PARO, a robotic pet, was designed to provide emotional and social support for older people with dementia. This project aims to explore the perception of persons with dementia about the role of PARO in a hospital setting. Video-ethnographic methods were applied. Patient and family partners were involved in the fieldwork of data collection and analysis. We conducted conversational interviews with ten patients with dementia staying in a geriatric unit and video observations. Thematic analysis yielded three substantive themes: (a) “it’s like a buddy”, the robot helps persons with dementia to uphold a sense of self in the world, (b) “it’s a conversation piece”, the baby seal facilitates social connection, and (c) “it’s all about love”, PARO transforms and humanizes the clinical setting. Our findings contribute to providing a better understanding of the direct perspectives of patients with dementia on the use of the social robot.


Moreover, Sirt1 protects cardiac function, reduces cardiac remodeling, inhibits cardiomyocyte apoptosis, and attenuates cardiomyocyte hypertrophy post-myocardial infarction. These results suggest that Sirt1-induced p21 deacetylation plays an essential role in cardiomyocyte proliferation and that it could be a novel therapeutic strategy for myocardial infarction.Inducing cardiomyocyte proliferation is a hopeful approach for cardiac regeneration following myocardial infarction. Previous studies have shown that p21 inhibits the cardiomyocyte proliferation and cardiac regeneration. Deacetylation of p21 by Sirt1 deacetylase may reduce p21 abundance and remove p21-induced cell cycle arrest. However, whether p21 deacetylation and Sirt1 deacetylate control cardiomyocyte proliferation is unclear. Here, we show that acetylation of p21 induces cardiomyocyte proliferation arrest, whereas blocking the acetylation of p21 increases cardiomyocyte proliferation. P21 can be acetylated by Sirt1, and Sirt1 activate p21 ubiquitination through deacetylation. Additionally, overexpression of Sirt1 induces EdU-, pH3-, and Aurora B-positive cardiomyocytes in neonatal and adult mice. In contrast, depletion of Sirt1 reduces cardiomyocyte proliferation  Acute myocardial infarction (MI) causes the rapid death of cardiomyocytes (CMs) with subsequent cardiac dysfunction. Approaches that could induce cardiac regeneration would help increase the number of CMs for the recovery of cardiac function post-MI –3. IndeeP21, encoded by cyclin-dependent kinase inhibitor 1A, directly inhibits G1, S, and G2 phase cyclin-dependent kinases in the cell cycle –8. PreviSirtuins (Sirt1-7) are a family of histone deacetylases (HDACs) that catalyze the deacetylation of protein lysine residues . SirtuinIn this study, we hypothesized that Sirt1 could induce CM proliferation and cardiac regeneration through deacetylating p21. The purpose of our study was to elucidate whether the deacetylation of p21 can attenuate CM proliferation arrest, and whether Sirt1 can deacetylate and ubiquitinate p21, thereby inducing CM proliferation and cardiac regeneration. Our study provides a novel strategy which could be used as an effective therapeutic approach following MI.We first examined the acetylation level of p21 in the hearts of mice of different ages. P21 was pulled down from mouse heart lysates Post-natal day 1 (P1) and post-natal day 28 (P28); then, the proteins acetylated on lysine residues were detected. The immunoprecipitate results showed that the acetylation of p21 in P28 CMs was 2.01±0.26-fold higher than in P1 CMs . The Wesin vitro. In order to test the efficiency and specificity of synthetic Sirt1 siRNAs to silence endogenous Sirt1, two siRNAs were initially designed for Sirt1. We transfected each of the two different Sirt1 siRNAs and mismatched control siRNA, respectively, into isolated P1 CMs, and found that si-Sirt1-1 can silence Sirt1 mRNA and protein expression effectively and specifically  show that Sirt1 is upregulated in mouse fetal hearts compared with adult hearts –4C. Thenin vitro . We founin vitro . In addiin vitro . P1 CM nin vitro . Next, win vitro . Comparein vitro , 4G. In in vitro . We furtin vitro  significin vitro , 4J. Morin vitro . Next, win vitro . Sirt1 kin vitro . Sirt1 din vitro . These din vivo. At 10 days after the injection of adenovirus, the depletion of Sirt1  in vitro and in vivo. Furthermore, we used adenovirus (AdV) vector injection for neonatal and AAV9 vector injection for adults in vivo to sustain the levels of Sirt1 for short-term and long-term expression, respectively. We examined CM proliferation using immunofluorescence. We used a diverse set of antibodies to distinguish between CMs and cardiac fibroblasts in vivo. We also visualized EdU-, pH3-, and Aurora B-positive CMs using Z-stack confocal images, which demonstrated that the signal of these markers indeed belong to the CMs. Our results reveal that overexpression of Sirt1 causes an increase in EdU-, pH3- and Aurora B-positive CMs, which are classical markers of DNA synthesis, mitosis and cytokinesis, respectively, used in previous studies [Previous studies have shown that Sirt1 promotes cell proliferation in malignant glioma cells , melanom studies , 44. On  studies  and prot studies . Taken tin vitro. It is better that when experiments were conducted on p21-/- knockout mice, and we will elucidate the effects between the acetylation/deacetylation of p21 and cardiac regeneration post-MI in vivo in further studies. Additionally, we demonstrated that p21 acetylation/deacetylation is involved in Sirt1-induced CM proliferation, whether p21 acetylation/deacetylation is involved in Sirt1-regulated CM hypertrophy and apoptosis remains unclear and requires further studies. In the present study, although we obtained that overexpression of Sirt1 is benefit for cardiac regeneration post MI, the accurate abundance of Sirt1 which promotes cardiac regeneration more effectively remains to be explored.The present study has several limitations. We performed the function of p21 acetylation/deacetylation in CM proliferation In summary, the present study demonstrates that p21 deacetylation by Sirt1 could attenuate proliferation arrest in CMs. In addition, overexpression of Sirt1 triggers CM proliferation and cardiac regeneration. We conclude that activating p21 deacetylation and ubiquitination by Sirt1 could be beneficial for treating MI.All animal care and experimental procedures were approved by the Institutional Animal Care and Use Committee at Southern Medical University, and they followed the NIH Guidelines for the Care and Use of Laboratory Animals. Animal studies are reported in compliance with the ARRIVE guidelines , 48. ThecAGAGAcAACCC. Si-NC, two Sirt1 siRNAs, and mismatched control siRNA (si-MM) were synthesized by Ribobio . Isolated P1 or P6 mouse CMs were seeded at 70% confluence for immunofluorescence analysis and 40% confluence for CM number analysis. After 48h of culturing, 5μl Lipofectamine 2000  and 50 nM plasmids, or siRNAs were added to the Opti-MEM medium . The mixed solution was incubated at room temperature for 20min and then added to the cells. This medium was replaced after 6h of incubation at 37°C with the same volume of DMEM/F12 medium. After 48h, the cells were subjected to RNA or protein isolation, or immunofluorescence analysis.P21-WT, p21-KR (which was mutated the K156 and K158 to Arg 156 and Arg 158 residue) and p21-KQ (which was mutated the K156 and K158 to Gln 156 and Gln 158 residue) was cloned into pcDNA3.1-FLAG plasmids, which were generated by Vigene . The sequences of each point mutation are as follows (mutated bases in lower case): p21-KR: CGCAGATTGGTCTTCTGCAgGAGAAgACCC; p21-KQ: CGCAGATTGGTCTTCTGC10 viral genome particles per animal using an insulin syringe with an incorporated 30-gauge needle . The virus was injected into the neonatal heart at 3 sites and the total volume injected into each heart was 20μl. Then, mice were placed under a heat lamp and warmed for several minutes until recovery. The hearts of the injected mice were collected 10 days after AdV injection. For long-distance experiments (up to 28 days), AAV9 vectors were used for transduction in vivo. Intracardiac injection of AAV9 vectors (AAV9-NC or AAV9-Sirt1 or AAV9-si-NC or AAV9-si-Sirt1) in 8-week-old (24-26 g) mice at a dose of 1 × 1011 viral genome particles per animal was performed as described below for the animals that underwent MI.The AdV-GFP overexpression or depletion Sirt1 and the AAV9 vector overexpression Sirt1 were synthesized by Vigene . In the experiments using AdV vectors, neonatal C57BL/6J mice  were anesthetized by cooling on an ice bed for 5 min. After the fourth intercostal was dissected, mice were intracardiac injected with NC or Ad-si-Sirt1 at a dose of 2 × 10Western blotting was performed as previously reported . IsolateCo-immunoprecipitation assay was performed as previous study . After tTo detect specific acetylated sites within the acetylated p21 peptide in CMs treated with or without Ad-Sirt1 or si-Sirt1, cell lysates were immunoprecipitated with an anti-p21 antibody and analyzed using SDS-PAGE. The gel was silver-stained to detect p21 and gel slices containing p21 bands were excised. Following reduction and alkylation, gel slices were digested with a modified sequencing grade trypsin . The digestion was carried out overnight at 37 °C and the fragmented peptides were extracted from the gel with 2% formic acid/67% acetonitrile. Then, the digestion mixture was packed with C18-resin . A capillary peptide trap was used to desalt and condense the tryptic peptides before separation on a reverse-phase 75 μm × 15 cm Chrom XP Eksigent column  packed with C18-resin. The column was directly mounted in the nanoelectrospray ion source  and the peptides were eluted by applying a linear gradient program  at a constant flow of 170 nl/ml. LC-MS/MS was carried out on a Triple TOF 5600 LC-MS .TM RT Master Mix . Real time qPCR was performed with the SYBRs Premix Ex TaqTM Kit  on Lightcycler480 . β-actin was used as a housekeeping control to normalize gene expression normalization using the ΔΔCt method. All primers were designed by Sangon Biotech  Co., Ltd. The sequences of the primers are as follows: Sirt1, 5′-TTGGCACCGATCCTCGAAC-3′ (forward), 5′-CCCAGCTCCAGTCAGAACTAT-3′ (reverse); Sirt2, 5′-AGCCAACCATCTGCCACTAC-3′ (forward), 5′-CCAGCCCATCGTGTATTCTT-3′ (reverse); Sirt3, 5′-CTACATGCACGGTCTGTCGAA-3′ (forward), 5′-GCCAAAGCGAAGTCAGCCATA-3′ (reverse); Sirt4, 5′-GGATGCATGCACAGAGTCCTG-3′ (forward), 5′-CTCAGTGAGGAACACGTCGC-3′ (reverse); Sirt5, 5′-TCTGGAAATCCACGGAACCT-3′ (forward), 5′-ACTGGGATTCTGGCGTCTTG-3′ (reverse); Sirt6, 5′-ATGTCGGTGAATTATGCAGCA-3′ (forward), 5′-GCTGGAGGACTGCCACATTA-3′ (reverse); Sirt7, 5′-GACTGAGCGTACTGCCCTTC-3′ (forward), 5′-ACAATGGTATCCCGAAGCTG-3′ (reverse); p21, 5′-CACAGCTCAGTGGACTGGAA-3′ (forward), 5′-CCACCACCACACACCATAGA-3′ (reverse); β-actin, 5′-TGCTGTCCCTGTATGCCTCTG-3′ (forward), 5′-TTGATGTCACGCACGATTTCC-3′ (reverse).Total RNA was extracted from isolated CMs or ventricular neonatal or adult mouse heart tissue samples using the E.Z.N.A. Total RNA Kit II  according to the manufacturer’s instructions. The RNAs were treated with DNase I  to exclude the possibility of DNA contamination. For the quantification of gene expression, cDNA was reverse transcribed from 1μg of total RNA according to the PrimeScriptad libitum. The animals were habituated to the animal facilities for at least 1 week before use. MI surgeries were performed as previous study [Healthy 6-week-old male C57BL/6J mice were purchased from the Laboratory Animal Center of Southern Medical University and singly housed in a temperature-controlled (22±1°C) environment with a 12 hour light/dark cycles with food and water available us study . RandomiTo evaluate cardiac dimensions and function, transthoracic two-dimensional echocardiography was performed on mice anaesthetized with 2% isoflurane at 7, 14, 21, and 28 days after LAD ligation, using a Vevo 2100 Imaging System  equipped with a 40-MHz probe. M-mode tracings in the parasternal short axis view were used to measure the left ventricular internal diameter at end-diastole (LVEDd) and end-systole (LVESd). These measurements were used to calculate the left ventricular fractional shortening (LVFS) and ejection fraction (LVEF).Tissue collection was performed as previous study . Mice weParaffin-fixed heart tissue slides were de-paraffinized via xylene and re-hydrating through sequential incubations in ethanol  and water. Then, the serial slices were incubated in Weigert hematoxylin iron for 5 min, differentiated in HCl-ethanol and incubated in ponceau acid fuchsin for 5 min, phosphomolybdic acid for 5 min, and aniline blue  for 5 min. The fibrotic area was measured as the percentage of the total left ventricular area showing fibrosis and quantified with ImageJ software.in vitro, the culture medium was washed with PBS. Then, the cells were fixed with 4% ice-old paraformaldehyde . For the tissue slices, frozen sections (5μm) were fixed with acetone. Then, cells or slides were permeabilized with 0.2% Triton X-100 PBS and blocked with 1% BSA in PBS. When indicated, cells or slides immunostained with EdU were further processed using a Click-iT EdU Alexa Fluor 555 Imaging Kit  to determine EdU incorporation according to the manufacturer’s instructions. Then, the cells or slides were incubated with primary antibodies, including the CM marker cardiac troponin T , the cardiac fibroblast marker vimentin , pH3 , or Aurora B , for 2h at room temperature, followed by incubation with goat anti-mouse IgG/Alexa Fluor 488  or goat anti-rabbit IgG/Alexa Fluor 555  or goat anti-chicken IgG/Alexa Fluor 647  secondary antibodies for 1h at room temperature. The cells or slides were subsequently washed and incubated with Hoechst 33342. CM numbers were counted using cTnT staining. CM borders were determined by staining of slides with WGA conjugated to Alexa Fluor 555  in PBS. CM apoptosis was defined by TUNEL staining  at 28 days after MI according to the manufacturer’s instructions. Image acquisition was performed with an LSM 880 confocal microscope .For cells cultured The previously published microarray data that were reanalyzed here are available under the accession codes GSE50704, GSE51483, and GSE93269.p value, and p<0.05 was considered statistically significant.All data are presented as the mean ± S.E.M. All statistical analyses were performed by SPSS 20.0 software  and only when a minimum of n = 5 independent samples was acquired. For statistical comparisons of two groups, an unpaired, two-tailed Student’s t-test was used; for comparisons of three or more groups, a one-way ANOVA followed by the least significant difference (LSD) post hoc test was used. We calculated the significance of each treatment as a Supplementary Figures


Research studies on facilitating professional development describe the knowledge and skills facilitators need to effectively attend to teachers’ learning processes. In this context, some studies gave rise to the question how to design learning opportunities to prepare facilitators to support teachers’ learning during professional development. The approaches share putting mathematics specialized content knowledge, pedagogical content knowledge on the professional development level and facilitation moves in the center. Research findings also highlight the role of video-based learning opportunities to qualify facilitators respectively. In particular, structured approaches that guide facilitators noticing toward advancing teacher learning have to be proven effective. Although research highlights using video-based material as a training tool for facilitators, what exactly the learning opportunities should consist of is up for discussion. In this article, we report on a validation study concerned with designing video cases, taken from a videotaped teacher professional development. We explored how eight experienced facilitators perceived the representativeness and the quality of the video cases for using them in facilitator professional development with respect to specialized content knowledge, pedagogical content knowledge on the professional development level, and facilitation moves. Additionally, we investigated what facilitation moves are noticeable in the video cases, and what noticing prompts can enhance these learning opportunities.Our results indicate that all video cases present vital opportunities to discuss how to support teacher learning in terms of specialized content knowledge, pedagogical content knowledge on the professional development level and facilitation moves. Our analyses provide insights into facilitators thinking processes, thus enriching their ratings by ideas and concerns considering the final implementation of the video cases in facilitator professional development. On the basis of our validation study, we were able to carefully check the learning opportunities that the chosen video cases can provide for facilitator professional development.This paper provides information on how to design video-based learning opportunities for facilitator professional development. Although our results are of course bound to the six video cases we selected, our approach can be transferred to other contexts. The procedure of compiling the video cases and validating them takes up the most prominent research findings on designing facilitator professional development and pays careful attention to experiences facilitators thinking. We exemplarily show how the empirical evidence can be used to prepare facilitator PD. The question arose after the PD facilitator introduced a task dealing with determining the probability distribution of heads and tails when a coin is flipped four times. The facilitator noticed Jane’s indecision, but decided to leave the question unanswered. Instead of responding directly, she asked the teachers to think about it while solving the task. The mathematical background addressed by the question was then reflected upon in an in-depth discussion. Thus, this small incident turned out to result in a fruitful learning opportunity for all of the teachers in the PD.Should I just give Jane an answer right away? What mathematics content am I going to address next? How can I value Jane’s question positively to not make her feel like she does not know much about probability and statistics? These are just some of the possible decisions mathematics PD facilitators might keep in mind when leading a PD course with the explicit goal to support teachers’ mathematics learning. The facilitator in our example has extensive experience in providing PD, and was thus able to allow for a little detour to clarify the underlying mathematical concept. The question remains, however, how would novice facilitators act in such a situation? And more importantly, how can they gain such an expertise that normally develops over time and with practice? In our research project, we build on such situations that are crucial for teacher learning and question how PD facilitators can enhance their capability to respond adequately. Particularly, we scrutinize how material for “facilitator PD” can be designed to enable facilitators-in-training to later provide robust opportunities for teachers’ mathematical learning in PD courses they facilitate on their own.PD facilitators encounter such situations on a regular basis. Just as teachers in the classroom, they have to constantly anticipate the mathematical relevance of a teacher statement and need to decide in-the-moment how to proceed. The in-the-moment decision-making includes reflections such as the following: As regards the general composition of PD courses, the last two decades have contributed research findings on the design and implementation of effective PD programs  and pedagogical content knowledge (PCK). SCK comprises “a sophisticated understanding of the mathematical concepts and relationships intended to be covered during the PD” .d Sherin , b demonSumming up, one essential aim of facilitator PD lies in providing learning opportunities on the SCK and PD-PCK level. In focus are aspects that aim at reaching the specific learning goals on the teacher PD level. In our study, these knowledge facets are one essential category for designing facilitator PD based on video cases and constitute one content dimension of our validation study.knowing becomes acting and what moves characterize effective facilitation. González et al. . In consideration of design principles 2 and 3, we will add prompts to each video case to ensure facilitators’ focus on noticing SCK, PD-PCK, and facilitation moves in the final design.When designing video cases of PD to aid leader noticing of the described knowledge facets and reflecting upon possible moves, we need to validate that the chosen scenes are suitable to reach these aims. The purpose of our validation study, immersing facilitators with different degrees of experiences, is twofold: On the one hand, we check the video cases for their content validity. We seek to explore whether the video cases allow for intense discussion on SCK, PD-PCK aspects, and facilitation moves. On the other hand, we ask for alternative facilitation moves and noticing prompts, revealing interpretive arguments that specify the proposed interpretations cf. Kane . Later, In the following, we provide further information on how we prepared the video cases and how we compiled the rating. Additionally, we exemplarily describe one video case in detail by outlining the context and setting as well as the SCK, PD-PCK, and facilitation moves involved.In late 2017, we videotaped 3 days of a PD course for primary mathematics teachers in the federal state of Berlin, Germany. The PD course was practice-based and focused on crucial features of teachers’ SCK and PCK in the domain of probability and statistics. The overall setting of the program required participating teachers to meet four times in one semester for collaborative learning with an experienced PD facilitator. Additionally, teachers were given tasks to build into their instructional practice for the time in between the meetings.In total, we recorded and prepared approximately 20 h of video material for further analysis. After an initial viewing of the entirety of the video material, we developed a coding system to describe specific sequences, showing crucial incidents of teachers’ learning of probability and statistics in the PD setting.In order to structure the coding process, we delineated units of meaning relevant to the research questions . The idea unit treats the understanding of key mathematical concepts and relationships. Hence, scenes showing teachers’ learning not related to SCK were excluded. The second criterion for exclusion is PD-PCK (EC2). The idea units depict vital opportunities for teachers to actively engage in learning. Scenes only showing the facilitator explaining mathematics concepts without further interaction or instruction were excluded. Third, we coded scenes indicative of facilitation moves (EC3). This criterion describes scenes that show facilitation moves to advance teachers’ learning of mathematics. We excluded, for example, scenes of the PD course showing participants working on tasks individually. The last criterion considers the quality of video and audio (EC4). To ensure high quality of our video data, we excluded scenes that were difficult to understand.For each idea unit, we then decided whether to include or exclude the scene as a video case for the rating study. The goal of this process was to provide video cases, which depict how the facilitator supports teachers’ mathematics learning in the PD course. For each idea unit, the decision to include or exclude the scene is based on the Two researchers pre-structured and coded the video material based on the four criteria. Disagreements were mutually discussed until consensus about including or excluding the respective scene was reached. As a result, we selected six video cases, lasting between 