To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
OBJECTIVES/GOALS: Murine and clinical data suggest that antibody-dependent cellular cytotoxicity (ADCC) is associated with greater protection against disseminated neonatal HSV disease. To quantify the relative transfer of Abs with different functions and targets, we conducted a prospective study of mother-infant term and preterm dyads pre and during COVID-19 METHODS/STUDY POPULATION: Total and HSV lysate, glycoprotein D (gD) and glycoprotein B (gB)-specific IgG, IgG1 and IgG3 as well as HSV neutralizing Abs (nAbs) and ADCC were quantified in paired 3rd-trimester pregnant women and their newborns (cord) blood. Transfer ratios (TR) were defined as cord:maternal Ab levels. IgG1 and IgG3 subclass and gD or gB-specific Abs were isolated by column purification and glycan profiles were assessed by mass spectrometry. The study population included 21 term and 15 preterm dyads who were HSV-1 (+/- HSV-2) seropositive enrolled between 2018-2019 (pre-COVID) and 25 additional HSV-1 (+/- HSV-2) seropositive term dyads whose mothers were SARS-CoV-2 PCR and COVID Ab+ at delivery; 14 were asymptomatic and 11 had mild-moderate COVID disease. None of the mothers had active genital HSV lesions during delivery RESULTS/ANTICIPATED RESULTS: Anti-HSV IgG, IgG1 and IgG3 TR were higher in term vs. preterm dyads (p<0.05). The nAb TR was 2.4 in term vs. 0.8 in preterm (p<0.001) but the ADCC TR was < 1.0 for both. To determine if the latter reflected antigenic target, subclass or glycans, we enriched for gD and gB specific and IgG1 and IgG3 Abs. The gD Abs were IgG1 and had only neutralizing activity. In contrast, gB Abs were polyfunctional and included IgG1 and IgG3 but only the IgG1 Abs had ADCC activity. The gD Abs were enriched for glycans associated with an affinity for the neonatal Fc receptor (FcRn); gB Abs expressed glycans associated with both FcRn and FcÎ³RIIIa binding. There was no significant difference in total HSV-specific IgG TR in pre-COVID vs post-COVID dyads but the nAb TR was lower (p=0.018) and ADCC TR higher (p<0.001) in the COVID compared to pre-COVID cohort DISCUSSION/SIGNIFICANCE: HSV ADCC Abs, which may provide greater protection than nAbs against neonatal disease, transfer poorly particularly to preterm newborns. However, in the setting of SARS-CoV-2, the TR of HSV ADCC is significantly higher. This may reflect alterations in the placental architecture and/or glycan composition which is currently being investigated.
Expert authority is regarded as the heart of international bureaucracies’ power. To measure whether international bureaucracies’ expert authority is indeed recognised and deferred to, we draw on novel data from a survey of a key audience: officials in the policy units of national ministries in 121 countries. Respondents were asked to what extent they recognised the expert authority of nine international bureaucracies in various thematic areas of agricultural and financial policy. The results show wide variance. To explain this variation, we test well-established assumptions on the sources of de facto expert authority. Specifically, we look at ministry officials’ perceptions of these sources and, thus, focus on a less-studied aspect of the authority relationship. We examine the role of international bureaucracies’ perceived impartiality, objectivity, global impact, and the role of knowledge asymmetries. Contrary to common assumptions, we find that de facto expert authority does not rest on impartiality perceptions, and that perceived objectivity plays the smallest role of all factors considered. We find some indications that knowledge asymmetries are associated with more expert authority. Still, and robust to various alternative specifications, the perception that international bureaucracies are effectively addressing global challenges is the most important factor.
