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This project convened a series of meetings and workshops to prioritize listening to multi-sector stakeholders from local government, advocacy, and industry in US cities where autonomous vehicles are operating. The objective was to listen and learn from all stakeholders, raise issues surrounding accessibility and equity, and to solicit responses. Key findings from the workshops include a consensus across the three sectors on the need for good channels of multi-stakeholder communication, and voices across all sectors agreed on the importance of disability access and serving diverse populations. Many parties, representing voices from all sectors, recognized that federal regulatory activities appear to be moving too slowly. Preventing any roadway incidents is a priority for many stakeholders, and some suggest a playbook for handling day-to-day roadway issues and common standards for first-responder interactions. Disability access is a high priority across all sectors, and there many see nearer term to accommodations for blind, hearing-impaired riders, but the timeline for providing service to people with non-folding wheelchairs is less clear. There is also ongoing debate surrounding the limits of regulatory purview, the role for cities, and how to actualize equitable expansion into rural areas. There is more work to do to advance a multi-sector dialogue around the role for local governments and community-based organizations in shepherding a safe, equitable and sustainable expansion of autonomous vehicles.

We interviewed eight subject-matter experts in California in 2023 tounderstand how travel behavior and priorities may change in response to direct experience with road collisions. Expertsrepresented a variety of perspectives, including medical doctors, advocates for active transportation safety, and advocates for people with disabilities. Their diverse specialties enabled us to capture a variety of concerns without triggering emotionally sensitive areas for people who have directly experienced road collisions. These experts identified common themes, including mental stress from the prospect of returning to driving—especially on freeways, lesser incidence of long-term changes in travel modes after experiencing a collision, dependence on others for rides in private vehicles, and changing routes or times of day of travel when traveling independently. These experts also explained how people’s mode choices are also affected by general concerns about collisions in the news more than by specific personal experiences with near misses. Interview subjects’ spoke of more specific concerns as well. These included but were not limited to, bicyclists using sidewalks instead of bike lanes when both are present, feeling stigmatized from using public transit or paratransit after experiencing a collision, and concerns with motorists treating bicyclists badly. These initial interviewsclarify areas of focus and methodology for future qualitative and quantitative studies on the intersection oftransportation safety and travel behavior change, particularly as they involve people who have directly experienced road collisions.

The mammalian orthoreovirus (reovirus) σNS protein is required for formation of replication compartments that support viral genome replication and capsid assembly. Despite its functional importance, a mechanistic understanding of σNS is lacking. We conducted structural and biochemical analyses of a σNS mutant that forms dimers instead of the higher-order oligomers formed by wildtype (WT) σNS. The crystal structure shows that dimers interact with each other using N-terminal arms to form a helical assembly resembling WT σNS filaments in complex with RNA observed using cryo-EM. The interior of the helical assembly is of appropriate diameter to bind RNA. The helical assembly is disrupted by bile acids, which bind to the same site as the N-terminal arm. This finding suggests that the N-terminal arm functions in conferring context-dependent oligomeric states of σNS, which is supported by the structure of σNS lacking an N-terminal arm. We further observed that σNS has RNA chaperone activity likely essential for presenting mRNA to the viral polymerase for genome replication. This activity is reduced by bile acids and abolished by N-terminal arm deletion, suggesting that the activity requires formation of σNS oligomers. Our studies provide structural and mechanistic insights into the function of σNS in reovirus replication.

We comprehensively review typical problems that people with disabilities face when using local transportation modes. We show how specific problems with each mode can affect many different disability subgroups at once and can affect or be affected by problems with other modes. Academic literature about transportation for adults with disabilities skews toward walking, driving one's own motor vehicle, using a ridehailing or taxi service, using a carsharing service as a driver, and using public transit, so this review focuses primarily but not exclusively on those modes. We frame these problems using the terms that we introduced in a previous work. Provider-view availability refers to where & when a transportation mode is present or legal to use. Immediate usability refers to features of a mode's vehicles or infrastructure, where and when such vehicles and infrastructure are present, that help or hurt a user. User-view availability captures how serious problems with immediate usability for some users can prevent them from using those modes at all, make some aspects of provider-view availability moot for them. Cumulative usability refers to problems with a mode that arise over frequent use, longer trips, or more complicated trips, that may discourage a user from using that mode. We explain how modes that have similar requirements, present or absent, for the user to drive or to make a first-/last-mile connection exhibit consequently similar problems with provider-view availability, immediate usability, user-view availability, and cumulative usability.

