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Fecal communities transplanted into individuals can eliminate recurrent Clostridioides difficile infection (CDI) with high efficacy. However, this treatment is only used once CDI becomes resistant to antibiotics or has recurred multiple times. We sought to investigate whether a fecal community transplant (FCT) pre-treatment could be used to prevent CDI altogether. We treated male C57BL/6 mice with either clindamycin, cefoperazone, or streptomycin, and then inoculated them with the microbial community from untreated mice before challenging with C. difficile. We measured colonization and sequenced the V4 region of the 16S rRNA gene to understand the dynamics of the murine fecal community in response to the FCT and C. difficile challenge. Clindamycin-treated mice became colonized with C. difficile but cleared it naturally and did not benefit from the FCT. Cefoperazone-treated mice became colonized by C. difficile, but the FCT enabled clearance of C. difficile. In streptomycin-treated mice, the FCT was able to prevent C. difficile from colonizing. Then we diluted the FCT and repeated the experiments. Cefoperazone-treated mice no longer cleared C. difficile. However, streptomycin-treated mice colonized with 1:102 dilutions resisted C. difficile colonization. Streptomycin-treated mice that received a FCT diluted 1:103, C. difficile colonized but later was cleared. In streptomycin-treated mice, inhibition of C. difficile was associated with increased relative abundance of a group of bacteria related to Porphyromonadaceae and Lachnospiraceae. These data demonstrate that C. difficile colonization resistance can be restored to a susceptible community with a FCT as long as it complements the missing populations.ImportanceAntibiotic use, ubiquitous with the healthcare environment, is a major risk factor for Clostridioides difficile infection (CDI), the most common nosocomial infection. When C. difficile becomes resistant to antibiotics, a fecal microbiota transplant from a healthy individual can effectively restore the gut bacterial community and eliminate the infection. While this relationship between the gut bacteria and CDI is well established, there are no therapies to treat a perturbed gut community to prevent CDI. This study explored the potential of restoring colonization resistance to antibiotic-induced susceptible gut communities. We described the effect gut bacteria community variation has on the effectiveness of a fecal community transplant for inhibiting CDI. These data demonstrated that communities susceptible to CDI can be supplemented with fecal communities but the effectiveness depended on the structure of the community following the perturbation. Thus, a simplified bacterial community may be able to recover colonization resistance to patients treated with antibiotics.

This phase 2 trial evaluated PET-adapted nivolumab alone or in combination with ifosfamide, carboplatin, and etoposide (NICE) as first salvage therapy and bridge to autologous hematopoietic cell transplantation (AHCT) in relapsed/refractory (RR) classical Hodgkin lymphoma (cHL). Patients with RR cHL received 240 mg nivolumab every 2 weeks for up to 6 cycles (C). Patients in complete response (CR) after C6 proceeded to AHCT, whereas patients with progressive disease at any point or not in CR after C6 received NICE for 2 cycles. The primary endpoint was CR rate per the 2014 Lugano classification at completion of protocol therapy. Forty-three patients were evaluable for toxicity; 42 were evaluable for response. Thirty-four patients received nivolumab alone, and 9 patients received nivolumab+NICE. No unexpected toxicities were observed after nivolumab or NICE. After nivolumab, the overall response rate (ORR) was 81%, and the CR rate was 71%. Among 9 patients who received NICE, all responded, with 8 (89%) achieving CR. At the end of protocol therapy, the ORR and CR rates were 93% and 91%. Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone. The 2-year progression-free survival (PFS) and overall survival in all treated patients (n = 43) were 72% and 95%, respectively. Among 33 patients who bridged directly to AHCT, the 2-year PFS was 94% (95% CI: 78-98). PET-adapted sequential salvage therapy with nivolumab/nivolumab+NICE was well tolerated and effective, resulting in a high CR rate and bridging most patients to AHCT without chemotherapy. This trial was registered at www.clinicaltrials.gov #NCT03016871.