3 and 8 min, for further rating. An overview of the video cases that were chosen for the rating is given in Table context and setting to give some background information on learning goals as well as the tasks and material used in the PD course. Second, we exemplify how the video cases address the relevant constructs of SCK, PD-PCK, and facilitation moves.In the following, we describe one video case in detail. First, we outline the The video case “Representing characteristics” was recorded on the first day of the PD course. The topic of the first half of the PD course was concerned with different types of data sets, methods of data collection, and data representation. The second half-day focused on statistic parameters to evaluate statements related to data collections. Furthermore, the implementation of statistics in school curricula was addressed and discussed. Prior to the content depicted in video case 1, the participating teachers worked in groups on the following tasks:a) Plan and conduct a data collection for a topic of your choice with the participants of this PD course. Work in groups of three or four.b) Illustrate your data collection for presentation and give reasons for the chosen topic and illustration.The video case shows two groups of teachers presenting their results to the above tasks. It also shows the PD facilitator taking notes on a flipchart during the teachers’ presentations. The video case ends with the PD facilitator sharing her notes with the teachers and summarizing the teachers’ learning processes.VS_DS1 is concerned with key concepts of descriptive statistics: evaluating different types of data, dealing with differences in characteristics, and adequate data representations. The two groups of teachers presenting their results focused their data collection on the characteristics “shoe size” and “grade level the participants teach.” In their presentations, teachers struggled with the question whether it makes a difference to use a distinct characteristic or one that allows multiple possible answers. Illustrations used include a bar graph for “shoe size” and a table for “grade level the participants teach.” Referring to the characteristic shoe size, one teacher mentioned that he expected a bell-shaped curve, making connections to the mathematics concept of a Gaussian distribution. Furthermore, the teachers discussed problems with discordant values such as very small or very large shoe sizes.Involving teachers in these tasks enabled them to independently plan, implement, and illustrate a data collection. Based on the examples that were presented, the teachers were asked to discuss characteristic features and pitfalls of illustrating different data sets. The teachers then reflected on possible student solutions on the basis of their own contributions and discussed possible reactions in depth to advance the learning of their students.posing precise questions when planning a data collection, specifics of distinct characteristics and scale and discordant values. Furthermore, the PD facilitator explained to the teachers what crucial incidents occurred and how they play a role when teaching data collection and illustration to students in class. She referred to similar problems and questions teachers might encounter when discussing results with their students, hence connecting the PD and the classroom level. At the end of the video case, the PD facilitator connected the notes she made to the content of the PD program, highlighting the importance of teachers’ learning goals. In Table At the beginning of the video case, the PD facilitator summarized the task the teachers were working on and then asked the first group to present their results. The PD facilitator first showed the bar graph the group had developed to the other teachers, but then she decided to take notes on a different flip chart. The notes the PD facilitator had been taking were not visible for the teachers. Then, the second group presented their data collection and illustration. The PD facilitator kept making notes without interrupting the second presentation. In the last part of the video case, the PD facilitator summarized the teachers’ results and shared her notes with the groups, which concerned: orienting the group to the task analysis, sustaining an inquiry stance, maintaining a focus on the professional development and the mathematics, and supporting group collaboration. Thus, the video case allows for discussing the relevant facilitation moves.In terms of the framework by González et al. , we attaHowever, decisive for designing facilitator PD is not what the researchers who possess a broad and thorough understanding of the scenes taken from teacher PD can see in the videos, but what facilitators who receive limited information on the setting might notice. Thus, by involving facilitators in a rating prior to using the video cases in facilitator PD, we ensure that the intended aim of the video cases, i.e., to facilitate teacher learning, can be pursued. In addition to validating for content, we asked the experts to suggest alternative moves and prompts that elicit facilitators’ noticing of teacher learning. With respect to designing the video cases for facilitator PD, we pursue the following research questions:RQ 1: a) How do facilitators rate the representativeness and the quality of the video cases for use in facilitator PD courses?b) When representativeness of the video cases with respect to SCK, PD-PCK, and facilitation moves was rated low, what reason do the facilitators provide for their estimation?RQ 2: What facilitation moves do participants notice in the video cases and what alternative moves do they suggest as being beneficial for supporting teacher learning in PD settings?RQ 3: What prompts do facilitators suggest to enhance noticing of facilitation moves in respect to the video cases?In this chapter, we first describe the sample of our study. In particular, we outline participants’ range of experience in teaching mathematics and in facilitating PD courses for other mathematics teachers. Second, we elaborate on how the rating study was conducted. Third, we report on how we carried out the data analysis based on the theoretical frameworks and our design decisions.In order to answer our research questions, we conducted a rating study with eight PD facilitators. The participants of our study all hold a diploma in teaching mathematics, but recounted different degrees of practical experience as mathematics teachers and PD facilitators. Seven out of the eight participants have been working as mathematics teachers in primary school and high school for an average of 6 years, and one participant has been working as a high school mathematics teacher for 20 years. In regards to experiences in PD facilitation, participants have, on average, 6 years of experience in developing and implementing mathematics PD courses. Two participating facilitators reported facilitation experiences for 1 year, respectively 2 years, and two other participants had more than 8 years of experience leading PD courses for teachers. Six out of the eight participants are currently practicing PD facilitators. The remaining two participants were involved in planning and advising PD-related research at the time the study was conducted.Prior to the rating, we divided the eight participants of our study into two groups of four, Thereby, we chose a distribution ensuring that in each group, participants had a similar average of years of experience in facilitating mathematics PD. By so doing, we could reach our goal to assign each video case to participants with a variety of experience and were able to cover a broad spectrum of different perceptions. Each participant gained access to three of the selected six video cases, so that in sum, each case was watched and rated by four facilitators.The rating process was structured by a rating protocol, including information on context and material used in each video case. What this information entailed was exemplarily outlined in chapter 3 for video case 1. Data was collected in open answer format according to the following categories: (1) mathematics content and its specific structure due to the learning goals (SCK); (2) teacher activities and crucial incidents of teachers’ artifact-based learning (PD-PCK); (3) perceived facilitation to advance teacher learning (facilitation moves); (4) alternative facilitation moves to support teacher learning ; and (5) prompts to foster facilitators’ noticing of teacher learning.: First, participants received detailed background information on the PD content of the video case: teacher learning goals, the mathematics tasks or results of teachers’ group work. Second, participants watched the whole video case for the first time and wrote down their answers to categories (1) to (4). After watching the scene a second time, participants provided their suggestions to category (5). Additionally, they evaluated the potential of each case for further use as a training tool during the course of a PD facilitator program. The potential as a training tool was operationalized as whether the video scene allows for intensive discussion about SCK, PD-PCK, and facilitation moves. On a four-point Likert scale ranging from 1 = strongly disagree to 4 = definitely agree, participants rated these categories. Scenes estimated below 3.0 will have further revision.The data collection for each video case comprised of the following stepspotential as a training tool. Participants’ answers to these questions gave us deeper insights in the observed SKC and PD-PCK aspects of each video case. Second, we analyzed the categories (3) and (4) concerning the perceived facilitation moves and the suggested alternative facilitation moves to foster teacher learning. For the analysis, we applied the facilitation move framework by van Es et al.  and (2) to clarify particularly high and low ratings on the scale s et al.  in its ms et al. . Two resThe aim of our study is to validate video cases as learning artifacts for facilitator PD. We report the results of our validation study according to our three research questions.Research question 1.a) addresses facilitators’ estimation of the video cases representativeness for use in facilitator PD with respect to the three main content categories SCK, PD-PCK, and facilitation moves. Furthermore, we asked the facilitators to rate the quality of video and audio for each case. Table All video cases received an average rating of 2.50 or higher for the two categories PD-PCK and facilitation moves. Participants considered the video cases as representing vital opportunities to discuss aspects of PD-PCK and facilitation moves. Video case 6 received the lowest rating on facilitation moves. A possible reason for the medium rating might be the PD facilitator standing back and allowing a vivid discussion among the teachers for most of the video duration. In the following, we exemplarily present one rater’s description of the SCK aspect she noticed to be most relevant in video case 1:The mathematics concepts involved in collecting statistical data require an open task such as the one the facilitator posed to the teachers. So that different questions are asked and different characteristics can be compared due to different illustrations. For some of the characteristics there are multiple options how to answer, eye-color for example. Others are more distinct and an interval is necessary. Facilitators have the opportunity to discuss these issues using the examples in the video .Regarding the video and audio quality, all cases that received a rating lower than 2.5 will be improved before final implementation.The PD facilitator shows an example that illustrates the symmetry of random events. The problems of teachers’ understanding are prominent. The facilitator mentions the intent to later shed light on the mathematics concepts involved but that’s not shown in the video case .Although the SCK aspect is not fully