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Sammar Fathy Elhabal,1 Nashwa Abdelaal,2 Saeed Abdul Kareem Saeed Al-Zuhairy,3 Mohamed Fathi Mohamed Elrefai,4,5 Ahmed Mohsen Elsaid Hamdan,6 Mohamed Mansour Khalifa,7 Sandra Hababeh,8 Mohammad Ahmad Khasawneh,9 Gehad M Khamis,10 Jakline Nelson,11 Passant M Mohie,10 Rania A Gad,12 Amira Rizk,13 Soad L Kabil,14 Mohamed Kandeel El-Ashery,15,16 Bhaskara R Jasti,17 Nahla A Elzohairy,18,19 Tayseer Elnawawy,20 Fatma E Hassan,21,22 Mohamed A El- Nabarawi23 1Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 2Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA; 3Department of Pharmacy, Kut University College, Kut, Wasit, Iraq; 4Department of Anatomy, Histology, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 5Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 6Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk, Saudi Arabia; 7Department of Human Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt; 8Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 9Department of Chemistry, College of Science U.A.E. University, Al-Ain, United Arab Emirates; 10Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 11Department of Microbiology and Immunology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 12Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt; 13Food Science and Technology Department, Faculty of Agricultural, Tanta University, Tanta, Egypt; 14Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 15Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 16Medicinal Chemistry Department, Faculty of Pharmacy, King Salman International University, Ras-Sedr, South Sinai, Egypt; 17Department of Pharmaceutics and Medicinal Chemistry, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA, USA; 18Air Force Specialized Hospital, Cairo, Egypt; 19Department of Microbiology and Immunology, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo, Egypt; 20Department of Pharmaceutics, Egyptian Drug Authority, Cairo, Egypt; 21Medical Physiology Department, Faculty of Medicine, Cairo University, Giza, Egypt; 22General Medicine Practice Program, Department of Physiology, Batterjee Medical College, Jeddah, Saudi Arabia; 23Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, EgyptCorrespondence: Sammar Fathy Elhabal, Email Sammar.Fathy@pharm.mti.edu.eg; sammar_fathy2007@yahoo.com; Mohamed A El- Nabarawi, Email mohamed.elnabarawi@pharm.cu.edu.egBackground: Diabetes Mellitus is a multisystem chronic pandemic, wound inflammation, and healing are still major issues for diabetic patients who may suffer from ulcers, gangrene, and other wounds from uncontrolled chronic hyperglycemia. Marshmallows or Althaea officinalis (A.O.) contain bioactive compounds such as flavonoids and phenolics that support wound healing via antioxidant, anti-inflammatory, and antibacterial properties. Our study aimed to develop a combination of eco-friendly formulations of green synthesis of ZnO-NPs by Althaea officinalis extract and further incorporate them into 2% chitosan (CS) gel.Method and Results: First, develop eco-friendly green Zinc Oxide Nanoparticles (ZnO-NPs) and incorporate them into a 2% chitosan (CS) gel. In-vitro study performed by UV-visible spectrum analysis showed a sharp peak at 390 nm, and Energy-dispersive X-ray (EDX) spectrometry showed a peak of zinc and oxygen. Besides, Fourier transforms infrared (FTIR) was used to qualitatively validate biosynthesized ZnO-NPs, and transmission electron microscope (TEM) showed spherical nanoparticles with mean sizes of 76 nm and Zeta potential +30mV. The antibacterial potential of A.O.-ZnO-NPs-Cs was examined by the diffusion agar method against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Based on the zone of inhibition and minimal inhibitory indices (MIC). In addition, an in-silico study investigated the binding affinity of A.O. major components to the expected biological targets that may aid wound healing. Althaea Officinalis, A.O-ZnO-NPs group showed reduced downregulation of IL-6, IL-1β, and TNF-α and increased IL-10 levels compared to the control group signaling pathway expression levels confirming the improved anti-inflammatory effect of the self-assembly method. In-vivo study and histopathological analysis revealed the superiority of the nanoparticles in reducing signs of inflammation and wound incision in rat models.Conclusion: These biocompatible green zinc oxide nanoparticles, by using Althaea Officinalis chitosan gel ensure an excellent new therapeutic approach for quickening diabetic wound healing. Keywords: wound healing, antimicrobial, antioxidant, Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, chitosan, wound concentration, wound incision

Abstract Objective: To estimate the economic burden associated with COVID-19 in Córdoba, Colombia, 2020 and 2021. Methods: Economic burden study. Direct costs were analyzed from the third-party payer perspective using healthcare administrative databases and interviews from a cohort of confirmed COVID-19 cases from Córdoba. Costing aggregation was performed by the bottom-up method. Indirect costs were estimated using the productivity loss approach. Contrast tests and statistical models were estimated at 5% significance. Results: We studied 1,800 COVID-19 cases. The average economic cost of COVID-19 per episode was estimated at US$ 2,519 (95%CI 1,980;3,047). The direct medical cost component accounted for 92.9% of the total; out-of-pocket and indirect costs accounted for 2% and 5.1%, respectively. Conclusion: COVID-19 economic cost was mainly due to direct medical costs. This study provided evidence of the economic burden faced by households due to COVID-19, with the most vulnerable households bearing much of the burden on their income.

ABSTRACT Streptococcus agalactiae [group B Streptococcus (GBS)] poses a major threat as the primary cause of early-onset neonatal invasive disease, particularly when mothers are colonized rectovaginally. Although culture remains the gold standard for antepartum GBS screening, quantitative polymerase chain reaction (qPCR) offers advantages in terms of sensitivity and turnaround time. The aim of this study was to validate the clinical utility of an automated qPCR laboratory-developed test (LDT) for antepartum GBS screening using the Panther Fusion Open Access system (Hologic, California, USA). The LDT targeted a conserved region of the GBS surface immunogenic protein gene, demonstrating no cross-reactivity and high coverage (99.82%–99.99%). The limit of detection (LoD) was 118 CFU/mL. Comparison with commercial qPCR assays (Panther Fusion GBS and VIASURE Streptococcus B Real-Time) revealed an overall agreement of 99.7%, with a robust Cohen’s kappa coefficient of 0.992. Testing of 285 rectovaginal swabs from pregnant women and 15 external quality assessment samples demonstrated exceptional diagnostic performance of the LDT, achieving a diagnostic sensitivity and specificity of 100%, underscoring its accuracy. Prevalence and predictive values were also determined to reinforce test reliability. Our research highlights the limitations of culture-based screening and supports the suitability of our qPCR-based LDT for GBS detection in a clinical setting.IMPORTANCERectovaginal colonization by GBS is a major risk factor for early-onset invasive neonatal disease. The most effective approach to reducing the incidence of early-onset disease (EOD) has been described as universal screening, involving assessment of GBS colonization status in late pregnancy and intrapartum antibiotic prophylaxis. Despite its turnaround time and sensitivity limitations, culture remains the gold standard method for GBS screening. However, nucleic acid amplification-based tests, such as qPCR, have been utilized due to their speed and high sensitivity and specificity. This study validated the clinical usefulness of an automated qPCR-LDT for antepartum GBS screening through the Panther Fusion Open Access system (Hologic). Our study addresses the critical need for more robust, sensitive, and rapid strategies for GBS screening in pregnant women that could favorably impact the incidence of EOD.

