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Background: Subthalamic deep brain stimulation (STN-DBS) is a well-established therapy to treat Parkinson's disease (PD). However, the STN-DBS sub-target remains debated. Recently, a white matter tract termed the hyperdirect pathway (HDP), directly connecting the motor cortex to STN, has gained interest as HDP stimulation is hypothesized to drive DBS therapeutic effects. Previously, we have investigated EEG-based evoked potentials (EPs) to better understand the neuroanatomical origins of the DBS clinical effect. We found a 3-ms peak (P3) relating to clinical benefit, and a 10-ms peak (P10) suggesting nigral side effects. Here, we aimed to investigate the neuroanatomical origins of DBS EPs using probabilistic mapping. Methods: EPs were recorded using EEG whilst low-frequency stimulation was delivered at all DBS-contacts individually. Next, EPs were mapped onto the patients’ individual space and then transformed to MNI standard space. Using voxel-wise and fiber-wise probabilistic mapping, we determined hotspots/hottracts and coldspots/coldtracts for P3 and P10. Topography analysis was also performed to determine the spatial distribution of the DBS EPs. Results: In all 13 patients (18 hemispheres), voxel- and fiber-wise probabilistic mapping resulted in a P3-hotspot/hottract centered on the posterodorsomedial STN border indicative of HDP stimulation, while the P10-hotspot/hottract covered large parts of the substantia nigra. Conclusion: This study investigated EP-based probabilistic mapping in PD patients during STN-DBS, revealing a P3-hotspot/hottract in line with HDP stimulation and P10-hotspot/hottract related to nigral stimulation. Results from this study provide key evidence for an electrophysiological measure of HDP and nigral stimulation.

Assisted migration is increasingly being considered as a potential climate change adaptation tactic even though it also comes with potential risk to ecosystems and society. When implementing conservation actions that involve risk, it is prudent to have policies and guidelines to ensure that such actions are conducted in ways that conform to regional standards and consider risks. Here, we report on a policy scan focused on assisted migration in the context of climate change adaptation originally as a protected areas tactic only, but then broadened to ecosystems in Canada beyond those boundaries. Policy scans are a useful strategy for understanding the evolving policy and regulatory landscape for a given topic and can guide the development of such policies in other jurisdictions. Our scan focused on Canada, where multi-scalar governance systems exist relevant to biodiversity and environmental management. Our comprehensive policy scan (involving scans of legislation, policies, and guidelines found online and through direct inquiries with government bodies) revealed major gaps in the assisted migration policy landscape with very few provincial/territorial or federal policies in Canada. A more rudimentary scan in the United States revealed a similar pattern. There was evidence that some jurisdictions anticipated need for such policies and even a few examples of very specific policies (e.g., seeds) that had already been developed, but there were not comprehensive policies or frameworks. Governments and other relevant bodies/organizations may wish to consider working collaboratively toward the development of robust, evidence-based policies for assisted migration given that we anticipate this conservation intervention becoming more popular as climate change impacts on ecosystems become more evident and dire.

Abstract The proposed AI-based diagnostic system aims to predict the respiratory support required for COVID-19 patients by analyzing the correlation between COVID-19 lesions and the level of respiratory support provided to the patients. Computed tomography (CT) imaging will be used to analyze the three levels of respiratory support received by the patient: Level 0 (minimum support), Level 1 (non-invasive support such as soft oxygen), and Level 2 (invasive support such as mechanical ventilation). The system will begin by segmenting the COVID-19 lesions from the CT images and creating an appearance model for each lesion using a 2D, rotation-invariant, Markov–Gibbs random field (MGRF) model. Three MGRF-based models will be created, one for each level of respiratory support. This suggests that the system will be able to differentiate between different levels of severity in COVID-19 patients. The system will decide for each patient using a neural network-based fusion system, which combines the estimates of the Gibbs energy from the three MGRF-based models. The proposed system were assessed using 307 COVID-19-infected patients, achieving an accuracy of $$97.72\%\pm 1.57$$ 97.72 % ± 1.57 , a sensitivity of $$97.76\%\pm 4.08$$ 97.76 % ± 4.08 , and a specificity of $$98.87\%\pm 2.09$$ 98.87 % ± 2.09 , indicating a high level of prediction accuracy.

Background: To maximize clinical benefit and minimize stimulation-induced side effects, optimising deep brain stimulation (DBS) parameters is paramount. Recent literature suggests a potential benefit of short pulse width DBS (spDBS; ≤40 μs) over conventional pulse width DBS (cDBS; ≥60 μs) in movement disorders. Objective: To compare therapeutic window (TW), therapeutic and side effects and energy consumption of spDBS and cDBS in movement disorders. Methods: We systematically searched Medline, Embase, Cochrane Library and Web of Science. Appropriate paired analyses were performed. Results: Nine Parkinson's disease (PD) (143 patients), 4 essential tremor (ET) (26 patients) and no dystonia studies were included in the meta-analysis. TW defined as therapeutic amplitude range was larger with spDBS vs. cDBS in PD (standardized mean difference (SMD) = -1.04, p

