The dominant hypothesis for the evolutionary origin of snakes from ‘lizards’ (non‐snake squamates) is that stem snakes acquired many snake features while passing through a profound burrowing ...(fossorial) phase. To investigate this, we examined the visual pigments and their encoding opsin genes in a range of squamate reptiles, focusing on fossorial lizards and snakes. We sequenced opsin transcripts isolated from retinal cDNA and used microspectrophotometry to measure directly the spectral absorbance of the photoreceptor visual pigments in a subset of samples. In snakes, but not lizards, dedicated fossoriality (as in Scolecophidia and the alethinophidian Anilius scytale) corresponds with loss of all visual opsins other than RH1 (λₘₐₓ 490–497 nm); all other snakes (including less dedicated burrowers) also have functional sws1 and lws opsin genes. In contrast, the retinas of all lizards sampled, even highly fossorial amphisbaenians with reduced eyes, express functional lws, sws1, sws2 and rh1 genes, and most also express rh2 (i.e. they express all five of the visual opsin genes present in the ancestral vertebrate). Our evidence of visual pigment complements suggests that the visual system of stem snakes was partly reduced, with two (RH2 and SWS2) of the ancestral vertebrate visual pigments being eliminated, but that this did not extend to the extreme additional loss of SWS1 and LWS that subsequently occurred (probably independently) in highly fossorial extant scolecophidians and A. scytale. We therefore consider it unlikely that the ancestral snake was as fossorial as extant scolecophidians, whether or not the latter are para‐ or monophyletic.
Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, ...in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability.
Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1–28 or 1–56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1–28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea.
Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0–2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold.
Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period.
NCT02400476.
•CONTROL trial investigated antidiarrheal strategies including dose escalation in neratinib-treated patients with early HER2+ breast cancer.•Preemptive prophylaxis and dose escalation reduced the rate, severity, and duration of grade 3 diarrhea compared with ExteNET.•Lower diarrhea-related discontinuations and dose reductions in multiple cohorts compared with ExteNET suggested improved tolerability.•Neratinib dose escalation is a particularly promising strategy as it eliminates mandatory prophylaxis and related side-effects.
THE COSMIC/FORMOSAT-3 MISSION Anthes, R. A.; Bernhardt, P. A.; Chen, Y. ...
Bulletin of the American Meteorological Society,
03/2008, Letnik:
89, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The radio occultation (RO) technique, which makes use of radio signals transmitted by the global positioning system (GPS) satellites, has emerged as a powerful and relatively inexpensive approach for ...sounding the global atmosphere with high precision, accuracy, and vertical resolution in all weather and over both land and ocean. On 15 April 2006, the joint Taiwan–U.S. Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC)/Formosa Satellite Mission 3 (COSMIC/FORMOSAT-3, hereafter COSMIC) mission, a constellation of six microsatellites, was launched into a 512-km orbit. After launch the satellites were gradually deployed to their final orbits at 800 km, a process that took about 17 months. During the early weeks of the deployment, the satellites were spaced closely, offering a unique opportunity to verify the high precision of RO measurements. As of September 2007, COSMIC is providing about 2000 RO soundings per day to support the research and operational communities. COSMIC RO data are of better quality than those from the previous missions and penetrate much farther down into the troposphere; 70%–90% of the soundings reach to within 1 km of the surface on a global basis. The data are having a positive impact on operational global weather forecast models.
With the ability to penetrate deep into the lower troposphere using an advanced open-loop tracking technique, the COSMIC RO instruments can observe the structure of the tropical atmospheric boundary layer. The value of RO for climate monitoring and research is demonstrated by the precise and consistent observations between different instruments, platforms, and missions. COSMIC observations are capable of intercalibrating microwave measurements from the Advanced Microwave Sounding Unit (AMSU) on different satellites. Finally, unique and useful observations of the ionosphere are being obtained using the RO receiver and two other instruments on the COSMIC satellites, the tiny ionosphere photometer (TIP) and the tri-band beacon.
The prediction of the ground movements above single tunnels in soft ground is well established and can be estimated using semi-empirical methods based on the Gaussian curve. However, the prediction ...of ground movements associated with closely spaced multiple tunnels, in particular side-by-side (sbs) tunnels, is not as well understood, and therefore simple predictive methods for this application are currently quite limited in terms of their accuracy. This paper describes results from a series of small-scale (1/50) laboratory model tests (conducted at 1g) carried out in Speswhite kaolin clay. These tests have been conducted to gain a greater understanding of the short-term ground movements associated with closely spaced multiple (sbs) tunnels. The observed ground movement results from these tests have shown many of the characteristics observed at full-scale in the published case studies. These results are compared to the commonly used Gaussian curve prediction method and demonstrate the potential inaccuracy in this approach for predicting ground movements associated with closely spaced multiple tunnels. A method that modifies the Gaussian curve approach is also applied to the laboratory data and shows improved predictions.Key words: tunnelling, ground movements, multiple side-by-side tunnels, physical modelling, settlement prediction.
