In breast cancer screening, two readers separately examine each woman’s mammograms for signs of cancer. We examined whether preventing the two readers from seeing each other’s decisions (blinding) affects behaviour and outcomes.This cohort study used data from the CO-OPS breast-screening trial  where all discrepant readings were arbitrated. Multilevel models were fitted using Markov chain Monte Carlo to measure whether reader 2 conformed to the decisions of reader 1 when they were not blinded, and the effect of blinding on overall rates of recall for further tests and cancer detection. Differences in positive predictive value (PPV) were assessed using Pearson’s chi-squared test.p value 0.832). PPV was 22.1% for blinded versus 20.6% for not blinded (p < 0.001).When reader 1 recalls, the probability of reader 2 also recalling was higher when not blinded than when blinded, suggesting readers may be influenced by the other’s decision. Overall, women were less likely to be recalled when reader 2 was blinded , with no clear pattern in cancer detection rate  which would result in bypassing arbitration and negate some of the benefits of double-reading. We found a relationship between blinding the second reader and slightly higher PPV of breast cancer screening, although this analysis may be confounded by other centre characteristics.• In Europe, it is recommended that breast screening mammograms are analysed by two readers but there is little evidence on the effect of ‘blinding’ the readers so they cannot see each other’s decisions.• We found evidence that when the second reader is not blinded, they are more likely to agree with a recall decision from the first reader and less likely to make an independent judgement . This may reduce overall accuracy through bypassing arbitration.• This observational study suggests an association between blinding the second reader and higher positive predictive value of screening, but this may be confounded by centre characteristics.The online version contains supplementary material available at 10.1007/s00330-021-07965-z. Breast cancer screening is implemented in many European countries. European quality assurance guidelines recommend that mammograms are examined for signs of cancer by two radiologists (readers) using two mammographic views , 2. Therp = 0.01) [p < 0.001 for ultrasound-guided core needle biopsy (CNB), and 5.9 vs 4.7 per 1000 screens p = 0.013 for stereotactic CNB) [An aspect of double reading that has received little research to date is the blinding of reader 2 to the decisions of reader 1. Previous European guidance has recommended blinding, but the most recent version omits any recommendation on blinding except for in research studies [ = 0.01) , albeit tic CNB) . These rtic CNB) .In his monograph on errors in radiology, Smith  introducIf non-blinded decision-making can introduce alliterative bias, this could affect rates of recall, cancer detection, and outcomes for women attending screening. Optimising reading conditions could improve the balance of benefits and harms of breast screening. The aim of this research was to determine the effect of blinding the second reader in breast cancer screening on alliterative error and subsequently the effect on screening accuracy , in a population breast screening programme which uses arbitration of discrepant reader decisions.This study is reported using the ‘STROBE’ statement . The stuData were extracted from the NBSS system. Fields which indicate the ‘blind’ status at the time reader 1 and reader 2 saved their opinions were extracted. Reader 1 selects whether reading is blinded and then the second reader can change this during their reading session. When the blind reporting option is selected in NBSS, it masks the opinions of the previous reader by showing ‘Entered’ in place of the opinions. In the blinded reading condition, reader 2 could still ascertain what reader 1 decided by looking through the paper notes; however, this would be rare due to time constraints in the high-volume screening environment.Summary statistics of the characteristics of the women screened and the outcomes by the first reader, second reader and after arbitration of discordant decisions were presented by whether reader 2 was blinded. To investigate whether alliterative bias was present, we compared the proportion of cases where there were discordant decisions between readers using a chi-squared test. The hypothesis was that blinding the second reader would increase disagreements by reducing alliterative bias. We then directly modelled whether the second reader was influenced by the first reader’s decision when not blinded, i.e. whether alliterative bias was present. The model outcome was the second reader decision, with fixed effects for whether reader 1 recalled the woman and whether reader 2 was blinded, and an interaction term between them.p value [We fitted a multi-level model using Markov chain Monte Carlo (MCMC) methods using R2MLwiN , which rp value –28. The p value of the z-score for an estimate (5% level) [To investigate whether any alliterative bias may affect screening accuracy, we modelled whether blinding the second reader was associated with differences in overall recall and cancer detection rates. Two interaction terms were considered for inclusion, based on the Bayesian deviance information criterion (DIC) to assess overall model fit and the % level) . An inte% level) . An inte2 test for independence, test for equality of two proportions and t test) to determine any significant differences. The positive predictive value (PPV) when blinding the second reader compared to not blinding was reported, using the reference standard of biopsy-proven cancer after recall from screening. Pearson’s chi-squared test was used to compare PPV in cases read blinded and not blinded. To assess the potential impact of centre confounding , all the above models were run with a subset of six centres which had a mix of blinded and non-blinded reading as a sensitivity analysis. A mixed protocol centre was one where there was at least 5% of blinded or not blinded out of the total number of mammograms read at the centre  were determined for blinded/non-blinded reader 2 with statistical testing ). We separated the women not recalled into ‘false negatives’  and ‘true negatives’ . For consistency within this analysis, anyone recalled, had no cancer detected, and had an interval cancer within 3 years of screen was classified as a true positive, rather than a false positive. We performed an equality of proportions test to determine whether these were statistically significant . The mean age of the women was 59, and 78.8% had previously attended screening . The study flow diagram is depicted in Fig. 2(1) = 32.46, p < 0.001). The disagreement rate difference increases to 5.60% points when the first reader recalls the case  when reader 2 is blinded versus  when reader 2 is not blinded (χ2(1) = 179.03, p < 0.001)  than when not   = 107.04, p < 0.001). However, reader 1  also recalled fewer women (0.26% points) when reader 2 was blinded  than when not blinded  (χ2(1) = 34.751, p < 0.001) indicating at least part of this effect may be due to confounding (Table Reader 2 (before arbitration) recalled 0.45% points fewer women when blinded  than when not blinded  (χ2(1) = 24.51, p < 0.001). A model assessing the effect of blinding reader 2 on the recall rate after arbitration is presented in Table Recall rate after arbitration was lower when reader 2 was blinded  compared to when they were not   (Supplementary Table 2(1) = 0.51, p = 0.48). The cancer detection rate overall (with arbitration) was similar when reader 2 was blinded  compared to when not  = 1.4, p = 0.2).Reader 2 (before arbitration) detected cancers in 0.84%  of women when blinded versus 0.83%  when not blinded (χp = 0.341), although the Bayesian p value suggests that 83.2% of estimates lie above an odds ratio of 1   where there is a mix of blinded/unblinded second readers showed similar results (Supplementary Table 2(1) = 4.0, p = 0.0449); with no significant evidence of any difference for disease grade (χ2(2) = 0.67, p = 0.7), the number of positive axillary nodes (χ2(2) = 3.0, p = 0.2), and the mean diameter of the tumour for blinded  12.6 mm) and not blinded . When invasive disease was not present, there was no evidence of an effect of blinding on grade of DCIS (χ2(2) = 1.99, p = 0.37).Tumour characteristics by whether reader 2 is blinded or not is shown in Supplementary Table D.2(1) = 14.9, p < 0.001)  for blinded and 20.6%  when not blinded (χ2(1) = 0.04, p = 0.84). The difference for specificity was statistically significant: 96.89% for blinded and 96.68% for not blinded (χ2(1) = 37.6, p < 0.001).Interval cancers within 3 years of screening were used to estimate test accuracy metrics and are shown in Table p < 0.001). We also found a difference  in reader 1 recall rates when reader 2 was blinded versus unblinded. This may be due to reader 1 changing their behaviour in anticipation of reader 2 viewing their decision, a training effect from independent reading, or it may be an indication of centre level confounding.We examined the effect that blinding reader 2 to the decision of reader 1 had on behaviour and outcomes using data from the English Breast Cancer Screening Programme. When reader 1 recalled, the probability of reader 2 recalling was around 5% points lower when blinded versus not (69.8% vs 74.7%), suggesting that without blinding they are influenced by the decision of reader 1 and alliterative bias is present. This has the potential to increase recall rates by bypassing arbitration in systems where there is arbitration of discordant decisions. We found that the overall odds of recalling women for further tests were lower and specificity was higher when reader 2 was blinded to the decision of reader 1 compared to when not blinded. Similarly, the PPV after arbitration when reader 2 was blinded was slightly higher (22.1%) versus when not . Differences between centres were however addressed by clustering by centre and reader as well as controlling by age and screening status. Finally, our 5% rule for designating a centre as blinded/not blinded/mixed was arbitrarily selected.In breast screening programmes with arbitration of discordant decisions between readers, blinding the second reader to the decision of the first may improve the PPV of breast cancer screening and reduce the number of women recalled for further testing. The results suggest that reader 2 might be influenced by, and conform to, reader 1’s decisions when not blinded, particularly if a woman has been recalled by reader 1 . So when reader 2 is not blinded, they appear to be copying some of the recall decisions of reader 1, and therefore bypassing the arbitration process and increasing recall rates and false positives. A previous study (where the arbitration was in a laboratory rather than screening practice context) predicted similar patterns , 14. TheOur results suggest that when not blinded reader 2 is influenced by reader 1’s decisions to recall  which would result in bypassing arbitration and negate some of the benefits of double reading. We found a relationship between blinding the second reader and slightly higher PPV of breast cancer screening, although this analysis may be confounded by other centre characteristics. We would recommend blinded over non-blinded double reading in centres that use arbitration of discordant decisions.ESM 1(DOCX 1934 kb)


