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This paper uses data from the 2019 Annual Business Survey to document that firms adopting advanced technologies are larger in terms of employment than other firms in their same industry and cohort. Using data from the Longitudinal Business Survey, we show that adopters were already large and growing faster before artificial intelligence, robotics, cloud computing, and specialized software systems became broadly available. These findings support the view that adopters are large because of selection and not because adopting advanced technologies for automation causally expands their employment.

BACKGROUND: Complex ureteric strictures and injuries occurring during major abdominal and pelvic operations may cause significant morbidity and distress to patients. A rendezvous procedure is an endoscopic technique used in case of such injuries. OBJECTIVE: To evaluate perioperative and long-term outcomes of rendezvous procedures to treat complex ureteric strictures and injuries. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed patients undergoing a rendezvous procedure for ureteric discontinuity including strictures and injuries, treated between 2003 and 2017 at our Institution and completing at least 12 mo of follow-up. We divided patients into two groups: early postsurgical obstruction, leakage, or detachment (group A) and late strictures (oncological/postsurgical; group B). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: If appropriate, we performed a retrograde study ± rigid ureteroscopy to assess the stricture 3 mo after the rendezvous procedure, followed by a MAG3 renogram at 6 wk, 6 mo, and 12 mo, and annually thereafter for 5 yr. RESULTS AND LIMITATIONS: Forty-three patients underwent a rendezvous procedure, 17 in group A (median age 50 yr, range 30–78) and 26 in group B (median age 60 yr, range: 28–83). Ureteric strictures and ureteric discontinuities were stented successfully in 15 out of 17 patients in group A (88.2%) and 22 out of 26 patients (84.6%) in group B. For both groups, the median follow-up was 6 yr. In group A, of 17 patients, 11 (64.7%) were stent free with no further interventions, two (11.7%) had a subsequent Memokath stent insertion (38%), and two (11.7%) required reconstruction. Of 26 patients in group B, eight (30.7%) required no further interventions and were stent free, ten (38.4%) were maintained with long-term stenting, and one was managed with a Memokath stent (3.8%). Of the 26 patients, only three (11.5%) required major reconstruction, while four patients with malignancy (15%) died during follow-up. CONCLUSIONS: With a combined antegrade and retrograde approach, the majority of complex ureteric strictures/injuries can be bridged and stented with an overall immediate technical success rate of above 80%, avoiding major surgery in unfavourable circumstances and allowing time for stabilisation and recovery of the patient. Additionally, in case of technical success, further interventions may be unnecessary in up to 64% of patients with acute injury and about 31% of patients with late stricture. PATIENT SUMMARY: The majority of complex ureteric strictures and injuries can be resolved using a rendezvous approach, avoiding major surgery in unfavourable circumstances. Moreover, this approach can help avoid further interventions in 64% of such patients.

Drug development is a complicated and lengthy process requiring a significant amount of intellectual and capital input, as well as extensive collaborations among various organizations and institutions. Contract research organizations play important roles at some or even all stages of the drug development process. To provide better service in in vitro drug absorption, disposition, metabolism and excretion studies, maintain data accuracy and promote work efficiency, we developed an integrated information system termed the ‘Drug Metabolism Information System’, and it is being used routinely by our drug metabolism department. The Drug Metabolism Information System assists scientists with assay design, data analysis and report drafting and thus reduces human error.

This paper describes multidimensional modeling of ablation heat transfer with a focus on ablative insulation materials used in rocket motor nozzles. Phenomenology is discussed, and detailed three-dimensional math models are presented along with a finite element solution strategy. Implementation into a computer program named Hero is described, including a description of the parallel processing capability that enables computational support for large finite element models. A validation case is presented using measurement data from booster motors of the space shuttle program. The validation results are quantified in terms of the probabilistic propensity for misprediction of the char depth at varying levels. The validation results show a trend toward the overprediction of char depth by around 4%. The standard deviation of percent misprediction is shown to be between 6 and 16%, depending on boundary condition fidelity. This suggests that accuracy to three standard deviations can be expected to fall in the range of 18–48% for ablation modeling in rocket nozzles. This paper provides an important reference for multidimensional ablation heat transfer analysis and quantification of related modeling uncertainty.

