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In this work, we consider a Shallow‐Water Quasi Geostrophic equation on the sphere, as a model for global large‐scale atmospheric dynamics. This equation, previously studied by Verkley (2009, https://doi.org/10.1175/2008jas2837.1) and Schubert et al. (2009, https://doi.org/10.3894/james.2009.1.2), possesses a rich geometric structure, called Lie‐Poisson, and admits an infinite number of conserved quantities, called Casimirs. In this paper, we develop a Casimir preserving numerical method for long‐time simulations of this equation. The method develops in two steps: first, we construct an N‐dimensional Lie‐Poisson system that converges to the continuous one in the limit N → ∞; second, we integrate in time the finite‐dimensional system using an isospectral time integrator, developed by Modin and Viviani (2020, https://doi.org/10.1017/jfm.2019.944). We demonstrate the efficacy of this computational method by simulating a flow on the entire sphere for different values of the Lamb parameter. We particularly focus on rotation‐induced effects, such as the formation of jets. In agreement with shallow water models of the atmosphere, we observe the formation of robust latitudinal jets and a decrease in the zonal wind amplitude with latitude. Furthermore, spectra of the kinetic energy are computed as a point of reference for future studies. Plain Language Summary We conducted a study on a model that represents the movements of planetary flows. This model has important physical and mathematical properties that are related to its long‐term behavior, which is essential for understanding geophysical turbulence. In this work, we developed a numerical method for simulation that preserves the key mathematical structure of the model through a two‐step process. We applied our method to simulate global atmospheric flow and investigate the impact of varying strengths of planetary rotation. Our findings demonstrate the expected formation of wind patterns known as zonal jets, where stronger winds occur near the equator and weaker winds near the poles. We also present energy spectra that illustrate the influence of planetary rotation on the transfer of turbulent energy, which aligns with existing theoretical predictions found in literature. These results highlight the potential of our numerical method for studying fundamental problems in geophysical fluid dynamics. Key Points We develop a numerical method preserving Casimirs to simulate balanced shallow water flow on the sphere We perform global high‐resolution simulations while accurately accounting for latitude‐dependent effects Our simulations show the formation of robust zonal jets and provide key insights into quasi‐geostrophic turbulence

Although today's US equipment is able to show very small lesions, those lesions that are smaller than 5 mm in size are still difficult to find and/or characterize on US. Frequently, correlation with mammographie findings provides an essential clue to find and/or characterize a lesion on US. Some of the very subtle US findings, such as completely isoechoic tiny lesions, can only be visible after correlation with mammography (Figure 1). Because USguided biopsy is usually more convenient for both the patient and the radiologist for most lesions that are seen on both mammogram and US, the ability to locate and image subtle lesions on US makes the biopsy procedure more efficient. After biopsy, a postbiopsy mammogram can confirm accurate sampling of the lesion. If a lesion itself has heterogeneous echogenicity, it can be challenging to find the lesion on US, even if it is identified on a mammogram (Figure 3). In this case, the \"mass effect\" on US frequently helps identify the lesion. Normal parenchyma does not deform surrounding tissue, whereas a true 3dimensional lesion tends to show some degree of mass effect, demonstrating compression of the normal tissue adjacent to the mass. This mass effect is better identified when the US probe is moving over the lesion. Also, normal tissues are smoothly continuous with adjacent tissue, whereas a true lesion is abruptly discontinuous at its edge from the surrounding normal tissue (Figure 4). This effect is also better identified when the US probe is moving over the lesion. Incorrect localization between different imaging modalities can result in a missed lesion (Figure 8). Localization and/or triangulation techniques of breast lesions have been described in the literature [9-14]. In addition to identifying the quadrant of the breast where the lesion is located, the depth of the lesion and its distance from the nipple must be considered when correlating between mammography and US (11). Mammography is performed with upright positioning and compression of breast tissue, whereas US is performed in a supine and rather relaxed position. Therefore, the findings on a mammogram are more of a \"side\" view, whereas the findings on US are a combination of both \"side\" and \"en face\" views, especially when correlating distance of the lesion from the nipple (Figure 9).