The current study focused on investigating the effectiveness of a flexible structural approach for mitigating local scour along longitudinal walls in rivers with well-levelled granular beds. To carry out this study, a hydraulic channel was used as the experimental setup. The experiment aimed to evaluate the influence of several key parameters, including slope (ranging from 1 % to 2.5 %), flow rate (set at 0.017 m3/s and 0.030 m3/s) and width of the flexible structure (which was varied at 0.08, 0.12, and 0.15 m). The results of this study are remarkable and have important implications for river engineering and erosion control. The 0.15 m flexible system exhibited a remarkable ability to decrease scouring, especially under conditions of high flows and steeper slopes. In such scenarios, the flexible structure demonstrated efficiencies exceeding 80 %, signifying a substantial reduction in local scour. These findings are important because they suggest that the flexible structural approach can be an effective solution for mitigating scour in rivers with well-levelled granular beds.

In this paper, a novel dual-slant polarized three-dimensional (3D) periodic Luneburg lens with a diameter of 390 mm ( $4.6\lambda _{0}$ at 3.55 GHz) is presented. Copper-plated cubes with truncated corners are placed in a body-centered cubic (BCC) lattice and held together with layers of Rohacell foam. The sizes of the cubes are varied to realize the gradient refractive index (GRIN) profile of a generalized Luneburg lens at a low cost, with a low weight and loss. The designed Luneburg lens operates from 3.3 to 3.8 GHz with a total weight of 1 kg. The quasi-isotropic response of the proposed periodic structure allows a wide angle coverage. Measured results show that the lens antenna can achieve a peak gain of 22 dBi with a scanning loss of less than 0.4 dB in a wide angular range in both the azimuth and the elevation plane. Importantly, the proposed lens antenna design achieves a cross-polarization level below peak gain of less than −19 dB at all angles for the two slant polarizations of the feed, while comparable designs report up to −11 dB at given angular directions. This high-gain multi-beam antenna with a commercially viable design is suitable for wireless communications at low microwave frequencies.

We consider the detection and characterization of brain state transitions based on ongoing electroencephalography (EEG). Here, a brain state represents a specific brain dynamical regime or mode of operation that produces a characteristic quasi-stable pattern of activity at the topography, sources, or network levels. These states and their transitions over time can reflect fundamental computational properties of the brain, shaping human behavior and brain function. The hidden Markov model (HMM) has emerged as a useful tool for uncovering the hidden dynamics of brain state transitions based on observed data. However, the limitations of the Geometric distribution of states’ durations (dwell times) implicit in the standard HMM, make it sub-optimal for modeling brain states in EEG. We propose using hidden semi Markov models (HSMM), a generalization of HMM that allows modeling the brain states duration distributions explicitly. We present a Bayesian formulation of HSMM and use the variational Bayes framework to efficiently estimate the HSMM parameters, the number of brain states, and select among candidate brain state duration distributions. We assess HSMM performance against HMM on simulated data and demonstrate that the accurate modeling of state durations is paramount for making reliable inference when the task at hand requires accurate model predictions. Finally, we use actual resting-state EEG data to illustrate the benefits of the approach in practice. We demonstrate that the possibility of modeling brain state durations explicitly provides a new way for investigating the nature of the neural dynamics that generated the EEG data.

Human–animal relations have been a fruitful research topic worldwide. The importance of deer in hunter–gatherer societies is undeniable, with cervids being commonly found in archaeological and past artistic records, with a notable amount of information recovered in the Iberian Peninsula. This relevance continues during Late Prehistory, but the attempt to discuss cervids under broader perspectives and based on different types of data is not as common. We intend to approach human–deer relations in Central and Southern Portuguese Late Prehistory by considering the zooarchaeological records, both deer abundance in faunal spectra and their presence in “meaningful” assemblages and structured depositions, as well as the use of deer and deer body parts in other socio–cultural and ideological practices. The synthesis of available data shows that human–deer relations changed through time and space, with different abundances related to hunting depending on chronology and geography. The use of deer or their body parts as a resource of symbolic nature also varied, being included in food-sharing events, offerings, structured depositions, and graphic representations. Changeability is part of the different relationships, ontologies, and cosmogonies that humans and deer developed in the Late Prehistoric relational world.

ObjectiveTo estimate the baseline to measure one of the three indicators of the World Health Organization (WHO) End TB strategy (2015-2035), measure the costs incurred by patients affected by tuberculosis (TB) during a treatment episode and estimate the proportion of households facing catastrophic costs (CC) and associated risk factors, in Colombia, 2021.Material and methodsA nationally representative cross-sectional survey was conducted among participants on TB treatment in Colombia, using telephone interviews due to the exceptional context of the COVID-19 pandemic. The survey collected household costs (direct [medical and non-medical out-of-pocket expenses] and indirect) over an episode of TB, loss of time, coping measures, self-reported income, and asset ownership. Total costs were expressed as a proportion of annual household income and analyzed for risk factors of CC (defined as costs above 20% annual household income).ResultsThe proportion of TB-affected households incurring in costs above 20% annual household income (CC) was 51.7% (95%CI: 45.4-58.0) overall, 51.3% (95%CI: 44.9-57.7) among patients with drug-sensitive (DS) TB, and 65.0% (95%CI: 48.0-82.0) among drug-resistant (DR). The average patient cost of a TB case in Colombia was $1,218 (95%CI 1,106-1,330) including $860.9 (95%CI 776.1-945.7) for non-medical costs, $339 (95%CI 257-421) for the indirect costs, and $18.1 (95%CI 11.9-24.4) for the medical costs. The factors that influenced the probability of facing CC were income quintile, job loss, DR-TB patient, and TB type.ConclusionMain cost drivers for CC were non-medical out-of-pocket expenses and income loss (indirect costs). Current social protection programs ought to be expanded to mitigate the proportion of TB-affected households facing CC in Colombia, especially those with lower income levels.

This study assesses the feasibility of hepatitis B (HBV) and C (HCV) elimination using an analysis of trends of epidemiology data (1990–2019) from the Global Burden of Disease Study. Joinpoint regression analysis was used to identify significantly changing points in the trends of Age-standardized Prevalence Rates (ASPR) and Age-standardized Mortality Rates (ASMR) and to estimate the annual percentage changes (APC) and the average annual percentage changes (AAPC) for the period. The Sociodemographic Index (SDI) was used to analyze trends between countries. The total percentage change of the ASPR (2019/1990) was −31.4% and −12.8% for HBV and HCV worldwide, respectively; the rate ratio (HBV/HCV) was 2.5. Mortality had decreased for HBV but not for HCV. The total percentage change for the ASMR (2019/1990) was −26.7% and 10.0% for HBV and HCV, respectively. While the ASMR of HBV decreased, HCV increased during this period. The percentage change in ASMR of HBV was highest in countries with high–middle SDI and lowest in countries with high SDI. For HCV, the percentage change in ASMR was highest in countries with high SDI (increase), and only in countries with low SDI did it decrease. The global HBV and HCV rates have fallen with different AAPCs associated with the SDI. Despite the advances, there is still a long way to go to achieve the 2030 elimination goals. An important challenge is related to finding a way to speed up the yearly rate at which the decline is happening.

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38).

This article provides for the first time a detailed discussion of the optimal assignment of adjacent output phase differences in terms of matrix performance out of all possible combinations in generalized one-dimensional parallel switching matrices with four beams. In this specific case, the topology of the proposed matrix reduces to that of a single-layer Butler matrix, connecting hybrid couplers and crossovers with adequate phase shifters. The values of the phase shift required are dependent on the assignment of the output phase differences, which in turn is shown to have an impact on the radiation characteristics of the linear array fed by such networks when imposing constraints on the matrix layout for a more generic implementation. The configuration having the smallest phase difference with reference to the transmission phase of a straight waveguide with the same length as the coupled region of the crossover is chosen and compared with the conventional well-known Butler matrix. The two matrix configurations are implemented using post-wall waveguides designed to operate over the band 20 GHz – 24 GHz. The prototypes are manufactured and tested, using transitions to standard waveguide WR42. The measured results confirm the benefits of the identified optimal adjacent phase difference assignment in terms of transmission coefficients, reflection coefficients, phase differences between adjacent output ports, and frequency dependence of the array factor. These results will also benefit the design of larger generalized one-dimensional parallel switching matrices.

This paper presents a design of a two-dimensional (2-D) $6\times 4$ -way hollow waveguide beam-switching matrix working at 28.25 GHz, with a fractional bandwidth of 7.1%. It is the first time that a 2-D one-body hollow waveguide beam-switching matrix is proposed with different number of beams in two orthogonal directions. This matrix is partially adopting two-plane couplers to reduce its overall dimensions. A prototype of the complete matrix is manufactured and measured using a planar scanning near-field setup to verify the simulation results. At the center frequency of 28.25 GHz, the highest directivity is obtained for the beam having the smallest tilting angle, with a value of 21.1 dBi in simulation and 21.3 dBi in measurement. The lowest directivity corresponds to the beam having the largest tilting angle, with a simulated value of 16.0 dBi and a tilting angle of 52° from the boresight, which represents a worst-case scan loss of 5.1 dB. The measured value is overestimated in that specific case, as a consequence of the truncation in the planar near-field test setup which has higher impact on the most tilted beams. The patterns are nevertheless in good agreement and the proposed matrix is a good candidate for applications requiring a different beam distribution in two orthogonal directions.

3D-printing is leading to a major transformation in many industrial and application sectors, ranging from medical to aerospace. In the space sector, 3D-printing has firstly been adopted for the development of structural and thermal parts, such as brackets and heat pipes. In more recent years, thanks to improvements in precision and surface roughness, 3D-printing technologies have steadily been investigated also for the development of radio frequency components and advanced payloads. Indeed, the unique features of 3D-printing, including the free-form capability and the ease for customization, make these manufacturing technologies very appealing in the development of complex radio-frequency front-ends for space applications, including New Space constellations and next generation software-defined communication satellites. They also enable a drastic simplification of mechanical designs by reducing the number of interfaces and assembling screws of large radio-frequency front-ends, thus leading to significant mass savings and higher integration. This paper briefly reports on recent advances in 3D-printing that have been carried out according to the current trends in radio-frequency front-ends for satellite communications.

This work presents a full metal circularly-polarized lens-like antenna for Satcom applications at Ka-band. The antenna is composed of two continuous parallel plate waveguide (PPW) quasi-optical beamformers (QOBF), feeding an array of septum polarizers to generate circular polarization. The QOBFs operate over a wide band and provide a multi-beam coverage over a large field of view in the azimuthal plane, while maintaining a relatively simple mechanical design. The array of septum polarizers is based on a stepped profile to generate circular polarization with a good polarization purity in the uplink of Ka-band (27 - 31 GHz). The antenna is fully realized in aluminium. The antenna system provides 14 beams with alternating right/left handed circular polarization (RHCP/LHCP) with an axial ratio (AR) below 3 Db over an angular range of ±19° in the uplink of Ka-Band. The maximum gain in the azimuthal plane at 30 GHz is about 21 dB over the whole angular range, with a scan loss lower than 1.5 dB. The antenna efficiency is better than 78% for all beams in the operative band.

Objectives: Venetoclax combinations are a new standard for patients with acute myeloid leukemia (AML). We aimed to evaluate the safety and efficacy of these combinations in a period of accelerated approval in Latin-America. Methods: This observational study evaluated adults with acute myeloid leukemia who received venetoclax-based therapy in 11 public or private centers in Mexico and Peru for both newly diagnosed or relapsed and refractory AML. Results: Fifty patients were included; 28 with newly diagnosed (ND) AML and 22 with relapsed/refractory (RR) disease. ND patients were older (64 vs. 40 years; p < 0.001) with a lower functional capacity (ECOG ≥2 64.3% vs 9%; p < 0.001). Venetoclax was frequently combined with azacytidine (60%) and prophylactic azoles (82%) with a median maximum dose of 200 mg (range, 100–600 mg). Hematologic toxicities were common. Complete response rates including patients with incomplete hematopoietic recovery were 78.6% in ND and 45.5% in RR patients, with a median overall survival of 9.6 (95% CI 3.7–15.5) and 8 months (95% CI 4.8–11.2). Discussion: Our study showed a preferred use of venetoclax plus azacytidine over cyatrabine. Patients in the first-line setting were similar to those in the landmark studies, while most patients with relapsed disease had received prior intensive therapies. Responses were favorable, with a median survival in agreement to other reports, albeit shorter than that observed in the randomized phase-3 trials. Conclusion: Venetoclax-based therapy in AML was effective despite dose reductions and prophylactic antifungals in two middle-income countries outside of a clinical trial setting.

Abstract Solid rotor induction motors (SRIMs) are asynchronous motors suited for high speed applications. This work presents an experimental case study where standard loss segregation procedures for induction motors are performed with a two-phase smooth solid rotor induction motor in order to verify their applicability. Even though the machine is supposed to operate at high frequency, the tests are performed at reduced frequency and voltage in order to avoid the effects of time harmonics. An adjustment in the separation of losses is proposed to contemplate the effects of the high no-load slip, and the behavior of the stray losses under high per-unit slip is analyzed in a load test. The test results are finally extrapolated for the rated condition.

The potential impact of climatic deterioration on societal breakdowns in prehistory is often based on the mere coincidence of archaeological and palaeoclimatological proxies. For a more profound discussion, climate-sensitive archaeological parameters need to be identified. As agriculture and livestock are significantly affected by the recent climate crisis, the analysis of archaeobotanical and archaeozoological remains can deepen our understanding of this topic. Here, we analyze regional trajectories in subsistence and seasonal precipitation variability across southern Iberia focusing on well-known prehistoric breakdowns around 2200 and 1600 BCE. Results suggest that the ratios of the importance of sheep/goat versus swine and sheep/goat versus cattle, respectively, may serve as a proxy for prehistoric mobility. The importance of hunting deer represents a proxy for societal turnover. While no direct link is evident between climate deterioration and the archaeozoological data, archaeobotanical data reveals a potential relation to precipitation variability. In particular, a close connection to reductions in cold-season precipitation in south-east Iberia appears likely for the ratio between barley and naked wheat. The increased importance of drought-tolerant barley correlates with a trend to reduced cold-season precipitation levels after ca. 2700 BCE. We hypothesize that prehistoric people in south-east Iberia cultivated more barley in order to adapt to periods of drier cold-season climate.

