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Abstract A role of gut microbiome in pathogenesis as well as response to treatment is documented in rheumatoid arthritis. Using a novel duodenal derived Prevotella histicola strain MCI 001, we have shown that it suppresses disease progression in a collagen-induced arthritis (CIA), a model for rheumatoid arthritis (RA) using humanized mice expressing HLA-DQ8 gene in the absence of endogenous class II genes. Here we compared efficacy of P. histicola MCI 001 with tumor necrosis factor inhibitor (TNFi) for treating arthritis. DQ8 arthritic mice treated with P. histicola by oral gavage or TNFi, were compared for disease onset, incidence and severity. We demonstrate that oral treatment with P. histicola mimics treatment with TNFi in arthritic DQ8 mice. A pangenome comparison of our P. histicola MCI 001 with its closest available neighbors depicted it as a novel strain with unique gene sequences that may contribute to immune modulatory effects. Notably, it possesses a unique sequence of an outer membrane protein, BtuB, which is involved in vitamin B12 transport. Our data indicate that P. histicola MC001 is an attractive candidate to prevent the progression of disease in RA patients with ongoing disease.

ABSTRACT Over 2.5 million prosthetic joint implantation surgeries occur annually in the United States. Periprosthetic joint infections (PJIs), though occurring in only 1–2% of patients receiving replacement joints, are challenging to diagnose and treat and are associated with significant morbidity. The Gram-positive bacterium Enterococcus faecalis, which can be highly antibiotic-resistant and is a robust biofilm producer on indwelling medical devices, accounts for 2–11% of PJIs. E. faecalis PJIs are understudied compared to those caused by other pathogens, such as Staphylococcus aureus. This motivates the need to generate a comprehensive understanding of E. faecalis PJIs to guide future treatments for these infections. To address this, we describe a panel of E. faecalis strains isolated from the surface of prosthetic joints in a cohort of individuals treated at the Mayo Clinic in Rochester, MN. Here, we present the first complete genome assemblage of E. faecalis PJI isolates. Comparative genomics shows differences in genome size, virulence factors, antimicrobial resistance genes, plasmids, and prophages, underscoring the genetic diversity of these strains. These isolates have strain-specific differences in in vitro biofilm biomass, biofilm burden, and biofilm morphology. We measured robust changes in biofilm architecture and aggregation for all isolates when grown in simulated synovial fluid (SSF). Finally, we evaluated the antibiotic efficacy of these isolates and found strain-specific changes across all strains when grown in SSF. Results of this study highlight the existence of genetic and phenotypic heterogeneity among E. faecalis PJI isolates which will provide valuable insight and resources for future E. faecalis PJI research.IMPORTANCEPeriprosthetic joint infections (PJIs) affect ~1–2% of those who undergo joint replacement surgery. Enterococcus faecalis is a Gram-positive opportunistic pathogen that causes ~10% of PJIs in the United States each year, but our understanding of how and why E. faecalis causes PJIs is limited. E. faecalis infections are typically biofilm-associated and can be difficult to clear with antibiotic therapy. Here, we provide complete genomes for four E. faecalis PJI isolates from the Mayo Clinic. These isolates have strain-specific differences in biofilm formation, aggregation, and antibiotic susceptibility in simulated synovial fluid. These results provide important insight into the genomic and phenotypic features of E. faecalis isolates from PJI.

Staphylococcus epidermidis is part of the commensal microbiota of the skin and mucous membranes, though it can also act as a pathogen in certain scenarios, causing a range of infections, including periprosthetic joint infection (PJI). Transcriptomic profiling may provide insights into mechanisms by which S. epidermidis adapts while in a pathogenic compared to a commensal state. Here, a total RNA-sequencing approach was used to profile and compare the transcriptomes of 19 paired PJI-associated S. epidermidis samples from an in vivo clinical source and grown in in vitro laboratory culture. Genomic comparison of PJI-associated and publicly available commensal-state isolates were also compared. Of the 1919 total transcripts found, 145 were from differentially expressed genes (DEGs) when comparing in vivo or in vitro samples. Forty-two transcripts were upregulated and 103 downregulated in in vivo samples. Of note, metal sequestration-associated genes, specifically those related to staphylopine activity (cntA, cntK, cntL, and cntM), were upregulated in a subset of clinical in vivo compared to laboratory grown in vitro samples. About 70% of the total transcripts and almost 50% of the DEGs identified have not yet been annotated. There were no significant genomic differences between known commensal and PJI-associated S. epidermidis isolates, suggesting that differential genomics may not play a role in S. epidermidis pathogenicity. In conclusion, this study provides insights into phenotypic alterations employed by S epidermidis to adapt to infective and non-infected microenvironments, potentially informing future therapeutic targets for related infections.

