We study the time lags between the continuum emission of quasars at different wavelengths, based on more than four years of multi-band (g, r, i, z) light curves in the Pan-STARRS Medium Deep Fields. ...As photons from different bands emerge from different radial ranges in the accretion disk, the lags constrain the sizes of the accretion disks. We select 240 quasars with redshifts of z 1 or z 0.3 that are relatively emission-line free. The light curves are sampled from day to month timescales, which makes it possible to detect lags on the scale of the light crossing time of the accretion disks. With the code JAVELIN, we detect typical lags of several days in the rest frame between the g band and the riz bands. The detected lags are ∼2-3 times larger than the light crossing time estimated from the standard thin disk model, consistent with the recently measured lag in NGC 5548 and microlensing measurements of quasars. The lags in our sample are found to increase with increasing luminosity. Furthermore, the increase in lags going from g − r to g − i and then to g − z is slower than predicted in the thin disk model, particularly for high-luminosity quasars. The radial temperature profile in the disk must be different from what is assumed. We also find evidence that the lags decrease with increasing line ratios between ultraviolet Fe ii lines and Mg ii, which may point to changes in the accretion disk structure at higher metallicity.
Understanding archaeological leather degradation helps inform economies, crafts, and technologies of historic communities. However, archaeological leather is at high risk of degradation due to ...deterioration and changes within the burial conditions. This research applied non-destructive FTIR-ATR to experimentally buried vegetable-tanned leather and archaeological leather excavated at the Roman site of Vindolanda, UK to explore survival, destruction, and preservation processes of tanned leather. Analyses focused on observing and monitoring changes in chemical functional groups related to leather tannins, collagen and lipid components following burial. FTIR-ATR results highlighted rapid changes following experimental burial in wet soil, tentatively associated with early onset microbial activity, which targeted readily available lipids but not tightly bound collagen. Prior to burial, differences in structural composition were present in leather spectra based on manufacture; however, following burial in wet soil, FTIR-ATR spectra indicated de-tanning occurs rapidly, especially in waterlogged conditions, with archaeological leather becoming more uniform and similar to untanned leather. Therefore, the comparison of FTIR-ATR results from archaeological leather to experimentally buried leather samples was informative for showing the destructive de-tanning in waterlogged environments. The comparison of FTIR-ATR data from modern unburied leather cannot be compared against archaeological samples. Importantly, despite de-tanning occurring soon after burial, the vegetable-tanning method promoted long-term preservation of leather in wet soil. The observed changes could not be directly associated with the proportion of condensed to hydrolysable tannin, suggesting alternate variables impacted the preservation. Furthermore, mineral components introduced into the leather through the animal skin, tannin material and/or tannin liquid are suggested to contribute to these changes. Crucially a high degree of heterogeneity in error results within the experimentally buried sample material underlined that any changes in collagen ratios cannot be overinterpreted and must be considered within the context of larger datasets.
Understanding archaeological leather degradation helps inform economies, crafts, and technologies of historic communities.
Medulloblastoma (MB) is a highly malignant brain tumor that occurs primarily in children. Although surgery, radiation and high-dose chemotherapy have led to increased survival, many MB patients still ...die from their disease, and patients who survive suffer severe long-term side effects as a consequence of treatment. Thus, more effective and less toxic therapies for MB are critically important. Development of such therapies depends in part on identification of genes that are necessary for growth and survival of tumor cells. Survivin is an inhibitor of apoptosis protein that regulates cell cycle progression and resistance to apoptosis, is frequently expressed in human MB and when expressed at high levels predicts poor clinical outcome. Therefore, we hypothesized that Survivin may have a critical role in growth and survival of MB cells and that targeting it may enhance MB therapy. Here we show that Survivin is overexpressed in tumors from patched (Ptch) mutant mice, a model of Sonic hedgehog (SHH)-driven MB. Genetic deletion of survivin in Ptch mutant tumor cells significantly inhibits proliferation and causes cell cycle arrest. Treatment with small-molecule antagonists of Survivin impairs proliferation and survival of both murine and human MB cells. Finally, Survivin antagonists impede growth of MB cells in vivo. These studies highlight the importance of Survivin in SHH-driven MB, and suggest that it may represent a novel therapeutic target in patients with this disease.
These investigators followed a large birth cohort with the use of questionnaires, lung-function tests, and allergy skin tests from the age of 3 to 26 years. Almost three quarters of the study ...participants had wheezing at one point in the follow-up, and 15 percent had wheezing at all points in the follow-up.
Clinical data on a large birth cohort.
