and multiple publicly available data sets. Patients within the Edinburgh cohort who had high EMSY expression were found to demonstrate greater rates of complete response to multiple platinum-containing chemotherapy regimens (radiological complete response rate of 44.4% vs 12.5% at second exposure; P = .035) and corresponding prolonged time to disease progression (median, 151.5 days vs 60.5 days after third platinum exposure; P = .004).Conclusions: Patients with HGSOCs demonstrating high EMSY expression appear to experience prolonged survival and greater platinum sensitivity, reminiscent of BRCA-mutant cases. These data are consistent with the notion that EMSY overexpression may render HGSOCs HR deficient. [ABSTRACT FROM AUTHOR]

There is a disconnect for a number of applied design students who utilise drawing from online, published and photographic sources, in the development of design collections. In practice they are engaged with a subject that physically demands the direct use of hands in the making of artefacts, particularly within textile fields. Drawing is at the core of the development of ideas but it is often seen as being different or awkward and can cause anxiety amongst students who may be more focused on the end [designed] result. This article reflects upon the teaching of a drawing class with year two undergraduates on a textiles degree course at a UK university. Rather than relying on that which is readily available (from museums, online content, galleries, archives or trend forecasting sites), students make their own 2D and 3D primary sources from which they develop drawn proposals for textile and surface samples. Does this approach allow fresh visuals, new languages and translations for design to emerge? Will it provide a further level of engagement for those students who already love drawing as well as those who don't (yet)? Data has been drawn from key texts, questionnaires, journals and observations of the work carried out by participating students. [ABSTRACT FROM AUTHOR]

This study investigated if and how children and teachers differ in their assessment of victim-aggressor relationships in kindergartens. Self-, peer, and teacher reports of victimization-aggression networks (who is victimized by whom) were investigated in 25 Swiss kindergartens with 402 5- to 7-years-old. It was examined whether child characteristics (sex and parent-reported internalizing and externalizing behavior) influence informant reports of victimization and/or aggression. Findings from statistical network models indicated higher concordance between self and peer reports than between one of these and teacher reports. Results further showed more agreement among informants on aggressors than on victims. Aggressors reported by self and peer reports were low on internalizing behavior, and aggressors reported by self and teacher reports were high on externalizing behavior; teacher-reported victims were also high on externalizing behavior. Internalizing behavior was unrelated to victimization. According to self and peer reports, boys as well as girls were victimized by boys and girls equally; teachers reported less cross-sex victimization than same-sex victimization. The different views of teachers and children on victim-aggressor relationships have implications for the identification of aggression in early childhood. Mutual sharing of information between children, their parents, peers, and teachers may contribute to signaling victims and aggressors in the early school years. [ABSTRACT FROM AUTHOR]

The literature points to a large distributed brain network involved in the estimation of time. Among these regions, the role of the insular cortex is still poorly understood. At the confluence of emotional, interoceptive, and environmental signals, this brain structure has been proposed to underlie awareness of the passage of time and emotion related time dilation. Yet, this assumption has not been tested so far. This study aimed at exploring how a lesion of the insula affects subjective duration, either in an emotional context or in a non‐emotional context. Twenty‐one patients with a stroke affecting the insula, either left or right, were studied for their perception of sub and supra second durations. A verbal estimation task and a temporal bisection task were used with either pure tones or neutral and emotional sounds lasting between 300 and 1500 ms and presented monaurally. Results revealed that patients with a right insular lesion, showed less temporal sensitivity than both control participants and patients with a left insular lesion. Unexpectedly, emotional effects were similar in patients and control participants. Altogether, these results suggest a specific role of the right insula in the discrimination of durations, but not in emotion related temporal distortion. In addition, an ear × emotion interaction in control participants suggests that temporal processing of positive and negative sounds may be lateralized in the brain. [ABSTRACT FROM AUTHOR]

Purpose: To measure the arterial input function (AIF), an essential component of tracer kinetic analysis, in a population of patients using an optimized dynamic contrast‐enhanced (DCE) imaging sequence and to estimate inter‐ and intrapatient variability. From these data, a representative AIF that may be used for realistic simulation studies can be extracted. Methods: Thirty‐nine female patients were imaged on multiple visits before and during a course of neoadjuvant chemotherapy for breast cancer. A total of 97 T1‐weighted DCE studies were analyzed including bookend estimates of T1 and model‐fitting to each individual AIF. Area under the curve and cardiac output were estimated from each first pass peak, and these data were used to assess inter‐ and intrapatient variability of the AIF. Results: Interpatient variability exceeded intrapatient variability of the AIF. There was no change in cardiac output as a function of MR visit (mean value 5.6 ± 1.1 L/min) but baseline blood T1 increased significantly following the start of chemotherapy (which was accompanied by a decrease in hematocrit). Conclusion: The AIF in an individual patient can be measured reproducibly but the variability of AIFs between patients suggests that use of a population AIF will decrease the precision of tracer kinetic analysis performed in cross‐patient comparison studies. A representative AIF is presented that is typical of the population but retains the characteristics of an individually measured AIF. [ABSTRACT FROM AUTHOR]

