Use of serum lactate levels to predict survival for patients with out-of-hospital cardiac arrest: A cohort study

Objectives: We examined the association of serum lactate levels and early lactate clearance with survival to hospital discharge for patients suffering an out-of-hospital cardiac arrest (OHCA). Methods: A retrospective cohort analysis was performed of patients with OHCA transported by ambulance to two adult tertiary hospitals in Perth, Western Australia. Exclusion criteria were traumatic cardiac arrest, return of spontaneous circulation prior to the arrival of the ambulance, age less than 18 years and no serum lactate levels recorded. Serum lactate levels recorded for up to 48h post-arrest were obtained from the hospital clinical information system, and lactate clearance over 48h was calculated. Descriptive and logistic regression analyses were conducted. Results: There were 518 patients with lactate values, of whom 126 (24.3%) survived to hospital discharge. Survivors and non-survivors had different mean initial lactate levels (mean±SD 6.9±4.7 and 12.2±5.5mmol/L, respectively; P<0.001). Lactate clearance was higher in survivors. Lactate levels for non-survivors did not decrease below 2mmol/L until at least 30h after the ambulance call. Conclusion: In OHCA patients who had serum lactate levels measured, both lower initial serum lactate and early lactate clearance in the first 48h following OHCA were associated with increased likelihood of survival. However, the use of lactate in isolation as a predictor of survival or neurological outcome is not recommended. Prospective studies that minimise selection bias are required to determine the clinical utility of serum lactate levels in OHCA patients. © 2016 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine

Spatial Fingerprint of Younger Dryas Cooling and Warming in Eastern North America

The Younger Dryas (YD, 12.9–11.7 ka) is the most recent, near‐global interval of abrupt climate change with rates similar to modern global warming. Understanding the causes and biodiversity effects of YD climate changes requires determining the spatial fingerprints of past temperature changes. Here we build pollen‐based and branched glycerol dialkyl glycerol tetraether‐based temperature reconstructions in eastern North America (ENA) to better understand deglacial temperature evolution. YD cooling was pronounced in the northeastern United States and muted in the north central United States. Florida sites warmed during the YD, while other southeastern sites maintained a relatively stable climate. This fingerprint is consistent with an intensified subtropical high during the YD and demonstrates that interhemispheric responses were more complex spatially in ENA than predicted by the bipolar seesaw model. Reduced‐amplitude or antiphased millennial‐scale temperature variability in the southeastern United States may support regional hotspots of biodiversity and endemism

Present Effects of Past Wildfires on Leaf Litter Breakdown in Stream Ecosystems

We investigated the present effects from a 10-year-old wildfire on leaf litter breakdown rates in 3 headwater streams in central Idaho. These systems experienced a massive debris flow one year after the fire. Based on soil instability and burn patterns, we identified 3 stream conditions: unburned, burned only, and burned/scoured. We placed leaf bags containing willow leaves (Salix sp.) in each stream type and removed bags at various time intervals until all bags were collected 100 days after their introduction. Leaf material was dried and weighed, and decay rate coefficients were calculated. Macroinvertebrates colonizing the bags were enumerated and identified, and selected taxa were placed into trophic groups. We found that the unburned stream had the fastest leaf litter breakdown rate, the lowest level of incident light reaching the stream, and the largest amount of benthic organic matter. The burned/scoured stream was nearly opposite in all respects. Numbers of 2 detritivore invertebrate taxa, Serratella tibialis and Zapada oregonensis, were highest in the unburned stream but lowest in the burned/scoured stream. A third taxon, Baetis sp., showed the opposite relationship. Presence of predatory invertebrates did not affect detritivore abundance or leaf decay rate in the bags. Our research suggests that recovery response variables of some stream systems may not have returned to prefire levels even a decade after the initial wildfire. In this study, the recovery of our streams appears to be connected to the return of the riparian zone, though fire-induced debris flows may slow or alter final recovery of the stream system

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Differential requirements for Tousled-like kinases 1 and 2 in mammalian development

The regulation of chromatin structure is critical for a wide range of essential cellular processes. The Tousled-like kinases, TLK1 and TLK2, regulate ASF1, a histone H3/H4 chaperone, and likely other substrates, and their activity has been implicated in transcription, DNA replication, DNA repair, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function during mammalian development and suggests that TLK1 and TLK2 have largely redundant roles in genome maintenance

Early and late skin reactions to radiotherapy for breast cancer and their correlation with radiation-induced DNA damage in lymphocytes

INTRODUCTION: Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects. METHODS: Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments. RESULTS: Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects. CONCLUSION: After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients

German S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" – long version of the update 2023

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutanepus squamous cell carcinoma in situ (Bowen’s disease) and actinic cheilitis. This guideline was developed at the highest evidence level (S3) and is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC