Gambaran Histologik Usus Halus Pada Hewan Coba Selama 24 Jam Postmortem

: Studies about histological changes in small intestine are still very limited. This study was aimed to obtain the histological changes of the small intestine in several time intervals during 24 hours postmortem. This was a descriptive observational study using domestic pig as model. Samples were obtained from the ileum section of the small intestine, taken at 0 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 12 hours, 14 hours, 16 hours, 18 hours, 20 hours, 22 hours, and 24 hours postmortem. The results showed that the earliest histological change was identified at 0 hours postmortem as congestion of the intestinal glands and formation of subepithelial cell spaces, followed by destruction of basal membranes of the glands at 3 hours postmortem, lysis of the glands at 16 hours postmortem. At 18-24 hours postmortem, almorst all intestinal glands could not be identified. Conclusion: The earliest histological change of small intestine was identified at 0 hours postmortem as congestion of the intestinal glands, followed by necrosis of the glands at 3 hours postmortem, and lysis of the glands at 16 hours postmortem

Hypoxia-induced SETX links replication stress with the unfolded protein response.

Tumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways

Evaluation of night-time aerosols measurements and lunar irradiance models in the frame of the first multi-instrument nocturnal intercomparison campaign

The first multi-instrument nocturnal aerosol optical depth (AOD) intercom-parison campaign was held at the high-mountain Iza ̃na Observatory (Tener-ife, Spain) in June 2017, involving 2-minutes synchronous measurements fromtwo different types of lunar photometers (Cimel CE318-T and Moon Preci-sion Filter Radiometer, LunarPFR) and one stellar photometer. The Robotic Lunar Observatory (ROLO) model developed by the U.S. Geological Survey(USGS) was compared with the open-access ROLO Implementation for Moonphotometry Observation (RIMO) model. Results showed rather small differ-ences at Iza ̃na over a 2-month time period covering June and July, 2017(±0.01 in terms of AOD calculated by means of a day/night/day coherencetest analysis and±2 % in terms of lunar irradiance). The RIMO model hasbeen used in this field campaign to retrieve AOD from lunar photometricmeasurements. No evidence of significant differences with the Moon’s phase angle wasfound when comparing raw signals of the six Cimel photometers involved inthis field campaign.The raw signal comparison of the participating lunar photometers (Cimeland LunarPFR) performed at coincident wavelengths showed consistent mea-surements and AOD differences within their combined uncertainties at 870 nmand 675 nm. Slightly larger AOD deviations were observed at 500 nm, point-ing to some unexpected instrumental variations during the measurement pe-riod.Lunar irradiances retrieved using RIMO for phase angles varying between0◦and 75◦(full Moon to near quarter Moon) were compared to the irradi-ance variations retrieved by Cimel and LunarPFR photometers. Our resultsshowed a relative agreement within±3.5 % between the RIMO model andthe photometer-based lunar irradiances.The AOD retrieved by performing a Langley-plot calibration each nightshowed a remarkable agreement (better than 0.01) between the lunar pho-tometers. However, when applying the Lunar-Langley calibration using RIMO,AOD differences of up to 0.015 (0.040 for 500 nm) were found, with differ-ences increasing with the Moon’s phase angle. These differences are thoughtto be partly due to the uncertainties in the irradiance models, as well asinstrumental deficiencies yet to be fully understood.High AOD variability in stellar measurements was detected during thecampaign. Nevertheless, the observed AOD differences in the Cimel/stellarcomparison were within the expected combined uncertainties of these twophotometric techniques. Our results indicate that lunar photometry is amore reliable technique, especially for low aerosol loading conditions.The uncertainty analysis performed in this paper shows that the com-bined standard AOD uncertainty in lunar photometry is dependent on thecalibration technique (up to 0.014 for Langley-plot with illumination-basedcorrection, 0.012-0.022 for Lunar-Langley calibration, and up to 0.1 for the 2 Sun-Moon Gain Factor method). This analysis also corroborates that theuncertainty of the lunar irradiance model used for AOD calculation is withinthe 5-10 % expected range.This campaign has allowed us to quantify the important technical diffi-culties that still exist when routinely monitoring aerosol optical propertiesat night-time. The small AOD differences observed between the three typesof photometers involved in the campaign are only detectable under pristinesky conditions such as those found in this field campaign. Longer campaignsare necessary to understand the observed discrepancies between instrumentsas well as to provide more conclusive results about the uncertainty involvedin the lunar irradiance model