Background. There is a prevailing belief that unfocused written corrective feedback may not be suitable to promote students’ academic writing development. Purpose. This perspective piece demonstrates how unfocused written corrective feedback reflects the principles of sociomateriality, which views learning as dynamic. Perspectives. Unfocused written corrective feedback has the potential to support university students’ academic discourse socialization. This perspective is based on the observation that actual written corrective feedback in a classroom setting is varied and contextual, and not focused on any particular grammar form or writing feature. Conclusion. Unfocused written corrective feedback represents an optimal approach to support university students’ awareness and engagement with variables found in their learning ecology. These variables can support students’ academic writing development.

PURPOSE To compare taxane maintenance chemotherapy, paclitaxel (P) and paclitaxel poliglumex (PP), with surveillance (S) in women with ovarian, peritoneal, or fallopian tube (O/PC/FT) cancer who attained clinical complete response after first-line platinum-taxane therapy. METHODS Women diagnosed with O/PC/FT cancer who attained clinical complete response after first-line platinum-taxane–based chemotherapy were randomly allocated 1:1:1 to S or maintenance, P 135 mg/m2 once every 28 days for 12 cycles, or PP at the same dose and schedule. Overall survival (OS) was the primary efficacy end point. RESULTS Between March 2005 and January 2014, 1,157 individuals were enrolled. Grade 2 or worse GI adverse events were more frequent among those treated with taxane (PP: 20%, P: 27% v S: 11%). Grade 2 or worse neurologic adverse events occurred more often with taxane treatment (PP: 46%, P: 36% v S: 14%). At the fourth scheduled interim analysis, both taxane regimens passed the OS futility boundary and the Data Monitoring Committee approved an early release of results. With a median follow-up of 8.1 years, 653 deaths were reported; none were attributed to the study treatment. Median survival durations were 58.3, 56.8, and 60.0 months for S, P, and PP, respectively. Relative to S, the hazard of death for P was 1.091 (95% CI, 0.911 to 1.31; P = .343) and for PP, it was 1.033 (95% CI, 0.862 to 1.24; P = .725). The median times to first progression or death (PFS) were 13.4, 18.9, and 16.3 months for S, P, and PP, respectively. Hazard ratio = 0.801; 95% CI, 0.684 to 0.938; P = .006 for P and hazard ratio = 0.854; 95% CI, 0.729 to 1.00; P = .055 for PP. CONCLUSION Maintenance therapy with P and PP did not improve OS among patients with newly diagnosed O/tubal/peritoneal cancer, but may modestly increase PFS. GI and neurologic toxicities were more frequent in the taxane treatment arms.

When a user shares her data with online platforms, she reveals information about others. In such a setting, externalities depress the price of data because once a user's information is leaked by others, she has less reason to protect her data and privacy. These depressed prices lead to excessive data sharing. We characterize conditions under which shutting down data markets improves welfare. Platform competition does not redress the problem of excessively low data prices and too much data sharing and may further reduce welfare. We propose a scheme based on mediated data sharing that improves efficiency. (JEL D62, D83, H23, L51, L86, L88)

Acne vulgaris is a chronic inflammatory skin disorder that affects patients of all skin types. Acne scarring affects up to 95% of patients. Laser treatment is the most effective treatment for acne scarring. Adverse effects (AEs) include pain, infection, erythema, postinflammatory hyperpigmentation (PIH), hypopigmentation and scarring. Patients with darker skin types are more prone to developing PIH, arising as a result of inflammation, which can be intrinsic or extrinsic. There is concern that laser treatment may not be suitable for patients with skin of colour (SOC) due to the risks of AEs. However, the use of appropriate treatment protocols can help to mitigate these risks. Clinicians should consider the type of acne scarring and skin type of the patient when choosing the most appropriate laser. Laser treatments should be offered to patients with SOC, who should be fully informed of the risks before embarking on treatment. It is important to note that no treatment will eliminate scarring completely, but lasers can significantly improve the appearance of acne scars. Laser treatment for acne scarring can be performed safely and effectively when tailored to the patient’s needs and skin type. Further studies are needed to evaluate the use of lasers for patients with SOC.

