State of the Practice in Application Programming Interfaces (APIs): A Case Study

Application Programming Interfaces (APIs) have become prevalent in today’s software systems and services. APIs are basically a technical means to realize the co-operation between software systems or services. While there are several guidelines for API development, the actually applied practices and challenges are less clear. To better understand the state of the practice of API development and management in the industry, we conducted a descriptive case study in four Finnish software companies: two consultancy companies developing software for their customers, and two companies developing their software products. As a result, we identified five different usage scenarios for APIs and emphasize that diversity of usage should be taken into account more explicitly especially in research. API development and technical management are well supported by the existing tools and technologies especially available from the cloud technology. This leaves as the main challenge the selection of the right technology from the existing technology stack. Documentation and usability are practical issues to be considered and often less rigorously addressed. However, understanding what kind of API management model to apply for the business context appears as the major challenge. We also suggest considering APIs more clearly a separate concern in the product management with specific practices, such as API roadmapping.Peer reviewe

Recovery of cortical effective connectivity and recovery of consciousness in vegetative patients

Patients surviving severe brain injury may regain consciousness without recovering their ability to understand, move and communicate. Recently, electrophysiological and neuroimaging approaches, employing simple sensory stimulations or verbal commands, have proven useful in detecting higher order processing and, in some cases, in establishing some degree of communication in brain-injured subjects with severe impairment of motor function. To complement these approaches, it would be useful to develop methods to detect recovery of consciousness in ways that do not depend on the integrity of sensory pathways or on the subject's ability to comprehend or carry out instructions. As suggested by theoretical and experimental work, a key requirement for consciousness is that multiple, specialized cortical areas can engage in rapid causal interactions (effective connectivity). Here, we employ transcranial magnetic stimulation together with high-density electroencephalography to evaluate effective connectivity at the bedside of severely brain injured, non-communicating subjects. In patients in a vegetative state, who were open-eyed, behaviourally awake but unresponsive, transcranial magnetic stimulation triggered a simple, local response indicating a breakdown of effective connectivity, similar to the one previously observed in unconscious sleeping or anaesthetized subjects. In contrast, in minimally conscious patients, who showed fluctuating signs of non-reflexive behaviour, transcranial magnetic stimulation invariably triggered complex activations that sequentially involved distant cortical areas ipsi- and contralateral to the site of stimulation, similar to activations we recorded in locked-in, conscious patients. Longitudinal measurements performed in patients who gradually recovered consciousness revealed that this clear-cut change in effective connectivity could occur at an early stage, before reliable communication was established with the subject and before the spontaneous electroencephalogram showed significant modifications. Measurements of effective connectivity by means of transcranial magnetic stimulation combined with electroencephalography can be performed at the bedside while by-passing subcortical afferent and efferent pathways, and without requiring active participation of subjects or language comprehension; hence, they offer an effective way to detect and track recovery of consciousness in brain-injured patients who are unable to exchange information with the external environment

Motor adaptation and internal model formation in a robot-mediated forcefield

Background: Motor adaptation relies on error-based learning for accurate movements in changing environments. However, the neurophysiological mechanisms driving individual differences in performance are unclear. TMS-evoked potential can provide a direct measure of cortical excitability. Objective: To investigate cortical excitability as a predictor of motor learning and motor adaptation in a robot-mediated forcefield. Methods: 15 right-handed healthy participants (mean age 23 years) performed a robot-mediated forcefield perturbation task. There were 2 conditions: unperturbed non-adaptation and perturbed adaptation. Transcranial magnetic stimulation (TMS) was applied in the resting state at baseline and following motor adaptation over the contralateral primary motor cortex (left M1). EEG was continuously recorded, and cortical excitability was measured by TMS-evoked potential (TEP). Motor learning was quantified by the motor learning index. Results: Larger error-related negativity (ERN) in fronto-central regions was associated with improved motor performance as measured by a reduction in trajectory errors. Baseline TEP N100 peak amplitude predicted motor learning (p = 0.005), which was significantly attenuated relative to baseline (p = 0.0018) following motor adaptation. Conclusions: ERN reflected the formation of a predictive internal model adapted to the forcefield perturbation. Attenuation in TEP N100 amplitude reflected an increase in cortical excitability with motor adaptation reflecting neuroplastic changes in the sensorimotor cortex. TEP N100 is a potential biomarker for predicting the outcome in robot-mediated therapy and a mechanism to investigate psychomotor abnormalities in depression