Transportation planning researchers use the term “accessibility” to characterize the ability of people to reach jobs, school, healthcare and other services and activities. Disability scholars use that term to characterize the ability of people with disabilities to use transportation modes where and when present. In the United States of America (US), transportation policymakers’ use of the latter definition only for minimal legal compliance at the expense of the former definition, without synthesizing both definitions, has led to real-world negative consequences for transportation for people with disabilities, including when new train lines lead to consolidation of bus routes and in regulatory debates about how ridehailing services may serve people with disabilities. Thus, in the context of transportation policy, we propose a new set of terms that, when used consistently, can more accurately distinguish these concepts. These terms are “provider-view availability”, referring to where & when a transportation mode is present or legal to use, “immediate usability”, referring to the ease of interacting with a vehicle or (physical or digital) infrastructure upon encountering it, “user-view availability”, referring to how some people cannot start trips on a given mode due to severe problems with immediate usability, and “cumulative usability”, referring to the challenges that users of a certain mode may face more often as trip times or distances increase. We argue that transportation policymakers in the US could more accurately characterize holistic problems with transportation facing people with disabilities by consistently using these terms and thereby mitigate similar negative consequences going forward.

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohens d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohens d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level.

Background: Pregnancy is a natural phenomenon associated with several changes including attention, learning motor function, and other psychological domains. Substantial evidence shows that decreased cognitive function and increased anxiety levels during pregnancy affect the day-to-day activities of pregnant women. Scientific investigations on yoga reported enhancement of cognition and improvement of mental health. Objective: The present study was planned to explore the effect of integrated yoga (IY) on attention, motor speed, and mental speed among expecting mothers. Materials and Methods: Total 96 expected mothers aged between 20 and 35 years and having 18­20 weeks of gestation were recruited for the study and randomized into the yoga group and control group. The yoga group practiced IY and the control group practiced standard exercise. Pre- and posttests were done at the baseline and at 36th week. Results: The result showed a significant improvement in divided attention (p < 0.001), focused attention (p < 0.001), sustained attention (p < 0.001), mental speed (p < 0.001), and motor speed (p < 0.001) in the yoga group. There was also improvement in the control group, but Mann­Whitney U-test revealed that the magnitude of change in the yoga group was higher than the control group. Conclusion: This study showed that integrated antenatal yoga starting from the second trimester helps in improving cognitive functions among expecting mothers.

Random DNA barcodes are a versatile tool for tracking cell lineages, with applications ranging from development to cancer to evolution. Here, we review and critically evaluate barcode designs as well as methods of barcode sequencing and initial processing of barcode data. We first demonstrate how various barcode design decisions affect data quality and propose a new design that balances all considerations that we are currently aware of. We then discuss various options for the preparation of barcode sequencing libraries, including inline indices and Unique Molecular Identifiers (UMIs). Finally, we test the performance of several established and new bioinformatic pipelines for the extraction of barcodes from raw sequencing reads and for error correction. We find that both alignment and regular expression-based approaches work well for barcode extraction, and that error-correction pipelines designed specifically for barcode data are superior to generic ones. Overall, this review will help researchers to approach their barcoding experiments in a deliberate and systematic way.

Abstract The mammalian orthoreovirus (reovirus) σNS protein is required for formation of replication compartments that support viral genome replication and capsid assembly. Despite its functional importance, a mechanistic understanding of σNS is lacking. We conducted structural and biochemical analyses of a σNS mutant that forms dimers instead of the higher-order oligomers formed by wildtype (WT) σNS. The crystal structure shows that dimers interact with each other using N-terminal arms to form a helical assembly resembling WT σNS filaments in complex with RNA observed using cryo-EM. The interior of the helical assembly is of appropriate diameter to bind RNA. The helical assembly is disrupted by bile acids, which bind to the same site as the N-terminal arm. This finding suggests that the N-terminal arm functions in conferring context-dependent oligomeric states of σNS, which is supported by the structure of σNS lacking an N-terminal arm. We further observed that σNS has RNA chaperone activity likely essential for presenting mRNA to the viral polymerase for genome replication. This activity is reduced by bile acids and abolished by N-terminal arm deletion, suggesting that the activity requires formation of σNS oligomers. Our studies provide structural and mechanistic insights into the function of σNS in reovirus replication.

