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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

The evolution of language has fascinated anthropologists, psychologists and biologists for centuries, seeking to infer language origins from the communication of primates, our closest living relatives. Capacity for intentional signalling is a key feature of transition to language in our hominin ancestors, facilitating complex social dynamics in complex social groups. However whether vocal, gestural and bimodal signals are differentiated according to intentional use and hence complex sociality has not been studied, making unclear the modality of language evolution. We addressed this question in wild chimpanzees. We found that larger social network size was associated with a larger network of gestural but not vocal or bimodal signals. Response waiting was more common in association with gestures than vocalizations, but elaborations were more common in vocal than gestural or bimodal signals. Overall, chimpanzees were more likely to manage weak social bonds through vocalizations, whereas strong social bonds were managed through gestures and bimodal signals. However, when social bonds were weak, gestures accompanied by response waiting were more likely to elicit approaches than vocalizations accompanied by elaboration, which elicited avoidance. This suggests that gestures were the primary modality of language evolution and that the use of more sophisticated gestural signalling led to evolution of complex social groups of hominin ancestors. This article is part of the theme issue 'Cognition, communication and social bonds in primates'.

Renin, encoded by REN, is an essential enzyme in the renin-angiotensin aldosterone system (RAAS) which is responsible for the maintenance of blood pressure homeostasis. Transcriptional regulation of REN has been linked to enhancer-promoter crosstalk, cAMP response element-binding protein (CREB), the active metabolite of vitamin D, 1,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ), and a less well-characterized intronic silencer element. We hypothesized that in addition to these, differential DNA methylation is linked to REN expression and influenced by 1,25(OH) 2 D 3 . REN expressing cells (HEK293) were used to elucidate the effect of 1,25(OH) 2 D 3 on REN methylation and expression as quantified by methylation-sensitive qPCR and RT-qPCR, respectively. In vitro 1,25(OH) 2 D 3 supplementation (10 nM) induced significant hypomethylation of the REN silencer (P < 0.050), which was linked to a significant reduction in REN expression (P < 0.010) but had no effect on enhancer methylation. In addition, 1,25(OH) 2 D 3 increased VDR (P < 0.05), as well as TET1 (P < 0.05) expression, suggesting an association between 1,25(OH) 2 D 3 and DNA methylation. Thus, it appears that the silencer element, which is controlled by DNA methylation and influenced by 1,25(OH) 2 D 3 , plays an essential role in regulating REN expression., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Counter-terrorism strategies rely on the assumption that it is possible to increase threat detection by providing explicit verbal instructions to orient people's attention to dangerous objects and hostile behaviours in their environment. Nevertheless, whether verbal cues can be used to enhance threat detection performance under laboratory conditions is currently unclear. In Experiment 1, student participants were required to detect a picture of a dangerous or neutral object embedded within a visual search display on the basis of an emotional strategy 'is it dangerous?' or a semantic strategy 'is it an object?'. The results showed a threat superiority effect that was enhanced by the emotional visual search strategy. In Experiment 2, whilst trainee police officers displayed a greater threat superiority effect than student controls, both groups benefitted from performing the task under the emotional than semantic visual search strategy. Manipulating situational threat levels (high vs. low) in the experimental instructions had no effect on visual search performance. The current findings provide new support for the language-as-context hypothesis. They are also consistent with a dual-processing account of threat detection involving a verbally mediated route in working memory and the deployment of a visual template developed as a function of training., (© 2019 The British Psychological Society.)