Exploratory Science Center, Merck & Co , Inc , Cambridge, Massachusetts, United States of America Affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America ORCID logo http://orcid org/0000-0003-3140-537X Patrick D Schloss * E-mail: pschloss@umich edu Affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America ORCID logo http://orcid org/0000-0002-6935-4275 Introduction For most biologists, the ability to generate data has outpaced the ability to analyze those data In addition to building upon material from traditional coursework and staying current on the literature, Journal Clubs help strengthen skills in critical thinking, communication, and integrating the literature [11] Because most Journal Clubs occur on a regular schedule, they are effective by virtue of repeated practice With this model in mind, over the past four years we have experimented with creating a Code Club model with the goal of improving reproducible data analysis skills in a laboratory environment [ ]presenters were reluctant to offer to present again

Introduction: Nivolumab (nivo) is an anti-PD-1 antibody that restores effective anti-tumor immune responses and is tolerable and effective in patients (pts) with relapsed/refractory (RR) Hodgkin lymphoma (HL). Nivo combined with brentuximab vedotin (BV) as first salvage therapy (tx) yields high response rates and favorable progression-free survival (PFS) as a bridge to autologous stem cell transplantation (ASCT) in pts with RR HL. With the frontline approval of BV, it is necessary to evaluate the role of nivo as salvage tx separate from BV. We report interim results of a phase 2 trial evaluating PET-adapted nivo or nivo + ICE (NICE) chemotherapy as first salvage tx in RR HL. Methods: In this prospective, multicenter trial, pts with biopsy-proven RR HL after frontline tx received 3 mg/kg nivo every 2 weeks for up to 6 cycles (C). PET-CT was performed after C3 and C6. After C6, pts in CR proceeded to ASCT while pts not in CR received NICE for 2 cycles. The primary endpoint was complete response rate according to 2014 Lugano classification. PFS and overall survival (OS) were calculated using the Kaplan Meier method. Results: 39 pts were evaluable for toxicity; 37 were evaluable for response. Baseline characteristics are shown in Table 1. 32 pts received nivo alone and 7 pts received nivo/NICE. 32 pts completed study tx, 2 pts continue on protocol tx, 1 pt discontinued early in CR to undergo ASCT, 2 pts discontinued nivo early due to nivo-related adverse events (AE, 1 pt = Gr 4 altered mental status, 1 pt = Gr 2 pneumonitis), 1 pt discontinued due to unrelated death during nivo (Gr 5 sepsis due to untreated dental abscess), 1 pt withdrew due to refusal to receive NICE following nivo. After C3 of nivo, the overall response rate (ORR) was 89% (33/37), with a CR rate of 59% (22/37), partial response (PR) rate of 30% (11/37), and 2 pts each had stable disease (SD) and PD. After C6 of nivo (n=31), the ORR was 90%, with 24 CR (77%), 4 PR (13%), and 3 PD. Thus, including pts who stopped nivo early (due to toxicity or insufficient response and switch to NICE), at the end of nivo (n=37, not including 2 pts with ongoing tx) the ORR was 78%, with 26 CR (70%), 3 PR (8%), 1 pt with SD and 5 with PD. 7 pts were treated with NICE and all responded (100% ORR) with 6 CR (86%) and 1 PR (14%). At the end of protocol tx (nivo or nivo/NICE) including all pts (n=37) except the 2 who remain on ongoing tx, the ORR was 89% with 32 CR (86%) and 1 PR (3%). Among 35 evaluable pts, the ORR was 94% and CR rate was 91% (Figure). 27 pts proceeded to ASCT directly after protocol tx, 1 pt is awaiting ASCT, and 4 pts in CR refused ASCT. One pt with PR after NICE responded to subsequent salvage tx and underwent ASCT. In pts who had ASCT, a median of 2 (range 1-4) stem cell collections were required, a median of 4.7x106 CD34+ cells/kg (range 3.12 - 16.23) were collected, and the median time to neutrophil and platelet engraftment were 11 and 12 days, respectively. The median follow-up time in all pts (n=39) was 10.5 months (range 1.6-24.5 mo). The 1-year PFS was 79% (95 CI, 63-98%) and 1-year OS was 97% (95 CI, 92-100%). Two PD events occurred in pts who had CR but refused ASCT. There were 2 PD events in pts who completed therapy and proceeded to ASCT - both were in pts who required NICE. The most common AEs related to nivo alone (n=39) were fatigue (28%), rash (18%), fever (15%), thrombocytopenia (10%), and dyspnea (10%), and all were grade (gr) 1-2. Only 2 pts had gr 3-4 nivo-related AE, 1 pt had gr 3 thrombocytopenia and another pt had gr 4 altered mental status and gr 3 tumor lysis syndrome. Among 7 pts who received NICE, the most common AEs were nausea (71%), vomiting (57%), anemia (43%), fatigue (43%), hypertension (43%), and hyponatremia (29%) - all were gr 1-2. The only Gr 3-4 NICE-related AE was gr 4 neutropenia in 1 pt. Conclusion: PET-adapted nivo followed by NICE in patients without CR is a well-tolerated and effective first salvage approach in pts with RR HL. In our cohort, nivo alone was an effective bridge to ASCT in a majority of pts, sparing them the toxicity of traditional salvage chemotherapy. Pts who did not achieve CR with nivo were effectively salvaged by NIVO+ICE Disclosures Herrera: Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Chen:Autolus Therapeutics: Employment. Palmer:Gilead Sciences: Consultancy. Mei:Seattle Genetics, Inc.: Research Funding. Popplewell:City of Hope: Employment. Kwak:Pepromene Bio: Consultancy, Equity Ownership, Research Funding; InnoLifes: Consultancy, Equity Ownership; Xeme BioPharma, Inc: Consultancy, Equity Ownership; Enzychem LifeSciences: Consultancy; Celltrion, Inc.: Consultancy; Celltrion Healthcare: Consultancy. Lee:Seattle Genetics, Inc.: Research Funding.

