Clinical Validation of Selected NIH Cognitive Toolbox Tasks in Pediatric Epilepsy.

The NIH Toolbox Cognition Battery (NIHTB-CB) is designed to assess cognitive functioning across the lifespan. We aimed to evaluate the clinical validity of two NIHTB-CB tasks as cognitive screening tools in pediatric epilepsy by comparing them to standard neuropsychological measures and their association with epilepsy characteristics. Forty-seven patients with epilepsy ages 5-18, including ten repeat evaluations, were assessed. Correlational analyses and agreement statistics were conducted to validate NIHTB-CB tasks (Flanker Inhibitory Control and Attention test (Flanker) and Pattern Comparison Processing Speed test (Pattern Comparison)) with standard clinical measures. We also examined if performance was related to epilepsy characteristics, including polytherapy, age of seizure onset, seizure type, and history of Electrical Status Epilepticus in Sleep (ESES). The NIHTB-CB tests had moderate to strong correlations with neuropsychological measures of executive functioning, processing speed, and intelligence. Agreement statistics indicated better sensitivity than specificity. Polytherapy and later age of seizure onset were associated with lower performance on Pattern Comparison. ESES patients did not significantly differ in performance on the tests compared to non-ESES patients. Pilot data from a subset of repeated measures indicated a good range of change scores. These two NIHTB tasks are feasible as a screening tool in a clinic given their correlation with clinical measures that assess executive function, processing speed, and IQ. This study supports the use of these tasks as brief, easily accessible screener tools to identify cognitive dysfunction in domains commonly impacted in patients with epilepsy and potential use for monitoring over time.

Jupiter Science Enabled by ESA's Jupiter Icy Moons Explorer.

ESA's Jupiter Icy Moons Explorer (JUICE) will provide a detailed investigation of the Jovian system in the 2030s, combining a suite of state-of-the-art instruments with an orbital tour tailored to maximise observing opportunities. We review the Jupiter science enabled by the JUICE mission, building on the legacy of discoveries from the Galileo, Cassini, and Juno missions, alongside ground- and space-based observatories. We focus on remote sensing of the climate, meteorology, and chemistry of the atmosphere and auroras from the cloud-forming weather layer, through the upper troposphere, into the stratosphere and ionosphere. The Jupiter orbital tour provides a wealth of opportunities for atmospheric and auroral science: global perspectives with its near-equatorial and inclined phases, sampling all phase angles from dayside to nightside, and investigating phenomena evolving on timescales from minutes to months. The remote sensing payload spans far-UV spectroscopy (50-210 nm), visible imaging (340-1080 nm), visible/near-infrared spectroscopy (0.49-5.56 µm), and sub-millimetre sounding (near 530-625 GHz and 1067-1275 GHz). This is coupled to radio, stellar, and solar occultation opportunities to explore the atmosphere at high vertical resolution; and radio and plasma wave measurements of electric discharges in the Jovian atmosphere and auroras. Cross-disciplinary scientific investigations enable JUICE to explore coupling processes in giant planet atmospheres, to show how the atmosphere is connected to (i) the deep circulation and composition of the hydrogen-dominated interior; and (ii) to the currents and charged particle environments of the external magnetosphere. JUICE will provide a comprehensive characterisation of the atmosphere and auroras of this archetypal giant planet.

Hydrogen peroxide at the poles of Ganymede.

Ganymede is the only satellite in the solar system known to have an intrinsic magnetic field. Interactions between this field and the Jovian magnetosphere are expected to funnel most of the associated impinging charged particles, which radiolytically alter surface chemistry across the Jupiter system, to Ganymede's polar regions. Using observations obtained with JWST as part of the Early Release Science program exploring the Jupiter system, we report the discovery of hydrogen peroxide, a radiolysis product of water ice, specifically constrained to the high latitudes. This detection directly implies radiolytic modification of the polar caps by precipitation of Jovian charged particles along partially open field lines within Ganymede's magnetosphere. Stark contrasts between the spatial distribution of this polar hydrogen peroxide, those of Ganymede's other radiolytic oxidants, and that of hydrogen peroxide on neighboring Europa have important implications for understanding water-ice radiolysis throughout the solar system.

Impact of Menopausal Status and Recurrent UTIs on Symptoms, Severity, and Daily Life: Findings from an Online Survey of Women Reporting a Recent UTI.