Recently, cancer mortality has been compared to research spending by the National Cancer Research Institute (NCRI), whose research budget is approximately pound sterling 250 million. The analysis ...shows a mis-match between mortality and research spending. As well as crude mortality rates, other measures of cancer burden should be considered because they contribute additional information. 'Years of life lost' (YLL) summed over each individual dying after a diagnosis of cancer represents a population-based mortality indicator of the impact of that disease on society. Years of life lost divided by the number of deaths for each cancer site produces an additional statistic, the average years of life lost (AYLL), which is a measure of the burden of cancer to the individual patient. For 17 cancer sites where data are available, four tumour sites have a rather large difference in mortality, comparing YLL to crude mortality. Years of life lost shows the population burden from cancers of the ovary, cervix, and CNS to be rather larger than suggested by crude mortality, despite screening programmes for cervix cancer. Using YLL, the underprovision of funding for lung cancer research is similar to that reported using percentage mortality. Breast cancer and leukaemia receive a relatively higher research spend than the population burden of these cancers, and the spending on leukaemia is quite extreme. Prostate cancer has a low per cent YLL but attracts a moderate amount of research spending. The use of AYLL as an indicator of individual cancer burden considerably changes the ranking of the mortality from different tumours. The mean AYLL is 12.5 years. Prostate cancer has the lowest AYLL, only 6.1 years; brain tumour patients have the highest, at just over 20 years. Comparing AYLL to research spending suggests four 'Cinderella' cancer sites with high individual cancer burden but low research spending: CNS tumours, cervix and kidney cancers, and melanoma. Breast cancer and leukaemia have roughly average AYLL but a considerable excess of research spending. YLL emphasises the discrepancy between research spending and mortality, and may be helpful for decisions concerning research support. Average years of life lost measures the burden to individual patients and may be helpful where individuals' needs are relevant, such as palliative care. As well as crude mortality, more subtle and comprehensive calculations of mortality statistics would be useful in debates on research funding and public health issues.
Histone acetylation affects many nuclear processes including transcription, chromatin assembly, and DNA damage repair. Acetylation of histone H3 lysine 56 (H3 K56ac) in budding yeast occurs during ...mitotic S phase and persists during DNA damage repair. Here, we show that H3 K56ac is also present during premeiotic S phase and is conserved in fission yeast. Furthermore, the H3 K56ac modification is not observed in the absence of the histone chaperone Asf1. asf1delta and H3 K56R mutants exhibit similar sensitivity to DNA damaging agents. Mutational analysis of Asf1 demonstrates that DNA damage sensitivity correlates with (i) decreased levels of H3 K56ac and (ii) a region implicated in histone binding. In contrast, multiple asf1 mutants that are resistant to DNA damage display WT levels of K56ac. These data suggest that maintenance of H3 K56 acetylation is a primary contribution of Asf1 to genome stability in yeast.
Introduction
For over fifty years, minorities in Burma have faced severe persecution and violence, forcing them to flee their homeland. In the past ten years there has been an influx in the number of ...refugees resettled in Denver, Colorado. Refugees often struggle to navigate the complexities of the American health care system and adapt to life in a foreign culture. The development of programs and partnerships to assist refugees in their pursuit of health and integration is essential to building stronger communities.
Objectives
This community based participatory research (CBPR) project was developed in collaboration with the refugee community from Burma living in the Denver area. After regular meetings with a group of motivated teenagers and young adults from this community to form our Youth Advisory Board (YAB), they identified alcohol use and misuse as a health concern within their community. With this identified issue, the project aimed to gather data from community members that could be leveraged to create, implement, and evaluate a culturally competent intervention to effectively address risky alcohol use in this community.
Methods
Data collection involved formal one-on-one, semi-structured, audio-recorded interviews with community members. Participants were recruited voluntarily at health information nights held by the student researchers at their local apartment complex. The interviews were conducted by one medical student researcher with one translator present and were transcribed afterward. The interview data was analyzed using Immersion Crystallization methodology.
Results
Initial results from the community meetings with the YAB, local organizations, formative community surveys, and key informant interviews highlighted the vulnerability of the refugee population, scarcity of culturally appropriate resources for alcohol abuse, and urgency of addressing problematic alcohol use. The analysis of the ten audio-recorded surveys showed several themes including negative consequences of alcohol use, specifically negative impacts on familial relationships, employment, and financial resources, and a perceived personal responsibility for managing one’s own alcohol consumption.
Conclusions
This project corroborates current literature regarding the scope and breadth of hazardous alcohol use within the community of refugees from Burma. Our data has expanded our understanding of the values of community members including the influence of religion and family on behaviors, and the negative impact on employment as the most impactful negative consequence. These findings need to be shared with the community to move forward in mapping the most effective and appropriate interventions.
Disclosure of Interest
None Declared
Several marine species have developed a magnetic perception that is essential for navigation and detection of prey and predators. One of these species is the transparent glass catfish that contains ...an ampullary organ dedicated to sense magnetic fields. Here we examine the behavior of the glass catfish in response to static magnetic fields which will provide valuable insight on function of this magnetic response. By utilizing state of the art animal tracking software and artificial intelligence approaches, we quantified the effects of magnetic fields on the swimming direction of glass catfish. The results demonstrate that glass catfish placed in a radial arm maze, consistently swim away from magnetic fields over 20 μT and show adaptability to changing magnetic field direction and location.
This article (1) explores the nature and origins of "high impact" (i.e., highly cited) articles in marketing, (2) argues that a major factor is that highly cited articles frequently are the result of ...their authors' executing time-consuming, research programs, rather than simply working on individual articles that appear to be immediately publishable, (3) develops a "six-stage model" of programmatic research, and (4) illustrates the six-stage model by means of the author's "marketing theory" research program.
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