The preparation of halogenated benzene-1,2,3,4-tetracarboxylic diimide derivatives is challenging because of the possibility of competitive incorrect cyclizations and S

Decoy receptor proteins that trick viruses to bind to them should be resistant to viral escape because viruses that require entry receptors cannot help but bind decoy receptors. Angiotensin-converting enzyme 2 (ACE2) is the major receptor for coronavirus cell entry. Recombinant soluble ACE2 was previously developed as a biologic against acute respiratory distress syndrome (ARDS) and verified to be safe in clinical studies. The emergence of COVID-19 reignited interest in soluble ACE2 as a potential broad-spectrum decoy receptor against coronaviruses. In this review, we summarize recent developments in preclinical studies using various high-affinity mutagenesis and Fc fusion approaches to achieve therapeutic efficacy of recombinant ACE2 decoy receptor against coronaviruses. We also highlight the relevance of stimulating effector immune cells through Fc-receptor engagement and the potential of using liquid aerosol delivery of ACE2 decoy receptors for defense against ACE2-utilizing coronaviruses.

Antibodies are key proteins produced by the immune system to target pathogen proteins termed antigens via specific binding to surface regions called epitopes. Given an antigen and the sequence of an antibody the knowledge of the epitope is critical for the discovery and development of antibody based therapeutics. In this work, we present a computational protocol that uses template-based modeling and docking to predict epitope residues. This protocol is implemented in three major steps. First, a template-based modeling approach is used to build the antibody structures. We tested several options, including generation of models using AlphaFold2. Second, each antibody model is docked to the antigen using the fast Fourier transform (FFT) based docking program PIPER. Attention is given to optimally selecting the docking energy parameters depending on the input data. In particular, the van der Waals energy terms are reduced for modeled antibodies relative to x-ray structures. Finally, ranking of antigen surface residues is produced. The ranking relies on the docking results, that is, how often the residue appears in the docking poses' interface, and also on the energy favorability of the docking pose in question. The method, called PIPER-Map, has been tested on a widely used antibody-antigen docking benchmark. The results show that PIPER-Map improves upon the existing epitope prediction methods. An interesting observation is that epitope prediction accuracy starting from antibody sequence alone does not significantly differ from that of starting from unbound (i.e., separately crystallized) antibody structure.

We develop a theory of the accumulation of state capacity as the outcome of a political competition between elites and (civil) society. State capacity is accumulated by elites, and it is productive as well as useful in controlling society. However, society can fight back and accumulate its own capacity, facilitating collective action. The theory leads to three distinct equilibria depending on initial conditions. One type, a weak state, emerges when society is strong relative to the elite. Another, a despotic state, originates where the elite is initially relatively powerful. A third type, an inclusive state, emerges when the elite and society are more evenly matched. The theory has several important implications; first, variation in state capacity does not require large structural differences; second, inclusive states have the highest levels of state capacity in the long run; third, the effects of shocks or external threats like wars are conditional on the balance of power between elites and society.

We investigate the determinants of radical (“creative”) innovations that break new ground in knowledge creation. We develop a model focusing on the choice between incremental and radical innovation and on how managers of different ages and human capital are sorted across firms. Firm- and patent-level evidence reveals that firms that are more “open to disruption” are significantly more likely to engage in radical innovation and hire younger managers and inventors with a comparative advantage in radical innovation. However, once the effect of the sorting is factored in, the (causal) impact of manager age on creative innovations, though positive, is small. (JEL D22, L26, M10, M14, O31, O34)

In 2020, the United States experienced twin pandemics disproportionately impacting BIPOC communities and their schools and school systems—one new, COVID-19, and one longstanding, that of white supremacy and anti-Black racism. This phenomenological study of 20 Black female principals in two states provides insights into how these leaders, who so often center racial justice and caring for BIPOC children and communities in their leadership practice, grappled with these pandemics and how doing so impacted their leadership and work. Findings suggest that leading through these twin pandemics further cemented these women’s commitments to engage in advocacy and justice work on behalf of their communities and students. They also reported, regarding racial inequity and white supremacy, feeling both a cautious optimism stemming from seeing the work they had long engaged in being taken up at scale, and by white colleagues in particular, and frustration, experiencing this engagement often as “performative” and thus unlikely to lead to real change. And yet they also spoke of their deep commitment to advocacy and social justice moving forward and their role in ensuring that all their students receive the education, opportunities, and outcomes they deserve.

