An Overview of Medicaid Managed Care Litigation

This Issue Brief is intended as one of several in the Managed Behavioral Health Care Issue Brief Series that deals with managed behavioral health care from a purely legal point of view. Since the enactment of Medicaid in 1965, states have had the option of offering beneficiaries enrollment in managed care arrangements. With the advent of mandatory managed care reaching millions of beneficiaries (including a growing proportion of disabled recipients), the amount and scope of litigation involving Medicaid managed care plans can be expected to grow. A review of the current litigation regarding Medicaid managed care reveals two basic types of lawsuits: (1) those that challenge the practices of managed care companies under various federal and state laws that safeguard consumer rights, protect health care quality, and prohibit discrimination; and (2) suits that assert claims arising directly under the Medicaid statute and implementing regulations, as well as claims related to Constitutional safeguards that undergird the program

The P4 promoter of the parvovirus minute virus of mice is developmentally regulated in transgenic P4-LacZ mice

AbstractActivation of the minute virus of mice (MVM) P4 promoter is a key step in the life cycle of the virus and is completely dependent on host transcription factors. Since transcription-factor composition varies widely in different cell types, there is the possibility that only some cell types in the host organism have the capacity to initiate expression from the P4 promoter and therefore that the promoter may be a factor in determining the tropism of MVM. In this study, the ability of various cell types to activate P4, independent of the other virus–host interactions, was examined in transgenic mouse lines bearing a β-galactosidase reporter sequence driven by the P4 promoter. It was found that lacZ was expressed during embryogenesis and in the adult in a cell-type-specific and differentiation-dependent pattern. The data are consistent with cell-type and stage-specific activation of the P4 promoter having a role in determining the host cell-type range of MVM. The ability of some parvoviruses to replicate in, and kill oncogenically transformed cells, and to destroy induced tumors in laboratory animals is the basis of recent approaches to use MVM-based vectors in cancer gene therapy. Since these vectors rely on the activation of the P4 promoter by the target tissues, understanding the promoter dependence on cell-type and differentiation status is important for their design and potential use

A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets

Leukocyte and platelet integrins rapidly alter their affinity and adhesiveness in response to various activation (inside-out) signals. A rare leukocyte adhesion deficiency (LAD), LAD-III, is associated with severe defects in leukocyte and platelet integrin activation. We report two new LAD cases in which lymphocytes, neutrophils, and platelets share severe defects in β1, β2, and β3 integrin activation. Patients were both homozygous for a splice junction mutation in their CalDAG-GEFI gene, which is a key Rap-1/2 guanine exchange factor (GEF). Both mRNA and protein levels of the GEF were diminished in LAD lymphocytes, neutrophils, and platelets. Consequently, LAD-III platelets failed to aggregate because of an impaired αIIbβ3 activation by key agonists. β2 integrins on LAD-III neutrophils were unable to mediate leukocyte arrest on TNFα-stimulated endothelium, despite normal selectin-mediated rolling. In situ subsecond activation of neutrophil β2 integrin adhesiveness by surface-bound chemoattractants and of primary T lymphocyte LFA-1 by the CXCL12 chemokine was abolished. Chemokine inside-out signals also failed to stimulate lymphocyte LFA-1 extension and high affinity epitopes. Chemokine-triggered VLA-4 adhesiveness in T lymphocytes was partially defective as well. These studies identify CalDAG-GEFI as a critical regulator of inside-out integrin activation in human T lymphocytes, neutrophils, and platelets

Otitis Media Practice During the COVID-19 Pandemic.