pursued in video case 4, it is of course noticeable, and allows for in-depth discussion on how teachers’ learning can be fostered. We were able to observe a corresponding result considering the SCK aspect in video case 5. This case shows teachers of the PD course explaining different solutions to the following task: In a bag there are three bonbons: a yellow one, a blue and a red one. You take two bonbons out of the bag. What is the probability of getting the red one? How does the probability change when adding more bonbons of different colors? A discussion among the teachers occurred, focusing predominately on representations and how to use the task in classroom situations. The PD facilitator moderated the discussion, but stood back when it came to clarifying the mathematical concepts. This is what one of the facilitators referred to by stating:It is very difficult to understand the SCK aspect in this video case because the discussion is all about suitable representations for the given task. But more, I would say, on a methodical level and not so much with respect to the mathematical concepts. The PD facilitator argues more from a pedagogical stance in her explanations so that the mathematics involved fades into the backlight .Particularly for the SCK dimension, the qualitative data helped to clarify low ratings and provided hints regarding how to structure the video cases to guarantee a SCK focus.Research question 1.b) focuses on facilitators’ specification of how the content categories are displayed in the video cases that perceived low to medium ratings. Only the video cases 4 and 5 fall into this category by showing low ratings of SCK. Video case 4, “Symmetry of random events”, shows a situation in which the PD facilitator asked the question whether selecting one element or four elements out of five objects is equal in terms of number. The participating teachers in the PD course at first could not answer the question and remained silent. The PD facilitator then tried to find a productive way to move on and left the question to be revisited at a later stage. Examining the qualitative data in terms of the raters’ explanations of the low score on SKC in this video case, we discovered the following: The facilitator in the video case decided to break the silence and to maintain an inquiry stance. These facilitation moves are dominant in this particular video case and therefore the SCK and PD-PCK aspects fade from the spotlight. One rater’s explanation alluded to this as follows:Research question 2 addresses the facilitation moves participants in our study assigned to the video cases. We classified the facilitation moves according to the framework by González et al. . Table 6highlighting (13.2%), lifting up (13.2%), and clarifying (10.5%). Together, these three moves make up more than a third (36.6%) of all incidents described by the participants of our study as facilitation moves.The table shows the number of facilitation moves by video case and the percentage of total moves. The three moves that were noticed the most are sustaining an inquiry stance (48.3%). The other facilitation moves categories show significantly lower percentages: orienting the group to the task analysis (20.2%), maintaining a focus on the PD and the mathematics (16.7%), and supporting group collaboration (15.8%).Considering the four main categories of the facilitation move framework by van Es et al. , modifieAdditionally, the participants proposed alternative moves that can support teachers’ learning of mathematics in the specific scene , and supporting group collaboration (14). The other categories that are mentioned less frequently concern orienting the group to the task analysis four times and maintaining a focus on the PD and the mathematics four times as well. Furthermore, we were able to elicit additional moves that were not covered in the framework so far. We label these moves foregrounding SCK because they have a strong focus on the mathematical aspects of the PD course.Facilitators in our study suggested different alternative moves for each video case. The majority of these moves stem from the categories facilitation moves participants of our study noticed in the video cases and what alternative moves they suggested. We presented the number of facilitation moves and provided the percentages of total moves. The reason behind this was to ensure that the selected six video cases, out of the many other possible sequences, hold the potential to exemplarily cover a wide range of possible learning opportunities for facilitating PD.So far, we provided a detailed look into what standing back and one participant suggested the move of offering an explanation as an additional possibility:For the second group, the facilitator delays a possible solution for an inappropriate representation. Without knowing the further progress of the PD, I am not sure if it might have been better to discuss the possible solution at this occasion as opposed to discussing it later. Another move for sustaining an inquiry stance was provided for video case 4 when teachers struggled with solving the task of whether one out of five equals four out of five:As there was no answer given to the question how many possibilities one has to choose one objects out of five, I would have given more time to the teachers to think about the problem either on their own or by offering a discussion phase. The additional move can be classified as clarifying the situation when teachers were confronted with a mathematical task they were not able to solve immediately. Regarding supporting group collaboration, one alternative move addressed the organization of a presentation phase. One participant suggested the following practice as alternative move for video case 1:Instead of having the different groups of teachers present their results to the data collection task, the PD facilitator might use a different form of collaborative learning. For example, she might have the teachers prepare a short summary of their results in order to detect crucial aspects of mathematics themselves. The move can be classified as supporting group collaboration, as this is the prominent intention of the move. However, one can see that the reason behind the suggested practice is connected to promoting teacher learning. Thus, the generic aspect of applying a different method to organize collaborative learning draws on the intention to connect the teachers’ work more strongly to the mathematics involved. In terms of the theoretical framework we used, the alternative move can be assigned to validating participant ideas. In the same main category, addressing the sub-category of standing back, one participant offered the subsequent alternative move:The PD facilitator in this video case seems to be highly skilled in keeping the attention on teachers’ presentations, and taking notes at the same time. She is also able to remember teachers’ statements in detail. As an alternative, I suggest that she could ask teachers of the non-presenting groups to list crucial aspects for her as well. The suggestion of involving other teachers, who are not actively presenting, would allow the facilitator to stand back and to concentrate on the presentation of results, and would simultaneously activate rather silent teachers to engage in the mathematics task. Thus, as a result of the move, the facilitator would also contribute to the category of distributing participation, but as this aim was not in the main focus of the proposal, we opted for coding the category with standing back.We will now exemplify what alternative moves the participants proposed for the existing categories, and will then turn our focus to the newly emerged category. First, we present two alternative moves to sustain an inquiry stance. In video case 3, the PD facilitator demonstrated the facilitation move foregrounding SCK. This category is strongly related to the ultimate goal of strengthening teachers’ mathematics learning and is thus directly connected to helping teachers attain the mathematical learning goals. The following examples illustrate what we consider as moves to especially foreground aspects of SCK:To illustrate the law of large numbers I would have used a different set of trial numbers like multiples of 36 for instance 72, 360 and 36000. This makes it easier to understand the distribution of the relative frequency. It would have been helpful to prepare some inappropriate representations to focus aspects such as missing labeling, skewed sample or missing zero (only the first aspect is mentioned in the video case). It might also be helpful to present different representations of the same data. In these statements, the two participants of our study provided some suggestions for focusing on additional aspects of SCK. Thus, teachers would get the chance to deepen their mathematical knowledge. In the same vein, the subsequent suggestions for alternative moves show how SCK aspects can be utilized as starting point to deepen PD-PCK:When the teacher stated “that it is logical for her that the result is 2/3”, I would have asked how one can explain that to students in the classroom. Thereby, one would have provoked explanations by the other participants as well. When the teacher explained “to draw them all at once, I get that I need to write down pairs,” the facilitator could have asked if this viewpoint is sufficient or if it would cause problems. The newly emerged sub-category foregrounding SCK thus enriches the main category of maintaining a focus on the PD and the mathematics.In addition to the theoretically derived facilitation moves, we were able to identify moves that are not comprehensively covered in the framework thus far and that aim at These examples enable a deeper look into experienced facilitators’ thinking processes on how to act as a PD facilitator in a challenging situation. As the six video cases stand out for many other possible scenes, we thereby ensure that the chosen cases provide enough variance with respect to discussing this content category. In the discussion (chapter 6), we will further elaborate on how these different types of information were used to compile the final video cases.SCK or PD-PCK and facilitation moves. Additionally, we were able to differentiate the prompts by applying the three processes of noticing: selective attention, knowledge-based reasoning, and decision-making. Table With research question 3, we turn our attention towards designing video-based PD to allow prospective facilitators to enhance their noticing of crucial incidents of teacher learning in PD. Thus, we investigated facilitators’ perception of crucial prompts and questions in order to enhance the noticing of facilitation moves in the video cases. Our rating study shows that the suggested prompts, in general, address the categories selective attention, 47 of them pertained to knowledge-based reasoning and 45 were related to decision-making. The amount of suggested noticing prompts demonstrates that the video cases contain enough variability to allow for noticing incidents of the three content categories. In our approach, the category of selective attention has minor relevance. As the video cases will be used in facilitator-led facilitator PD, the facilitator will pose noticing prompts to deliberately focus selective attention on specific incidents.As the suggested noticing prompts did not address SCK or PD-PCK separately from each other, we coded the two categories together. In sum, facilitators suggested 38 prompts focusing on both SCK and PD-PCK for the 6 video cases. The remaining 57 prompts concerned facilitation moves, and only 3 could not be assigned to any of these categories. In total, 38.8% of all prompts were related to SCK/PD-PCK while 58.2% addressed facilitation moves. The distribution among the 6 cases was balanced: at the lowest, 13 prompts were suggested for video cases 2 and 3, and at the highest, cases 1 and 5 received 19 suggestions for noticing