Results illustrate that the short video, as part of our food communications, positively shapes consumer perception towards meat quality, labelling and traceability trust of Australian beef but has only slight or even negative effects on WTP. This could be due to the short video offering consumers a sense of supply chain visibility but not delivering the right messages to meet their expectation of blockchain credentials. Furthermore, short video storytelling effects vary among consumers with different socio-economic characteristics. Our results posit that short video storytelling can be a useful tool in communicating blockchain-credentialed food products but require the design of a tailor-made storytelling experience for diverse consumers.Short videos have become the most-liked medium for Chinese consumers to learn about a brand’s products or services. This paper assesses how short video storytelling shapes Chinese consumers’ perceptions towards blockchain-credentialed Australian beef and their willingness to pay (WTP). A controlled experiment with a one-minute short video was implemented in an online survey. Respondents in the treatment group watched the video before filling out the survey, whereas respondents in the control group did not. The paper analyses and compares the empirical results from local ( Globally consumers are looking for authentic food products that are safe and healthy . This isAustralian beef products are exposed to a higher counterfeiting risk in China . To builDigital technology has significantly changed the way to access and consume information. It is reported that 72% of people prefer watching a video over texts to learn about a product or service . ChineseThis paper fills these research gaps and examines the effects of short video storytelling in delivering blockchain-credentialed Australian beef products following an exploratory research approach. The study investigates the effects of a one-minute short video storytelling on consumer perceptions with respect to meat quality, trust in labelling and traceability data, and willingness to pay (WTP) using an in-field survey administered in control and treatment settings. The contribution of this study is two-fold. First, it offers an understanding of how a one-minute short video can shape Chinese consumers’ quality and trust perceptions towards blockchain-credentialed Australian beef products and its impact on WTP from a storytelling perspective. Second, it identifies those effects of short video storytelling vary among consumers with different socio-economic characteristics, which highlights the need for using diverse video strategies when targeting different groups of consumers.Following the introduction section, We review relevant literature pertaining to digital storytelling and short videos  and foodDigital storytelling refers to the way of using digital tools to tell stories, and store and exchange those stories on websites and social media networks in the Internet era ,22. The Digital technology has changed the ways of creating and consuming narrative stories ,35. AlthConsumer perception refers to an information process involving consumer exposure and attention to marketing stimuli and consumer interpretation to create a meaningful image and brand identity ,43. WhilA growing number of studies have explored customer perception of food products in terms of quality, label, traceability, authenticity and so on ,54,55,56The effects of how short video storytelling shapes consumers’ perceptions towards food quality, label trust and traceability of blockchain-credentialed Australian beef and affects their willingness to pay (WTP) were measured with a controlled experiment. The controlled experiment is exploratory in nature, consisting of a one-minute short video and six questions  that comThe one-minute video -illustrated the use of blockchain to verify key stages from paddock to plate and introduced people and stakeholders from local food production communities in regional South Australia and other supply chain participants. To ascertain food quality perception, the study examined whether Chinese consumers perceive Australian beef products cut and packed in Australia to be superior to those processed in China. Consumer trust in food labelling was measured by examining consumers’ level of certainty in the food provenance of the beef labelled ‘Australian cut and packed.’ The traceability trust refers to the level of consumer trust in the traceability information attached with the beef package via a digital fingerprint . The WTPRespondents were randomly assigned into either the control or the treatment group to answer the questions illustrated in wj.qq.com) that allows the delivery via WeChat to invited event attendees.The survey was conducted during a series of showcase dinner events across China’s four metropolitan cities Shanghai, Shenzhen, Beijing and Guangzhou from 18 to 25 November 2019. The survey was administered using an online survey platform  with respect to trust and meat quality perceptions between the control and treatment groups are found at a 95% confidence level for both local and foreign respondents. In other words, while our short video storytelling increases consumer perceptions towards meat quality, label trust and traceability trust, it did not yield significantly comparative differences.U test for WTP variables between groups. No significant differences  for WTP between the control and treatment groups were observed at a 95% confidence level for both local and foreign respondents. This means that our short video intervention did not yield significant differences.Little is known about the effect of digital storytelling on consumer perceptions and behaviours in the food industry. Our results corroborate findings of previous studies that focuses on consumer perceptions and purchase decisions but also demonstrate new insights into the use of digital video storytelling in a new field. Comparing the responses from the control and treatment groups shows that our short video storytelling intervention increases consumer trust in the Australian ‘portion cut and packaged’ label and traceability information. This can be attributed to the improved transparency of the supply chain processes, which has been revealed in previous work . Most loFüzesi et al.  found a U tests for consumer trust and quality perceptions between the control and treatment groups show no significant differences at a 95% confidence level for both local and foreign respondents. Similarly, there are no significant differences at a 95% confidence level between treatments and controls in WTP price thresholds. These results show that while our current short video storytelling intervention increases consumer perceptions towards trust in food labelling and traceability data as well as quality, it is not powerful enough to yield significant differences when comparing results between the control and treatment groups.Our research investigated consumer trust and perception research in a comparative setting, which differs from early research. The Mann–Whitney Aligning with early consumer behaviour research in the food industry, our study explored if the effect of short video storytelling differs among consumers’ social-demographic characteristics. Our results contradict previous studies exploring consumers’ willingness to pay a premium for traceability certified beef  and consThis study underpins the Stimulus-Organism-Response (S-O-R) theory from the perspective of a short video storytelling intervention. The S-O-R theory posits that an individual’s response is driven by their exposure to environmental stimuli  and therThis study also offers practical contributions to knowledge. Videos have become a powerful marketing tool, which is used by 86% businesses surveyed in 2021 . AccordiUsing short video storytelling to interpret blockchain credentials leads to changes in consumer confidence and trust in Australian beef products processed in Australia and China. This finding provides additional benefits to Australian businesses building China-based processing plants and Chinese food importers. Our ANOVA results reveal that short video storytelling effects vary among consumers according to different socio-economic characteristics. With this understanding, businesses should be aware of the importance of identifying how to deliver the right digital content information to the targeted population when they use short video for product storytelling. Furthermore, short videos can be an effective and entertaining tool to convey authentic food provenance stories and offer a new and emerging genre of consumer information in the complex and rapidly changing digital world, where consumers are already exposed to an overabundance of information in their everyday lives.This present study implemented and tested a controlled experiment to investigate the effects of a short video storytelling intervention on consumer perceptions of meat quality, label, and traceability trust and on willingness to pay among consumers in China. By comparing the responses from local and foreign respondents in the control and treatment settings, our exploratory study revealed that while the short video storytelling intervention did not yield significant differences between the control and treatment groups, it did have a positive influence on consumer  perception of quality and trust of Australian beef. Further, the effect of the short video storytelling intervention varies among consumers according to different socio-economic characteristics. The novelty of this study lies in offering an understanding of how short video storytelling can shape consumers’ quality and trust perceptions towards Blockchain-credentialed Australian beef and affect WTP from a short video storytelling perspective.Although offering valuable early insights, this study has a few limitations that can prompt inspiration for further research. First, our study is exploratory in nature with a relatively small sample of 103 consumers situated in four metropolitan cities in China, which could lead to biased results. Accordingly, further research is required in order to produce findings generalisable to a broader context. Additionally, comparative research looking at potential differences in consumer perceptions depending on residency in different Chinese city tiers may deliver interesting results . Second,Given the exploratory nature of our study and the abovementioned limitations, further studies are suggested to evaluate the role and impact of short video storytelling more comprehensively, with either more controlled experiments or qualitative research approaches. Measuring the effectiveness of short videos in comparison with other multimedia tools is also a promising research direction. As short videos can be presented with user-generated content (UGC) and professional-generated content (PGC), future research could also be tasked with providing new insights into the value of short video storytelling by comparing the effects of UGC and PGC. Finally, as consumer perceptions are not stable but rapidly evolving over time , future