Murtumapotilaiden osteoporoosin lääkehoidossa on isoja alueellisia eroja

Lähtökohdat : Lääkekattavuudesta osteoporoottisten murtumien sekundaaripreventiossa Suomessa ei ole tietoa. Tässä tutkimuksessa tarkastellaan pienienergiaisen murtuman jälkeen osteoporoosi-lääkemääräyksen saaneiden potilaiden osuutta ja lääkemääräyskattavuuden alueellisia eroja. Menetelmät : Tutkimus on retrospektiivinen rekisteritutkimus, joka toteutettiin hoitoilmoitusten ja Kelan reseptitietojen pohjalta. Tulokset : Potilaista 9 %:lle määrättiin osteoporoosilääkitys 6 kuukauden sisällä murtumasta. Lääkemääräyskattavuus suureni 12 %:iin 12 kuukauden sisällä murtumasta. Lonkka- (11 %) ja nikamamurtumien (18 %) kohdalla lääkemääräyksen saaneiden osuus oli hiukan keskiarvoa suurempi. Lonkkamurtuman jälkeinen lääkemääräyskattavuus oli eri sairaanhoitopiireissä 3–32 %. Päätelmät : Kansainvälisiin tuloksiin verrattuna osteoporoosilääkemääräyksen saaneiden murtumapotilaiden osuutta voi pitää pienenä. Lääkemääräyskattavuudessa oli eroja sairaanhoitopiirien välillä, joskaan tulokset eivät ota huomioon tsoledronihappohoitoja. Osteoporoosin sekundaariprevention tehostamiselle ja lääkehoidon yhtenäistämiselle on tarvetta.Peer reviewe

The Effect of Lamotrigine and Levetiracetam on TMS-Evoked EEG Responses Depends on Stimulation Intensity

The combination of transcranial magnetic stimulation and electroencephalography (TMS-EEG) has uncovered underlying mechanisms of two anti-epileptic medications: levetiracetam and lamotrigine. Despite their different mechanism of action, both drugs modulated TMS-evoked EEG potentials (TEPs) in a similar way. Since both medications increase resting motor threshold (RMT), the current aim was to examine the similarities and differences in post-drug TEPs, depending on whether stimulation intensity was adjusted to take account of post-drug RMT increase. The experiment followed a placebo controlled, double blind, crossover design, involving a single dose of either lamotrigine or levetiracetam. When a drug-induced increase of RMT occurred, post-drug measurements involved two blocks of stimulations, using unadjusted and adjusted stimulation intensity. A cluster based permutation analysis of differences in TEP amplitude between adjusted and unadjusted stimulation intensity showed that lamotrigine induced a stronger modulation of the N45 TEP component compared to levetiracetam. Results highlight the impact of adjusting stimulation intensity

Long Lasting Modulation of Cortical Oscillations after Continuous Theta Burst Transcranial Magnetic Stimulation