questions. Only 6 questions addressed knowledge-based reasoning and decision-making. The suggested prompts differ in respect to their nature. Some of them are rather generic and might be applied to different scenes, and others are specific and closely related to the learning of mathematics displayed in the video case.In the next section, we will exemplify what questions the facilitators suggested to the different categories of SCK/PD-PCK and facilitation moves as well as the two noticing categories In the final design of the video cases, we will consider the suggested prompts to redirect facilitators’ noticing to the essential content categories Table .Table 9Sknowing and acting of facilitation , identifying important teachers’ contributions for fruitful discussions (lifting up) as well as restating and clarifying the common understanding of teachers’ ideas (clarifying). On the other hand, it stood out to us that the facilitation move standing back was noticed quite often as well, displaying a crucial move that the facilitator in the video performs often to keep participants involved in a vibrant mutual exchange of thoughts. The video cases also allow for discussing alternative moves as the results of our validation study show. In sum, 48 alternative facilitation moves were suggested; thus the video cases possess rich variance with respect to discussing different actions that facilitators might perform. Twelve out of these moves could be assigned a newly emerging category that focuses on foregrounding SCK aspects during the course of the PD. As the participants in our study were explicitly asked to suggest facilitation moves to foster substantial teacher learning, it is not surprising that the main category of maintaining a focus on the PD and the mathematics was further developed. Summing up, we can conclude that the six video cases exemplarily allow for discussing a rich variety of facilitation moves.The six video cases predominately show situations of a PD course in which the PD facilitator interacts with the teachers to foster their mathematics learning. Thus it is not surprising that the moves our participants noticed are concerned with attending to crucial teachers’ ideas (The third research question was concerned with exploring how the video cases can be used to compile structured facilitator PD. That is, when the video cases will be used in a facilitator PD, noticing prompts will enrich the scenes. As research findings confirm, such structured video clubs (cf. van Es and Sherin So far, we could reach the main aim of our validation study with respect to the content of the video cases: All six video cases present valid examples of facilitators fostering teacher learning and can be used as artifacts to foster PD facilitators’ learning. The suggested alternative facilitation moves and noticing prompts specified the proposed intention of discussing the video cases. Based on our results, we will be able to finally compile the video cases and to enrich them with respect to the noticing categories that will play a prominent role in the PD for prospective facilitators.In reflecting upon our study, we encountered several challenges, which on the one hand are crucial for our future work, but on the other hand extend to the research on PD facilitation in general. The first challenge lies within bridging different frameworks and conceptualizations to describe what knowledge and skills PD facilitators need to foster mathematics teachers’ learning. Applying the facilitation move framework by van Es et al.  and Gonzevidence of validity these video cases need to provide reliable learning opportunities for prospective PD facilitators. Even though our results show sufficient ratings in terms of SCK, PD-PCK, or possible facilitation moves involved, we could show that specific prompts are needed to unlock the full potential of the video cases as learning incidents. This observation is in line with research on facilitating video-based discussion (cf. Borko et al. The second challenge concerns our approach to develop and validate video cases from authentic PD courses with the purpose of qualifying prospective PD facilitators. From a methodical perspective, we raised the question what Although our results are of course bound to the six video cases we selected, our approach can easily be transferred to other contexts. The procedure of compiling the video cases and validating them is in line with the most prominent research findings on designing facilitator PD. We exemplarily showed how empirical evidence could be used to prepare facilitator PD.


Setbacks are an integral part of a scientific career, yet little is known about their long-term effects. Here we examine junior scientists applying for National Institutes of Health R01 grants. By focusing on proposals fell just below and just above the funding threshold, we compare near-miss with narrow-win applicants, and find that an early-career setback has powerful, opposing effects. On the one hand, it significantly increases attrition, predicting more than a 10% chance of disappearing permanently from the NIH system. Yet, despite an early setback, individuals with near misses systematically outperform those with narrow wins in the longer run. Moreover, this performance advantage seems to go beyond a screening mechanism, suggesting early-career setback appears to cause a performance improvement among those who persevere. Overall, these findings are consistent with the concept that “what doesn’t kill me makes me stronger,” which may have broad implications for identifying, training and nurturing junior scientists. Little is known about the long-term effects of early-career setback. Here, the authors compare junior scientists who were awarded a NIH grant to those with similar track records, who were not, and find that individuals with the early setback systematically performed better in the longer term. In addition to community recognition, bringing future attention and resources15, success may also influence individual motivation16, where positive feedback bolsters self-confidence. Together, these views indicate that it is early-career success, not failure, that would lead to future success. Yet at the same time other mechanisms suggest that the opposite may also be true. Indeed, screening mechanisms18 suggest that, if early-career failures screen out less-determined researchers, early setbacks among those who remain could, perhaps counterintuitively, become a marker for future achievement. Further, failure may teach valuable lessons that are hard to learn otherwise21, while also motivating individuals to redouble effort23, whereas success may be associated with complacency16 or reduced future effort due to utility maximization24. Such positive views of failure are reflected in Nietzsche’s classic phrase “what doesn’t kill me makes me stronger”25, in the celebration-of-failure mindset in Silicon Valley26, and in a recent commencement address by U.S. Supreme Court chief justice John Roberts, who told graduating students “I wish you bad luck.” Overall, these divergent perspectives indicate that the net effect of an early-career setback is unclear. Given the consequential nature of this question to individual careers and the institutions that support and nurture them, and building on the remarkable progress in our quantitative understanding of science51, here we ask: Can an early-career setback lead to future career impact?“Science is 99 percent failure, and that’s an optimistic view”, said Robert Lefkowitz, who was awarded the Nobel prize in 2012 for his groundbreaking studies of G protein-coupled receptors. Despite the ubiquitous nature of failures, it remains unclear if a setback in an early career may augment or hamper an individual’s future career impact. Indeed, the Matthew effectTo offer quantitative answers to this question, we leverage a unique dataset, containing all R01 grant applications ever submitted to the NIH, to examine early-career success and failure. NIH funding decisions are largely determined by paylines derived from evaluation scores. Our empirical strategy harnesses the highly nonlinear relationship between funding success and evaluation score around the funding threshold Fig. . Indeed,We examine performance and demographic characteristics for the two groups of PIs, finding that prior to treatment, they are statistically indistinguishable along all dimensions we measured Fig. . Yet the52. We then computed, out of the papers published by the near-miss and narrow-win group, the probability of finding hit papers . This performance advantage persisted: We analyzed papers produced in the second five-year window (6–10 years after treatment), uncovering a similar gap . To ensure the observed effect is not just limited to hit papers, we also quantified performance using other commonly used measures, including average citations received within five years of publication  and 12.0% more citations  than those by the narrow-win group, respectively , which is consistent with prior studies59. Yet the funding difference between the two groups disappeared in the second five-year period . Although the NIH is the world’s largest funder for biomedical research, near misses might have obtained more funding elsewhere , which might also drive future career outcomes. To rule out alternative explanations, we leverage two additional inference techniques, Coarsened Exact Matching (CEM)62 and fuzzy Regression Discontinuity (RD)64. We first matched near misses and narrow wins with respect to a wide range of observable characteristics (see Methods section for further description of CEM), and find that after matching, near misses still outperformed narrow wins in terms of both hit papers  and average citations per paper , and the average citations per paper by 34%  (see Methods section). The RD analyses help establish the causal interpretation of our results, and the agreement in results across all the methods further demonstrates the robustness of our findings.Is the uncovered difference in outcomes causally attributable to the early-career setback? Or, could it be explained by other alternative forces? Indeed, there might still exist observable or otherwise unobserved factors that affect funding success near the threshold . This difference is not simply because narrow wins received an initial grant. Indeed, the gap persisted and extended beyond the first five years, remaining at 11.8% in year seven , followed by a drop afterwards. The RD analysis indicates that an early-career near miss on average led to a 12.6% chance of disappearing permanently from the NIH system over the next ten years (see Methods section). These results thus highlight the fragility of a junior scientific career, with one early near miss being associated with significantly higher attrition from the NIH system, despite the fact that to become an NIH PI, one had to go through years of training with a demonstrated track record of research. Notwithstanding the evidence that PhDs who left science are disproportionally employed at large, high-wage establishments65, Fig. We first investigate attrition rates by studying the percentage of the initial PIs who remained active in the NIH system and find that the attrition rate of the two groups differed significantly Fig. . In the To understand the nature of the potential screening effect, we first test its underlying assumption by comparing pre-treatment characteristics of near misses and narrow wins who remained ex post, finding a lack of difference between these two groups in any observable dimension ex ante  or normalized citations   whether a paper is a clinical trial publication ; (2) whether a paper has been cited by at least one clinical trial publication , and (3) whether a paper has potential to become translational research70 . We compared works produced by near misses and narrow wins over the ten-year period, finding that across all three translational dimensions, near misses