International student mobility is a common phenomenon observed globally, especially in higher education settings where English is used as the main medium of instruction. In such settings, international students may find themselves using English along with their first language for social or academic purposes. This study examines international students’ perspectives towards translanguaging in a university setting. With a mixed-methods approach, an anonymous online questionnaire and open-ended survey were distributed to international students. A total of 74 international students comprising 16 nationalities completed the survey. From the quantitative data, the students indicated a generally positive perspective towards translanguaging, especially to become more confident in English use and to relate better with other international students. Further quantitative analysis indicated that the perceptions differed significantly across years of study. The qualitative data provided further insights regarding translanguaging, namely the suitability of using a shared language in a formal learning context, such as in the classroom. All in all, this study was able to provide further insights into international students’ perspectives towards translanguaging.

Since the early 2000s, an array of experimental research has demonstrated that face-to-face canvassing is the most effective form of get-out-the-vote campaigning. Recent scholarship, however, suggests that text messaging can also have powerful mobilization effects. Can the effects of text messaging match those of canvassing? We present a field experiment gauging the effects of text messaging, canvassing, mail, and phone calls among medium propensity evangelical Christian voters in three California battleground congressional districts for the 2018 midterm election. The results show significant turnout effects associated with texting as well as any form of outreach followed by a late-October text message. This challenges the widely held notion that personalized contacting is required to get voters to the polls; rather, we find that peripheral voters—often targeted by campaigns for mobilization—may be receptive to anonymous but timely outreach.

N-benzylcinchonidinium bromide, C26H29N2O+·Br−, with the systematic name (R)-[(2S,4S,5R)-1-benzyl-5-ethenyl-1-azoniabicyclo[2.2.2]octan-2-yl](quinolin-4-yl)methanol bromide, is a quaternary ammonium salt of the cinchona alkaloid cinchonidine. This salt is widely used as a chiral phase-transfer catalyst and chiral resolution agent. Both classical and non-classical hydrogen-bonding interactions, as well as anion effects have been shown to play key mechanistic roles in the catalysis of cinchona alkaloids. In an effort to understand the effects of water on these intermolecular interactions, the structures of anhydrous N-benzylcinchonidinium bromide, (I), and the sesquihydrate, C26H29N2O+·Br−·1.5H2O, (II), were determined.

Modernization theory is a cornerstone of much of political science, despite the mounting evidence against its predictions. We outline a theory in which the distribution of political power critically combines with political culture. We call the basic components of culture “attributes” and argue that these can be combined into larger cultural configurations. These configurations interact with the distribution of power and lead to three distinct self-reinforcing paths of political development, with very different state–society relations, institutions, and economic structures. These are paths to Despotic, Absent, and Shackled Leviathans. The role of cultural configurations is critical in legitimizing the social arrangements in each path. None of the three different paths we highlight support modernization theory. We discuss how political equilibria can change in ways critically dependent on cultural and political entrepreneurship in order to formulate and popularize new cultural configurations and institutionalize political changes.

Interpretive frameworks may be helpful to understand narratives, yet they also risk displacing unique information of the research context. In this paper, we argue that such is the case in narrative inquiry studies of English language teaching set in the Asian context, perhaps due to the pressure to use familiar interpretive frameworks that are sanctioned by scholars. Through meta-ethnography, we examined recent narrative inquiry studies set in Asia. It was observed that the research findings do not offer any critical insights about the context of the study; instead, they add to the prevalence of broad constructs of English language education, such as the components of identity. For future narrative inquiry research, we recommend researchers to consider utilizing local meanings pertinent to the study context as an analytical lens, as a means to Asianize the field.

Warfare is increasing in complexity, speed, and scale—not only due to enhanced technological capabilities but also from the employment methodologies associated with them. Incorporating artificial i...