Apicomplexan parasites are well-known to modulate their host cells at diverse functional levels. As such, apicomplexan-induced alteration of host cellular cell cycle was described and appeared dependent on both, parasite species and host cell type. As a striking evidence of species-specific reactions, we here show that Eimeria bovis drives primary bovine umbilical vein endothelial cells (BUVECs) into a senescence-like phenotype during merogony I. In line with senescence characteristics, E. bovis induces a phenotypic change in host cell nuclei being characterized by nucleolar fusion and heterochromatin-enriched peripheries. By fibrillarin staining we confirm nucleoli sizes to be increased and their number per nucleus to be reduced in E. bovis-infected BUVECs. Additionally, nuclei of E. bovis-infected BUVECs showed enhanced signals for HH3K9me2 as heterochromatin marker thereby indicating an infection-induced change in heterochromatin transition. Furthermore, E. bovis-infected BUVECs show an enhanced β-galactosidase activity, which is a well-known marker of senescence. Referring to cell cycle progression, protein abundance profiles in E. bovis-infected endothelial cells revealed an up-regulation of cyclin E1 thereby indicating a cell cycle arrest at G1/S transition, signifying a senescence key feature. Similarly, abundance of G2 phase-specific cyclin B1 was found to be downregulated at the late phase of macromeront formation. Overall, these data indicate that the slow proliferative intracellular parasite E. bovis drives its host endothelial cells in a senescence-like status. So far, it remains to be elucidated whether this phenomenon indeed reflects an intentionally induced mechanism to profit from host cell-derived energy and metabolites present in a non-dividing cellular status.
The design of an active seat suspension for a mid-class passenger vehicle based on the given set of requirements is considered a combination of four subsystems; the carrier, the actuator, the spring, and the damper. The design of the former two is considered through the 10 and 16 concepts for each, respectively. Two overall designs are proposed for further development. One based on a dual Scott-Russell mechanism and one based on Sarrus mechanism. The first one is evaluated to have high stiffness, the second to be more cost-effective. The detailed design of the first concept is presented.
Patients with untreated obstructive sleep apnea often report depressive symptoms, such as low mood, loss of interest and reduction of drive. In this study we examined the frequency of significant depressive symptoms amongst patients with untreated obstructive sleep apnea over a one year period.
From January to December 2008 we screened 1260 consecutive patients with untreated obstructive sleep apnea (AHI > 9) seen at our Center for Sleep Medicine were screened for depression. Based on self-administered questionnaires, patients with significant depressive symptoms were defined as having either a BDI II score ≥ 14 or WHO-5 ≤ 13. Additionally, severity of depression was rated based on BDI II scores.
Depressive symptoms were reported frequently. Based on BDI-II, 27.9% of patients report significant depressive symptoms. Of these, 46.2% were mild, 35.9% moderate and 17.9% severe. In addition, 52.6% of patients self-reported feeling unwell based on their WHO-5 scores.
Significant depressive symptoms measured by standardised self-rating scales were detected in over a quarter of our patients with untreated sleep apnea. It remains unknown whether treatment of OSA alone abolishes depressive symptoms, or whether depressive mood may reduce the compliance with treatment. Patients may need an interdisciplinary approach to initial treatment.
A group of schizophrenic patients perform well in known theory of mind (ToM) tasks. Still most of them have difficulties to understand social situations in real life.
We used a new test of ToM to find out if this group of patients really have the ability to understand other people´s mental states or they might use some compensatory strategies.
49 schizophrenic patients and 38 matched control inviduals were evaluated. Participants were asked to read short stories and answer simple yes/no comprehension questions. We used three experimental conditions: “false-irony” condition (FI), “control” condition (C), and “false-irony with linguistic help” condition (FIH).
P atients with schizophrenia performed sinificantly worse than control subjects in each of the three conditions (FI:p=0.01;C:p=0.04;FIH:p=0.01). Among the 49 patients 22 did well the FIH tasks (44.89%). Among these 22 patients 12 did the FI tasks well (24.48%) and the other 10 did the FIH tasks well (20.4%).
P atients with schizophrenia performed a sinificant impairment in the new ToM test. Beside a group of patients is able to understand other people´s mental states. To understand these situations some patients probably use real mentalisation strategies, some of them can use the given linguistic help as a compensatory strategy, and some patients have difficulties in representing of the mental states of others.
Irony is a form of speech used to convey feelings in an indirect way. Patients with schizophrenia demonstrated an impaired irony processing, associated with poor theory of mind.
We used fMRI to examine neural circuitry underlying deficits in understanding irony in schizophrenia.