systematically outperformed narrow wins. Specifically, near misses were 50% more likely to publish a clinical trial paper compared with narrow wins , and  whether on), and  whether 25.Overall, these results document that an early-career setback has powerful, opposing effects, hurting some careers, but also, quite surprisingly, strengthening outcomes for others. As such, these findings show that prior setback can indeed be a mark of future success. Screening effects may partly be responsible yet appeared insufficient to explain the magnitude of the observed effects, supporting the idea that failure may teach valuable lessons23 or sacred sparks71. Crucially, the empirical findings and conclusions reported in the paper hold the same, regardless of the underlying processes. Indeed, while most empirical and theoretical evidence in science thus far documents that individuals benefit tremendously from success59, our results offer among the first empirical evidence showing that some individuals can also benefit from setbacks, which may have broad implications for both individual investigators and institutions that aim to support and nurture them.The uncovered effects may operate according to multidimensional mechanisms. We explored ten different observable dimensions, including shifts in intellectual direction and leadership, institutional locus, and collaboration patterns (see Methods section). We find only a suggestive tendency for near-miss scientists to publish in hot topic areas following treatment, although accounting for this factor did not reduce the observed performance gap , to what degree our findings may generalize substantially beyond near misses is a question we cannot yet answer conclusively. Moreover, the opposing effects of early setbacks also suggest there may exist population heterogeneities in responses that are worth exploring further. Who tends to be the most vulnerable, and who the most resilient? Quantitative answers to these questions may be crucial for the interpretation of our insights to inform policies and intervention strategies for building a robust scientific workforce74.The design of our study necessitates the focus on near-miss individuals among all others who had setbacks36 and beyond13, where past success begets future success, these results suggest that powerful, offsetting mechanisms may be at work. This implies that, in areas where the Matthew effect operates less, the net advantage of failure may be more pronounced, suggesting that other domains provide important additional avenues for future work.Moreover, our analyses estimate the net advantage of near misses over narrow wins, which is only detectable if the gross advantage of early-career failure outweighs any benefits conferred by success. Given the widespread, convincing evidence supporting the validity of the Matthew effect in scienceFinally, note that our results do not imply that one should strategically put roadblocks in the way of junior scientists, as the precondition of becoming stronger is to not be killed in the first place. The findings do suggest, however, that for those who persevere, early failure should not be taken as a negative signal—but rather the opposite, in line with Shinya Yamanaka’s advice to young scientists, after winning the Nobel prize for the discovery of iPS cells, “I can see any failure as a chance.”75, the observed performance gap might reflect collaborations, whereby near misses more frequently teamed up with higher-impact scientists and/or published fewer lead-author publications than their narrow-win counterparts. Alternatively, the uncovered difference might reflect an observable personal change process in terms of intellectual or physical mobility, as captured by research direction shifts (hypothesis C)76 or changing institutions (hypothesis D)78. We tested hypotheses A–D from our data, finding that there is only a suggestive tendency for near-miss scientists to publish in hot topic areas following treatment, although accounting for this finding does not reduce the observed performance gap  did early-career setbacks propel persistent junior scientists to attempt more novel research, whereas narrow wins were bound to their original ideas? (B) Did early-career setbacks lead junior scientists to seek out advantageous collaborations? Indeed, as teams are increasingly responsible for producing high-impact work52 i.e., there might be other factors that influence both the funding decision and future career outcome. The finding that observable features of the two groups are statistically indistinguishable prior to the funding decisions helps diminish this concern. Further, were there some unobserved factor determining outcomes, such a factor would need to both advantage the narrow wins in getting initial funding yet disadvantage them over the longer run, which may be implausible. Nevertheless, to fully eliminate such endogeneity concerns, one needs to employ a causal inference framework called fuzzy regression discontinuity design (RD)63. In this section, we describe in detail our econometric model specification and estimation procedures.A possible concern with the comparison between the near misses and narrow wins near the threshold is endogeneity;64, in addition to prior research on funding data79.The key idea of RD is that if decision rules create a jump in the likelihood of treatment, often at an arbitrary threshold, we can exploit this local discontinuity as an exogenous variable to predict outcome, instead of using the specific, realized treatment outcome, which could be influenced by endogenous factors. Such RD approaches have been widely used in the fields of education, labor, political economy, health, crime, and environmental studies79. The highly nonlinear relationship between the evaluation score and funding success  is largely determined by the score of each proposaless Fig.  makes ouMore specifically, we estimate the causal effect of early-career setbacks on future career outcomes using two-stage least squares regression (2SLS): in the first stage, the instrumental variable (being above or below the score threshold) is used to predict the funding outcome; in the second stage future career outcomes are regressed on the predicted funding outcome from the first stage. As illustrated in Supplementary Fig. s0 , we havesj is the running variable, i.e., normalized score for proposal j, Fj is the funding decision outcome, and s0. The probability to receive treatment iszj = 1, if sj ≥ s0 and zj = 0 otherwise. Since s0 is the normalized score with a funding threshold that divides the proposals at an arbitrary point, the dummy variable zj is uncorrelated with any observed or unobserved factors52. To this end, we treat zj as the instrument variable and employ a simple two-stage least square (2SLS) regression estimation. Let yit be some scientific outcome of individual i during time period t, i.e., probability to publish hit papers, number of publications, or number of hit papers. We conduct the estimation as follows:Xi,pre is the prior performance of researcher i, i.e., prior number of publications, prior number of hit papers; μt and ηn and p is the order of the polynomial control of the running variable, and ηj and ∈i are error terms from the first and second stage, respectively. Moreover, ∈i, and λ is the causal effect of near miss on future career outcomes. For a large sample that span a significant fraction of PIs around 0, we need careful controls of priority score. In the following analyses, we added the linear control of score when considering ±10 discontinuity sample (p = 1), and 3rd order polynomial control for ±25 discontinuity sample (p = 3). Finally, we eliminate these polynomial controls as we restrict the sample to the very narrow region around the discontinuity point63 .More specifically, given the jump in the probability of receiving the funding at s0, so that individual scientists cannot precisely manipulate the score to be above or below the threshold. This assumption is valid in our setting, because the scores are given by external reviewers, and cannot be determined precisely by the applicants. To offer quantitative support for the validity of our approach, we run the McCrary test80 to check if there is any density discontinuity of the running variable near the cutoff, and find that the running variable does not show significant density discontinuity at the cutoff . Together, these results validate the key assumptions of the fuzzy RD approach.The credibility of these estimates hinges on the assumption of the lack of prior knowledge of the cutoff, p-value < 0.05). The average citations gained by the near-miss group is 9.67 more than the narrow-win group . By focusing on the number of hit papers in the next 10 years after treatment, we again find significant difference: near-miss applicants publish 3.6 more hit papers compared with narrow-win applicants . All these results are consistent with when we expand the sample size to incorporate wider score bands and control for the running variable χ2-test p-value < 0.001, odds ratio = 1.20, Supplementary Fig. t-test p-value < 0.001, Cohen’s d = 0.05, Supplementary Fig. Following the algorithm, we use a set of ex ante features to control for individual grant experiences, scientific achievements, demographic features, and academic environments; these features include the number of prior R01 applications, number of hit papers published within three years prior to treatment, PI gender, ethnicity, reputation of the applicant’ institution as matching covariates. In total, we matched 475 of near misses out of 623; and among all 561 narrow wins, we can match 453. We then repeated our analyses by comparing career outcomes of matched near misses and narrow wins in the subsequent ten-year period after the treatment. We find near misses have 16.4% chances to publish hit papers, while for narrow wins this number is 14.0% (Further information on research design is available in the Supplementary InformationPeer Review FileReporting Summary


Alcohol-related problems affect increasing numbers of older adults. Recent studies have begun to investigate problem drinking among older adults based on a conceptual model proposing correlations between personal characteristics, life context , treatment, and drinking-related outcomes. In a community sample of older problem and nonproblem drinkers, alcohol consumption, life stressors, social resources, and coping responses differed between the two groups, although these factors did not directly and uniformly affect late-life drinking behavior. Furthermore, drinking behavior did not always have the expected effects on older drinkers’ life contexts. Findings from a sample of treated alcohol and other drug-abusing older patients demonstrated the importance of providing mental health aftercare for this group. Historically, most efforts to understand and treat problem drinkingThis heightened interest in the alcohol-related problems of older adults has inspired studies yielding considerable information about the scope and correlates of alcohol consumption and problem drinking in late adulthood. The current prevalence of alcohol abuse and dependence in the general population of older adults is between 2 and 4 percent; it is considerably higher—5 to 30 percent—in clinical populations . Most stRecent research highlights the importance of distinguishing between two groups of older problem drinkers: late onset and early onset. Late onset problem drinkers, of whom a significant proportion are women, first develop drinking problems later in life . Early onset problem drinkers, in contrast, develop drinking problems earlier during adolescence or adulthood and maintain them into late life. Compared with early onset problem drinkers, late onset problem drinkers generally are in better health , have better social relations , and are less likely to have been treated for alcohol and other drug (AOD) abuse , preventing inferences about the