Frankincense (Boswellia spp.) resin is an internationally renowned non-timber forest product (NTFP), generating more than $1 billion USD annually for its use in aromatherapy, incenses, perfumery, cosmetics, and medicines. However, many Boswellia species that produce commercially traded frankincense resins grow in arid, resource-poor environments where human conflict and warfare are common, such as the Sahel and the Horn of Africa. Despite this, the impacts of violent conflict on frankincense or other NTFP production systems have been underexplored in the literature. Drawing on anecdotal reports in frankincense and case studies from other species and geographies, we discuss the likely impacts of both acute warfare, such as the recent Tigray war in Ethiopia, and chronic, low-level conflict, such as the ongoing insurgencies by ISIS and Al-Qaeda-linked groups in Somalia and the Sahel. The effects of conflict are wide-ranging and may include direct damage to forests, disruptions of land tenure, management, and governance systems, reduced monitoring capabilities, and limited capacity for sustainable supply chain operations. We explore these potential impacts, outline an agenda for further research, and urge that further attention be given to conflict as an important driver of forest management and conservation outcomes.

Abstract The origin of fecal floatation phenomenon remains poorly understood. Following our serendipitous discovery of differences in buoyancy of feces from germ-free and conventional mice, we characterized microbial and physical properties of feces from germ-free and gut-colonized (conventional and conventionalized) mice. The gut-colonization associated differences were assessed in feces using DNA, bacterial-PCR, scanning electron microscopy, FACS, thermogravimetry and pycnometry. Based on the differences in buoyancy of feces, we developed levô in fimo test (LIFT) to distinguish sinking feces (sinkers) of germ-free mice from floating feces (floaters) of gut-colonized mice. By simultaneous tracking of microbiota densities and gut colonization kinetics in fecal transplanted mice, we provide first direct evidence of causal relationship between gut microbial colonization and fecal floatation. Rare discordance in LIFT and microbiota density indicated that enrichment of gasogenic gut colonizers may be necessary for fecal floatation. Finally, fecal metagenomics analysis of ‘floaters’ from conventional and syngeneic fecal transplanted mice identified colonization of > 10 gasogenic bacterial species including highly prevalent B. ovatus, an anaerobic commensal bacteria linked with flatulence and intestinal bowel diseases. The findings reported here will improve our understanding of food microbial biotransformation and gut microbial regulators of fecal floatation in human health and disease.

Abstract Determining the relative energies of transport states in organic semiconductors is critical to understanding the properties of electronic devices and in designing device stacks. Futhermore, defect states are also highly important and can greatly impact material properties and device performance. Recently, energy‐resolved electrochemical impedance spectroscopy (ER‐EIS) is developed to probe both the ionization energy (IE) and electron affinity (EA) as well as sub‐bandgap defect states in organic semiconductors. Herein, ER‐EIS is compared to cyclic voltammetry (CV) and photoemission spectroscopies for extracting IE and EA values, and to photothermal deflection spectroscopy (PDS) for probing defect states in both polymer and molecular organic semiconductors. The results show that ER‐EIS determined IE and EA are in better agreement with photoemission spectroscopy measurements as compared to CV for both polymer and molecular materials. Furthermore, the defect states detected by ER‐EIS agree with sub‐bandgap features detected by PDS. Surprisingly, ER‐EIS measurements of regiorandom and regioregular poly(3‐hexylthiophene) (P3HT) show clear defect bands that occur at significantly different energies. In regioregular P3HT the defect band is near the edge of the occupied states while it is near the edge of the unoccupied states in regiorandom P3HT.