Introduction: Current UKHSA UTI diagnostic guidance advises empirical antibiotics if two of the following symptoms are present: cloudy urine, dysuria, and new onset nocturia. Hormonal changes during menopause may impact UTI symptoms, and qualitative studies suggest women with recurrent UTIs may present with different UTI symptoms. This study aims to assess whether menopausal status and the presence of recurrent UTIs impact UTI symptoms in women. Methods: An e-survey was conducted between 13 March 2021 and 13 April 2021. Women aged 16 years or older with a history of a UTI in the last year were eligible for inclusion. We defined menopause as those aged 45-64 years; pre-menopause as those less than 45 years; and post-menopause as those 65 years and older. Recurrent UTIs were defined as three or more UTIs in the last year. The data were weighted to be representative of the UK population. Crude unadjusted and adjusted odds ratios were estimated using logistic regression. Results: In total, 1096 women reported a UTI in the last year. There were significant differences in UTI symptoms based on menopausal status and the presence of recurrent UTIs. Post-menopausal women self-reported more incontinence (OR 2.76, 95% CI 1.50,5.09), whereas menopausal women reported more nocturia. Women with recurrent UTIs reported less dysuria, more severe symptoms (OR 1.93 95% CI 1.37,2.73) and a greater impact on daily life (OR 1.68, 95% CI 1.19,2.37). Conclusions: This survey provides evidence that acute UTIs present differently based on menopausal status and in women with recurrent UTIs. It is important that healthcare professionals are aware of these differences when assessing women presenting with an acute UTI and, therefore, further research in this area is needed.

MRI Features and Their Association With Outcomes in Children With Anti-NMDA Receptor Encephalitis.

OBJECTIVES: How brain MRI lesions associate with outcomes in pediatric anti-NMDA receptor encephalitis (pNMDARE) is unknown. In this study, we correlate T2-hyperintense MRI brain lesions with clinical outcomes in pNMDARE. METHODS: This was a multicenter retrospective cohort study from 11 institutions. Children younger than 18 years with pNMDARE were included. One-year outcomes were assessed by the modified Rankin Score (mRS) with good (mRS ≤2) and poor (mRS ≥3) outcomes. RESULTS: A total of 175 pNMDARE subjects were included, with 1-year mRS available in 142/175 (81%) and 60/175 (34%) had abnormal brain MRIs. The most common T2-hyperintense lesion locations were frontal, temporal, and parietal. MRI features that predicted poor 1-year outcomes included abnormal MRI, particularly T2 lesions in the frontal and occipital lobes. After adjusting for treatment within 4 weeks of onset, improvement within 4 weeks, and intensive care unit admission, MRI features were no longer associated with poor outcomes, but after multiple imputation for missing data, T2 frontal and occipital lesions associated with poor outcomes. DISCUSSION: Abnormal frontal and occipital lesions on MRI may associate with 1-year mRS in pNMDARE. MRI of the brain may be a helpful prognostication tool that should be examined in future studies.

Patients' and Healthcare Professionals' Experiences and Views of Recurrent Urinary Tract Infections in Women: Qualitative Evidence Synthesis and Meta-Ethnography.

BACKGROUND: Urinary tract infections (UTIs) are a common and significant problem for patients, clinicians, and healthcare services. Recurrent UTIs (rUTIs) are common, with a 3% prevalence in the UK. Although acute UTIs have a significant negative impact on the lives of patients, evidence of the impact of rUTIs is limited. To enhance shared decision-making around rUTI management, it is important to understand both the patients' and healthcare professionals' (HCPs') perspectives. The objective of this qualitative evidence synthesis is to understand patients' and HCPs' experiences and views in the management of rUTIs. METHODS: A qualitative evidence synthesis (QES) was performed that included primary qualitative studies involving patients with rUTIs or primary care HCPs who manage patients with rUTIs, up to June 2022. The following databases were searched: MEDLINE, Embase, CINAHL, PsycInfo, ASSIA, Web of Science, Cochrane Database of Systematic Reviews, Epistemonikos, Cochrane Central Registry of Controlled Trials, OpenGrey, and the Health Management Information Consortium (HMIC). The QES was prospectively registered on PROSPERO (CRD42022295662). Reciprocal translation was conducted and developed into a line of argument synthesis. We appraised the confidence in our review findings by using GRADE-CERQual. RESULTS: Twelve studies were included in the final review; ten of those included patients, and three included HCPs (one study included both). Our review demonstrates that women with rUTIs have a unique experience, but it is generally of a chronic condition with significant impacts on numerous aspects of their lives. Antibiotics can be "transformative", but patients have serious concerns about their use and feel non-antibiotic options need further research and discussion. HCPs share similar views about the impacts of rUTIs and concerns about antibiotic use and find the management of rUTIs to be complex and challenging. Based on our GRADE-CERQual assessment of the review findings, we have moderate confidence in those related to patients and low confidence in those related to HCPs. New conceptual models for both patients and HCPs are presented. CONCLUSIONS: This review has significant clinical implications. Patients require information on antibiotic alternative acute and preventative treatments for rUTIs, and this is not currently being addressed. There are communication gaps around the impact of rUTIs on patients, their perceived expectation for antibiotics, and the reasons for treatment failure. Further development of current clinical guidance and a patient decision aid would help address these issues.