direction of causality between variables . Moreover, most studies have focused on correlations between personal characteristics  and late-life drinking behavior; few have considered the influence of the drinkers’ environmental contexts . Finally, little is known about either the factors that prompt older adults to seek help for their alcohol-related problems or the treatment efficacy for this group. This article presents a model for conceptualizing late-life drinking behavior. Based on this research model, the article also describes the findings of two long-term  research studies aimed at elucidating predictors of alcohol consumption, drinking problems, treatment seeking, and treatment outcome in older adults.The conceptual framework presented in The late-life drinking behavior model posits several relationships between these four domains :Both personal characteristics and life context affect treatment seeking as well as drinking behavior and outcomes.Drinking behavior, in turn, influences a person’s life context and certain personal characteristics.Some personal characteristics moderate the relationship between life context and outcomes.Treatment, including specific aspects of treatment programs, influences drinking-related outcomes.The validity of these assumptions was tested using a sample of older community residents as well as a sample of treated older AOD-abuse patients. The findings obtained with these two samples are described in the following sections.To examine the relationships between personal characteristics, life context, treatment seeking, and late-life drinking behavior, Brennan, Moos, and colleagues  studied Focusing on the latter two groups, the investigators addressed four questions: (1) Do the personal characteristics, life contexts, and coping responses of older problem drinkers differ from those of older nonproblem drinkers? (2) Do personal and life context factors at the beginning of the study predict drinking behavior 1 and 4 years later? (3) How does initial alcohol use in older problem drinkers affect their subsequent life context and psychological well-being? (4) What factors prompt older community residents to seek treatment for alcohol-related problems?Older problem and nonproblem drinkers differed with respect to several personal characteristics . As expeProblem drinkers also had more stressful life contexts than did nonproblem drinkers . Thus, tFinally, problem drinkers and nonproblem drinkers differed in their coping responses to stressful situations. Two broad categories of coping responses are approach coping and avoidance coping. Approach coping involves attempts to master or resolve a stressful situation; avoidance coping consists of efforts to avoid thinking about a stressor and its implications and includes the expression of stress-related emotions without attempting a resolution. A comparison of older problem and nonproblem drinkers showed that although both groups used comparable levels of approach-coping strategies to manage stressors, problem drinkers were more likely to use avoidance-coping strategies  Moos et.Consistent with earlier research  several Overall, these results implied that experiencing more stressors, having fewer social resources, and relying more heavily on avoidance coping could lead to late-life drinking problems. The results also suggested that drinking problems might harm the life contexts and psychological well-being of older adults. To learn more about these causal relationships, the participants were reassessed over extended periods of time.reduced alcohol consumption over intervals ranging from 1 to 10 years  tends to determine how social resources influence drinking behavior . Thus, iThe study’s findings also illustrate the influence of an older person’s drinking history on the relationship between life context and drinking behavior: The more alcohol the older drinkers consumed at the beginning of the study, the more likely were certain stressful life events, such as a relative’s sickness or injury, to cause an increase or a smaller-than-expected decrease in alcohol consumption at followup . SimilarThe use of certain coping responses also appears to moderate the effects of life context on late-life drinking behavior. For instance, more non-health-related negative life events predicted elevated drinking problems among older drinkers who relied heavily on avoidance coping. In contrast, among drinkers who used fewer avoidance-coping strategies, negative life events prompted a decline in drinking problems . SimilarTaken together, these observations belie the idea that life context directly and uniformly affects drinking behavior in later life. Whether and how stressors and social resources influence late-life drinking appear to depend on several factors, including (1) the specific type of stressors , (2) the type of drinking behavior being assessed , and (3) personal risk factors .Although several studies have analyzed the effects of life context on late-life drinking, few have considered the effects of older adults’ drinking behavior on their subsequent life contexts and personal well-being. Contrary to intuitive expectations, these studies indicate that ongoing drinking problems generally do not adversely affect the life contexts of older drinkers. For example, at the 1-year followup in the community study of older adults, problem-drinking women experienced a decline in spouse stressors, and problem-drinking men reported a reduction in conflicts with friends . MoreoveSimilarly, older adults’ drinking behavior affected their psychological well-being in unexpected ways. For example, heavier initial alcohol consumption among women predicted fewer subsequent depressive symptoms; among men, more initial drinking problems predicted reduced depression .Finally, one would expect remission from drinking problems to improve the life contexts of older men and women. However, remission had little influence on the life contexts of male problem drinkers. Moreover, women who remitted experienced a loss of support from extended family members and reported more family stressors at followup than did remitted men . Thus, fLonger term followups are needed to determine the permanence of these effects as well as their consequences. For example, do ongoing drinking problems eventually lead to increased interpersonal stressors? And do adverse family contexts or self-medication with alcohol to avoid depression pose relapse risks for older, remitted women? The answers to these questions might have treatment implications; older women in early remission, for example, may need enhanced support to cope with family conflict and depressive symptoms.Older adults rarely seek formal treatment . ConsistSeveral factors predicted whether these community residents sought treatment. The most important predictors were prior treatment seeking and a greater number of health problems compared with the rest of the group. Frequently using avoidance-coping responses, experiencing more negative life events, and having fewer friends who approved of drinking also predicted more treatment seeking . FinallyThese findings suggest that older adults in the community are reluctant to identify themselves as having drinking problems and therefore delay treatment until their health problems and stressful life contexts require it. This result highlights the importance of identifying and treating older adults’ drinking problems early. In addition, more information is needed about the personal characteristics, life contexts, and treatment features that deter older adults from seeking help for alcohol-related problems.Despite their reluctance to seek treatment, older adults constitute at least 20 percent of the AOD-abuse population in inpatient settings . Yet litBased on this information, the researchers addressed two broad sets of questions: (1) What are the extent and the predictors of health service use by older AOD-abuse patients? (2) To what extent is AOD-abuse treatment effective for older patients, and which specific treatment program characteristics predict better outcome?The VA AOD-abuse patients used health care services heavily. They received more than 920,000 days of care for AOD abuse or psychiatric disorders in the 4 years before their index episodes of care as well as 1.2 million days of care in the 4 years afterwards b. MoreovOlder and younger AOD-abuse patients received different types of treatment. Compared with younger patients, older patients received care focused more on their medical needs  than on their AOD-abuse and psychiatric treatment needs . MoreoveThe readmission rates of older patients depended in part on their AOD-abuse histories. First-time AOD-abuse patients had lower readmission rates than the total sample b. This fCo-occurring psychiatric disorders also affected the frequency of health service use and complicated the treatment of older AOD abusers. At the index episode of care, almost 30 percent of the patients suffered from concomitant psychiatric disorders, most commonly depressive disorders, personality disorders, and schizophrenia . These dIn addition to AOD-abuse history and the presence of psychiatric disorders, the study identified several other predictors of higher readmission rates for older AOD-abuse patients at both the 1- and 4-year followups. These predictors included being unmarried, more prior service use, more severe and complex psychiatric diagnoses, disrupted or shorter length of treatment, and insufficient mental health aftercare b, 1995.The question of treatment effectiveness among older AOD-abuse patients usually is framed as a comparison: Do older patients respond as well to AOD-abuse treatment as younger patients do? No definitive answer exists for this question (for reviews, see Some recent investigations have begun to clarify this issue by examining the match between age and specific treatment modalities. For example, Although the studies reviewed here have contributed new data about late-life drinking behavior, many questions remain. For example, further information is needed on the relationships between life context and drinking behavior in later life. Moreover, longitudinal studies should investigate the predictors of late onset problem drinking and its remission. Researchers must identify factors that deter older adults from seeking assistance for their alcohol-related problems and devise new screening and referral methods that facilitate earlier recognition and treatment of late-life drinking problems.The study of VA patients has demonstrated that older, treated AOD-abuse patients—especially those with long histories of alcohol abuse and psychiatric comorbidity—place a heavy burden on the health care system. Consequently, researchers and other professionals must work to evaluate and improve the treatment effectiveness in this patient population. Factors such as continuity of care and followup mental health care appear to promote better outcomes among older patients and may be especially important for patients who have fewer informal social resources from which to draw. Accordingly, researchers must determine how much and what kind of mental health aftercare is optimal for maintaining successful treatment outcomes among older patients.Future research also should address the match between the treatment needs of older AOD-abuse patients and particular treatment program characteristics. Currently, the data more clearly indicate which treatment approaches do not work well for older patients than which ones do. More broadly, a need exists for further theory development in the study of late-life drinking behavior and for more longitudinal investigations of older adults’ drinking behavior, especially among understudied populations, such as older women and older adults in racial minority groups. Such work should enhance our understanding of the course and predictors of late-life drinking behavior and assist clinicians in treating older adults’ alcohol-related problems.