Stereotactic core biopsy is performed primarily on mammographically identified lesions that consist of clustered suspicious microcalcifications; however, it can also be used for small masses or, rarely, for some other mammographie findings, for example, focal asymmetry. Stereotactic core biopsy involves definitively calculating the 3-dimensional location (x, y, z coordinates) of a nonpalpable lesion within the breast and properly deploying a sampling device to obtain pathologic samples from the lesion [6-9]. To correctly determine the 3-dimensional location (x, y, z coordinates) of a nonpalpable lesion, the lesion must be identified on 2 mammographie views. These should be acquired during the routine diagnostic mammogram, before the biopsy date, to avoid wasting time or unsuccessful performance of the biopsy procedure. Proper knowledge of localization and/or triangulation of the lesion is required [10-15]. Most stereotactic core biopsies are performed these days with vacuum-assisted devices. The devices developed initially used multiple separate vacuum-assisted cuttings of the tissue. Recently developed devices, however, allow continuous vacuum-assisted cutting of the tissue. These new devices also provide \"petite needles\" with shorter biopsy excursion, with or without a blunted tip, that allow biopsy in thinner breasts. Generally, at least 3 cm thickness of breast tissue is required for regular biopsy needles; however, breasts less than 3 cm thick are amenable for stereotactic core biopsy with these \"petite needles.\" Among the x, y, z coordinates, the z-coordinate is probably the most important number used during the biopsy procedure. The z-coordinate indicates the location of the lesion that will be in the centre of the biopsy excursion of the needle after firing. This number is used to calculate the stroke margin for a safe biopsy without the risk of contacting the back support panel by the needle (Figure 1A). The z-coordinate is calculated from the z-zero position; therefore, it includes the thickness of the compression paddle, which is 12 mm for the most widely used biopsy table. The length of the biopsy excursion, the length of the tip of each needle, the thickness of the compression paddle, the thickness of the breast, and the depth of the lesion must be considered altogether to calculate the safety margin. For example, for a needle with a 20-mm biopsy excursion and an 8-mm tip, the compressed breast thickness must be thicker than z + 6 (z + 10 + 8 ≤ 12 + breast compression thickness) (Figure 1B). If the biopsy excursion of another needle is 24 mm with an 8-mm tip, then the compressed breast thickness must be thicker than z + 8 (z + 12 + 8 ≤ 12 + breast compression thickness). If the tip of this needle becomes 10 mm, then the compressed breast thickness must also be thicker than z + 10 (z+ 12+ 10 ≤ 12 + breast compression thickness). If the z-coordinate does not give proper stroke margin, then the first solution can be to simply rotate the breast to get thicker tissue towards the supporting panel (Figure 1C, D). All the above calculations are based on the assumption that the targeted lesion is located in the centre of the biopsy excursion after firing. Because the 20-mm length of biopsy excursion of a regular needle is quite long, lesions need not be precisely located in the centre of the biopsy excursion. If the z-coordinate of a lesion results in an inadequate stroke margin, then the stereotactic biopsy system may provide a warning alarm when the operator inserts the needle to the prefire position. In this instance, simply manually \"pullingback\" the needle to a more superficial prefire position will disengage the alarm and place the needle in a position that will prevent it from contacting the posterior breast support plate at firing while the targeted lesion is still within the biopsy excursion of the needle in a slightly distal position in the excursion. This adjustment is also applied to lesions located close to the skin. In this case, the stroke margin is within the acceptable range, but the biopsy excursion is initially seen outside of the skin after firing, which indicates inevitable cutting of the skin. Manual \"pulling-in\" of the needle until the biopsy excursion is no longer seen outside of the skin will exclude possible skin biopsy while the targeted lesion is still within the biopsy excursion of the needle in a slightly proximal position (Figure 2B).

Several current theories emphasize the role of cognitive control in addiction. The present review evaluates neural deficits in the domains of inhibitory control and error processing in individuals with substance dependence and in those showing excessive addiction-like behaviours. The combined evaluation of event-related potential (ERP) and functional magnetic resonance imaging (fMRI) findings in the present review offers unique information on neural deficits in addicted individuals. We selected 19 ERP and 22 fMRI studies using stop-signal, go/no-go or Flanker paradigms based on a search of PubMed and Embase. The most consistent findings in addicted individuals relative to healthy controls were lower N2, error-related negativity and error positivity amplitudes as well as hypoactivation in the anterior cingulate cortex (ACC), inferior frontal gyrus and dorsolateral prefrontal cortex. These neural deficits, however, were not always associated with impaired task performance. With regard to behavioural addictions, some evidence has been found for similar neural deficits; however, studies are scarce and results are not yet conclusive. Differences among the major classes of substances of abuse were identified and involve stronger neural responses to errors in individuals with alcohol dependence versus weaker neural responses to errors in other substance-dependent populations. Task design and analysis techniques vary across studies, thereby reducing comparability among studies and the potential of clinical use of these measures. Current addiction theories were supported by identifying consistent abnormalities in prefrontal brain function in individuals with addiction. An integrative model is proposed, suggesting that neural deficits in the dorsal ACC may constitute a hallmark neurocognitive deficit underlying addictive behaviours, such as loss of control.

