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Intellectual property (IP) law operates with the ontological assumption that immaterial goods such as works, inventions, and designs exist, and that these abstract types can be owned like a piece of land. Alexander Peukert provides a comprehensive critique of this paradigm, showing that the abstract IP object is a speech-based construct, which first crystalised in the eighteenth century. He highlights the theoretical flaws of metaphysical object ontology and introduces John Searle's social ontology as a more plausible approach to the subject matter of IP. On this basis, he proposes an IP theory under which IP rights provide their holders with an exclusive privilege to use reproducible 'Master Artefacts.' Such a legal-realist IP theory, Peukert argues, is both descriptively and prescriptively superior to the prevailing paradigm of the abstract IP object. This work was originally published in German and was translated by Gill Mertens.
Fertility preservation, especially in women of reproductive age undergoing gonadotoxic treatment, has become an important part of our practice. This is reflected in the increasing number of publications on the subject. A recent PubMed search yields 518 articles on fertility preservation published in the time period of 1980–2000 and 4,288 others between 2000 and 2017. Today, failure to discuss fertility preservation with young women scheduled to undergo radiotherapy or chemotherapy could be considered as malpractice.
Cryptosporidiosis is a gastrointestinal illness with profuse diarrhoea. Although there are no other Food and Drug Administration (FDA)-approved alternatives for the treatment of cryptosporidiosis, nitazoxanide (NTZ) can be qualified as partially effective. In immunosuppressed conditions, severe and/or disseminated cryptosporidiosis may occur and patients should be treated parenterally. To achieve the goal of developing parenteral treatment for cryptosporidiosis, the current study was undertaken to investigate the in vitro and in vivo anticryptosporidial activity of aminoxanide. This new l-tert-leucyl thiazolide is a soluble prodrug of tizoxanide (TIZ), the main metabolite of NTZ. Confirming the good efficacy of aminoxanide in Cryptosporidium parvum-infected HCT-8 cells with a 50% inhibitory concentration of 1.55 μm (±0.21), in immunosuppressed C. parvum-infected Mongolian gerbils (Meriones unguiculatus), a 5-day treatment with a daily intramuscular dose of 100 mg kg−1 aminoxanide resulted in a 72.5% oocyst excretion inhibition, statistically equivalent to 75.5% in gerbils treated with a 4-fold lower oral dose of NTZ. Cryptosporidium parvum-induced intestinal pathology and inflammation were improved. Aminoxanide provides an injectable form of TIZ that NTZ was unable to do and is a promising drug for which optimization of the formulation should be further explored. These results represent a first promising step towards the goal of developing a parenteral treatment for cryptosporidiosis.
Diverse and increasingly comprehensive data about our personal lives is collected. When these personal data are linked to health records or linked to other data collected in our environment, such as that collected by state administrations or financial systems, the data have huge potential for public health research and society in general. Precision medicine, including pharmacogenomics, particularly depends on the potential of data linkage. With new capacities to analyze linked data, researchers today can retrieve and assess valuable and clinically relevant information. One way to develop such linked data sets and to make them available for research is through health data cooperatives. An example of such a health data cooperation is MIDATA – a health data cooperative recently established in Switzerland and the main focus of this chapter. In response to concerns about the present health data economy, MIDATA was founded to provide a governance structure for data storage that supports individual’s digital self-determination by allowing MIDATA members to control their own personal data flow and to store such data in a secure environment.
This article examines a subset of multilateral forums dealing with security problems posed by digital technologies, such as cyber warfare, cyber crime and lethal autonomous weapons systems (LAWS).1 It identifies structural issues that make it difficult for multilateral forums to discuss fast-moving digital issues and respond in time with the required norms and policy measures. Based on this problem analysis, and the recent experience of regulating cyber conflict and LAWS through Groups of Governmental Experts, the article proposes a schema for multilateral governance of digital technologies in armed conflict. The schema includes a heuristic for understanding human–machine interaction in order to operationalize accountability with international humanitarian law principles and international law applicable to armed conflict in the digital age. The article concludes with specific suggestions for advancing work in multilateral forums dealing with cyber weapons and lethal autonomy.
We have previously argued that the 2008 global financial and economic crisis was a clear manifestation of an unstable and contradictory world characterized by a disjunction between (1) massive economic growth and unprecedented advances in science, technology, and medical care and (2) the widening of disparities in wealth and health within and between nations. We also argued that the global financial crisis was much more than a crisis of capitalist accumulation or a necessary self-correction aided by macroeconomic intervention and bailouts.