The demand for information capacity in data center networks has grown exponentially during past decades. Such growth promotes consideration for adoption of coherent transmission technologies in this application space to achieve current and future high data rate requirements at 400G, 800G, and higher. Coherent systems offer higher capacity than direct detection systems using more degrees of freedom to carry information, but with higher system complexity. To meet the cost and power consumption requirements for data center transceivers, coherent-lite technologies have been proposed. Among them, self-homodyne coherent (SHC) is a promising candidate which allows the use of low cost lasers and simplifies digital signal processing (DSP). We study SHC systems and focus on the use of a multicore fiber (MCF) to obtain small channel skew, which allows for further simplification of DSP. We observe and manage stimulated Brillouin scattering (SBS) effects in the local oscillator path. We analyze the optimal power split ratio between the data path and the local oscillator path to maximize data capacity. Moreover, we compare the channel skew and transmission performance between multicore fiber and ribbon fiber. SHC with MCF delivers high data capacity with significant complexity reduction, which may be a promising solution for data center links.

Background: Stromal and immune cell composition alterations in benign breast tissue associate with future cancer risk. Pilot data suggest the innate microbiome of normal breast tissue differs between women with and without breast cancer. Microbiome alterations might explain tissue microenvironment variations associated with disease status. Methods: Prospectively-collected sterile normal breast tissues from women with benign (n=16) or malignant (n=17) disease underwent 16SrRNA sequencing with Illumina MiSeq and Hybrid-denovo pipeline processing. Breast tissue was scored for fibrosis and fat percentages and immune cell infiltrates (lobulitis) classified as absent/mild/moderate/severe. Alpha and beta diversity were calculated on rarefied OTU data and associations analyzed with multiple linear regression and PERMANOVA. Results: Breast tissue stromal fat% was lower and fibrosis% higher in benign disease versus cancer (median 30% versus 60%, p=0.01, 70% versus 30%, p=0.002, respectively). The microbiome varied with stromal composition. Alpha diversity (Chao1) correlated with fat% (r=0.38, p=0.02) and fibrosis% (r=-0.32, p=0.05) and associated with different microbial populations as indicated by beta diversity metrics (weighted UniFrac, p=0.08, fat%, p=0.07, fibrosis%). Permutation testing with FDR control revealed taxa differences for fat% in Firmicutes, Bacilli, Bacillales, Staphylococcaceae and genus Staphylococcus, and fibrosis% in Firmicutes, Spirochaetes, Bacilli, Bacillales, Spirochaetales, Proteobacteria RF32, Sphingomonadales, Staphylococcaceae, and genera Clostridium, Staphylococcus, Spirochaetes, Actinobacteria Adlercreutzia. Moderate/severe lobulitis was more common in cancer (73%) than benign disease (13%), p=0.003, but no significant microbial associations were seen. Conclusion: These data suggest a link between breast tissue stromal alterations and its microbiome, further supporting a connection between the breast tissue microenvironment and breast cancer.

Frankincense is an oleo-gum-resin collected from wild Boswellia spp. trees, and widely used in perfumery, cosmetics, aromatherapy, incense, and other industries. Boswellia rivae, growing in Ethiopia, Somalia, and Kenya, is one source of frankincense, but is little-commercialized compared to species such as B. sacra, B. frereana, and B. papyrifera. In this study, we examine the resin essential oil chemistry and harvesting systems of B. rivae in order to evaluate its potential for increased trade and potential positive livelihood benefits. Boswellia rivae produces an essential oil rich in α-thujene (0.1–12.4%), α-pinene (5.5–56.4%), β-pinene (0.3–13.0%), δ-3-carene (0.1–31.5%), p-cymene (1.4–31.2%), limonene (1.8–37.3%), β-phellandrene (tr-5.6%), trans-pinocarveol (0.1–5.0%), trans-verbenol (0.1–11.2%), and trans-β-elemene (0–5.7%), similar to major commercial species, although it is difficult to detect mixing of B. rivae and Commiphora africana resins from chemistry alone. The B. rivae trees are not actively tapped, so resin collection has a neutral impact on the health of the trees, and resin production is unaffected by drought. Consequently, collecting resins acts as a key income supplementing livestock herding, as well as a safety net protecting pastoral communities from the severe negative effects of climate change-exacerbated drought on livestock. Therefore, Boswellia rivae is well positioned chemically, ecologically, and socially to support expanded trade.