Endovascular therapy is the primary treatment modality for dural arteriovenous fistulas. Pre-treatment angiographic evaluation of dural fistulas must rule out the presence of a mixed pial component or supply from pial-dural collaterals, as the pial supply must be closed before definitive occlusion of the draining vein to prevent iatrogenic rupture. In this report, we described a case of a mixed pial-dural arterial venous malformation (AVM), which was effectively treated with a sequential transarterial and trans-cortical venous embolization. Endovascular therapy is the primary treatment modality for dural arteriovenous fistulas (dAVFs). The presence of a mixed pial component or supply from pial-dural collaterals is rare, however should be identified prior to treatment. In this report, we described a case of a mixed pial-dural arterial venous malformation (AVM), which was effectively treated with a sequential transarterial and trans-cortical venous embolization.via a bridging vein into the anterior pontomesencephalic system. This in turn drained into the right basal vein of Rosenthal via the peduncular vein. At the junction of the anterior mesencephalic and peduncular veins was a posteriorly directed bilobed venous varix which measured 13 mm in length × 5 mm in width  was placed at the right jugular bulb. Through the Ballast, a Sofia Flow Plus 6F catheter  intermediate catheter was advanced over a Headway Duo 156-cm microcatheter and Synchro Select microwire into the right vein of Galen. To reach the recipient vein, the microcatheter was replaced with a Headway Duo 167 cm  microcatheter. Over a Traxcess microwire , this microcatheter was carefully advanced past the varix, through the anterior pontomesencephalic system, and into the venous pouch using a roadmap from the left vertebral artery injection .Then, through the Behnchmark catheter , a Sofia 5F catheter  was navigated into the basilar artery over a Headway Duo 156 cm, 167 cm  microcatheter and Synchro select microwire . The microcatheter was placed into the right SCA and advanced into one of the branches supplying the AVM nidus. The microcatheter was placed just proximal to the takeoff of a tiny pedicle supplying the lateral aspect of the nidus. Given the small caliber of the pedicle, it was decided to close the branch from this position with additional non-target embolization of supply to the superior and lateral aspect of the right cerebellum. A small amount of Onyx 18  (<0.2 ml) was injected to achieve proximal closure of the small feeding pedicle, and the microcatheter was retrieved. Through the 5F SOFIA, another Headway Duo 156-cm microcatheter was advanced into a direct feeder supplying the medial aspect of the AVM nidus. A small amount of Onyx 18 (<0.2 ml) was injected achieving closure of the pedicle with partial penetration of the nidus. The microcatheter was retrieved.via the petrosal branch of the right MMA. To facilitate controlled Onyx embolization of the venous pouch, two Target 360 Nano coils  were placed into the pouch through the Headway 167-cm microcatheter.After the closure of the pial supply to the AVM, a second Benchmark catheter was placed into the right common carotid artery where angiography confirmed arterial supply to the dural component of the AVM via the petrosal branch of the right MMA. To facilitate controlled Onyx embolization of the venous pouch, two Target 360 Nano coils  were placed into the pouch through the Headway 167-cm microcatheter. Then, ~0.3 ml Onyx 18 was injected until the recipient vein was occluded , as endovascular treatment must occlude the pial supply prior to closure of the dural fistula. Because definitive treatment of dural fistulas requires closure of the recipient vein, the presence of a mixed pial component or pial collateral supply can result in AVM rupture due to outflow obstruction as seen with brain AVMs , 2.Owing to the dural supply from the petrosal branch in this case, transvenous embolization was necessary to prevent injury to the facial arcade. The ability to traverse the cortical veins of the posterior fossa to reach the venous pouch illustrates the increased safety profile afforded by the current generation of highly compliant and deliverable intermediate catheters and microcatheters. Endovascular closure of the draining vein can be achieved using coils, liquid embolic agent, or a combination as in this case. Flow-directed microcatheters that can also deliver detachable coils are particularly useful for this application. Depending on the length and tortuosity of the cortical venous drainage, it is often not possible to achieve transvenous access to the fistula site, in which case a multimodal approach using radiosurgery or neurosurgery is necessary.A unique feature of this case was the relative prominence of the venous varix which was disproportionate to the overall degree of venous ectasia. The size of the varix and its eloquent location with the cerebral peduncle contributed to the patient's neurological deficit in the absence of rupture.Endovascular therapy is the mainstay of treatment for dAVFs. Mixed pial-dural AVMs are rare lesions that are important to identify because treatment must target the pial supply prior to definitive closure of the draining vein to prevent iatrogenic rupture.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author(s).Ethical review and approval was not required for the current study in accordance with the local legislation and institutional requirements. Written informed consent was not required for the current study in accordance with the local legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Objective: This article examines the influence of the implementation of Soteria elements on coercive measures in an acute psychiatric ward after reconstruction in 2017, thereby comparing the year 2016 to the year 2019. The special feature is that this is the only acute psychiatric ward in Hennigsdorf Hospital, connected now both spatially and therapeutically to an open ward and focusing on the treatment of patients suffering from schizophrenia and schizophrenia spectrum disorders.Methods: The following parameters were examined: aggressive assaults, use of coercion , duration of treatment in open or locked ward, type of discharge, coercive medication, and dosage of applied antipsychotics. For this purpose, the data of all legally accommodated patients in the year 2016 (before the reconstruction) and 2019 (after the reconstruction) were statistically analyzed in a pre–post mirror quasi-experimental design.Results: In 2019, the criteria of the Soteria Fidelity Scale for a ward with Soteria elements were reached. In comparison to 2016 with a comparable care situation and a comparable patient clientele, there was now a significant decrease in aggressive behavior toward staff and fellow patients, a significantly reduced number of fixations, a significantly reduced overall duration of inpatient stay, and a significant increase in treatment time in the open area of our acute ward.Conclusion: The establishment of Soteria elements in the acute psychiatric ward leads to a verifiable less violent environment of care for severely ill patients and to a drastic reduction in coercive measures. Since more than 100 years, there were efforts in psychiatry to reduce coercive measures with the goal not only to treat inpatients with respect but also to protect those working there and thus avoid a “brutalization” of the staff . In the In German-speaking countries, the Soteria concept was implemented in some hospitals in open wards . In the LWL Klinik Gütersloh, under the chief medical direction of Professor Klaus Dörner, Soteria elements were also established in the acute psychiatric ward, showing a reduction in coercive and violent measures. They also report an improvement in the ward atmosphere for patients and staff , howeverIn addition, there have been continuing efforts to reduce coercive measures in the acute wards of psychiatric hospitals. Last but not least, the ratification of the UN Convention on the Rights of Persons with Disabilities , which oIn 2017, our acute psychiatric ward was reconstructed and, in order to reduce coercive measures, in the following year we tried to establish an alternative way to treat our acutely ill patients by introducing Soteria elements. We are responsible for the psychiatric treatment of the Oberhavel (Brandenburg) catchment area in Germany and can thus compare the same patient clientele before and after the reconstruction and implementation of Soteria elements.To the best of our knowledge, we are at that time the only hospital in Europe to try to establish Soteria elements in the only existing acute psychiatric inpatient unit of the hospital. With the structural change to divide the acute locked ward into a large open and a small, locked area, spatially and therapeutically connected, experiences of the Soteria concept are linked with those of the open door projects. In contrast to open door, Soteria wards, or a classic Soteria setting though, we have created a setting whereby patients requiring acute psychiatric treatment are cared for by the same team and on the same ward as those now less acute. We were thus able to provide all patients suffering from schizophrenia or schizophrenia spectrum disorder individually need-adapted with elements of the Soteria treatment, regardless of the severity of the present state. The effects of the complex intervention carried out on the frequency of special incidents, coercive measures, treatment duration as well as the level of neuroleptic dosage and frequency of the given coercive medication are the goal of our study presented here.The principal idea was to change an acute psychiatric ward with 23 beds, optionally closed, to an open acute ward with Soteria elements (15 beds) and, additionally, a small protected area with six beds [corresponding to the requirement of the Psychiatry-Enquête of 1975: the size of an acute psychiatric ward should not exceed 16 beds ]. Both wThe Oberhavel catchment area is located in the north of the greater Berlin area in the federal land of Brandenburg and has a population of about 202,000. The Department of Psychiatry and Psychotherapy of the Oberhavel Hospitals, with 101 beds and 57 day clinic places at the locations such as Hennigsdorf, Oranienburg, and Gransee as well as a large outpatient clinic, is responsible for the psychiatric treatment in the Oberhavel county. The overall aim of the hospital is to work according to a disorder-specific group therapy concept. In addition to the acute ward with Soteria elements and the crisis intervention ward, we also have an interdisciplinary geriatric–gerontopsychiatric ward, a ward for patients with affective disorders and a ward for addiction and comorbid disorders. The disorder-specific organization of our department leads to a desired focus on psychotic disorders in our acute ward and allows this ward to be kept small. The acute care unit continues to provide care for patients in the Oberhavel catchment area who are detained according to state law or according to legal guardian law in the case of reduced ability to have insight and control and for patients who voluntarily seek inpatient treatment with an acute psychosis.The opening of the acute care ward with Soteria elements took place in June 2018 (a detailed description of the concept and its implementation is reported elsewhere). The process was monitored in weekly, multi-professional working group meetings. The team members were given various internal and external training opportunities, and the team was externally supervised once a month. During the entire period from 2016 to 2019 (and beyond), the senior staff of the ward and the hospital did not change. In addition, there was no change in the organization of our other inpatient units or the care provided by our day-care treatment places and our outpatient services. The above-mentioned Soteria facilities provided additional support through professional exchange. The Soteria Fidelity Scale was used to evaluate the implementation, on which recognition by the International Working Group Soteria (IAS) is based . In the via CPZ, the determination of which was based on Benkert and Hippius  and 2019  were analyzed in a pre–post mirror quasi-experimental design: special incidents Hippius .Data collection was based on the compulsory annual reports to the Ministry of Health in Brandenburg on patients' legally accommodated and on special events. The data were supplemented and expanded by the letters of discharge and, since the introduction of the electronic patient file in January 2019, the electronic records on the medical order of coercive measures were added. The discharge medication documented in the discharge letter was used to analyze the CPZ. As CPZ levels can be influenced by comorbid substance use disorder , 29, we The statistical evaluation was done with the programs SPSS 22.0 and Microsoft Excel. The target parameters were evaluated regarding differences in the groups (treatment in 2016 vs. treatment in 2019). Since the CPZ variable was not normally distributed, the Kruskal–Wallis test was used for group comparison. The chi-square test was used to calculate the frequency differences of nominally scaled variables. For metric variables, we used uni- or multivariate analysis of variance with Bonferroni adjustment for multiple testing.https://soteria-netzwerk.de/soteria-einrichtungen).The criteria according to the Soteria Fidelity Scale  as “ward2(5/97) = 6.91, p = 0.228). For the years 2016 and 2019, the care situation and the characteristics of the patients in the catchment area can generally be considered comparable.2(2/24) = 11.68, p = 0.003].For the years 2016 and 2019, a total of 24 special incidents were reported to the Ministry of Health, all of which concerned patients with involuntary treatment. In 2016, no unauthorized leaving and no destruction of furniture were reported; however, 13 incidents of physical assault were reported. In 2019, four incidents of unauthorized leaving, four incidents of physical assault, and three incidents of destruction of furniture were reported see . The ana2(2/17) = 2.55, p = 0.279] since the number of reported cases is low. Nevertheless, not a single case of serious assault was reported in 2019.The difference in severity of assaults misses statistical significance  or actual  involuntary accommodation time. Due to the large scattering, the differences in mean values are not significant. For 2019, however, a slight reduction is seen (see F(1/97) = 4.93, p = 0.029] just as the treatment time in the open area had significantly increased . Nevertheless, there was no difference in the number of days that the patients decided to continue treatment voluntarily . The exclusion of patients with long-term involuntary accommodation did not also result in any significant difference in values or statistics and is therefore not shown.The comparison of frequencies of hospitalization and detention time was analyzed. Between the years 2016 and 2019, there was no significant difference in the approved . The exclusion of the patients with long-term involuntary hospital treatments according to BGB  showed no difference in outcome and is therefore not reported.There was no significant difference in the number of multiple hospitalizations of an involuntarily accommodated patient  was not statistically significant. This means that, in spite of the possibility of a treatment in the open ward for accommodated patients in 2019, there was no increase in the number of unauthorized leavings.Comparing 2016 and 2019, the relation between planned discharge and premature discontinuation  nor the frequency of court-approved continuous medication  changed.The frequency of administered acute forced medication, the frequency of court-approved continuous medication, and the number of mechanical fixations were analyzed see . BetweenF(1/97) = 6.27, p = 0.014, see As 2(1/97) = 0.405, p = 0.524]. Out of the resulting 74 patients receiving psychopharmacological medication, 65 patients were receiving antipsychotic medication. We evaluated the CPZ for those 65 patients (see 2(1/65) = 1.57, p = 0.692]. Even for the group of patients with a psychotic crisis with or without additional substance use disorder (N = 63), we could not find a CPZ change . Similarly, we found no significant difference in CPZ levels between patients with additional substance use disorder and patients with a psychotic crisis solely . Statistical significance was missed here in both 2016 and 2019 and is therefore not reported.In 2016, 12 of 45 involuntarily accommodated patients were discharged without psychopharmacological medication. In 2019, 11 of 52 were discharged without medication; this difference is not statistically significant . In Henvia CPZ), bed occupancy of the acute ward, number of staff on duty, professional experience of staff, and attempts at de-escalation prior to implementation of restraint  was introduced (01.01.2019), which may also have had an effect on the shortening of the length of stay. The extended length of stay in the open area of our acute ward will probably not have been affected by this and can therefore be associated with the implementation of Soteria elements.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Since the analysis of the data did not imply the direct involvement of patients, an ethics approval for the study was not required. The Oberhavel Klinik Hennigsdorf is obligated to report all cases of coercive measures to the Ministry of Health in Brandenburg/Germany annually. We exclusively analyzed data extracted from those annual reports and completed the data with anonymized information from the hospital information system.All the authors listed have made a substantial, direct and intellectual contribution to this work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Contrary to spontaneous yawning, which is widespread in vertebrates and probably evolutionary ancient, contagious yawning—yawning triggered by others’ yawns—is considered an evolutionarily recent phenomenon, found in species characterized by complex sociality. Whether the social asymmetry observed in the occurrence of contagious yawning is related to social and emotional attachment and may therefore reflect emotional contagion is a subject of debate. In this study we assessed whether yawn contagion was enhanced in pregnant women, a cohort of subjects who develop prenatal emotional attachment in preparation for parental care, via hormonal and neurobiological changes. We predicted that if yawn contagion underlies social and emotional attachment, pregnant women would be more likely to contagiously yawn than nonpregnant, nulliparous women of reproductive age. We gathered data in two different settings. In the experimental setting, 49 women were exposed to video stimuli of newborns either yawning or moving their mouth (control) and we video-recorded the women during repeated trials to measure their yawning response. In the naturalistic setting, 131 women were observed in a social environment and their yawning response was recorded. We tested the factors influencing the yawning response, including the reproductive status (pregnant vs. not pregnant). In both settings, yawn contagion occurred significantly more in pregnant than nonpregnant women. By showing that pregnant women were most likely to respond to others’ yawns, our results support the hypothesis that the social variation observed in yawn contagion may be influenced by emotional attachment and that yawning in highly social species might have been coopted for emotional contagion during evolution. Pan troglodytes, Vick and Paukner Theropithecus gelada, Palagi et al. Macaca tonkeana, and Japanese macaque, M. fuscata, Zannella et al. Homo sapiens, Provine Pongo pygmaeus; van Berlo et al. Pan paniscus: Demuru and Palagi Panthera leo: Casetta et al. Canis lupus lupus: Romero et al. Ovis aries: Yonezawa et al. Mirounga leonina: Wojczulanis-Jakubas et al. Sus scrofa: Norscia et al. Melopsittacus undulates: Gallup et al. Whereas spontaneous