Context Although percutaneous nephrolithotomy (PCNL) has been performed for decades and has gone through many refinements, there are still concerns regarding its more widespread utilization because of the long learning curve and the potential risk of severe complications. Many technical details are not included in the guidelines because of their nature and research protocol. Objective To achieve an expert consensus viewpoint on PCNL indications, preoperative patient preparation, surgical strategy, management and prevention of severe complications, postoperative management, and follow-up. Evidence acquisition An international panel of experts from the Urolithiasis Section of the European Association of Urology, International Alliance of Urolithiasis, and other urology associations was enrolled, and a prospectively conducted study, incorporating literature review, discussion on research gaps (RGs), and questionnaires and following data analysis, was performed to reach a consensus on PCNL. Evidence synthesis The expert panel consisted of 36 specialists in PCNL from 20 countries all around the world. A consensus on PCNL was developed. The expert panel was not as large as expected, and the discussion on RGs did not bring in more supportive evidence in the present consensus. Conclusions Adequate preoperative preparation, especially elimination of urinary tract infection prior to PCNL, accurate puncture with guidance of fluoroscopy and/or ultrasonography or a combination, keeping a low intrarenal pressure, and shortening of operation time during PCNL are important technical requirements to ensure safety and efficiency in PCNL. Patient summary Percutaneous nephrolithotomy (PCNL) has been a well-established procedure for the management of upper urinary tract stones. However, according to an expert panel consensus, core technical aspects, as well as the urologist’s experience, are critical to the safety and effectiveness of PCNL.

Since the discovery of natural malaria vector populations infected by the endosymbiont bacteriumWolbachia, a renewed interest has arisen for using this bacterium as an alternative for malaria control. Among naturally infected mosquitoes,Anopheles moucheti, a major malaria mosquito in Central Africa, exhibits one of the highest prevalences ofWolbachiainfection. To better understand whether this maternally inherited bacterium could be used for malaria control, we investigatedWolbachiainfluence inAn. mouchetipopulations naturally infected by the malaria parasitePlasmodium falciparum. To this end, we collected mosquitoes in a village from Cameroon, Central Africa, where this mosquito is the main malaria vector. We found that the prevalence ofWolbachiabacterium was almost fixed in the studied mosquito population, and was higher than previously recorded. We also quantifiedWolbachiain whole mosquitoes and dissected abdomens, confirming that the bacterium is also elsewhere than in the abdomen, but at lower density. Finally, we analyzed the impact ofWolbachiapresence and density onP. falciparuminfection.Wolbachiadensity was slightly higher in mosquitoes infected with the malaria parasite than in uninfected mosquitoes. However, we observed no correlation between theP. falciparumandWolbachiadensities. In conclusion, our study indicates that naturally occurringWolbachiainfection does not affectP. falciparumdevelopment withinAn. mouchetimosquitoes.

Literature has shown that unit coordinators at universities, who are considered middle managers, occupy a rather ambiguous space. This is because the nature of oversight employed by unit coordinators could be that of managing or leading. These types of oversights, however, may not be easily distinguished. This caveat serves as the basis for this study, which seeks to explore the professional identity of two unit coordinators — Aileen and Daron. Data was collected from reflections written by Aileen and Daron over one academic year (two semesters) about their experiences of oversight of two separate modules.

Plasmodium falciparum, the most virulent agent of human malaria, spread from Africa to all continents following the out-of-Africa human migrations. During the transatlantic slave trade between the 16thand 19thcenturies, it was introduced twice independently to the Americas where it adapted to new environmental conditions (new human populations and mosquito species). Here, we analyzed the genome-wide polymorphisms of 2,635 isolates across the currentP. falciparumdistribution range in Africa, Asia, Oceania, and the Americas to investigate its genetic structure, invasion history, and selective pressures associated with its adaptation to the American environment. We confirmed that American populations originated from Africa with at least two independent introductions that led to two genetically distinct clusters, one in the North (Haiti and Columbia) and one in the South (French Guiana and Brazil), and the admixed Peruvian group. Genome scans revealed recent and more ancient signals of positive selection in the American populations. Particularly, we detected positive selection signals in genes involved in interactions with host (human and mosquito) cells and in genes involved in resistance to malaria drugs in both clusters. We found that some genes were under selection in both clusters. Analyses suggested that for five genes, adaptive introgression between clusters or selection on standing variation was at the origin of this repeated evolution. This study provides new genetic evidence onP. falciparumcolonization history and on its local adaptation in the Americas.