Abstract Although Streptococcus agalactiae periprosthetic joint infection (PJI) is not as prevalent as staphylococcal PJI, invasive S. agalactiae infection is not uncommon. Here, RNA‐seq was used to perform transcriptomic analysis of S. agalactiae PJI using fluid derived from sonication of explanted arthroplasties of subjects with S. agalactiae PJI, with results compared to those of S. agalactiae strain NEM316 grown in vitro. A total of 227 genes with outlier expression were found (164 upregulated and 63 downregulated) between PJI sonicate fluid and in vitro conditions. Functional enrichment analysis showed genes involved in mobilome and inorganic ion transport and metabolism to be most enriched. Genes involved in nickel, copper, and zinc transport, were upregulated. Among known virulence factors, cyl operon genes, encoding β‐hemolysin/cytolysin, were consistently highly expressed in PJI versus in vitro. The data presented provide insight into S. agalactiae PJI pathogenesis and may be a resource for identification of novel PJI therapeutics or vaccines against invasive S. agalactiae infections.

Boswellia ogadensis is a critically endangered species of frankincense tree, restricted to a small area of the Shabelle river valley in southern Ethiopia. It has only been recorded from two botanical collecting trips, in 1972 and 2006, with no indication of the abundance, threats, or population status of the trees, and it was listed on the IUCN Red List of Endangered Species as “Critically Endangered” in 2018. More recent expeditions, in 2019 and 2021, were not able to locate the species, raising concerns about its continued survival. We carried out a field survey in June 2022 to re-locate the species, assess the threat level it is facing, and collect samples of resin for analysis. This survey revealed that B. ogadensis is present in more locations than previously recorded, and is more abundant than thought. While it is facing multiple threats, including grazing, cutting for firewood, and insect attacks, these threats vary geographically, and there are populations that appear to be healthy and regenerating well. While more research is needed, the current survey indicates that downlisting to “Endangered” status may be appropriate. Samples of resin were also collected and analyzed using gas chromatographic techniques, revealing that while the essential oil profile is similar to that of other Boswellia species (dominated by α-thujene, α-pinene, p-cymene, and terpenin-4-ol), there are chemical markers that can distinguish it from other sympatric Boswellia species, indicating the potential for this to be used as a tool to monitor whether B. ogadensis is being harvested alongside other more common Boswellia species.

Giving birth too soon accounts for half of all newborn deaths worldwide. Clinical symptoms alone are not sufficient to identify women at risk of giving birth too early, as such a pragmatic approach to reducing the incidence of preterm birth entails developing early strategies for intervention before it materializes.

Abstract Background Antibiotic resistance (ABR) is a serious threat that requires coordinated global intervention to prevent its spread. There is limited data from the English-speaking Caribbean. Methods As part of a national programme to address antibiotic resistance in Jamaica, a survey of the knowledge, attitudes and antibiotic prescribing practices of Jamaican physicians was conducted using a 32-item self-administered questionnaire. Results Of the eight hundred physicians targeted, 87% responded. The majority thought the problem of resistance very important globally (82%), less nationally (73%) and even less (53%) in personal practices. Hospital physicians were more likely to consider antibiotic resistance important in their practice compared to those in outpatient practice or both (p 80%, average if 60–79% and poor if four years post graduation (p = 0.03). Empiric therapy was often directed by international guidelines and cultures were not routinely done. Limited laboratory and human resources were identified as challenges. Conclusion Physicians in this study were aware of the problem of ABR, but downplayed its significance nationally and personally. These results will guide a national antibiotic stewardship programme.

Since 2017, CARICOM member states have been divided in the positions they take on Organization of American States (OAS) resolutions addressing political instability in Venezuela. This article uses a neorealism framework to determine whether or not the provision of energy investments by Venezuela and the United States to CARICOM member countries is an attempt on their part to skew the OAS voting mechanism in their national interests. The article also examines the extent to which CARICOM member states’ response to Venezuela’s and United States’ interest in the OAS demonstrates a pattern of rationality. The findings suggest that though the OAS provides a medium for states to negotiate mutually beneficial solutions, states are rational actors and even where they do corporate, dominant states may try to manifest their self-interest.

