A dynamical measure of the black hole mass in a quasar 11 billion years ago.

Tight relationships exist in the local Universe between the central stellar properties of galaxies and the mass of their supermassive black hole (SMBH)1-3. These suggest that galaxies and black holes co-evolve, with the main regulation mechanism being energetic feedback from accretion onto the black hole during its quasar phase4-6. A crucial question is how the relationship between black holes and galaxies evolves with time; a key epoch to examine this relationship is at the peaks of star formation and black hole growth 8-12 billion years ago (redshifts 1-3)7. Here we report a dynamical measurement of the mass of the black hole in a luminous quasar at a redshift of 2, with a look back in time of 11 billion years, by spatially resolving the broad-line region (BLR). We detect a 40-µas (0.31-pc) spatial offset between the red and blue photocentres of the Hα line that traces the velocity gradient of a rotating BLR. The flux and differential phase spectra are well reproduced by a thick, moderately inclined disk of gas clouds within the sphere of influence of a central black hole with a mass of 3.2 × 108 solar masses. Molecular gas data reveal a dynamical mass for the host galaxy of 6 × 1011 solar masses, which indicates an undermassive black hole accreting at a super-Eddington rate. This suggests a host galaxy that grew faster than the SMBH, indicating a delay between galaxy and black hole formation for some systems.

First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

ClO-driven degradation of graphene oxide: new insights from DFT calculations.

We present an extensive investigation using density functional theory (DFT) calculations on various model graphene oxide (GO) nanostructures interacting with chlorine monoxide ClO, aiming to understand the role of this highly oxidizing species in C-C bond breakage and the formation of significant holes on GO sheets. During its function, the myeloperoxidase (MPO) enzyme abundantly generates chlorine-oxygen-containing species and their presence has been identified as the cause of degradation in carbon nanotubes of diverse sizes, morphologies, and chemical compositions, both in in vivo and in vitro samples. Notably, Kurapati et al. (Small, 2015, 11, 3985-3994) demonstrated efficient degradation of single GO monolayers through MPO catalysis, though the exact degradation mechanism remains unclear. In our study, we discover that breaking C-C bonds in a single graphene oxide sheet is achievable through a simple mechanism involving the dissociation of two ClO molecules that are chemically attached as nearest neighbor species but bonded to opposite sides of the GO layer (up/down configuration). Two new carbonyl oxygens appear on the surface and the Cl atoms can be transferred to the carbon layer or as physisorbed species near the GO surface. Relatively small energy barriers are associated with these molecular events. Continuing this process on neighboring sites leads to the presence of larger holes on the GO surface, accompanied by an increase in carbonyl species on the carbon network, consistent with X-ray photoelectron spectroscopy measurements. Indeed, the distribution of oxygen functionalities is found to be crucial in defining the damage pattern induced in the carbon layer. We emphasize the important role played by the local charge distribution in the stability or instability of chemical bonds, as well as in the energy barriers and reaction pathways. Finally, we explore the possibility of achieving chlorination of GO following MPO exposure. The here-reported predictions could be the root cause of the experimentally observed low stability of individual GO sheets during the MPO catalytic cycle.

Arterial vascularization of the mandible and soft tissues. Anatomic study.

PURPOSE: The literature has for too long described the arterial supply of the mandible as coming from a single artery, the inferior alveolar artery, and being of the terminal type. Rather, it appears to come from an extensive and complex arterial network dependent on the lingual, facial, and maxillary arteries and their collateral branches. Our study aims to confirm and demonstrate the arterial vascular richness of the mandible and to establish arterial mapping. METHODS: The arterial vascularization of the mandible was revealed in six anatomic specimens after performing selective injections of the lingual, facial, and maxillary arteries with different dyes. A specimen was injected intra-arterially with colored latex at the level of the maxillary artery for a morphometric study. RESULTS: Eighteen selective arterial injections were performed on six anatomic specimens. The mucocutaneous, musculoperiosteal, and intramedullary vascularizations were analyzed. Each of the arteries has a defined and delimited cutaneo-mucous vascular territory. The facial and maxillary arteries supply the musculoperiosteal vascularization of the mandible from the condyle to the symphysis. The lingual artery supplies only the inner cortex of the parasymphyseal and symphyseal regions. The facial and maxillary arteries provide intramedullary vascularization from the angle of the mandible to the parasymphysis. The vascularization of the symphysis depends on the facial artery. No staining was found in the condyle region. Neoprene latex injection was performed on an anatomic specimen, revealing a permeable anastomosis between the inferior alveolar and facial arteries. CONCLUSION: The arterial vascularization of the mandible is dependent on the maxillary, facial, and lingual arteries. This is a network vasculature. This study makes it possible to establish an arterial map of the mandible. The presence of an anastomosis between the inferior alveolar artery and the facial artery confirms the existence of dynamic and borrowed vascularization. Knowledge of this arterial system makes it possible to adapt maxillofacial surgical care and to anticipate possible intraoperative complications.