Pancreatic neuroendocrine tumors (PNETs) represent a heterogeneous group of neuroendocrine neoplasms with varying biological behavior and response to treatment. Although targeted therapies have been shown to improve the survival for patients at advanced stage, resistance to current therapies frequently occurs during the course of therapy. Previous reports indicate that the infiltration of tumor‐associated macrophages (TAMs) in PNETs might correlate with tumor progression and metastasis formation. We aimed to evaluate the prognostic and functional impact of TAMs in human PNETs in vitro and in vivo and to investigate the effect of therapeutic targeting TAMs in a genetic PNET mouse model. TAM expression pattern was assessed immunohistochemically in human PNET tissue sections and a tissue‐micro‐array of PNET tumors with different functionality, stage, and grading. The effect of liposomal clodronate on TAM cell viability was analyzed in myeloid cell lines and isolated murine bone macrophages (mBMM). In vivo, RIP1Tag2 mice developing insulinomas were treated with liposomal clodronate or PBS‐Liposomes. Tumor progression, angiogenesis and immune cell infiltration were assessed by immunohistochemistry. In human, insulinomas TAM density was correlated with invasiveness and malignant behavior. Moreover, TAM infiltration in liver metastases was significantly increased compared to primary tumors. In vitro, Liposomal clodronate selectively inhibited the viability of myeloid cells and murine bone macrophages, leaving PNET tumor cell lines largely unaffected. In vivo, repeated application of liposomal clodronate to RIP1Tag2 mice significantly diminished the malignant transformation of insulinomas, which was accompanied by a reduced infiltration of F4/80‐positive TAM cells and simultaneously by a decreased microvessel density, suggesting a pronounced effect of clodronate‐induced myeloid depletion on tumor angiogenesis. Concomitant treatment with the antiangiogenic TKI sunitinib, however, did not show any synergistic effects with liposomal clodronate. TAMs are crucial for malignant transformation in human PNET and correlate with metastatic behavior. Pharmacological targeting of TAMs via liposomal clodronate disrupts tumor progression in the RIP1Tag2 neuroendocrine tumor model and was associated with reduced tumor angiogenesis. Based on these results, using liposomal clodronate to target proangiogenic myeloid cells could be employed as novel therapeutic avenue in highly angiogenic tumors such as PNET. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracranial hemorrhage (ICH) is the most feared complication in patients treated with oral anticoagulants due to non‐valvular atrial fibrillation. Non‐vitamin K oral anticoagulants (NOACs) reduce the risk of ICH compared with vitamin K antagonists (VKAs). We performed a systematic review and meta‐analysis to evaluate the risk of fatal NOAC‐related ICH compared with VKA‐related ICH. Methods: We calculated the corresponding risk ratios (RRs) in each included study to express the relative risk of fatal ICH amongst all patients receiving oral anticoagulation with either NOACs or VKAs. We additionally evaluated the mortality rates in NOAC‐related ICH in patients treated with and without NOAC‐specific reversal agents (idarucizumab and factor Xa inhibitors antidote). Case fatality was evaluated at 30–90 days following symptom onset. Results: Our literature search identified six eligible studies (four randomized controlled trials and two open‐label trials of NOAC‐specific reversal agents). In pairwise analyses, NOACs were found to have a lower risk of fatal ICH compared with VKAs [RR, 0.46; 95% confidence interval (CI), 0.36–0.58] with no heterogeneity (I2 = 0%) across included randomized controlled trials. However, the case fatality rate was similar in NOAC‐related and VKA‐related (RR, 1.00; 95% CI, 0.84–1.19) ICH with no evidence of heterogeneity (I2 = 0%). In the indirect analysis, the case fatality rate of NOAC‐related ICH in patients treated with specific reversal agents was lower compared with the remainder of the patients [17% (95% CI, 11–24%) vs. 41% (95% CI, 34–49%); P < 0.001]. Conclusions: Non‐vitamin K oral anticoagulants halve the risk of fatal ICH in patients with non‐valvular atrial fibrillation compared with VKAs, whereas indirect comparisons indicate that NOAC‐specific reversal agents may be associated with a lower case fatality rate in NOAC‐related ICH. [ABSTRACT FROM AUTHOR]