Abstract Nanobody molecules, derived from heavy‐chain only antibodies in camelids, represent the next generation of biotherapeutics. In addition to low immunogenicity, high stability, and potency, their single‐domain format facilitates the construction of multivalent molecules for therapeutic applications. Although predominantly administered using a hypodermic syringe and needle, alternative delivery methods are under investigation. That said, the transdermal route has yet to be explored. Therefore, microarray patch (MAP) technology, offering a potentially high dose, pain‐free transdermal system, is employed in this study. Trivalent Nanobody molecules, with and without half‐life extension (VHH and VHH[HLE]), are formulated into hydrogel‐forming MAPs, with pharmacokinetic parameters assessed in Sprague–Dawley rats. VHH MAPs exhibited a sustained release profile, with a serum concentration of 19 ± 9 ng mL−1 24 h post‐administration. In contrast, a subcutaneous (SC) injection showed faster clearance, with a serum concentration of 1.1 ± 0.4 ng mL−1 at 24 h. For VHH(HLE), both SC and MAP cohorts achieved a maximum serum concentration (Tmax) at 24 h. The MAP cohort displayed a notable increase in VHH(HLE) serum levels between 6–24 h, dropping after MAP removal. This study has exemplified MAPs potential for delivering advanced biologics, indicating the transdermal route's promise for pain‐free, patient‐friendly administration of Nanobody molecules.

IntroductionSymmetric biphasic pulses have been shown to increase the therapeutic window compared to standard cathodic pulses in ET Vim-DBS patients. Furthermore, three hours of stimulation with biphasic pulses caused less stimulation-induced ataxia compared to cathodic pulses. Therefore, an investigation of the longer-term safety of biphasic pulses is warranted.MethodsSeven ET patients were included in a randomized double-blind, cross-over design of one week home-use of symmetric biphasic stimulation (anodic phase first) versus cathodic stimulation. Amplitude was set in a double-blinded way, at the tremor arrest threshold. The primary outcome was safety assessed by documenting the adverse events. Secondary outcome parameters were stimulation amplitude, tremor (Fahn-Tolosa-Marin Tremor Rating Scale) and ataxia (International Cooperative Ataxia Rating Scale) severity, quality of life (Quality of Life in Essential Tremor Questionnaire) and cognition (Montreal Cognitive Assessment). Three patients continued in the open-label extension phase for 3 months, during which biphasic stimulation-only was further assessed by the same outcome parameters.ResultsDuring the 1 week testing, no adverse effects were reported. To obtain equivalent tremor control, the amplitude of the biphasic pulse was significantly higher compared to that of the cathodic pulse (p = 0.003). The other outcome parameters were not significantly different. During the open-label study, one patient used the remote control to increase the amplitude, leading to two falls caused by stimulation-induced ataxia. No other adverse effects occurred.Discussion and conclusionIn a small cohort, when tested for one week, symmetric biphasic pulses suggest to be safe, but require higher stimulation amplitudes. Further follow-up studies are needed to investigate long-term effects and safety.

Objectives To determine the well-being of physicians and nurses in hospital practice in Europe, and to identify interventions that hold promise for reducing adverse clinician outcomes and improving patient safety.Design Baseline cross-sectional survey of 2187 physicians and 6643 nurses practicing in 64 hospitals in six European countries participating in the EU-funded Magnet4Europe intervention to improve clinicians’ well-being.Setting Acute general hospitals with 150 or more beds in six European countries: Belgium, England, Germany, Ireland, Sweden and Norway.Participants Physicians and nurses with direct patient contact working in adult medical and surgical inpatient units, including intensive care and emergency departments.Main outcome measures Burnout, job dissatisfaction, physical and mental health, intent to leave job, quality of care and patient safety and interventions clinicians believe would improve their well-being.Results Poor work/life balance (57% physicians, 40% nurses), intent to leave (29% physicians, 33% nurses) and high burnout (25% physicians, 26% nurses) were prevalent. Rates varied by hospitals within countries and between countries. Better work environments and staffing were associated with lower percentages of clinicians reporting unfavourable health indicators, quality of care and patient safety. The effect of a 1 IQR improvement in work environments was associated with 7.2% fewer physicians and 5.3% fewer nurses reporting high burnout, and 14.2% fewer physicians and 8.6% fewer nurses giving their hospital an unfavourable rating of quality of care. Improving nurse staffing levels (79% nurses) and reducing bureaucracy and red tape (44% physicians) were interventions clinicians reported would be most effective in improving their own well-being, whereas individual mental health interventions were less frequently prioritised.Conclusions Burnout, mental health morbidities, job dissatisfaction and concerns about patient safety and care quality are prevalent among European hospital physicians and nurses. Interventions to improve hospital work environments and staffing are more important to clinicians than mental health interventions to improve personal resilience.

Abstract Background Women with advanced uterine cervical cancer suffer from a combination of moderate to severe physical, psychological, social, and spiritual distress due to their disease and are in need of palliative care to improve their quality of life. Approximately 85% of the women live in the low- and middle-income countries. Whether these women and their families access palliative care is not known. Objectives To understand the geographic accessibility, availability, financial accessibility, and acceptability of palliative care by patients with advanced cervical cancer and their families. Methods We conducted a Systematic review following PRISMA guidelines in CINAHL, Cochrane Central Register of Controlled Trials, MEDLINE, PsychINFO, PubMed and Scopus for the core concepts: palliative care, access, advanced uterine cervical cancer. Eligible articles were published in English, contained original data on experiences of patients and/or caregivers including symptoms management, and discussed available resources, communication, satisfaction, and healthcare utilization. Results Overall there was limited access to palliative care with the few available facilities located in cities, far from the rural areas where most women lived. Pervasive poverty was common with poor affordability of healthcare, travelling, accommodation, and subsistence expenses. Misconceptions and poor knowledge of the disease, cultural beliefs and attitudes, and other health system insufficiencies also presented challenges for access. Conclusion Concerted effort should be made to improve availability of palliative care facilities. Health education to address misconceptions and other cognitive barriers that limit access among cervical cancer patients and their families should be urgently undertaken in the LMICs.