yawning is independent from the perception of others’ yawns, contagious yawning occurs when the yawn emitted by a subject (trigger) acts as a releasing stimulus , the evidence of interspecific yawn contagion (dog/human) and its modulation is mixed , and pregnant women represent a cohort of subjects that is biologically and psychologically “equipped” for mother-infant emotional attachment , and the naturalistic setting, with the observational data collected on the study subjects in their environmental social context . The study subjects were different for the two data collection types . On one hand, the experimental approach allowed the control or removal of certain variables  but subjects were extrapolated from their social context. On the other hand, the naturalistic approach allowed the verification of the possible influence of pregnancy on the yawning response in ecological  conditions. Because either setting has advantages and drawbacks, we combined the experimental and naturalistic approach.0 increases the probability to have another yawn by the same subject at t(0+X), where X is the increasing unit of time; Kapitány and Nielsen A yawn response can be considered to occur within 5 min after perceiving someone else’s yawn (the trigger’s yawn) Provine , with a The video used for the experimental procedure (detailed in the next section) was composed of a black-and-white stimulus video and black-and-white neutral landscape videos. The stimulus video was built by joining 4–8 s clips showing two newborns  while yawning  or moving their mouth (control condition) Fig. . The expThe videos with neutral landscapes were built from clips downloaded from a specialized website (pixabay.com). A beep sound added at the beginning of the video was downloaded (as.wav file) from freesound.org. Both the videos and the beep are available under Creative Commons CC0 license (Public Domain Dedication). Under this license, video and sound uploaders have waived their copyright and related or neighboring rights to the videos, which can be freely adapted and used without attributing the original author or source.The full video (.avi) was obtained by merging the different videos into a single video (1820 × 720 px) in the following order: 20 s of neutral landscape video, the first stimulus video (45 s), 5 min of neutral landscape video, the second stimulus video (45 s), 3 min of neutral landscape video. The central period of 5 min of neutral landscape ensured that 3 + 2 min elapsed from the first to the second round of stimuli, in order to reduce the probability of autocorrelation.The whole video was converted into black and white to remove any possible reference to the baby’s gender (based on color of clothing or other cues). The video editing was carried out via the freeware Avidemux 2.7. Two versions of the full video were assembled, and both videos showed yawning and control stimuli; one video showed the yawning stimuli before the control (YC video), and the other showed the control stimuli before the yawn (CY video).N = 26, age range: 24–43 years old) participated in the trials on a voluntary basis during their monthly checkups at the clinic. Pregnancies ranged from 105 to 277 days (delayed delivery). Depending on their availability, the women underwent 1–6 trials . Nulliparous women of reproductive age  were tested at the Department of Life Sciences and Systems Biology  or in private houses. The sample size, with variably repeated measures, allows the use of Generalized Linear Mixed Models.A total of 292 experimental trials were carried out from June 2018 to January 2020, between 9:00 am and 7:00 pm. The trials with pregnant women were carried out at Dr. C. Vardé’s Obstetrics and Gynecology Clinic . Pregnant women . The subjects were white Italians, as inferred from physical traits and their last names. The newborns were unknown to all the tested subjects.In compliance with the applicable regulations , women signed an informed consent in which they agreed to participate in the trials and granted permission (1) to be video-recorded during the experiment and (2) to have the video used for the purposes of this study. The exact purpose of the trials (recording yawning during pregnancy) was not revealed until the end of the study period when the women were told that the experiment was about the evaluation of attentional levels during pregnancy.For each woman the trials were carried out by same experimenter . Right before the trial began, the woman was accompanied from the waiting room to a separate room and invited to sit on a chair in front of the screen, located at the height of the woman’s eyes. A camera had been previously located behind the screen at about 1.20 m distance, above the screen, so the face of the woman could be entirely recorded on video. The operator pressed the start button and the video started, preceded by 1-s blue screen with a beep sound. 20 s of neutral landscape clips were shown, while the operator left the room. After the first 20 s of neutral landscapes, when the woman was alone in the room, the first stimuli video started, marking the actual beginning of the trial. The woman watched the entire video, including stimuli and neutral sequences, lasting 9.21 min. The stimulus sequence (yawning/control or control/yawning) was randomized both within and across subjects .The face of the woman was recorded during the entire duration of the trial via a Canon Legria HFR36 to measure the number of yawns she exhibited while watching the experimental and the control video and in the following three minutes. The trials were carried out using a 15″ screen laptop . The videos shown to the women occupied the entire screen.Video analyses and data collection. Data were entered anonymously, by assigning an alphanumeric code to each woman. Videos were analyzed via the free software VLC 3.0.6 (©VideoLAN). For each trial the following pieces of information were included in the dataset: time, woman’s code, reproductive status (nulliparous or pregnant), age, whether the woman yawned or not in the three minutes following the display of the first yawning or control stimulus, condition (yawning/control), the seconds the woman spent looking at the screen , stimulus presentation sequence (yawning/control or control/yawning).We categorized a yawn as such in these cases: (a) jaws open in a wide gape, deep inhalation, eye closing or narrowing (open yawns); (b) lip sealing, deep inhalation and at least one of the following patterns: nostril opening, eye narrowing, vacuum swallowing (nose yawns) .The levels of attention to the stimuli were overall excellent (n = 81) were collected live (with no video) in the waiting rooms of the Department of Obstetrics and Gynecology of the Hospital of Pinerolo  and data on the nulliparous women  of reproductive age  were collected at the Department of Life Sciences and Systems Biology  and in other settings  in 2019. These data also included observations of two pregnant women. Data were collected when conditions allowed unobstructed observation of all the individuals present, focusing on small, isolated groups, in absence of external perturbing events . During data collection the identity of each subject was anonymously indicated via an alphanumeric code. The women included in the database were observed for at least 30 min and did not show repeated or abnormal displacement behavior.For the data collection in the naturalistic setting we also considered pregnant and nulliparous women (as defined above). Observational data on the pregnant women , their basic information was known, including their reproductive state. As a further confirmation, none of the nulliparous woman showed signs of pregnancy or delivered between the end of data collection and the time this article was written. The pregnant women were not known personally, but the basic information needed for this study was obtained through conversation with the data collector (LA). Data were collected from between around 9:00 am and 11:00 pm by using the all-occurrences sampling method Altmann , with thWhen a subject yawned spontaneously (no faked yawn) in presence of at least one observer , the following data were entered in the calculation sheet: time, yawner dummy coded identity (trigger), the dummy coded identity of the woman  who could perceive the yawn (distance within 5 m), reproductive status of the potential responder (whether the woman was pregnant or nulliparous), social bond between trigger and potential responder (stranger or acquaintances), whether the woman yawned in the three minutes after the trigger’s yawn (yawning response). We collected 308 yawning bouts in the presence of pregnant and/or nulliparous women.Based on Norscia and Palagi , the socAs explained above, we considered the yawning response as occurring within a three-minute time slot from the yawn emitted by the trigger. To reduce the possible autocorrelation effect during yawn trains (subsequent yawns occurring within 3 min following a triggering yawn), only the first yawn following the last trigger’s yawn was recorded as response.t-test for two independent samples on age  and nonparametric Mann–Whitney tests for two independent samples (Siegel and Castellan p < 0.05). Montecarlo randomization  was applied for experimental time and sleep hours to account for pseudoreplication .To check for possible differences in the two cohorts of women (pregnant and nulliparous), we ran the parametric N = 292 cases). The occurrence of a yawning response was entered as a dependent, binomial variable . The following fixed factors were included in the full model: condition , attention level (numeric variable: number of seconds the woman looked toward the video stimuli), video sequence , time period  . A GLMM was run to verify what contextual factors could have an effect on the presence of yawning response (N = 146) or the control (N = 146) condition. In both models, the occurrence of yawning response was entered as a dependent, binomial variable . The fixed factors in the full model were age (numeric variable) and reproductive status . The woman’s dummy coded identity  was entered as random factor.Two additional GLMMs were ran to check which individual factors could influence the yawning response for either the yawning (N = 308 cases). The occurrence of yawning response was entered as a dependent, binomial variable . The fixed factors in the full model were (a) reproductive status , (b) social bond linking trigger and potential responder , and (c) time period  so they were included in the model as possibly having a divergent influence on the yawning response. The dummy coded identities of trigger and potential responder were