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A woman in her 50s was undergoing a repeat liver resection surgery for recurrence of liver metastasis when the intravenous fluid flow was noted to be sluggish on multiple occasions. On the third examination of the right hand where the intravenous cannula was located, surgery was halted as there was extensive swelling from the hand to the biceps and the hand had started turning blue. A diagnosis of acute upper limb compartment syndrome secondary to extravasation exacerbated by metaraminol was made by the anaesthetist and surgeon. Fasciotomies of the right upper limb were performed, and perfusion was restored. A hand surgeon arrived shortly after and completed decompressing the upper limb compartments.A literature review revealed risk factors such as communication barriers, age and chemotherapy were present in this case. Enhanced monitoring is needed in the context of unsatisfactory infusion flow rates perioperatively.

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Purpose: Reading and speech difficulties are common in childhood, yet it is not fully understood how much of their etiology is shared. This partly derives from methodological issues related to overlooking the potential co-occurrence between the two sets of difficulties. This study investigated the effects of five bioenvironmental predictors in a sample assessed for such co-occurrence. Method: A combination of exploratory and confirmatory analyses was performed on longitudinal data from the National Child Development Study. Exploratory latent class analysis was performed on children's reading, speech, and language outcomes at ages 7 and 11 years. Membership in the obtained classes was modeled using a regression with sex and four early-life predictors: gestation period, socioeconomic status, maternal education, and the home reading environment. Results: The model yielded four latent classes that broadly reflected (1) average reading and speech, (2) excellent reading, (3) reading difficulties, and (4) speech difficulties. Early-life factors significantly predicted class membership. Male sex and preterm birth emerged as risk factors for both reading and speech difficulties. Protective effects against reading difficulties were identified for maternal education, and lower (but not higher) levels of socioeconomic status and the home reading environment. Conclusions: Co-occurrence of reading and speech difficulties in the sample was low, and differential patterns of effect of the social environment were supported. Reading outcomes were under stronger malleable influence than speech outcomes.

Solvents are increasingly known to influence chemical reactivity. However, the microscopic origin of solvent effects is scarcely understood, particularly at the individual molecule level. To shed light on this, we explored a well-defined model system of water (D2O) and carbon monoxide on a single-crystal copper surface with time-lapsed low-temperature scanning tunneling microscopy (STM) and ab initio calculations. Through detailed measurements on a time scale of minutes to hours at the limit of single-molecule solvation, we find that at cryogenic temperatures CO-D2O complexes are more mobile than individual CO or water molecules. We also obtain detailed mechanistic insights into the motion of the complex. In diffusion-limited surface reactions, such a solvent-triggered increase in mobility would substantially increase the reaction yield.

Single-atom alloy catalysts combine catalytically active metal atoms, present as dopants, with the selectivity of coinage metal hosts. Determining whether adsorbates stick at the dopant or spill over onto the host is key to understanding catalytic mechanisms on these materials. Despite a growing body of work, simple descriptors for the prediction of spillover energies (SOEs), i.e., the relative stability of an adsorbate on the dopant versus the host site, are not yet available. Using Density Functional Theory (DFT) calculations on a large set of adsorbates, we identify the dopant charge and the SOE of carbon as suitable descriptors. Combining them into a linear surrogate model, we can reproduce DFT-computed SOEs within 0.06 eV mean absolute error. More importantly, our work provides an intuitive theoretical framework, based on the concepts of electrostatic interactions and covalency, that explains SOE trends and can guide the rational design of future single-atom alloy catalysts.

Amorphous ices govern a range of cosmological processes and are potentially key materials for explaining the anomalies of liquid water. A substantial density gap between low-density and high-density amorphous ice with liquid water in the middle is a cornerstone of our current understanding of water. However, we show that ball milling “ordinary” ice I h at low temperature gives a structurally distinct medium-density amorphous ice (MDA) within this density gap. These results raise the possibility that MDA is the true glassy state of liquid water or alternatively a heavily sheared crystalline state. Notably, the compression of MDA at low temperature leads to a sharp increase of its recrystallization enthalpy, highlighting that H 2 O can be a high-energy geophysical material.

The brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-basedOprm1-Creknock-in transgenic rat that provides cell type-specific genetic access to MOR-expressing cells. After performing anatomic and behavioral validation experiments, we used theOprm1-Creknock-in rats to study the involvement of NAc MOR-expressing cells in heroin self-administration in male and female rats. Using RNAscope, autoradiography, and FISH chain reaction (HCR-FISH), we found no differences inOprm1expression in NAc, dorsal striatum, and dorsal hippocampus, or MOR receptor density (except dorsal striatum) or function betweenOprm1-Creknock-in rats and wildtype littermates. HCR-FISH assay showed thatiCreis highly coexpressed withOprm1(95%-98%). There were no genotype differences in pain responses, morphine analgesia and tolerance, heroin self-administration, and relapse-related behaviors. We used the Cre-dependent vector AAV1-EF1a-Flex-taCasp3-TEVP to lesion NAc MOR-expressing cells. We found that the lesions decreased acquisition of heroin self-administration in maleOprm1-Crerats and had a stronger inhibitory effect on the effort to self-administer heroin in femaleOprm1-Crerats. The validation of anOprm1-Creknock-in rat enables new strategies for understanding the role of MOR-expressing cells in rat models of opioid addiction, pain-related behaviors, and other opioid-mediated functions. Our initial mechanistic study indicates that lesioning NAc MOR-expressing cells had different effects on heroin self-administration in male and female rats.SIGNIFICANCE STATEMENTThe brain µ-opioid receptor (MOR) is critical for the analgesic, rewarding, and addictive effects of opioid drugs. However, in rat models of opioid-related behaviors, the circuit mechanisms of MOR-expressing cells are less known because of a lack of genetic tools to selectively manipulate them. We introduce a CRISPR-basedOprm1-Creknock-in transgenic rat that provides cell type-specific genetic access to brain MOR-expressing cells. After performing anatomical and behavioral validation experiments, we used theOprm1-Creknock-in rats to show that lesioning NAc MOR-expressing cells had different effects on heroin self-administration in males and females. The newOprm1-Crerats can be used to study the role of brain MOR-expressing cells in animal models of opioid addiction, pain-related behaviors, and other opioid-mediated functions.

The focus of the article is the electro-magneto-hydrodynamics of an Oldroyd 6-constants fluid flow through parallel micro-plates with heat transfer. The medium between the micro-plates is porous and we use the Darcy-Brinkman-Forchheimer model for it. Numerical calculations, using the shooting method, were performed to solve the non-linear equations that emanate from the modeling. The results for the velocity mechanism, the Nusselt number and the temperature distribution are graphically shown. The analysis of the problem focuses on the effects of several fluid and heat transfer parameters, such as the Hartmann number, the Brinkmann number, the Darcy-Brinkman-Forchheimer parameter, the Darcy parameter, the viscous dissipation, and the Joule heating coefficient.

Abstract. The present study investigated the relationship between Big Five traits-based profiles and humor styles in a sample of 426 Greek preadolescents. Latent Profile Analysis yielded three distinct personality profiles: resilients, average, and undercontrollers. These profiles exhibited significant group differences in humor styles. The resilient profile displayed the highest scores on the two benign humor styles and the lowest on the two malign styles. On the contrary, the under controllers scored lowest on the two benign humor styles and highest on self-defeating humor. Findings showed that the patterns identified in the extant literature between humor, personality, and adjustment generalize to preadolescents. These are discussed with reference to prior work and relevant theoretical implications.

To investigate baseline mesopic microperimetry (MP) and spectral domain optical coherence tomography (OCT) in the Rate of Progression in USH2A-related Retinal Degeneration (RUSH2A) study.Natural history study METHODS: Setting: 16 clinical sites in Europe and North AmericaStudy Population: Participants with Usher syndrome type 2 (USH2) (N = 80) or autosomal recessive nonsyndromic RP (ARRP) (N = 47) associated with biallelic disease-causing sequence variants in USH2AObservation Procedures: General linear models were used to assess characteristics including disease duration, MP mean sensitivity and OCT intact ellipsoid zone (EZ) area. The associations between mean sensitivity and EZ area with other measures, including best corrected visual acuity (BCVA) and central subfield thickness (CST) within the central 1 mm, were assessed using Spearman correlation coefficients.Mean sensitivity on MP; EZ area and CST on OCT.All participants (N = 127) had OCT, while MP was obtained at selected sites (N = 93). Participants with Usher syndrome type 2 (USH2, N = 80) and nonsyndromic autosomal recessive Retinitis Pigmentosa (ARRP, N = 47) had the following similar measurements: EZ area (median (interquartile range [IQR]): 1.4 (0.4, 3.1) mmLonger disease duration correlated with more severe retinal structure and function abnormalities, and there were associations between MP and OCT metrics. Monitoring changes in retinal structure-function relationships during disease progression will provide important insights into disease mechanism in USH2A-related retinal degeneration.