(1) Background: Dysregulation in serotonergic and noradrenergic systems may be implicated in the neurobiophysiological mechanisms underlying pain-related cognitive impairment in chronic whiplash-associated disorders (CWAD). This study aimed to unravel the role of serotonergic and noradrenergic descending pathways in cognitive functioning at rest and in response to exercise in people with CWAD. (2) Methods: 25 people with CWAD were included in this double-blind, randomized, controlled crossover study. Endogenous descending serotonergic and noradrenergic inhibitory mechanisms were modulated by using a single dose of a selective serotonin reuptake inhibitor (Citalopram) or a selective norepinephrine reuptake inhibitor (Atomoxetine). Cognitive performance was studied at rest and in response to exercise (1) without medication intake; (2) after intake of Citalopram; and (3) after intake of Atomoxetine. (3) Results: After Atomoxetine intake, selective attention improved compared with the no medication day (p < 0.05). In contrast, a single dose of Citalopram had no significant effect on cognitive functioning at rest. When performing pairwise comparisons, improvements in selective attention were found after exercise for the no medication condition (p < 0.05). In contrast, after intake of Citalopram or Atomoxetine, selective and sustained attention worsened after exercise. (4) Conclusions: A single dose of Atomoxetine improved selective attention only in one Stroop condition, and a single dose of Citalopram had no effect on cognitive functioning at rest in people with CWAD. Only without medication intake did selective attention improve in response to exercise, whereas both centrally acting medications worsened cognitive performance in response to a submaximal aerobic exercise bout in people with CWAD.

ObjectiveSubthalamic deep brain stimulation (STN-DBS) is a neurosurgical therapy to treat Parkinson’s disease (PD). Optimal therapeutic outcomes are not achieved in all patients due to increased DBS technological complexity; programming time constraints; and delayed clinical response of some symptoms. To streamline the programming process, biomarkers could be used to accurately predict the most effective stimulation configuration. Therefore, we investigated if DBS-evoked potentials (EPs) combined with imaging to perform prediction analyses could predict the best contact configuration.MethodsIn 10 patients, EPs were recorded in response to stimulation at 10 Hz for 50 s on each DBS-contact. In two patients, we recorded from both hemispheres, resulting in recordings from a total of 12 hemispheres. A monopolar review was performed by stimulating on each contact and measuring the therapeutic window. CT and MRI data were collected. Prediction models were created to assess how well the EPs and imaging could predict the best contact configuration.ResultsEPs at 3 ms and at 10 ms were recorded. The prediction models showed that EPs can be combined with imaging data to predict the best contact configuration and hence, significantly outperformed random contact selection during a monopolar review.ConclusionEPs can predict the best contact configuration. Ultimately, these prediction tools could be implemented into daily practice to ease the DBS programming of PD patients.

Acute traumatic aortic injuries are of the most lethal sequelae of penetrating thoracic injuries and require rapid detection and management. The American College of Radiology currently recommends the use of noncontrast CT, followed by computed tomography angiography (CTA) as the first-line imaging modalities when traumatic aortic injury is suspected. Direct signs of aortic injury on CTA include pseudoaneurysm, focal contour abnormality, intimal flap, intramural hematoma, an abrupt change in aortic caliber, and contrast extravasation. Aortic pseudoaneurysms are most often caused by blunt or penetrating trauma that results in damage to the vessel wall, turbulent blood flow, and formation of a surrounding hematoma contained by a wall of products from the clotting cascade. This wall is weaker than those of a true aneurysm and will ultimately rupture over time if not repaired. Traumatic aortic pseudoaneurysms are preferably treated by thoracic endovascular aortic repair using a prosthetic stent graft. Here, we present a 44-yearold female with a history of homelessness, polysubstance use disorder, and HIV who presented to the emergency department after being found down. She reported being shot by a pellet gun, and physical examination revealed a penetrating left-sided chest wound that appeared to be several days old. A STAT CTA was obtained and revealed a hemopneumothorax and possible thoracic aortic pseudoaneurysm. A left-sided chest tube was placed and the patient underwent thoracic endovascular aortic repair through right femoral arterial access and tolerated the procedure well. The patient was placed on daily aspirin postoperatively and discharged on post-op day 5.

