Search

In my research I examine the linguistic practices of Moroccans in Spain, many of whom speak Moroccan Arabic as well as Modern Standard Arabic, Tamazight, French, English and Spanish at varying levels of proficiency. As part of my research, I conducted a 10-month linguistic ethnography. I was able to rely on my native English and near-native Spanish language skills for my research, but it was also necessary to use Modern Standard Arabic and even Moroccan Arabic in my sociolinguistic interviews. I possess limited working knowledge of Modern Standard Arabic and even more limited knowledge of Moroccan Arabic. In this paper, I discuss one instance of conducting a sociolinguistic interview in Moroccan Arabic and Modern Standard Arabic. I conduct a discursive analysis of the interactional positioning and linguistic resources in this 46-min interview based on a perspective of "spaces of linguistic non-understanding." I show how spaces of "linguistic semi-understanding" arise in the sociolinguistic interview which require the researcher to move beyond the genre of the interview. I also demonstrate how these spaces are intertwined with negotiations of social and cultural knowledge. Lastly, I highlight the challenges and opportunities afforded to researchers who work in communities and languages outside of their own.

PURPOSE: Seizure-related homolog protein 6 (SEZ6) is a novel target expressed in small cell lung cancer (SCLC). ABBV-011, a SEZ6-targeted antibody conjugated to calicheamicin, was evaluated in a phase I study (NCT03639194) in patients with relapsed/refractory SCLC. We report initial outcomes of ABBV-011 monotherapy. PATIENTS AND METHODS: ABBV-011 was administered intravenously once every 3 weeks (Q3W) during dose escalation (0.3-2 mg/kg) and expansion. Patients with SEZ6-positive tumors (≥25% of tumor cells with ≥1+ staining intensity by immunohistochemistry) were preselected for expansion. Safety, tolerability, antitumor activity, and pharmacokinetics were evaluated. RESULTS: As of August 2022, 99 patients received ABBV-011 monotherapy (dose escalation, n=36; Japanese dose evaluation, n=3; dose expansion, n=60 [1 mg/kg, n=40]); median age was 63 years (range, 41-79). Thirty-two percent, 41%, and 26% of patients received 1, 2, and ≥3 prior therapies, respectively. The maximum tolerated dose was not reached through 2.0 mg/kg. Most common treatment-emergent adverse events (TEAEs) were fatigue (50%), nausea (42%), and thrombocytopenia (41%). Most common hepatic TEAEs were increased aspartate aminotransferase (22%), increased g-glutamyltransferase (21%), and hyperbilirubinemia (17%); 2 patients experienced veno-occlusive liver disease. Objective response rate (ORR) was 19% (19/98). In the 1-mg/kg dose-expansion cohort (n=40), ORR was 25%; median response duration was 4.2 months (95% CI, 2.6-6.7) and median progression-free survival was 3.5 months (95% CI, 1.5-4.2). CONCLUSIONS: ABBV-011 1.0 mg/kg Q3W monotherapy was well tolerated and demonstrated encouraging antitumor activity in heavily pretreated patients with relapsed/refractory SCLC. SEZ6 is a promising novel SCLC target and warrants further investigation.

Bioconjugation of polymers to proteins is a method to impart improved stability and pharmacokinetic properties to biologic systems. However, the precise effects of polymer architecture on the resulting bioconjugates are not well understood. Particularly, cyclic polymers are known to possess unique features such as a decreased hydrodynamic radius when compared to their linear counterparts of the same molecular weight, but have not yet been studied. Here, we report the first bioconjugation of a cyclic polymer, poly(ethylene glycol) (PEG), to a model protein, T4 lysozyme, containing a single engineered cysteine residue (V131C). We compare the stability and activity of this conjugate with those of a linear PEG-T4 lysozyme analogue of similar molecular weight. Furthermore, we used molecular dynamics (MD) simulations to determine the behavior of the polymer-protein conjugates in solution. We introduce cyclic polymer-protein conjugates as potential candidates for the improvement of biologic therapeutics.

