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Aim: The aim of this paper is to evaluate biomaterial cues combined with physical therapy (PT) on functional recovery in a rat sciatic nerve injury model. Materials & methods: Nerve growth conduits were filled with longitudinally aligned hyaluronic acid fibers and microspheres containing neurotrophic factor (growth factor [GF]). All animals received behavior and functional testing throughout the study, which concluded with measurement of compound muscle action potentials and contractile force of the gastrocnemius muscle. Results & conclusion: Including GF improved recovery of gross motor function and increased sensory pain sensation. During the 4 weeks that animals participated in PT, these groups showed higher static sciatic index scores. Including GF and PT has the potential to improve clinical outcomes following peripheral nerve injury.

PURPOSE: This study assessed the safety and tolerability of therapeutic immunization against the human papillomavirus (HPV) viral oncoproteins E6 and E7 in patients with cervical cancer after chemoradiation. METHODS AND MATERIALS: MEDI0457 (INO-3112) is a DNA-based vaccine targeting E6 and E7 of HPV-16/18 that is coinjected with an IL-12 plasmid followed by electroporation with the CELLECTRA 5P device. At 2 to 4 weeks after chemoradiation, patients with newly diagnosed stage IB1-IVA (cohort 1) or persistent/recurrent (cohort 2) cervical cancers were treated with 4 immunizations of MEDI0457 every 4 weeks. The primary endpoints were incidence of adverse events and injection site reactions. Immune responses against HPV antigens were measured by ELISpot for interferon-γ (IFNγ), enzyme-linked immunosorbent assay for antibody responses and multiplexed immunofluorescence for immune cells in cervical biopsy specimens. RESULTS: Ten patients (cohort 1, n = 7; cohort 2, n = 3) with HPV16 (n = 7) or HPV18 (n = 3) cervical cancers received MEDI0457 after chemoradiation. Treatment-related adverse events were all grade 1, primarily related to the injection site. Eight of 10 patients had detectable cellular or humoral immune responses against HPV antigens after chemoradiation and vaccination: 6 of 10 patients generated anti-HPV antibody responses and 6 of 10 patients generated IFNγ-producing T cell responses. At the completion of chemoradiation and vaccination, cervical biopsy specimens had detectable CD8(+) T cells and decreased PD-1(+)CD8(+), PD-L1(+)CD8(+), and PD-L1(+)CD68(+) subpopulations. All patients cleared detectable HPV DNA in cervical biopsies by completion of chemoradiation and vaccination. CONCLUSIONS: Adjuvant MEDI0457 is safe and well tolerated after chemoradiation for locally advanced or recurrent cervical cancers, supporting further investigation into combining tumor-specific vaccines with radiation therapy.

Building on the premises that institutional ownerships vary in their impact on corporate social responsibility (CSR) decisions and that geographic proximity facilitates the valuation of benefits from CSR, we hypothesize that local long-term institutional ownership is a driver for corporate social performance, in particular positive CSR (CSR strengths). Using a panel data of S&P 500 firms over a 15-year window, we show that long-term institutional ownership that varies in geographic proximity to the focal firm does have a heterogeneous impact on CSR. Whereas both local and non-local long-term institutional ownership has a similar negative effect on CSR concerns, only local long-term institutional ownership has a positive effect on CSR strengths. The positive relation between local long-term institutional ownership and CSR is stronger in firms that are more involved in dealing with soft information which is difficult to quantify from a distance, such as those with high levels of research and development and intangible assets.

This article draws upon the theories of entrepreneurial cognition, planned behavior, and criminal desistance to understand the role of entrepreneurship education in the behavioral and cognitive transformation of incarcerated individuals. Specifically, this article considers how participation in an entrepreneurship education program should influence entrepreneurial opportunity recognition, cognitive transformation, and institutional misconduct. It suggests these changes are more likely to influence an incarcerated person’s entrepreneurial intentions and criminal desistance. The six propositions presented shed light on how an incarcerated individual’s willingness to change his or her attitudes and develop an entrepreneurial mind-set influence his or her behavior in prison and prepares him or her to prosper in a dynamic and complex world after release. This article argues that the study of one’s transformation while incarcerated through the discovery, evaluation, and exploitation of opportunities is likely to advance empirical and theoretical perspectives of the fields of entrepreneurship. The examination of how incarcerated persons deal with fear of failure, risk aversion, and identity, in particular, presents great opportunities for future research.