This paper introduces an innovative model for precise extraction of lung nodules from 3D computed tomography (CT) scans. Our approach comprises two essential preprocessing stages aimed at refining search accuracy and nodule segmentation. Initially, we leverage a two-level joint Markov-Gibbs random field (MGRF) model to delineate the lung region, effectively distinguishing lung wall nodules from the chest region with shared visual characteristics. Subsequently, employing a deep learning U-net technique, we pinpoint the region of interest (ROI) housing the lung nodule, minimizing the inclusion of surrounding lung tissues. Further enhancement comes from a 3D U-net, trained with a novel loss function to mitigate under- or over-segmentation issues. The resulting segmentation robustly outlines lung nodules in terms of morphology and volume metrics, validated by Dice coefficient (DCE), absolute volume difference (AVD), $95^{th}$ -percentile Hausdorff distance (HD), sensitivity, and specificity metrics. To assess our approach, we conducted comprehensive experiments. Our evaluation encompasses in vivo data from 50 patients and employs 679 subjects from the publicly available dataset of the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI). The LIDC-IDRI dataset, a seminal resource for computer-aided diagnosis (CAD) in lung nodules, offers annotations enabling tasks like detection, segmentation, classification, and quantification. Our experiments showcase our model’s superiority over existing deep learning methods, particularly evident in metrics such as the $95^{th}$ -percentile HD and DCE. While limited demographic information constrains a comprehensive analysis, our approach’s robust performance underlines its potential integration into nodule assessment AI systems.

Chronic pain is the most prevalent disease worldwide, leading to substantial disability and socioeconomic burden. Therefore, it can be regarded as a public health disease and major challenge to scientists, clinicians and affected individuals. Behavioral lifestyle factors, such as, physical (in)activity, stress, poor sleep and an unhealthy diet are increasingly recognized as perpetuating factors for chronic pain. Yet, current management options for patients with chronic pain often do not address lifestyle factors in a personalized multimodal fashion. This state-of-the-art clinical perspective aims to address this gap by discussing how clinicians can simultaneously incorporate various lifestyle factors into a personalized multimodal lifestyle intervention for individuals with chronic pain. To do so the available evidence on (multimodal) lifestyle interventions targeting physical (in)activity, stress, sleep and nutritional factors, specifically, was reviewed and synthetized from a clinical point of view. First, advise is provided on how to design a personalized multimodal lifestyle approach for a specific patient. Subsequently, best-evidence recommendations on how to integrate physical (in)activity, stress, sleep and nutritional factors as treatment targets into a personalized multimodal lifestyle approach are outlined. Evidence supporting such a personalized multimodal lifestyle approach is growing, but further studies are needed.

Abstract The multicenter observational BiRD study investigated the real-world effectiveness and safety of ibrutinib in patients with chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL) and Waldenström’s macroglobulinemia (WM) in Belgium. This interim analysis reports results for patients with CLL, with a median follow-up of 34 months. Overall, patients had predominantly relapsed/refractory disease (73%) and were elderly (median age 72 years) with high-risk features such as del17p and/or TP53 mutations (59%). Patients were included either prospectively or retrospectively, and the total patient population effectiveness results were adjusted with left truncation. In the effectiveness population (N = 221: prospective, n = 71; retrospective, n = 150), the overall response rate was 90.0%. Median progression-free survival was 38.3 months (prospective, not estimable; retrospective, 51.5 months) and median overall survival was not yet estimable in the total, prospective and retrospective groups. Treatment-emergent adverse events (TEAEs) for the prospective and retrospective groups are reported separately. Any-grade TEAEs of interest in the prospective/retrospective groups included infections (67.1%/60.1%), diarrhea (20.5%/10.5%), hypertension (16.4%/9.8%) and atrial fibrillation (12.3%/7.2%). Major bleeding was reported in 5.5%/3.3% of prospective/retrospective patients, with little difference observed between those receiving versus not receiving antithrombotic treatment. Discontinuations due to toxicity were reported in 10.5% of patients. Results from this interim analysis show treatment with ibrutinib to be effective and tolerable, with no new safety signals observed. Future analyses will report on longer-term follow-up.

IntroductionEarly exposure to a rich linguistic environment is essential as soon as the diagnosis of deafness is made. Cochlear implantation (CI) allows children to have access to speech perception in their early years. However, it provides only partial acoustic information, which can lead to difficulties in perceiving some phonetic contrasts. This study investigates the contribution of two spoken speech and language rehabilitation approaches to speech perception in children with CI using a lexicality judgment task from the EULALIES battery. Auditory Verbal Therapy (AVT) is an early intervention program that relies on auditory learning to enhance hearing skills in deaf children with CI. French Cued Speech, also called Cued French (CF), is a multisensory communication tool that disambiguates lip reading by adding a manual gesture.MethodsIn this study, 124 children aged from 60 to 140 months were included: 90 children with typical hearing skills (TH), 9 deaf children with CI who had participated in an AVT program (AVT), 6 deaf children with CI with high Cued French reading skills (CF+), and 19 deaf children with CI with low Cued French reading skills (CF-). Speech perception was assessed using sensitivity (d’) using both the hit and false alarm rates, as defined in signal-detection theory.ResultsThe results show that children with cochlear implants from the CF- and CF+ groups have significantly lower performance compared to children with typical hearing (TH) (p < 0.001 and p = 0.033, respectively). Additionally, children in the AVT group also tended to have lower scores compared to TH children (p = 0.07). However, exposition to AVT and CF seems to improve speech perception. The scores of the children in the AVT and CF+ groups are closer to typical scores than those of children in the CF- group, as evidenced by a distance measure.DiscussionOverall, the findings of this study provide evidence for the effectiveness of these two speech and language rehabilitation approaches, and highlight the importance of using a specific approach in addition to a cochlear implant to improve speech perception in children with cochlear implants.