entered as random factors owing to the variably repeated or unrepeated measures on the subjects.A GLMM was also run to verify what factors could have an effect on the presence of yawning response in naturalistic conditions , experiment time , and declared sleep hours .No significant difference was found between the two cohorts with respect to age distribution . Therefore, we moved on with a drop1 procedure. The GLMM indicated a significant effect of the condition  on the yawning response. We found a significant difference between the full model fitted versus the null model , with no predictor having a significant main effect on the response variable . Regarding the yawning video condition model, we found a significant difference between the full and the null models . Only reproductive status had a significant main effect on the response variable  on the yawning response. For the control video condition model, we found no difference between the full and the null models  on the yawning response.2 = 11.183, df = 5, p = 0.048). Therefore, we moved on with a drop1 procedure. The GLMM indicated a significant effect of bond and reproductive status . As a matter of fact, pregnant women were more likely to respond than nulliparous women to both video yawns of unknown infants in the experimental trials and live yawns from adults in the naturalistic setting Tables  and 5. TSince yawn contagion has been found to vary across the day  owing to data constraints, and despite showing an inverse correlation with reproductive status, the bond had a significant effect on yawn contagion, which was more likely between subjects who knew each other than between strangers. This finding is in agreement with previous literature showing that relationship quality has an influence on yawn contagion, whose likelihood increases as the strength of the social bond increases  had a significant effect on the yawning response in the yawning video condition but not in the control video condition (cf. Tables Overall, the different yawning response of pregnant women relative to women with no children can fall within the broad range of the behavioral changes that start occurring during pregnancy, such as motor activity and dietary choice variations (Crozier et al. The possible connection between yawn contagion and increased social and emotional bonding is also suggested by the fact that some of the areas that seem to be involved in yawn contagion (such as the ventromedial-prefrontal cortex, superior temporal sulcus, amygdala, insula, posterior cingulate, and precuneus; Nahab et al. In summary, by showing increased occurrence of yawn contagion in pregnant women—a cohort of subjects that is specifically “programmed” to recognize and respond to others’ emotions—this study provides support for the hypothesis that yawn contagion may, at least under certain circumstances, underlie emotional contagion (EBH; Palagi et al. The perception–action and the offspring care model both predict that subjects can preferentially attend the stimuli coming from closely bonded others, particularly caregiving individuals such as pregnant women toward babies Preston . Visual,Importantly, not all contagious yawning is triggered by emotional resonance, and that is not the point in question here. Contagious yawning also occurs between strangers (Norscia and Palagi Hence, although we cannot discard the possibility that other priming and motor mechanisms may also underlie the social asymmetry of yawn contagion, the hypothesis that this behavior has been coopted during evolution for emotional contagion still stands and gains further support.


Respiratory monitoring is receiving growing interest in different fields of use, ranging from healthcare to occupational settings. Only recently, non-contact measuring systems have been developed to measure the respiratory rate ( The monitoring of vital signs, such as the respiratory rate, heart rate, body temperature, and blood pressure, is essential to assess the general health status . Among oeglected ,3. Howevbalances . For inse of 21% . Additioiagnosed . In occureathing . For thereathing , depth sreathing , laser vreathing , and RGBreathing ,15,16. AAmong all non-contact methods, those based on optical sensors integrated into commercial video cameras introduce several advantages, such as low cost, the possibility of being used by a non-expert, and ease of use .There are different studies in which video cameras have been tested to monitor le, ref.  uses varle, ref.  tracks hle, ref.  tracks tle, ref. ,22 use tle, ref. ,19 are hle, ref.  if therele, ref. ,22 use Fle, ref.  uses LucIn literature, there are only a few studies aiming at investigating performances with different user postures and distance from the video camera  and thatWithin this context, the method that we propose tries to overcome the above mentioned limitations through a non-contact and unobtrusive measuring system for respiratory monitoring based on the analysis of RGB video-frames recorded with a mobile device for respiratory monitoring. The method includes an automatic selection of the ROI and a method for the recognition and elimination of movements not related to the breathing activity. Moreover, compared with the literature in which a narrower range of x,y) distribution of intensity A component proportional to the amount of direct light incident on the scene, called the illumination component A component proportional to the amount of light reflected by objects in the scene, called the reflectance A video captured with a CCD camera can be considered as a sequence of RGB frames (polychrome images). Each frame in RGB space is an image matrix consisting of primary elements called pixels to which an intensity level in the form of a numerical value expressed in bits is associated. In commercial RGB cameras, as in this work, 8 bits per channel are used (24-bit for RGB space). Indeed, images in RGB space are characterized by the property that each color can be represented using the superposition of three values , which encode the intensities of red (R), green (G), and blue (B) contributing to the specific color. Therefore, each RGB frame can be seen as a two-dimensional I<1 .Respiratory activity causes cyclical movements of the chest wall characterized by an expansion of the rib cage during inhalation, resulting in an upward movement of the thorax and a relaxation of the same during exhalation, resulting in a downward movement of the thorax. This cyclic movement generates consecutive changes in reflected light intensity that can be used to indirectly monitor respiratory activity through a CCD camera. In this work, two techniques  have been used to post-process data to extract the user’s respiratory pattern and, then, the Once the video is acquired from the RGB camera =xUB,0 which quations :(2)xROI=By recording a video of the chest wall region with a camera, the red, green, and blue (RGB) channels collect a mixture of the reflected signal together. So that, at each frame, three different intensity signals are recorded , as in Since the respiratory signal is pseudoperiodic, it is possible to associate the respiratory pattern with the periodic intensity of the pixels variations over time .f, the intensity components of each channel c is the color channel , green (G), and blue (B)). The proposed algorithm sums the intensity components obtained in the three channels and then averages them for each line y of the ROI, according to the following equation:Applying this method, an intensity signal is obtained over time for each pixel in the RGB channels. Therefore, at each frame f  were enrolled in this study to investigate the performance of the proposed measuring system with the proposed algorithms. Per each volunteer, trials were carried out at different postures  and user-camera distances , as shortly summarized in All the tests were carried out in compliance with the Ethical Approvals (ST-UCBM 27/18 OSS) and, prior to the tests, all the participants provided their informed consent. All the trials were carried out following COVID-19 restrictions .x = 1280 px, y = 720 px). All experiments were carried out indoor and with a stable amount of light delivered by neon lights. No restrictions have been placed on the clothing of the subjects, as shown in To capture the video, the built-in smartphone RGB camera  was used. The camera was configured to acquire 30 frames per second (fps) with a high definition resolution , was used to record the reference respiratory signal contextually to the video recording. This system consists of a thoracic belt and an electronic module and acquires the breathing pattern of the user by sensing the volumetric changes in the thorax by the means of a strain gauge . The refIn the first three trials see B each paThe collected videos were post-processed in MATLAB environment to extract the breathing patterns with the proposed algorithms. Per each trial, we retrieved ents see A. A thirIn this paper, we compared the To monitor the Before starting monitoring the The derivative of the signals extracted from the video , the siAfter the motion artefacts removal, the apnea stages were identified in all the signals. A typical apnea stage is characterized by a reduced signal variation. To automatically identify the apneas in all the signals we performed the following steps:As an example, the first subplot in Removing the mean from the signal ;Normalization between 0 and 1, so that even lower amplitude peaks were detectable within the window;Identification of all the local maxima on the signal by using a MATLAB nce with ;n breathing periods (n is the number of identified breaths), and of the average breathing period  at 2 m of distance from the camera. These results are in line with , in whic devices  (MOD ± L devices  (MOD ± L devices  (MOD ± L devices  (MOD ± LThe results obtained in this study are promising in the context of monitoring the