The majority of people with disabilities in the United States of America (US) are licensed drivers or use transportation modes based on private vehicles. Despite this, people with disabilities, including licensed drivers, still often encounter difficulties that limit their overall mobility and quality of life. Research about the problems with private vehicular modes facing people with disabilities remains sparse. Existing research suggests that some disabilities make driving impossible, while poverty often associated with disability makes owning and modifying vehicles to fit users’ needs unaffordable. People with disabilities who cannot drive or cannot afford to own a vehicle may use rental cars or carsharing services, get rides from friends or family, or use ridehailing services or taxis, but car-oriented land use patterns and the higher costs of modified vehicles together may compromise the availability of these modes for people with disabilities. Better understanding of the challenges that people with disabilities face with these modes and of associated land use issues is critical for new modes & policies to sustainably improve the mobility of people with disabilities.

A significant fraction of people with disabilities in the United States of America (US) do not drive, and these people disproportionately use public transit and paratransit services compared to drivers with disabilities. Substantial research exists regarding not only the ease for people with disabilities to use public transit and paratransit services but also the availability of such services and the availability of nearby pedestrian infrastructure. However, much less research exists regarding the effects of shared micromobility services, car-free areas, and consolidation of public transit services on the mobility of people with disabilities. This systems-level thinking about not only first-order effects but also second- and higher-order effects is critical for the development of policies that more effectively address the mobility needs of people with disabilities.

Summary: Background: Vitiligo is a chronic autoimmune disease characterised by depigmented skin patches, which can pose substantial psychosocial challenges particularly in individuals with dark skin tones. Despite its impact on quality of life, there is an absence of standardised global epidemiological data. We sought to address this gap with the present study. Methods: In this study we did a systematic review and modelling analysis to estimate the global, regional, and national prevalence and incidence of vitiligo. We did a comprehensive search of nine digital libraries (PubMed, Embase, Web of Science, Scientific Electronic Library Online, KCI Korean Journal Database, Russian Science Citation Index, Western Pacific Region Index Medicus, Informit, and Health Research and Development Information Network) from inception up to May 25, 2023. We included cross-sectional or cohort studies reporting the incidence rate or prevalence of vitiligo, or data from which incidence rate or prevalence could be calculated, in the general population of a country or area of a country. Summary estimate data were extracted. A main outcome was to estimate the worldwide, regional, and country-specific lifetime prevalence of vitiligo diagnosed by physicians or dermatologists among the general population and in adults and children (as per age groups defined in included studies). We used a Bayesian hierarchical linear mixed model to estimate prevalence, and calculated number of affected individuals using the UN population structure in 2022. In estimating lifetime prevalence, studies reporting point or period prevalence were excluded. Our other main outcome was to estimate incidence rates of vitiligo, but due to a small number of studies, the data on incidence were presented in a descriptive summary. This study was registered on PROSPERO, CRD42023390433. Findings: Our search identified 22 192 records, of which 90 studies met our inclusion criteria. Of these studies, six focused on the incidence of vitiligo, 79 reported on the prevalence of vitiligo, and five provided data on both incidence and prevalence. 71 studies reported on lifetime prevalence. In the most recent years studied, incidence rates in the general population ranged from 24·7 cases (95% CI 24·3–25·2) per 100 000 person-years in South Korea in 2019, to 61·0 cases (60·6–61·4) in the USA in 2017. In individual studies, incidence rates showed an increasing trend over the periods studied. The global lifetime prevalence of vitiligo diagnosed by a physician or dermatologist was estimated at 0·36% (95% credible interval [CrI] 0·24–0·54) in the general population (28·5 million people [95% CrI 18·9–42·6]), 0·67% (0·43–1·07) in the adult population (37·1 million adults [23·9–58·9]), and 0·24% (0·16–0·37) in the child population (5·8 million children [3·8–8·9]). Vitiligo prevalence was higher in adults than in children across all regions. Central Europe and south Asia reported the highest prevalence (0·52% [0·28–1·07] and 0·52% [0·33–0·82], respectively, in the general population). Interpretation: This study highlights the need for standardised epidemiological data collection globally to inform public health policies and improve vitiligo diagnosis and management. Emphasis on the impact on individuals with darker skin tones is crucial to reducing stigma and improving quality of life. Furthermore, our study highlights the need to conduct more research in regions and populations that have been historically under-represented, to effectively address the worldwide burden of vitiligo. Funding: None.