Thalassospira sp. strain KO164 was isolated from eastern Mediterranean seawater and sediment laboratory microcosms enriched on insoluble organosolv lignin under oxic conditions. The near-complete genome sequence presented here will facilitate analyses into this deep-ocean bacterium's ability to degrade recalcitrant organics such as lignin.

AIMS: To test the null hypothesis that a novel disposable "tampon like" electrostimulation device (Pelviva�) is no better than unsupervised pelvic floor muscle exercise for treatment of urinary incontinence in women. METHODS: Pre/post-intervention assessor blinded, single center RCT. A total of 123 community dwelling self referred women with symptoms of stress, urge, or mixed incontinence were randomly assigned to one of two 12-week duration treatments: Pelviva� used for 30?min a day plus unsupervised pelvic floor muscle exercise or unsupervised exercises alone. Outcome measures included ICIQ-UI (primary), ICIQ FLUTSex and global impression of severity and improvement (secondary) completed at recruitment, after 4 weeks of unsupervised exercise and immediately post-treatment. Diary of exercise frequency/type, overall impression, and usage of device was completed mid- and post-treatment. RESULTS: Pelviva� plus exercise produced significantly better outcome than unsupervised exercise alone: 5 points (45%) versus 1 point (10%) for ICIQ-UI (P?=?0.014); 67% versus 33% for leak frequency (P?=?0.005); 40% versus 20% for leak interference with life (P?=?0.018). Incontinence was less bothersome during sex to a greater extent in the Pelviva� group (P?=?0.026). Women were enthusiastic about the device, found it comfortable/easy to use and experienced no adverse events. CONCLUSIONS: The Pelviva� device plus unsupervised exercise is more successful than unsupervised pelvic floor muscle exercise alone in treating urinary incontinence. The device is easy/comfortable to use, there are no apparent adverse incidents, and women can manage their incontinence in the privacy of their own home. The product will be launched 2013. Neurourol. Urodynam. � 2012 Wiley Periodicals, Inc.

The Nuclear Waste Policy Act of 1982 (NWPA), as amended, assigned the Department of Energy (DOE) responsibility for developing and managing a Federal system for the disposal of spent nuclear fuel (SNF) and high-level radioactive waste (HLW). The Office of Civilian Radioactive Waste Management (OCRWM) is responsible for accepting, transporting, and disposing of SNF and HLW at the Yucca Mountain repository in a manner that protects public health, safety, and the environment; enhances national and energy security; and merits public confidence. OCRWM faces a near-term challenge—to develop and demonstrate a transportation system that will sustain safe and efficient shipments of SNF and HLW to a repository. To better inform and improve its current planning, OCRWM has extensively reviewed plans and other documents related to past high-visibility shipping campaigns of SNF and other radioactive materials within the United States. This report summarizes the results of this review and, where appropriate, lessons learned.

The complete DNA sequence was determined of a pathogenic British isolate of equine herpesvirus-1, a respiratory virus which can cause abortion and neurological disease. The genome is 150,223 bp in size, has a base composition of 56.7% G + C, and contains 80 open reading frames likely to encode protein. Since four open reading frames are duplicated in the major inverted repeat, two are probably expressed as a spliced mRNA, and one may contain an internal transcriptional promoter, the genome is considered to contain 76 distinct genes. The genes are arranged collinearly with those in the genomes of the two previously sequenced alphaherpesviruses, varicella-zoster virus, and herpes simplex virus type-1, and comparisons of predicted amino acid sequences allowed the functions of many equine herpesvirus 1 proteins to be assigned.