Repetitive spinal motor neuron discharges following single transcranial magnetic stimulation: relation to dexterity

Transcranial magnetic stimulation allows to study the properties of the human corticospinal tract non-invasively. After a single transcranial magnetic stimulus, spinal motor neurons (MNs) sometimes fire not just once, but repetitively. The biological significance of such repetitive MN discharges (repMNDs) is unknown. To study the relation of repMNDs to other measures of cortico-muscular excitability and to physiological measures of the skill for finely tuned precision movements, we used a previously described quadruple stimulation (QuadS) technique (Z'Graggen et al. 2005) to quantify the amount of repMNDs in abductor digiti minimi muscles (ADMs) on both sides of 20 right-handed healthy subjects. Skillfulness for finger precision movements of both hands was assessed using a finger tapping task. In 16 subjects, a follow-up examination was performed after training of either precision movements (n=8) or force (n=8) of the left ADM. The size of the QuadS response (amplitude and area ratios) was greater in the dominant right hand than in the left hand (QuadS amplitude ratio: 47.1±18.1 versus 37.7±22.0%, Wilcoxon test: P<0.05; QuadS area ratio: 49.7±16.2% versus 36.9±23.0%, Wilcoxon test: P<0.05), pointing to a greater amount of repMNDs. Moreover, the QuadS amplitude and area increased significantly after finger precision training, but not after force training. This increase of repMNDs correlated significantly with the increase in performance in the finger tapping task. Our results demonstrate that repMNDs are related to handedness and therefore probably reflect supraspinal excitability differences. The increase of repMNDs after skills training but not after force training supports the hypothesis of a supraspinal origin of repMND

Classifying Public Key Certificates

In spite of the fact that there are several companies that (try to) sell public key certificates, there is still no unified or standardized classification scheme that can be used to compare and put into perspective the various offerings. In this paper, we try to start filling this gap and propose a four-dimensional scheme that can be used to uniformly describe and classify public key certificates. The scheme distinguishes between (i) who owns a certificate, (ii) how the certificate owner is registered, (iii) on what medium the certificate (or the private key, respectively) is stored, and (iv) what type of functionality the certificate is intended to be used for. We think that using these or similar criteria to define and come up with unified or even standardized classes of public key certificate is useful and urgently needed in practice

Age-Dependent Dissimilarity of the Nasopharyngeal and Middle Ear Microbiota in Children With Acute Otitis Media.

Acute bacterial otitis media is usually caused by otopathogens ascending to the middle ear from the nasopharynx (NP). However, it is unknown if the nasopharyngeal microbiota of children with acute otitis media (AOM) can serve as an age-dependent or independent proxy for the microbial communities of the middle ear fluid (MEF) as there is a lack of 16S rRNA amplicon sequencing studies simultaneously analyzing the microbial communities of the two sites. Within this study, we performed 16S rRNA next generation sequencing on a total of 286 nasopharyngeal swabs (NPSs) collected between 2004 and 2013 within a Swiss national AOM surveillance program from children (0-6 years) with AOM. In addition, 42/286 children had spontaneous tympanic membrane perforation and, therefore, those MEF could also be analyzed. We found that alpha [Richness, Shannon diversity index (SDI) and Evenness] and beta diversity measurements of the nasopharyngeal bacterial microbiota showed a clear dependency of the increasing age of the children. In more detail, bacterial richness and personalized profiles (measured by beta dispersion) were higher and more frequent in older children, respectively. Dissimilarity values based on the binary distance matrix of the microbiota patterns of the NP and the MEF also correlated with increasing age. In general, positive (PPV) and negative predictive values (NPV) of the most abundant operational taxonomic units (OTUs) in the NP were moderately and well predictive for their presence in the MEF, respectively. This data is crucial to better understand polymicrobial infections and therefore AOM pathogenesis

Wharton's Jelly Mesenchymal Stem Cells Protect the Immature Brain in Rats and Modulate Cell Fate.