Random prime numbers are an essential resource for many asymmetric cryptographic protocols. However, despite the emerging popularity of quantum random number generators (QRNGs) as sources of secure randomness, physical prime number generators have not yet been explored. In this work, we experimentally implement and characterize a vacuum-based probabilistic prime number generation scheme with an error probability of 3.5×10−15. By removing the quantum source (QS), an additional scheme based on electronic noise is derived, and a comparative analysis for increasing prime lengths is made. We observed that the QS significantly outperforms the classical scheme for small prime generation, where increases up to 585.0% in the diversity of unique primes obtained are seen. Moreover, we propose a length-agnostic statistical test for prime number sequences and apply it to the output of the uniformized randomness source, which was successful in revealing underlying biases in the output prime distributions. The resultant sequences were subsequently submitted to the NIST statistical test suite, where the quantum and classical sources passed, respectively, 86.96% and 45.34% of the total test set applied.

Enhanced Recovery After Surgery (ERAS) protocols are associated with improved clinical outcomes in cisgender breast surgery patients. However, a paucity of research exists regarding transgender and gender-diverse individuals (TGD) in the ERAS framework. The primary objective of this observational cohort study is to describe the implementation of a gender-affirming ERAS protocol and its relationship to hospital length of stay (LOS) in TGD patients following chest reconstruction surgery. The secondary aim is to identify intraoperative predictors of LOS and define variables associated with adverse outcomes. We identified 362 patients in three epochs: a traditional group (n = 144), a partial ERAS implementation group (n = 92), and an ERAS group (n = 126). Exploratory multivariable median regression modeling was performed to identify independent predictors of LOS. We report that the traditional group’s median hospital LOS was 1.1 days compared to 0.3 days in the ERAS group. Intraoperative tranexamic acid administration was associated with significantly shorter LOS (p < 0.001), reduced postoperative drainage (p < 0.001), and fewer returns to the operating room within 24 h (p = 0.047). Our data suggest that implementing a multimodal ERAS gender-affirming pathway was associated with improved patient-centered surgical outcomes such as decreased return to the operating room for hematoma evacuation, higher rates of discharge home, and reduced postoperative drainage output.

Abstract Introduction Long‐acting and extended delivery (LAED) regimens for HIV treatment and prevention offer unique benefits to expand uptake, effective use and adherence. To date, research has focused on basic and clinical science around the safety and efficacy of these products. This commentary outlines opportunities in HIV prevention and treatment programmes, both for the health system and clients, that could be addressed through the inclusion of LAED regimens and the vital role of differentiated service delivery (DSD) in ensuring efficient and equitable access. Discussion The realities and challenges within HIV treatment and prevention programmes are different. Globally, more than 28 million people are accessing HIV treatment—the vast majority on a daily fixed‐dose combination oral pill that is largely available, affordable and well‐tolerated. Many people collect extended refills outside of health facilities with clinical consultations once or twice a year. Conversely, uptake of daily oral pre‐exposure prophylaxis (PrEP) has consistently missed global targets due to limited access with high individual cost and lack of choice contributing to substantial unmet PrEP need. Recent trends in demedicalization, simplification, additional method options and DSD for PrEP have led to accelerated uptake as its availability has become more aligned with user preferences. How people currently receive HIV treatment and prevention services and their barriers to adherence must be considered for the introduction of LAED regimens to achieve the expected improvements in access and outcomes. Important considerations include the building blocks of DSD: who (provider), where (location), when (frequency) and what (package of services). Ideally, all LAED regimens will leverage DSD models that emphasize access at the community level and self‐management. For treatment, LAED regimens may address challenges with adherence but their delivery should provide clear advantages over existing oral products to be scaled. For prevention, LAED regimens expand a potential PrEP user's choice of methods, but like other methods, need to be delivered in a manner that can facilitate frequent re‐initiation. Conclusions To ensure that innovative LAED HIV treatment and prevention products reach those who most stand to benefit, service delivery and client considerations during development, trial and early implementation are critical.

Alloreactivity can drive autoimmune syndromes. After allogeneic hematopoietic stem cell transplantation (allo-HCT), chronic graft-versus-host disease (cGVHD), a B cell–associated autoimmune-like syndrome, commonly occurs. Because donor-derived B cells continually develop under selective pressure from host alloantigens, aberrant B cell receptor (BCR) activation and IgG production can emerge and contribute to cGVHD pathobiology. To better understand molecular programing of B cells in allo-HCT, we performed scRNA-Seq analysis on high numbers of purified B cells from patients. An unsupervised analysis revealed 10 clusters, distinguishable by signature genes for maturation, activation, and memory. Within the memory B cell compartment, we found striking transcriptional differences in allo-HCT patients compared with healthy or infected individuals, including potentially pathogenic atypical B cells (ABCs) that were expanded in active cGVHD. To identify intrinsic alterations in potentially pathological B cells, we interrogated all clusters for differentially expressed genes (DEGs) in active cGVHD versus patients who never had signs of immune tolerance loss (no cGVHD). Active cGVHD DEGs occurred in both naive and BCR-activated B cell clusters. Remarkably, some DEGs occurred across most clusters, suggesting common molecular programs that may promote B cell plasticity. Our study of human allo-HCT and cGVHD provides understanding of altered B cell memory during chronic alloantigen stimulation.

Abstract Electromagnetic linear-to-circular polarization converters with wide- and multi-band capabilities can simplify antenna systems where circular polarization is required. Multi-band solutions are attractive in satellite communication systems, which commonly have the additional requirement that the sense of polarization is reversed between adjacent bands. However, the design of these structures using conventional ad hoc methods relies heavily on empirical methods. Here, we employ a data-driven approach integrated with a generative adversarial network to explore the design space of the polarizer meta-atom thoroughly. Dual-band and triple-band reflective polarizers with stable performance over incident angles up to and including 30°, corresponding to typical reflector antenna system requirements, are synthesized using the proposed method. The feasibility and performance of the designed polarizer is validated through measurements of a fabricated prototype.

Recent studies have shown that microtransplant (MST) could improve outcome of patients with elderly acute myeloid leukemia (EAML). To further standardize the MST therapy and improve outcomes in EAML patients, based on analysis of the literature on MST, especially MST with EAML from January 1st, 2011 to November 30th, 2022, the International Microtransplant Interest Group provides recommendations and considerations for MST in the treatment of EAML. Four major issues related to MST for treating EAML were addressed: therapeutic principle of MST (1), candidates for MST (2), induction chemotherapy regimens (3), and post-remission therapy based on MST (4). Others included donor screening, infusion of donor cells, laboratory examinations, and complications of treatment.