The global coronavirus disease-2019 (COVID-19) pandemic has changed the prevalence and management of many pediatric infectious diseases, including acute otitis media (AOM). Coronaviruses are a group of RNA viruses that cause respiratory tract infections in humans. Before the COVID-19 pandemic, coronavirus serotypes OC43, 229E, HKU1, and NL63 were infrequently detected in middle ear fluid (MEF) specimens and nasopharyngeal aspirates in children with AOM during the 1990s and 2000s and were associated with a mild course of the disease. At times when CoV was detected in OM cases, the overall viral load was relatively low. The new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen responsible for the eruption of the COVID-19 global pandemic. Following the pandemic declaration in many countries and by the World Health Organization in March 2020, preventive proactive measures were imposed to limit COVID-19. These included social distancing; lockdowns; closure of workplaces; kindergartens and schools; increased hygiene; use of antiseptics and alcohol-based gels; frequent temperature measurements and wearing masks. These measures were not the only ones taken, as hospitals and clinics tried to minimize treating non-urgent medical referrals such as OM, and elective surgical procedures were canceled, such as ventilating tube insertion (VTI). These changes and regulations altered the way OM is practiced during the COVID-19 pandemic. Advents in technology allowed a vast use of telemedicine technologies for OM, however, the accuracy of AOM diagnosis in those encounters was in doubt, and antibiotic prescription rates were still reported to be high. There was an overall decrease in AOM episodes and admissions rates and with high spontaneous resolution rates of MEF in children, and a reduction in VTI surgeries. Despite an initial fear regarding viral shedding during myringotomy, the procedure was shown to be safe. Special draping techniques for otologic surgery were suggested. Other aspects of OM practice included the presentation of adult patients with AOM who tested positive for SARS-2-CoV and its detection in MEF samples in living patients and in the mucosa of the middle ear and mastoid in post-mortem specimens

Galaxy Pairs in the Sloan Digital Sky Survey - II: The Effect of Environment on Interactions

We use a sample of close galaxy pairs selected from the Sloan Digital Sky Survey Data Release 4 (SDSS DR4) to investigate in what environments galaxy mergers occur and how the results of these mergers depend on differences in local galaxy density. The galaxies are quantified morphologically using two-dimensional bulge-plus-disk decompositions and compared to a control sample matched in stellar mass, redshift and local projected density. Lower density environments have fractionally more galaxy pairs with small projected separations (r_p) and relative velocities (Delta v), but even high density environments contain significant populations of pairs with parameters that should be conducive to interactions. Metrics of asymmetry and colour are used to identify merger activity and triggered star formation. The location of star formation is inferred by distinguishing bulge and disk colours and calculating bulge fractions from the SDSS images. Galaxies in the lowest density environments show the largest changes in star formation rate, asymmetry and bulge-total fractions at small separations, accompanied by bluer bulge colours. At the highest local densities, the only galaxy property to show an enhancement in the closest pairs is asymmetry. We interpret these results as evidence that whilst interactions (leading to tidal distortions) occur at all densities, triggered star formation is seen only in low-to-intermediate density environments. We suggest that this is likely due to the typically higher gas fractions of galaxies in low density environments. Finally, by cross-correlating our sample of galaxy pairs with a cluster catalogue, we investigate the dependence of interactions on clustercentric distance. It is found that for close pairs the fraction of asymmetric galaxies is highest in the cluster centres.Comment: Accepted by MNRAS, 15 page

Galaxy Pairs in the Sloan Digital Sky Survey - III: Evidence of Induced Star Formation from Optical Colours

We have assembled a large, high quality catalogue of galaxy colours from the Sloan Digital Sky Survey Data Release 7, and have identified 21,347 galaxies in pairs spanning a range of projected separations (r_p < 80 h_{70}^{-1} kpc), relative velocities (\Delta v < 10,000 km/s, which includes projected pairs that are essential for quality control), and stellar mass ratios (from 1:10 to 10:1). We find that the red fraction of galaxies in pairs is higher than that of a control sample matched in stellar mass and redshift, and demonstrate that this difference is likely due to the fact that galaxy pairs reside in higher density environments than non-paired galaxies. We detect clear signs of interaction-induced star formation within the blue galaxies in pairs, as evidenced by a higher fraction of extremely blue galaxies, along with blueward offsets between the colours of paired versus control galaxies. These signs are strongest in close pairs (r_p < 30 h_{70}^{-1} kpc and \Delta v < 200 km/s), diminish for more widely separated pairs (r_p > 60 h_{70}^{-1} kpc and \Delta v < 200 km/s) and disappear for close projected pairs (r_p < 30 h_{70}^{-1} kpc and \Delta v > 3000 km/s). These effects are also stronger in central (fibre) colours than in global colours, and are found primarily in low- to medium-density environments. Conversely, no such trends are seen in red galaxies, apart from a small reddening at small separations which may result from residual errors with photometry in crowded fields. When interpreted in conjunction with a simple model of induced starbursts, these results are consistent with a scenario in which close peri-centre passages trigger induced star formation in the centres of galaxies which are sufficiently gas rich, after which time the galaxies gradually redden as they separate and their starbursts age.Comment: 17 pages. Accepted for publication in MNRA