11 right-handed patients with paranoid schizophrenia and 11 right-handed healthy subjects were studied. Participants were asked to listen short scenarios. The 15 irony condition consisted an ironic statement, and the 15 control condition was physical causality. We used an event-related design. Every scenario started with a two sentences long context, followed by a 2-4 s (jittered) inter-stimulus interval. The third, critical ironic sentence appeared next, and finally a simple yes/no comprehension question followed. Between trials an inter-trial interval of 5-7 s (jittered) were used.
The schizophrenic group performed significantly worse in the irony condition than the control group (p=0.0008). Ironic statements resulted in significant activations in the left inferior frontal gyrus (IFG) and insula, right superior and medial frontal gyrus, left postcentral gyrus, posterior division of right superior and left middle temporal gyrus, left lingual gyrus, left cuneus and right inferior parietal lobule in the schizophrenic group. The control group showed significantly greater activity in the left IFG and insula compared to the schizophrenic group.
Among schizophrenic patients we found a significant underactivation in the left IFG and insula during irony comprehension, which may contribute to the impairements of social behavior in schizophrenia.
Theory of mind (ToM) has been proved to play a crucial role in social cognition and functioning. In our study, higher order mentalization performance of euthymic bipolar I patients were compared with that of healthy controls. The impact of demographic data, course of the disorder and patients’ current functioning were also considered while interpreting mentalization data.
The mentalizing performance (computerized faux pas task and false irony task), neurocognitive functioning, and IQ of twenty-three euthymic bipolar I patients and 31 matched (IQ, age) healthy controls were examined. In the patients group, the age at onset, the occurrence of psychotic symptoms, age, education, current employment status, and global functioning were also taken into account.
Bipolar patients scored significantly lower in false irony tasks than healthy controls (p< 0,02). The deficit in irony tasks positively correlated with the number of episodes. Among the examined variables, the performance in the faux pas task predicted most closely the functional outcome in bipolar I disorder. No correlation was found between the ToM and irony deficits and the occurrence of psychotic symptoms, the length of the bipolar disorder or neurocognitive functioning.
Our results showed impaired performance in faux pas and irony tasks, which correlates with the number of previous episodes. Additionally, the impairment of ToM functions predicts a worse functional outcome.
Deficits of social cognition are a relevant predictor of functioning and outcome. Several studies have found that euthymic bipolar patients perform worse in social cognition tasks than healthy controls. Some data show a higher relapse risk in bipolar patients with concomitant mentalization deficits. However, relatively little is known about the neurobiological base of these deficits.
12 euthymic bipolar I patients and 14 age- and IQ-matched healthy controls underwent event-related functional MRI study while performing 15 irony, and 15 control tasks (auditory stimulus) in the scanner. Both within group (irony versus control task) and random effects between group analyses were performed on fMRI data.
Bipolar patients were significantly compromised in their ability to appropriately answer irony tasks. Bipolar patients showed a reduced activation in right cingulate, right anterior paracingulate cortex, right precuneus, left superior parietal lobule, left hippocampus, left insula in comparison to healthy controls. However, bipolar patients brain activation was significantly increased in the left inferior frontal gyrus, left superior temporal gyrus, and left secondary somatosensory cortex.
The findings of this neuroimaging study suggest that euthymic bipolar patients are restricted in their ability to mentalize fully. They show less activation in brain regions involved in mental imaginery, emotional processing and self-representation. Therefore, bipolar patients have difficulties in understanding others’ intentions and emotions, which impacts on interpersonal relationships and the functional outcome.
It is well known that schizophrenia is characterized by structural brain abnormalities with neurodevelopmental origin. These abnormalities can be detected with quantitative and structural MRI methods that have an emergent role in psychiatric disorders. In our study we used voxel-based morphometry (VBM) that is the most frequently used structural MRI method.
We compared eight patients with first episode schizophrenia and eight, age-matched healthy subjects to detect focal tissue differences in gray and white matter, and cerebrospinal fluids between groups. High resolution T1 weighted 3D MPRAGE structural volumes were acquired with a 1.0 T Siemens Harmony Expert scanner. Imaging data were preprocessed and voxel based morphometry was performed by SPM2. Optimized VBM method was used.