Mu opioid receptor (MOR) agonists comprise the most effective analgesics, but their therapeutic utility is limited by adverse effects. One approach for limiting such effects has been to develop "biased" MOR agonists that show preference for activating G protein over β-Arrestin signaling. However, the notion of biased agonism has been challenged by recent studies. Oliceridine (Olinvyk

Leber congenital amaurosis type 4 (LCA4), caused by AIPL1 mutations, is characterized by severe sight impairment in infancy and rapidly progressing degeneration of photoreceptor cells. We generated retinal organoids using induced pluripotent stem cells (iPSCs) from renal epithelial cells obtained from four children with AIPL1 nonsense mutations. iPSC-derived photoreceptors exhibited the molecular hallmarks of LCA4, including undetectable AIPL1 and rod cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE6) compared with control or CRISPR-corrected organoids. Increased levels of cGMP were detected. The translational readthrough-inducing drug (TRID) PTC124 was investigated as a potential therapeutic agent. LCA4 retinal organoids exhibited low levels of rescue of full-length AIPL1. However, this was insufficient to fully restore PDE6 in photoreceptors and reduce cGMP. LCA4 retinal organoids are a valuable platform for in vitro investigation of novel therapeutic agents.

Friction at water-carbon interfaces remains a major puzzle with theories and simulations unable to explain experimental trends in nanoscale waterflow. A recent theoretical framework -- quantum friction (QF)-- proposes to resolve these experimental observations by considering nonadiabatic coupling between dielectric fluctuations in water and graphitic surfaces. Here, using a classical model that enables fine-tuning of the solid's dielectric spectrum, we provide evidence from simulations in general support of QF. In particular, as features in the solid's dielectric spectrum begin to overlap with water's librational and Debye modes, we find an increase in friction in line with that proposed by QF. At the microscopic level, we find that this contribution to friction manifests more distinctly in the dynamics of the solid's charge density than that of water. Our findings suggest that experimental signatures of QF may be more pronounced in the solid's response rather than liquid water's.

It has been indicated that strength imbalances following an ACL reconstruction are essential indicators of incomplete rehabilitation programs and increased risk for re-injury. This study evaluated the effectiveness of an isokinetic training protocol on muscular imbalances in soccer players who underwent ACL surgery. Twenty-four elite male soccer players who were found to have strength imbalances six months post-surgery were recruited and randomly assigned to either the control or the experimental group. The isokinetic knee strength was assessed before and after the 5-week intervention program. Two-way analysis of variance (ANOVA) revealed a significant main effect of training intervention on torque production for the quadriceps [F(1,22)= 34.95, p

Single atoms or ions on surfaces affect processes from nucleation 1 to electrochemical reactions 2 and heterogeneous catalysis 3. Transmission electron microscopy is a leading approach for visualizing single atoms on a variety of substrates 4,5. It conventionally requires high vacuum conditions, but has been developed for in situ imaging in liquid and gaseous environments 6,7 with a combined spatial and temporal resolution that is unmatched by any other method—notwithstanding concerns about electron-beam effects on samples. When imaging in liquid using commercial technologies, electron scattering in the windows enclosing the sample and in the liquid generally limits the achievable resolution to a few nanometres 6,8,9. Graphene liquid cells, on the other hand, have enabled atomic-resolution imaging of metal nanoparticles in liquids 10. Here we show that a double graphene liquid cell, consisting of a central molybdenum disulfide monolayer separated by hexagonal boron nitride spacers from the two enclosing graphene windows, makes it possible to monitor, with atomic resolution, the dynamics of platinum adatoms on the monolayer in an aqueous salt solution. By imaging more than 70,000 single adatom adsorption sites, we compare the site preference and dynamic motion of the adatoms in both a fully hydrated and a vacuum state. We find a modified adsorption site distribution and higher diffusivities for the adatoms in the liquid phase compared with those in vacuum. This approach paves the way for in situ liquid-phase imaging of chemical processes with single-atom precision.

Comparison of outcomes and billing costs of patients treated at our institution using transmastoid (TM), middle cranial fossa (MCF), and combined approaches for repair of otogenic cerebrospinal fluid (CSF) leaks and encephaloceles.Retrospective cohort review.Tertiary-care hospital.Seventy-seven cases of otogenic CSF leaks or encephaloceles.Surgical repair of an otogenic encephalocele or CSF leak using either a TM, MCF, or combined approach.Success of repair, length of operation, cost of operating room materials, postoperative need for intensive care, and postoperative length of stay.Forty cases (52%) were performed by the TM approach, 27 (35%) by MCF, and 10 (13%) by combined TM/MCF. Mean length of stay was not statistically different amongst TM patients (2.1 d), MCF patients (3.3 d), and combined TM/MCF patients (3.70; p = 0.112). Only 3/40 TM cases required intensive care during their admission while all MCF and combined TM/MCF approach cases were admitted to the intensive care unit for at least one night ( p0.001). On follow-up, CSF leak recurred in 3/77 (4%) cases: 3/27 (11%) MCF, 0/40 TM, and 0/10 combined TM/MCF patients ( p = 0.056). The mean cost of operating room materials charged to the patient was significantly greater in the MCF group ($9,883) than the TM group ($3,748; p = 0.001).In carefully selected patients, the TM approach is an effective and less costly alternative to MCF approaches for repair of otogenic CSF leaks and encephaloceles.