Leveraging expertise and optimizing clinical research: Initial success of a pediatric epilepsy surgery collaborative.

OBJECTIVE: Improve data-driven research to inform clinical decision-making with pediatric epilepsy surgery patients by expanding the Pediatric Epilepsy Research Consortium Epilepsy Surgery (PERC-Surgery) Workgroup to include neuropsychological data. This article reports on the process and initial success of this effort and characterizes the cognitive functioning of the largest multi-site pediatric epilepsy surgery cohort in the United States. METHODS: Pediatric neuropsychologists from 18 institutions completed surveys regarding neuropsychological practice and the impact of involvement in the collaborative. Neuropsychological data were entered through an online database. Descriptive analyses examined the survey responses and cognitive functioning of the cohort. Statistical analyses examined which patients were evaluated and if composite scores differed by domain, demographics, measures used, or epilepsy characteristics. RESULTS: Positive impact of participation was evident by attendance, survey responses, and the neuropsychological data entry of 534 presurgical epilepsy patients. This cohort, ages 6 months to 21 years, were majority White and non-Hispanic, and more likely to have private insurance. Mean intelligence quotient (IQ) scores were below to low average, with weaknesses in working memory and processing speed. Full-scale IQ (FSIQ) was lowest for patients with younger age at seizure onset, daily seizures, and magnetic resonance imaging (MRI) abnormalities. SIGNIFICANCE: We established a collaborative network and fundamental infrastructure to address questions outlined by the Epilepsy Research Benchmarks. There is a wide range in the age and IQ of patients considered for pediatric epilepsy surgery, yet it appears that social determinants of health impact access to care. Consistent with other national cohorts, this US cohort has a downward shift in IQ associated with seizure severity.

Impact of development and recent-onset epilepsy on language dominance.

OBJECTIVE: Reorganization of the language network from typically left-lateralized frontotemporal regions to bilaterally distributed or right-lateralized networks occurs in anywhere from 25%-30% of patients with focal epilepsy. In patients who have been recently diagnosed with epilepsy, an important question remains as to whether it is the presence of seizures or the underlying epilepsy etiology that leads to atypical language representations. This question becomes even more interesting in pediatric samples, where the typical developmental processes of the language network may confer more variability and plasticity in the language network. We assessed a carefully selected cohort of children with recent-onset epilepsy to examine whether it is the effects of seizures or their underlying cause that leads to atypical language lateralization. METHODS: We used functional magnetic resonance imaging (fMRI) to compare language laterality in children with recently diagnosed focal unaware epilepsy and age-matched controls. Age at epilepsy onset (age 4 to 6 years vs age 7 to 12 years) was also examined to determine if age at onset influenced laterality. RESULTS: The majority of recent-onset patients and controls exhibited left-lateralized language. There was a significant interaction such that the relationship between epilepsy duration and laterality differed by age at onset. In children with onset after age 6, a longer duration of epilepsy was associated with less left-lateralized language dominance. In contrast, in children with onset between 4 and 6 years of age, a longer duration of epilepsy was not associated with less left language dominance. SIGNIFICANCE: Our results demonstrate that although language remained largely left-lateralized in children recently diagnosed with epilepsy, the impact of seizure duration depended on age at onset, indicating that the timing of developmental and disease factors are important in determining language dominance.

Resting-state functional MRI for motor cortex mapping in childhood-onset focal epilepsy.