N 1s core-level binding energies in nitrogen-doped carbon nanotubes: a combined experimental and theoretical study.

We report a combined experimental and theoretical study dedicated to analyze the N 1s core-level binding energies (CLBE) in N-doped carbon nanotubes (N-CNTs). X-ray photoelectron spectroscopy (XPS) data are obtained from N-CNT samples synthesized using the chemical vapor deposition technique. Extensive density functional theory (DFT) calculations are performed on various model single- and double-walled N-CNTs where N 1s CLBEs are determined using Koopman's theorem. However, we also present additional calculations within the (Z + 1) approximation to analyze the role of final-state effects. From XPS data up to 2 at% of N content was found in our samples and the high resolution analysis of the N 1s line shows, according to previous experimental results, that N species exist in CNTs as graphitic, pyrrolic, pyridinic, and molecular configurations. However, peak decomposition is characterized by five broad Gaussian curves that overlap considerably among them, having different widths and heights, implying a more complex distribution of N atoms within the structures. DFT calculations performed on model N-CNTs reveal a strong dependence of N 1s CLBE values and their shifts on the local atomic environment. Different types of graphitic N cover an energy range of 3 eV, while various configurations for pyridinic, pyrrolic, and molecular species reveal a dispersion in their energy values of 5.7, 2.7, and 5.2 eV, respectively. The previous distributions of theoretical CLBEs also strongly overlap, implying that some peaks in the XPS spectra must be understood as composite signals where the signals of different N defects coexist. We find, in agreement with the experimental data, that freestanding molecular nitrogen and (weakly interacting) encapsulated N2 within the hollow core of model CNTs have very similar CLBEs. Furthermore, we predict that chemisorbed N2 on defective regions of the nanotube walls has N 1s binding energy values that are considerably larger when compared to encapsulated N2, thus making possible their identification. In contrast to previous reports, we find a nontrivial dependence between CLBEs and the local electronic occupation at N sites. The assignment of spectral details in the XPS data to well-defined N-defects on CNTs is not straightforward and needs to be more deeply analyzed.

Significant and variable linear polarization during the prompt optical flash of GRB 160625B.

Newly formed black holes of stellar mass launch collimated outflows (jets) of ionized matter that approach the speed of light. These outflows power prompt, brief and intense flashes of γ-rays known as γ-ray bursts (GRBs), followed by longer-lived afterglow radiation that is detected across the electromagnetic spectrum. Measuring the polarization of the observed GRB radiation provides a direct probe of the magnetic fields in the collimated jets. Rapid-response polarimetric observations of newly discovered bursts have probed the initial afterglow phase, and show that, minutes after the prompt emission has ended, the degree of linear polarization can be as high as 30 per cent-consistent with the idea that a stable, globally ordered magnetic field permeates the jet at large distances from the central source. By contrast, optical and γ-ray observations during the prompt phase have led to discordant and often controversial results, and no definitive conclusions have been reached regarding the origin of the prompt radiation or the configuration of the magnetic field. Here we report the detection of substantial (8.3 ± 0.8 per cent from our most conservative simulation), variable linear polarization of a prompt optical flash that accompanied the extremely energetic and long-lived prompt γ-ray emission from GRB 160625B. Our measurements probe the structure of the magnetic field at an early stage of the jet, closer to its central black hole, and show that the prompt phase is produced via fast-cooling synchrotron radiation in a large-scale magnetic field that is advected from the black hole and distorted by dissipation processes within the jet.

Nocturnal agitation: From sleep state dissociation to sleep-related dissociative state.