This study contributes to the literature on assessment centre (AC) measurement structure by evaluating whether dimension, exercise or mixed-model theoretical perspectives are supported by reliability outcomes. In a large-scale study (Ncandidates = 2917) utilizing Bayesian generalizability theory, we tested reliability estimates configured to conform to dimension, exercise or mixed-model perspectives. Our findings reveal that reliability outcomes for AC ratings greatly depend on the measurement intentions of the researcher. When this intent aligned with the traditional dimension perspective, we found evidence that reliability was unacceptably low (mean reliability = .38, SD = .15). However, when the intent aligned with the exercise perspective, we found evidence that reliability exceeded acceptable criteria (mean reliability = .91, SD = .09). The addition of dimension- to exercise-related effects to reflect a mixed-model perspective did not make an appreciable difference to reliability.

The present study aimed to assess the differences in pre-season knee strength asymmetries, flexibility, and aerobic capacity of soccer players that sustained lower-body injuries during the in-season period compared to those that did not have a lower-body injury. A secondary purpose was to compare the aforementioned parameters between the players that sustained a knee ligament injury and hamstring strain. One hundred and thirty-three division 1 soccer players participated in the study. Fitness testing was conducted at the end of the pre-season period, and the players were followed for a total of 20 games. The anthropometric, lower body strength, flexibility and aerobic capacity parameters were compared between the players that sustained hamstring strains and knee ligament injuries and those that did not sustain any injuries. Results indicated that injured players were significantly older and less flexible than non-injured players (p

The O vacancy (Ov) formation energy, $E_\textrm{Ov}$, is an important property of a metal-oxide, governing its performance in applications such as fuel cells or heterogeneous catalysis. These defects are routinely studied with density functional theory (DFT). However, it is well-recognized that standard DFT formulations (e.g. the generalized gradient approximation) are insufficient for modeling the Ov, requiring higher levels of theory. The embedded cluster method offers a promising approach to compute $E_\textrm{Ov}$ accurately, giving access to all electronic structure methods. Central to this approach is the construction of quantum(-mechanically treated) clusters placed within suitable embedding environments. Unfortunately, current approaches to constructing the quantum clusters either require large system sizes, preventing application of high-level methods, or require significant manual input, preventing investigations of multiple systems simultaneously. In this work, we present a systematic and general quantum cluster design protocol that can determine small converged quantum clusters for studying the Ov in metal-oxides with accurate methods such as local coupled cluster with single, double and perturbative triple excitations [CCSD(T)]. We apply this protocol to study the Ov in the bulk and surface planes of rutile TiO2 and rocksalt MgO, producing the first accurate and well-converged determinations of $E_\textrm{Ov}$ with this method. These reference values are used to benchmark exchange-correlation functionals in DFT and we find that all studied functionals underestimate $E_\textrm{Ov}$, with the average error decreasing along the rungs of Jacob's ladder. This protocol is automatable for high-throughput calculations and can be generalized to study other point defects or adsorbates., Comment: Accepted for publication in Journal of Chemical Physics on 2022-03-10

Introduction: Intralabyrinthine schwannomas, including the intracochlear variety, are rare benign tumors. They can cause a number of symptoms and have the potential to grow to involve other critical structures of the inner ear and skull base. While surgical resection is feasible, there is typically permanent hearing dysfunction as a result of resection and subsequent fibrosis. Here, we present 2 cases of intracochlear schwannomas (ICS) that were successfully resected with simultaneous cochlear implant placement. Methods: Patient 1 presented with an intravestibulocochlear schwannoma. This patient underwent a translabyrinthine approach. Endoscopic assistance was used to dissect the tumor from the vestibule and basal turn of the cochlea, through an enlarged round window approach. A cochlear implant was placed via a round window cochleostomy. Patient 2 presented with an intracochlear schwannoma involving the basal and middle turns of the cochlea. The patient underwent a trans-otic approach for resection. A large portion of the cochlear promontory required unroofing for complete exposure of the tumor. A cochlear implant was then placed via a round window cochleostomy. Results: Upon cochlear implant activation, Patient 1’s sound field thresholds using the implant were near the normal range of hearing, ranging from 25 to 50 dB HL from 250 to 6000 Hz. Patient 2’s 6-month post-operative cochlear implant sound field testing ranged from 20 to 30 dB HL from 250 to 6000 Hz and speech recognition testing revealed 59% on AZ Bio sentences compared to 0% pre-operatively. Conclusion: Simultaneous cochlear implantation after resection of intracochlear schwannomas is safe and successful in restoring hearing. Attention to adequate exposure and endoscopic assistance, when required, allow for gross total resection while minimizing trauma to cochlear structures. In such cases, immediate cochlear implantation allows for hearing rehabilitation before likely cochlear fibrosis can occur.