BACKGROUND AND PURPOSE: Task-based functional MRI (fMRI) mapping of the motor function prior to epilepsy surgery has limitations in children with epilepsy. We present a data-driven method to automatically delineate the motor cortex using task-free, resting-state fMRI (rsfMRI) data. METHODS: We used whole-brain rsfMRI for independent component analysis (ICA). A template matching process with Discriminability Index-based Component Identification score was used for each participant to select and combine motor ICA components in their native brain space, resulting in a whole-brain ICA Motor Map (wIMM). We validated wIMM by comparing individual results with bilateral finger-tapping motor task fMRI activation, and evaluated its reproducibility in controls. RESULTS: Data from 64 patients and 12 controls were used to generate group wIMM maps. The hit rate between wIMM and motor task activation ranged from 60% to 79% across all participants. Sensitivity of wIMM for capturing the task activation peak was 87.5% among 32 patients and 100% in 12 controls with available motor task results. We also showed high similarity in repeated runs in controls. CONCLUSIONS: Our results show the sensitivity and reproducibility of an automated motor mapping method based on ICA analysis of rsfMRI in children with epilepsy. The ICA maps may provide different, but useful, information than task fMRI. Future studies will expand our method to mapping other brain functions, and may lead to a surgical planning tool for patients who cannot perform task fMRI and help predict their postsurgical function.

Networks Underlie Temporal Onset of Dysplasia-Related Epilepsy: A MELD Study.

OBJECTIVE: The purpose of this study was to evaluate if focal cortical dysplasia (FCD) co-localization to cortical functional networks is associated with the temporal distribution of epilepsy onset in FCD. METHODS: International (20 center), retrospective cohort from the Multi-Centre Epilepsy Lesion Detection (MELD) project. Patients included if >3 years old, had 3D pre-operative T1 magnetic resonance imaging (MRI; 1.5 or 3 T) with radiologic or histopathologic FCD after surgery. Images processed using the MELD protocol, masked with 3D regions-of-interest (ROI), and co-registered to fsaverage_sym (symmetric template). FCDs were then co-localized to 1 of 7 distributed functional cortical networks. Negative binomial regression evaluated effect of FCD size, network, histology, and sulcal depth on age of epilepsy onset. From this model, predictive age of epilepsy onset was calculated for each network. RESULTS: Three hundred eighty-eight patients had median age seizure onset 5 years (interquartile range [IQR] = 3-11 years), median age at pre-operative scan 18 years (IQR = 11-28 years). FCDs co-localized to the following networks: limbic (90), default mode (87), somatomotor (65), front parietal control (52), ventral attention (32), dorsal attention (31), and visual (31). Larger lesions were associated with younger age of onset (p = 0.01); age of epilepsy onset was associated with dominant network (p = 0.04) but not sulcal depth or histology. Sensorimotor networks had youngest onset; the limbic network had oldest age of onset (p values <0.05). INTERPRETATION: FCD co-localization to distributed functional cortical networks is associated with age of epilepsy onset: sensory neural networks (somatomotor and visual) with earlier onset, and limbic latest onset. These variations may reflect developmental differences in synaptic/white matter maturation or network activation and may provide a biological basis for age-dependent epilepsy onset expression. ANN NEUROL 2022;92:503-511.

AGN as potential factories for eccentric black hole mergers.

There is some weak evidence that the black hole merger named GW190521 had a non-zero eccentricity1,2. In addition, the masses of the component black holes exceeded the limit predicted by stellar evolution3. The large masses can be explained by successive mergers4,5, which may be efficient in gas disks surrounding active galactic nuclei, but it is difficult to maintain an eccentric orbit all the way to the merger, as basic physics would argue for circularization6. Here we show that active galactic nuclei disk environments can lead to an excess of eccentric mergers, if the interactions between single and binary black holes are frequent5 and occur with mutual inclinations of less than a few degrees. We further illustrate that this eccentric population has a different distribution of the inclination between the spin vectors of the black holes and their orbital angular momentum at merger7, referred to as the spin-orbit tilt, compared with the remaining circular mergers.

Functional Connectivity as a Potential Mechanism for Language Plasticity.