Similar to earlier studies, patients with schizophrenia showed decreased gray matter tissue density in frontotemporal and insular regions bilaterally. Moreover, the left–sided parietal operculum and the calcarina showed focal decrease in tissue density. Frontotemporal and insular white matter density decrease were detected bilaterally similar to gray matter changes. The left sided precuneus and lingual gyrus were also involved in reduced white matter density. Increased cerebrospinal fluid spaces were detected in the frontal regions and the ventricles.
We detected structural brain abnormalities in the early course of schizophrenia. Our results with the optimized voxel-based morphometry are in line with earlier imaging studies and correspond with neuropsychologically detectable frontotemporal deficits in schizophrenia.
Irony is a form of speech used to convey feelings in an indirect way. Schizophrenic patients usually demonstrate impaired irony processing, associated with poor theory of mind.
We used fMRI to examine neural circuitry underlying deficits in understanding irony in schizophrenia.
21 schizophrenic patients and 24 healthy subjects were studied. Short scenarios and three conditions were used: irony condition (IC), irony with linguistic help condition (IHC), and control condition (CC). We used event-related design. Scenarios started with a contextual part, followed by a 2–4s ISI. The ironic sentence appeared next, and a question followed. Between trials an ITI of 5–7s were used.
Patients performed significantly worse in the conditions (IC:p = 0.0003;IHC:p = 0.0034;CC:p = 0.0036). In the IC: patients activated the left insula, left anterior cingulum, right and left superior frontal gyrus (SFG), right middle frontal gyrus (MFG) during the contextual part, and activated the left inferior frontal gyrus (IFG), left middle temporal gyrus (MTG) and right superior temporal gyrus during the statement. In the IHC: patients activated the left precuneus, left IFG, left SFG, left and right MFG, right cuneus and left MTG during the context, and activated right SFG and left posterior cingulum during the statement.
Patients probably have an abnormal contextual processing and a missing activation of the theory of mind network during the interpretation of ironic statements. The given linguistic help proved to be efficient help for many patients in processing the context correctly, and in understanding ironic situations more successfully.
The aim was to determine the relation between characteristics of [123I]-ADAM binding to serotonin transporters (SERT) in several brain regions to different symptoms in patients diagnosed with major depressive disorder (MDD) and to analyze data for males and females separately. Differences of [123I]-ADAM binding in patients before and after treatment with Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant Citalopram were assessed.
12 non medicated patients (5 females and 7 males) diagnosed with MDD were examined by SPECT with specific Serotonin transporter radioligand [123I]-ADAM before and after treatment with SSRI Citalopram. We administered the dose of 10 mg Citalopram per day intravenously at first day, followed by a 6 days period of oral application. After 7 days of treatment patients were examined for second time with SPECT. The relationships between [123I]-ADAM binding and different aspects of major depression represented by HAMD items, assessed twice by Hamilton Depression-Scale (HAMD) once at baseline and second after treatment period, were evaluated.
We found significant correlations with significant gender differences between singular sub items of HAMD and indices of [123I]-ADAM binding in midbrain before and after treatment. These findings points to the need of data analysis separately in males and females. No correlations between HAMD total scores at baseline and indices were found.
SERT availability for 123-ADAM binding in the midbrain in drug naives as well as in treated patients with major depression disorder seems to be related to intensity of sub items in the HAMD and the outcome of treatment.
Patients with schizophrenia have difficulties in representing the mental states of others. the capacity to appreciate others’ mental states is called Theory of Mind (ToM). Usually patients in remission are able to pass first- and second order ToM tasks, but they have difficulties with understanding more complex situations. A faux pas (FP) task contains a social situation when someone says something he or she should not have said, or something awkward. Understanding these situations requires higher-order ToM skills. in our study faux pas tasks were used to assess mentalization deficits among patients with schizophrenia in remission.
Seventeen patients and seventeen matched control individuals were evaluated. ToM skills were assessed by computerized FP tasks. the answers and the time the participants used to read the stories and answer the questions were recorded. the participants carried out 5 FP tasks and 5 control tasks.