LIPID MAPS (LIPID Metabolites and Pathways Strategy), www.lipidmaps.org, provides a systematic and standardized approach to organizing lipid structural and biochemical data. Founded 20 years ago, the LIPID MAPS nomenclature and classification has become the accepted community standard. LIPID MAPS provides databases for cataloging and identifying lipids at varying levels of characterization in addition to numerous software tools and educational resources, and became an ELIXIR-UK data resource in 2020. This paper describes the expansion of existing databases in LIPID MAPS, including richer metadata with literature provenance, taxonomic data and improved interoperability to facilitate FAIR compliance. A joint project funded by ELIXIR-UK, in collaboration with WikiPathways, curates and hosts pathway data, and annotates lipids in the context of their biochemical pathways. Updated features of the search infrastructure are described along with implementation of programmatic access via API and SPARQL. New lipid-specific databases have been developed and provision of lipidomics tools to the community has been updated. Training and engagement have been expanded with webinars, podcasts and an online training school.

The province of Saskatchewan, Canada, has a geographically dispersed population, with about 60% living more than an hour away from a tertiary care centre and 48% living more than an [...], Background: The aim of our work was to examine differences between trauma patients in rural and urban areas who presented to a tertiary trauma centre in the province of Saskatchewan, Canada. Methods: We identified a historical cohort of all level 1 trauma activations presenting to Royal University Hospital (RUH) from April 1, 2020, to March 31, 2022. We divided the cohort into 2 groups (urban and rural), according to the trauma location. The primary outcome of interest was 30-day mortality. Secondary outcomes of interest were hospital length of stay, readmission to hospital within 30 days of discharge, and complication rate. Results: Trauma patients in rural areas were younger (34.1 v. 37 yr; p = 0.002) and more likely to be male (80.3% v. 74.4%; p = 0.040), with higher Injury Severity Scores (12.3 v. 8.3; p < 0.0001). Trauma patients in urban areas were more likely to sustain penetrating trauma (42.5% v. 28.5%; p < 0.0001). We saw no differences in morbidity and mortality between the 2 groups, but the rural trauma group had longer median lengths of stay (5 v. 3 d; p < 0.0007). Conclusion: Although we identified key differences in patient demographics, injury type, and injury severity, outcomes were largely similar between the urban and rural trauma groups. This finding contradicts comparable studies within Canada and the United States, a difference that may be attributable to the lack of inclusion of prehospital mortality in the rural trauma group. The longer length of stay in trauma patients from rural areas may be attributed to disposition challenges for patients who live remotely. Contexte: Notre travail avait pour but d'analyser les diff rences entre les patient les de traumatologie provenant de milieux ruraux et urbains ayant consult dans un centre de traumatologie tertiaire de la province de la Saskatchewan, au Canada. M thodes: Nous avons constitu une cohorte historique de tous les cas d'activation de niveau 1 en traumatologie ayant consult l'H pital universitaire royal entre le 1er avril 2020 et le 31 mars 2022. Nous avons scind la cohorte en 2 groupes (milieux urbains et ruraux), selon le lieu de survenue du traumatisme. Le param tre principal tait la mortalit 30 jours. Les param tres secondaires taient la dur e du s jour hospitalier, la r hospitalisation dans les 30 jours suivant le cong , et le taux de complications. R sultats: La patient le de traumatologie provenant de r gions rurales tait plus jeune (34,1 c. 37 ans; p = 0,002) et plus susceptible d' tre de sexe masculin (80,3% c. 74,4%; p = 0,040) et de pr senter des indices de gravit des blessures plus lev s (12,3 c. 8,3; p < 0,0001). La patient le de traumatologie provenant de milieux urbains tait plus susceptible d'avoir subi un traumatisme p n trant (42,5% c. 28,5%; p < 0,0001). Nous n'avons observ aucune diff rence aux plans de la morbidit et de la mortalit entre les 2 groupes, mais la dur e m diane du s jour hospitalier du groupe provenant de milieux ruraux a t plus longue (5 c. 3 j; p < 0,0007). Conclusion: M me si nous avons observ des diff rences cl s aux plans des donn es d mographiques ainsi que du type et de la gravit des blessures, les param tres se sont r v l s assez semblables entre les patient les de traumatologie des milieux urbains et ruraux. Cette observation se d marque de celles d' tudes canadiennes et am ricaines comparables, ce qui pourrait s'expliquer par l'exclusion de la mortalit pr hospitali re dans le groupe de milieux ruraux. La dur e plus longue du s jour chez la patient le de traumatologie de milieux ruraux pourrait tre attribuable des enjeux relatifs l' tat de ces malades au moment de leur cong .