Rich behavioural biases, mistakes, and limits on rational decision-making are often thought to make equilibrium analysis much more intractable. We establish that this is not the case in the context of one-sector growth models such as Ramsey–Cass–Koopmans or Bewley–Aiyagari models. We break down the response of the economy to a change in the environment or policy into two parts: the direct response at the given (pre-tax) prices, and the equilibrium response which plays out as prices change. Our main result demonstrates that under weak regularity conditions, regardless of the details of behavioural preferences, mistakes and constraints on decision-making, the long-run equilibrium will involve a greater capital-labour ratio if and only if the direct response (from the corresponding consumption-saving model) involves an increase in aggregate savings. One implication of this result is that, from a qualitative point of view, behavioural biases matter for long-run equilibrium if and only if they change the direction of the direct response. We provide detailed illustrations of how this result can be applied and generate new insights using models of misperceptions, self-control and temptation, and naive and sophisticated quasi-hyperbolic discounting.

Background In-depth knowledge of the cellular and molecular composition of dental pulp (DP) and the crosstalk between DP cells that drive tissue homeostasis are not well understood. To address these questions, we performed a comparative analysis of publicly available single-cell transcriptomes of healthy adult human DP to 5 other reference tissues: peripheral blood mononuclear cells, bone marrow, adipose tissue, lung, and skin. Results Our analysis revealed that DP resident cells have a unique gene expression profile when compared to the reference tissues, and that DP fibroblasts are the main cell type contributing to this expression profile. Genes coding for pleiotrophin (PTN) and midkine (MDK), homologous heparin-binding growth-factors, possessed the highest differential expression levels in DP fibroblasts. In addition, we identified extensive crosstalk between DP fibroblasts and several other DP resident cells, including Schwann cells, mesenchymal stem cells and odontoblasts, mediated by PTN and MDK. Conclusions DP fibroblasts emerge as unappreciated players in DP homeostasis, mainly through their crosstalk with glial cells. These findings suggest that fibroblast-derived growth factors possess major regulatory functions and thus have a potential role as dental therapeutic targets.

Background Serogroup A Neisseria meningitidis was the major cause of meningococcal meningitis epidemics in the African meningitis belt before 2010 when the monovalent meningococcal A conjugate vaccine (MenAfriVac) was introduced in the region. Therefore, this study aimed to establish the trends in N. meningitidis serogroups from 2016 to 2020 in Ghana’s meningitis belt. Methods Polymerase chain reaction (PCR) confirmed laboratory results of suspected cases of cerebrospinal meningitis from January, 2016 to March, 2020 were obtained from the Tamale Public Health Laboratory. The data were subjected to trend analysis using Statistical Package for the Social Sciences version 25. Differences between discrete variables were analyzed using the Cochran–Armitage trend test. Results Of the 2,426 suspected cases, 395 (16.3%) were confirmed positive for N. meningitidis using PCR. Serogroup X showed a significant upward trend (P P Conclusion This study showed the emergence of serogroup X, a non-vaccine type, as the predominant N. meningitidis serogroup in the wake of a declining serogroup W in Ghana’s meningitis belt.

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Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18–related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18–related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18–related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.

The commercialization of atomic technologies requires replacing laboratory-scale laser setups with compact and manufacturable optical platforms. Complex arrangements of free-space beams can be generated on chip through a combination of integrated photonics and metasurface optics. In this work, we combine these two technologies using flip-chip bonding and demonstrate an integrated optical architecture for realizing a compact strontium atomic clock. Our planar design includes twelve beams in two co-aligned magneto-optical traps. These beams are directed above the chip to intersect at a central location with diameters as large as 1 cm. Our design also includes two co-propagating beams at lattice and clock wavelengths. These beams emit collinearly and vertically to probe the center of the magneto-optical trap, where they will have diameters of ≈100 µm. With these devices we demonstrate that our integrated photonic platform is scalable to an arbitrary number of beams, each with different wavelengths, geometries, and polarizations.