The increase in the prevalence of wheezing disorders, whether or not they are labeled as asthma, could be related to an increased incidence or an increased persistence of asthma.
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Studies of the natural history of asthma have often focused on selected populations. However, the outcomes in children referred to university clinics
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or selected in high-risk cohorts
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may not reflect the outcomes in the general population, since the initial selection criteria may predetermine the risk factors for persistence or relapse.
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Most children attending asthma specialty clinics who have been followed have had atopy, with frequent symptoms and airway hyperresponsiveness, . . .
Density matrix exponentiation (DME) is a general technique for using a quantum stateρto enact the quantum operatione−iρθon a target system. It was first proposed in the context of quantum machine ...learning, but has since been shown to have broad applications in quantum metrology and computation. No experimental demonstration of DME has been performed thus far due to its demanding circuit depths and the need to efficiently generate multiple identical copies ofρduring the finite lifetime of the target system. In this work, we describe the first demonstration of the DME algorithm, which we accomplish using a superconducting quantum processor. Our demonstration relies on a 99.7% fidelity controlled-phase gate implemented using two tunable superconducting transmon qubits. We achieve a fidelity surpassing 90% at circuit depths exceeding 70 when comparing the output of the circuit executed on our quantum processor to a simulation assuming perfect operations and measurements.
Aim
Mitochondria‐encoded proteins are necessary for oxidative phosphorylation; however, no report has examined how physical activity (PA) and obesity affect mitochondrial mRNA translation machinery. ...Our purpose was to determine whether Western diet (WD)‐induced obesity and voluntary wheel running (VWR) impact mitochondrial mRNA translation machinery and whether expression of this machinery is dictated by oxidative phenotype.
Methods
Obesity was induced with 8‐wk WD feeding, and in the final 4 wks, half of mice were allowed VWR. Mitochondrial mRNA translation machinery including initiation factors (mtIF2/3), elongation factor Tu (TUFM) and translational activator (TACO1), and mitochondria‐encoded proteins (CytB and ND4) was assessed by immunoblotting. The relation of mitochondrial mRNA translation to muscle oxidative phenotype was assessed using PGC‐1α transgenic overexpression (MCK‐PGC‐1α vs. wild‐type mice) and comparing across muscle groups in wild‐type mice.
Results
mtIF3 and TACO1 proteins were ~45% greater in VWR than sedentary (SED), and TACO1 and mtIF2 proteins were ~60% and 125% greater in WD than normal chow (NC). TUFM protein was ~50% lower in WD‐SED than NC‐SED, but ~50% greater in WD‐VWR compared to NC‐SED. CytB and ND4 were ~40% greater in VWR and ND4 was twofold greater with WD. TUFM, TACO1, ND4 and CytB were greater in MCK‐PGC‐1α compared to wild‐type, and mtIF2/3 contents were not different. In oxidative muscle (soleus), mitochondrial translation machinery was elevated compared to mixed (gastrocnemius) or glycolytic (extensor digitorum longus) muscles.
Conclusion
These data suggest a novel mechanism promoting mitochondrial function by translation of mitochondrial protein following PA. This may act to promote muscle health by PA in obesity.
Background
The need for dental rehabilitation under general anesthesia is increasing, with varying needs between patients. Mortality has been found to be a rare event in these patients; however other ...perioperative events can and do occur. Previous studies have established increased incidence of perioperative events with younger, sicker children, and longer anesthetics, however, no studies to date have evaluated if the incidence of perioperative events is more closely associated with one long anesthetic or multiple anesthetics per patient.
Aims
To evaluate the association of perioperative events related to single anesthetic duration or number of anesthetics per patient for dental rehabilitation.
Methods
After Children's Wisconsin Human Research Protection Program determined this quality activity did not meet the definition of human subjects research, we performed an epidemiologic observational evaluation by extracting all dental related cases (dental alone or with oral surgeon vs. dental with other specialties) with an associated general anesthesia encounter from Children's Wisconsin electronic data warehouse from June 1, 2015 to December 31, 2021. These cases occurred at a free‐standing children's hospital or associated pediatric‐only ambulatory surgery center. The risk of perioperative safety events was analyzed for previously identified risk groups such as American Society of Anesthesiologists Physical Status (ASA‐PS), patient age, anesthesia case time with the addition of number of dental cases per patient.