Background and Purpose: Stent retrievers have revolutionized endovascular treatment of acute ischemic stroke (AIS). Animal studies showed that mechanical thrombectomy (MT) may cause endothelial injury and intimal layer edema. Using transcranial color-coded duplex-sonography (TCCS) we observed postprocedural hemodynamic changes in the treated vessel.Methods: We studied AIS patients with large intracranial artery occlusion in whom MT with stent retrievers was performed. Only those with complete recanalization (modified TICI-2b or 3) as assessed by postprocedural digital subtraction angiography (DSA) and in whom early control TCCS was performed were retained. Patients treated with intra-arterial thrombolysis or stenting were excluded.Results: In 31 patients treated within a time period of 4 years (29 with middle cerebral artery [MCA] and 2 with basilar artery [BA] occlusion), postacute stroke brain-DSA confirmed complete recanalization without residual stenosis or vasospasm. However, in 27 (17 men, mean age 66.3 years) of them TCCS (mean 3.4 days after MT) showed very segmental acceleration of blood flow velocities in the affected arteries (MCA maximum peak systolic velocity [PSVmax] at least >35% as compared to the contralateral side at the same depth; BA PSVmax >40% as compared to velocities at different depths of the same vessel). None showed clinical deterioration. TCCS follow-up (mean 20 days) showed normalization in 14 of 16 cases.Conclusion: Our TCCS study provides preliminary evidence of focal acceleration of blood flow velocities after MT. Without residual stenosis or vasospasm, this may be a sign of endothelial layer disruption/intimal injury. Further studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a pressing burden on our developed and consequently aging society. Misfolded protein aggregates are a critical aspect of several neurodegenerative diseases. Nevertheless, several questions remain unanswered regarding the role of misfolded protein aggregates and the cause of neuronal cell death. Recently, it has been postulated that neuroinflammatory processes might play a crucial role in the pathogenesis of PD. Numerous postmortem, brain imaging, epidemiological, and animal studies have documented the involvement of the innate and adaptive immunity in neurodegeneration. Whether these inflammatory processes are directly involved in the etiology of PD or represent secondary consequences of nigrostriatal pathway injury is the subject of intensive research. Immune alterations in response to extracellular α-synuclein may play a critical role in modulating Parkinson's disease progression. In this review, we address the current concept of neuroinflammation and its involvement in PD-associated neurodegeneration. [ABSTRACT FROM AUTHOR]

ABSTRACT: Ignoring children's bedtime crying (ICBC) is an issue that polarizes parents as well as pediatricians. While most studies have focused on the effectiveness of sleep interventions, no study has yet questioned which parents use ICBC. Parents often find children's sleep difficulties to be very challenging, but factors such as the influence of Western approaches to infant care, stress, and sensitivity have not been analyzed in terms of ICBC. A sample of 586 parents completed a questionnaire to investigate the relationships between parental factors and the method of ICBC. Data were analyzed using structural equation modeling. Latent variables were used to measure parental stress (Parental Stress Scale; J.O. Berry & W.H. Jones, 1995), sensitivity (Situation‐Reaction‐Questionnaire; Y. Hänggi, K. Schweinberger, N. Gugger, & M. Perrez, 2010), Western‐oriented parental beliefs (Rigidity), and children's temperament (Parenting Stress Index; H. Tröster & R.R. Abidin). ICBC was used by 32.6% (n = 191) of parents in this study. Parents’ Western‐oriented beliefs predicted ICBC. Attitudes such as feeding a child on a time schedule and not carrying it out to prevent dependence were associated with letting the child cry to fall asleep. Low‐sensitivity parents as well as parents of children with a difficult temperament used ICBC more frequently. Path analysis shows that parental stress did not predict ICBC. The results suggest that ICBC has become part of Western childrearing tradition. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: This study was conducted to determine whether an intra‐operative ratio of at least 1:1:2 of fresh frozen plasma (FFP):platelets (PLTs):packed red blood cells (pRBCs) improves outcomes in orthotopic liver transplantation (OLT). Methods: A single‐center, retrospective study of deceased donor OLT recipients (MELD ≥15) requiring intra‐operative pRBC transfusion (years 2013‐2016). Patients were grouped into those receiving an intra‐operative ratio of ≥1:1:2 of FFP:PLTs:pRBCs vs ratios <1:1:2. Results: Patients in ≥1:1:2 group (n = 150) and patients in <1:1:2 group (n = 80) were matched for baseline characteristics (P > .05). Patients in the ≥1:1:2 group had lower pRBC and intra‐operative blood product requirements (11 ± 0.5 vs 19 ± 1.4 units, P < .001, and 33 ± 1.3 vs 43 ± 3.3 units, P = .006, respectively), improved 1‐month mortality (0 vs 8%, P = .002), improved 1‐year survival (P = .004), less intra‐operative cardiac arrest (3% vs 10%, P = .03), and shorter operating room time (389 ± 7.2 vs 431 ± 17.2 minutes, P = .03). After multivariate adjustment for baseline and intra‐operative variables, balanced blood product transfusion (BBPT) was significantly associated with less intra‐operative pRBC transfusion (95% confidence interval: 0.60‐0.72). Conclusion: Balanced blood product transfusion is associated with reduced transfusion requirements in OLT. [ABSTRACT FROM AUTHOR]