Patients with schizophrenia performed significantly worse in faux pas tasks (p=0,0033), and memory questions (p=0,0033). Patients needed significantly more time to read both faux pas (p=0,0098) and control stories (p=0,0002). However the patients did not spend significantly more time to answer the questions then the control subjects (p=0,9966 p=0,8705).
Patients with schizophrenia performed a sinificant impairment in ToM tasks. Beside, an improving tendency was found also in the patient's and in the control group's answers suggesting a capacity to “learn” in the dimension of mentalization.
The endophenotype concept of schizophrenia represents an important approach in the exploration of the neurobiology of the illness. An important characteristic of an endophenotype, that it can be found among the healthy, first-degree relatives of patients with schizophrenia.
We evaluated two systematic reviews of studies on two potential endophenotypes (theory of mind and informative morphogenetic variants) to confirm the possibility of them as biological and cognitive markers of the illness.
We planned to explore data from theory of mind and informative morphogenetic variant studies among the relatives of schizophrenia patients.
We evaluated two researches of studies published in PubMed, Medline,Web of Science and PsycINFO between the period of 1968 and 2014 (informative morphogenetic variants studies) and 1980 and 2014 (theory of mind studies).
11 studies on the appearence of informative morphogenetic variants in the relatives of schizophrenia patients were found with mixed results, while 15 studies and two meta-analyses were analysed on theory of mind studies among the first-degree relatives of patients with schizophrenia,the exploration of the latter studies showed also diverse findings.
Futher research is needed to clarify theory of mind and informative morphogentic variant alternations as endophenotypic markers of schizophrenia.
Acknowledgement: This study was supported by the National Brain Research Program Grant no. NAP KTIA NAP-A-II/12.
Pragmatic language skills were examined in schizophrenia patients compared to IQ-matched control subjects measured by the decoding of the flouting of the four Gricean maxims.
19 schizophrenic patients and 19 matched controls were evaluated. Five experimental conditions (all included four stories) were used, such as „quantity maxim” (QNM) condition, „quality maxim” (QLM) condition, „relevance maxim” (RM) condition, „manner maxim” (MM) condition and "control” (C) condition. An investigator presented the stories and asked for the hidden communicative intentions. PANSS scores and general intelligence were also measured.
Patients with schizophrenia performed significantly worse than controls in each of the conditions containig the flouting of the Gricean maxims. The response accuracy in the C condition was not differed significantly between the two groups (QNM:p< 0.001; QLM:p< 0.001; RM:p< 0.001; MM:p< 0.001; C:p=0.487). Significant positive correlations were found between QLM and IQ (p< 0.001) and between RM and IQ (p=0.025), and there was no significant correlatios between PANSS scores and response accuracy. Full scale IQ was not differed significantly between the two groups (p=0.095).
We found that a complex pragmatic language deficit exists in schizophrenia. The impairment do not seem to have a relationship with symptom severity. Besides, it seems, that good intellectual function supports pragmatic language skills in schizophrenia.
Although companies increasingly focus on the social dimension in corporate sustainability, there seems to be a lack of understanding how and to what extent disability and accessibility frameworks and activities are integrated in corporate sustainability reports. In this article, we aim to close this gap by (a) analysing the disability and accessibility (D&A) activities from the largest 50 companies in Europe based on their corporate sustainability reports, and (b) advancing a simplified conceptual framework for D&A that can be used in corporate reporting. In particular, we provide an overview about corporate D&A reporting and associated activities according to three identified areas: (a) workforce, (b) workplace, and (c) products and services. Our findings are twofold: First, the majority of the companies address D&A in their corporate sustainability reports mainly under the diversity umbrella, but lack a detailed debate about the three identified areas. Second, we found that existing frameworks for D&A are hardly used because either they are not focused on corporate reporting or seem too difficult or complicated to complete. Thus, our framework not only represents a first opportunity to foster the implementation of a D&A framework within the social dimension of corporate sustainability reports, but also presents a holistic yet flexible management tool that takes into account the most critical elements while shaping implementation, directing evaluation and encouraging future planning of D&A initiatives. As such, this study contributes to and extends the limited amount of research of D&A activities in the social dimension in corporate sustainability reporting.