Abstract Abnormalities in the gut microbiome are associated with suppressed Th2 response (Belizario et al., 2018 Mediators Inflamm. 2018:2037838) and predisposition to atopic disease such as asthma and eczema. We investigated if this applies to eosinophilic esophagitis (EoE). Stool bacterial DNA was extracted and followed by 16S rRNA amplification from 12 patients with eosinophilic esophagitis and 12 controls. Alpha‐ and beta‐diversity were analyzed. Only two patients had asthma or atopy and one patient was on budesonide. No patients were on PPIs. Patients with EoE had lower gut microbiota alpha diversity (species richness, P = 0.09; Shannon index, P = 0.01). The microbial composition was distinct as evidenced by significantly different beta diversity (P = 0.03) when compared to healthy controls. There were also significant differences in relative abundance at multiple taxonomic levels when comparing the two communities; at the phylum level, we observed a marked decrease in Firmicutes and increase in Bacteroidetes and at the order and family level there were significant decreases in Clostridia and Clostridiales in patients with EoE (q ≤ 0.1). We conclude that there are significant differences in microbial community structure, microbial richness, and evenness and a significant decrease in taxa within the Clostridia in patients with EoE. Our data suggest that Clostridia based interventions could be tested as adjuncts to current therapeutic strategies in EoE.

Introduction: The objective of this study was to review and critically appraise the medical education literature pertaining to a flipped-classroom (FC) education model, and to highlight influential papers that inform our current understanding of the role of the FC in medical education. Methods: A search of the English-language literature querying Education Resources Information Center (ERIC), PsychINFO, PubMed, and Scopus identified 296 papers related to the FC using either quantitative, qualitative, or review methods. Two reviewers independently screened each category of publications using previously established exclusion criteria. Eight reviewers then independently scored the remaining 54 publications using either a qualitative, quantitative, or review-paper scoring system. Each scoring system consisted of nine criteria and used parallel metrics that have been previously used in critical appraisals of education research. Results: A total of 54 papers (33 quantitative, four qualitative, and 17 review) on FC met a priori criteria for inclusion and were critically appraised and reviewed. The top 10 highest scoring articles (five quantitative studies, two qualitative studies, and three review papers) are summarized in this article. Conclusion: This installment of the Council of Emergency Medicine Residency Directors (CORD) Academy Critical Appraisal series highlights 10 papers that describe the current state of literature on the flipped classroom, including an analysis of the benefits and drawbacks of an FC approach, practical implications for emergency medicine educators, and next steps for future research.

Recent human microbiome studies have revealed an essential role of the human microbiome in health and disease, opening up the possibility of building microbiome-based predictive models for individualized medicine. One unique characteristic of microbiome data is the existence of a phylogenetic tree that relates all the microbial species. It has frequently been observed that a cluster or clusters of bacteria at varying phylogenetic depths are associated with some clinical or biological outcome due to shared biological function (clustered signal). Moreover, in many cases, we observe a community-level change, where a large number of functionally interdependent species are associated with the outcome (dense signal). We thus develop “glmmTree,” a prediction method based on a generalized linear mixed model framework, for capturing clustered and dense microbiome signals. glmmTree uses the similarity between microbiomes, which is defined based on the microbiome composition and the phylogenetic tree, to predict the outcome. The effects of other predictive variables (e.g., age, sex) can be incorporated readily in the regression framework. Additional tuning parameters enable a data-adaptive approach to capture signals at different phylogenetic depth and abundance level. Simulation studies and real data applications demonstrated that “glmmTree” outperformed existing methods in the dense and clustered signal scenarios.

