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What are the constraints, cues, and mechanisms that help learners create successful word-meaning mappings? This study takes up linguistic disjunction and looks at cues and mechanisms that can help children learn the meaning of or. We first used a large corpus of parent-child interactions to collect statistics on or uses. Children started producing or between 18-30 months and by 42 months, their rate of production reached a plateau. Second, we annotated for the interpretation of disjunction in child-directed speech. Parents used or mostly as exclusive disjunction, typically accompanied by rise-fall intonation and logically inconsistent disjuncts. But when these two cues were absent, disjunction was generally not exclusive. Our computational modeling suggests that an ideal learner could successfully interpret an English disjunction (as exclusive or not) by mapping forms to meanings after partitioning the input according to the intonational and logical cues available in child-directed speech.

For both children and adults, communicating with each other effectively depends on having enough knowledge about particular entities, actions, or relations to understand and produce the words being used. Speakers draw on conventional meanings shared with their interlocutors, but do they share every detail of word meaning? They need not have identical, or fully specified, representations for the meanings of all the terms they make use of. Rather, they need only have representedenoughabout the meanings of the words used by another speaker to understand what is intended in context on a particular occasion. Reliance on partial meanings is common in both children and adults. More detailed, shared, representations of word meanings for a domain depend on acquiring additional knowledge about that domain and its contents.

Guided by the job demand-control-support model of workplace strain, this study tested a theoretical model of academic work environments to explain workplace bullying in academia. College professors ( N = 503) completed a questionnaire about working in academia and experiencing bullying at work. Results of a conditional process analysis revealed that psychological job demands affected workplace bullying incidents directly, and indirectly through increased occupational stress; however, the mediated effect depended on how supportive the supervisor was and how much control professors had over their job duties (moderated moderated mediation). In departments where supervisors provided low to average social support to faculty, the indirect effect on bullying was weakened when professors had more decision authority over how they completed their job demands (moderated mediation). However, in departments where supervisors were highly supportive, there was no indirect effect of demands on workplace bullying through stress, despite how much or little decision authority professors had in doing their jobs (no moderated mediation). These findings speak to the importance of appointing a chairperson who will encourage professors’ autonomy in completing their work, and, more crucially, provide social support to discourage faculty bullying in response to job stressors.

To examine the outcomes and cost effectiveness of expectant management versus immediate delivery of women who experience preterm premature rupture of membranes (PPROM) at 34 weeks.A cost-effectiveness model was built using TreeAge software to compare outcomes in a theoretical cohort of 37,455 women with PPROM at 34 weeks undergoing expectant management until 37 weeks versus immediate delivery. Outcomes included fetal death, neonatal sepsis, neonatal death, neonatal neurodevelopmental delay, healthy neonate, maternal sepsis, maternal death, cost, and quality-adjusted life years. Probabilities were derived from the literature, and a cost-effectiveness threshold was set at $100,000 per quality-adjusted life year.In our theoretical cohort of 37,455 women, expectant management yielded 58 fewer neonatal deaths and 164 fewer cases of neonatal neurodevelopmental delay. However, it resulted in 407 more cases of neonatal sepsis and 2.7 more cases of maternal sepsis. Expectant management resulted in 3,531 more quality-adjusted life years and a cost savings of $71.9 million per year, making it a dominant strategy. Univariate sensitivity analysis demonstrated expectant management was cost effective until the weekly cost of antepartum admission exceeded $17,536 (baseline estimate: $12,520) or the risk of maternal sepsis following intraamniotic infection exceeded 20%.Our model demonstrated that expectant management of PPROM at 34 weeks yielded better outcomes on balance at a lower cost than immediate delivery. This analysis is important and timely in light of recent studies suggesting improved neonatal outcomes with expectant management. However, individual risks and preferences must be considered in making this clinical decision as expectant management may increase the risk of adverse perinatal outcomes when the risk of puerperal infection increases.