People with disabilities travel less than their peers without disabilities. Much research about the travel patterns of people with disabilities focuses on problems they experience with specific transportation modes, under the assumption that fixing those specific problems is enough to fully include people with disabilities in the broader world. This doesn’t account for the connections of different transportation modes to land use patterns, and it presumes what people with disabilities want without asking them. This project aims to understand the extent to which disability may affect the choices and desires that people have for transportation mode usage frequencies, activity frequencies, and neighborhood features.

People with disabilities often encounter more and different problems with transportation compared to their socioeconomic peers without disabilities, but their desires for transportation mode choices, usage frequencies, activity frequencies, and neighborhood features have been poorly understood. The authors have begun to rectify those deficiencies with this study, developed in close cooperation with disability advocacy organizations (DAOs). The authors conducted a focus group in 2021 November involving 20 adults with various disabilities across California, including rural, suburban, and urban parts of the major coastal metropolitan areas as well as areas in the interior of the state. Focus group participants’ comments evinced a broad theme of problems for people with disabilities arising from car-oriented land use patterns, as they asked for more street lighting, seating, and shade, more frequent public transit service with more geographic coverage, and similar support for infrequent yet critical longer-distance trips. Based on focus group participants’ suggestions and pre-testing as well as feedback from DAOs, the authors developed a survey of adults across California to capture how disability affects the choices and desires that people make for transportation mode frequencies, activity frequencies, and neighborhood features. The survey collected nearly 2,000 cleaned responses, reflecting the diversity in disability, geography, and socioeconomic conditions in California.

CTX-M β-lactamases are prevalent antibiotic resistance enzymes and are notable for their ability to rapidly hydrolyze the extended-spectrum cephalosporin, cefotaxime. We hypothesized that the active site sequence requirements of CTX-M-mediated hydrolysis differ between classes of β-lactam antibiotics. Accordingly, we use codon randomization, antibiotic selection, and deep sequencing to determine the CTX-M active-site residues required for hydrolysis of cefotaxime and the penicillin, ampicillin. The study reveals positions required for hydrolysis of all β-lactams, as well as residues controlling substrate specificity. Further, CTX-M enzymes poorly hydrolyze the extended-spectrum cephalosporin, ceftazidime. We further show that the sequence requirements for ceftazidime hydrolysis follow those of cefotaxime, with the exception that key active-site omega loop residues are not required, and may be detrimental, for ceftazidime hydrolysis. These results provide insights into cephalosporin hydrolysis and demonstrate that changes to the active-site omega loop are likely required for the evolution of CTX-M-mediated ceftazidime resistance.

Abstract The lasting threat of viral pandemics necessitates the development of tailorable first-response antivirals with specific but adaptive architectures for treatment of novel viral infections. Here, such an antiviral platform has been developed based on a mixture of hetero-peptides self-assembled into functionalized β-sheets capable of specific multivalent binding to viral protein complexes. One domain of each hetero-peptide is designed to specifically bind to certain viral proteins, while another domain self-assembles into fibrils with epitope binding characteristics determined by the types of peptides and their molar fractions. The self-assembled fibrils maintain enhanced binding to viral protein complexes and retain high resilience to viral mutations. This method is experimentally and computationally tested using short peptides that specifically bind to Spike proteins of SARS-CoV-2. This platform is efficacious, inexpensive, and stable with excellent tolerability.