ABSTRACT Variability in representation of microbial communities can be caused by differences in microbial composition or artifacts introduced at sample collection or processing. Alterations in community representation introduced by variations in starting DNA concentrations have not been systematically investigated in stool samples. The goal of this study was to evaluate the effect of the genomic DNA (gDNA) concentration in the resulting 16S rRNA gene library composition and compare its effect to other sample processing variables in homogenized human fecal material. Compared to a gDNA input of 1 ng/μl, inputs of ≤1.6 × 10−3 ng/μl resulted in a marked decrease in the concentration of the 16S rRNA gene amplicon (P < 0.001). Low gDNA concentrations (≤1.6 × 10−3 ng/μl) were also associated with a decrease (P < 0.001) in the number of operational taxonomic units and significant divergence in β-diversity profiles (unweighted UniFrac distance, P < 0.001), as characterized by an overestimation of Proteobacteria and underestimation of Firmicutes. Even a gDNA concentration of 4 × 10−2 ng/μl showed a significant impact on the β-diversity profile (unweighted UniFrac distance, P = 0.03). Overall, the gDNA concentration explained 22.4% to 38.1% of the microbiota variation based on various β-diversity measures (P < 0.001). By comparison, the DNA extraction methods and PCR volumes tested did not significantly affect the microbial composition profile, and the PCR cycling method explained less than 3.7% of the microbiota variation (weighted UniFrac distance, P = 0.03). The 16S rRNA gene yield and the microbial community representation of human homogenized stool samples are significantly altered by gDNA template concentrations of ≤1.6 × 10−3 ng/μl. In addition, data from studies with a gDNA input of ≤4 × 10−2 ng/μl should be interpreted with caution. IMPORTANCE The genomic DNA input for stool samples utilized for microbiome composition has not been determined. In this study, we determined the reliable threshold level under which conclusions drawn from the data may be compromised. We also determined the type of microbial bias introduced by less-than-ideal genomic input.

Frankincense, the oleogum resin from members of Boswellia, has been used as medicine and incense for thousands of years, and essential oils derived from frankincense are important articles of commerce today. A new source of frankincense resin, Boswellia dalzielii from West Africa has been presented as a new, alternative source of frankincense. In this work, the oleogum resins from 20 different Boswellia dalzielii trees growing in Burkina Faso, West Africa were collected. Hydrodistillation of the resins gave essential oils that were analyzed by GC-MS and GC-FID. The essential oils were dominated by α-pinene (21.0%−56.0%), followed by carvone (2.1%−5.4%) and α-copaene (1.8%−5.0%). Interestingly, there was one individual tree that, although rich in α-pinene (21.0%), also had a substantial concentration of myrcene (19.2%) and α-thujene (9.8%). In conclusion, the oleogum resin essential oil compositions of B. dalzielii, rich in α-pinene, are comparable in composition to other frankincense essential oils, including B. sacra, B. carteri, and B. frereana. Additionally, the differences in composition between samples from Burkina Faso and those from Nigeria are very slight. There is, however, a rare chemotype of B. dalzielii that is dominated by myrcene, found both in Burkina Faso as well as Nigeria.

Frankincense, the oleo-gum-resin of Boswellia trees, has been an important religious and medicinal element for thousands of years, and today is used extensively for essential oils. One of the most popular frankincense species is Boswellia sacra Flueck. (syn. Boswellia carteri Birdw.) from Somalia and Somaliland. Recent increases in demand have led to many areas being overharvested, emphasizing the need for incentives and monitoring for sustainable harvesting, such as certification schemes. Concurrently, a new chemical component, called methoxydecane, has emerged in oils claimed to be B. carteri, suggesting the possibility of a chemical marker of overharvesting or other stress that could aid in monitoring. To find the source of this new chemical component, we sampled resin directly from trees in areas producing the new methoxydecane chemotype. This revealed that methoxydecane comes not from Boswellia carteri, but from a newly described frankincense species, Boswellia occulta. The presence of Boswellia occulta oil in essential oil sold as pure B. carteri, including certified organic oil, emphasizes the current lack of traceability in the supply chain and the ineffectiveness of organic certification to secure purity and sustainable harvesting in wildcrafted species.