BACKGROUND AND OBJECTIVES: Task fMRI is a clinical tool for language lateralization, but has limitations, and cannot provide information about network-level plasticity. Additional methods are needed to improve the precision of presurgical language mapping. We investigate language resting-state functional connectivity (RS fMRI; FC) in typically developing children (TD) and children with epilepsy. Our objectives were to (1) understand how FC components differ between TD children and those with epilepsy; (2) elucidate how the location of disease (frontal/temporal epilepsy foci) affects FC; and (3) investigate the relationship between age and FC. METHODS: Our sample included 55 TD children (mean age 12 years, range 7-18) and 31 patients with focal epilepsy (mean age 13 years, range 7-18). All participants underwent RS fMRI. Using a bilateral canonical language map as target, vertex-wise intrahemispheric FC map and interhemispheric FC map for each participant were computed and thresholded at top 10% to compute an FC laterality index (FCLI; [(L - R)/(L + R)]) of the frontal and temporal regions for both integration (intrahemispheric FC; FCLIi) and segregation (interhemispheric FC; FCLIs) maps. RESULTS: We found FC differences in the developing language network based on disease, seizure foci location, and age. Frontal and temporal FCLIi was different between groups (t[84] = 2.82, p < 0.01; t[84] = 4.68, p < 0.01, respectively). Frontal epilepsy foci had the largest differences from TD (Cohen d frontal FCLIi = 0.84, FCLIs = 0.51; temporal FCLIi = 1.29). Development and disease have opposing influences on the laterality of FC based on groups. In the frontal foci group, FCLIi decreased with age (r = -0.42), whereas in the temporal foci group, FCLIi increased with age (r = 0.40). Within the epilepsy group, increases in right frontal integration FCLI relates to increased right frontal task activation in our mostly left language dominant group (r = 0.52, p < 0.01). Language network connectivity is associated with higher verbal intelligence in children with epilepsy (r = 0.45, p < 0.05). DISCUSSION: These findings lend preliminary evidence that FC reflects network plasticity in the form of adaptation and compensation, or the ability to recruit support and reallocate resources within and outside of the traditional network to compensate for disease. FC expands on task-based fMRI and provides complementary and potentially useful information about the language network that is not captured using task-based fMRI alone.

Rapid and sensitive detection of SARS-CoV-2 infection using quantitative peptide enrichment LC-MS analysis.

Reliable, robust, large-scale molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for monitoring the ongoing coronavirus disease 2019 (COVID-19) pandemic. We have developed a scalable analytical approach to detect viral proteins based on peptide immuno-affinity enrichment combined with liquid chromatography-mass spectrometry (LC-MS). This is a multiplexed strategy, based on targeted proteomics analysis and read-out by LC-MS, capable of precisely quantifying and confirming the presence of SARS-CoV-2 in phosphate-buffered saline (PBS) swab media from combined throat/nasopharynx/saliva samples. The results reveal that the levels of SARS-CoV-2 measured by LC-MS correlate well with their correspondingreal-time polymerase chain reaction (RT-PCR) read-out (r = 0.79). The analytical workflow shows similar turnaround times as regular RT-PCR instrumentation with a quantitative read-out of viral proteins corresponding to cycle thresholds (Ct) equivalents ranging from 21 to 34. Using RT-PCR as a reference, we demonstrate that the LC-MS-based method has 100% negative percent agreement (estimated specificity) and 95% positive percent agreement (estimated sensitivity) when analyzing clinical samples collected from asymptomatic individuals with a Ct within the limit of detection of the mass spectrometer (Ct ≤ 30). These results suggest that a scalable analytical method based on LC-MS has a place in future pandemic preparedness centers to complement current virus detection technologies.

The depth of Jupiter's Great Red Spot constrained by Juno gravity overflights.

Jupiter's Great Red Spot (GRS) is the largest atmospheric vortex in the Solar System and has been observed for at least two centuries. It has been unclear how deep the vortex extends beneath its visible cloud tops. We examined the gravity signature of the GRS using data from 12 encounters of the Juno spacecraft with the planet, including two direct overflights of the vortex. Localized density anomalies due to the presence of the GRS caused a shift in the spacecraft line-of-sight velocity. Using two different approaches to infer the GRS depth, which yielded consistent results, we conclude that the GRS is contained within the upper 500 kilometers of Jupiter's atmosphere.

Functional connectivity hemispheric contrast (FC-HC): A new metric for language mapping.

Development of a task-free method for presurgical mapping of language function is important for use in young or cognitively impaired patients. Resting state connectivity fMRI (RS-fMRI) is a task-free method that may be used to identify cognitive networks. We developed a voxelwise RS-fMRI metric, Functional Connectivity Hemispheric Contrast (FC-HC), to map the language network and determine language laterality through comparison of within-hemispheric language network connections (Integration) to cross-hemispheric connections (Segregation). For the first time, we demonstrated robustness and efficacy of a RS-fMRI metric to map language networks across five groups (total N = 243) that differed in MRI scanning parameters, fMRI scanning protocols, age, and development (typical vs pediatric epilepsy). The resting state FC-HC maps for the healthy pediatric and adult groups showed higher values in the left hemisphere, and had high agreement with standard task language fMRI; in contrast, the epilepsy patient group map was bilateral. FC-HC has strong but not perfect agreement with task fMRI and thus, may reflect related and complementary information about language plasticity and compensation.