Background The nine equivalents of nursing manpower use score ( NEMS) is used to evaluate critical care nursing workload and occasionally to define hospital reimbursements. Little is known about the caregivers' accuracy in scoring, about factors affecting this accuracy and how validity of scoring is assured. Methods Accuracy in NEMS scoring of Swiss critical care nurses was assessed using case vignettes. An online survey was performed to assess training and quality control of NEMS scoring and to collect structural and organizational data of participating intensive care units ( ICUs). Aggregated structural and procedural data of the Swiss ICU Minimal Data Set were used for matching. Results Nursing staff from 64 (82%) of the 78 certified adult ICUs participated in this survey. Training and quality control of scoring shows large variability between ICUs. A total of 1378 nurses scored one out of 20 case vignettes: accuracy ranged from 63.7% (intravenous medications) to 99.1% (basic monitoring). Erroneous scoring (8.7% of all items) was more frequent than omitted scoring (3.2%). Mean NEMS per case was 28.0 ± 11.8 points (reference score: 25.7 ± 14.2 points). Mean bias was 2.8 points (95% confidence interval: 1.0-4.7); scores below 37.1 points were generally overestimated. Data from units with a greater nursing management staff showed a higher bias. Conclusion Overall, nurses assess the NEMS score within a clinically acceptable range. Lower scores are generally overestimated. Inaccurate assessment was associated with a greater size of the nursing management staff. Swiss head nurses consider themselves motivated to assure appropriate scoring and its validation. [ABSTRACT FROM AUTHOR]

Background. Reliable ICU severity scores have been achieved by various healthcare workers but nothing is known regarding the accuracy in real life of severity scores registered by untrained nurses. Methods. In this retrospective multicentre audit, three reviewers independently reassessed 120 SAPS II scores. Correlation and agreement of the sum-scores/variables among reviewers and between nurses and the reviewers' gold standard were assessed globally and for tertiles. Bland and Altman (gold standard- nurses) of sum scores and regression of the difference were determined. A logistic regression model identifying risk factors for erroneous assessments was calculated. Results. Correlation for sum scores among reviewers was almost perfect (mean ICC = 0.985). The mean (±SD) nurse-registered SAPS II sum score was 40.3±20.2 versus 44.2±24.9 of the gold standard (P < 0.002 for difference) with a lower ICC (0.81). Bland and Altman assay was +3.8 ± 27.0 with a significant regression between the difference and the gold standard, indicating overall an overestimation (underestimation) of lower (higher; >32 points) scores. The lowest agreement was found in high SAPS II tertiles for haemodynamics (k = 0.45-0.51). Conclusions. In real life, nurse-registered SAPS II scores of very ill patients are inaccurate. Accuracy of scores was not associated with nurses' characteristics. [ABSTRACT FROM AUTHOR]

Background: In order to differentiate between the different causes of intracranial stenosis, we compared the diagnostic results of transcranial color-coded duplex (TCCD) sonography with the recently developed 3D high-resolution black blood MR sequence.Methods: We studied retrospectively 20 patients referred to our hospital after acute ischemic stroke who were diagnosed with intracranial stenosis and in whom a repetitive TCCD and a 3D MR T1 FAT SAT (black blood) sequence at 3T (TR/TE 350/20 ms, FOV 160×182×120 mm, 0.4×0.4×0.4 size of pixel, 300 slices, Fat Sat spair, acquisition time 6 minutes 14) were performed. Etiological diagnosis was based on one hand on the morphological aspect of the arterial wall (black blood T1 FAT SAT sequence) and on the hemodynamic aspect (TCCD) on the other hand. Analysis of black blood T1 FAT SAT MR sequence and TCCD agreement on the etiological diagnosis was performed using sign test.Results: TCCD was performed at admission and at least at two different intervals during follow-up. Eleven patients had diffuse intracranial arterial disease and nine had involvement of a single intracranial artery. Etiology of intracranial arterial stenosis included: atheromatosis, thrombosis, vasculitis and reversible vasoconstriction syndrome. There was 80% agreement (sign test P = .0059) between these two methods.Conclusions: These two combined imaging techniques might be promising for the differentiation of arteriosclerotic changes from stenosis of another origin, especially when follow-up TCCD studies are completed early before a possible regression of the atherosclerotic plaque that might be observed 6 months after initial diagnosis. [ABSTRACT FROM AUTHOR]