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Hypoxia-induced SETX links replication stress with the unfolded protein response

YesTumour hypoxia is associated with poor patient prognosis and therapy resistance. A unique transcriptional response is initiated by hypoxia which includes the rapid activation of numerous transcription factors in a background of reduced global transcription. Here, we show that the biological response to hypoxia includes the accumulation of R-loops and the induction of the RNA/DNA helicase SETX. In the absence of hypoxia-induced SETX, R-loop levels increase, DNA damage accumulates, and DNA replication rates decrease. Therefore, suggesting that, SETX plays a role in protecting cells from DNA damage induced during transcription in hypoxia. Importantly, we propose that the mechanism of SETX induction in hypoxia is reliant on the PERK/ATF4 arm of the unfolded protein response. These data not only highlight the unique cellular response to hypoxia, which includes both a replication stress-dependent DNA damage response and an unfolded protein response but uncover a novel link between these two distinct pathways.SR, KBL, PV and MH were supported by a CRUK grant C5255/A23755 (awarded to E.M.H.). N.N. was supported by an MRC studentship (MC_ST_U16007). I. P.F. was supported by CRUK Oxford Centre Prize DPhil Studentship C38302/A12981. N.G. was supported by a Royal Society University Research fellowship. W.-C.C. was funded by CRUK grant 23969 (awarded to F.M.B.). S.F.E.-K. was supported by a Wellcome Trust Investigator Award (103844) and a Lister Institute of Preventative Medicine Fellowship (137661). J.G. was supported by a Jean Shanks Foundation/ Pathological Society of Great Britain and Ireland Clinical PhD Fellowship (JSPS CPhD 2018 01)

Evaluation of night-time aerosols measurements and lunar irradiance models in the frame of the first multi-instrument nocturnal intercomparison campaign