This article concerns English proper noun modifiers denoting organizations, people and places and their German and Swedish correspondences. It supplements previous studies touching upon contrastive comparisons by providing large-scale systematic findings on the translation correspondences of the three aforementioned semantic types. The data are drawn from the Linnaeus University English–German–Swedish Corpus (LEGS), which contains popular non-fiction, a genre previously not studied in connection with proper noun modifiers. The results show that organization-based modifiers are the most common and person-based ones the rarest in English originals. Compounds are the most frequent correspondences in German and Swedish translations and originals with genitives and prepositional phrases as other common options. The preference for compounds is stronger in German, while it is stronger for prepositional phrases in Swedish translations, reflecting earlier findings on language-specific tendencies. Organization-based modifiers tend to be translated into compounds, and place-based modifiers into prepositional phrases. German and Swedish translators relatively often opt for similar target-language structures. Two important target-language differences emerge: (i) compounds with complex heads are dispreferred in Swedish (US news show > *USA-nyhetsprogram) but unproblematic in German (US-Nachrichtensendung), and (ii) compounds with acronyms (WTO ruling > WTO-Entscheidung) are more frequent in German.
Vorderwald cattle are a regional cattle breed from the Black Forest in south western Germany. In recent decades, commercial breeds have been introgressed to upgrade the breed in performance traits. On one hand, native genetic diversity of the breed should be conserved. On the other hand, moderate rates of genetic gain are needed to satisfy breeders to keep the breed. These goals are antagonistic, since the native proportion of the gene pool is negatively correlated to performance traits and the carriers of introgressed alleles are less related to the population. Thus, a standard Optimum Contribution Selection (OCS) approach would lead to reinforced selection on migrant contributions (MC). Our objective was the development of strategies for practical implementation of an OCS approach to manage the MC and native genetic diversity of regional breeds. Additionally, we examined the organisational efforts and the financial impacts on the breeding scheme of Vorderwald cattle. We chose the advanced Optimum Contribution Selection (aOCS) to manage the breed in stochastic simulations based on real pedigree data. In addition to standard OCS approaches, aOCS facilitates the management of the MC and the rate of inbreeding at native alleles. We examined two aOCS strategies. Both strategies maximised genetic gain, while strategy (I) conserved the MC in the breeding population and strategy (II) reduced the MC at a predefined annual rate. These two approaches were combined with one of three flows of replacement of sires (FoR strategies). Additionally, we compared breeding costs to clarify about the financial impact of implementing aOCS in a young sire breeding scheme. According to our results, conserving the MC in the population led to significantly (P < 0.01) higher genetic gain (1.16 ± 0.13 points/year) than reducing the MC (0.88 ± 0.10 points/year). In simulation scenarios that conserved the MC, the final value of MC was 57.6% ± 0.004, while being constraint to 58.2%. However, reducing the MC is only partially feasible based on pedigree data. Additionally, this study proves that the classical rate of inbreeding can be managed by constraining only the rate of inbreeding at native alleles within the aOCS approach. The financial comparison of the different breeding schemes proved the feasibility of implementing aOCS in Vorderwald cattle. Implementing the modelled breeding scheme would reduce costs by 1.1% compared with the actual scheme. Reduced costs were underpinned by additional genetic gain in superior simulation scenarios compared to expected genetic gain in reality (+4.85%).
A comparison of Vienna and Berlin, the two most significant centres of German-speaking decadence, provides insight into the relationship of social class and aesthetic experience in the waning years of the Austro-Hungarian Empire (1897–1914) prior to World War I and during the tumultuous period of the Weimar Republic (1919–1933). The cultural and urban development of both cities, in their shared departure from nineteenth-century certainties, qualifies them for comparison in the context of decadence: Vienna’s imperial decline clashed with a radical re-thinking of tradition in art, and Berlin’s expressionistic distortions brought forth a brutal modernity that conservative thinkers considered to be the expression of racial degeneracy. To show how social history shaped the aesthetics of decadence at the time, the chapter focuses on the decadent art and writing of Gustav Klimt, Sigmund Freud, and Arthur Schnitzler in Vienna, followed by Otto Dix, Alfred Döblin, and Christopher Isherwood in Berlin.