The inflammatory tumoral-immune response alters the physiology of the tumor microenvironment, which may attenuate genomic instability. In addition to inducing inflammatory immune responses, several pathogenic bacteria produce genotoxins. However the extent of microbial contribution to the tumor microenvironment biology remains unknown. We utilized The Cancer Genome Atlas, (TCGA) breast cancer data to perform a novel experiment utilizing unmapped and mapped RNA sequencing read evidence to minimize laboratory costs and effort. Our objective was to characterize the microbiota and associate the microbiota with the tumor expression profiles, for 668 breast tumor tissues and 72 non-cancerous adjacent tissues. The prominent presence of Proteobacteria was increased in the tumor tissues and conversely Actinobacteria abundance increase in non-cancerous adjacent tissues. Further, geneset enrichment suggests Listeria spp to be associated with the expression profiles of genes involved with epithelial to mesenchymal transitions. Moreover, evidence suggests H. influenza may reside in the surrounding stromal material and was significantly associated with the proliferative pathways: G2M checkpoint, E2F transcription factors, and mitotic spindle assembly. In summary, further unraveling this complicated interplay should enable us to better diagnose and treat breast cancer patients.

The original article [1] contains a major error whereby the present title does not display the correct wording as intended by the authors.

Mantle cell lymphoma is an incurable and generally aggressive lymphoma that is more common in elderly patients. Whilst a number of different chemotherapeutic regimens are active in this disease, there is no established gold standard therapy. Rituximab has been used widely to good effect in B-cell malignancies but there is no evidence that it improves outcomes when added to chemotherapy in this disease. We performed a randomized, open-label, multicenter study looking at the addition of rituximab to the standard chemotherapy regimen of fludarabine and cyclophosphamide in patients with newly diagnosed mantle cell lymphoma. A total of 370 patients were randomized. With a median follow up of six years, rituximab improved the median progression-free survival from 14.9 to 29.8 months (P

Abstract Background The hip is one of the most common sites of osteoarthritis in the body, second only to the knee in prevalence. However, current animal models of hip osteoarthritis have not been assessed using many of the functional outcome measures used in orthopaedics, a characteristic that could increase their utility in the evaluation of therapeutic interventions. The canine hip shares similarities with the human hip, and functional outcome measures are well documented in veterinary medicine, providing a baseline for pre‐clinical evaluation of therapeutic strategies for the treatment of hip osteoarthritis. The purpose of this study was to evaluate a surgical model of hip osteoarthritis in a large laboratory animal model and to evaluate functional and end‐point outcome measures. Methods Seven dogs were subjected to partial surgical debridement of cartilage from one femoral head. Pre‐ and postoperative pain and functional scores, gait analysis, radiographs, accelerometry, goniometry and limb circumference were evaluated through a 20‐week recovery period, followed by histological evaluation of cartilage and synovium. Results Animals developed histological and radiographic evidence of osteoarthritis, which was correlated with measurable functional impairment. For example, Mankin scores in operated limbs were positively correlated to radiographic scores but negatively correlated to range of motion, limb circumference and 20‐week peak vertical force. Conclusions This study demonstrates that multiple relevant functional outcome measures can be used successfully in a large laboratory animal model of hip osteoarthritis. These measures could be used to evaluate relative efficacy of therapeutic interventions relevant to human clinical care.

Organic agricultural production has become a major economic and cultural force. However, in water-limited environments the tools used for weed control and nutrient supply, namely tillage and cover crops, may not be environmentally or economically sustainable as tillage damages soil and cover crops use valuable water. Thus, a major challenge has been finding appropriate ways to minimize tillage and terminate cover crops while still controlling weeds and obtaining cover crop ecosystem services. One approach to achieve this is through the economically viable integration of crop and livestock enterprises to manage weeds and terminate cover crops. In this article we (1) review research needs and knowledge gaps in organic agriculture with special focus on water-limited environments; (2) summarize research aimed at developing no-till and reduced tillage in organic settings; (3) assess approaches to integrate crop and livestock production in organic systems; and (4) present initial results from a project assessing the agronomic and weed management challenges of integrated crop-livestock organic systems aimed at reducing tillage intensity in a water-limited environment. The goal of eliminating tillage in water-limited environments remains elusive, and more research is needed to successfully integrate tactics, such as cover crops and livestock grazing to increase organic farm sustainability.