In Chapter 18, we outlined a reading of the present global conjuncture that we characterized as one of organic crisis. The term was meant to invoke a paradoxical situation, one pregnant with possibilities for alternative ways in which global health might be improved, yet nevertheless a situation in which new alternatives have yet to emerge or indeed to be born.
Spectacular progress, both intellectual and material, has been achieved through the Enlightenment notion of the centrality of the individual and the supremacy of science and technology in advancing health and healthcare practices. The modern Western belief system and its frames for global thinking that have now become powerful worldwide are succinctly characterized by an individualistic, self-determining, and rights-bearing concept of being; an epistemological framework that centers on abstract thinking, objectivity in observation, logical reasoning processes, verifiable knowledge, and a positivist version of the scientific method; and moral and political values of autonomy supportive of individual rights. Scientific and technological progress and diverse socioeconomic systems contributed to fostering great “accelerations” in the scale of production, consumption, communication, and transportation that in particular since 1945 have improved the duration and quality of life for many people.
This study is focused on the prediction of coherent structures, propagating within a turbulent channel flow. We propose a derivation of the linearised problem based on a stochastic formulation of the Navier–Stokes equations. It consists in considering the transport of quantities by a resolved velocity (i.e. solution of the model) perturbed by a Brownian motion which models the unresolved turbulent fluctuations over the time-averaged field, here thought of as the underlying background turbulence. The associated linearised model, considering the mean velocity profile as given, predicts linear solutions evolving within a corrected mean velocity field and perturbed by modelled background turbulence. Two ways to define the statistics of the Brownian motion are proposed and compared: one based on full simulation data, and the second, data free, based on preliminary predictions from resolvent analysis. The technique is applied on turbulent channel flows at friction Reynolds numbers $Re_\tau =180$ and $Re_\tau =550$, and predictions are compared with direct numerical simulation results. We show that the principal components of an ensemble of solutions of this stochastic linearised system are able to represent the leading spectral proper orthogonal decomposition modes with a similar accuracy to optimal responses coming from resolvent analysis with an eddy-viscosity model at scales where strong production occurs. For the other scales, receiving energy by nonlinear redistribution, the present strategy improves the prediction. Moreover, the second mode is systematically well predicted over all scales. This behaviour is understood by the ability of the stochastic modelling to model positive and negative inter-scale energy transfers through stochastic diffusion and random stochastic transport, while the eddy-viscosity term in resolvent analysis is purely diffusive.
Several individual, environmental and parasitic factors can influence the impacts of parasites on host's fitness and on host's ability to transmit these parasites to new hosts. Identifying these factors and the individuals who play a greater role in parasite transmission is of main concern for the development of parasite control strategies. In the present study, we aimed to describe the diversity of gastrointestinal parasites and to identify the individual factors influencing the faecal spreading of parasites in a free-ranging population of Mediterranean mouflon. From the analysis of 433 faecal samples, we found Eimeria spp. and gastrointestinal strongyles (GIS) were the most common parasites (>94%). The faecal oocyst counts of Eimeria spp. were the highest during the first years of life. It was 1.6 times higher in females than in males and 2.5 times higher in individuals in poor than in good body condition. Similarly, the faecal egg count of GIS was higher in females and decreased with age, but only in males. Finally, reproductive females had GIS faecal egg count values 2.6 times higher than non-reproductive females. Management strategies of parasites should thus primarily focus on reproductive females and young individuals in poor body condition as they represent the main contamination source of the environment.
To compare the genetic testing results of neonates with CHD by chromosomal microarray to karyotyping and fluorescence in situ hybridisation analysis.
This was a single-centre retrospective comparative study of patients with CHD and available genetic testing results admitted to the cardiac ICU between January, 2004 and December, 2017. Patients from 2004 to 2010 were tested by karyotyping and fluorescence in situ hybridisation analysis, while patients from 2012 to 2017 were analysed by chromosomal microarray.
Eight-hundred and forty-nine neonates with CHD underwent genetic testing, 482 by karyotyping and fluorescence in situ hybridization, and 367 by chromosomal microarray. In the karyotyping and fluorescence in situ hybridisation analysis group, 86/482 (17.8%) had genetic abnormalities detected, while in the chromosomal microarray group, 135/367 (36.8%) had genetic abnormalities detected (p < 0.00001). Of patients with abnormal chromosomal microarray results, 41/135 (30.4%) had genetic abnormality associated with neurodevelopmental disorders that were exclusively identified by chromosomal microarray. Conotruncal abnormalities were the most common diagnosis in both groups, with karyotyping and fluorescence in situ hybridisation analysis detecting genetic abnormalities in 26/160 (16.3%) patients and chromosomal microarray detecting abnormalities in 41/135 (30.4%) patients (p = 0.004). In patients with d-transposition of the great arteries, 0/68 (0%) were found to have genetic abnormalities by karyotyping and fluorescence in situ hybridisation compared to 7/54 (13.0%) by chromosomal microarray.
Chromosomal microarray identified patients with CHD at genetic risk of neurodevelopmental disorders, allowing earlier intervention with multidisciplinary care and more accurate pre-surgical prognostic counselling.
Three resistant (R) rigid ryegrass (Lolium rigidum Gaudin) populations from southern Australia (EP162, 375-14, and 198-15) with cross-resistance to thiocarbamate, chloroacetamide, and sulfonylisoxazoline herbicides displayed reduced sensitivity to the isoxazolidinone herbicides bixlozone and clomazone. Each of these R populations was exposed to two cycles of recurrent selection (RS) in which plants were treated with the field rate of bixlozone, survivors were bulk crossed, and seed was collected. After the first cycle of recurrent selection (RS1), the LD50 to bixlozone in population 198-15 increased to 17.5-fold compared with the S population and increased further to 26.9-fold after a second cycle of recurrent selection (RS2). The recurrent selection process also increased the level of resistance to bixlozone in populations EP162 and 375-14 (7.8- to 18.4-fold) compared with the S population. Phorate antagonized bixlozone and clomazone in SLR4 (34.6- and 28.1-fold increase in LD50) and both herbicides in populations EP162 (36.5- to 46.6-fold), 375-14 (71.4- to 73.9-fold), and 198-15 (86.4- to 91.5-fold) compared with the absence of phorate. The increase in LD50 of all L. rigidum RS populations when treated with phorate suggests a lack of herbicide activation is not the likely resistance mechanism to these herbicides. This research highlights the elevated risk of thiocarbamate-resistant L. rigidum populations to rapidly evolve resistance to the isoxazolidinone herbicides bixlozone and clomazone.
The EVOSHEEP project combines archaeozoology, geometric morphometrics and genetics to study archaeological sheep assemblages dating from the sixth to the first millennia BC in eastern Africa, the Levant, the Anatolian South Caucasus, the Iranian Plateau and Mesopotamia. The project aims to understand changes in the physical appearance and phenotypic characteristics of sheep and how these related to the appearance of new breeds and the demand for secondary products to supply the textile industry.
Since 2015, increased numbers of newly immigrated schoolchildren in Europe have resulted in divergent, often ad hoc measures to provide for their education. Because the basis of classroom learning is information found in written texts, the development of grade-level reading skills is of central importance. However, little is known about immigrant students’ reading skills at and following transition, and no data is available for Germany, where the study was conducted. We report the results of a longitudinal study in which migrant students’ (N = 136) reading subskills after transition into mainstream were investigated at three points over the course of 2 years and compared to cohort performance (N = 517) in grades 7 through 9. Results showed that immigrant students performed significantly below mainstream students on all measures for all data points, with little evidence that they are beginning to close the gap even after several years in mainstream.
Benzodiazepine (BZD) prescription rates have increased over the past decade in the United States. Available literature indicates that sociodemographic factors may influence diagnostic patterns and/or prescription behaviour. Herein, the aim of this study is to determine whether the gender of the prescriber and/or patient influences BZD prescription.
Cross-sectional study using data from the Florida Medicaid Managed Medical Assistance Program from January 1, 2018 to December 31, 2018. Eligible recipients ages 18 to 64, inclusive, enrolled in the Florida Medicaid plan for at least 1 day, and were dually eligible. Recipients either had a serious mental illness (SMI), or non-SMI and anxiety.
Total 125 463 cases were identified (i.e., received BZD or non-BZD prescription). Main effect of patient and prescriber gender was significant F(1, 125 459) = 0.105, P = 0 .745, partial η2 < 0.001. Relative risk (RR) of male prescribers prescribing a BZD compared to female prescribers was 1.540, 95% confidence intervals (CI) [1.513, 1.567], whereas the RR of male patients being prescribed a BZD compared to female patients was 1.16, 95% CI [1.14, 1.18]. Main effects of patient and prescriber gender were statistically significant F(1, 125 459) = 188.232, P < 0.001, partial η2 = 0.001 and F(1, 125 459) = 349.704, P < 0.001, partial η2 = 0.013, respectively.