The development of a mammalian brain is a complex and long-lasting process. Not surprisingly, preterm birth is the leading cause of death in newborns and children. Advances in perinatal care reduced mortality, but morbidity still represents a major burden. New therapeutic approaches are thus desperately needed. Given that mesenchymal stem/stromal cells (MSCs) emerged as a promising candidate for cell therapy, we transplanted MSCs derived from the Wharton's Jelly (WJ-MSCs) to reduce the burden of immature brain injury in a murine animal model. WJ-MSCs transplantation resulted in protective activity characterized by reduced myelin loss and astroglial activation. WJ-MSCs improved locomotor behavior as well. To address the underlying mechanisms, we tested the key regulators of responses to DNA-damaging agents, such as cyclic AMP-dependent protein kinase/calcium-dependent protein kinase (PKA/PKC), cyclin-dependent kinase (CDK), ataxia-telangiectasia-mutated/ATM- and Rad3-related (ATM/ATR) substrates, protein kinase B (Akt), and 14-3-3 binding protein partners. We characterized WJ-MSCs using a specific profiler polymerase chain reaction array. We provide evidence that WJ-MSCs target pivotal regulators of the cell fate such as CDK/14-3-3/Akt signaling. We identified leukemia inhibitory factor as a potential candidate of WJ-MSCs' induced modifications as well. We hypothesize that WJ-MSCs may exert adaptive responses depending on the type of injury they are facing, making them prominent candidates for cell therapy in perinatal injuries

Challenging local realism with human choices

A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism 1, in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings 2,3 . Although technology can satisfy the first two of these requirements 4-7, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests 8 . Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology 9 . The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons 5,6, single atoms 7, atomic ensembles 10 and superconducting devices 11 . Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bipartite and tripartite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties 13 ), the utilization of video-game methods 14 for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science

Challenging local realism with human choices

A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings. Although technology can satisfy the first two of these requirements, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human `free will' could be used rigorously to ensure unpredictability in Bell tests. Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology. The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons, single atoms, atomic ensembles, and superconducting devices. Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bipartite and tripartite scenarios. Project outcomes include closing the `freedom-of-choice loophole' (the possibility that the setting choices are influenced by `hidden variables' to correlate with the particle properties), the utilization of video-game methods for rapid collection of human generated randomness, and the use of networking techniques for global participation in experimental science.Comment: This version includes minor changes resulting from reviewer and editorial input. Abstract shortened to fit within arXiv limit

Blood Parasites in Owls with Conservation Implications for the Spotted Owl (Strix occidentalis)

The three subspecies of Spotted Owl (Northern, Strix occidentalis caurina; California, S. o. occidentalis; and Mexican, S. o. lucida) are all threatened by habitat loss and range expansion of the Barred Owl (S. varia). An unaddressed threat is whether Barred Owls could be a source of novel strains of disease such as avian malaria (Plasmodium spp.) or other blood parasites potentially harmful for Spotted Owls. Although Barred Owls commonly harbor Plasmodium infections, these parasites have not been documented in the Spotted Owl. We screened 111 Spotted Owls, 44 Barred Owls, and 387 owls of nine other species for haemosporidian parasites (Leucocytozoon, Plasmodium, and Haemoproteus spp.). California Spotted Owls had the greatest number of simultaneous multi-species infections (44%). Additionally, sequencing results revealed that the Northern and California Spotted Owl subspecies together had the highest number of Leucocytozoon parasite lineages (n = 17) and unique lineages (n = 12). This high level of sequence diversity is significant because only one Leucocytozoon species (L. danilewskyi) has been accepted as valid among all owls, suggesting that L. danilewskyi is a cryptic species. Furthermore, a Plasmodium parasite was documented in a Northern Spotted Owl for the first time. West Coast Barred Owls had a lower prevalence of infection (15%) when compared to sympatric Spotted Owls (S. o. caurina 52%, S. o. occidentalis 79%) and Barred Owls from the historic range (61%). Consequently, Barred Owls on the West Coast may have a competitive advantage over the potentially immune compromised Spotted Owls

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic