Transverse beam instabilities are a major cause of emittance dilution and beam losses in high intensity hadron accelerators. This paper presents an overview of the system that has been developed for ...automatic detection of transverse beam instabilities in the Large Hadron Collider at CERN. It relies on the detection of very small transverse beam oscillations using a high sensitivity tune measurement system. These oscillations are then processed online in a field programmable gate array to monitor the growth of any instabilities. When an instability is detected, the acquisition of intrabunch beam position data with a multi-gigahertz bandwidth is triggered. This data allows identification of unstable bunches within bunch trains and provides information on the temporal signature of the instability. The design of these systems and the different algorithms for instability detection that have been tested with beam will be presented along with a detailed description of their performance.
Crab cavities (CCs) constitute a key component of the High Luminosity LHC (HL-LHC) project. In case of a failure, they can induce significant transverse beam offsets within tens of microseconds, ...necessitating a fast removal of the circulating beam to avoid damage to accelerator components due to losses from the displaced beam halo. In preparation for the final design to be employed in the LHC, a series of tests were conducted on prototype crab cavities installed in the Super Proton Synchrotron (SPS) at CERN. This paper summarizes the machine protection requirements and observations during the first tests of crab cavities with proton beams in the SPS. In addition, the machine protection implications for future SPS tests and for the use of such equipment in the HL-LHC are discussed.
OBJECTIVE: To estimate the effect of the embryo stage, trophectoderm (TE) morphology grade, and inner cell mass (ICM) morphology grade on live birth in single-blastocyst transfers. DESIGN: ...Retrospective cohort study. SETTING: Large private assisted reproductive technologies (ART) practice. PATIENT(S): Fresh autologous ART cycles. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): A total of 694 single-blastocyst transfers met the inclusion criteria. Univariate regression analysis showed embryo stage and TE score to be correlated with implantation and live birth. Live birth rates were 57%, 40%, and 25% for TE grades A, B, and C, respectively. There was no significant association between ICM grade and implantation or live birth. Live birth rates were 53%, 52%, and 0% for ICM grades A, B, and C respectively. Multiple logistic regression analysis showed that only patient age and TE grade were significantly associated with implantation and live birth, whereas ICM grade was not significantly associated with outcome. The TE score had the strongest correlation with live birth. CONCLUSION(S): TE grading, but not ICM grading, significantly correlated with implantation and live birth for single-blastocyst transfers.
OBJECTIVE: To evaluate the effect of recombinant LH in assisted reproduction technology (ART) cycles in patients of advanced reproductive age. DESIGN: A systematic review and meta-analysis. SETTING: ...Published randomized controlled clinical trials comparing recombinant LH plus recombinant FSH versus recombinant FSH only in patients of advanced reproductive age. PATIENT(S): Patients 35 years and older undergoing assisted reproduction. INTERVENTION(S): Recombinant LH plus recombinant FSH controlled ovarian hyperstimulation (COH) versus recombinant FSH stimulation only in assisted reproduction cycles. MAIN OUTCOME MEASURE(S): Implantation and clinical pregnancy. RESULT(S): Seven trials were identified that met inclusion criteria and comprised 902 assisted reproduction technology cycles. No differences in serum E₂ on the day of hCG administration were reported in any trials. Two trials reported lower oocyte yield and one trial reported lower metaphase II oocyte yield in the recombinant LH-supplemented group. One trial reported higher fertilization rates in the recombinant LH-supplemented group. In a fixed effect model, implantation was higher in the recombinant LH-supplemented group (odds ratio 1.36, 95% confidence interval 1.05–1.78). Similarly, clinical pregnancy was increased in the recombinant LH-supplemented group (odds ratio 1.37, 95% confidence interval 1.03–1.83). CONCLUSION(S): The addition of recombinant LH to ART cycles may improve implantation and clinical pregnancy in patients of advanced reproductive age.
Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures ...in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.
An individual investor calls his broker and requests $100,000 of a certain stock for his portfolio. The broker sees that shares of that stock are currently being offered at $10 a share, and that ...there are 4,000 shares available on the New York Stock Exchange (NYSE), 3,000 on NASDAQ, and 3,000 on the BATS Global Exchange, for a total of 10,000 shares. Satisfied with his ability to fulfill his client's request, the broker hits "submit"- only to find that these offerings have disappeared and that the cheapest offering price of the stock is now above $10 a share, resulting in a purchase of fewer than the expected 10,000 shares for his client.
Physical activity offers substantial mind-body health benefits and reduced mortality, yet many individuals are chronically underactive. Physical activity interventions may benefit from integrative ...approaches that join components of mindfulness and neurobiological models of behavior. Mindfulness increases one's awareness of cognitions and physical sensations to potentially facilitate self-regulation, while neurobiological models such as the dual system model of health behavior offer guidance on improving physical activity intervention targets. This 2-phase study includes an initial development process to create brief (∼4 min) mindfulness informed guided imagery audio files that target distinct cognitive and affective processes to promote physical activity. In the second phase, participants completed a 2-week pilot intervention study to gather qualitative and quantitative data on intervention feasibility and acceptability. Participants endorsed the mindfulness informed guided imagery as easy to use, enjoyable and helpful. Over a 2-week intervention period participants reported positive shifts in behavior change, physical activity enjoyment, increased mindfulness during physical activity, and increased physical exercise self-efficacy and satisfaction. Interview data revealed that participants increased their frequency of physical activity and tended to experience positive affect during physical activity, engaged in future oriented thinking and were able to view physical activity in a more positive light. Findings support the feasibility and acceptability of an integrative online mindfulness informed guided imagery intervention to promote physical activity enjoyment and engagement. This study extends health behavior change intervention research and provides supporting evidence for a flexible and tailorable online mindfulness-based intervention.