The effectiveness of repetitive transcranial Direct Current Stimulation (tDCS) on reducing smoking behaviour has been studied with mixed results. Smoking behaviour is influenced by affect and context, therefore we choose to use mobile ecological momentary assessments (EMA) to measure changes in smoking behaviour after tDCS. In a randomized, placebo-controlled, between subject study, we applied tDCS bilaterally with the anodal electrode targeting the right DLPFC (https://clinicaltrials.gov/ct2/show/NCT03027687). Smokers were allocated to six sessions of either active tDCS (n = 35) or sham tDCS (n = 36) and received two sessions on three different days in one week. They were asked to keep track of their daily cigarette consumption, craving and affect in an application on their mobile phones for three months starting one week before the first tDCS session. Number of smoked cigarettes a day progressively decreased up to one week after the last tDCS session in both conditions. Active treatment had no additional effect on cigarette consumption, craving and affect. In this exploratory study, repetitive bilateral tDCS over the DLPFC had no effect on daily smoking behaviour. Future research needs to investigate how motivation to quit smoking and the number of tDCS sessions affect the efficacy of repetitive tDCS.

Research suggests that mindfulness-practices may aid smoking cessation. Yet, the neural mechanisms underlying the effects of mindfulness-practices on smoking are unclear. Response inhibition is a main deficit in addiction, is associated with relapse, and could therefore be a candidate target for mindfulness-based practices. The current study hence investigated the effects of a brief mindfulness-practice on response inhibition in smokers using behavioral and electroencephalography (EEG) measures. Fifty participants (33 females, mean age 20 years old) underwent a protocol of cigarette exposure to induce craving (cue-exposure) and were then randomly assigned to a group receiving mindfulness-instructions or control-instructions (for 15 minutes approximately). Immediately after this, they performed a smoking Go/NoGo task, while their brain activity was recorded. At the behavioral level, no group differences were observed. However, EEG analyses revealed a decrease in P3 amplitude during NoGo vs. Go trials in the mindfulness versus control group. The lower P3 amplitude might indicate less-effortful response inhibition after the mindfulness-practice, and suggest that enhanced response inhibition underlies observed positive effects of mindfulness on smoking behavior.

The need for accessible and motivating treatment approaches within mental health has led to the development of an Internet-based serious game intervention (called \"Plan-It Commander\") as an adjunct to treatment as usual for children with attention-deficit/hyperactivity disorder (ADHD). The aim was to determine the effects of Plan-It Commander on daily life skills of children with ADHD in a multisite randomized controlled crossover open-label trial. Participants (N=170) in this 20-week trial had a diagnosis of ADHD and ranged in age from 8 to 12 years (male: 80.6%, 137/170; female: 19.4%, 33/170). They were randomized to a serious game intervention group (group 1; n=88) or a treatment-as-usual crossover group (group 2; n=82). Participants randomized to group 1 received a serious game intervention in addition to treatment as usual for the first 10 weeks and then received treatment as usual for the next 10 weeks. Participants randomized to group 2 received treatment as usual for the first 10 weeks and crossed over to the serious game intervention in addition to treatment as usual for the subsequent 10 weeks. Primary (parent report) and secondary (parent, teacher, and child self-report) outcome measures were administered at baseline, 10 weeks, and 10-week follow-up. After 10 weeks, participants in group 1 compared to group 2 achieved significantly greater improvements on the primary outcome of time management skills (parent-reported; P=.004) and on secondary outcomes of the social skill of responsibility (parent-reported; P=.04), and working memory (parent-reported; P=.02). Parents and teachers reported that total social skills improved over time within groups, whereas effects on total social skills and teacher-reported planning/organizing skills were nonsignificant between groups. Within group 1, positive effects were maintained or further improved in the last 10 weeks of the study. Participants in group 2, who played the serious game during the second period of the study (weeks 10 to 20), improved on comparable domains of daily life functioning over time. Plan-It Commander offers an effective therapeutic approach as an adjunct intervention to traditional therapeutic ADHD approaches that improve functional outcomes in daily life. International Standard Randomized Controlled Trial Number (ISRCTN): 62056259; http://www.controlled-trials.com/ISRCTN62056259 (Archived by WebCite at http://www.webcitation.org/6eNsiTDJV).