BackgroundDespite numerous attempts to improve interprofessional collaboration and integration (IPCI) in primary care, patients, care providers, researchers, and governments are still looking for tools and guidance to do this more efficiently. To address these issues, we decided to develop a generic toolkit, based on sociocracy and psychological safety principles, to guide care providers in their collaboration within and outside their practice. Finally, we reasoned that, in order to obtain integrated primary care, different strategies should be combined.MethodsDevelopment of the toolkit consisted of a multiyear co-development process. Data originating from 65 care providers, through 13 in-depth interviews and five focus groups were analysed and subsequently evaluated in eight co-design workshop sessions, organised with a total of 40 academics, lecturers, care providers and members of the Flemish patient association. Findings from the qualitative interviews and co-design workshops were gradually, and inductively adapted and transformed into the content for the IPCI toolkit.ResultsTen themes were identified: (i) awareness of the importance of interprofessional collaboration, (ii) the need for a self-assessment tool to measure team performance, (iii) preparing a team to use the toolkit, (iv) enhancing psychological safety, (v) developing and determining consultation techniques, (vi) shared decision making, (vii) developing workgroups to tackle specific (neighbourhood) problems, (viii) how to work patient-centred, (ix) how to integrate a new team member, and (x) getting ready to implement the IPCI toolkit. From these themes, we developed a generic toolkit, consisting of eight modules.ConclusionIn this paper, we describe the multiyear co-development process of a generic toolkit for the improvement of interprofessional collaboration. Inspired by a mix of interventions from in and outside healthcare, a modular open toolkit was produced that includes aspects of Sociocracy, concepts as psychological safety, a self-assessment tool and other modules concerned with meetings, decision-making, integrating new team members and population health. Upon implementation, evaluation and further development and improvement, this compounded intervention should have a beneficial effect on the complex problem of interprofessional collaboration in primary care.

The carrying capacity for vertical loads of well-maintained masonry arch bridges is reasonably high. This might not be the case for horizontal loads, the effects of which have not been the subject of extensive research aside from seismic occurrences. Arch bridges crossing rivers are subjected to sudden horizontal loads, due to river torrents, carrying debris from higher grounds. The magnitude of these horizontal loads is similar to those of coastal waves and debris; however, their effect on these structures has yet to be explored in detail. The narrow and high Devil’s Bridge across the Arda River (BG) and the wide, low Candia Viaduct across the Sesia River (I) were chosen as examples. Both are strongly exposed to fast-washing flow in the river during spring. FE simulations show that the impact of the rapidly rising river water influences the general stability, while the effect of debris mainly causes local damage. The results exhibit that tall, slender masonry arch structures fail due to the brittle fracture of the material, followed by the shear failure of a pier body. In contrast, lower and wider viaducts fail due to exaggerated tensile cracking in the upstream parts of a pier and the associated increasing pressure at its downstream parts.

BackgroundSubthalamic deep brain stimulation (DBS) is an established therapy to treat Parkinson’s disease (PD). To maximize therapeutic outcome, optimal DBS settings must be carefully selected for each patient. Unfortunately, this is not always achieved because of: (1) increased technological complexity of DBS devices, (2) time restraints, or lack of expertise, and (3) delayed therapeutic response of some symptoms. Biomarkers to accurately predict the most effective stimulation settings for each patient could streamline this process and improve DBS outcomes.ObjectiveTo investigate the use of evoked potentials (EPs) to predict clinical outcomes in PD patients with DBS.MethodsIn ten patients (12 hemispheres), a monopolar review was performed by systematically stimulating on each DBS contact and measuring the therapeutic window. Standard imaging data were collected. EEG-based EPs were then recorded in response to stimulation at 10 Hz for 50 s on each DBS-contact. Linear mixed models were used to assess how well both EPs and image-derived information predicted the clinical data.ResultsEvoked potential peaks at 3 ms (P3) and at 10 ms (P10) were observed in nine and eleven hemispheres, respectively. Clinical data were well predicted using either P3 or P10. A separate model showed that the image-derived information also predicted clinical data with similar accuracy. Combining both EPs and image-derived information in one model yielded the highest predictive value.ConclusionEvoked potentials can accurately predict clinical DBS responses. Combining EPs with imaging data further improves this prediction. Future refinement of this approach may streamline DBS programming, thereby improving therapeutic outcomes.Clinical trial registrationClinicalTrials.gov, identifier NCT04658641.

Background: Since the inception of DBS, cathodic pulses have been used. Objective: To investigate the effect of anodic and symmetric biphasic pulses on the therapeutic window (TW) in essential tremor (ET) patients. Methods: A randomized, doubled-blinded, cross-over design was used to test the effect of cathodic, anodic and symmetric biphasic pulses (cathode-first and anode-first) on the TW in an acute clinical setting. TW was defined as the difference between the minimal stimulation amplitude provoking side effects and minimal stimulation amplitude inducing tremor arrest. Results: 9 ET patients (10 hemispheres) were included. Anodic stimulation induced a significantly larger TW compared to cathodic stimulation (p = 0.008). Symmetric biphasic stimulation also widened the TW compared to cathodic stimulation for both cathode- (p = 0.047) and anode-first (p = 0.008) biphasic pulses. For both anodic and biphasic pulses, the effect on TW was mainly driven by the change in side effect threshold. The order of the phases in the biphasic pulse had a significant effect on the side effect threshold (p = 0.039), with biphasic-anode first having the highest value. All pulse shapes were safe in the acute setting. Conclusion: Anodic and symmetric biphasic pulses increase TW in ET patients.