Results
In this study, 8468 procedures were performed on 8082 patients. Of this cohort, 7765 patients underwent one procedure for dental care while 317 patients underwent a total of 703 dental‐related procedures, ranging from two to five procedures per patient. Multivariable logistic regression identified increased risk of perioperative events in patients with ASA‐PS 3 (n = 1459, rate 1.78%, p value .001, OR 5.7, CI 2.1–15.5) and ASA‐PS 4 (n = 86, rate 5.8%, p < .001, OR 17.2, CI 4.4–67.3), anesthesia duration (p < .001, OR 1.46, CI 1.21–1.76), but no increased risk with number of anesthetics per patient (p value .54, OR 0.81, CI 0.4–1.61).
Conclusions
Limiting dental care under general anesthesia to multiple short cases may decrease the risk of perioperative events when compared to completing all treatment in one long operative session.
The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the ...agreement that all bedside medical toxicology consultation will be entered. The objective of this ninth annual report is to summarize the Registry’s 2018 data and activity with its additional 7043 cases. Cases were identified for inclusion in this report by a query of the ToxIC database for any case entered from 1 January to 31 December 2018. Detailed data was collected from these cases and aggregated to provide information which included demographics, reason for medical toxicology evaluation, agent and agent class, clinical signs and symptoms, treatments and antidotes administered, mortality, and whether life support was withdrawn. A total of 51.5% of cases were female, 48% were male, and 0.6% transgender. Non-opioid analgesics were the most commonly reported agent class, followed by antidepressants and opioids. Acetaminophen was once again the most common agent reported. There were 106 fatalities, comprising 1.5% of all registry cases. Major trends in demographics and exposure characteristics remained similar to past years’ reports. Sub-analyses were conducted to describe exposures in elderly patients, addiction consultation practices, and risk factors for bupropion-induced seizures. The launch of the ToxIC Qualified Clinical Data Registry (TQCDR) is also described.
Aim
PGC‐1α4 is a novel regulator of muscle hypertrophy; however, there is limited understanding of the regulation of its expression and role in many (patho)physiological conditions. Therefore, our ...purpose was to elicit signalling mechanisms regulating gene expression of Pgc1α4 and examine its response to (patho)physiological stimuli associated with altered muscle mass.
Methods
IL‐6 knockout mice and pharmacological experiments in C2C12 myocytes were used to identify regulation of Pgc1α4 transcription. To examine Pgc1α4 gene expression in (patho)physiological conditions, obese and lean Zucker rats with/without resistance exercise (RE), ageing mice and muscle regeneration from injury were examined.
Results
In IL‐6 knockout mice, Pgc1α4mRNA was ~sevenfold greater than wild type. In C2C12 cells, Pgc1α4mRNA was suppressed ~70% by IL‐6. Suppression of Pgc1α4 by IL‐6 was prevented by MEK–ERK–MAPK inhibition. RE led to ~260% greater Pgc1α4mRNA content in lean rats. However, obese Zucker rats exhibited ~270% greater Pgc1α4mRNA than lean, sedentary with no further augmentation by RE. No difference was seen in IL‐6mRNA or ERK‐MAPK phosphorylation in Zucker rats. Aged mice demonstrated ~50% lower Pgc1α4mRNA and ~fivefold greater ERK‐MAPK phosphorylation than young despite unchanged Il‐6mRNA. During muscle regeneration, Pgc1α4 content is ~30% and IL‐6mRNA >threefold of uninjured controls 3 days following injury; at 5 days, Pgc1α4 was >twofold greater in injured mice with no difference in IL‐6mRNA.
Conclusion
Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL‐6–ERK‐MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions.
Value-based health care aims to optimize the balance of patient outcomes and health care costs. To improve value in perinatal care using this strategy, standard outcomes must first be defined. The ...objective of this work was to define a minimum, internationally appropriate set of outcome measures for evaluating and improving perinatal care with a focus on outcomes that matter to women and their families.
An interdisciplinary and international Working Group was assembled. Existing literature and current measurement initiatives were reviewed. Serial guided discussions and validation surveys provided consumer input. A series of nine teleconferences, incorporating a modified Delphi process, were held to reach consensus on the proposed Standard Set.
The Working Group selected 24 outcome measures to evaluate care during pregnancy and up to 6 months postpartum. These include clinical outcomes such as maternal and neonatal mortality and morbidity, stillbirth, preterm birth, birth injury and patient-reported outcome measures (PROMs) that assess health-related quality of life (HRQoL), mental health, mother-infant bonding, confidence and success with breastfeeding, incontinence, and satisfaction with care and birth experience. To support analysis of these outcome measures, pertinent baseline characteristics and risk factor metrics were also defined.
We propose a set of outcome measures for evaluating the care that women and infants receive during pregnancy and the postpartum period. While validation and refinement via pilot implementation projects are needed, we view this as an important initial step towards value-based improvements in care.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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