Physical modelling of water, fauna and flora: knowledge gaps, avenues for future research and infrastructural needs

peer reviewedPhysical modelling is a key tool for generating understanding of the complex interactions between aquatic organisms and hydraulics, which is important for management of aquatic environments under environmental change and our ability to exploit ecosystem services. Many aspects of this field remain poorly understood and the use of physical models within eco-hydraulics requires advancement in methodological application and substantive understanding. This paper presents a review of the emergent themes from a workshop tasked with identifying the future infrastructure requirements of the next generation of eco-hydraulics researchers. The identified themes are: abiotic factors, adaptation, complexity and feedback, variation, and scale and scaling. The paper examines these themes and identifies how progress on each of them is key to existing and future eðorts to progress our knowledge of eco-hydraulic interactions. Examples are drawn from studies on biofilms, plants, and sessile and mobile fauna in shallow water fluvial and marine environments. Examples of research gaps and directions for educational, infrastructural and technological advance are also presented.PISCES work package of HYDRALAB FP

EuCARE-POSTCOVID Study: a multicentre cohort study on long-term post-COVID-19 manifestations

BACKGROUND: Post-COVID-19 condition refers to persistent or new onset symptoms occurring three months after acute COVID-19, which are unrelated to alternative diagnoses. Symptoms include fatigue, breathlessness, palpitations, pain, concentration difficulties ("brain fog"), sleep disorders, and anxiety/depression. The prevalence of post-COVID-19 condition ranges widely across studies, affecting 10-20% of patients and reaching 50-60% in certain cohorts, while the associated risk factors remain poorly understood. METHODS: This multicentre cohort study, both retrospective and prospective, aims to assess the incidence and risk factors of post-COVID-19 condition in a cohort of recovered patients. Secondary objectives include evaluating the association between circulating SARS-CoV-2 variants and the risk of post-COVID-19 condition, as well as assessing long-term residual organ damage (lung, heart, central nervous system, peripheral nervous system) in relation to patient characteristics and virology (variant and viral load during the acute phase). Participants will include hospitalised and outpatient COVID-19 patients diagnosed between 01/03/2020 and 01/02/2025 from 8 participating centres. A control group will consist of hospitalised patients with respiratory infections other than COVID-19 during the same period. Patients will be followed up at the post-COVID-19 clinic of each centre at 2-3, 6-9, and 12-15 months after clinical recovery. Routine blood exams will be conducted, and patients will complete questionnaires to assess persisting symptoms, fatigue, dyspnoea, quality of life, disability, anxiety and depression, and post-traumatic stress disorders. DISCUSSION: This study aims to understand post-COVID-19 syndrome's incidence and predictors by comparing pandemic waves, utilising retrospective and prospective data. Gender association, especially the potential higher prevalence in females, will be investigated. Symptom tracking via questionnaires and scales will monitor duration and evolution. Questionnaires will also collect data on vaccination, reinfections, and new health issues. Biological samples will enable future studies on post-COVID-19 sequelae mechanisms, including inflammation, immune dysregulation, and viral reservoirs. TRIAL REGISTRATION: This study has been registered with ClinicalTrials.gov under the identifier NCT05531773

Broad Kinase Inhibition Mitigates Early Neuronal Dysfunction in Tauopathy

Tauopathies are a group of more than twenty known disorders that involve progressive neurodegeneration, cognitive decline and pathological tau accumulation. Current therapeutic strategies provide only limited, late-stage symptomatic treatment. This is partly due to lack of understanding of the molecular mechanisms linking tau and cellular dysfunction, especially during the early stages of disease progression. In this study, we treated early stage tau transgenic mice with a multi-target kinase inhibitor to identify novel substrates that contribute to cognitive impairment and exhibit therapeutic potential. Drug treatment significantly ameliorated brain atrophy and cognitive function as determined by behavioral testing and a sensitive imaging technique called manganese-enhanced magnetic resonance imaging (MEMRI) with quantitative R1 mapping. Surprisingly, these benefits occurred despite unchanged hyperphosphorylated tau levels. To elucidate the mechanism behind these improved cognitive outcomes, we performed quantitative proteomics to determine the altered protein network during this early stage in tauopathy and compare this model with the human Alzheimer’s disease (AD) proteome. We identified a cluster of preserved pathways shared with human tauopathy with striking potential for broad multi-target kinase intervention. We further report high confidence candidate proteins as novel therapeutically relevant targets for the treatment of tauopathy. Proteomics data are available via ProteomeXchange with identifier PXD023562