β-lactamases inactivate β-lactam antibiotics leading to drug resistance. Consequently, inhibitors of β-lactamases can combat this resistance, and the β-lactamase inhibitory protein (BLIP) is a naturally occurring inhibitor. The widespread CTX-M-14 and CTX-M-15 β-lactamases have an 83% sequence identity. In this study, we show that BLIP weakly inhibits CTX-M-14 but potently inhibits CTX-M-15. The structure of the BLIP/CTX-M-15 complex reveals that binding is associated with a conformational change of an active site loop of β-lactamase. Surprisingly, the loop structure in the complex is similar to that in a drug-resistant variant (N106S) of CTX-M-14. We hypothesized that the pre-established favorable loop conformation of the N106S mutant would facilitate binding. The N106S substitution results in a ~100- and 10-fold increase in BLIP inhibition potency for CTX-M-14 and CTX-M-15, respectively. Thus, this indicates that an active site loop in β-lactamase toggles between conformations that control antibiotic hydrolysis and inhibitor susceptibility. These findings highlight the role of accessible active site conformations in controlling enzyme activity and inhibitor susceptibility as well as the influence of mutations in selectively stabilizing discrete conformations.

Abstract Acute gastroenteritis caused by human noroviruses (HuNoVs) is a significant global health and economic burden and is without licensed vaccines or antiviral drugs. The GII.4 HuNoV causes most epidemics worldwide. This virus undergoes epochal evolution with periodic emergence of variants with new antigenic profiles and altered specificity for histo-blood group antigens (HBGA), the determinants of cell attachment and susceptibility, hampering the development of immunotherapeutics. Here, we show that a llama-derived nanobody M4 neutralizes multiple GII.4 variants with high potency in human intestinal enteroids. The crystal structure of M4 complexed with the protruding domain of the GII.4 capsid protein VP1 revealed a conserved epitope, away from the HBGA binding site, fully accessible only when VP1 transitions to a “raised” conformation in the capsid. Together with dynamic light scattering and electron microscopy of the GII.4 VLPs, our studies suggest a mechanism in which M4 accesses the epitope by altering the conformational dynamics of the capsid and triggering its disassembly to neutralize GII.4 infection.

The great success of single-particle electron cryo-microscopy (cryoEM) during the last decade has involved the development of powerful new computer programs and packages that guide the user along a recommended processing workflow, in which the wisdom and choices made by the developers help everyone, especially new users, to obtain excellent results. The ability to carry out novel, non-standard or unusual combinations of image-processing steps is sometimes compromised by the convenience of a standard procedure. Some of the older programs were written with great flexibility and are still very valuable. Among these, the original MRC image-processing programs for structure determination by 2D crystal and helical processing alongside general-purpose utility programs such as Ximdisp, label, imedit and twofile are still available. This work describes an updated version of the MRC software package (MRC2020) that is freely available from CCP-EM. It includes new features and improvements such as extensions to the MRC format that retain the versatility of the package and make it particularly useful for testing novel computational procedures in cryoEM.

We comprehensively review typical problems that people with disabilities face when using local transportation modes. We show how specific problems with each mode can affect many different disability subgroups at once and can affect or be affected by problems with other modes. Academic literature about transportation for adults with disabilities skews toward walking, driving one’s own motor vehicle, using a ridehailing or taxi service, using a carsharing service as a driver, and using public transit, so this review focuses primarily but not exclusively on those modes. We frame these problems using the terms that we introduced in a previous work. Provider-view availability refers to where & when a transportation mode is present or legal to use. Immediate usability refers to features of a mode’s vehicles or infrastructure, where and when such vehicles and infrastructure are present, that help or hurt a user. User-view availability captures how serious problems with immediate usability for some users can prevent them from using those modes at all, make some aspects of provider-view availability moot for them. Cumulative usability refers to problems with a mode that arise over frequent use, longer trips, or more complicated trips, that may discourage a user from using that mode. We explain how modes that have similar requirements, present or absent, for the user to drive or to make a first-/last-mile connection exhibit consequently similar problems with provider-view availability, immediate usability, user-view availability, and cumulative usability.

The VP8* domain of spike protein VP4 in group A and C rotaviruses, which cause epidemic gastroenteritis in children, exhibits a conserved galectin-like fold for recognizing glycans during cell entry. In group B rotavirus, which causes significant diarrheal outbreaks in adults, the VP8* domain (VP8*B) surprisingly lacks sequence similarity with VP8* of group A or group C rotavirus. Here, by using the recently developed AlphaFold2 for ab initio structure prediction and validating the predicted model by determining a 1.3-Å crystal structure, we show that VP8*B exhibits a novel fold distinct from the galectin fold. This fold with a β-sheet clasping an α-helix represents a new fold for glycan recognition based on glycan array screening, which shows that VP8*B recognizes glycans containing N-acetyllactosamine moiety. Although uncommon, our study illustrates how evolution can incorporate structurally distinct folds with similar functionality in a homologous protein within the same virus genus.