To analyze the retino-choroidal vascular characteristics of patients affected by pigmented paravenous chorio-retinal atrophy by means of optical coherence tomography (OCT) angiography.This study was designed as an observational, cross-sectional case series. Multimodal imaging included fundus autofluorescence, structural OCT, and OCT angiography. The quantitative OCT angiography analyses included the calculation of the vessel density and choriocapillaris porosity.Overall, 12 patients (24 eyes) affected by pigmented paravenous chorio-retinal atrophy were recruited. Structural OCT of the areas involved by pigmented paravenous chorio-retinal atrophy as visualized on the fundus autofluorescence showed a complete ellipsoid zone and external limiting membrane absence, with thinning of ganglion cell complex, outer nuclear layer, and outer plexiform layer, but associated with the optical partial preservation of the retinal pigment epithelium. Optical coherence tomography angiography quantitative assessment of the retinal regions affected by PPRCA, as visualized by fundus autofluorescence, was characterized by normal vessel density at the level of superficial capillary plexus but significantly altered vessel density of deep capillary plexus and choriocapillaris, with higher choriocapillaris porosity. The presence of macular atrophy was significantly correlated with worse deep capillary plexus and choriocapillaris vessel density values. Furthermore, a statistically significant correlation between the fundus autofluorescence patterns and the retinal vascular status was found.Optical coherence tomography angiography quantitative analyses in pigmented paravenous chorio-retinal atrophy demonstrate a specific impairment at the level of the deep capillary plexus, which could in turn bring about a thinning of ganglion cell complex and outer nuclear layer. The alterations at the level of the choriocapillaris and the choroid, in general, could then represent a secondary effect.

PURPOSE: To estimate and compare cross-sectional scotopic versus mesopic macular sensitivity losses measured by microperimetry, and to report and compare the longitudinal rates of scotopic and mesopic macular sensitivity losses in ABCA4 gene associated Stargardt Disease (STGD1). DESIGN: Multicenter prospective cohort study. METHODS: PARTICIPANTS: 127 molecular confirmed STGD1 patients enrolled from 6 centers in the USA and Europe and followed every 6 months for up to 2 years. OBSERVATION PROCEDURES: The Nidek MP-1S device was used to measure macular sensitivities of the central 20° under mesopic and scotopic conditions. The mean deviations (MD) from normal for mesopic macular sensitivity for the fovea (within 2° eccentricity) and extrafovea (4°−10° eccentricity), and the MD for scotopic sensitivity for the extrafovea were calculated. Linear mixed effects models were used to estimate mesopic and scotopic changes. MAIN OUTCOME MEASURES: Baseline mesopic mean deviation (mMD) and scotopic MD (sMD) and rates of longitudinal changes in the mMDs and sMD. RESULTS: At baseline, all eyes had larger sMD, and the difference between extrafoveal sMD and mMD was 10.7 dB (p

We propose target date funds modified to exploit stock return predictability driven by the variance risk premium. The portfolio rule of these tactical target date funds (TTDFs) is extremely simplified relative to the optimal one, making it easy to implement and to communicate to investors. We show that saving for retirement in TTDFs generates economically large welfare gains, even after we introduce turnover restrictions and transaction costs, and after taking into account parameter uncertainty. This predictability also appears to be uncorrelated with individual household risk, suggesting that households are in a prime position to exploit it. This paper was accepted by Tomasz Piskorski, finance.

Contains fulltext : 251572.pdf (Publisher’s version ) (Closed access) We assessed genotype-phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) (n = 47) due to USH2A variants, using clinical data and molecular diagnostics from the Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A) study. USH2A truncating alleles were associated with USH2 and had a dose-dependent effect on hearing loss severity with no effect on visual loss severity within the USH2 subgroup. A group of missense alleles in an interfibronectin domain appeared to be hypomorphic in ARRP. These alleles were associated with later age of onset, larger visual field area, better sensitivity thresholds, and better electroretinographic responses. No effect of genotype on the severity of olfactory deficits was observed. This study unveils a unique, tissue-specific USH2A allelic hierarchy with important prognostic implications for patient counseling and treatment trial endpoints. These findings may inform clinical care or research approaches in others with allelic disorders or pleiotropic phenotypes.

