Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural ...by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known. This study confirms individual variation in CH4 production was influenced by individual host (cow) genotype, as well as the host's rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host's genotype and certain taxa were associated with CH4 emissions. However, the cumulative effect of all bacteria and archaea on CH4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH4 emissions in the cattle industry.
Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free ...survival among patients with resectable stage III or IV melanoma is unknown.
In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated.
At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval CI, 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group.
Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).
Spatiotemporal mode-locking in multimode fiber lasers Wright, Logan G.; Christodoulides, Demetrios N.; Wise, Frank W.
Science (American Association for the Advancement of Science),
10/2017, Volume:
358, Issue:
6359
Journal Article
Peer reviewed
Open access
A laser is based on the electromagnetic modes of its resonator, which provides the feedback required for oscillation. Enormous progress has been made toward controlling the interactions of ...longitudinal modes in lasers with a single transverse mode. For example, the field of ultrafast science has been built on lasers that lock many longitudinal modes together to form ultrashort light pulses. However, coherent superposition of longitudinal and transverse modes in a laser has received little attention. We show that modal and chromatic dispersions in fiber lasers can be counteracted by strong spatial and spectral filtering. This allows locking of multiple transverse and longitudinal modes to create ultrashort pulses with a variety of spatiotemporal profiles. Multimode fiber lasers thus open new directions in studies of nonlinear wave propagation and capabilities for applications.
Advances in methods for longitudinal data collection and analysis have prompted a surge of research on psychological processes. However, decisions about how to time assessments are often not ...explicitly tethered to theories about psychological processes but are instead justified on methodological (e.g., power) or practical (e.g., feasibility) grounds. In many cases, methodological decisions are not explicitly justified at all. The disconnect between theories about processes and the timing of assessments in longitudinal research has contributed to misspecified models, interpretive errors, mixed findings, and nonspecific conclusions. In this article, we argue that higher demands should be placed on researchers to connect theories to methods in longitudinal research. We review instances of this disconnect and offer potential solutions as they pertain to four general questions for longitudinal researchers: how time should be scaled, how many assessments are needed, how frequently assessments should occur, and when assessments should happen.
Ambulatory assessment (AA; also known as ecological momentary assessment) has enjoyed enthusiastic implementation in psychological research. The ability to assess thoughts, feelings, behavior, ...physiology, and context intensively and repeatedly in the moment in an individual's natural ecology affords access to data that can answer exciting questions about sequences of events and dynamic processes in daily life. AA also holds unique promise for developing personalized models of individuals (i.e., precision or person-specific assessment) that might be transformative for applied settings such as clinical practice. However, successfully translating AA from bench to bedside is challenging because of the inherent tension between idiographic and nomothetic principles of measurement. We argue that the value of applied AA will be most fully realized by balancing the ability to develop personalized models with ensuring comparability among individuals.
Public Significance Statement
Psychological research is increasingly measuring human functioning in life as it is lived, by assessing thoughts, feelings, behavior, physiology, and context using tools like smartphones and other mobile sensors. This article proposes some basic principles for adapting these research tools for applied clinical settings.
Introduction
Current recommendations for early-stage breast cancer are largely based on the NSABP B-06 trial demonstrating equivalent survival between mastectomy and lumpectomy. We sought to compare ...breast-conserving therapy (BCT) with mastectomy for treatment of early-stage breast cancer in a contemporary patient population.
Methods
A query of the NCDB PUF identified female breast cancer patients diagnosed from 2004 to 2015. Patients with stage I or II disease were included. BCT was defined as the receipt of lumpectomy plus radiation. Propensity scores were tabulated using race, age, Charlson/Deyo score, tumor site, laterality, histology, grade, size, number of nodes positive, lymph-vascular invasion, receptor status, receipt of chemotherapy, and endocrine therapy. Patients who received BCT versus mastectomy were matched using a 1:1 nearest neighbor technique. The primary outcome measured was overall survival.
Results
After exclusions and matching, two equal groups of 101,118 patients remained. Median follow-up was 42 months. The majority had invasive ductal histology (77%), and node-negative disease (84%). Receptor status included ER-positive (83%), PR-positive (73%), and HER2/Neu-positive (15%). Chemotherapy was received in 38% and endocrine therapy in 71%. Propensity score matching yielded equivalent groups across all target variables. The 5-year overall survival was superior for BCT compared with mastectomy (92.9% vs. 89.7%,
p
< 0.001; Fig.
1
). This survival advantage persisted for both stage I (
p
< 0.001) and stage II (
p
< 0.001) disease on subgroup analysis.
Fig. 1
Overall survival in female patients with early stage invasive breast cancer (stage I or II) undergoing breast conservation surgery with radiation compared with mastectomy.
BCS
breast conservation surgery
Conclusions
BCT is associated with superior overall survival compared with mastectomy for early-stage breast cancer using well-matched, contemporary data.
To summarize the available evidence for the efficacy of various treatments for unexplained infertility.
Systematic review.
Not applicable.
Patients aged 18-40 years with unexplained infertility.
...Clomiphene citrate, letrozole, timed intercourse, IUI, gonadotropins, IVF, and IVF-intracytoplasmic sperm injection.
Clinical pregnancy rate, ongoing pregnancy rate, and live birth rate.