Chinese hamster ovary (CHO) cells comprise a variety of lineages including CHO-DXB11, CHO-K1, CHO-DG44, and CHO-S. Despite all CHO cell lines sharing a common ancestor, extensive mutagenesis, and clonal selection has resulted in substantial genetic heterogeneity among them. Data from sequencing show that different genes are missing in individual CHO cell lines and each cell line harbors a unique set of mutations with relevance to the bioprocess. However, not much literature is available about the influence of genetic differences of CHO on the performance of bioprocess operations. In this study, the host cell-specific differences among three widely used CHO cell lines (CHO-K1, CHO-S, and CHO-DG44) and recombinantly expressed the same monoclonal antibody (mAb) in an isogenic format by using bacterial artificial chromosomes (BACs) as transfer vector in all cell lines is examined. Cell-specific growth and product formation are studied in batch, fed-batch, and semi-continuous perfusion cultures. Further, two different cell culture media are used to investigate their effects. The authors find CHO cell line-specific preferences for mAb production or biomass synthesis that are determined by the host cell line. Additionally, quality attributes of the expressed mAb are influenced by the host cell line and media., (© 2018 The Authors. Biotechnology Journal Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Feed supplements are concentrated cell culture media that contain a variety of nutrients, which can be added during a bioprocess. During fed-batch cultivation, feed media are typically added to a growing cell culture to maximize cell and product concentrations. In this study, only a single shot of feed medium was added on day 0 to a basal cell culture medium and compared to non-supplemented basal medium (feed-spiked at day 0 versus control experiments) by cultivation of a recombinant mAb expressing CHO cell line in batch mode under controlled conditions in a bioreactor. Since the feed-spike at day 0 was based on existing medium components without introducing additional supplements, a desirable process with decreased complexity was generated. Unlike cells in basal medium, feed-spiked cultures reached almost 2× higher peak cell concentrations (10 × 10 6 c/mL vs. 18 × 10 6 c/mL) and 3× higher antibody concentrations (0.8 g/L vs. 2.4 g/L). Batch process time and the integral over the viable cell count were similar for both process types. Constantly high cell-specific production rates in feed-spiked cultures (70 pg/cell/day) compared to continuously declining rates in basal medium (from 70 to 10 pg/cell/day) were responsible for an overall 70% higher cell-specific production rate and the higher product concentrations. To associate gene expression patterns to different process proceedings, transcriptome analysis was performed using microarrays. Several transcripts that are involved with glutamine de novo synthesis and citric acid cycle were significantly upregulated on several days in feed-spiked cultures. The top identified gene ontology (GO) terms related well to cell cycle and primary metabolism, cellular division as well as nucleobase formation or regulation, which indicated a more active proliferative state for feed-spiked cultures. KEGG biochemical pathway analysis and Gene set enrichment analysis (GSEA) further confirmed these findings from a complementary perspective. Moreover, several interesting gene targets, which have not yet been associated with recombinant protein expression, were identified that related to a higher proliferative state, growth, protein synthesis, cell-size control, metabolism, cell survival as well as genes that are associated with the control of the mammalian target of rapamycin (mTOR) in feed-spiked cultures. Analysis of critical product quality attributes (i.e. glycosylation, charge variants and size distribution) showed that feed-spiking did not change antibody quality., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

The current study investigated the extent to which the concurrent presentation of pleasant and unpleasant odors could modulate the perceptual saliency of happy facial expressions in an emotional visual search task. Whilst a search advantage for happy faces was found in the no odor and unpleasant odor conditions, it was abolished under the pleasant odor condition. Furthermore, phasic properties of visual search performance revealed the malleable nature of this happiness advantage. Specifically, attention towards happy faces was optimized at the start of the visual search task for participants presented with pleasant odors, but diminished towards the end. This pattern was reversed for participants in the unpleasant odor condition. These patterns occur through the emotion-inducing capacities of odors and highlight the circumstances in which top-down factors can override perceptually salient facial features in emotional visual search.

A theoretical concern in addressing the unconscious perception of emotion is the extent to which participants can access experiential properties of masked facial stimuli. Performance on a two alternative forced choice (2AFC) task as a measure of objective awareness was compared with a new measure developed to access experiential phenomena of the target-mask transition, the perceptual contrast-change sensitivity (PCCS) measure in a backward-masking paradigm with angry, happy and neutral facial expressions. Whilst 2AFC performance indicated that the targets were successfully masked, PCCS values were significantly higher in the happy-neutral face condition than in the angry-neutral face and the neutral-neutral face conditions (Experiment 1). Furthermore, objective measures of awareness were more readily displayed by individuals with high trait anxiety, whereas individuals with low trait anxiety showed greater access to the experiential quality of happy faces (Experiment 2). These findings provide important insights into the methodological considerations involved in the study of non-conscious processing of emotions, both with respect to individual differences in anxiety and the extent to which certain expressions can be successfully masked relative to others. Furthermore, our results may be informative to work investigating the neural correlates of conscious versus unconscious perception of emotion., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Independent lines of evidence suggest that the representation of emotional evaluation recruits both vertical and horizontal spatial mappings. These two spatial mappings differ in their experiential origins and their productivity, and available data suggest that they differ in their saliency. Yet, no study has so far compared their relative strength in an attentional orienting reaction time task that affords the simultaneous manifestation of both types of mapping. Here, we investigated this question using a visual search task with emotional faces. We presented angry and happy face targets and neutral distracter faces in top, bottom, left, and right locations on the computer screen. Conceptual congruency effects were observed along the vertical dimension supporting the 'up = good' metaphor, but not along the horizontal dimension. This asymmetrical processing pattern was observed when faces were presented in a cropped (Experiment 1) and whole (Experiment 2) format. These findings suggest that the 'up = good' metaphor is more salient and readily activated than the 'right = good' metaphor, and that the former outcompetes the latter when the task context affords the simultaneous activation of both mappings.