ABSTRACT Polyaxial locking screws are increasingly applied in fracture fixation. To investigate the durability of the head-locking mechanism, the removal torque of variable angle (VA) and fixed angle (FA) stainless steel and titanium locking screws was investigated without and after a cyclic loading test. Stainless steel (St) and titanium (Ti) 2.4 mm orthogonally inserted FA screws and 2.4 mm VA screws inserted in different inclinations (0°-15°) ( n = 6 per group) were locked at 0.8 Nm. Removal torque was determined without (W) and after (A) cyclic loading (sinusoidal load, 5 Hz, constant amplitude of 25 N, up to 10′000 cycles, or failure). Significant differences in-between the groups were detected by Student's t-test ( p < 0.05). Except VA Ti in 0deg and FA, all groups exhibited a drop in removal torque below the insertion torque without and after cyclic testing. The removal torque was (St: FA W:0.81 Nm ± 0.04 A:0.72Nm ± 0.04; VA0deg W:0.73 Nm ± 0.04 A:0.65 Nm ± 0.05; VA15deg W:0.51 Nm ± 0.05 A:0.50 Nm ± 0.08; Ti: FA W:0.82 Nm ± 0.03 A:0.70 Nm ± 0.04; VA0deg W:0.80 Nm ± 0.02 A:0.72 Nm ± 0.05; VA15deg W:0.55 Nm ± 0.03 A:0.54 Nm ± 0.06). In all groups, the removal torque after cyclic testing did not drop below 16% of the removal torque without cyclic testing. No head loosening was observed after cyclic testing. Stainless steel and titanium 2.4 mm fixed and variable angle locking screws provide a stable and lasting head-locking mechanism. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:949-952, 2016. [ABSTRACT FROM AUTHOR]

Purpose: Paradoxical thrombotic embolism via right-to-left cardiac shunt (RLS) is a risk factor of cryptogenic ischemic stroke. Transtemporal Doppler (TTD) is a valid method used in the detection of patent foramen ovale (PFO). Temporal acoustic bone windows are missing with increasing age and in some younger subjects. We studied prospectively whether Doppler ultrasound of the cervical arteries (submandibular internal carotid artery [ICA] and vertebral artery [VA]) is an alternative, when compared to TTD, in the detection and quantification of PFO.Material and Methods: A total of 94 patients with sufficient temporal bone windows suffering from recent ischemic stroke underwent TTD and ICA (n = 51) or TTD and VA (n = 43). After injection of microbubbles, the numbers of artificial high-intensity signals (HITS) were recorded at rest and after Valsalva maneuver.Results: For 47 patients in the ICA group, an RLS was found at rest in 23 patients and after Valsalva in 28 patients. At rest, sensitivity was 100%, specificity 96%, positive predictive value (ppv) 95.6%, and negative predictive value (npv) 100%. After Valsalva, sensitivity was 100%, specificity 95%, ppv 96.4%, npv 100%. For 43 patients in the VA group an RLS was found at rest in 14 patients and after Valsalva in 19 patients. At rest, sensitivity was 71.4%, specificity 100%, ppv 100%, and npv 87.8%. After Valsalva, 94.4%, 96%, 94.4%, and 96%, respectively. Pearson's correlations of the number of HITS between TTD and ICA and between TTD and VA were highly significant.Conclusions: When transcranial acoustic bone windows are missing, Doppler ultrasound of the cervical submandibular ICA and VAs are valid screening methods to detect RLS due to a PFO. [ABSTRACT FROM AUTHOR]

ABSTRACT OBJECTIVES To assess the evidence on the safety and efficacy of sonothrombolysis in acute stroke. SEARCH METHODS Electronic databases and grey literature were searched under different MeSH terms from 1970 to present. SELECTION CRITERIA Randomized control trials (RCTs) and case control studies (CCSs) on sonolysis and sonothrombolysis alone or with microsphere in acute stroke patients (>18 old). Outcome measures included complete recanalization (CR) at 1-2 and 24 hours, 3 months modified Rankin Scale (mRS), and symptomatic intracerebral hemorrhage (sICH). Data was extracted to Review Manager software. RESULTS Fifty-seven studies were retrieved and analyzed. Ten studies (7 RCTs and 3 CCSs) were included in our meta-analysis, which revealed that sonolysis and sonothrombolysis are safe (OR of sICH: 1.14; 95% confidence interval (CI): 0.56- 2.34;P=0.71) and effective (OR of CR at 1-2 hours: 2.95;95% CI: 1.81-4.81;P<0.00001) and have more than two-fold higher likelihood of favourable long-term outcome (3-month mRS 0-2; OR: 2.20; CI:1.52-3.19;P<0.0001). Further subgroup analysis based on the presence of microsphere revealed that it is safe (OR of sICH: 1.18; CI:0.433.24;P=0.75) and effective (OR of CR: 2.61; CI: 1.36-4.99;P=0.004). Subgroup analysis based on sonolysis revealed to be safe and effective. CONCLUSIONS This novel treatment appears safe and effective. The evidence of microsphere as an enhancement of sonothrombolysis is evolving. [ABSTRACT FROM AUTHOR]

Malfunctioning of the protein α-synuclein is critically involved in the demise of dopaminergic neurons relevant to Parkinson's disease. Nonetheless, the precise mechanisms explaining this pathogenic neuronal cell death remain elusive. Endonuclease G (EndoG) is a mitochondrially localized nuclease that triggers DNA degradation and cell death upon translocation from mitochondria to the nucleus. Here, we show that EndoG displays cytotoxic nuclear localization in dopaminergic neurons of human Parkinson-diseased patients, while EndoG depletion largely reduces α-synuclein-induced cell death in human neuroblastoma cells. Xenogenic expression of human α-synuclein in yeast cells triggers mitochondria-nuclear translocation of EndoG and EndoG-mediated DNA degradation through a mechanism that requires a functional kynurenine pathway and the permeability transition pore. In nematodes and flies, EndoG is essential for the α-synuclein-driven degeneration of dopaminergic neurons. Moreover, the locomotion and survival of α-synuclein-expressing flies is compromised, but reinstalled by parallel depletion of EndoG. In sum, we unravel a phylogenetically conserved pathway that involves EndoG as a critical downstream executor of α-synuclein cytotoxicity. [ABSTRACT FROM AUTHOR]

Background and Purpose Available medications for chronic pain provide only partial relief and often cause unacceptable side effects. There is therefore a need for novel molecular targets to develop new therapeutics with improved efficacy and tolerability. Despite encouraging efficacy data in rodents with inhibitors of the neuronal glycine transporter-2 ( GlyT2), there are also some reports of toxicity and their development was discontinued. Experimental Approach In order to clarify the possibility of targeting GlyT2 for the treatment of pain, we have used an integrated approach comprising in vitro pharmacology, selectivity, bioavailability, in vivo efficacy and safety assessment to analyse the properties and efficacy of ALX-1393 and Org-25543, the two published GlyT2 inhibitors from which in vivo data are available. Key Results We report that these compounds have a different set of undesirable properties that limit their usefulness as pharmacological tools. Importantly, we discover that inhibitors of GlyT2 can exert an apparent reversible or irreversible inhibition of the transporter and describe a new class of reversible GlyT2 inhibitors that preserves efficacy while avoiding acute toxicity. Conclusions and Implications Our pharmacological comparison of two closely related GlyT2 inhibitors with different modes of inhibition provides important insights into their safety and efficacy profiles, uncovering that in the presence of a GlyT2 mechanism-based toxicity, reversible inhibitors might allow a tolerable balance between efficacy and toxicity. These findings shed light into the drawbacks associated with the early GlyT2 inhibitors and describe a new mechanism that might serve as the starting point for new drug development. [ABSTRACT FROM AUTHOR]

The purpose of this article is to share pedagogical materials and activities which can help TESOL practitioners prepare service-learning activities inside and outside the classroom. This study utilizes action research tools to improve academic service-learning in TESOL as a holistic approach to problem solving rather than a single method for collecting and analyzing data. The article describes the experiences of planning, implementing, participating in, and evaluating a successful university intensive English course at a midwestern U.S. university. Qualitative research methods used included document collection and analysis, authentic instructional artifacts, and a survey to exemplify the experiences of students and community partners. Students expressed their preferences for service-learning as both community building and personal growth opportunities with student reflection data. The results of this study suggest that the seven steps for service-learning in the TESOL model may be the starting point for developing additional context-specific service-learning courses in TESOL depending on the nature and location of an English language program. Based on the findings of the present research, the author also argues that this study shows that there are certain identifiable boundaries and combinations of useful steps for an acceptable TESOL service-learning project. [ABSTRACT FROM AUTHOR]

This article describes three service-learning projects implemented in three different ESL programs in the United States. Each description includes typical course goals, service-learning assignments, reflection activities, student learning outcomes, and pedagogical challenges. The first project was developing digital literacy through service-learning projects in southeast Michigan. In this ESL program, two groups of ESL students created two types of written publications about their service and civic engagement learning experiences. The documents were subsequently posted to the Internet. The second project involved international students at the University of Richmond. Students completed weekly service-learning by tutoring underserved children in a low-income urban neighborhood in Virginia. The third project at the University of Denver involved observing how students' attitudes changed throughout the quarter during the process of learning about and serving the homeless community using a series of five written reflections. The three service-learning projects presented in this article demonstrate how community engagement can promote a sense of empowerment in ESL students. This is accomplished by making them feel part of their community, allowing them to work cooperatively to develop authorial voice, increasing their audience awareness in writing, and fostering critical reflection that leads to a better understanding of social problems and civic responsibility. [ABSTRACT FROM AUTHOR]

