The challenges of regulatory pluralism.

Countries with small and/or less-resourced regulatory authorities that operate outside of a larger medical product regulatory system face a regulatory strategy dilemma. These countries may rely on foreign well-resourced regulators by recognising the regulatory decisions of large systems and following suit (regulatory reliance); alternatively, such countries may extend formal decision recognition to regulators in multiple other jurisdictions with similar oversight and public health goals, following a system which we call regulatory pluralism. In this policy comment, we discuss three potential limitations to regulatory pluralism: (i) regulatory escape, in which manufacturers exploit regulatory variation and choose the lowest regulatory threshold for their product; (ii) increased fragmentation and complexity for countries adopting this approach, which may, in turn, lead to inconsistent processes; and (iii) loss of international bargaining power in developing regulatory policies.

The modernisation of newborn screening as a pan-European challenge - An international delphi study.

Newborn screening is a public health measure to diagnose rare diseases at birth, thereby minimising negative effects of late treatment. Genomic technologies promise an unprecedented expansion of screened diseases at low cost and with transformative potential for newborn screening programmes. However, barriers to the public funding of genomic newborn screening are poorly understood, particularly in light of the heterogenous European newborn screening landscape.

Radiofrequency for chronic lumbosacral and cervical pain: Results of a consensus study using the RAND/UCLA appropriateness method.

Background: Despite the routine use of radiofrequency (RF) for the treatment of chronic pain in the lumbosacral and cervical region, there remains uncertainty on the most appropriate patient selection criteria. This study aimed to develop appropriateness criteria for RF in relation to relevant patient characteristics, considering RF ablation (RFA) for the treatment of chronic axial pain and pulsed RF (PRF) for the treatment of chronic radicular pain.

Methods: The RAND/UCLA Appropriateness Method (RUAM) was used to explore the opinions of a multidisciplinary European panel on the appropriateness of RFA and PRF for a variety of clinical scenarios.

[Radiofrequency denervation of the spine and the sacroiliac joint : A systematic literature search according to GRADE with new German S3 guideline].

Background: This article summarizes the results of the German guideline on radiofrequency denervation of the facet joints and the sacroiliac joint. Evidence on the indications, test blocks and technical parameters are presented.

Objective: The aim is to avoid overtreatment and undertreatment, which is also of socioeconomic importance.

How social networks influence the local implementation of initiatives developed in quality improvement collaboratives in health care: A qualitative process study.

Background: Quality improvement collaboratives (QICs) have facilitated cross-organizational knowledge exchange in health care. However, the local implementation of many quality improvement (QI) initiatives continues to fail, signaling a need to better understand the contributing factors. Organizational context, particularly the role of social networks in facilitating or hindering implementation within organizations, remains a potentially critical yet underexplored area to addressing this gap.

Radiofrequency Denervation of the Spine and the Sacroiliac Joint: A Systematic Review based on the Grades of Recommendations, Assesment, Development, and Evaluation Approach Resulting in a German National Guideline.

Study Design: Systematic review of the literature and subsequent meta-analysis for the development of a new guideline.

Objectives: This manuscript summarizes the recommendations from a new clinical guideline published by the German Spine Society. It covers the current evidence on recommendations regarding the indication, test blocks and use of radiofrequency denervation.

Are the European reference networks for rare diseases ready to embrace machine learning? A mixed-methods study.

Background: The delay in diagnosis for rare disease (RD) patients is often longer than for patients with common diseases. Machine learning (ML) technologies have the potential to speed up and increase the precision of diagnosis in this population group. We aim to explore the expectations and experiences of the members of the European Reference Networks (ERNs) for RDs with those technologies and their potential for application.

We're implementing AI now, so why not ask us what to do? - How AI providers perceive and navigate the spread of diagnostic AI in complex healthcare systems.

Despite high expectations of artificial intelligence (AI) in medical diagnostics, predictions of its extensive and rapid adoption have so far not been matched by reality. AI providers seeking to promote and perpetuate the use of this technology are faced with the complex reality of embedding AI-enabled diagnostics across variable implementation contexts. In this study, we draw upon a complexity science approach and qualitative methodology to understand how AI providers perceive and navigate the spread of AI in complex healthcare systems.

Genetic newborn screening and digital technologies: A project protocol based on a dual approach to shorten the rare diseases diagnostic path in Europe.

Since 72% of rare diseases are genetic in origin and mostly paediatrics, genetic newborn screening represents a diagnostic "window of opportunity". Therefore, many gNBS initiatives started in different European countries. Screen4Care is a research project, which resulted of a joint effort between the European Union Commission and the European Federation of Pharmaceutical Industries and Associations.

Effect of low-frequency dorsal root ganglion stimulation in the treatment of chronic pain.