Background: Dupilumab is a treatment approved for uncontrolled moderate-to-severe atopic dermatitis (AD). Tropical and developing countries such as Colombia have characteristics that may impact the natural history of AD and access to medical treatments. In that sense, we aimed to describe the effectiveness and safety of dupilumab in adults with moderate to severe AD in a Colombian multicenter cohort. Methods: Multicenter descriptive study that included patients who started treatment between March 2018 and May 2020 in 6 centers. Disease severity was assessed using the following: Scoring Atopic Dermatitis (SCORAD), Eczema Area and Severity Index (EASI), Patient Oriented Eczema Measure (POEM), and Dermatology Life Quality Index (DLQI). These measurements were collected according to availability at baseline, 3–5 months, 6–12 months, and more than 12 months. Days of sick leave, hospitalizations, and AD flares before and after dupilumab treatment were reported. Adverse events (AEs) were recorded during follow-up. Results: Ninety-three patients were included, with a median age of 32 years (IQR: 24.0; 40.0) and a disease evolution time of 21 years (IQR: 16.0; 29.5). 88.2% had at least 1 allergic disease other than AD. An improvement greater than or equal to 75% EASI was observed in 41.7% of patients at 3–5 months, in 73.7% of patients at 6–12 months, and in 75.0% of patients after 12 months. For those reporting SCORAD and POEM, the median percent change ([IQR], n) from baseline in SCORAD was −67.1 ([−79.2; −54.2], n = 16), −70.5 ([−85.8; −47.9], n = 36) and −66.7 ([−77.3; −51.0], n = 13); and POEM, −58.6 ([−66.4; −55.5], n = 4), −73.0 ([−86.5; −66.7], n = 16) and −87.3 ([−93.4; −69.6], n = 8), respectively. Before initiation of dupilumab treatment, 82 (88.2%) patients reported at least 1 flare of AD in the past 12 months. During the follow-up period, 30 (32.3%) patients reported at least 1 exacerbation or flare. Twelve patients (12.9%) presented an AE and 3 (3.2%) patients discontinued dupilumab for this cause. Conclusions: Dupilumab was effective and safe for the treatment of moderate to severe AD in point-of-care settings, with results similar to randomized controlled and other real-life studies. These positive results are still maintained even though a high number of patients had short interruptions in the use of dupilumab due to administrative problems.

Summary: Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation: There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Funding: Bill & Melinda Gates Foundation.

Advances in functional magnetic resonance spectroscopy (fMRS) have enabled the quantification of activity-dependent changes in neurotransmitter concentrations in vivo. However, the physiological basis of the large changes in GABA and glutamate observed by fMRS (>10%) over short time scales of less than a minute remain unclear as such changes cannot be accounted for by known synthesis or degradation metabolic pathways. Instead, it has been hypothesized that fMRS detects shifts in neurotransmitter concentrations as they cycle from presynaptic vesicles, where they are largely invisible, to extracellular and cytosolic pools, where they are detectable. The present paper uses a computational modelling approach to demonstrate the viability of this hypothesis. A new mean-field model of the neural mechanisms generating the fMRS signal in a cortical voxel is derived. The proposed macroscopic mean-field model is based on a microscopic description of the neurotransmitter dynamics at the level of the synapse. Specifically, GABA and glutamate are assumed to cycle between three metabolic pools: packaged in the vesicles; active in the synaptic cleft; and undergoing recycling and repackaging in the astrocytic or neuronal cytosol. Computational simulations from the model are used to generate predicted changes in GABA and glutamate concentrations in response to different types of stimuli including pain, vision, and electric current stimulation. The predicted changes in the extracellular and cytosolic pools corresponded to those reported in empirical fMRS data. Furthermore, the model predicts a selective control mechanism of the GABA/glutamate relationship, whereby inhibitory stimulation reduces both neurotransmitters, whereas excitatory stimulation increases glutamate and decreases GABA. The proposed model bridges between neural dynamics and fMRS and provides a mechanistic account for the activity-dependent changes in the glutamate and GABA fMRS signals. Lastly, these results indicate that echo-time may be an important timing parameter that can be leveraged to maximise fMRS experimental outcomes.

A double-layer lens consists of a first gradient-index/geodesic profile in an upper waveguide, partially surrounded by a mirror that reflects the wave into a lower guide where there is a second profile. A family of such lens profiles are derived.

Objetivo: El intervalo Tpico-Tfinal de la onda T es un marcador electrocardiográfico de la dispersión transmural aumentada de la repolarización ventricular. Investigamos la presencia de trastornos del sistema de conducción cardíaca en pacientes con hipertensión arterial sistémica (HA) que poseen alterado el intervalo Tpico-Tfinal de la onda T. Métodos: Los 67 pacientes con HA fueron divididos en dos grupos. Aquellos con intervalos de Tpico-Tfinal prolongados (≥ 77 ms), 21 (31%) pacientes (grupo de estudio). Aquellos con intervalos normales (< 77 ms) Tpico-Tfinal, 46 (69%) pacientes (grupo control). Los intervalos Tpico-Tfinal fueron medidos por herramientas de análisis electrocardiográfico computarizado. Resultados: El valor mediano de la duración del complejo QRS fue significativamente más amplio en el grupo de estudio (110 ± 12 ms vs. 94 ± 8 ms p < 0.001). Hubo una incidencia significativamente mayor de hemibloqueo anterior izquierdo en el grupo de estudio (14% vs. 0% p < 0.04). El valor mediano del intervalo QTc fue significativamente mayor en el grupo de estudio (440 ± 26 vs. 422 ± 15 p < 0.01). Hubo una incidencia significativamente mayor de pacientes con intervalo QTc prolongado en el grupo de estudio (33% vs. 11% p < 0.02). El valor mediano del intervalo Tpico-Tfinal fue significativamente mayor en el grupo de estudio (84 ± 5 ms vs. 65 ± 4 ms p < 0.001), así como el cociente Tpico-Tfinal/QTc (0.19 ± 0.1 vs. 0.16 ± 0.1 p < 0.001). Conclusión: Existe una alteración de la repolarización ventricular significativamente mayor y anomalías del sistema de conducción cardíaca en pacientes con HA que poseen alteración del intervalo Tpico- Tfinal de la onda T.

This paper presents the results of the excavations carried out in the Chalcolithic contexts from the walled enclosure of Ota (Alenquer, Portugal). Six new absolute dates allow the discussion of the stratigraphical evidence and chronologically frame the zooarchaeological and taphonomical analysis of the faunal assemblage. Domesticated swine, caprine and bovine are prevalent, while wild species, most notably leporids, but also red deer, auroch and wild boar, among others, are less common. Exploitation and management of animals for the acquisition of primary and secondary products are inferred. Existing data suggests that the economic intensification that started during the previous phases was ongoing.

The Chalcolithic time is a period widely debated in Southwestern Iberia Late Prehistory. During the last few decades, the number of contexts known has grown, especially with the discovery and publication of several ditched enclosures from Southern Portugal. To contribute to ongoing discussions, three Chalcolithic pits –13, 16, 54– from the Complex of ditched enclosures of Monte das Monte das Cabeceiras 2, in Beja, were analysed from a zooarchaeological and taphonomical perspective. The results are combined with information from the material culture, human remains and stratigraphy in order to discuss infilling sequences. Hypothesis on the possible meaning of social practices related to the management of animals are addressed. Bovine, caprine, swine, cervids, leporids and canids were identified with different abundances. A possible feasting or offerings of bovine –including auroch– and to a lesser extent red deer, wild boar and domestic species is suggested for pit 13, where a burial was also identified. Pottery and animal depositions were recorded in this pit, and the contiguous pit 54 that also had human remains. Pit 16 had a possible selection of horns and antlers from bovine, caprine and cervids, as well as a deposition of canid limb bones inside a large pot. The pits analysed can be framed in the wider Southwestern Iberian Peninsula phenomena of ditched enclosures where structured deposits including animal remains are recurrent.

Satellite, fifth generation (5G), and sixth generation (6G) mobile communication systems operating at micro- and millimeter wave frequencies are an essential pillar in advanced network architectures for high-throughput low latency services. The decisive factors for this current development were the significant technological advances accomplished over the last two decades, which meanwhile enable highly integrated, feature-rich, and cost-effective realizations of complete phased array transceiver topologies. Motivated through the today's trend for heterogeneous constellation types to provide truly global coverage, this contribution reviews the current state-of-the-art of electronically steerable antennas for terrestrial and non-terrestrial communication systems up to 100 GHz. First, the potential benefits and limitations of the most relevant technologies are contrasted and put into context with recent system architectures for adaptive beamforming. Their operating principles along with various experimental implementation and achievements providing advanced capabilities such as multi-band/multi-beam operation, polarization agility, and wide-angle scanning are thoroughly presented. Particular emphasis is laid on the review of direct radiating arrays, quasi-optical antenna configurations, and metasurface-based antennas.

Septum polarizers have been used in waveguide systems for over 50 years and are very popular in communication satellites operating in circular polarization. With the progress of computational electromagnetics and computer hardware, combined with advances in manufacturing techniques, there has been a growing interest in septum polarizers with smooth profiles. In particular, a design using Legendre polynomials was recently introduced by the authors. This paper reports on the first experimental validation of this component and introduces also alternative profiles based on cubic splines. The new designs account for considerations on the overhang angle, which is an important parameter in additive layer manufacturing. The axial ratio of these designs is evaluated using a simple and accurate technique based on a back-to-back configuration, which can be implemented outside an anechoic chamber. The proposed characterization technique relies on the custom flanges implemented on the circular common port of septum polarizers to interface with horn antennas. These flanges typically have an 8-fold rotational symmetry, which enables to perform multiple measurements of a back-to-back configuration without requiring further equipment. The measured data is then processed to obtain the axial ratio of the two septum polarizers. This characterization technique is particularly advantageous when a large number of feeds needs to be tested, which is relevant in current and future broadband communication satellites. The technique is validated by comparing with measured data acquired in an anechoic chamber using a standard technique. Various prototypes, designed for operation in C-band communication satellite downlink, are characterized and promising results are obtained, showing very good agreement between simulated and measured data.

Spherically-symmetric lenses can create sharp virtual images, but a general expression for their refractive index profiles had not yet been developed. Here, this expression is provided via analogy between classical mechanics and geometrical optics, yielding solutions complementary to existing lenses obtained from the generalized Luneburg lens problem.

Abstract This paper addresses the influence of the primary and secondary resistances on the behavior of minor hysteresis loops when the electromagnetic device is fed by three-level PWM (pulse width modulation) voltage. To study the device transferring energy to a load, the experimental approaches are different of traditional procedures to material characterization, where problems inherent to the process are added. Analytical, FEM and experimental analysis are performed on a toroidal transformer equipped with a flux sensing coil. The leakage fluxes related to the primary and secondary currents are shown to cause errors in the measurement of the core magnetization current. A solution to mitigate this problem is employed, consisting in twisting and winding together primary and secondary conductors. Experimental methodologies for obtaining the value of the iron losses when the device is transferring energy to a load are also performed. The study shown showed that supply voltage with three-level PWM waveform causes minor hysteresis loops and the greater the resistance value of the excitation winding, the larger the areas of the minor hysteresis loops. On the other hand, by increasing the energy transferring to a load the minor loops areas tend to decrease.

Abstract In this work we propose a new method to separate iron losses by removing low frequency tests and reducing the number of experiments. The article deals with methodologies that use numerical methods to find the mathematical model coefficients of magnetic loss separation in hysteresis loss (Wh), eddy current loss (Wed) and excess loss (Wex). Three methodologies are presented and depend on experimental tests such as (i) varying magnetic induction Bm and constant supply frequency (f) of 50 Hz, (ii) constant magnetic induction around 1 T and varying frequency. The first methodology is based on Newton’s method to solve the numerical system generated with experimental data from two laboratory experiments. These data were reported in past references. Another two methodologies are based on genetic algorithms (GA). One of them depends on experimental data from both experiments and the another depends on experimental data only from experiment (i). Results indicate that genetic algorithms method presents excellent solutions in comparison with other ones. The GA method with two tests allows a better representation of the experimental behavior of the sample with maximum errors varying from 1.10% to 0.20%. In GA method with one test, minimization varied from 6.924 × 10−05 to 3.186 × 10−05.

This paper reports on the design and experimental validation of a fully-metallic double-ridged waveguide 10 × 10 Rotman lens additively manufactured as a single part. The wide band operation of this quasi-optical beamformer enables us to cover the uplink and downlink frequencies allocated to satellite communications in the K/Ka-band, from 17.3 GHz to 30 GHz. The feeding port design was adjusted to enable vertical printing, thus minimizing the use of supporting structures. A prototype was manufactured and tested. The reported results indicate losses in the range of 0.5 dB in the lower-frequency band and 0.8 dB in the upper-frequency band, including the waveguide transitions added for test purposes. The measured reflection and coupling coefficients remain below −11.5 dB over the operating band. The standard deviation of the residual phase error across the array ports is below 5° in simulation and below 10° in measurements. Array factors synthesized using the scattering parameters confirm the good stability of the beamforming functionality over the wide frequency band analyzed. This monolithic design is a promising step toward more integrated antenna systems, such as a compact dual-stack configuration for planar array design.

Abstract Compressors operating in refrigeration systems, typically with built-in induction motors, represent an important energy demand. The applicability of standard methods for efficiency determination of induction motors is limited in this context by the constructive characteristics of these motors, such as the shared compressor frame and the inaccessibility of the shaft. The main contributions of this paper are to provide an overview of standard and alternative methods for efficiency testing of single and polyphase motors, according to technical standards and to the state of the art, and to offer guidelines for the method selection. The options cover dynamometer tests, loss segregation and equivalent circuit methods, some even applicable without direct access to the motor. Experimental application examples in single and three- phase motors are presented. Beyond the context of compressors, the discussion is relevant for inaccessible motors in general.

Although the recent advances on the relationship of its major groups, the systematics of the rich fauna of Neotropical snakes is far from being a consensus. In this sense, derived groups presenting continental distributions have represented a main challenge. The taxonomy of the snake tribe Echinantherini is one of the most contentious among the diverse family known as Dipsadidae. The tribe is poorly sampled in phylogenetic studies, resulting in conflicting hypotheses of relationships among its taxa. Moreover, several rare and micro endemic species of Echinantherini have never been evaluated within a comprehensive phylogenetic framework. Here, we assess for the first time the phylogenetic position of the rare Echinanthera amoena within Echinantherini. We based our analyses on a comprehensive multilocus dataset including 14 of the 16 species described for the tribe. Our results support the monophyly of Echinantherini and strongly indicate E. amoena as a unique lineage, phylogenetically positioned apart from all other congeners. From the three current genera (Echinanthera, Taeniophallus, and Sordellina) our results indicate that Echinanthera and Taeniophallus are paraphyletic, since the T. affinis species group is positioned as sister to Echinanthera (except E. amoena) clustering apart from the clade formed by the T. brevirostris and T. occipitalis groups. We describe new genera for the T. affinis and T. occipitalis species groups and an additional monospecific genus for E. amoena. Although we did not evaluate the phylogenetic position of T. nebularis, we described a new genus and removed it from Echinantherini since its morphology strikingly departs from all species now included in the tribe. Finally, we redefine the genera Echinanthera and Taeniophallus and we provide comments about further directions to study the biogeography and the evolution of morphological traits in Echinantherini.