Despite the advances in β-lactamase inhibitor development, limited options exist for the class D carbapenemase known as OXA-48. OXA-48 is one of the most prevalent carbapenemases in carbapenem-resistant Enterobacteriaceae infections and is not susceptible to most available β-lactamase inhibitors. Here, we screened various low-molecular-weight compounds (fragments) against OXA-48 to identify functional scaffolds for inhibitor development. Several biphenyl-, naphthalene-, fluorene-, anthraquinone-, and azobenzene-based compounds were found to inhibit OXA-48 with low micromolar potency despite their small size. Co-crystal structures of OXA-48 with several of these compounds revealed key interactions with the carboxylate-binding pocket, Arg214, and various hydrophobic residues of β-lactamase that can be exploited in future inhibitor development. A number of the low-micromolar-potency inhibitors, across different scaffolds, synergize with ampicillin to kill Escherichia coli expressing OXA-48, albeit at high concentrations of the respective inhibitors. Additionally, several compounds demonstrated micromolar potency toward the OXA-24 and OXA-58 class D carbapenemases that are prevalent in Acinetobacter baumannii. This work provides foundational information on a variety of chemical scaffolds that can guide the design of effective OXA-48 inhibitors that maintain efficacy as well as potency toward other major class D carbapenemases.

Prenylated indole alkaloids featuring spirooxindole rings possess a 3R or 3S carbon stereocenter, which determines the bioactivities of these compounds. Despite the stereoselective advantages of spirooxindole biosynthesis compared with those of organic synthesis, the biocatalytic mechanism for controlling the 3R or 3S-spirooxindole formation has been elusive. Here, we report an oxygenase/semipinacolase CtdE that specifies the 3S-spirooxindole construction in the biosynthesis of 21R-citrinadin A. High-resolution X-ray crystal structures of CtdE with the substrate and cofactor, together with site-directed mutagenesis and computational studies, illustrate the catalytic mechanisms for the possible β-face epoxidation followed by a regioselective collapse of the epoxide intermediate, which triggers semipinacol rearrangement to form the 3S-spirooxindole. Comparing CtdE with PhqK, which catalyzes the formation of the 3R-spirooxindole, we reveal an evolutionary branch of CtdE in specific 3S spirocyclization. Our study provides deeper insights into the stereoselective catalytic machinery, which is important for the biocatalysis design to synthesize spirooxindole pharmaceuticals.

Transportation planning researchers use the term “accessibility” to characterize the ability of people to reach jobs, school, healthcare and other services and activities. Disability scholars use that term to characterize the ability of people with disabilities to use transportation modes where and when present. In the United States of America (US), transportation policymakers’ use of the latter definition only for minimal legal compliance at the expense of the former definition, without synthesizing both definitions, has led to real-world negative consequences for transportation for people with disabilities, including when new train lines lead to consolidation of bus routes and in regulatory debates about how ridehailing services may serve people with disabilities. Thus, in the context of transportation policy, we propose a new set of terms that, when used consistently, can more accurately distinguish these concepts. These terms are “provider-view availability”, referring to where & when a transportation mode is present or legal to use, “immediate usability”, referring to the ease of interacting with a vehicle or (physical or digital) infrastructure upon encountering it, “user-view availability”, referring to how some people cannot start trips on a given mode due to severe problems with immediate usability, and “cumulative usability”, referring to the challenges that users of a certain mode may face more often as trip times or distances increase. We argue that transportation policymakers in the US could more accurately characterize holistic problems with transportation facing people with disabilities by consistently using these terms and thereby mitigate similar negative consequences going forward.