Aims This study aims to assess the feasibility of conducting a pragmatic, multicentre randomized controlled trial (RCT) to test the clinical and cost-effectiveness of an informal caregiver training programme to support the recovery of people following hip fracture surgery. Methods This will be a mixed-methods feasibility RCT, recruiting 60 patients following hip fracture surgery and their informal caregivers. Patients will be randomized to usual NHS care, versus usual NHS care plus a caregiver-patient dyad training programme (HIP HELPER). This programme will comprise of three, one-hour, one-to-one training sessions for the patient and caregiver, delivered by a nurse, physiotherapist, or occupational therapist. Training will be delivered in the hospital setting pre-patient discharge. It will include practical skills for rehabilitation such as: transfers and walking; recovery goal setting and expectations; pacing and stress management techniques; and introduction to the HIP HELPER Caregiver Workbook, which provides information on recovery, exercises, worksheets, and goal-setting plans to facilitate a ‘good’ recovery. After discharge, patients and caregivers will be supported in delivering rehabilitation through three telephone coaching sessions. Data, collected at baseline and four months post-randomization, will include: screening logs, intervention logs, fidelity checklists, quality assurance monitoring visit data, and clinical outcomes assessing quality of life, physical, emotional, adverse events, and resource use outcomes. The acceptability of the study intervention and RCT design will be explored through qualitative methods with 20 participants (patients and informal caregivers) and 12 health professionals. Discussion A multicentre recruitment approach will provide greater external validity across population characteristics in England. The mixed-methods approach will permit in-depth examination of the intervention and trial design parameters. The findings will inform whether and how a definitive trial may be undertaken to test the effectiveness of this caregiver intervention for patients after hip fracture surgery. Cite this article: Bone Jt Open 2021;2(11):909–920.

In this article, we ask how well Australian households are matched to their neighbourhood social environments. We broadly replicate a previous study of matching and ask to what extent households live in communities that are similar in socio-economic status to their characteristics. And, when households move, do they relocate in such a way as to increase similarity to their neighbours? The processes are at the heart of understanding the urban structure, how it changes over time and the links to urban inequality. The article uses data on household incomes from the Household, Income and Labour Dynamic (HILDA) Survey to measure the degree of similarity between households and their neighbours. We study the variation in matching for the population as a whole, and by quintiles of median neighbourhood income. We also measure how individuals that change neighbourhoods increase their similarity to the destination neighbourhood. We find that with respect to matching there is considerable diversity in the levels of matching; and that with respect to residential change, households in general do not make major shifts to increase matching when we control for housing tenure and other household characteristics. There is a need for further replications to understand the nature of matching and the outcomes.

This paper provides an empirical overview of housing tenure transitions in Australia, the UK and the USA during a period of unprecedented economic instability in 2001–2017. Focusing on the neglected theme of episodic homeownership, we profile those who straddle the tenure divide by moving into and out of renting from time to time. Using panel data we model this ‘churn’ in three jurisdictions, showing that even the dislocation of a global financial crisis does not eclipse the independent impact of life events during rental spells. We find that whatever individuals bring from prior ownership, shocks occurring during a rental spell – unemployment, loss of a partner, additional dependent children – can be sufficient to prevent return. Churning is also health- and age-selective, adding ‘drop-out’ among the old to ‘lock-out’ for the young as a policy concern. Even those who successfully regain owner-occupation increase their credit and investment risks without necessarily improving their housing position. Overall ‘churners’ are a diverse constituency whose life chances are powerfully shaped by episodic ownership: what they share is time spent in an unacknowledged, under-instituted space between tenures where there is latent demand for innovative financial services and untapped potential for radical policy shifts.