Malnutrition negatively impacts on health, quality of life and disease outcomes in older adults. The reported factors associated with, and determinants of malnutrition, are inconsistent between studies. These factors may vary according to differences in rate of ageing. This review critically examines the evidence for the most frequently reported sociodemographic factors and determinants of malnutrition and identifies differences according to rates of ageing.N = 68) were categorised according to their ageing rate: ‘successful’, ‘usual’ or ‘accelerated’.A systematic search of the PubMed Central and Embase databases was conducted in April 2019 to identify papers on ageing and poor nutritional status. Numerous factors were identified, including factors from demographic, food intake, lifestyle, social, physical functioning, psychological and disease-related domains. Where possible, community-dwelling populations assessed within the included studies (Low education level and unmarried status appear to be more frequently associated with malnutrition within the successful ageing category. Indicators of declining mobility and function are associated with malnutrition and increase in severity across the ageing categories. Falls and hospitalisation are associated with malnutrition irrespective of rate of ageing. Factors associated with malnutrition from the food intake, social and disease-related domains increase in severity in the accelerated ageing category. Having a cognitive impairment appears to be a determinant of malnutrition in successfully ageing populations whilst dementia is reported to be associated with malnutrition within usual and accelerated ageing populations.This review summarises the factors associated with malnutrition and malnutrition risk reported in community-dwelling older adults focusing on differences identified according to rate of ageing. As the rate of ageing speeds up, an increasing number of factors are reported within the food intake, social and disease-related domains; these factors increase in severity in the accelerated ageing category. Knowledge of the specific factors and determinants associated with malnutrition according to older adults’ ageing rate could contribute to the identification and prevention of malnutrition. As most studies included in this review were cross-sectional, longitudinal studies and meta-analyses comprehensively assessing potential contributory factors are required to establish the true determinants of malnutrition. Improvements in healthcare, along with the development of medical treatments and vaccines, have increased life expectancy worldwide . This haOne such challenge among older adults living in the community is risk of malnutrition and more specifically undernutrition  , 6. OldeWith the global increase in life expectancy, more attention is being drawn to different rates of ageing. In particular, the concept of successful ageing is now acknowledged to be an important area of research. Nonetheless, whilst there is general agreement on the characteristics typical of a person ageing at a successful rate, to date, there is no consensus on how this concept should be defined. One of the most used definitions for successful ageing is someone who is ‘free of disease and disability, has a high physical and cognitive functioning ability and has an active engagement with life in general’ . Rate ofMalnutrition in older adults is often under-recognised and poorly managed . This caUnderstanding and identifying factors that lead to malnutrition is critical for developing interventions aimed at preventing or delaying disability in older adults. This is particularly important in the community, where although prevalence is low, the greatest number of at-risk individuals reside , 28. ComTwo independent systematic searches  of PubMed Central and Embase databases were conducted in April 2019 to identify relevant papers on ageing and poor nutritional status. Duplicates were excluded (LAB and KL), and titles examined to assess suitability for inclusion (LAB and ML). Studies examining the sociodemographic factors associated with, or determinants of, malnutrition were included. The key search terms were as follows: the primary outcome ; the population sub-group ; and the exposure . Figure > 65 years, majority community-dwelling (> 80%), and conducted in Western populations  were selected for consideration. Studies containing populations from multiple countries were only included if the majority of the population came from the specified Western countries. As the standardised criteria for diagnosing malnutrition were only published in 2019 [Studies with populations with mean age  in 2019 , 27, pap in 2019 –31.Abstracts were screened for inclusion by two authors independently (LAB and ML). If a study appeared to meet the inclusion criteria, full text articles were read and analysed for inclusion by two authors working independently (LAB and MGB). Final inclusion was decided by consensus discussion with a senior researcher working on the topic of community malnutrition (PDC).> 60%), not frail (< 40%), low prevalence of polypharmacy (< 40%), and low prevalence of multi-morbidity (< 40%).Successful ageing: predominantly functionally independent (> 60%), not frail (< 40%), a high proportion regularly attending a GP (> 50%), high prevalence of multi-morbidity (> 50%) and polypharmacy (> 50%).Usual ageing: predominantly functionally independent (> 60%), functionally dependent (> 60%), users of home-care services (> 40%), and a high proportion was recently hospitalised (> 50%).Accelerated ageing: predominantly frail  or longitudinal design (N = 11). There were two systematic reviews of observational studies and one meta-analysis of longitudinal studies. Sample size of the studies ranged from 49 to 15,669 participants. The majority of included studies were conducted within European countries.The articles included were heterogeneous in study design Table . StudiesNine studies were classified as ageing at a usual rate , 84, 99.Factors in the demographic and disease-related domains were most-commonly examined (63 and 54 studies respectively), followed by the social (50 studies), psychological and physical functioning domains (46 studies each) Table . FactorsN = 2; usual, N = 1; accelerated, N = 1) and increasing age  were commonly reported as associated with malnutrition/malnutrition risk across all ageing rate categories. Other demographic (unmarried status (N = 4) [N = 2) [The frequency of factors reported as associated with malnutrition according to the rate of ageing category is presented in Table  (N = 4) , 85, 100 [N = 2) , 68) andThis review found that factors reported to be associated with malnutrition from the food intake domain increased in frequency and severity across the three ageing categories . Food insecurity was reported as a risk factor in the successfully ageing category , choosinWithin this review, lifestyle factors were rarely reported as being associated with malnutrition or malnutrition risk in any of the ageing categories. Lack of physical activity was reported once in both the successfully  and acceN = 1) [N = 2) [N = 2) [N = 3) [N = 2) [Cognitive impairment, a factor within the psychological domain was reported as being associated with malnutrition by one study in the successful ageing category , whilst N = 1)  and acce [N = 2) , 94 agei [N = 2) , 45, usu [N = 3) , 36, 49  [N = 2) , 53 cateN = 2) [N = 1) [N = 1) [Indicators of declining mobility  were reported in the successful ageing category only (N = 2) , 87. FacN = 2) . Falls w [N = 1)  and acce [N = 1)  categoriN = 1) [N = 2) [N = 2) [N = 2) [Living with others was associated with reduced risk of developing malnutrition in the successful ageing category (N = 1) , whilst  [N = 2) , 39. Soc [N = 2) , 100 and [N = 2) , 99 ageiN = 1) [N = 2) [N = 2)  whilst individual diseases such as cancer and osteoporosis (N = 1) [N = 1) [This review found factors from the disease-related domain were commonly reported across all ageing rate categories but increased in severity as the ageing rate progressed into the accelerated ageing category. Recent hospitalisation was reported in the successful (N = 1)  and acce [N = 2) , 96 agei (N = 1)  and exteThis review provides a summary of the factors associated with malnutrition and malnutrition risk reported in community-dwelling older adults with an emphasis on differences identified according to rate of ageing . This noThe findings presented in this paper contribute to our understanding of the factors associated with, and determinants of, malnutrition in older adults and may explain differences in factors associated with, and determinants of, malnutrition reported in previously published studies. Standardised criteria for the diagnosis of malnutrition were only published as recently as 2019 , 27. TheNumerous cross-sectional studies included in this review reported no association between marital status and malnutrition , 88, 93.Age and female sex are reported to be associated with malnutrition and malnutrition risk across all ageing rate categories. It has been reported that females have a 45% higher chance of developing malnutrition compared to their male counterparts . This coFactors affecting food intake, such as the amount of food eaten or the ability to eat/feed oneself, appear to be particularly associated with malnutrition within the accelerated ageing category, compared to the other categories. This may be in line with the fact that this group comprises a sicker, and more diseased population group. The escalation in the severity of these factors across the ageing categories (from food insecurity to factors affecting food choice to having difficulty or being unable to self-feed), highlights that as older adults deteriorate in health and function, they become more vulnerable to developing malnutrition.In this review, a reduced/poor appetite appears to be associated with malnutrition across all ageing rate categories. Reduced appetite can be a consequence of many factors known or suggested to be associated with, or determinants of, malnutrition, including depression, cognitive decline, chewing or swallowing difficulties and sensory changes , 109. TwEvidence surrounding the association between dental status and presence of chewing problems and malnutrition is conflicting , 111. HaLifestyle factors were seldom reported across all categories of ageing rate; thus, the evidence surrounding lifestyle factors, such as alcohol consumption, smoking and low physical activity and malnutrition is weak. Few associations have been reported for physical activity as a protective factor , 56, 68 Factors within the social domain, predominantly factors related to social support, were apparent within the successful and usual ageing categories, where social factors related to use of services were more prevalent amongst the accelerated ageing category, likely reflecting increased dependency among this group and subsequently, a higher need for these services. This finding is supported by two longitudinal studies which reported that meals-on-wheels use, which may be linked to reduced social  functioning, was associated with increased risk of malnutrition , 94. AmoEvidence surrounding a relationship between inability or difficulty completing activities of daily living (ADLs) and malnutrition is conflicting , 97, 111Low handgrip strength (HGS) did not appear to be associated with malnutrition