Chemogenetics enables precise, noninvasive, and reversible modulation of neural activity via the activation of engineered receptors that are pharmacologically selective to endogenous or exogenous ligands. With recent advances in therapeutic gene delivery, chemogenetics is poised to support novel interventions against neuropsychiatric diseases and disorders. To evaluate its translational potential, we performed a scoping review of applications of chemogenetics that led to the reversal of molecular and behavioral deficits in studies relevant to neuropsychiatric diseases and disorders. In this review, we present these findings and discuss the potential and challenges for using chemogenetics as a precision medicine-based neuromodulation strategy.

This study corresponds to the first large-scale genetic analysis of inherited eye diseases (IED) in Argentina and describes the comprehensive genetic profile of a large cohort of patients. Medical records of 22 ophthalmology and genetics services throughout 13 Argentinian provinces were analyzed retrospectively. Patients with a clinical diagnosis of an ophthalmic genetic disease and a history of genetic testing were included. Medical, ophthalmological and family history was collected. A total of 773 patients from 637 families were included, with 98% having inherited retinal disease. The most common phenotype was retinitis pigmentosa (RP, 62%). Causative variants were detected in 379 (59%) patients. USH2A, RPGR, and ABCA4 were the most common disease-associated genes. USH2A was the most frequent gene associated with RP, RDH12 early-onset severe retinal dystrophy, ABCA4 Stargardt disease, PROM1 cone-rod dystrophy, and BEST1 macular dystrophy. The most frequent variants were RPGR c.1345 C > T, p.(Arg449*) and USH2A c.15089 C > A, p.(Ser5030*). The study revealed 156/448 (35%) previously unreported pathogenic/likely pathogenic variants and 8 possible founder mutations. We present the genetic landscape of IED in Argentina and the largest cohort in South America. This data will serve as a reference for future genetic studies, aid diagnosis, inform counseling, and assist in addressing the largely unmet need for clinical trials to be conducted in the region.

The presence of aerosol and clouds constitutes one of the highest uncertainties regarding the energy budget of the Earth. Therefore, their continuous observation can help reduce these uncertainties, by providing more information about aerosol-cloud interactions and how these atmospheric components contribute to climate change.To study the properties of aerosols and clouds, new infrastructure will soon be set up in Cyprus by the Eratosthenes Centre of Excellence, which was recently established through the ‘EXCELSIOR’ H2020 Widespread Teaming Project. Eratosthenes Centre of Excellence is a digital innovation hub for Earth Observation, Space Technology and Geospatial Information, aiming to become the reference centre in the East Mediterranean, north Africa and the Middle East (EMMENA region). The infrastructure will be installed in Limassol, on the south coast of the island. Apart from the fact that the site is less than 2 km from the island’s coastline, this location is extremely important in terms of the regional atmospheric composition, as the air masses affecting the site originate from the surrounding areas of EMMENA, as well as from south-eastern Europe.Infrastructure to sample aerosol is already represented by a state-of-the-art PollyXT lidar, with measurements being registered continuously since October 2020. By the end of 2023, a similar LACROS multi-instrument platform will be available for the continuous monitoring of clouds and aerosols. This new ground-based remote sensing platform consists of a 35GHz cloud radar, a ceilometer, a microwave radiometer, a Doppler lidar, and a disdrometer. The infrastructure will be integrated into the Cyprus Atmospheric Remote Sensing Observatory (CARO).An example of the value of the observations about cloud formation and the role of aerosol in the process of cloud formation that will be provided from the site in Limassol, can be reflected in the data collected during the CyCARE campaign, executed between October 2016 and March 2018, during which similar ground-based infrastructure was deployed. The authors acknowledge the ‘EXCELSIOR’: ERATOSTHENES: EΧcellence Research Centre for Earth Surveillance and Space-Based Monitoring of the Environment H2020 Widespread Teaming project (www.excelsior2020.eu). The ‘EXCELSIOR’ project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 857510, from the Government of the Republic of Cyprus through the Directorate General for the European Programmes, Coordination and Development and the Cyprus University of Technology.

Drought is a multidimensional phenomenon that is imperceptible at its early stages, it evolves slowly and cumulatively and results to adverse consequences, for example depletion of water volumes from rivers and reservoirs, decrease of carbon uptake in vegetation etc. Cyprus is characterized by semi-arid to arid climate conditions, experiencing extensive droughts that have a negative impact on the ecosystem, the economy and the agricultural production.Existing research on drought events in Cyprus is limited to the usage of in-situ data, mainly temperature and precipitation measurements at meteorological stations. Polarimetric weather radars can offer more detailed information regarding precipitation phenomena, especially in areas with sparse network of meteorological stations or remote areas of interest.This study compares reflectivity measurements from the two ground-based X-band dual polarization radars of the Department of Meteorology of the Republic of Cyprus with measurements obtained from NASA’s Global Precipitation Measurement (GPM) mission.The DPR (Dual-frequency Precipitation Radar) aboard of GPM is employed in order to derive the radar reflectivity factor with a spatial resolution of 5-25 km for 120 km wide swath. The ground-based radars operate since 2017. They scan in PPI mode at eight (8) constant elevation angles, whereas their azimuth angle varies with a spatial resolution of 0.1° and the radius of each scan is 150 km. The radar stations are located in Rizoelia, Larnaca district, and Nata, Paphos district, providing a full coverage of the island.Satellite-based radar reflectivity values are used to adjust the ground-based radar measurements. Consequently, the adjusted values of the ground-based radar reflectivity are used as input to modelling expressions for estimating the ground-based radar precipitation.In order to ensure that the observations are spatially coincident, we have developed a collocated grid, hereafter called universal grid, on which both the ground- and satellite-based radar observations are interpolated at the same locations. The universal grid is a three-dimensional (3D) grid with grid cell size of approximately 2500 m along both horizontal directions, whereas the vertical resolution is set equal to the height resolution of GPM, i.e. 150 m. Regarding temporal resolution, GPM overpasses Cyprus approximately once a week. For the purposes of this study, we selected overflights after the beginning of the ground-based radar operation that coincide with precipitation events.Additionally, statistical analysis of the reflectivity measurements has been conducted to understand the relationship between the ground-based and the satellite-based datasets and identify spatio-temporal patterns of precipitation.Acknowledgements:The authors acknowledge the ‘EXCELSIOR’: ERATOSTHENES: EΧcellence Research Centre for Earth Surveillance and Space-Based Monitoring of the Environment H2020 Widespread Teaming project (www.excelsior2020.eu). The ‘EXCELSIOR’ project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 857510, from the Government of the Republic of Cyprus through the Directorate General for the European Programmes, Coordination and Development and the Cyprus University of Technology.The authors acknowledge also the Department of Meteorology of the Republic of Cyprus for the provision of the X-band radar data.

Soil degradation implies a long-term decline in soil productivity and quality. Therefore, soil health restoration constitutes an urgent priority to achieve sustainable ecosystem services that are vital to life on Earth. That requires the development of targeted agricultural policy maps. To generate them on a national scale, a large number of hydrogeological models should be built for selected representative agricultural fields. However, the parameterization of the effective properties as input in hydrogeological models for simulating water flow and solute transport is a time-consuming and costly process characterized by high uncertainty because of the spatial variability of soil physical and hydraulic properties. In the long-term, the usage of Earth Observation (EO) data in parameterizing effective soil properties, meteorological conditions, and vegetation indexes have a clear advantage over other methods based on ground-only measured data since using EO data allows repeated monitoring of land degradation dynamics over larger spatial scales and multiple climatic/biogeographical regions at lower costs and less time-consuming. In this study, integrating EO models and global pedotransfer functions, a concept is proposed for covering the absence of data and estimating the effective parameters as input in a single porosity model for simulating the water flow dynamics in a selected agricultural field in Cyprus. For the calibration and validation of the models, groundwater level data from two different periods were utilized. The performance statistics of the developed water flow model for the entire simulation were characterized fairly well, setting the suggested concept as a valuable tool for parameterizing the effective hydraulic parameters.Acknowledgement“The authors acknowledge the ‘EXCELSIOR’: ERATOSTHENES: EΧcellence Research Centre for Earth Surveillance and Space-Based Monitoring of the Environment H2020 Widespread Teaming project (www.excelsior2020.eu). The ‘EXCELSIOR’ project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 857510, from the Government of the Republic of Cyprus through the Directorate General for the European Programmes, Coordination and Development and the Cyprus University of Technology.”

Permafrost soils in boreal forests and tundra store more than two atmospheres worth of carbon, yet the vigorous permafrost-carbon-climate feedback loop remains poorly understood. In addition to ongoing strong warming, fires can further accelerate permafrost degradation and trigger the release of ancient carbon into the atmosphere. Despite the urgency after the recent Arctic fire seasons of 2019, 2020 and 2021, fire-permafrost interactions are currently not included in Earth system models from the sixth assessment of the Intergovernmental Panel on Climate Change (IPCC). This is because large-scale observations of fire-induced permafrost degradation are lacking. Therefore, we studied fire-induced permafrost degradation using the Interferometric Synthetic Aperture Radar (InSAR) technique and time series of Sentinel-1 (S-1) imagery. In this pilot study, we tested our approach on fires from 2019 and 2020 in the Chokurdakh area, Northeastern Siberia. We processed time series S-1 SAR data from a snow-free season (June-October) where S-1 SAR image selection was automated by using the Moderate Resolution Imaging Spectroradiometer snow cover products. To understand the drivers of InSAR-derived subsidence, we applied the XGBoost regression algorithm using subsidence as a response variable and ten other environmental variables as predictor variables. First, we found that the time series InSAR technique is suitable for deriving subsidence over fire-affected permafrost terrain. Second, the fire-affected permafrost terrain exhibited four to five times greater subsidence compared to the surrounding unburned area. Third, the XGBoost regression model revealed land surface temperature (LST) and albedo (derived from Landsat data) as the primary predictor variables of surface subsidence, accounting for more than 50% of the predictive power. The permafrost degradation in many tundra areas is likely dominated by fire-induced changes in the surface energy balance. From this pilot study, we conclude that our approach has the potential to study fire-permafrost interaction and environmental drivers of surface subsidence at the northern circumpolar scale. Models can also use our data to parameterize subsidence and thermokarst processes associated with permafrost degradation due to fire.