Editorial for This Article from Incident Cervical HPV Infections in Young Women: Transition Probabilities for CIN and Infection Clearance

Background: We describe transition probabilities for incident human papillomavirus (HPV) 16/18/31/33/35/45/52/58/59 infections and cervical intraepithelial neoplasia (CIN) 1 lesions.Methods: Women ages 16 to 23 years underwent cytology and cervical swab PCR testing for HPV at approximately 6-month intervals for up to 4 years in the placebo arm of an HPV vaccine trial. The cumulative proportion of incident HPV infections with diagnosed CIN, clearing (infection undetectable), or persisting without CIN, were estimated.Results: Most incident infections cleared, without detection of CIN, ranging at 36 months from 66.9% for HPV31 to 91.1% for HPV59. There was little variation in the 36-month proportion of incident HPV16, 18, and 31 infections followed by a CIN1 lesion positive for the relevant HPV type (range 16.7%–18.6%), with lower risks for HPV59 (6.4%) and HPV33 (2.9%). Thirty-six–month transition probabilities for CIN2 ranged across types from 2.2% to 9.1%; however, the number of events was generally too small for statistically significant differences to be seen across types for this endpoint, or CIN3.Conclusions: Some incident HPV types appear more likely to result in diagnosed CIN1 than others. The relative predominance of HPV16, vis-à-vis some other high-risk HPV types (e.g., HPV33) in prevalent CIN2/3, appears more directly associated with relatively greater frequency of incident HPV16 infections within the population, than a higher risk of infection progression to CIN2/3.Impact: Nearly all incident HPV infections either manifest as detectable CIN or become undetectable within 36 months. Some HPV types (e.g., 16 and 33) appear to have similar risk of CIN2/3 despite widely varied incidence. Cancer Epidemiol Biomarkers Prev; 20(2); 287–96. ©2011 AACR.

Table 1A. 12, 24 and 36 month transition probabilities for incident HPV 16, 18, 31, 33, 35, 45, 52, 58 and 59 infections without adjudication of CIN lesions positive for multiple HPV types. Table 1B. 12 and 24 month transition probabilities for incident HPV 16, 18, 31, 45, 52 and 58 infected CIN 1 lesions without adjudication of CIN lesions positive for multiple HPV types. Table 2A. Prevalence of HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 infections in CIN 1, CIN 2 and CIN 3 lesions (data derived from placebo arms of all Phase III trials)Table 2B. Prevalence of HPV 6, 11, 16, 18 with and without other tested HPV types* in CIN 1, CIN 2 and CIN 3 lesions (data derived from placebo arms of all Phase III trials). Table 3A. Distribution of HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 in CIN 1, CIN 2 and CIN 3 lesions testing positive for a concordant HPV type as observed in a prior or concurrent incident HPV 16/18/31/33/35/45/52/58/59 infection. Table 3B. Distribution of HPV types 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 in CIN 2 and CIN 3 lesions testing positive for a concordant HPV type as observed in a prior incident HPV 16/18/31/33/35/45/52/58/59 infected CIN 1 lesion.

Background: We estimated the prevalence and incidence of 14 human papillomavirus (HPV) types (6/11/16/18/31/33/35/39/45/51/52/56/58/59) in cervicovaginal swabs, and the attribution of these HPV types in cervical intraepithelial neoplasia (CIN), and adenocarcinoma in situ (AIS), using predefined algorithms that adjusted for multiple-type infected lesions.Methods: A total of 10,656 women ages 15 to 26 years and 1,858 women ages 24 to 45 years were enrolled in the placebo arms of one of three clinical trials of a quadrivalent HPV vaccine. We estimated the cumulative incidence of persistent infection and the proportion of CIN/AIS attributable to individual carcinogenic HPV genotypes, as well as the proportion of CIN/AIS lesions potentially preventable by a prophylactic 9-valent HPV6/11/16/18/31/33/45/52/58 vaccine.Results: The cumulative incidence of persistent infection with ≥1 of the seven high-risk types included in the 9-valent vaccine was 29%, 12%, and 6% for women ages 15 to 26, 24 to 34, and 35 to 45 years, respectively. A total of 2,507 lesions were diagnosed as CIN or AIS by an expert pathology panel. After adjusting for multiple-type infected lesions, among women ages 15 to 45 years, these seven high-risk types were attributed to 43% to 55% of CIN1, 70% to 78% of CIN2, 85% to 91% of CIN3, and 95% to 100% of AIS lesions, respectively. The other tested types (HPV35/39/51/56/59) were attributed to 23% to 30% of CIN1, 7% to 14% of CIN2, 3% to 4% of CIN3, and 0% of AIS lesions, respectively.Conclusions: Approximately 85% or more of CIN3/AIS, >70% CIN2, and approximately 50% of CIN1 lesions worldwide are attributed to HPV6/11/16/18/31/33/45/52/58.Impact: If 9-valent HPV vaccination programs are effectively implemented, the majority of CIN2 and CIN3 lesions worldwide could be prevented, in addition to approximately one-half of CIN1. Cancer Epidemiol Biomarkers Prev; 23(10); 1997–2008. ©2014 AACR.