In this study, eight commercially available, chemically defined Chinese hamster ovary (CHO) cell culture media from different vendors were evaluated in batch culture using an IgG-producing CHO DG44 cell line as a model. Medium adaptation revealed that the occurrence of even small aggregates might be a good indicator of cell growth performance in subsequent high cell density cultures. Batch experiments confirmed that the culture medium has a significant impact on bioprocess performance, but high amino acid concentrations alone were not sufficient to ensure superior cell growth and high antibody production. However, some key amino acids that were limiting in most media could be identified. Unbalanced glucose and amino acids led to high cell-specific lactate and ammonium production rates. In some media, persistently high glucose concentrations probably induced the suppression of respiration and oxidative phosphorylation, known as Crabtree effect, which resulted in high cell-specific glycolysis rates along with a continuous and high lactate production. In additional experiments, two of the eight basal media were supplemented with feeds from two different manufacturers in six combinations, in order to understand the combined impact of media and feeds on cell metabolism in a CHO fed-batch process. Cell growth, nutrient consumption and metabolite production rates, antibody production, and IgG quality were evaluated in detail. Concentrated feed supplements boosted cell concentrations almost threefold and antibody titers up to sevenfold. Depending on the fed-batch strategy, fourfold higher peak cell concentrations and eightfold increased IgG titers (up to 5.8 g/L) were achieved. The glycolytic flux was remarkably similar among the fed-batches; however, substantially different specific lactate production rates were observed in the different media and feed combinations. Further analysis revealed that in addition to the feed additives, the basal medium can make a considerable contribution to the ammonium metabolism of the cells. The glycosylation of the recombinant antibody was influenced by the selection of basal medium and feeds. Differences of up to 50 % in the monogalacto-fucosylated (G1F) and high mannose fraction of the IgG were observed.

People make sense of objects and events around them by classifying them into identifiable categories. The extent to which language affects this process has been the focus of a long-standing debate: Do different languages cause their speakers to behave differently? Here, we show that fluent German-English bilinguals categorize motion events according to the grammatical constraints of the language in which they operate. First, as predicted from cross-linguistic differences in motion encoding, bilingual participants functioning in a German testing context prefer to match events on the basis of motion completion to a greater extent than do bilingual participants in an English context. Second, when bilingual participants experience verbal interference in English, their categorization behavior is congruent with that predicted for German; when bilingual participants experience verbal interference in German, their categorization becomes congruent with that predicted for English. These findings show that language effects on cognition are context-bound and transient, revealing unprecedented levels of malleability in human cognition., (© The Author(s) 2015.)

We explored how varying levels of professional expertise in hostile crowd management could enhance threat detection capabilities as assessed by the face in the crowd paradigm. Trainee police officers and more experienced police officers specialized in, and having extensive experience with, riot control, were compared with participants with no experience in hostile crowd management on their search times and accuracy levels in detecting angry and happy face targets against a display of emotional and neutral distractor faces. The experienced officers relative to their trainee counterparts and nonpolice controls showed enhanced detection for threatening faces in both types of display along with a greater degree of inhibitory control over angry face distractors. These findings help to reinforce the ecological validity of the face in the crowd paradigm and provide a new theoretical link for the role of individual differences on the attentional processing of socially relevant stimuli.

Cognitive models propose that auditory verbal hallucinations arise through inner speech misidentification. However, such models cannot explain why the voices in hallucinations often have identities different from the hearer. This study investigated whether a general voice identity recognition difficulty might be present in schizophrenia and related to auditory verbal hallucinations. Twenty-five schizophrenia patients and 13 healthy controls were tested on recognition of famous voices. Signal detection theory was used to calculate perceptual sensitivity and response criterion measures. Schizophrenia patients obtained fewer hits and had lower perceptual sensitivity to detect famous voices than healthy controls did. There were no differences between groups in false alarm rate or response criterion. A symptom-based analysis demonstrated that especially those patients with auditory verbal hallucinations performed poorly in the task. The results indicate that patients with hallucinations are impaired at voice identity recognition because of decreased sensitivity, which may result in inner speech misidentification.

There are considerable gaps in our knowledge on cell biological effects induced by the heavy metals mercury (Hg) and lead (Pb). In the present study we aimed to explore the effects of these toxicants on proliferation and cell size of primary human amniotic fluid stem (AFS) cells. Monoclonal human AFS cells were incubated with three dosages of Hg and Pb (single and combined treatment; ranging from physiological to cytotoxic concentrations) and the intracellular Hg and Pb concentrations were analyzed, respectively. At different days of incubation the effects of Hg and Pb on proliferation, cell size, apoptosis, and expression of cyclins and the cyclin-dependent kinase inhibitor p27 were investigated. Whereas we found Hg to trigger pronounced effects on proliferation of human AFS cells already at low concentrations, anti-proliferative effects of Pb could only be detected at high concentrations. Exposure to high dose of Hg induced pronounced downregulation of cyclin A confirming the anti-proliferative effects observed for Hg. Co-exposure to Hg and Pb did not cause additive effects on proliferation and size of AFS cells, and on cyclin A expression. Our here presented data provide evidence that the different toxicological effects of Pb and Hg on primary human stem cells are due to different intracellular accumulation levels of these two toxicants. These findings allow new insights into the functional consequences of Pb and Hg for mammalian stem cells and into the cell biological behavior of AFS cells in response to toxicants.

Recent evidence comparing recognition memory for famous faces and famous voices reveals an advantage for faces to elicit greater levels of episodic and semantic information than voices, even when overall levels of difficulty are matched between the two modalities. The paper by Barsics and Brédart makes a significant advance to this literature by demonstrating that even when encoding strategies are maximized to favor voice over face encoding by using personally familiar stimuli, facial cues continue to provide a more successful means for associating episodic and semantic memories than voices. The implications of these findings are discussed in terms of the role of familiarity and its associated links to semantic memory as captured by person recognition memory models., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Damjanovic and Hanley (2007) showed that episodic information is more readily retrieved from familiar faces than familiar voices, even when the two presentation modalities are matched for overall recognition rates by blurring the faces. This pattern of performance contrasts with the results obtained by Hanley and Turner (2000) who showed that semantic information could be recalled equally easily from familiar blurred faces and voices. The current study used the procedure developed by Hanley and Turner (2000) and applied it to the stimuli used by Damjanovic and Hanley (2007). The findings showed a marked decrease in retrieval of occupations and names from familiar voices relative to blurred faces even though the two modalities were matched for overall levels of recognition and rated familiarity. Similar results were obtained in Experiment 2 in which the same participants were asked to recognise both faces and voices. It is argued that these findings pose problems for any model of person recognition (e.g., Burton, Bruce, & Johnston, 1990) in which familiarity decisions occur beyond the point at which information from different modalities has been integrated.

Four experiments probed the nature of categorical perception (CP) for facial expressions. A model based on naming alone failed to accurately predict performance onthese tasks. The data are instead consistentwith an extension of the category adjustment model (Huttenlocher et al., 2000), in which the generation of a verbal code (e.g., "happy") activated knowledge ofthe expression category's range andcentral tendency (prototype) in memory, which was retained as veridical perceptual memory faded.Further support for amemory bias toward the category center came from a consistently asymmetric pattern of within-category errors. Verbal interference in the retention interval selectively removed CP for facial expressions, under blocked, but not under randomized presentation conditions. However, verbal interference at encoding removed CPeven under randomized conditions and these effects were shown to extend even to caricatured expressions, which lie outside the normal range of expression categories.

In this study, we used the distinction between remember and know (R/K) recognition responses to investigate the retrieval of episodic information during familiar face and voice recognition. The results showed that familiar faces presented in standard format were recognized with R responses on approximately 50% of the trials. The corresponding figure for voices was less than 20%. Even when overall levels of recognition were matched between faces and voices by blurring the faces, significantly more R responses were observed for faces than for voices. Voices were significantly more likely to be recognized with K responses than were blurred faces. These findings indicate that episodic information was recalled more often from familiar faces than from familiar voices. The results also showed that episodic information about a familiar person was never recalled unless some semantic information, such as the person's occupation, was also retrieved.

The research described in this article used a visual search task and demonstrated that the eye region alone can produce a threat superiority effect. Indeed, the magnitude of the threat superiority effect did not increase with whole-face, relative to eye-region-only, stimuli. The authors conclude that the configuration of the eyes provides a key signal of threat, which can mediate the search advantage for threat-related facial expressions., ((c) 2006 APA, all rights reserved)