BackgroundDirect comparisons of sepsis screening tools for prognostication have largely been limited to single-centre or high-income countries despite a disproportionately high burden of sepsis in low- and middle-income countries (LMICs). We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the United States, Cambodia, and Ghana.MethodsFrom 2014 to 2021, participants with 2 or more SIRS (Systemic Inflammatory Response Syndrome) criteria and suspected infection were enrolled in emergency departments and medical wards at hospitals in the Cambodia and Ghana and hospitalized participants with suspected infection were enrolled in the United States. Cox proportional hazards regression was performed, and Harrell’s C-statistic calculated to determine 28-day mortality prediction performance of the qSOFA score ≥2, SIRS score ≥3, NEWS ≥5, MEWS ≥5, or UVA score ≥2, Screening tools were compared to baseline risk (age and sex) with the Wald test.ResultsThe cohorts included 567 participants (42.9% female) including 187 participants from Kumasi, Ghana, 200 participants from Takeo, Cambodia, and 180 participants from Durham, North Carolina in the United States. The pooled mortality was 16.4% at 28-days. The mortality prediction accuracy increased from baseline risk with the MEWS (C-statistic: 0.63, 95% CI: 0.58, 0.68; p=0.002), NEWS (C-statistic: 0.68; 95% confidence interval [CI]: 0.64, 0.73; pConclusionsAmong the cohorts, MEWS, NEWS, qSOFA, and UVA scores performed better than baseline risk, largely driven by accuracy improvements in Ghana, while SIRS scores did not improve prognostication accuracy. Prognostication scores should be validated within the target population prior to clinical use.Key questionsWhat is already known on this topic – While single-centre cohorts and retrospective analyses have been performed, the optimal sepsis screening tool for prognostication in low- and middle-income countries is unknown.What this study adds – The MEWS, NEWS, qSOFA scores, but not SIRS, were additive over baseline risk for prognostication in prospective hospitalized infection cohorts, but with variable additive performance within each cohort.How this study might affect research, practice or policy - Prognostication scores should be validated within the target population prior to clinical use.

Treatment of gestational diabetes mellitus has been demonstrated to improve perinatal outcomes. However, the role of the Special Supplemental Nutrition Program for Women, Infants, and Children in maternal and neonatal outcomes for qualifying patients with gestational diabetes mellitus is less understood.The objective of this study is to observe the relationship of enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children with pregnancy outcomes in patients with gestational diabetes.This was a retrospective cohort study using National Vital Statistics Birth Data of pregnant persons diagnosed with gestational diabetes mellitus between 2014 and 2018. The study population was composed of patients who had Medicaid coverage for maternity care; patients with Medicaid are automatically qualified for the Special Supplemental Nutrition Program for Women, Infants, and Children. The study groups were defined as those who enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children vs those who did not enroll. In addition, maternal and neonatal outcomes for these groups were analyzed. Univariate and multivariable logistic regression analyses adjusted for significant covariates were performed.Of 460,377 pregnant persons with pregnancies complicated by gestational diabetes mellitus, 73% were enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children, and 27% were not. Pregnant persons with gestational diabetes mellitus enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children had decreased odds of preterm delivery before 34 and 37 weeks of gestation. Although the Special Supplemental Nutrition Program for Women, Infants, and Children group had higher odds of large-for-gestational-age neonates and cesarean delivery, the overall rates of these outcomes in both cohorts were high.The Special Supplemental Nutrition Program for Women, Infants, and Children provides a resource for perinatal support, supplemental food, and nutritional education. The decrease in the rates of preterm deliveries in pregnant persons with gestational diabetes mellitus that enroll in the Special Supplemental Nutrition Program for Women, Infants, and Children, Infants, and Children relative to those that qualified for the program but did not enroll suggested that having access to available education and food sources may influence perinatal outcomes.