The first multi-instrument nocturnal aerosol optical depth (AOD) intercomparison campaign was held at the high-mountain Izaña Observatory (Tenerife, Spain) in June 2017, involving 2-min synchronous measurements from two different types of lunar photometers (Cimel CE318-T and Moon Precision Filter Radiometer, LunarPFR) and one stellar photometer. The Robotic Lunar Observatory (ROLO) model developed by the U.S. Geological Survey (USGS) was compared with the open-access ROLO Implementation for Moon photometry Observation (RIMO) model. Results showed rather small differences at Izaña over a 2-month time period covering June and July, 2017 (±0.01 in terms of AOD calculated by means of a day/night/day coherence test analysis and ± 2% in terms of lunar irradiance). The RIMO model has been used in this field campaign to retrieve AOD from lunar photometric measurements. No evidence of significant differences with the Moon's phase angle was found when comparing raw signals of the six Cimel photometers involved in this field campaign. The raw signal comparison of the participating lunar photometers (Cimel and LunarPFR) performed at coincident wavelengths showed consistent measurements and AOD differences within their combined uncertainties at 870 nm and 675 nm. Slightly larger AOD deviations were observed at 500 nm, pointing to some unexpected instrumental variations during the measurement period. Lunar irradiances retrieved using RIMO for phase angles varying between 0° and 75° (full Moon to near quarter Moon) were compared to the irradiance variations retrieved by Cimel and LunarPFR photometers. Our results showed a relative agreement within ± 3.5% between the RIMO model and the photometer-based lunar irradiances. The AOD retrieved by performing a Langley-plot calibration each night showed a remarkable agreement (better than 0.01) between the lunar photometers. However, when applying the Lunar-Langley calibration using RIMO, AOD differences of up to 0.015 (0.040 for 500 nm) were found, with differences increasing with the Moon's phase angle. These differences are thought to be partly due to the uncertainties in the irradiance models, as well as instrumental deficiencies yet to be fully understood. High AOD variability in stellar measurements was detected during the campaign. Nevertheless, the observed AOD differences in the Cimel/stellar comparison were within the expected combined uncertainties of these two photometric techniques. Our results indicate that lunar photometry is a more reliable technique, especially for low aerosol loading conditions. The uncertainty analysis performed in this paper shows that the combined standard AOD uncertainty in lunar photometry is dependent on the calibration technique (up to 0.014 for Langley-plot with illumination-based correction, 0.012–0.022 for Lunar-Langley calibration, and up to 0.1 for the Sun-Moon Gain Factor method). This analysis also corroborates that the uncertainty of the lunar irradiance model used for AOD calculation is within the 5–10% expected range. This campaign has allowed us to quantify the important technical difficulties that still exist when routinely monitoring aerosol optical properties at night-time. The small AOD differences observed between the three types of photometers involved in the campaign are only detectable under pristine sky conditions such as those found in this field campaign. Longer campaigns are necessary to understand the observed discrepancies between instruments as well as to provide more conclusive results about the uncertainty involved in the lunar irradiance models.This work has been developed within the framework of the activities of the World Meteorological Organization (WMO) Commission for Instruments and Methods of Observations (CIMO) Izaña Testbed for Aerosols and Water Vapour Remote Sensing Instruments. AERONET sun photometers at Izaña have been calibrated within the AERONET Europe TNA, supported by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 654109 (ACTRIS‒2). CE318-T linearity check has been performed as part of the ESA-funded project “Lunar spectral irradiance measurement and modelling for absolute calibration of EO optical sensors” under ESA contract number: 4000121576/17/NL/AF/hh. LunarPFR has been performing measurements since 2014 in Norway thanks to Svalbard Science Forum funded project, 2014–2016. The authors would like to thank AERONET team for their support and also to NASA’s Navigation and Ancillary Information Facility (NAIF) at the Jet Propulsion Laboratory to help the implementation of the “SPICE” ancillary information system used in this study. We also thank Izaña's ITs for their work to implement the RIMO model in the free-access server. Special thanks should be given to Tom Stone, who has kindly provided us with the USGS/ROLO irradiance values used in the model comparison analysis. This work has also received funding from the European Union’s Horizon 2020 research and innovation programme and from Marie Skłodowska-Curie Individual Fellowships (IF) ACE-GFAT (grant agreement no. 659398). The authors are grateful to Spanish MINECO (CTM2015-66742-R) and Junta de Castilla y León (VA100P17)

Distant Voices: Learners' Stories About the Affective Side of Learning a Language at a Distance

Learning a language at a distance has its own special challenges. The remoteness of the learning context can mean isolation for the learner, communication difficulties for the teacher and problems of access for the researcher. Yet distance language learners are likely to be no more skilled in self-regulation than classroom learners, and to require high levels of support. Research tools are needed, therefore, which allow them to talk freely about their learning in order to help distance educators target support appropriately. This paper draws on data from two pilot ethnographic studies of distance language learners using think-aloud protocols to access their thought processes as they tackled two designated language tasks. They were carried out as part of a wider study in each case to investigate aspects of affect including beliefs, motivation and anxiety. The audio-taped voices provided rich insights into the advantages and disadvantages, pleasures and frustrations, comforts and anxieties of learning a language at a distance, and the strategies learners use to manage in a distance environment. The studies underlined the importance of listening to students and using their voices as a basis for discussion on improving aspects of the design and delivery of distance language courses