Abstract Aim To evaluate the impact and the possible role of psychological resilience in the COVID‐19 pandemic outbreak on healthcare workers’ mental and physical well‐being in Belgium. Design This cross‐sectional, survey‐based study enrolled 1376 healthcare workers across Belgium from 17 April 2020 to 24 April 2020. Methods The study sample consisted of direct care workers (nurses and doctors), supporting staff and management staff members. The main outcomes are resilience, distress and somatization. Results Higher educational level was associated with lower symptoms of distress and somatization. Physicians exhibited the lowest risk of experiencing heightened levels of distress and somatization. Controlling for confounding factors, higher levels of resilience were associated with a 12% reduced chance of increased distress levels and 5% lower chance of increased somatization levels. Our results suggest the potentially buffering role of mental resilience on those working on the frontline during the COVID‐19 pandemic outbreak.

Abstract Starmerella bombicola is a non-conventional yeast mainly known for its capacity to produce high amounts of the glycolipids ‘sophorolipids’. Although its product has been used as biological detergent for a couple of decades, the genetics of S. bombicola are still largely unknown. Computational analysis of the yeast’s genome enabled us to identify 254 putative transporter genes that make up the entire transportome. For each of them, a potential substrate was predicted using homology analysis, subcellular localization prediction and RNA sequencing in different stages of growth. One transporter family is of exceptional importance to this yeast: the ATP Binding Cassette (ABC) transporter Superfamily, because it harbors the main driver behind the highly efficient sophorolipid export. Furthermore, members of this superfamily translocate a variety of compounds ranging from antibiotics to hydrophobic molecules. We conducted an analysis of this family by creating deletion mutants to understand their role in the export of hydrophobic compounds, antibiotics and sophorolipids. Doing this, we could experimentally confirm the transporters participating in the efflux of medium chain fatty alcohols, particularly decanol and undecanol, and identify a second sophorolipid transporter that is located outside the sophorolipid biosynthetic gene cluster.

Subthalamic deep brain stimulation (STN-DBS) is a well-established therapy to treat Parkinson's disease (PD). However, the STN-DBS sub-target remains debated. Recently, a white matter tract termed the hyperdirect pathway (HDP), directly connecting the motor cortex to STN, has gained interest as HDP stimulation is hypothesized to drive DBS therapeutic effects. Previously, we have investigated EEG-based evoked potentials (EPs) to better understand the neuroanatomical origins of the DBS clinical effect. We found a 3-ms peak (P3) relating to clinical benefit, and a 10-ms peak (P10) suggesting nigral side effects. Here, we aimed to investigate the neuroanatomical origins of DBS EPs using probabilistic mapping. EPs were recorded using EEG whilst low-frequency stimulation was delivered at all DBS-contacts individually. Next, EPs were mapped onto the patients' individual space and then transformed to MNI standard space. Using voxel-wise and fiber-wise probabilistic mapping, we determined hotspots/hottracts and coldspots/coldtracts for P3 and P10. Topography analysis was also performed to determine the spatial distribution of the DBS EPs. In all 13 patients (18 hemispheres), voxel- and fiber-wise probabilistic mapping resulted in a P3-hotspot/hottract centered on the posterodorsomedial STN border indicative of HDP stimulation, while the P10-hotspot/hottract covered large parts of the substantia nigra. This study investigated EP-based probabilistic mapping in PD patients during STN-DBS, revealing a P3-hotspot/hottract in line with HDP stimulation and P10-hotspot/hottract related to nigral stimulation. Results from this study provide key evidence for an electrophysiological measure of HDP and nigral stimulation. • Probabilistic mapping is proposed to investigate the origins of EEG-based EPs. • Probabilistic mapping revealed a P3-hotspot/tract indicative of HDP stimulation. • Probabilistic mapping revealed a P10-hotspot/tract indicative of nigral stimulation. • Topographic heat map analysis confirmed the probabilistic mapping analyses. [ABSTRACT FROM AUTHOR]

This study aims to investigate the optical properties of multiple neodymium-doped gadolinium compounds as a means to examine their eligibility as optical probes for fluorescence imaging. GdVO4, GdPO4, GdAlO3, Gd2SiO5 and Gd3Ga5O12 (GGG) samples were synthesized through solid-state reactions with varying neodymium doping levels to compare their optical properties in great detail. The optimal doping concentration was generally found to be approximately 2%. Furthermore, the luminescence lifetime, which is a valuable parameter for time-gated imaging, was determined to range from 276 down to 14 µs for the highest doping concentrations, resulting from energy transfer and migration assisted decay.

Abstract A 73-year-old man with a history of marginal zone lymphoma was admitted to the emergency room for diplopia and ipsilateral headache. The Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) demonstrated intense and symmetrical hypermetabolism of the cavernous sinuses, and hypermetabolic lesions diffusely in the lymph nodes and bones. The diagnosis of high-grade relapse of lymphomatous disease was made. In this context, the homogenous and symmetric lesion of the cavernous sinuses, without any other encephalic or meningeal lesions, raised the hypothesis of a paraneoplastic origin. A plausible paraneoplastic link between the neuro-ophthalmological lesion and the malignant disorder is IgG4-related disease, a condition that may be associated with lymphoma. As in our case, this diagnosis is often presumptive because histopathological confirmation is difficult to obtain.