Purported benefits of human-grade pet foods include reduced inflammation, enhanced coat quality, and improved gut health, but research is scarce. Therefore, we compared gene expression, skin and coat health measures, and the fecal microbiome of dogs consuming a mildly cooked human-grade or extruded kibble diet. Twenty beagles (BW = 10.25 ± 0.82 kg; age = 3.85 ± 1.84 yr) were used in a completely randomized design. Test diets included: 1) chicken and brown rice recipe [feed-grade; extruded; blue buffalo (BB)]; and 2) chicken and white rice [human-grade; mildly cooked; Just Food for Dogs (JFFD)]. The study consisted of a 4-week baseline when all dogs ate BB, and a 12-week treatment phase when dogs were randomized to either diet (n = 10/group). After the baseline and treatment phases, fresh fecal samples were scored and collected for pH, dry matter (DM), and microbiome analysis; blood samples were collected for gene expression analysis; hair samples were microscopically imaged; and skin was analyzed for delayed-type hypersensitivity (DTH), sebum concentration, hydration status, and transepidermal water loss (TEWL). Data were analyzed as a change from baseline (CFB) using the Mixed Models procedure of SAS (version 9.4). At baseline, fecal pH was higher (P0.05) and hair surface score, superoxide dismutase (SOD) expression, and tumor necrosis factor-α (TNF-α) expression was lower (P0.05) in dogs allotted to JFFD. The decrease in CFB fecal pH and DM was greater (P0.05) in dogs fed JFFD, but fecal scores were not different. The increase in CFB hair surface score was higher (P0.05) in dogs fed JFFD. The decrease in CFB TEWL (back region) was greater (P0.05) in dogs fed JFFD, but TEWL (inguinal and ear regions), hydration status, and sebum concentrations in all regions were not different. Hair cortex scores and DTH responses were not affected by diet. The increase in CFB gene expression of SOD, COX-2, and TNF-α was greater (P0.05) in dogs fed JFFD. PCoA plots based on Bray-Curtis distances of bacterial genera and species showed small shifts over time in dogs fed BB, but dramatic shifts in those fed JFFD. JFFD increased (adj. P0.05) relative abundances of 4 bacterial genera, 11 bacterial species, 68 KEGG pathways, and 167 MetaCyc pathways, and decreased (adj. P0.05) 16 genera, 25 species, 98 KEGG pathways, and 87 MetaCyc pathways. In conclusion, the JFFD diet dramatically shifted the fecal microbiome but had minor effects on skin and coat measures and gene expression.This study tested the effects of a mildly cooked human-grade diet and a feed-grade extruded kibble diet on the fecal microbiome, skin and coat health measures, and expression of genes related to inflammation and oxidative stress in healthy adult dogs. During a 4-week baseline, 20 beagles consumed the kibble diet. After baseline, 10 dogs continued to consume that diet, while 10 dogs consumed the mildly cooked diet for 12 weeks. After baseline and treatment phases, fresh fecal, blood, and hair samples were collected and skin was analyzed. The mildly cooked diet led to lower fecal pH and dry matter percentage, but fecal scores were not affected. The mildly cooked diet dramatically altered the fecal microbiome, shifting the relative abundances of over 30 bacterial species and 165 bacterial metabolic pathways. Measures of skin sebum content and hydration status were not different between groups, but skin water loss was lower in dogs consuming the mildly cooked diet. Baseline and post-treatment gene expression and hair surface scores were noted, but hair cortex and delayed-type hypersensitivity testing were not altered by diet. Our results demonstrate that mildly cooked diets dramatically change the fecal microbiome, but may not impact skin and coat in healthy adult dogs over a short time period.

Burkholderia pseudomallei is a Gram-negative soil saprophyte with the potential to cause melioidosis, an opportunistic disease with a high mortality potential. Periodic case reports of melioidosis in or imported from Africa occur in the literature dating back decades. Furthermore, statistical models suggest Western sub-Saharan Africa as a high-risk zone for the presence of B. pseudomallei. A recent case report from the United Kingdom of a returning traveler from Ghana highlights the need for environmental studies in Ghana. We examined 100 soil samples from a rice farm in south-central Ghana. Soil was subjected to selective enrichment culture for B. pseudomallei using threonine-basal salt solution with colistin (TBSS-C50) and erythritol medium, as described in the literature. Bacterial cultures were identified with standard biochemical tests, a rapid antigen detection assay, and real-time PCR specific for B. pseudomallei. Of the 100 soil samples, 55% yielded cultures consistent with B. pseudomallei on Ashdown’s agar as well as by capsular polysaccharide antigen production. This is the first confirmatory report of culture-confirmed B. pseudomallei in the environment of Ghana. Our study emphasizes the need for further exploration of the burden of human melioidosis in Ghana. We recommend that local clinicians familiarize themselves with the diagnosis and clinical management of melioidosis, while laboratories develop capacity for the safe isolation and identification of B. pseudomallei. IMPORTANCE We present the first confirmation of the presence of B. pseudomallei in the environment of Ghana. This study will bring attention to a disease with the potential to cause significant morbidity and mortality in Ghana, but which has gone completely unrecognized until this point. Furthermore, this work would encourage local clinicians to familiarize themselves with the diagnosis and clinical management of melioidosis and laboratories to develop capacity for the safe isolation and identification of B. pseudomallei.

In four decades, China has transitioned from a controlled housing economy to one in which choices (and constraints) are more central drivers of residential change, although government roles in inne...