Os autores descrevem caso clínico de tumor de células gigantes refratário a vários tratamentos, onde empregou-se com sucesso a ressecção distal do úmero com colocação de endoprótese não convencional de Fabroni (ENCF). Esta prótese parcial preserva o olecrânio, evitando a luxação e ulceração cutânea do cotovelo, e apresenta chapa de metal no sulco intercondiliano para evitar necrose óssea. Um ótimo resultado funcional foi obtido, além de seguimento de 3 anos sem recidiva ou complicações cirúrgicas.

Summary: Background: More than 3 billion people do not have access to clean energy and primarily use solid fuels to cook. Use of solid fuels generates household air pollution, which was associated with more than 2 million deaths in 2019. Although local patterns in cooking vary systematically, subnational trends in use of solid fuels have yet to be comprehensively analysed. We estimated the prevalence of solid-fuel use with high spatial resolution to explore subnational inequalities, assess local progress, and assess the effects on health in low-income and middle-income countries (LMICs) without universal access to clean fuels. Methods: We did a geospatial modelling study to map the prevalence of solid-fuel use for cooking at a 5 km × 5 km resolution in 98 LMICs based on 2·1 million household observations of the primary cooking fuel used from 663 population-based household surveys over the years 2000 to 2018. We use observed temporal patterns to forecast household air pollution in 2030 and to assess the probability of attaining the Sustainable Development Goal (SDG) target indicator for clean cooking. We aligned our estimates of household air pollution to geospatial estimates of ambient air pollution to establish the risk transition occurring in LMICs. Finally, we quantified the effect of residual primary solid-fuel use for cooking on child health by doing a counterfactual risk assessment to estimate the proportion of deaths from lower respiratory tract infections in children younger than 5 years that could be associated with household air pollution. Findings: Although primary reliance on solid-fuel use for cooking has declined globally, it remains widespread. 593 million people live in districts where the prevalence of solid-fuel use for cooking exceeds 95%. 66% of people in LMICs live in districts that are not on track to meet the SDG target for universal access to clean energy by 2030. Household air pollution continues to be a major contributor to particulate exposure in LMICs, and rising ambient air pollution is undermining potential gains from reductions in the prevalence of solid-fuel use for cooking in many countries. We estimated that, in 2018, 205 000 (95% uncertainty interval 147 000–257 000) children younger than 5 years died from lower respiratory tract infections that could be attributed to household air pollution. Interpretation: Efforts to accelerate the adoption of clean cooking fuels need to be substantially increased and recalibrated to account for subnational inequalities, because there are substantial opportunities to improve air quality and avert child mortality associated with household air pollution. Funding: Bill & Melinda Gates Foundation.

Pain-related catastrophising is a maladaptive coping strategy known to have a strong influence on clinical pain outcomes and treatment efficacy. Notwithstanding, little is known about its neurophysiological correlates. There is evidence to suggest catastrophising is associated with resting-state EEG frontal alpha asymmetry (FAA) patterns reflective of greater relative right frontal activity, which is known to be linked to withdrawal motivation and avoidance of aversive stimuli. The present study aims to investigate whether such a relationship occurs in the situational context of experimental pain. A placebo intervention was also included to evaluate effects of a potential pain-relieving intervention on FAA. 35 participants, including both chronic pain patients and healthy subjects, completed the Pain Catastrophising Scale (PCS) questionnaire followed by EEG recordings during cold pressor test (CPT)-induced tonic pain with or without prior application of placebo cream. There was a negative correlation between FAA and PCS-subscale helplessness scores, but not rumination or magnification, during the pre-placebo CPT condition. Moreover, FAA scores were shown to increase significantly in response to pain, indicative of greater relative left frontal activity that relates to approach-oriented behaviours. Placebo treatment elicited a decrease in FAA in low helplessness scorers, but no significant effects in individuals scoring above the mean on PCS-helplessness. These findings suggest that, during painful events, FAA may reflect the motivational drive to obtain reward of pain relief, which may be diminished in individuals who are prone to feel helpless about their pain. This study provides valuable insights into biomarkers of pain-related catastrophising and prospects of identifying promising targets of brain-based therapies for chronic pain management.

Summary: Background: In February 2021, Colombia began mass vaccination against COVID-19 using mainly BNT162b2 and CoronaVac vaccines. We aimed to estimate vaccine effectiveness (VE) to prevent COVID-19 symptomatic cases, hospitalization, critical care admission, and deaths in a cohort of 796,072 insured subjects older than 40 years in northern Colombia, a setting with a high SARS-CoV-2 transmission. Methods: We identified individuals vaccinated between March 1st of 2021 and August 15th of 2021. We included symptomatic cases, hospitalizations, critical care admissions, and deaths in patients with confirmed COVID-19 as main outcomes. We calculated VE for each outcome from the hazard ratio in Cox proportionally hazards regressions (adjusted by age, sex, place of residence, diabetes, human immunodeficiency virus, cancer, hypertension, tuberculosis, neurological diseases, and chronic renal disease), with 95% confidence intervals (CI). Findings: A total of 719,735 insured participants of 40 and more years were followed. We found 21,545 laboratory-confirmed symptomatic COVID-19 among unvaccinated population, along with 2874 hospitalizations, 1061 critical care admissions, and 1329 deaths, for a rate of 207.2 per million person-days, 27.1 per million person-days, 10.0 per million person-days, and 12.5 per million person-days, respectively. We found CoronaVac was not effective for any outcome in subjects above 80 years old; but for people 40-79 years of age, we found two doses of CoronaVac reduced hospitalization (33.1%; 95% CI, 14.5–47.7), critical care admission (47.2%; 95% CI, 18.5–65.8), and death (55.7%; 95% CI, 32.5–70.0). We found BNT162b2 was effective for all outcomes in the entire population of subjects above 40 years of age, significantly declining for subjects ≥80 years. Interpretation: Two doses of either CoronaVac in population between 40 and 79 years of age, or BNT162b2 among vaccinated above 40 years old significantly reduced deaths of confirmed COVID-19 in a cohort of individuals from Colombia. Vaccine effectiveness for CoronaVac and BNT162b2 declined with increasing age. Funding: UK National Institute for Health Research, the European Union's Horizon 2020 research and innovation programme, and the Bill & Melinda Gates Foundation.

The mechanics of the migration of T cells into tumours is an important aspect of tumour immunity. Here the authors engineer complex 3D environments to explore functions of microtubules and cell contractility as strategies to enhance T cell migration in tumour microenvironments.