Male prescribers are more likely to prescribe BZDs, and male patients are more likely to receive BZDs. Further studies are required to characterize factors that influence this gender-by-gender interaction.
The coronavirus disease 2019 (COVID-19) pandemic led to measures that reduced social contact and support. We explored whether UK residents with more frequent or supportive social contact had fewer depressive symptoms during March−August 2020, and potential factors moderating the relationship.
A convenience sample of UK dwelling participants aged ⩾18 in the internet-based longitudinal COVID-19 Social Study completed up to 22 weekly questionnaires about face-to-face and phone/video social contact frequency, perceived social support, and depressive symptoms using the PHQ-9. Mixed linear models examined associations between social contact and support, and depressive symptoms. We examined for interaction by empathic concern, perspective taking and pre-COVID social contact frequency.
In 71 117 people with mean age 49 years (standard deviation 15), those with high perceived social support scored 1.836 (1.801–1.871) points lower on PHQ-9 than those with low support. Daily face-to-face or phone/video contact was associated with lower depressive symptoms (0.258 (95% confidence interval 0.225–0.290) and 0.117 (0.080–0.154), respectively) compared to no contact. The negative association between social relationships and depressive symptoms was stronger for those with high empathic concern, perspective taking and usual sociability.
We found during lockdown that those with higher quality or more face-to-face or phone/video contact had fewer depressive symptoms. Contact quality was more strongly associated than quantity. People who were usually more sociable or had higher empathy had more depressive symptoms during enforced reduced contact. The results have implications for COVID-19 and potential future pandemic management, and for understanding the relationship between social factors and mental health.
Early withdrawal from the workforce is associated with a diagnosis of multiple sclerosis (MS), with employment retention rates also lower than in the general population. Despite legal requirements, equality in the workplace for people with MS has not been achieved. Disclosure of multiple sclerosis at work is essential for the implementation of accommodations enabling employment retention.
An interpretive descriptive study explored participants’ decision to disclose or not disclose their diagnosis of multiple sclerosis and the implications this had on work participation and working relationships. Semistructured interviews were used to collect data from 6 participants.
Three themes were identified, using a reflective approach to analysis, from the data: (a) Accommodations; (b) Workplace Relationships; and (c) Balancing Work and Home Life. Participants had mixed experiences of disclosing their diagnosis. Findings supported the implementation of workplace accommodations including physical, cognitive, and structural supports. Concealment of MS was associated with fear of workplace stigmatisation.
Disclosure is multidimensional and subjective. It is based on personal, systematic, and social factors. This study was limited by the small number of participants and not including stakeholders in the creation of the topic guide. The results are important for those involved in supporting people with multiple sclerosis to remain in the workplace.
Patients unsuccessfully treated by neurostimulation may represent a highly intractable subgroup of depression. While the efficacy of intravenous (IV) ketamine has been established in patients with treatment-resistant depression (TRD), there is an interest to evaluate its effectiveness in a subpopulation with a history of neurostimulation.
This retrospective, posthoc analysis compared the effects of four infusions of IV ketamine in 135 (x̄ = 44 ± 15.4 years of age) neurostimulation-naïve patients to 103 (x̄ = 47 ± 13.9 years of age) patients with a history of neurostimulation. The primary outcome evaluated changes in depression severity, measured by the Quick Inventory for Depression Symptomatology-Self Report 16-Item (QIDS-SR16). Secondary outcomes evaluated suicidal ideation (SI), anxiety severity, measured by the Generalized Anxiety Disorder 7-Item (GAD-7), and consummatory anhedonia, measured by the Snaith–Hamilton Pleasure Scale (SHAPS).
Following four infusions, both cohorts reported a significant reduction in QIDS-SR16 Total Score (F (4, 648) = 73.4, P < .001), SI (F (4, 642) = 28.6, P < .001), GAD-7 (F (2, 265) = 53.8, P < .001), and SHAPS (F (2, 302) = 45.9, P < .001). No between-group differences emerged. Overall, the neurostimulation-naïve group had a mean reduction in QIDS-SR16 Total Score of 6.4 (standard deviation [SD] = 5.3), whereas the history of neurostimulation patients reported a 4.3 (SD = 5.3) point reduction.
IV ketamine was effective in reducing symptoms of depression, SI, anxiety, and anhedonia in both cohorts in this large, well-characterized community-based sample of adults with TRD.