Chronic obstructive pulmonary disease (COPD) is the world's third leading cause of death, posing a significant public health challenge. Heart failure is an important milestone in the natural history of this disease's ever-decreasing course. Cor pulmonale alone is sometimes insufficient to explain the scenario, as many heart failures are refractory even after standard treatment. A possible explanation is involvement of the left ventricle (LV). However, there is currently no consensus on a therapeutic approach to LV dysfunction in COPD. Some previous studies were conducted on COPD patients regardless of the presence or absence of other factors influencing LV function. This study attempted to rule out all known confounding factors/co-morbidities that influence LV function. We discovered that LV diastolic dysfunction was common in subjects at all stages of COPD. We believe that all COPD patients, regardless of stage, should have screening echocardiography.

Background: Somatic symptoms especially in the early postpartum period may be common, but their frequency and severity may indicate underlying childbirth-related Post Traumatic Stress Disorder (PTSD) and postpartum depression. Materials and Methods: This study aimed to assess somatic symptoms in women during the early postpartum period and their association to childbirth-related PTSD and depression. This was a community-based cross-sectional study conducted in South India. The Scale for Assessment of Somatic Symptoms (SASS), Childbirth Experience Questionnaire (CEQ), PTSD Checklist (PCL), and Edinburgh Postnatal Depression Scale (EPDS) were used to assess somatic symptoms, negative childbirth experience, PTSD symptoms, and depression, respectively. Results: Among 95 primigravida women who were in their 2–6 weeks postpartum, the occurrence of somatic symptoms varied from 4% to 79% depending on the nature of symptoms. Pain symptoms, fatigue and weakness, and alteration in biological functions such as libido, sleep, and appetite were more commonly noted. The total severity score on SASS correlated negatively with the CEQ (r = −0.544, p = .001) and positively with scores on the PCL (r = 0.494, p = .001) and EPDS (r = 0.565, p = .001), indicating that somatic symptoms were associated with negative childbirth experience, childbirth-related PTSD, and depression. The frequencies of somatic symptoms were noted to be higher in women with childbirth-related PTSD and depression. Conclusion: Women presenting with multiple and severe somatic complaints in the early postnatal period may have underlying PTSD or depression following a negative childbirth experience. A detailed and sensitive enquiry along with appropriate care should be provided to such women to enhance maternal well-being.

Culture methods for studying human norovirus infection have been recently established. Here, Ayyar and colleagues use human intestinal enteroids to dissect viral entry mechanisms and show that CLIC-mediated endocytosis and wound repair pathways are exploited by pandemic norovirus.

Melasma, a chronic pigmentary skin condition mainly affecting the face, remains a challenge despite the availability of several options for treatment. Many melasma patients are not satisfied with treatment outcomes. Tranexamic acid (TXA), an anti-fibrinolytic drug has shown promising results in patients with melasma. Evidence from several clinical studies has surfaced on efficacy and tolerability of TXA in these patients. It can be used as monotherapy or adjuvant with other therapies. Currently, there is no published consensus or guideline document for its use in the treatment of melasma. TXA is available for oral use, topical use as well as an injection. In this article, a consensus of Indian experts is prepared based on the available literature and experience with use of oral TXA in melasma. This review article might help clinicians for use of oral TXA appropriately while treating melasma.

Structural analysis, antibiotic selection, and deep sequencing of CTX-M-14 mutants identify residues required for β-lactamase activity.

BackgroundThe rarity of hand acrometastases hampers the consensus-building for their optimal management among the involved oncology professionals. In the current literature, demolitive surgery overcomes the use of palliative radiotherapy, which proved to be ineffective in more than 30% of cases treated with classic palliative dose schemes, carrying also a not negligible radiation-related adverse event rate. Against this background, stereotactic body radiation therapy (SBRT) could emerge as a well-balanced therapeutic option.Case summaryHere we describe the methods and outcomes of a SBRT treatment of a painful and function-limiting hand acrometastasis in a patient with a history of stage IIIB lung adenocarcinoma. We delivered a total dose of 30 Gy in five daily fractions to a soft-tissue metastasis abutting the fifth metacarpal bone through the SBRT protocol generally used for intracranial treatments. A few weeks later, the patient reported a clinical complete response with acrometastasis and pain disappearance, function recovery, and no significant toxicity. The acrometastasis was the first sign of an atypical cancer progression.ConclusionsSBRT for hand acrometastases is feasible and might have the best therapeutic profile among the currently available treatment options for this rare clinical scenario. Larger investigations are needed to confirm the present single-case experience.