Background: The role of stimulation parameters, especially stimulation frequency is not well understood in dorsal root ganglion stimulation. Previous studies documented higher effectiveness for frequencies as low as 20 Hz, but there is evidence that even lower values could lead to better outcomes. In this study, we investigate the influence of low-frequency DRG-S.

Frequency dependency of therapeutic efficacy in dorsal root ganglion stimulation for neuropathic pain.

Background: The influence of the stimulation frequency on the outcomes of dorsal root ganglion stimulation (DRG-S) to treat pain is not well understood. It is assumed that specific neural components dedicated to different tasks in the DRG can be preferably influenced at specific frequencies. The identification of frequencies designed for the type of pain and the ratio of neuropathic versus nociceptive pain might improve overall pain control and open new indications in DRG-S.

Combination of waveforms in modern spinal cord stimulation.

Background: After the surge of burst stimulation, different waveforms were developed to optimize results in spinal cord stimulation. Studies have shown higher responder rates for multiwave therapy, but since the launch of such multiwave systems, little is known about the patients' preference regarding waveforms in the long-term follow-up. No study connected particular waveforms to specific pain etiologies or required stimulation parameters so far.

Early-Warning Signals of Individual Tree Mortality Based on Annual Radial Growth.

Tree mortality is a key driver of forest dynamics and its occurrence is projected to increase in the future due to climate change. Despite recent advances in our understanding of the physiological mechanisms leading to death, we still lack robust indicators of mortality risk that could be applied at the individual tree scale. Here, we build on a previous contribution exploring the differences in growth level between trees that died and survived a given mortality event to assess whether changes in temporal autocorrelation, variance, and synchrony in time-series of annual radial growth data can be used as early warning signals of mortality risk.

A synthesis of radial growth patterns preceding tree mortality.

Tree mortality is a key factor influencing forest functions and dynamics, but our understanding of the mechanisms leading to mortality and the associated changes in tree growth rates are still limited. We compiled a new pan-continental tree-ring width database from sites where both dead and living trees were sampled (2970 dead and 4224 living trees from 190 sites, including 36 species), and compared early and recent growth rates between trees that died and those that survived a given mortality event. We observed a decrease in radial growth before death in ca.

Cold-induced injury to lung epithelial cells can be inhibited by iron chelators - implications for lung preservation.

Objectives: Hypothermia has been shown to lead to cell death via an iron-dependent formation of reactive oxygen species (ROS) in diverse cell types. The susceptibility of lung cells to this injury is unknown - but is of great interest as oxygen is used in lung preservation. Therefore, we studied whether preservation injury to lung epithelial cells can be influenced by iron chelators.

Visual homing in the absence of feature-based landmark information.

Despite that fact that landmarks play a prominent role in human navigation, experimental evidence on how landmarks are selected and defined by human navigators remains elusive. Indeed, the concept of a 'landmark' is itself not entirely clear. In everyday language, the term landmark refers to salient, distinguishable, and usually nameable objects, rendering the problem of landmark recognition a special case of the general object recognition problem.

Head and eye movements and the role of memory limitations in a visual search paradigm.

The image information guiding visual behavior is acquired and maintained in an interplay of gaze shifts and visual short-term memory (VSTM). If storage capacity of VSTM is exhausted, gaze shifts can be used to regain information not currently represented in memory. By varying the separation between relevant image regions, S.

Route navigating without place recognition: what is recognised in recognition-triggered responses?

The use of landmark information in a route-navigation task has been investigated in a virtual environment. After learning a route, subjects were released at intermediate points along the route and asked to indicate the next movement direction required to continue the route. At each decision point, three landmarks were present, one of which was viewed centrally and two which appeared in the periphery of the visual field when approaching the decision point.

Navigation and acquisition of spatial knowledge in a virtual maze.

Spatial behavior in humans and animals includes a wide variety of behavioral competences and makes use of a large number of sensory cues. Here we studied the ability of human subjects to search locations, to find shortcuts and novel paths, to estimate distances between remembered places, and to draw sketch maps of the explored environment; these competences are related to goal-independent memory of space, or cognitive maps. Information on spatial relations was restricted to two types: a visual motion sequence generated by simulated movements in a virtual maze and the subject's own movement decisions defining the path through the maze.

Is correspondence search in human stereo vision a coarse-to-fine process?

One possible strategy for the solution of the correspondence problem of stereo matching is the coarse-to-fine mechanism: The matching process starts with a lowpass-filtered version of the stereogram where only a few, high-contrast image features can be extracted and the probability of false matches is therefore low. In subsequent stages, information from higher spatial frequencies is used gradually to improve the correspondence data obtained on the coarser scales. Coarse-to-fine strategies predict that information from coarse scale is used to disambiguate matching information on finer scales.