Introduction: In 2010, experts in osteoporosis and bone densitometry were convened by the Space Life Sciences Directorate at NASA Johnson Space Center to identify a skeletal outcome in astronauts after spaceflight that would require a clinical response to address fracture risk. After reviewing astronaut data, experts expressed concern over discordant patterns in loss and recovery of bone mineral density (BMD) after spaceflight as monitored by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). The pilot study described herein demonstrates the use of QCT to evaluate absence of recovery in hip trabecular BMD by QCT as an indicator of a clinically actionable response. Methodology: QCT and DXA scans of both hips were performed on 10 astronauts: once preflight and twice postflight about 1 wk and 1 yr after return. If trabecular BMD had not returned to baseline (i.e., within QCT measurement error) in 1 or both hips 1 yr after flight, then another QCT hip scan was obtained at 2 yr after flight. Results: Areal BMD by DXA recovered in 9 of 10 astronauts at 1 yr postflight while incomplete recovery of trabecular BMD by QCT was evident in 5 of 10 astronauts and persisted in 4 of the 5 astronauts 2 yr postflight. Conclusion: As an adjunct to DXA, QCT is needed to detect changes to hip trabecular BMD after spaceflight and to confirm complete recovery. Incomplete recovery at 2 yr should trigger the need for further evaluation and possible intervention to mitigate premature fragility and fractures in astronauts following long-duration spaceflight.

Telephone surveys have been a ubiquitous method of collecting survey data, but the environment for telephone surveys is changing. Many surveys are transitioning from telephone to self-administration or combinations of modes for both recruitment and survey administration. Survey organizations are conducting these transitions from telephone to mixed modes with only limited guidance from existing empirical literature and best practices. This article summarizes findings by an AAPOR Task Force on how these transitions have occurred for surveys and research organizations in general. We find that transitions from a telephone to a self-administered or mixed-mode survey are motivated by a desire to control costs, to maintain or improve data quality, or both. The most common mode to recruit respondents when transitioning is mail, but recent mixed-mode studies use only web or mail and web together as survey administration modes. Although early studies found that telephone response rates met or exceeded response rates to the self-administered or mixed modes, after about 2013, response rates to the self-administered or mixed modes tended to exceed those for the telephone mode, largely because of a decline in the telephone mode response rates. Transitioning offers opportunities related to improved frame coverage and geographic targeting, delivery of incentives, visual design of an instrument, and cost savings, but challenges exist related to selecting a respondent within a household, length of a questionnaire, differences across modes in use of computerization to facilitate skip patterns and other questionnaire design features, and lack of an interviewer for respondent motivation and clarification. Other challenges related to surveying youth, conducting surveys in multiple languages, collecting nonsurvey data such as biomeasures or consent to link to administrative data, and estimation with multiple modes are also prominent.

Background: DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A formulation in clinical development. A phase 2 dose-ranging study identified an optimal dose and demonstrated efficacy with a median duration of 24 weeks. Methods: In two phase 3, multicenter, randomized, double-blind, placebo-controlled studies (SAKURA 1 and SAKURA 2), subjects with moderate or severe glabellar lines at maximum frown were assigned randomly to receive placebo or 40 U of DAXI. Glabellar lines were evaluated at least every 4 weeks for at least 24 weeks until severity returned to baseline (≤36 weeks). Results: Overall, 609 subjects were enrolled (DAXI, n = 405; placebo, n = 204). DAXI was significantly more effective than placebo in achieving the primary efficacy outcome (≥2-point improvement in glabellar line severity at maximum frown at week 4 according to both investigator and subject ratings): 73.6 percent versus 0.0 percent (SAKURA 1), and 74.0 percent versus 1.0 percent (SAKURA 2) (both p < 0.0001). Composite investigator and subject ratings of maximum frown after DAXI treatment showed that glabellar line severity of none or mild was maintained for a median of 24.0 weeks (SAKURA 1) and 23.9 weeks (SAKURA 2), and glabellar line severity did not return to baseline levels for a median of 27.7 and 26.0 weeks, respectively. DAXI was generally well tolerated, with the most common adverse events related to DAXI treatment being headache (SAKURA 1, 7.0 percent; SAKURA 2, 5.9 percent) and injection-site pain (5.0 percent and 2.4 percent, respectively). Conclusions: Results from both studies were highly consistent. DAXI may offer a prolonged duration of response (median, ≥24 weeks) and is generally well tolerated. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Les formes br��ves orales tels que les ��nonc��s par��miologiques, les g��n��alogies et les anecdotes sont ench��ss��s dans la trame narrative de Soundjata ou l'��pop��e mandingue dans le but non seulement de rythmer ce texte narratif oral, mais ��galement d'amplifier sa densit�� po��tique. Leur r��currence t��moigne autant de la dimension intertextuelle d'une telle ��pop��e orale que de son dynamisme esth��tique. Comme rep��res discursifs, elles participent du style formulaire de l'��pop��e. D'o�� leur usage abusif par les diff��rents griots dans le tissu narratif du texte. Notam��ment durant la r��citation de cette ��pop��e mandingue devant l'auditoire.

We investigated the perceptions of young computing science students about older people with regard to computer-based systems. Participants were shown a picture of either an old or young woman or man and asked to assess that persons computer literacy and suggest appropriate design aspects for them. The goal of this study was to see if the biases against older people and their perceived computer literacy extend to the design of systems for them.The results draw on 216 questionnaires from students in the first year of their Information and Communications Technology (ICT) studies at an Austrian university of applied sciences. Mixed methods were used to explore the differences between the perceived design needs for older and younger people, and how these relate to the components of user experience and accessibility.The results show that the design aspects mentioned for older people differ greatly from those mentioned for younger. Whereas for younger people many aspects that could be considered valuable and desirable are mentioned, for older people the focus is on accessibility and usability, almost to the exclusion of aspects that are valuable and desirable. Regarding accessibility, despite the perceived lack of expertise, the focus was on aspects like large fonts. This is concerning, as future systems will be designed by the students of today. These biases may influence whether future systems are acceptable to older people, and hence whether older people will benefit from them.

Les formes br��ves orales tels que les ��nonc��s par��miologiques, les g��n��alogies et les anecdotes sont ench��ss��s dans la trame narrative de Soundjata ou l'��pop��e mandingue dans le but non seulement de rythmer ce texte narratif oral, mais ��galement d'amplifier sa densit�� po��tique. Leur r��currence t��moigne autant de la dimension intertextuelle d'une telle ��pop��e orale que de son dynamisme esth��tique. Comme rep��res discursifs, elles participent du style formulaire de l'��pop��e. D'o�� leur usage abusif par les diff��rents griots dans le tissu narratif du texte. Notam��ment durant la r��citation de cette ��pop��e mandingue devant l'auditoire.

Les formes br��ves orales tels que les ��nonc��s par��miologiques, les g��n��alogies et les anecdotes sont ench��ss��s dans la trame narrative de Soundjata ou l'��pop��e mandingue dans le but non seulement de rythmer ce texte narratif oral, mais ��galement d'amplifier sa densit�� po��tique. Leur r��currence t��moigne autant de la dimension intertextuelle d'une telle ��pop��e orale que de son dynamisme esth��tique. Comme rep��res discursifs, elles participent du style formulaire de l'��pop��e. D'o�� leur usage abusif par les diff��rents griots dans le tissu narratif du texte. Notam��ment durant la r��citation de cette ��pop��e mandingue devant l'auditoire.

HPV remains the most common sexually transmitted disease worldwide, despite improvements in awareness, screening, prophylactic vaccination uptake, and surgical treatment. VGX-3100 is an immunotherapy that uses electroporation to introduce DNA encoding for modified HPV-16 and HPV-18, E6-and E7 proteins into myocytes to stimulate an effector T cell response. We now report immunogenicity and safety of VGX-3100 for a refrigeration-stable formulation, which improves patient-care setting usability. This multi-arm, double-blinded, randomized trial enrolled 235 healthy men and women to receive either a refrigerated (RF) or frozen formulation (FF) of VGX-3100. Three doses were administered intramuscularly with electroporation at 0, 4, and 12 weeks. Non-inferiority of RF to FF was assessed by comparing the proportion of subjects who achieved a ≥2-fold increase from baseline to Week 14 in Spot Forming Units/106 PMBCs using an interferon-γ enzyme-linked immunospot assay. There were no related SAEs. Injection site reactions were the most common adverse event (54%, RF; 66%, FF) the majority of which resolved within a few minutes following administration. The primary endpoint was met with 89.9% of RF recipients and 97.2% of FF recipients reaching a ≥2-fold rise in SFU/106 PBMC, 2 weeks following the last dose; RF was statistically non-inferior to FF (p = .022). A systemic, immunologic approach has the potential to fill a critical gap in the ability to treat men and women with high grade HPV diseases. These safety and immunogenicity data are supportive of the continued development of a refrigerated formulation of VGX-3100.

Food waste recycling is needed to create a more sustainable, circular food system; however, the process must be carefully managed to avoid the introduction and build-up of contaminants. We collected and screened source-separated food waste for five classes of contaminants (physical contaminants, heavy metals, halogenated organics, pathogens and antibiotic resistance genes) from two regulatory environments (voluntary vs mandated food separation) to quantify contamination. Physical contamination was frequently found; 57% of samples contained non-compostable waste. Most heavy metals were not detected, and although copper and zinc were present in most samples, they were always below the most stringent global standards for compost. Some samples had detectable halogenated organics, including perfluoroalkyl substances (PFAS), which is cause for concern because some of these accumulate in the food chain. PFBA was detected in 60%, PFHxS in 8% and PFNA in 4% of samples tested. The pathogen Salmonella was present in 3% (2/71) and L. monocytogenes in 11% (8/71) of samples. Shiga toxin-producing E. coli was not detected. Next generation sequencing showed the presence of several genera that contain foodborne pathogens, most commonly Yersinia. Antibiotic resistance genes tet(M) and bla

Our thesis, devoted to the Legislative Committee of the National Convention (1792-1795), invites an unprecedented and in-depth study by a central body of the Assembly which brought France into the Republic. Founded under the Legislative Assembly (October 1791), this committee of fundamental importance is responsible for preparing the laws to be debated in the Assembly, but also for ensuring their fair application in the national space. Our project aims to examine the functioning of a legislative body that became a government body from the summer of 1794, to reflect on the place of the law in the construction of the Republic as well as to study the concrete participation of citizens in the development of new law. The objective of our research is to deepen the analysis of Hippolyte Taine who, referring to parliamentary committees, explained "that the work and success of an assembly ... order, practicality, discipline under competent and accepted drivers. ”. The Committee's study thus sheds light on an essential cog of the First Republic, a laboratory of law, a receptacle for the aspirations of an entire people, but also a community of jurists, citizens and legislators responsible for founding order and set the standard. Our work explores the daily meetings of this essential committee and yet far from the theoretical struggles or political effusions that recurrently captivate the interest of revolutionary historians. By adopting this focus, our study seeks to renew the approach of the years 1792-1795 by turning away from the analysis of speeches, events and postures to focus on the more technical study of texts, on the study from the shadows in which the matter of government was developed in intimate, complex and often finicky discussions. By focusing on the participation of citizens in the creation of new law, the action of jurists in times of exception or even the characteristics of our first republican pact, our research finds an almost daily echo in the most recent news.; Notre thèse, consacrée au Comité de législation de la Convention nationale (1792- 1795), invite à l’étude inédite et approfondie d’un organisme central de l’Assemblée qui a fait entrer la France en République. Fondé sous la Législative (octobre 1791), ce comité d’une importance fondamentale est chargé de préparer les lois qui doivent être débattues au sein de l’Assemblée, mais aussi de veiller à leur juste application dans l’espace national. Notre projet ambitionne d’examiner le fonctionnement d’un organe législatif devenu organe de gouvernement à partir de l’été 1794, de réfléchir à la place de la loi dans la construction républicaine ainsi que d’étudier la participation concrète des citoyens à l’élaboration du droit nouveau. L’objectif de notre recherche est d’approfondir l’analyse d’Hippolyte Taine qui, en faisant allusion aux comités parlementaires, expliquait « qu’il faut au travail et au succès d’une assemblée [...] du silence et de l’ordre, de l’esprit pratique, de la discipline sous des conducteurs compétents et acceptés.». L’étude du Comité vient ainsi éclairer un rouage essentiel de la Première République, un laboratoire de la loi, un réceptacle des aspirations de tout un peuple, mais aussi une communauté de juristes, citoyens et législateurs chargés de fonder l’ordre et d’établir la norme. Nos travaux explorent les réunions quotidiennes de ce comité essentiel et pourtant loin des luttes théoriques ou des effusions politiques qui captivent de manière récurrente l’intérêt des historiens de la Révolution. En adoptant cette focale, notre étude cherche à renouveler l’approche des années 1792-1795 en se détournant de l’analyse des discours, des événements et des postures pour s’atteler à l’étude plus technique des textes, à l’étude de l’ombre où s’ élaboraient, dans des discussions intimes, complexes et souvent tatillonnes, la matière du gouvernement. En s’intéressant à la participation des citoyens à la création du droit nouveau, à l’action des juristes en temps d’exception ou encore aux caractéristiques de notre premier pacte républicain, nos recherches trouvent un écho presque quotidien dans l’actualité la plus récente.