Nocturnal agitation refers to a broad spectrum of symptoms from simple movements to aggressive behaviors with partial or complete loss of awareness. An accurate identification of its etiology is critical for appropriate therapeutic intervention. In children and young adults, distinguishing between non-rapid eye movement (NREM) sleep parasomnias and psychogenic non-parasomniac manifestations, a condition known as sleep-related dissociative disorder (SRDD), can be challenging. This review aims to summarize current clinical, neurophysiological, and epidemiological knowledge on NREM parasomnia and SRDD, and to present the pathophysiological hypotheses underlying these nocturnal manifestations. Sleepwalking, sleep terror and confusional arousals are the three main presentations of NREM parasomnias and share common clinical characteristics. Parasomniac episodes generally occur 30minutes to three hours after sleep-onset, they are usually short, lasting no more than few minutes and involve non-stereotyped, clumsy behaviors with frequent amnesia. The prevalence of NREM parasomnia decreases from 15-30% in children to 2-4% in adults. Parasomniac episodes are incomplete awakening from the deepest NREM sleep and are characterized by a dissociated brain activity, with a wake-like activation in motor and limbic structures and a preserved sleep in the fronto-parietal regions. SRDD is a less known condition characterized by dramatic, often very long episodes with frequent aggressive and potentially dangerous behaviors. SRDD episodes frequently occur in quiet wakefulness before falling asleep. These dissociative manifestations are frequently observed in the context of psychological trauma. The pathophysiology of SRDD is poorly understood but could involve transient changes in brain connectivity due to labile sleep-wake boundaries in predisposed individuals. We hypothesize that SRDD and NREM parasomnia are forms of sleep-related dissociative states favored by a sleep-wake state dissociation during sleep-onset and awakening process, respectively.

Evaluation of hypersomnolence: From symptoms to diagnosis, a multidimensional approach.

Hypersomnolence is a major public health issue given its high frequency, its impact on academic/occupational functioning and on accidentology, as well as its heavy socio-economic burden. The positive and aetiological diagnosis is crucial, as it determines the therapeutic strategy. It must consider the following aspects: i) hypersomnolence is a complex concept referring to symptoms as varied as excessive daytime sleepiness, excessive need for sleep, sleep inertia, or drowsiness, all of which warrant specific dedicated investigations; ii) the boundary between physiological and abnormal hypersomnolence is blurred, since most symptoms can be encountered in the general population to varying degrees without being considered as pathological, meaning that their severity, frequency, context of occurrence and related impairment need to be carefully assessed; iii) investigation of hypersomnolence relies on scales/questionnaires as well as behavioural and neurophysiological tests, which measure one or more dimensions, keeping in mind the possible discrepancy between objective and subjective assessment; iv) aetiological reasoning is driven by knowledge of the main sleep regulation mechanisms, epidemiology, and associated symptoms. The need to assess hypersomnolence is growing, both for its management, and for assessing the efficacy of treatments. The landscape of tools available for investigating hypersomnolence is constantly evolving, in parallel with research into sleep physiology and technical advances. These investigations face the challenges of reconciling subjective perception and objective data, making tools accessible to as many people as possible and predicting the risk of accidents.

[Multidisciplinary approach of the sequelae one month after hospital discharge in patients with severe bilateral COVID-19 pneumonia, are there differences depending on the respiratory therapy used during admission to intensive care?] / Valoración multidisciplinar de las secuelas al mes del alta hospitalaria por neumonía grave COVID-19, ¿existen diferencias en función de la terapia respiratoria empleada durante su ingreso en Cuidados Intensivos?

Objective: To describe the sequelae one month after hospital discharge in patients who required admission to intensive care for severe COVID-19 pneumonia and to analyze the differences between those who received therapy exclusively with high-flow oxygen therapy compared to those who required invasive mechanical ventilation. Design: Cohort, prospective and observational study. Setting: Post-intensive care multidisciplinary program. Patients or participants: Patients who survived admission to the intensive care unit (ICU) for severe COVID-19 pneumonia from April 2020 to October 2021. Interventions: Inclusion in the post-ICU multidisciplinary program. Main variables of interest: Motor, sensory, psychological/psychiatric, respiratory and nutritional sequelae after hospital admission. Results: One hundred and four patients were included. 48 patients received high-flow nasal oxygen therapy (ONAF) and 56 invasive mechanical ventilation (IMV). The main sequelae found were distal neuropathy (33.9% IMV vs. 10.4% ONAF); brachial plexopathy (10.7% IMV vs. 0% ONAF); decrease in grip strength: right hand 20.67 kg (± 8.27) in VMI vs. 31.8 kg (± 11.59) in ONAF and left hand 19.39 kg (± 8.45) in VMI vs. 30.26 kg (± 12.74) in ONAF; and limited muscle balance in the lower limbs (28.6% VMI vs. 8.6% ONAF). The differences observed between both groups did not reach statistical significance in the multivariable study. Conclusions: The results obtained after the multivariate study suggest that there are no differences in the perceived physical sequelae one month after hospital discharge depending on the respiratory therapy used, whether it was high-flow nasal oxygen therapy or prolonged mechanical ventilation, although more studies are needed to be able to draw conclusions.