Background: Fragmented QRS (fQRS) is defined as any QRS complex with duration of less than 120 ms (ms) and at least one notch in the R or S wave in two or more leads belonging to the same coronary territory. The fQRS represents a delay in ventricular conduction caused by a myocardial scar associated to arrhythmic events. Methods: This is a descriptive, retrospective, cross-sectional study of a total of 123 patientsadmitted with ischemic heart disease. The aim was to correlate the presence of fQRS in a conventional 12-leads electrocardiogram (ECG) with myocardial regional motility disorders. Results: A total of 62% of the patients were male, the mean age was 63 ± 12 SD. fQRS was observed in 44% (64% men and 36% women), the most frequent location being the inferior wall (61%), followed by the anteroseptal and lateral walls (14% for both). Of the 36 patients with fQRS, 30 had segmental disorders, while 6 did not. Of the 45 patients without fQRS, 28 had segmental disorders, but 17 did not, which gives us a sensitivity of 52% (moderate SnNout) and specificity of 74% (high SpPin), with a positive predictive value of 83%, a negative predictive value of 38% and a prevalence of 72%. Conclusion: The presence of fQRS in the ECG has high specificity and a high positive predictive value of the existence of segmental myocardial motility disorders in patients with documented coronary artery disease.

Chloroplast ascorbate peroxidases exert an important role in the maintenance of hydrogen peroxide levels in chloroplasts by using ascorbate as the specific electron donor. In this work, we performed a functional study of the stromal APX in rice (OsAPX7) and demonstrated that silencing of OsAPX7 did not impact plant growth, redox state, or photosynthesis parameters. Nevertheless, when subjected to drought stress, silenced plants (APX7i) show a higher capacity to maintain stomata aperture and photosynthesis performance, resulting in a higher tolerance when compared to non-transformed plants. RNA-seq analyses indicate that the silencing of OsAPX7 did not lead to changes in the global expression of genes related to reactive oxygen species metabolism. In addition, the drought-mediated induction of several genes related to the proteasome pathway and the down-regulation of genes related to nitrogen and carotenoid metabolism was impaired in APX7i plants. During drought stress, APX7i showed an up-regulation of genes encoding flavonoid and tyrosine metabolism enzymes and a down-regulation of genes related to phytohormones signal transduction and nicotinate and nicotinamide metabolism. Our results demonstrate that OsAPX7 might be involved in signaling transduction pathways related to drought stress response, contributing to the understanding of the physiological role of chloroplast APX isoforms in rice.

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here, in both murine and human PDA, we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through tumor-associated collagen signatures (TACS). This results in early dissemination from histologically premalignant lesions and continual invasion from well-differentiated disease, and it suggests TACS as a biomarker to aid in the pathologic assessment of early disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in potentially novel microfluidic-derived microtissues and in vivo demonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to reengineer and normalize tumor microenvironments may have roles not only in very early disease, but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma-targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination.

Alloreactive donor T cells undergo extensive metabolic reprogramming to become activated and induce graft-versus-host disease (GVHD) upon alloantigen encounter. It is generally thought that glycolysis, which promotes T cell growth and clonal expansion, is employed in this process. However, conflicting data have been reported regarding the requirement of glycolysis to induce T cell-mediated GVHD due to the lack of T cell-specific treatments using glycolysis inhibitors. Importantly, previous studies have not evaluated whether graft-versus-leukemia (GVL) activity is preserved in donor T cells deficient for glycolysis. As a critical component affecting the clinical outcome, it is necessary to assess the anti-tumor activity following treatment with metabolic modulators in preclinical models. In the present study, we utilized T cells selectively deficient for glucose transporter 1 (Glut1T-KO), to examine the role of glycolysis exclusively in alloreactive T cells without off-targeting effects from antigen presenting cells and other cell types that are dependent on glycolysis. We demonstrated that transfer of Glut1T-KO T cells significantly improved acute GVHD outcomes through increased apoptotic rates, impaired expansion, and decreased proinflammatory cytokine production. In addition to impaired GVHD development, donor Glut1T-KO T cells mediated sufficient GVL activity to protect recipients from tumor development. A clinically relevant approach using donor T cells treated with a small molecule inhibitor of glycolysis, 2-Deoxy-D-glucose ex vivo, further demonstrated protection from tumor development. These findings indicate that treatment with glycolysis inhibitors prior to transplantation selectively eliminates alloreactive T cells, but spares non-alloreactive T cells including those that protect against tumor growth. The present study has established a definitive role for glycolysis in acute GVHD and demonstrated that acute GVHD can be selectively prevented through targeting glycolysis.

Objective. To describe the mortality trends of diabetes mellitus (DM) in Colombia, by sex and age group, from 1979 to 2017. Methods. We carried out an ecological study using mortality data from the Colombian National Administrative Department of Statistics. Crude and age-standardized annual mortality rates per 100 000 people were estimated. Trends of standardized rates were described by sex and age groups. Joinpoint regression models were performed to study mortality trends. Results. Throughout the whole period, the total number of DM recorded deaths in Colombia was 200 650, 58% (116 316) in women (p

Multi-beam antennas are critical components in future terrestrial and non-terrestrial wireless communications networks. The multiple beams produced by these antennas will enable dynamic interconnection of various terrestrial, airborne and space-borne network nodes. As the operating frequency increases to the high millimeter wave (mmWave) and terahertz (THz) bands for beyond 5G (B5G) and sixth-generation (6G) systems, quasi-optical techniques are expected to become dominant in the design of high gain multi-beam antennas. This paper presents a timely overview of the mainstream quasi-optical techniques employed in current and future multi-beam antennas. Their operating principles and design techniques along with those of various quasi-optical beamformers are presented. These include both conventional and advanced lens and reflector based configurations to realize high gain multiple beams at low cost and in small form factors. New research challenges and industry trends in the field, such as planar lenses based on transformation optics and metasurface-based transmitarrays, are discussed to foster further innovations in the microwave and antenna research community.

This paper introduces a novel family of one-dimensional switching matrices, also known as beamforming networks (BFNs), which can be sized for an arbitrary number of beams. It also describes the associated numerical design method, supported by several design examples. The concept is further validated with a full-wave model of a generic 5 × 5 switching matrix designed at 76 GHz. The proposed matrices are obtained by cascading units consisting of a two-way coupler and a phase shifter in a parallel configuration, providing theoretically lossless operation as a direct consequence of the orthogonal BFN topology and equalized path lengths, expected to benefit the frequency bandwidth. The design method is general, also including the configurations equivalent to Butler matrices when the number of beams is a power of two. The obtained planar matrix designs combine some benefits of the well-known Butler and Nolen matrices, namely the parallel topology and the arbitrary number of beams. The minimum number of cascaded units required by the proposed topology, also corresponding to the number of layers, is found to be $N$, where $N$ is the number of beams, which is less than the number of cascaded units for the corresponding “parallel” Nolen matrix, for $N$ larger than three, thus providing a reduction in the number of layers of up to 38% for an 8-beam matrix. This reduction is close to the theoretical upper boundary of 50%, reached for large values of $N$. This significant reduction is expected to have a positive impact on RF performance, and in particular insertion losses, as well as amplitude and phase dispersion over the operating band. Interestingly, the proposed switching matrix configuration reduces to a standard Butler matrix when the number of beams is equal to 4, and demonstrates a reduction in the number of layers of 20% over the corresponding planar Butler matrix for a design with 8 beams. The proposed matrix configuration is a promising solution for the design of low-cost single-layer beam-switching matrices.