Infliximab is a humanized antibody against tumor necrosis factor alpha (TNF-alpha) that is used in the treatment of Crohn's disease and rheumatoid arthritis. Approximately 147,000 patients throughout ...the world have received infliximab. Excess TNF-alpha in association with tuberculosis may cause weight loss and night sweats, yet in animal models it has a protective role in the host response to tuberculosis. There is no direct evidence of a protective role of TNF-alpha in patients with tuberculosis.
We analyzed all reports of tuberculosis after infliximab therapy that had been received as of May 29, 2001, through the MedWatch spontaneous reporting system of the Food and Drug Administration.
There were 70 reported cases of tuberculosis after treatment with infliximab, for a median of 12 weeks. In 48 patients, tuberculosis developed after three or fewer infusions. Forty of the patients had extrapulmonary disease (17 had disseminated disease, 11 lymph node disease, 4 peritoneal disease, 2 pleural disease, and 1 each meningeal, enteric, paravertebral, bone, genital, and bladder disease). The diagnosis was confirmed by a biopsy in 33 patients. Of the 70 reports, 64 were from countries with a low incidence of tuberculosis. The reported frequency of tuberculosis in association with infliximab therapy was much higher than the reported frequency of other opportunistic infections associated with this drug. In addition, the rate of reported cases of tuberculosis among patients treated with infliximab was higher than the available background rates.
Active tuberculosis may develop soon after the initiation of treatment with infliximab. Before prescribing the drug, physicians should screen patients for latent tuberculosis infection or disease.
Single-dose mass drug administration of azithromycin (AZT) is underway to eliminate trachoma worldwide. Studies in Ethiopia showed a reduction in all-cause childhood deaths after administration. To ...examine the effect of single-dose AZ MDA on prevalent malaria infections in a large prospective cohort of children and parents in Dodoma Province, Tanzania, we quantified the temporal prevalence of malaria parasitemia by real-time PCR for 6 months after single-dose AZT. In the first month after treatment but not in subsequent months, Plasmodium falciparum infections were reduced by 73% (95% CI 43%-89%) in treatment versus control villages and differences remained significant (p = 0.00497) in multivariate models with village-level random effects. Genetic sequencing of P. falciparum ribosomal L4 protein showed no mutations associated with AZT resistance. AZT mass drug administration caused a transient, 1-month antimalarial effect without selecting for P. falciparum ribosomal L4 resistance mutations in a region with a 10-year history of treating trachoma with this drug.
Intestinal epithelial cell (IEC) mitochondrial dysfunction involvement in inflammatory bowel diseases (IBD), including Crohn's disease affecting the small intestine, is emerging in recent studies. As ...the interface between the self and the gut microbiota, IECs serve as hubs of bidirectional cross-talk between host and luminal microbiota. However, the role of mitochondrial-microbiota interaction in the ileum is largely unexplored. Prohibitin 1 (PHB1), a chaperone protein of the inner mitochondrial membrane required for optimal electron transport chain function, is decreased during IBD. We previously demonstrated that mice deficient in PHB1 specifically in IECs (Phb1
) exhibited mitochondrial impairment, Paneth cell defects, gut microbiota dysbiosis, and spontaneous inflammation in the ileum (ileitis). Mice deficient in PHB1 in Paneth cells (epithelial secretory cells of the small intestine; Phb1
) also exhibited mitochondrial impairment, Paneth cell defects, and spontaneous ileitis. Here, we determined whether this phenotype is driven by Phb1 deficiency-associated ileal microbiota alterations or direct effects of loss of PHB1 in host IECs.
Depletion of gut microbiota by broad-spectrum antibiotic treatment in Phb1
or Phb1
mice revealed a necessary role of microbiota to cause ileitis. Using germ-free mice colonized with ileal microbiota from Phb1-deficient mice, we show that this microbiota could not independently induce ileitis without host mitochondrial dysfunction. The luminal microbiota phenotype of Phb1
mice included a loss of the short-chain fatty acid butyrate. Supplementation of butyrate in Phb1-deficient mice ameliorated Paneth cell abnormalities and ileitis. Phb1-deficient ileal enteroid models suggest deleterious epithelial-intrinsic responses to ileal microbiota that were protected by butyrate.
These results suggest a mutual and essential reinforcing interplay of gut microbiota and host IEC, including Paneth cell, mitochondrial health in influencing ileitis. Restoration of butyrate is a potential therapeutic option in Crohn's disease patients harboring epithelial cell mitochondrial dysfunction. Video Abstract.
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