Aims Follicular thyroid carcinoma ( FTC) has been a diagnostic challenge for decades. The PAX8- PPARγ rearrangement has been detected in FTC and classic papillary thyroid carcinomas ( PTCs). The aims of this study were to assess the presence of PAX8- PPARγ by using tissue microarrays in a large cohort of different thyroid neoplasms, and to assess its diagnostic and prognostic implications. Methods and results Fluorescence in-situ hybridization ( FISH) analysis for PAX8- PPARγ was performed on 226 thyroid tumours, comprising FTCs ( n = 59), PTCs ( n = 126), poorly differentiated thyroid carcinomas ( PDs; n = 34), follicular thyroid adenomas ( FTAs; n = 5), and follicular tumours of unknown malignant potential ( FTUMPs; n = 2). PAX8- PPARγ was detected in 12% of FTCs, 1% of PTCs, 7% of PDs, and in both cases of FTUMP. There was no correlation between the extent of capsular or vascular invasion and PAX8- PPARγ, or between lymph node or haematogenous metastasis and PAX8- PPARγ. Overall survival ( OS), tumour-specific survival ( TSS) and relapse-free-survival ( RFS) were not influenced by PAX8- PPARγ. Conclusions In this study, we demonstrate for the first time the presence of PAX8- PPARγ in PDs and FTUMPs, whereas in FTCs and PTCs the prevalence of PAX8- PPARγ is lower than previously reported. PAX8- PPARγ did not correlate with invasiveness or affect prognosis in any tumour type. [ABSTRACT FROM AUTHOR]

I. Marinoni, M. Lee, S. Mountford, A. Perren, I. Bravi, L. Jennen, A. Feuchtinger, J. Drouin, F. Roncaroli and N. S. Pellegata (2013) Neuropathology and Applied Neurobiology 39, 256-269 Characterization of MENX-associated pituitary tumours Aims: The aim of this study is to evaluate the pathological features, serum hormone levels and ex vivo cultures of pituitary adenomas that occur in rats affected by MENX syndrome. MENX is multiple endocrine neoplasia syndrome caused by a germline mutation in the cell cycle inhibitor p27. Characterization of MENX adenomas is a prerequisite to exploit this animal model for molecular and translational studies of pituitary adenomas. Methods: We investigated MENX pituitary adenomas with immunohistochemistry, double immunofluorescence, electron microscopy, reverse transcription polymerase chain reaction (RT-PCR), measurement of serum hormone levels and ex vivo cultures. Results: Adenomas in MENX rats belong to the gonadotroph lineage. They start from 4 months of age as multiple neoplastic nodules and progress to become large lesions that efface the gland. Adenomas are composed of chromophobic cells predominantly expressing the glycoprotein alpha-subunit (αGSU). They show mitotic activity and high Ki67 labelling. A few neoplastic cells co-express gonadotropins and the transcription factor steroidogenic factor 1, together with growth hormone or prolactin and Pit-1, suggesting that they are not fully committed to one cell lineage. Ex vivo cultures show features similar to the primary tumour. Conclusions: Our results suggest that p27 function is critical to regulate gonadotroph cells growth. The MENX syndrome represents a unique model to elucidate the physiological and molecular mechanisms mediating the pathogenesis of gonadotroph adenomas. [ABSTRACT FROM AUTHOR]

Sleep electroencephalogram spindles are associated with efficient cortical-subcortical connectivity, and intellectual and learning abilities. In the present study, we assessed healthy preschoolers with a twofold aim: (i) to explore associations of non-rapid eye movement S2 spindles with emotional/behavioural characteristics cross-sectionally; and (ii) longitudinally. A total of 43 children who were 5 years old underwent objective sleep electroencephalogram monitoring in their homes. Emotional and behavioural dimensions were assessed by parents and teachers with the Strengths & Difficulties Questionnaire at baseline and at follow-up 1 year later. Non-rapid eye movement S2 spindles were visually scored and compared with Strengths & Difficulties Questionnaire dimensions. High non-rapid eye movement S2 spindle density was associated with less internalizing behaviour, more prosocial behaviour and a low total problem score. In girls, high non-rapid eye movement S2 spindle density was related to low hyperactivity, while in boys it was associated with less internalizing behaviour, more externalizing behaviour and more hyperactivity. Longitudinally, a higher number of non-rapid eye movement S2 spindles at 5 years old predicted fewer peer problems 12 months later. In kindergarten children, high non-rapid eye movement S2 spindle density is associated with observable current and future favourable emotional/behavioural patterns. However, gender differences were also found, as should be taken into account in future studies. [ABSTRACT FROM AUTHOR]

Background: Evidence indicates that being a victim of bullying or peer aggression has negative short- and long-term consequences. In this study, we investigated the mediating and moderating role of two types of attributional mechanisms (hostile and self-blaming attributions) on children's maladjustment (externalizing and internalizing problems). Methods: In total, 478 children participated in this longitudinal study from grade 5 to grade 7. Children, parents, and teachers repeatedly completed questionnaires. Peer victimization was assessed through peer reports (T1). Attributions were assessed through self-reports using hypothetical scenarios (T2). Parents and teachers reported on children's maladjustment (T1 and T3). Results: Peer victimization predicted increases in externalizing and internalizing problems. Hostile attributions partially mediated the impact of victimization on increases in externalizing problems. Self-blame was not associated with peer victimization. However, for children with higher levels of self-blaming attributions, peer victimization was linked more strongly with increases in internalizing problems. Conclusions: Results imply that hostile attributions may operate as a potential mechanism through which negative experiences with peers lead to increases in children's aggressive and delinquent behavior, whereas self-blame exacerbates victimization's effects on internalizing problems. [ABSTRACT FROM AUTHOR]