across any of the rate of ageing categories. Furthermore, HGS, was reported to have no association with incident malnutrition following a meta-analysis of longitudinal cohorts . AlthougFalls among older adults, can be an indicator of declining cognition or onset of frailty , 115 andThe prevalence of malnutrition is significantly higher among people with dementia; however, this is more likely to impact on the determinants of malnutrition in long-term care settings where dependency is higher compared to the community setting , 119. DiDisease-related factors appear across all ageing categories; however, specific diseases such as cancer and osteoporosis only appear within the accelerated ageing category. Malnutrition is common among older adults with cancer, with the prevalence ranging from 30 to 85% depending on the cancer type . Recent Numerous studies have reported associations between poor self-rated (SR) health and malnutrition , 122 witThis review used a novel approach of categorising community-dwelling older adults according to their rate of ageing  and assessed whether differences occurred in the factors associated with malnutrition for each category. To the best of our knowledge, no other study has taken this approach previously. This approach may contribute to reducing the heterogeneity in factors reported to be associated with malnutrition among older adults in the community setting.There are a number of limitations associated with the published literature on the determinants of malnutrition in older adults. Whilst 68 studies were initially identified as relevant for inclusion in this review, 40 could not be categorised according to rate of ageing due to the lack of detailed information on the characteristics of the study population provided within the published manuscripts. These studies were, therefore, omitted from the synthesis of factors associated with, and determinants of, malnutrition by rate of ageing. Had these manuscripts contained sufficient information to permit categorisation by rate of ageing, our results would have been strengthened or potentially different. Where possible, the current review sub-categorised the study populations from the included studies into successful, usual or accelerated ageing. It is likely that there was heterogeneity between the participants included in individual studies; however, group means were used to categorise the populations from individual papers as a whole into rate of ageing categories. Furthermore, there was variation in the parameters used in different studies, for example, number of medications to define polypharmacy and method of measuring functional independence.The majority of studies included in this review used convenience samples, often with small sample sizes. This limits the use of the results as they cannot be extrapolated to represent the general population of community-dwelling older adults. A number of studies only investigated factors from one or two domains, thus, failing to acknowledge the multifactorial aetiology of malnutrition. Furthermore, a factor or determinant could not be identified as associated with malnutrition if it had not been included in the original study. The majority of current published literature is cross-sectional in design. Studies of longitudinal design are superior to definitively determine the factors which predict malnutrition as cross-sectional studies cannot distinguish between the causes and consequences of malnutrition. This review included only studies published in the English language and from the year 2000 onwards. The timeframe chosen was to ensure a more standardised approach to the identification of malnutrition and malnutrition risk and allowed for the identification of potential factors and determinants of malnutrition relevant to the health of older adults in the past 20 years. Nonetheless, these factors may have introduced selection bias into our results.Numerous changes occur with ageing, increasing the vulnerability of older adults to developing malnutrition. Older adults are a heterogeneous group; thus, assessment of individuals’ rate of ageing could aid in identifying specific determinants for different cohorts of community-dwelling older adults. In the future, categorising community-dwelling older adults according to their rate of ageing could also be incorporated into malnutrition screening methods; this would allow for a more personalised approach to identifying malnutrition in older adults as different domains and different individual factors appear to be important depending on the ageing category. Further longitudinal studies and meta-analyses, segregating elderly by ageing rate, are warranted to clearly distinguish which factors are true determinants of malnutrition and not simply the consequences of the condition.


FGFR2 mutation and CCNE2 amplification. The former was targeted with the FGFR inhibitor lenvatinib while the latter with the cell cycle inhibitor palbociclib. The combination of the two drugs exhibited synergistic therapeutic effects against in vivo tumor growth. Collectively, these data illustrate the value of PDX models for preclinical testing of new molecularly informed therapies in difficult-to-treat gynecologic malignancies. Our results may also prompt further clinical research to examine whether the combination of lenvatinib and palbociclib has potential to improve clinical outcomes of women with DEC.Reliable animal models of human malignancies are paramount for preclinical studies of novel treatment approaches. Here, we successfully developed a patient-derived xenograft (PDX) model of dedifferentiated endometrial carcinoma (DEC)–an uncommon uterine malignancy that is generally unresponsive to standard chemo- and radiotherapy. The murine model–termed PDX-mLung–was established through the implantation of lung metastatic lesions obtained from a woman with DEC. Histologic and molecular findings revealed that PDX-mLung was highly similar to the parent human malignant lesions (both primary DEC and lung metastases). Importantly, molecular analyses revealed that PDX-mLung exhibited druggable alterations including a FGFR2 mutation and CCNE2 amplification. Targeted combined treatment with the FGFR inhibitor lenvatinib and the cell cycle inhibitor palbociclib was found to exert synergistic therapeutic effects against in vivo tumor growth. Based on the results of RNA sequencing, lenvatinib and palbociclib were found to exert anti-tumor effects by interfering interferon signaling and activating hormonal pathways, respectively. Collectively, these data provide proof-of-concept evidence on the value of PDX models for preclinical testing of molecularly informed drug therapy in difficult-to-treat human malignancies. Further clinical research is needed to examine more rigorously the potential usefulness of the lenvatinib and palbociclib combination in patients with DEC.Conventional treatment of dedifferentiated endometrial carcinoma (DEC)–an uncommon and highly aggressive uterine malignancy–is beset by high failure rates. A line of research that holds promise to overcome these limitations is tailored treatments targeted on specific molecular alterations. However, suitable preclinical platforms to allow a reliable implementation of this approach are still lacking. Here, we developed a patient-derived xenograft (PDX) model for preclinical testing of investigational drugs informed by molecular data. The model–termed PDX-mLung was established in mice implanted with lung metastatic lesions obtained from a patient with DEC. Histologic and whole-exome genetic analyses revealed a high degree of identity between PDX-mLung and the patient’s parental lesions (both primary DEC and lung metastases). Interestingly, molecular analyses revealed that PDX-mLung harbored druggable alterations including a  SMARCA4), INI-1 (protein of SMARCB1), and ARID1A . ThFGFR2 (S137W), LRP1B (D2048N), and KMT2C (R199Hfs*6) genes  genes B. The reications C, and thications D. Given  lesions E.FGFR2 (p.S137W) mutation with the FGFR inhibitor erdafitinib–an orally administered drug that has been previously used for advanced cancer [18F-FDG PET imaging (The results of annotated variants (missense mutations and non-sense mutations) detected in three tumors are provided in d cancer . Howeverd cancer  and bread cancer , we furtGFR2 p.S1W mutatio imaging .We further examined whether lenvatinib and palbociclib were able to exert synergistic therapeutic effects in the PDX-mLung model. Compared to either lenvatinib (10 mg/kg) alone or palbociclib (100 mg/kg) alone, a combination of the two drugs  exhibited synergistic effects . Therefohttps://github.com/kevinblighe/EnhancedVolcano, accessed on 14 November 2021, p value < 0.05) were subjected to functional annotation through the GO enrichment tool of clusterProfiler (R package). Signature-enriched pathways following lenvatinib treatment included the suppression of ATP synthesis, interferon (IFN) signaling, and extracellular organization pathways. Raw gene counts for all tested tumor samples are summarized in https://david-d.ncifcrf.gov/, accessed on 28 September 2021) dataset. Specifically, we sought to identify genes that showed a log2 downregulation higher than 1.5 folds following exposure to lenvatinib and palbociclib  database. After dichotomization of patients with EC according to optimal cutoff for CCNE2 copy number variations . On analyzing the prognostic effect of CCNE2 mRNA expression levels (cutoff: 0.68), patients with an increased expression (n = 185) were characterized by a less favorable OS   that mayFGFR2 mutation targeted by lenvatinib and CCNE2 amplification targeted by palbociclib). Consequently, PDX-mLung was used as a preclinical model to test the efficacy of both drugs, given either alone or in combination. The significant role played by the IFN pathway in response to lenvatinib treatment [In this study, we found that DEC had two main druggable molecular alterations,  may explain the biological aggressiveness of DEC. Moreover, lenvatinib is already known to be effective in endometrial carcinoma and approved in combination with immunotherapy [FGFR2 mutations and CCNE2 amplifications may serve as markers of treatment response.The concomitant presence of two key molecular alterations that drive human tumorigenesis (i.e., a otherapy . While rotherapy , aggressThe results of our study provide proof-of-concept evidence on the value of PDX models for preclinical testing of molecularly informed drug therapy in difficult-to-treat human malignancies. Further clinical research is needed to examine more rigorously the potential usefulness of the lenvatinib and palbociclib combination in patients with DEC.