Patent Litigation in Europe

We compare patent litigation cases across four European jurisdictions—Germany, the UK (England and Wales), France, The Netherlands—using case-level data gathered from cases filed in the four jurisdictions during the period 2000–2008. Overall, we find substantial differences across jurisdictions in terms of caseloads—notably, courts in Germany hear by far the largest number of cases, not only in absolute terms, but also when taking macro-economic indicators into account—and we further find important cross-country variances in terms of case outcomes. Moreover, we show empirically that a considerable number of patents are litigated across multiple European jurisdictions; and further, that in the majority of these cases divergent case outcomes are reached across the different jurisdictions, suggesting that the long-suspected problem of inconsistency of decision-making in European patent litigation is in fact real. Finally, we note that the coming into force of the Unified Patent Court in Europe may, in the long term, help to alleviate this inconsistency problem

Global alterations to the choroid plexus blood-CSF barrier in amyotrophic lateral sclerosis

© 2020 The Author(s). The choroid plexus (CP) is a highly vascularized structure located in the ventricles that forms the blood-CSF barrier (BCSFB) and separates the blood from the cerebrospinal fluid (CSF). In addition to its role as a physical barrier, the CP functions in CSF secretion, transport of nutrients into the central nervous system (CNS) and a gated point of entry of circulating immune cells into the CNS. Aging and neurodegeneration have been reported to affect CP morphology and function and increase protein leakage from blood to the CSF. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both upper and lower motor neuron loss, as well as altered proteomic and metabolomic signatures in the CSF. The role of the BCSFB and the CP in ALS is unknown. Here we describe a transcriptomic and ultrastructural analysis of BCSFB and CP alterations in human postmortem tissues from ALS and non-neurologic disease controls. ALS-CP exhibited widespread disruptions in tight junctional components of the CP epithelial layer and vascular integrity. In addition, we detected loss of pericytes around ALS blood vessels, accompanied by activation of platelet aggregation markers vWF and Fibrinogen, reminiscent of vascular injury. To investigate the immune component of ALS-CP, we conducted a comprehensive analysis of cytokines and chemokine panels in CP lysates and found a significant down-regulation of M-CSF and V-CAM1 in ALS, as well as up-regulation of VEGF-A protein. This phenotype was accompanied by an infiltration of MERTK positive macrophages into the parenchyma of the ALS-CP when compared to controls. Taken together, we demonstrate widespread structural and functional disruptions of the BCSFB in human ALS increasing our understanding of the disease pathology and identifying potential new targets for ALS therapeutic development

Serum Neurofilament Light is elevated in COVID-19 Positive Adults in the ICU and is associated with Co-Morbid Cardiovascular Disease, Neurological Complications, and Acuity of Illness

In critically ill COVID-19 patients, the risk of long-term neurological consequences is just beginning to be appreciated. While recent studies have identified that there is an increase in structural injury to the nervous system in critically ill COVID-19 patients, there is little known about the relationship of COVID-19 neurological damage to the systemic inflammatory diseases also observed in COVID-19 patients. The purpose of this pilot observational study was to examine the relationships between serum neurofilament light protein (NfL, a measure of neuronal injury) and co-morbid cardiovascular disease (CVD) and neurological complications in COVID-19 positive patients admitted to the intensive care unit (ICU). In this observational study of one-hundred patients who were admitted to the ICU in Tucson, Arizona between April and August 2020, 89 were positive for COVID-19 (COVID-pos) and 11 was COVID-negative (COVID-neg). A healthy control group (n=8) was examined for comparison. The primary outcomes and measures were subject demographics, serum NfL, presence and extent of CVD, diabetes, sequential organ failure assessment score (SOFA), presence of neurological complications, and blood chemistry panel data. COVID-pos patients in the ICU had significantly higher mean levels of Nfl (229.6 ± 163 pg/ml) compared to COVID-neg ICU patients (19.3 ± 5.6 pg/ml), Welch's t-test, p =.01 and healthy controls (12.3 ± 3.1 pg/ml), Welch's t-test p =.005. Levels of Nfl in COVID-pos ICU patients were significantly higher in patients with concomitant CVD and diabetes (n=35, log Nfl 1.6±.09), and correlated with higher SOFA scores (r=.5, p =.001). These findings suggest that in severe COVID-19 disease, the central neuronal and axonal damage in these patients may be driven, in part, by the level of systemic cardiovascular disease and peripheral inflammation. Understanding the contributions of systemic inflammatory disease to central neurological degeneration in these COVID-19 survivors will be important to the design of interventional therapies to prevent long-term neurological and cognitive dysfunction