Abstract Background Efficient and scalable solutions are needed to identify patients who qualify for germline cancer genetic testing. We evaluated the clinical validity of a brief, patient-administered hereditary cancer risk assessment digital tool programmed to assess if patients meet criteria for germline genetic testing, based on personal and family history, and in line with national guidelines. Methods We applied the tool to cases seen in a nationwide telehealth genetic counseling practice. Validity of the tool was evaluated by comparing the tool’s assessment to that of the genetic counselor who saw the patient. Patients’ histories were extracted from genetic counselor-collected pedigrees and input into the tool by the research team to model how a patient would complete the tool. We also validated the tool’s assessment of which specific aspects of the personal and family history met criteria for genetic testing. Descriptive statistics were used. Results Of the 152 cases (80% female, mean age 52.3), 56% had a personal history of cancer and 66% met genetic testing criteria. The tool and genetic counselor agreed in 96% of cases. Most disagreements (4/6; 67%) occurred because the genetic counselor’s assessment relied on details the tool was not programmed to collect since patients typically don’t have access to the relevant information (pathology details, risk models). We also found complete agreement between the tool and research team on which specific aspects of the patient’s history met criteria for genetic testing. Conclusion We observed a high level of agreement with genetic counselor assessments, affirming the tool’s clinical validity in identifying individuals for hereditary cancer predisposition testing and its potential for increasing access to hereditary cancer risk assessment.

New York City's Pre-K for All (PKA) is the nation's largest universal early childhood initiative, serving over 64,000 four-year-olds annually. Stemming from the program's choice architecture as well as the city's stark residential segregation, PKA programs are extremely segregated by child race/ethnicity. Our current study explores the complex forces that influence this segregation, including the interplay between family choices, seat availability, site-level enrollment priorities, and the PKA algorithm that weighs these and other considerations. We find that a majority of PKA segregation lies within local communities, and that areas with increased options and greater racial/ethnic diversity exhibit the most extreme segregation. We also conduct a simulation that leverages family PKA choices to maximize site-level racial/ethnic diversity and reduce between-site segregation.

Current malaria treatments are threatened by drug resistance, and new drugs are urgently needed. In a phenotypic screen for new antimalarials, we identified (S)-SW228703 ((S)-SW703), a tyrosine amide with asexual blood and liver stage activity and a fast-killing profile. Resistance to (S)-SW703 is associated with mutations in the Plasmodium falciparum cyclic amine resistance locus (PfCARL) and P. falciparum acetyl CoA transporter (PfACT), similarly to several other compounds that share features such as fast activity and liver-stage activity. Compounds with these resistance mechanisms are thought to act in the ER, though their targets are unknown. The tyramine of (S)-SW703 is shared with some reported PfCARL-associated compounds; however, we observed that strict S-stereochemistry was required for the activity of (S)-SW703, suggesting differences in the mechanism of action or binding mode. (S)-SW703 provides a new chemical series with broad activity for multiple life-cycle stages and a fast-killing mechanism of action, available for lead optimization to generate new treatments for malaria.

At each stage of the HIV life cycle, host cellular proteins are hijacked by the virus to establish and enhance infection. We adapted the virus packageable HIV-CRISPR screening technology at a genome-wide scale to comprehensively identify host factors that affect HIV replication in a human T cell line. Using a smaller, targeted HIV Dependency Factor (HIVDEP) sublibrary, we then performed screens across HIV strains representing different clades and with different biological properties to define which T cell host factors are important across multiple HIV strains. Nearly 90% of the genes selected across various host pathways validated in subsequent assays as bona fide host dependency factors, including numerous proteins not previously reported to play roles in HIV biology, such as UBE2M, MBNL1, FBXW7, PELP1, SLC39A7, and others. Our ranked list of screen hits across diverse HIV-1 strains form a resource of HIV dependency factors for future investigation of host proteins involved in HIV biology. IMPORTANCE With a small genome of ~9.2 kb that encodes 14 major proteins, HIV must hijack host cellular machinery to successfully establish infection. These host proteins necessary for HIV replication are called "dependency factors." Whole-genome, and then targeted screens were done to try to comprehensively identify all dependency factors acting throughout the HIV replication cycle. Many host processes were identified and validated as critical for HIV replication across multiple HIV strains.

This visual essay in "The Photographer's Frame" describes the restoration of oak and pine forests on an island in Channel Islands National Park, California.

In this article, we situate the relatively new wave of technology-enabled personalized learning platforms within the broader policy context of institutional accountability. Although many education technology innovations were developed in response to heightened accountability pressures, technology-enabled personalization introduces new institutional rules, cultures, and norms that may be at odds with the goals of accountability. Using the adoption of a personalized, blended learning mathematics program at five U.S. schools as a case study, we describe how teachers, school leaders, and program staff navigated institutional pressures to improve state grade-level standardized test scores while implementing tasks and technologies designed to personalize student learning.

Over the past several decades large philanthropies have adopted aggressive approaches to education reform that scholars have labeled "venture philanthropy." These efforts focused on broad changes to schooling and education policy, borrowing techniques from the venture capital world. But many foundations have recently become convinced that market forces and macro-level policymaking alone cannot drive educational improvement, particularly in areas related to classroom teaching and learning. In response, foundations have begun to design their own instructional innovations and identify providers to implement them. This paper interprets these recent efforts as early evidence of a distinct adaptation in the evolving role of philanthropies, which we dub design philanthropy. Although this approach represents an attempt by foundations to simultaneously increase democratic engagement, directly influence the instructional core, and spur educational innovation, it poses new risks for coherence, scalability, and sustainability in education policymaking.

Abstract Athletes are at high risk of dehydration, fatigue, and cardiac disorders due to extreme performance in often harsh environments. Despite advancements in sports training protocols, there is an urgent need for a non‐invasive system capable of comprehensive health monitoring. Although a few existing wearables measure athlete's performance, they are limited by a single function, rigidity, bulkiness, and required straps and adhesives. Here, an all‐in‐one, multi‐sensor integrated wearable system utilizing a set of nanomembrane soft sensors and electronics, enabling wireless, real‐time, continuous monitoring of saliva osmolality, skin temperature, and heart functions is introduced. This system, using a soft patch and a sensor‐integrated mouthguard, provides comprehensive monitoring of an athlete's hydration and physiological stress levels. A validation study in detecting real‐time physiological levels shows the device's performance in capturing moments (400–500 s) of synchronized acute elevation in dehydration (350%) and physiological strain (175%) during field training sessions. Demonstration with a few human subjects highlights the system's capability to detect early signs of health abnormality, thus improving the healthcare of sports athletes.

Sex chromosomes are evolutionarily labile in many animals and sometimes fuse with autosomes, creating so-called neo-sex chromosomes. Fusions between sex chromosomes and autosomes have been proposed to reduce sexual conflict and to promote adaptation and reproductive isolation among species. Recently, advances in genomics have fuelled the discovery of such fusions across the tree of life. Here, we discovered multiple fusions leading to neo-sex chromosomes in the sapho subclade of the classical adaptive radiation of Heliconius butterflies. Heliconius butterflies generally have 21 chromosomes with very high synteny. However, the five Heliconius species in the sapho subclade show large variation in chromosome number ranging from 21 to 60. We find that the W chromosome is fused with chromosome 4 in all of them. Two sister species pairs show subsequent fusions between the W and chromosomes 9 or 14, respectively. These fusions between autosomes and sex chromosomes make Heliconius butterflies an ideal system for studying the role of neo-sex chromosomes in adaptive radiations and the degeneration of sex chromosomes over time. Our findings emphasize the capability of short-read resequencing to detect genomic signatures of fusion events between sex chromosomes and autosomes even when sex chromosomes are not explicitly assembled.

Knowledge on species composition is the first step necessary for the proper conservation and management of biological resources and ecologically relevant species. High species diversity and a lack of diagnostic characters for some groups can impose difficulties for taxonomic identification through traditional methodologies, and ichthyoplankton (fish larvae and eggs) are a good example of such a scenario. With more than 35.000 valid species of fishes worldwide and overall similar anatomies in early developmental stages in closely related groups, fish larvae are often hard to be identified at the species or even more encompassing taxonomic levels. To overcome this situation, molecular techniques have been applied, with different markers tested over the years. Cytochrome c oxidase I (COI) is the most commonly used marker and now has the broadest public reference libraries, providing consistent results for species identification in different metazoan studies. Here we sequenced the mitochondrial COI-5P fragment of 89 fish larvae collected in the Campos Basin, coastal southeastern Brazil, and compared these sequences with references deposited in public databases to obtain taxonomic identifications. Most specimens identified are species of the Blenniiformes, with Parablennius and Labrisomus the most frequently identified genera. Parablennius included two species (P. marmoreus and P. pilicornis), while Labrisomus included three species (L. cricota, L. conditus and L. nuchipinnis). Anatomy of these molecularly identified specimens were then analyzed with the intention of finding anatomical characters that might be diagnostically informative amongst the early development stage (pre-flexion) larvae. Ventral pigmentation patterns are proposed as useful markers to identify Labrisomus species. However, additional specimens are needed to confirm if the character holds stability through the geographic distribution of the species.

Students enter school with a vast range of individual differences, resulting from the complex interplay between genetic dispositions and unequal environmental conditions. Schools thus face the challenge of organizing instruction and providing equal opportunities for students with diverse needs. Schools have traditionally managed student heterogeneity by sorting students both within and between schools according to their academic ability. However, empirical evidence suggests that such tracking approaches increase inequalities. In more recent years, driven largely by technological advances, there have been calls to embrace students' individual differences in the classroom and to personalize students' learning experiences. A central justification for personalized learning is its potential to improve educational equity. In this paper, we discuss whether and under which conditions personalized learning can indeed increase equity in K-12 education by bringing together empirical and theoretical insights from different fields, including the learning sciences, philosophy, psychology, and sociology. We distinguish between different conceptions of equity and argue that personalized learning is unlikely to result in "equality of outcomes" and, by definition, does not provide "equality of inputs". However, if implemented in a high-quality way, personalized learning is in line with "adequacy" notions of equity, which aim to equip all students with the basic competencies to participate in society as active members and to live meaningful lives.

This visual essay in "The Photographer's Frame" focuses on small life forms that are easily overlooked — which means that their important contributions to ecosystems are all too often undervalued.

Author(s): Heather Wolbers [sup.1], Jeffrey Ackerman [sup.1], Justin Ready [sup.1] Author Affiliations: (1) grid.1022.1, 0000 0004 0437 5432, School of Criminology and Criminal Justice, Griffith University, , 4222, Southport, QLD, [...], Purpose This study builds on knowledge of intimate partner violence (IPV) perpetration by examining theoretically important aspects of this crime within an Australian community sample. More specifically, the current study examines the relationship between IPV offenders' levels of self-control and offense specialization and determines whether this relationship differs by gender. Method An online survey advertised on social media yielded an analysis sample of 155 females and 170 males. Self-control was measured using the Brief Self-Control scale and specialization was measured with the Offense Specialization Coefficient (OSC) and a multilevel item response theory measurement approach. Results Findings indicate that IPV offenders with low levels of self-control are more versatile in their offending and that this relationship was more evident and pronounced for females. Conclusions Findings are mostly supportive of Gottfredson and Hirschi's General Theory of Crime and highlight important differences within IPV offender populations that should be considered when designing targeted prevention and intervention methods.