ABSTRACT Cyberbullying has emerged as a new form of antisocial behaviour in the context of online communication over the last decade. The present study investigates potential longitudinal risk factors for cyberbullying. A total of 835 Swiss seventh graders participated in a short-term longitudinal study (two assessments 6 months apart). Students reported on the frequency of cyberbullying, traditional bullying, rule-breaking behaviour, cybervictimisation, traditional victimisation, and frequency of online communication (interpersonal characteristics). In addition, we assessed moral disengagement, empathic concern, and global self-esteem (intrapersonal characteristics). Results showed that traditional bullying, rule-breaking behaviour, and frequency of online communication are longitudinal risk factors for involvement in cyberbullying as a bully. Thus, cyberbullying is strongly linked to real-world antisocial behaviours. Frequent online communication may be seen as an exposure factor that increases the likelihood of engaging in cyberbullying. In contrast, experiences of victimisation and intrapersonal characteristics were not found to increase the longitudinal risk for cyberbullying over and above antisocial behaviour and frequency of online communication. Implications of the findings for the prevention of cyberbullying are discussed. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study investigated different facets of moral development in bullies, victims, and bully-victims among Swiss adolescents. Extending previous research, we focused on both bullying and victimization in relation to adolescents' morally disengaged and morally responsible reasoning as well as moral emotion attributions. A total of 516 adolescents aged 12-18 (57% females) reported the frequency of involvement in bullying and victimization. Participants were categorized as bullies (14.3%), bully-victims (3.9%), and victims (9.7%). Moral judgment, moral justifications, and emotion attributions to a hypothetical perpetrator of a moral transgression (relational aggression) were assessed. Bullies showed more morally disengaged reasoning than non-involved students. Bully-victims more frequently indicated that violating moral rules is right. Victims produced more victim-oriented justifications (i.e., more empathy) but fewer moral rules. Among victims, the frequency of morally responsible justifications decreased and the frequency of deviant rules increased with age. The findings are discussed from an integrative moral developmental perspective. [ABSTRACT FROM AUTHOR]

Firm size is found to affect strategic decisions significantly, whereas technology and market stability stimulate product development and innovation. [ABSTRACT FROM AUTHOR]

Dettmer M, Schmitt A, Steinert H, Moch H, Komminoth P & Perren A (2012) Histopathology 60, 1045-1051 Poorly differentiated oncocytic thyroid carcinoma - diagnostic implications and outcome Aims: Poorly differentiated thyroid carcinomas (PDTC) are an ongoing diagnostic challenge. Although the Turin consensus criteria for PDTC excluded consideration of oncocytic tumours, the World Health Organization (WHO) classification does recognise an oncocytic variant of conventional PDTC. The aims of this study were to establish whether the Turin criteria can be applied to oncocytic PDTC, and to determine if there are prognostic differences between conventional and oncocytic PDTC. Methods and results: We applied the Turin criteria to 129 thyroid carcinomas. We identified 18 oncocytic PDTC and 16 conventional PDTC. Kaplan-Meier analysis revealed a significantly worse outcome for oncocytic PDTC with regard to overall and tumour-specific survival but no difference for relapse-free survival, all of which were confirmed by multivariate analysis. There was no association of survival with gender, age or tumour stage. Conclusions: The Turin criteria can be applied to oncocytic PDTC and patients with this variant have a decreased survival using conventional radioiodine treatment compared to conventional PDTC and might therefore be candidates for novel treatment modalities. [ABSTRACT FROM AUTHOR]

SUMMARY Aims: Lacosamide (LCM; SPM 927, Vimpat®) is an antiepileptic drug (AED) used as adjunctive treatment for adults with partial-onset seizures. LCM has a different mode of action from traditional sodium channel blocking AEDs in that it selectively enhances slow inactivation of sodium channels without affecting fast inactivation. Initial investigations suggested that LCM might have an additional mode of action by binding to the collapsin response mediator protein 2 (CRMP-2), which is further investigated here. Methods: LCM binding to native and cloned human CRMP-2 was determined using radioligand binding experiments and surface plasmon resonance measurements. Results: No specific binding of [3H]LCM (free concentration 100-1450 nM) to isolated or membrane bound human CRMP-2 expressed in mammalian cell systems and bacteria was observed. Surface plasmon resonance analysis also showed that LCM, over a concentration range of 0.39-100 μM, does not specifically bind to human CRMP-2. Conclusion: The diverse drug binding methods employed here are well suited to detect specific binding of LCM to CRMP-2 in the micromolar range, yet the results obtained were all negative. Results of this study suggest that LCM does not specifically bind to CRMP-2. [ABSTRACT FROM AUTHOR]

Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or 11C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P = .03). The increase in mean tumor-to-liver ratio of 11C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P = .0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats. [ABSTRACT FROM AUTHOR]