Objective To assess whether a superior hypogastric plexus block performed during laparoscopic hysterectomy reduces postoperative pain. Methods We conducted a multicenter, randomized, single-blind, controlled trial of superior hypogastric plexus block at the start of laparoscopic hysterectomy. Women undergoing a laparoscopic hysterectomy for any indication and with any other concomitant laparoscopic procedure were eligible. Standardized preoperative medications and incisional analgesia were provided to all patients. Our primary outcome was the proportion of patients with a mean visual analog scale (VAS) pain score lower than 4 within 2 hours postoperatively. Patients but not surgeons were blinded to the treatment group. Twenty-nine patients per group was estimated to be sufficient to detect a 38% absolute difference in the proportion of patients with a VAS score lower than 4 at 2 hours postoperatively, with 80% power and an α of 0.05. To account for loss to follow-up and potential imbalances in patient characteristics, we planned to enroll 50 patients per group. All analyses were intention to treat. Results Between January 2018 and February 2019, 186 patients were eligible; 100 were randomized and analyzed. Demographic and clinical characteristics were similar between the two groups. There was no significant difference in the proportion of patients with a mean VAS score lower than 4 within 2 hours postoperatively between patients who received a superior hypogastric plexus block (57%) and patients who did not (43%) (odds ratio 1.63, 95% CI 0.74-3.59; adjusted odds ratio 1.84, 95% CI 0.75-4.51). Conclusion Among patients undergoing laparoscopic hysterectomy with standardized enhanced perioperative recovery pathways, superior hypogastric plexus block did not significantly reduce postoperative pain. Clinical trial registration ClinicalTrials.gov, NCT03283436.

Background: Prior to COVID-19 there had been a renewed policy focus in the National Health Service on the health and well-being of the healthcare workforce, with the ambulance sector identified as a priority area. This focus is more important than ever as the sector deals with the acute and longer-term consequences of a pandemic. Aim: To systematically identify, summarise and map the evidence regarding mental health, well-being and support interventions for United Kingdom ambulance services staff and to identify evidence gaps. Method: Evidence mapping methodology of published and grey original research published in English from 1 January 2000 to 23 May 2020 describing the health risk, mental health and/or well-being of UK ambulance services staff including retired staff, volunteers and students. MEDLINE, EMBASE, PsychINFO, CINAHL and AMED databases, plus EThOS, Zetoc, OpenGrey and Google, were searched, alongside hand-searching of grey literature and bibliographies. Information was extracted on study aims, sample, design and methodology, funding source, country and key findings. Included studies were categorised into seven a priori theme areas. Results: Of 1862 identified articles, 45 peer-reviewed studies are included as well as 24 grey literature documents. Peer-reviewed research was largely observational and focused on prevalence studies, post-traumatic stress disorder or organisational and individual social factors related to health and well-being. Most grey literature reported the development and testing of interventions. Across all study types, underpinning theory was often not cited. Conclusion: To date, intervention research has largely been funded by charities and published in the grey literature. Few studies were identified on self-harm, bullying, sleep and fatigue or alcohol and substance use. Theoretically informed intervention development and testing, including adaptation of innovations from other countries and 24-hour workforces, is needed. This evidence map provides important context for planning of staff well-being provision and research as the sector responds to and recovers from the pandemic. PROSPERO registration number: CRD42018104659.

Over the past few decades, research has established that the cerebellum is involved in executive functions; however, its specific role remains unclear. There are numerous theories of cerebellar function and numerous cognitive processes falling under the umbrella of executive function, making investigations of the cerebellum's role in executive functioning challenging. In this review, we explored the role of the cerebellum in executive functioning through clinical and cognitive neuroscience frameworks. We reviewed the neuroanatomical systems and theoretical models of cerebellar functions and the multifaceted nature of executive functions. Using attention deficit hyperactivity disorder and cerebellar tumor as clinical developmental models of cerebellar dysfunction, and the functional magnetic resonance imaging literature, we reviewed evidence for cerebellar involvement in specific components of executive function in childhood, adolescence, and adulthood. There is evidence for posterior cerebellar contributions to working memory, planning, inhibition, and flexibility, but the heterogeneous literature that largely was not designed to study the cerebellum makes it difficult to determine specific functions of the cerebellum or cerebellar regions. In addition, while it is clear that cerebellar insult in childhood affects executive function performance later in life, more work is needed to elucidate the mechanisms by which executive dysfunction occurs and its developmental course. The limitations of the current literature are discussed and potential directions for future research are provided.

Purpose: Pharmacotherapy is one cornerstone of chronic obstructive pulmonary disease (COPD) management. Published U.S. data seldom includes patient-reported COPD medication use and adherence. We add this patient perspective to the commonly reported administrative prescribing and fill data. Methods: This survey study used inhaler and nebulizer pictures and lists of oral COPD medications to query members of the COPD Foundation Patient-Powered Research Network, a national, self-reported online registry. Medications used, adherence, inhaler education, cost concerns, previous exacerbations, and COPD Assessment Test scores were assessed and summarized using simple descriptive statistics and hazard ratios controlling for age, gender, and disease burden. Results: Respondents mean age was 68 years, 60% were women, >69% had COPD Assessment Test (CAT) scores >15, and >50% reported 2 or more exacerbations in the past 12 months. Overall, >98% used 1 or more inhaled COPD medications, 7.6% used a rescue inhaler only, 17.8% used long-acting bronchodilator only therapy (11.1% dual), and 72.8% used corticosteroid therapies, including 53% who were on triple therapy. Nebulizers were used by 59.4% and 34.8% used oral COPD medications. Reported adherence rates were high (80.1%), but 41% reported trouble paying for medications, with 20.1% reporting missing medications due to cost. Conclusions: In this population, COPD had a high burden with >50% of respondents using triple therapy, and 1 in 8 using maintenance oral corticosteroids. Self-reported adherence was high, but with significant cost concerns reported, resulting in missed medications.

CRISPR technology has demonstrated broad utility for controlling target gene expression; however, there remains a need for strategies capable of modulating expression via the precise editing of non-coding regulatory elements. Here we demonstrate that CRISPR base editors, a class of gene-modifying proteins capable of creating single-base substitutions in DNA, can be used to perturb gene expression via their targeted mutagenesis of cis-acting sequences. Using the promoter region of the human huntingtin (HTT) gene as an initial target, we show that editing of the binding site for the transcription factor NF-κB led to a marked reduction in HTT gene expression in base-edited cell populations. We found that these gene perturbations were persistent and specific, as a transcriptome-wide RNA analysis revealed minimal off-target effects resulting from the action of the base editor protein. We further demonstrate that this base-editing platform could influence gene expression in vivo as its delivery to a mouse model of Huntington’s disease led to a potent decrease in HTT mRNA in striatal neurons. Finally, to illustrate the applicability of this concept, we target the amyloid precursor protein, showing that multiplex editing of its promoter region significantly perturbed its expression. These findings demonstrate the potential for base editors to regulate target gene expression.