Recent studies have shown that climate change is likely to affect the agricultural sector in Cyprus. In the present study, crop water requirements in each of the 1995–2004 and 2010-2019 decades are estimated, by employing the same methodology, and subsequently compared. The aim is to investigate whether there has been any significant change regarding the crop water requirements of the most water-intensive crops in Cyprus. For the estimation of the crop evapotranspiration, the FAO Penman-Monteith methodology is used, as this has been adapted to satellite data. Remote-sensing data from Landsat TM/ETM+/OLI were employed.Five water-intensive crops are in the focus of this research: citrus, bananas, colocasi, potatoes, and avocado. For each of these crops, estimations of the crop evapotranspiration were performed, considering three agricultural areas on the island where these crops are grown: Pafos, Polis, and Famagusta.The results have shown that there is no significant effect of climate variation on crop evapotranspiration, despite the fact that some climatic factors have exhibited a change on the island of Cyprus; the mean values for the most water-intensive trees/crops in Cyprus in the 1994–2004 decade have shown no significant difference from the mean values in the 2010–2019 decade, for all the crops and all agricultural areas. From the statistical analysis performed, it can be concluded that the climate change which has been documented in the past decades has not impacted significantly the crop evapotranspiration.The authors would like to express their thanks to the Agricultural Research Institute for providing the proper resources for applying the specific methodology. Also, the authors acknowledge the ‘EXCELSIOR’: ERATOSTHENES: EΧcellence Research Centre for Earth Surveillance and Space-Based Monitoring of the Environment H2020 Widespread Teaming project (www.excelsior2020.eu). The ‘EXCELSIOR’ project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 857510, from the Government of the Republic of Cyprus through the Directorate General for the European Programmes, Coordination and Development and the Cyprus University of Technology.

Retinal diseases are a leading cause of blindness in developed countries, accounting for the largest share of visually impaired children, working-age adults (inherited retinal disease), and elderly individuals (age-related macular degeneration). These conditions need specialised clinicians to interpret multimodal retinal imaging, with diagnosis and intervention potentially delayed. With an increasing and ageing population, this is becoming a global health priority. One solution is the development of artificial intelligence (AI) software to facilitate rapid data processing. Herein, we review research offering decision support for the diagnosis, classification, monitoring, and treatment of retinal disease using AI. We have prioritised diabetic retinopathy, age-related macular degeneration, inherited retinal disease, and retinopathy of prematurity. There is cautious optimism that these algorithms will be integrated into routine clinical practice to facilitate access to vision-saving treatments, improve efficiency of healthcare systems, and assist clinicians in processing the ever-increasing volume of multimodal data, thereby also liberating time for doctor-patient interaction and co-development of personalised management plans.

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.

BACKGROUND Accessible self-management interventions are required to support people living with breast cancer. OBJECTIVE This was an industry-academic partnership study designed that aimed to gather user experience data of a prototype app with built-in peer and coach support designed to support management of health behaviours and weight in women living with breast cancer. METHODS Participants were >18 years old, diagnosed with breast cancer of any stage within the last 5 years (full inclusion/exclusion in main text). Participants completed demographic surveys then were asked to use the app for four weeks. Following this, they took part in in-depth qualitative interviews about their experiences. Interviews were analysed using thematic analysis. RESULTS Eight participants (mean age 45 years, 88% white, 75% educated to degree level or above, 75% with stage I-III breast cancer), took part. Four overarching themes were identified; 1) Support for providing an app earlier in the care pathway, 2) Desire for more weight focused content tailored to the breast cancer experience 3) Tracking of health behaviours generally popular and 4) High value of in-app social support. CONCLUSIONS This early user experience work found that women with breast cancer found an app with integrated social and psychological support an appealing way to receive support for behaviour change and weight/self-management. However, a number of features were recommended for further development. This work is the first step in an academic-industry collaboration that would ultimately aim to develop and empirically test a supportive app that could be integrated into the cancer care pathway