Transcranial magnetic theta burst stimulation (TBS) differs from other high-frequency rTMS protocols because it induces plastic changes up to an hour despite lower stimulus intensity and shorter duration of stimulation. However, the effects of TBS on neuronal oscillations remain unclear. In this study, we used electroencephalography (EEG) to investigate changes of neuronal oscillations after continuous TBS (cTBS), the protocol that emulates long-term depression (LTD) form of synaptic plasticity. We randomly divided 26 healthy humans into two groups receiving either Active or Sham cTBS as control over the left primary motor cortex (M1). Post-cTBS aftereffects were assessed with behavioural measurements at rest using motor evoked potentials (MEPs) and at active state during the execution of a choice reaction time (RT) task in combination with continuous electrophysiological recordings. The cTBS-induced EEG oscillations were assessed using event-related power (ERPow), which reflected regional oscillatory activity of neural assemblies of θ (4–7.5 Hz), low α (8–9.5 Hz), µ (10–12.5 Hz), low β (13–19.5 Hz), and high β (20–30 Hz) brain rhythms. Results revealed 20-min suppression of MEPs and at least 30-min increase of ERPow modulation, suggesting that besides MEPs, EEG has the potential to provide an accurate cortical readout to assess cortical excitability and to investigate the interference of cortical oscillations in the human brain post-cTBS. We also observed a predominant modulation of β frequency band, supporting the hypothesis that cTBS acts more on cortical level. Theta oscillations were also modulated during rest implying the involvement of independent cortical theta generators over the motor network post cTBS. This work provided more insights into the underlying mechanisms of cTBS, providing a possible link between synchronised neural oscillations and LTD in humans

Divergent Cortical Generators of MEG and EEG during Human Sleep Spindles Suggested by Distributed Source Modeling

Background: Sleep spindles are,1-second bursts of 10–15 Hz activity, occurring during normal stage 2 sleep. In animals, sleep spindles can be synchronous across multiple cortical and thalamic locations, suggesting a distributed stable phaselocked generating system. The high synchrony of spindles across scalp EEG sites suggests that this may also be true in humans. However, prior MEG studies suggest multiple and varying generators. Methodology/Principal Findings: We recorded 306 channels of MEG simultaneously with 60 channels of EEG during naturally occurring spindles of stage 2 sleep in 7 healthy subjects. High-resolution structural MRI was obtained in each subject, to define the shells for a boundary element forward solution and to reconstruct the cortex providing the solution space for a noise-normalized minimum norm source estimation procedure. Integrated across the entire duration of all spindles, sources estimated from EEG and MEG are similar, diffuse and widespread, including all lobes from both hemispheres. However, the locations, phase and amplitude of sources simultaneously estimated from MEG versus EEG are highly distinct during the same spindles. Specifically, the sources estimated from EEG are highly synchronous across the cortex, whereas those from MEG rapidly shift in phase, hemisphere, and the location within the hemisphere. Conclusions/Significance: The heterogeneity of MEG sources implies that multiple generators are active during huma

Organs to Cells and Cells to Organoids: The Evolution of in vitro Central Nervous System Modelling

With 100 billion neurons and 100 trillion synapses, the human brain is not just the most complex organ in the human body, but has also been described as “the most complex thing in the universe.” The limited availability of human living brain tissue for the study of neurogenesis, neural processes and neurological disorders has resulted in more than a century-long strive from researchers worldwide to model the central nervous system (CNS) and dissect both its striking physiology and enigmatic pathophysiology. The invaluable knowledge gained with the use of animal models and post mortem human tissue remains limited to cross-species similarities and structural features, respectively. The advent of human induced pluripotent stem cell (hiPSC) and 3-D organoid technologies has revolutionised the approach to the study of human brain and CNS in vitro, presenting great potential for disease modelling and translational adoption in drug screening and regenerative medicine, also contributing beneficially to clinical research. We have surveyed more than 100 years of research in CNS modelling and provide in this review an historical excursus of its evolution, from early neural tissue explants and organotypic cultures, to 2-D patient-derived cell monolayers, to the latest development of 3-D cerebral organoids. We have generated a comprehensive summary of CNS modelling techniques and approaches, protocol refinements throughout the course of decades and developments in the study of specific neuropathologies. Current limitations and caveats such as clonal variation, developmental stage, validation of pluripotency and chromosomal stability, functional assessment, reproducibility, accuracy and scalability of these models are also discussed