Background Most studies on health disparities during the coronavirus disease 2019 (COVID-19) pandemic focused on reported cases and deaths, which are influenced by testing availability and access to care. This study aimed to examine severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody seroprevalence in the United States and its associations with race/ethnicity, rurality, and social vulnerability over time. Methods This repeated cross-sectional study used data from blood donations in 50 states and Washington, DC, from July 2020 through June 2021. Donor zip codes were matched to counties and linked with Social Vulnerability Index (SVI) and urban-rural classification. SARS-CoV-2 antibody seroprevalences induced by infection and infection-vaccination combined were estimated. Association of infection-induced seropositivity with demographics, rurality, SVI, and its 4 themes were quantified using multivariate regression models. Results Weighted seroprevalence differed significantly by race/ethnicity and rurality, and increased with increasing social vulnerability. During the study period, infection-induced seroprevalence increased from 1.6% to 27.2% and 3.7% to 20.0% in rural and urban counties, respectively, while rural counties had lower combined infection- and vaccination-induced seroprevalence (80.0% vs 88.1%) in June 2021. Infection-induced seropositivity was associated with being Hispanic, non-Hispanic Black, and living in rural or more socially vulnerable counties, after adjusting for demographic and geographic covariates. Conclusions The findings demonstrated increasing SARS-CoV-2 seroprevalence in the United States across all geographic, demographic, and social sectors. The study illustrated disparities by race-ethnicity, rurality, and social vulnerability. The findings identified areas for targeted vaccination strategies and can inform efforts to reduce inequities and prepare for future outbreaks.

Background Mosaicism in Klinefelter Syndrome (KS) is reported in 15–20%, but 46,XX/47,XXY mosaicismis extremely rare and presents either during infancy with ambiguous genitalia or during adolescence with gynecomastia or microorchidism. In view of the scarce data on adult outcomes (1,2), we here comprehensively report the skeletal and reproductive health outcome in two individuals with 46,XX/47,XXY KS. Clinical cases The first case was born at 40 weeks after a spontaneous conception with a birth length of 49 cm. At birth right cryptorchidism, but a normally developed penis and scrotum was present. Surgical intervention at the age of 1 year, showed a right abdominal testicular nubbin. He was investigated at the age of 17 years for left microorchidism (6ml) contrasting with a normal genital development (Tanner G5). Hormonal investigation showed hypergonadotropinemia with a normal serum testosterone. Peripheral blood karyotype showed mosaicism 46,XX (60%)/47,XXY (40%). At the age of 18 years, standing height was 164.5 cm (mid-parental height (MPH) 173.5 cm). BMI was 19 kg/m2. Hormonal evaluation showed an unmeasurable serum inhibin B, elevated gonadotropins (LH 43 IU/L and FSH 65 IU/L), but a normal testosterone and estradiol. Ultrasound of the left testis showed a normal echo pattern. Azoospermia was documented. Lumbar spine bone mineral density (LS-BMD) was -1 SDS. The second case was born at 37 weeks after ICSI with a birth length of 49 cm. External genitalia at birth were normal. However, routine karyotyping after ICSI conception showed a mosaicism 46,XX (50)/ 47,XXY (50). A normal pubertal development apart from an arrest in testicular development at the age of 15 years was documented. At the age of 18 years, his height was 176.8 cm (MPH 184 cm), BMI 26 kg/m2, Tanner stage G5 and testes volumes 8/8 ml. Hormonal evaluation showed low inhibin B (43.4 ng/l), slightly elevated gonadotropins (LH 16.1 IU/L and FSH 12.5 IU/L), and normal testosterone and estradiol. Ultrasonography of the scrotum showed normal testicular structure. LS-BMD SDS was 1. Conclusion 46,XX/47,XXY KS men, who present with normal male genitals at birth, can have a normal pubertal progression with the exception of a mid-pubertal testicular regression, but in contrast to men with a 46,XY/ 47,XXY constitution, appear at risk for a shorter stature than expected for parental height. References Velissariou V et al., European Journal of Medical Genetics (2006) 49, 331-337Matsuki S, Journal of Urology (1999) 161 (5), 1573-74 Presentation: No date and time listed