HPV DNA Detection

Supplementary Table 1 - Study design and comparison of protocols 013, 015 and 019. Supplementary Table 2 - Selected Characteristics at Baseline by Histologic Diagnosis.

Celastrol, a bioactive molecule extracted from the Tripterygium wilfordii plant, has been shown to exhibit anti-inflammatory properties. However, its mechanism of action has not been fully elucidated. Here, we show that celastrol suppresses humoral immune responses and autoimmunity by disabling a protein complex consisting of copper metabolism MURR1 domain–containing (COMMD) 3 and COMMD8 (COMMD3/8 complex), a signaling adaptor for chemoattractant receptors. Having demonstrated the involvement of the COMMD3/8 complex in a mouse model of rheumatoid arthritis, we identified celastrol as a compound that covalently bound to and dissociated the COMMD3/8 complex. Celastrol inhibited B cell migration, reduced antibody responses, and blocked arthritis progression, recapitulating deficiency of the COMMD3/8 complex. These effects of celastrol were abolished in mice expressing a celastrol-resistant mutant of the COMMD3/8 complex. These findings establish that celastrol exerts immunosuppressive activity by targeting the COMMD3/8 complex. Our study suggests that the COMMD3/8 complex is a potentially druggable target in autoimmune diseases and points to celastrol as a lead pharmacologic candidate in this capacity.

Made available in DSpace on 2022-04-29T08:39:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Total synthesis of taiwanin C was realised efficiently in a global yield of 52%. Taiwanin C in aggregation assays inhibited platelet aggregation in a concentration-dependent manner with an IC50 of 0.46 μM after exposure of human platelet to AA. Similarly, to AA, taiwanin C inhibited significantly TRAP-6-induced platelet aggregation with IC50 of 0.56 μM. Molecular docking studies were carried out using the molecular target the COX-1, COX-2 and PAR-1 proteins. These studies suggest that taiwanin inhibits COX-1 more strongly than COX-2. Taiwanin C showed better antiplatelet action in the presence of TRAP-6 than indomethacin and molecular docking studies suggest different mechanisms of action for the two compounds on PAR-1. These results demonstrate that taiwanin C acts very efficiently in two different signaling pathways of platelet aggregation. Although preliminary, these results indicate that taiwanin C has potential for further studies on its use for the development of new antiplatelet. Departamento de Física e Química Faculdade de Engenharia de Ilha Solteira Unesp- Univ Estadual Paulista Centro Universitário UNIFUNEC Faculdade de Medicina Santa Fé do Sul Departamento de Farmacologia Faculdade de Ciências Médicas Universidade Estadual de Campinas Departamento de Física e Química Faculdade de Engenharia de Ilha Solteira Unesp- Univ Estadual Paulista

We present a novel approach to developing a unified radiocarbon-based chronology for multiple sediment cores from a location where radiocarbon dating is challenging. We used 36 radiocarbon ages from eight terminal Pleistocene and Holocene sediment cores with correlated stratigraphies. Stratigraphic correlation was accomplished using a combination of high-resolution photography, high-resolution X-ray fluorescence-based elemental composition data, and volcanic tephra identification. Results show that despite problems associated with potential contamination or radiocarbon reservoir effect, a useful age-depth model has been created for the correlated lacustrine sections of these eight sediment cores, providing chronological controls for future paleoenvironmental analyses of the cores.