Thirteen studies with a total of 3,081 patients were identified by systematic search and met inclusion criteria. The available literature demonstrates that expectant management may be comparable to treatment with clomiphene and timed intercourse or IUI. Clomiphene may be more effective than letrozole, and treatment with gonadotropins seems more effective, albeit with significantly higher risk of multiple gestations than either oral agent. On the basis of current data, IVF, with or without intracytoplasmic sperm injection, is no more effective than gonadotropins with IUI for unexplained infertility.
Adequately powered, randomized controlled trials that compare all of the available treatments for unexplained infertility are needed. Until such data are available, clinicians should individualize the management of unexplained infertility with appropriate counseling regarding the empiric nature of current treatment options including IVF.
Worldwide, there is a need to enhance our understanding of vulnerability and to develop methodologies and tools to assess vulnerability. One of the most important goals of assessing coastal flood ...vulnerability, in particular, is to create a readily understandable link between the theoretical concepts of flood vulnerability and the day-to-day decision-making process and to encapsulate this link in an easily accessible tool. This article focuses on developing a Coastal City Flood Vulnerability Index (CCFVI) based on exposure, susceptibility and resilience to coastal flooding. It is applied to nine cities around the world, each with different kinds of exposure. With the aid of this index, it is demonstrated which cities are most vulnerable to coastal flooding with regard to the system’s components, that is, hydro-geological, socio-economic and politico-administrative. The index gives a number from 0 to 1, indicating comparatively low or high coastal flood vulnerability, which shows which cities are most in need of further, more detailed investigation for decision-makers. Once its use to compare the vulnerability of a range of cities under current conditions has been demonstrated, it is used to study the impact of climate change on the vulnerability of these cities over a longer timescale. The results show that CCFVI provides a means of obtaining a broad overview of flood vulnerability and the effect of possible adaptation options. This, in turn, will allow for the direction of resources to more in-depth investigation of the most promising strategies.
Clomiphene is the current first-line infertility treatment in women with the polycystic ovary syndrome, but aromatase inhibitors, including letrozole, might result in better pregnancy outcomes.
In ...this double-blind, multicenter trial, we randomly assigned 750 women, in a 1:1 ratio, to receive letrozole or clomiphene for up to five treatment cycles, with visits to determine ovulation and pregnancy, followed by tracking of pregnancies. The polycystic ovary syndrome was defined according to modified Rotterdam criteria (anovulation with either hyperandrogenism or polycystic ovaries). Participants were 18 to 40 years of age, had at least one patent fallopian tube and a normal uterine cavity, and had a male partner with a sperm concentration of at least 14 million per milliliter; the women and their partners agreed to have regular intercourse with the intent of conception during the study. The primary outcome was live birth during the treatment period.
Women who received letrozole had more cumulative live births than those who received clomiphene (103 of 374 27.5% vs. 72 of 376 19.1%, P=0.007; rate ratio for live birth, 1.44; 95% confidence interval, 1.10 to 1.87) without significant differences in overall congenital anomalies, though there were four major congenital anomalies in the letrozole group versus one in the clomiphene group (P=0.65). The cumulative ovulation rate was higher with letrozole than with clomiphene (834 of 1352 treatment cycles 61.7% vs. 688 of 1425 treatment cycles 48.3%, P<0.001). There were no significant between-group differences in pregnancy loss (49 of 154 pregnancies in the letrozole group 31.8% and 30 of 103 pregnancies in the clomiphene group 29.1%) or twin pregnancy (3.4% and 7.4%, respectively). Clomiphene was associated with a higher incidence of hot flushes, and letrozole was associated with higher incidences of fatigue and dizziness. Rates of other adverse events were similar in the two treatment groups.
As compared with clomiphene, letrozole was associated with higher live-birth and ovulation rates among infertile women with the polycystic ovary syndrome. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; ClinicalTrials.gov number, NCT00719186.).
While the use of anaerobic digestion to generate methane as a source of bioenergy is increasing worldwide, our knowledge of the microbial communities that perform biomethanation is very limited. ...Using next-generation sequencing, bacterial population profiles were determined in three full-scale mesophilic anaerobic digesters operated on dairy farms in the state of Vermont (USA). To our knowledge, this is the first report of a metagenomic analysis on the bacterial population of anaerobic digesters using dairy manure as their main substrate. A total of 20,366 non-chimeric sequence reads, covering the V1-V2 hypervariable regions of the bacterial 16S rRNA gene, were assigned to 2,176 operational taxonomic units (OTUs) at a genetic distance cutoff value of 5 %. Based on their limited sequence identity to validly characterized species, the majority of OTUs identified in our study likely represented novel bacterial species. Using a naïve Bayesian classifier, 1,624 anaerobic digester OTUs could be assigned to 16 bacterial phyla, while 552 OTUs could not be classified and may belong to novel bacterial taxonomic groups that have yet to be described. Firmicutes, Bacteroidetes, and Chloroflexi were the most highly represented bacteria overall, with Bacteroidetes and Chloroflexi showing the least and the most variation in abundance between digesters, respectively. All digesters shared 132 OTUs, which as a “core” group represented 65.4 to 70.6 % of sequences in individual digesters. Our results show that bacterial populations from microbial communities of anaerobic manure digesters can display high levels of diversity despite sharing a common core substrate.
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