Antibiotic resistance poses rapidly increasing global problems in combatting multidrug-resistant (MDR) infectious diseases like MDR tuberculosis, prompting for novel approaches including host-directed therapies (HDT). Intracellular pathogens like Salmonellae and Mycobacterium tuberculosis ( Mtb ) exploit host pathways to survive. Only very few HDT compounds targeting host pathways are currently known. In a library of pharmacologically active compounds (LOPAC)-based drug-repurposing screen, we identify multiple compounds, which target receptor tyrosine kinases (RTKs) and inhibit intracellular Mtb and Salmonellae more potently than currently known HDT compounds. By developing a data-driven in silico model based on confirmed targets from public databases, we successfully predict additional efficacious HDT compounds. These compounds target host RTK signaling and inhibit intracellular (MDR) Mtb . A complementary human kinome siRNA screen independently confirms the role of RTK signaling and kinases (BLK, ABL1, and NTRK1) in host control of Mtb . These approaches validate RTK signaling as a drugable host pathway for HDT against intracellular bacteria. Multidrug resistance necessitates novel approaches to treating bacterial infections. Here, the authors apply their high-throughput screening and in silico prediction approaches to show that host receptor tyrosine kinases are good targets for host-directed therapies against intracellular bacteria.

Embedding multi-wavelength lasers in photonic waveguide circuits is of interest for next-generation ion traps, such as for miniaturizing optical clocks or upscaling ion-based quantum computing. Critically, this path involves photonic integration of highly coherent lasers in the ultraviolet (UV) range, which is presently obstructed by the transparency limit of materials used in established integrated waveguides. Here, we demonstrate the first integrated, extended cavity diode laser based solely on UV-transparent materials. We integrate aluminum oxide waveguide circuits with gallium nitride amplifiers to generate milliwatt-level on-chip output power near the ultraviolet range. The extended cavity approach allows for wide wavelength coverage and precise frequency control, which is demonstrated by tuning mode-hop-free to a Sr-transition frequency. Due to the inherent stability of photonic circuits and UV-compatible integration, the intrinsic laser linewidth reaches a record-low value around 300 kHz with better than 43-dB side-mode suppression. These results announce the viability of a novel class of integrated lasers that opens access to the UV. Integrating UV lasers is of interest for portable optical clocks and ion-based quantum computers, but material absorption has impeded progress. Here, authors demonstrate a violet integrated laser using UV-transparent materials with mW-level output, narrow linewidth and precise frequency control.

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of childhood chronic kidney disease. Congenital nephrotic syndrome of the Finnish type (CNF) (MIM# 256300) is caused by biallelic variants in the gene NPHS1 , encoding nephrin, an integral component of the kidney filtration barrier. No causal treatments exist, and children inevitably require kidney replacement therapy. In preparation for gene replacement therapy (GRT) in CNF, we established a quantifiable and reproducible phenotypic assessment of the nephrin-deficient CNF mouse model: 129/Sv- Nphs1 tm1Rkl /J . We assessed the phenotypic spectrum of homozygous mice ( Nphs1 tm1Rkl /Nphs1 tm1Rkl ) compared to heterozygous controls ( Nphs1 tm1Rkl /Nphs1 WT ) by the following parameters: 1. cohort survival, 2. podocyte foot process (FP) density per glomerular basement membrane (GBM) using transmission electron microscopy, 3. tubular microcysts in brightfield microscopy, and 4. urinary albumin/creatinine ratios. Nphs1 tm1Rkl /Nphs1 tm1Rkl mice exhibited: 1. perinatal lethality with median survival of 1 day, 2. FP effacement with median FP density of 1.00 FP/µm GBM (2.12 FP/µm in controls), 3. tubular dilation with 65 microcysts per section (6.5 in controls), and 4. increased albumin/creatinine ratio of 238 g/g (4.1 g/g in controls). We here established four quantifiable phenotyping features of a CNF mouse model to facilitate future GRT studies by enabling sensitive detection of phenotypic improvements.