There are few network resources in wireless multimedia sensor networks (WMSNs). Compressing media data can reduce the reliance of user’s Quality of Experience (QoE) on network resources. Existing video coding software, such as H.264 and H.265, focuses only on spatial and short-term information redundancy. However, video usually contains redundancy over a long period of time. Therefore, compressing video information redundancy with a long period of time without compromising the user experience and adaptive delivery is a challenge in WMSNs. In this paper, a semantic-aware super-resolution transmission for adaptive video streaming system (SASRT) for WMSNs is presented. In the SASRT, some deep learning algorithms are used to extract video semantic information and enrich the video quality. On the multimedia sensor, different bit-rate semantic information and video data are encoded and uploaded to user. Semantic information can also be identified on the user side, further reducing the amount of data that needs to be transferred. However, identifying semantic information on the user side may increase the computational cost of the user side. On the user side, video quality is enriched with super-resolution technologies. The major challenges faced by SASRT include where the semantic information is identified, how to choose the bit rates of semantic and video information, and how network resources should be allocated to video and semantic information. The optimization problem is formulated as a complexity-constrained nonlinear NP-hard problem. Three adaptive strategies and a heuristic algorithm are proposed to solve the optimization problem. Simulation results demonstrate that SASRT can compress video information redundancy with a long period of time effectively and enrich the user experience with limited network resources while simultaneously improving the utilization of these network resources. In recent years, wireless multimedia sensor networks (WMSNs), such as those used in transport management, health-care monitoring and live streaming services, have become increasingly popular. Users can watch videos taken by multimedia sensors everywhere at any time. The new generation of multimedia sensor nodes, such as DeepLens (a deep learning wireless camera released by Amazon), has superior hardware capabilities and can run deep learning algorithms. In WMSNs, there are few network resources due to multipath fading, shadowing and noise disturbance of wireless channels . HoweverCompressing media data can reduce the user’s quality of experience (QoE) reliance on network resources. Existing video coding software, such as H.264 and H.265, focuses only on spatial and short-term information redundancy. However, videos usually contain redundancy over a long period of time. For example, in transport management, some objects (traffic police) and scenes (highways) are repeated. Therefore, compressing video information redundancy with a long period of time without compromising the user experience is a challenge.In research on video coding, the general idea is to increase the compression efficiency of video coding . HoweverIn this paper, we have compressed long-term information redundancy through super-resolution technology and video transmission technology in WMSNs. It is feasible to compress video data by reducing data of the transmitted video and enriching the received video quality with super-resolution. Image super-resolution technology allows a higher-resolution image to be reconstructed from lower resolution during image processing. Super-resolution technologies have undergone significant development based on artificial intelligence . StudiesIn this paper, we propose a semantic-aware super-resolution transmission for an adaptive video streaming system (SASRT) for WMSNs. The idea of SASRT is presented in In contrast to applications in the field of image processing, more semantic information can be obtained from the original image in WMSNs. However, the identification of more detailed semantic information increases the consumption of network resources. Another method is utilized when limited semantic information is recognized on the user side. This method can reduce the consumption of network resources but increases the computational costs faced by the user side. Therefore, the major challenges faced by SASRT include where semantic information is identified, how to choose the bit rates of semantic and video information to encode, and how network resources are allocated to video and semantic information.The above challenges are solved in the SASRT framework. In addition, in contrast to traditional transmission methods, the objective of SASRT is to encode and transmit different bit-rate video and semantic information. Then, we introduce a novel mathematical model for characterizing the user experience to be affected by certain factors in the proposed SASRT. Based on the model, the problem of maximum income is considered. Then, the problem is proven to be an NP-hard problem. Finally, three adaptive strategies and a heuristic algorithm are proposed to solve the NP-hard problem. The SASRT scheme can be used in the scene of smart cities ,9,10,11.The remainder of this paper is organized as follows. In In this section, we review research on video coding, video transmission and super-resolution technologies.Studies on video coding are based primarily on reliable systems. Regardless of the compression algorithm, the same data are required before and after compression. A new image-coding scheme that uses a region-adaptive prediction method with modified current specifications on JPEG XT Part 7 is proposed in . In 2],,2], a viMany scholars have performed research on video transmission in WMSNs. In , a powerMany papers have studied super-resolution technologies. Two types of methods are used for super-resolution imagery. The first type is the use of traditional mathematical interpolation methods to achieve super-resolution images e.g., ,22,23). ,23. 22,2Some scholars are also working on topics related to deep learning and video e.g., ,31). In . In 31])In summary, coding technology and network transmission technology have been extensively developed. However, video data will increasingly dominate mobile network traffic. It is predicted that, by 2022, 79 percent of mobile data traffic will be video, up from 59 percent in 2017 . Video tIn this section, we introduce the concept of SASRT over WMSNs and describe the system architecture and model. Then, three adaptive strategies are proposed and analyzed individually.SFTGAN is one of the best super-resolution technologies, as presented in . More viNote that our method does not depend on SFTGAN. For other super-resolution methods, the gain in super-resolution performance achieved through semantic information is different. Thus, our method is still effective.The transmission process of SASRT is shown in In this section, we describe the system model and formulate the optimization problem.E is used to express the user experience.s is the number of video segments. ith segment. Assume that each video segment plays for jth frame in the ith segment. In the formulas above, the value of k in the jth frame. kth piece of semantic information. C and the semantic information bit rate of quality level ℑ is a function of the relationship between the video bit rate and the video quality level, l is the video frame level, B is the bandwidth at the current time. The selection of B, which can be estimated byB is the predicted network bandwidth, There are many multimedia sensor application scenarios in daily life such as health-care monitoring and live streaming. The application of different super-resolution models for different multimedia sensor scenarios can improve the efficiency of super-resolution technologies. Assume that a scenario for a multimedia sensor is or SSIM) .(2)Ei=QNo super-resolution model is perfect; different models achieve different super-resolution reconstruction efficiencies. For example, a human image super-resolution model used to improve the resolution of an animal image will be less effective. Therefore, it is necessary to use different super-resolution models to improve the resolution of different types of images. The collection Assuming the traditional method under the above conditions, the bit rate of the video is In its most generic form, the problem can be formulated as follows.We first find a special scene of the problem given by Equation . Then, wTheorem 1.The problem defined by Equation  is an NPProof. Consider a special case of Equation  with ℓ1=Equation  reduces quation . Dynamic video sensors have a large background change in the video. Super-resolution performance is different in different video scenes. More quality differences exist between video segments, which reduces the quality stability of video playback. Another limitation is that the scene shot by the sensor needs a super-resolution model for this scene. The strategy proposed in this paper requires running deep learning algorithms. Especially user equipment could have power restrictions. Weighing the energy consumption and performance is another issue. The above limitations are also our goal of optimization in the future.