Jupiter's Overturning Circulation: Breaking Waves Take the Place of Solid Boundaries.

Cloud-tracked wind observations document the role of eddies in putting momentum into the zonal jets. Chemical tracers, lightning, clouds, and temperature anomalies document the rising and sinking in the belts and zones, but questions remain about what drives the flow between the belts and zones. We suggest an additional role for the eddies, which is to generate waves that propagate both up and down from the cloud layer. When the waves break they deposit momentum and thereby replace the friction forces at solid boundaries that enable overturning circulations on terrestrial planets. By depositing momentum of one sign within the cloud layer and momentum of the opposite sign above and below the clouds, the eddies maintain all components of the circulation, including the stacked, oppositely rotating cells between each belt-zone pair, and the zonal jets themselves.

A Survey of Small-Scale Waves and Wave-Like Phenomena in Jupiter's Atmosphere Detected by JunoCam.

In the first 20 orbits of the Juno spacecraft around Jupiter, we have identified a variety of wave-like features in images made by its public-outreach camera, JunoCam. Because of Juno's unprecedented and repeated proximity to Jupiter's cloud tops during its close approaches, JunoCam has detected more wave structures than any previous surveys. Most of the waves appear in long wave packets, oriented east-west and populated by narrow wave crests. Spacing between crests were measured as small as ~30 km, shorter than any previously measured. Some waves are associated with atmospheric features, but others are not ostensibly associated with any visible cloud phenomena and thus may be generated by dynamical forcing below the visible cloud tops. Some waves also appear to be converging, and others appear to be overlapping, possibly at different atmospheric levels. Another type of wave has a series of fronts that appear to be radiating outward from the center of a cyclone. Most of these waves appear within 5° of latitude from the equator, but we have detected waves covering planetocentric latitudes between 20°S and 45°N. The great majority of the waves appear in regions associated with prograde motions of the mean zonal flow. Juno was unable to measure the velocity of wave features to diagnose the wave types due to its close and rapid flybys. However, both by our own upper limits on wave motions and by analogy with previous measurements, we expect that the waves JunoCam detected near the equator are inertia-gravity waves.

How Well Do We Understand the Belt/Zone Circulation of Giant Planet Atmospheres?

The atmospheres of the four giant planets of our Solar System share a common and well-observed characteristic: they each display patterns of planetary banding, with regions of different temperatures, composition, aerosol properties and dynamics separated by strong meridional and vertical gradients in the zonal (i.e., east-west) winds. Remote sensing observations, from both visiting spacecraft and Earth-based astronomical facilities, have revealed the significant variation in environmental conditions from one band to the next. On Jupiter, the reflective white bands of low temperatures, elevated aerosol opacities, and enhancements of quasi-conserved chemical tracers are referred to as 'zones.' Conversely, the darker bands of warmer temperatures, depleted aerosols, and reductions of chemical tracers are known as 'belts.' On Saturn, we define cyclonic belts and anticyclonic zones via their temperature and wind characteristics, although their relation to Saturn's albedo is not as clear as on Jupiter. On distant Uranus and Neptune, the exact relationships between the banded albedo contrasts and the environmental properties is a topic of active study. This review is an attempt to reconcile the observed properties of belts and zones with (i) the meridional overturning inferred from the convergence of eddy angular momentum into the eastward zonal jets at the cloud level on Jupiter and Saturn and the prevalence of moist convective activity in belts; and (ii) the opposing meridional motions inferred from the upper tropospheric temperature structure, which implies decay and dissipation of the zonal jets with altitude above the clouds. These two scenarios suggest meridional circulations in opposing directions, the former suggesting upwelling in belts, the latter suggesting upwelling in zones. Numerical simulations successfully reproduce the former, whereas there is a wealth of observational evidence in support of the latter. This presents an unresolved paradox for our current understanding of the banded structure of giant planet atmospheres, that could be addressed via a multi-tiered vertical structure of "stacked circulation cells," with a natural transition from zonal jet pumping to dissipation as we move from the convectively-unstable mid-troposphere into the stably-stratified upper troposphere.