Comparison of chromium and cobalt serum levels between a modular neck stem and its monoblock counterpart in primary total hip arthroplasty.

BACKGROUND: The addition of junctions in modular stems implies a greater susceptibility to corrosion. PURPOSE: The aim of this study is to compare serum chromium and cobalt levels after using a bimodular stem and its monoblock counterpart in primary total hip arthroplasty. Postoperative clinical scores were also compared. PATIENTS AND METHODS: A prospective cohort study between 2012 and 2015 was designed. One arm of the cohort included patients with the cementless modular neck stem H-Max M® and the other with the cementless monoblock stem counterpart H-Max S®. RESULTS: No statistically significant difference was found in chromium value between groups (p = 0.621) at two years postoperative. Cobalt value was higher in the modular group (p = < 0.001). No statistically significant difference was found in clinical postoperative scores except for the Harris Hip Score, with better results at six months in modular group (p = 0.007). CONCLUSIONS: Higher serum cobalt level in the modular group has limited the use of modular stems in our daily practice. Advantages of modular stem were not found. LEVEL OF EVIDENCE: II.

Real-life analysis on safety and efficacy of asciminib for ponatinib pretreated patients with chronic myeloid leukemia.

Failure of second-generation tyrosine kinase inhibitors (2GTKI) is a challenging situation in patients with chronic myeloid leukemia (CML). Asciminib, recently approved by the US Federal Drug Administration, has demonstrated in clinical trials a good efficacy and safety profile after failure of 2GTKI. However, no study has specifically addressed response rates to asciminib in ponatinib pretreated patients (PPT). Here, we present data on responses to asciminib from 52 patients in clinical practice, 20 of them (38%) with prior ponatinib exposure. We analyzed retrospectively responses and toxicities under asciminib and compared results between PPT and non-PPT patients.After a median follow-up of 30 months, 34 patients (65%) switched to asciminib due to intolerance and 18 (35%) due to resistance to prior TKIs. Forty-six patients (88%) had received at least 3 prior TKIs. Regarding responses, complete cytogenetic response was achieved or maintained in 74% and 53% for non-PPT and PPT patients, respectively. Deeper responses such as major molecular response and molecular response 4.5 were achieved in 65% and 19% in non-PPT versus 32% and 11% in PPT, respectively. Two patients (4%) harbored the T315I mutation, both PPT.In terms of toxicities, non-PPT displayed 22% grade 3-4 TEAE versus 20% in PPT. Four patients (20% of PPT) suffered from cross-intolerance with asciminib as they did under ponatinib.Our data supports asciminib as a promising alternative in resistant and intolerant non-PPT patients, as well as in intolerant PPT patients; the resistant PPT subset remains as a challenging group in need of further therapeutic options.

Beyond tobacco - the secondary impact of substance misuse in chronic obstructive lung disease.

BackgroundChronic obstructive lung disease, specifically chronic asthma and COPD, impacts more than 500 million adults worldwide, and is associated with high healthcare spending and significant disease-related morbidity. While the direct impact of substance use disorder is well documented, little is known about the indirect impact of substance misuse within this patient population. The healthcare cost and indirect morbidity secondary to substance misuse in obstructive lung disease has yet to be quantified.ObjectiveTo determine the indirect impact of substance misuse on disease severity, healthcare utilization and healthcare costs in patients with chronic obstructive lung disease across the United States.MethodsUtilizing data from the 2012-2015 National Readmissions Database (NRD) patients with a diagnosis of COPD or asthma were identified. Documented substance misuse, rates of hospitalization, frequency of hospital readmission, markers of admission severity and cost were assessed utilizing weighted regression analysis.ResultsA total of 1,087,226 patients with an index admission for asthma or COPD were identified. Substance misuse was documented in 4.0% of patients. Substance misuse was associated with a 30% increase in odds of readmission and a higher cost per index admission. The additional index admission costs totaled $24 million for our cohort.Conclusion Substance misuse is associated with an increase in healthcare utilization and healthcare cost in patients with chronic obstructive lung disease. Targeting substance misuse in this patient population has the potential for significant cost savings to the healthcare system.