Clostridioides difficile remains a key cause of healthcare-associated infection, with multi-drug-resistant (MDR) lineages causing high mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship a key control. A mechanism underlying raised cephalosporin MICs has not been identified in C. difficile, but among other species resistance is often acquired via amino acid substitutions in cell wall transpeptidases (penicillin binding proteins, PBPs). Here, we investigated five C. difficile transpeptidases (PBP1-5) for recent substitutions. Previously published genome assemblies (n=7096) were obtained, representing sixteen geographically widespread lineages, including healthcare-associated MDR ST1(027), ST3(001) and ST17(018). Recent amino acid substitutions were found within PBP1 (n=50) and PBP3 (n=48), ranging from 1-10 substitutions per genome. β-lactam MICs were measured for closely related pairs of wild-type and PBP substituted isolates separated by 20-273 SNPs. Recombination-corrected, dated phylogenies were constructed to date substitution acquisition. Key substitutions such as PBP3 V497L and PBP1 T674I/N/V emerged independently across multiple lineages. They were associated with extremely high cephalosporin MICs; 1-4 doubling dilutions >wild-type up to ≤1506μg/ml. Substitution patterns varied by lineage and clade, showed geographic structure, and notably occurred post-1990, coincident with the acquisition of gyrA/B substitutions conferring fluoroquinolone resistance. In conclusion, recent PBP1 and PBP3 substitutions are associated with raised cephalosporin MICs in C. difficile. The co-occurrence of resistance to cephalosporins and fluoroquinolones hinders attempts to understand their relative importance in the dissemination of epidemic lineages. Further controlled studies of cephalosporin and fluoroquinolone stewardship are needed to determine their relative effectiveness in outbreak control.IMPORTANCEFluoroquinolone and cephalosporin prescribing in healthcare settings have triggered outbreaks of high-mortality, multi-drug resistant C. difficile infection. Here, we identify a mechanism of acquired cephalosporin resistance in C. difficile, comprising amino acid substitutions in two cell-wall transpeptidase enzymes (penicillin binding proteins). The higher the number of substitutions, the greater the impact on phenotype. Dated phylogenies revealed that resistance to both cephalosporins and fluoroquinolones was co-acquired immediately before clinically important, outbreak strains emerged. PBP substitutions were geographically structured within genetic lineages, suggesting adaptation to local antimicrobial prescribing. Antimicrobial stewardship of cephalosporins and fluoroquinolones is an effective means of C. difficile outbreak control. Genetic changes conferring resistance likely impart a ‘fitness-cost’ after antibiotic withdrawal. Our study identifies a mechanism that may explain the contribution of cephalosporin stewardship to resolving outbreak conditions. However, due to the co-occurrence of cephalosporin and fluoroquinolone resistance, further work is needed to determine the relative importance of each.

Dietary fiber has become increasingly recognized as a key factor in maintaining gastrointestinal health. Dietary fiber sources are often comprised of several different fiber fractions, each with unique physicochemical properties. These properties can have varying physiological effects on the gastrointestinal tract that include modulation of microbiota, production of fermentation-derived metabolites, and laxation. The objectives of this study were 1) to determine the effects of a novel dietary fiber source, miscanthus grass fiber (MF), and prebiotic and fiber blends on gastrointestinal tolerance, apparent total tract digestibility, fecal metabolites, and fecal microbiota and 2) to evaluate the palatability of extruded diets containing MF in comparison to traditional dietary fiber sources. All animal procedures were approved by the University of Illinois Institutional Animal Care and Use Committee. Six dietary treatments were formulated to meet or exceed the AAFCO nutrient profile of 2018 and included either cellulose (CO), beet pulp (BP), MF, or a blend of MF and tomato pomace, MF and resistant starch, or MF and fructooligosaccharide. A total of 12 adult neutered female beagles (mean age 5.8 ± 1.1 yr; mean body weight 10.9 ± 1.0 kg; mean body condition score 5.7 ± 0.7) were randomly assigned to one of the six treatment diets in a replicated 6 × 6 Latin square design. Each dog was fed their assigned diet for a treatment period of 21 d with 17 d of diet adaptation followed by 4 d of total and fresh fecal collection. All diets were well accepted and digested by the dogs. Dogs fed BP had greater fecal total short-chain fatty acid concentration than the CO treatment (P0.05), while the dogs fed diets containing MF were intermediate. In a two-bowl palatability trial, no significant preference was observed between the extruded diets containing MF and CO (P0.05). However, a significant preference for the extruded diet containing BP over the diet containing only MF was observed (P0.05). The α-diversity of fecal microbial communities was not impacted by treatment (P0.05), but β-diversity indicated that dogs fed the BP diet differed from the other treatment groups (P0.05). The data from this study suggest that miscanthus grass can be successfully utilized in fiber blends in extruded diets for adult dogs, with modulatory effects similar to the traditional dietary fiber source, cellulose.There are many ingredients utilized in dog foods that provide a source of dietary fiber. However, new ingredient sources can help to add variety to diet formulas and may provide benefits to pet food processing and animal health. Miscanthus grass is a novel ingredient for dog food that provides an excellent source of dietary fiber. In a dog feeding trial and palatability test, diets containing miscanthus grass had similar results to diets containing cellulose, a traditionally used dietary fiber ingredient. The inclusion of this novel ingredient did not produce any observed negative effects on digestion, stool quality, diet palatability, or overall animal health. This indicates that miscanthus grass is a viable ingredient for use in commercial dog foods as a source of dietary fiber.