Long-Term Physical Exercise and Mindfulness Practice in an Aging Population

Previous studies have shown that physical exercise and mindfulness meditation can both lead to improvement in physical and mental health. However, it is unclear whether these two forms of training share the same underlying mechanisms. We compared two groups of older adults with 10 years of mindfulness meditation (integrative body-mind training, IBMT) or physical exercise (PE) experience to demonstrate their effects on brain, physiology and behavior. Healthy older adults were randomly selected from a large community health project and the groups were compared on measures of quality of life, autonomic activity (heart rate, heart rate variability, skin conductance response, respiratory amplitude/rate), immune function (secretory Immunoglobulin A, sIgA), stress hormone (cortisol) and brain imaging (resting state functional connectivity, structural differences). In comparison with PE, we found significantly higher ratings for the IBMT group on dimensions of life quality. Parasympathetic activity indexed by skin conductance response and high-frequency heart rate variability also showed more favorable outcomes in the IBMT group. However, the PE group showed lower basal heart rate and greater chest respiratory amplitude. Basal sIgA level was significantly higher and cortisol concentration was lower in the IBMT group. Lastly, the IBMT group had stronger brain connectivity between the dorsal anterior cingulate cortex (dACC) and the striatum at resting state, as well as greater volume of gray matter in the striatum. Our results indicate that mindfulness meditation and physical exercise function in part by different mechanisms, with PE increasing physical fitness and IBMT inducing plasticity in the central nervous systems. These findings suggest combining physical and mental training may achieve better health and quality of life results for an aging population

A multilevel neo-institutional analysis of infection prevention and control in English hospitals: coerced safety culture change?

Despite committed policy, regulative and professional efforts on healthcare safety, little is known about how such macro-interventions permeate organisations and shape culture over time. Informed by neo-institutional theory, we examined how inter-organisational influences shaped safety practices and inter-subjective meanings following efforts for coerced culture change. We traced macro-influences from 2000 to 2015 in infection prevention and control (IPC). Safety perceptions and meanings were inductively analysed from 130 in-depth qualitative interviews with senior- and middle-level managers from 30 English hospitals. A total of 869 institutional interventions were identified; 69% had a regulative component. In this context of forced implementation of safety practices, staff experienced inherent tensions concerning the scope of safety, their ability to be open and prioritisation of external mandates over local need. These tensions stemmed from conflicts among three co-existing institutional logics prevalent in the NHS. In response to requests for change, staff flexibly drew from a repertoire of cognitive, material and symbolic resources within and outside their organisations. They crafted 'strategies of action', guided by a situated assessment of first-hand practice experiences complementing collective evaluations of interventions such as 'pragmatic', 'sensible' and also 'legitimate'. Macro-institutional forces exerted influence either directly on individuals or indirectly by enriching the organisational cultural repertoire

Privacy, Ethics, and Institutional Research

Despite widespread agreement that privacy in the context of education is important, it can be difficult to pin down precisely why and to what extent it is important, and it is challenging to determine how privacy is related to other important values. But that task is crucial. Absent a clear sense of what privacy is, it will be difficult to understand the scope of privacy protections in codes of ethics. Moreover, privacy will inevitably conflict with other values, and understanding the values that underwrite privacy protections is crucial for addressing conflicts between privacy and institutional efficiency, advising efficacy, vendor benefits, and student autonomy. My task in this paper is to seek a better understanding of the concept of privacy in institutional research, canvas a number of important moral values underlying privacy generally (including several that are explicit in the AIR Statement), and examine how those moral values should bear upon institutional research by considering several recent cases

Associations between plasma neurofilament light, in vivo brain pathology, and cognition in non-demented individuals with autosomal-dominant Alzheimer's disease

BACKGROUND: Neurofilament light (NfL) is a promising biomarker of early neurodegeneration in Alzheimer's disease (AD). We examined whether plasma NfL was associated with in vivo amyloid beta and tau, and cognitive performance in non-demented presenilin-1 (PSEN1) E280A mutation carriers. METHODS: Twenty-five mutation carriers and 19 non-carriers (age range: 28 to 49 years) were included in this study. Participants underwent 11C Pittsburgh compound B (PiB)-PET (positron emission tomography), flortaucipir-PET, blood sampling, and cognitive testing. RESULTS: Mutation carriers exhibited higher plasma NfL levels than non-carriers. In carriers, higher NfL levels were related to greater regional tau burden and worse cognition, but not amyloid beta load. When we adjusted for age, a proxy of disease progression, elevated plasma NfL levels were only correlated with worse memory recall. CONCLUSIONS: Findings support an association between plasma NfL, cognition, and tau pathology in non-demented individuals at genetic risk for developing AD dementia. Plasma NfL may be useful for selecting individuals at increased risk and tracking disease progression in AD