Oral microbiome and systemic antineoplastics in cancer treatment: A systematic review.

BACKGROUND: Oral mucositis is one of the most common side effects in cancer patients receiving systemic antineoplastics. However, the underlying biological mechanisms leading to this condition are still unclear. For this reason, it has been hypothesised that systemic antineoplastics may cause an imbalance on the oral microbiota that subsequently triggers oral mucosa damage. MATERIAL AND METHODS: A systematic review was performed following the PRISMA protocol and the PICO question established was: patients diagnosed with cancer, who are candidates for receiving systemic antineoplastics (P=Patients), that undergo oral microbiome determinations (I=Intervention), before and after systemic antineoplastics administration (C=Comparison), to analyse changes in the oral microbiome composition (O=Outcome). The bibliographic search was carried out in PubMed and other scientific repositories. RESULTS: Out of 166 obtained articles, only 5 met eligibility criteria. Acute myeloid leukaemia (AML) was the most frequent type of cancer (40 %) among the participants. Only one of the studies included a control group of healthy subjects. Heterogeneity in the protocols and approaches of the included studies hindered a detailed comparison of the outcomes. However, it was stated that a decrease in bacteria α diversity is often associated with oral mucositis. On the other hand, fungal diversity was not associated with oral mucositis although α diversity was lower at baseline on patients developing oral candidiasis. CONCLUSIONS: There is insufficient scientific evidence of oral microbiological changes in patients undergoing systemic antineoplastics. Further investigations ought to be carried out to identify microorganisms that might play a key role in the pathogenesis of oral mucosa damage in patients undergoing systemic antineoplastics.

Umbilical cord clamping and skin-to-skin contact in deliveries from women positive for SARS-CoV-2: a prospective observational study.

OBJECTIVE: To demonstrate that delayed cord clamping (DCC) is safe in mothers with confirmed SARS-CoV-2 infection. DESIGN, SETTING AND PARTICIPANTS: Prospective observational study involving epidemiological information from 403 pregnant women with SARS-CoV-2 between 1 March and 31 May 2020. Data were collected from 70 centres that participate in the Spanish Registry of COVID-19. METHODS: Patients' information was collected from their medical chart. MAIN OUTCOMES AND MEASURES: The rate of perinatal transmission of SARS-CoV-2 and development of the infection in neonates within 14 days postpartum. RESULTS: The early cord clamping (ECC) group consisted of 231 infants (57.3%) and the DCC group consisted of 172 infants (42.7%). Five positive newborns (1.7% of total tests performed) were identified with the nasopharyngeal PCR tests performed in the first 12 hours postpartum, two from the ECC group (1.7%) and three from the DCC group (3.6%). No significant differences between groups were found regarding neonatal tests for SARS-CoV-2. No confirmed cases of vertical transmission were detected. The percentage of mothers who made skin-to-skin contact within the first 24 hours after delivery was significantly higher in the DCC group (84.3% versus 45.9%). Breastfeeding in the immediate postpartum period was also significantly higher in the DCC group (77.3% versus 50.2%). CONCLUSIONS: The results of our study show no differences in perinatal outcomes when performing ECC or DCC, and skin-to-skin contact, or breastfeeding. TWEETABLE ABSTRACT: This study demonstrates that delayed cord clamping is safe in mothers with confirmed SARS-CoV-2 infection.

Protocol for presurgical and anesthetic management of pheochromocytomas and sympathetic paragangliomas: a multidisciplinary approach.

OBJECTIVE: To offer a practical guide for the presurgical and anesthetic management of pheochromocytomas and sympathetic paragangliomas (PGLs). METHODS: This protocol was based on a comprehensive review of the literature and on our own multidisciplinary team's experience from managing pheochromocytoma and sympathetic PGLs at a referral center. RESULTS: Patients with pheochromocytomas and sympathetic paragangliomas (PGLs) may develop potentially life-threatening complications, especially during surgical procedures. A complete biochemical, radiological, genetic, and cardiological assessment is recommended in the preoperative stage as it provides an evaluation of the risk of surgical complications and malignancy, allowing individualization of the presurgical treatment. Treatment with α-blockade and proper volume expansion in the preoperative stage significantly reduces the perioperative morbidity. During surgery, the anesthesiologist should look for a deep anesthetic level that inhibits the cardiovascular effects of catecholamines to minimize the risk of intraoperative complications. CONCLUSIONS: An optimal presurgical evaluation of pheochromocytomas/ sympathetic PGL requires a multidisciplinary approach, including a complete hormonal, radiological, cardiac, genetic, and functioning evaluation in most cases. A proper preoperative evaluation in combination with strict blood pressure and heart rate control, and blood volume status optimization, will significantly reduce the risk of intraoperative and perioperative complications. In those patients who unfortunately develop intraoperative complications, the role of the anesthesiologist is essential since the selection of the appropriate management has a direct impact on morbimortality reduction.

Sex-based differences in timely emergency department evaluations for patients with drug poisoning.

OBJECTIVES: Unintentional poisoning was the leading cause of injury-related death in the United States in 2017. Prescribed and illicit drugs are the most common cause of poisoning, and timely management in the emergency department (ED) is important. Our aim was to identify any disparities in wait times associated with sex for drug poisoning-related ED visits. STUDY DESIGN: We examined ED visits using data from the 2009-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS). METHODS: Drug poisoning-related visits were identified using the International Classification of Diseases, Ninth or Tenth Revision, Clinical Modification codes. Delayed assessment was defined as wait times exceeding the recommended triage time. Weighted logistic regression was used. RESULTS: The average age was 36 years (standard error = 1.1), 54% female, 87% White and 29% had delayed assessment. Most common drugs were psychotropics (45%) and opioids (32%). Adjusting for race, payment source, urgency, multiple drug types and NSAIDs, females who had poisoning by substances other than opioids had 2.1 times higher likelihood of having a delayed assessment compared with males (odds ratio [95% confidence interval]: 2.1 [1.03-4.2]), although there was no difference between sexes among visits with opioid poisoning (P = 0.27). Neither race (P = 0.23) nor payment source (P = 0.22) were associated with delayed assessment, and the sex association was consistent across these groups. CONCLUSIONS: Females with non-opioid drug poisoning were more likely to have delayed assessment than men. None of the other demographic factors demonstrated a correlation. Identifying more populations vulnerable to delays in the ED can help guide the development of interventions and policies to expedite care and attenuate existing disparities.

Factors that affect physicochemical and acid-base properties of compost and vermicompost and its potential use as a soil amendment.

Composting and vermicomposting have attracted attention in relation to both waste management and the potential to produce organic amendments that could improve soil quality. The main differences between compost depend on the feedstock, the production process, and the degree of maturity. In the present study, samples of compost of different origin (food and green waste, livestock waste, algae waste, urban waste or sewage sludge) or subjected to different composting methods (traditional or using earthworms) were collected for analysis. Additionally, samples collected at various stages of the composting process were compared (raw material, 15 and 30 days of composting, and final compost). Different analysis and techniques were used to establish the chemical composition, physicochemical and acid-base properties of compost samples and the organic matter extracts. The correlations obtained (between the abundance of acid groups in different extracts of the compost or between the cation exchange capacity and the C/N atomic ratio) would allow for predicting the compost behaviour based on certain characteristics, and a reduction in the number of parameters determined experimentally, thus facilitating comparisons between different compost. In addition, the potential value of the compost as amendment was tested with a Haplic Cambisol from a mining area. The application of compost increased the pH, the organic matter and nutrient content, and promoted seed germination and root growth.

Non-Invertible Public Key Certificates.

Post-quantum public cryptosystems introduced so far do not define a scalable public key infrastructure for the quantum era. We demonstrate here a public certification system based on Lizama's non-invertible key exchange protocol which can be used to implement a secure, scalable, interoperable and efficient public key infrastructure (PKI). We show functionality of certificates across different certification domains. Finally, we discuss a method that enables non-invertible certificates to exhibit perfect forward secrecy (PFS).

Beyond the Limits of Shannon's Information in Quantum Key Distribution.

We present a new post-processing method for Quantum Key Distribution (QKD) that raises cubically the secret key rate in the number of double matching detection events. In Shannon's communication model, information is prepared at Alice's side, and it is then intended to pass it over a noisy channel. In our approach, secret bits do not rely in Alice's transmitted quantum bits but in Bob's basis measurement choices. Therefore, measured bits are publicly revealed, while bases selections remain secret. Our method implements sifting, reconciliation, and amplification in a unique process, and it just requires a round iteration; no redundancy bits are sent, and there is no limit in the correctable error percentage. Moreover, this method can be implemented as a post-processing software into QKD technologies already in use.

Advanced-stage mycosis fungoides: role of the signal transducer and activator of transcription 3, nuclear factor-κB and nuclear factor of activated T cells pathways.

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.