Objective To identify strategies and interventions used to improve interprofessional collaboration and integration (IPCI) in primary care.Design Scoping reviewData sources Specific Medical Subject Headings terms were used, and a search strategy was developed for PubMed and afterwards adapted to Medline, Eric and Web of Science.Study selection In the first stage of the selection, two researchers screened the article abstracts to select eligible papers. When decisions conflicted, three other researchers joined the decision-making process. The same strategy was used with full-text screening. Articles were included if they: (1) were in English, (2) described an intervention to improve IPCI in primary care involving at least two different healthcare disciplines, (3) originated from a high-income country, (4) were peer-reviewed and (5) were published between 2001 and 2020.Data extraction and synthesis From each paper, eligible data were extracted, and the selected papers were analysed inductively. Studying the main focus of the papers, researchers searched for common patterns in answering the research question and exposing research gaps. The identified themes were discussed and adjusted until a consensus was reached among all authors.Results The literature search yielded a total of 1816 papers. After removing duplicates, screening titles and abstracts, and performing full-text readings, 34 papers were incorporated in this scoping review. The identified strategies and interventions were inductively categorised under five main themes: (1) Acceptance and team readiness towards collaboration, (2) acting as a team and not as an individual; (3) communication strategies and shared decision making, (4) coordination in primary care and (5) integration of caregivers and their skills and competences.Conclusions We identified a mix of strategies and interventions that can function as ‘building blocks’, for the development of a generic intervention to improve collaboration in different types of primary care settings and organisations.

Research on aquatic plant viruses is lagging behind that of their terrestrial counterparts. To address this knowledge gap, here we identified viruses associated with freshwater macrophytes, a taxonomically diverse group of aquatic phototrophs that are visible with the naked eye. We surveyed pooled macrophyte samples collected at four spring sites in Florida, USA through next generation sequencing of RNA extracted from purified viral particles. Sequencing efforts resulted in the detection of 156 freshwater macrophyte associated (FMA) viral contigs, 37 of which approximate complete genomes or segments. FMA viral contigs represent putative members from all five major phyla of the RNA viral kingdom Orthornavirae. Similar to viral types found in land plants, viral sequences identified in macrophytes were dominated by positive-sense RNA viruses. Over half of the FMA viral contigs were most similar to viruses reported from diverse hosts in aquatic environments, including phototrophs, invertebrates, and fungi. The detection of FMA viruses from orders dominated by plant viruses, namely Patatavirales and Tymovirales, indicate that members of these orders may thrive in aquatic hosts. PCR assays confirmed the presence of putative FMA plant viruses in asymptomatic vascular plants, indicating that viruses with persistent lifestyles are widespread in macrophytes. The detection of potato virus Y and oat blue dwarf virus in submerged macrophytes suggests that terrestrial plant viruses infect underwater plants and highlights a potential terrestrial-freshwater plant virus continuum. Defining the virome of unexplored macrophytes will improve our understanding of virus evolution in terrestrial and aquatic primary producers and reveal the potential ecological impacts of viral infection in macrophytes.

Introduction The increasing burden of mental distress reported by healthcare professionals is a matter of serious concern and there is a growing recognition of the role of the workplace in creating this problem. Magnet hospitals, a model shown to attract and retain staff in US research, creates positive work environments that aim to support the well-being of healthcare professionals.Methods and analysis Magnet4Europe is a cluster randomised controlled trial, with wait list controls, designed to evaluate the effects of organisational redesign, based on the Magnet model, on nurses’ and physicians’ well-being in general acute care hospitals, using a multicomponent implementation strategy. The study will be conducted in more than 60 general acute care hospitals in Belgium, England, Germany, Ireland, Norway and Sweden. The primary outcome is burnout among nurses and physicians, assessed in longitudinal surveys of nurses and physicians at participating hospitals. Additional data will be collected from them on perceived work environments, patient safety and patient quality of care and will be triangulated with data from medical records, including case mix-adjusted in-hospital mortality. The process of implementation will be evaluated using qualitative data from focus group and key informant interviews.Ethics and dissemination This study was approved by the Ethics Committee Research UZ/KU Leuven, Belgium; additionally, ethics approval is obtained in all other participating countries either through a central or decentral authority. Findings will be disseminated at conferences, through peer-reviewed manuscripts and via social media.Trial registration number ISRCTN10196901.

Pain is an individualized experience for the person suffering from chronic pain. Significant strides have been made in the last few decades in understanding various biological changes that coincide with chronic pain. This state-of-the-art overview looks at the current evidence related to the biology of chronic pain and the implications these findings have on the delivery of pain neuroscience education (PNE). The paper summarizes the various (epi)genetic, neural, endocrine, and immune factors discovered and explored in the scientific literature concerning chronic pain. Each of these biological factors has various implications for the content and delivery of PNE. We discuss the future directions these biological factors have for the clinical implementation of PNE by linking the importance of behavior change, optimizing the learning environment, and using an individualized multimodal treatment approach with PNE. In addition, future directions for research of PNE based on these biological factors are provided with importance placed on individualized patient-centered care and how PNE can be used with traditional modes of care and growing trends with other care methods. PNE was originally and continues to be rooted in understanding chronic pain biology and how that understanding can improve patient care and outcomes.

Globally, renal cancer (RC) is the 10th most common cancer among men and women. The new era of artificial intelligence (AI) and radiomics have allowed the development of AI-based computer-aided diagnostic/prediction (AI-based CAD/CAP) systems, which have shown promise for the diagnosis of RC (i.e., subtyping, grading, and staging) and prediction of clinical outcomes at an early stage. This will absolutely help reduce diagnosis time, enhance diagnostic abilities, reduce invasiveness, and provide guidance for appropriate management procedures to avoid the burden of unresponsive treatment plans. This survey mainly has three primary aims. The first aim is to highlight the most recent technical diagnostic studies developed in the last decade, with their findings and limitations, that have taken the advantages of AI and radiomic markers derived from either computed tomography (CT) or magnetic resonance (MR) images to develop AI-based CAD systems for accurate diagnosis of renal tumors at an early stage. The second aim is to highlight the few studies that have utilized AI and radiomic markers, with their findings and limitations, to predict patients’ clinical outcome/treatment response, including possible recurrence after treatment, overall survival, and progression-free survival in patients with renal tumors. The promising findings of the aforementioned studies motivated us to highlight the optimal AI-based radiomic makers that are correlated with the diagnosis of renal tumors and prediction/assessment of patients’ clinical outcomes. Finally, we conclude with a discussion and possible future avenues for improving diagnostic and treatment prediction performance.

Objectives Healthcare workers in the emergency department are exposed to a wide range of physical and psycho-social risks or hazards in the workplace. The aim of this study was to investigate the impact of exposure to, the occurrence and perceived risks of, and the worry about, occupational hazards among emergency and hospital physicians in the time of COVID. Material and Methods Based on the review of occupational hazards in emergency physicians, a questionnaire already used and validated in another study, conducted in 2016, was constructed. The questionnaire consisted of both socio-demographic questions and questions regarding the exposure to, the occurrence and perceived risks of, and the worry about, the following occupational hazards: infectious diseases, COVID-19, physical hazards, violence at work, and stressful situations at work that can cause burnout. A total of 497 questionnaires were distributed to Belgian emergency and hospital physicians in April 20–May 26, 2020. Results Overall, 319 responses (out of 497 questionnaires) were collected, of which 196 were eligible for statistical analysis. Of the respondents, 32% stated to be confronted with violence and 54% to suffer from health problems related to their work. The exposure to, and the occurrence and perceived risks of, occupational hazards and, more specifically, the exposure to COVID-19 (88%) and its occurrence (10%), and also the worry about these hazards, appear to be high in physicians working in the emergency department. The worry about each of these outcomes is predicted by the supposed exposure, occurrence, and perceived risks. Conclusions The exposure to, and the occurrence and perceived risks of, physical hazards, violence and burnout are generally high in physicians in the time of COVID-19. Emergency and hospital physicians in Belgium worry the most about the impact of violence, burnout and COVID-19. Int J Occup Med Environ Health. 2021;34(3):373–83

Abstract Background Cardiovascular diseases are the world’s leading cause of morbidity and mortality. An active lifestyle is one of the cornerstones in the primary prevention of cardiovascular disease. An initial step in guiding primary prevention programs is to refer to clinical guidelines. We aimed to systematically review clinical practice guidelines on primary prevention of cardiovascular disease and their recommendations regarding physical activity. Methods We systematically searched Trip Medical Database, PubMed and Guidelines International Network from January 2012 up to December 2020 using the following search strings: ‘cardiovascular disease’, ‘prevention’, combined with specific cardiovascular disease risk factors. The identified records were screened for relevance and content. We methodologically assessed the selected guidelines using the AGREE II tool. Recommendations were summarized using a consensus-developed extraction form. Results After screening, 27 clinical practice guidelines were included, all of which were developed in Western countries and showed consistent rigor of development. Guidelines were consistent about the benefit of regular, moderate-intensity, aerobic physical activity. However, recommendations on strategies to achieve and sustain behavior change varied. Multicomponent interventions, comprising education, counseling and self-management support, are recommended to be delivered by various providers in primary health care or community settings. Guidelines advise to embed patient-centered care and behavioral change techniques in prevention programs. Conclusions Current clinical practice guidelines recommend similar PA lifestyle advice and propose various delivery models to be considered in the design of such interventions. Guidelines identify a gap in evidence on the implementation of these recommendations into practice.

BackgroundDeep brain stimulation (DBS) is an effective neuromodulation therapy to treat people with medication-refractory Parkinson’s disease (PD). However, the neural networks affected by DBS are not yet fully understood. Recent studies show that stimulating on different DBS-contacts using a single current source results in distinct EEG-based evoked potentials (EPs), with a peak at 3 ms (P3) associated with dorsolateral subthalamic nucleus stimulation and a peak at 10 ms associated with substantia nigra stimulation. Multiple independent current control (MICC) technology allows the center of the electric field to be moved in between two adjacent DBS-contacts, offering a potential advantage in spatial precision.ObjectiveDetermine if MICC precision targeting results in distinct neurophysiological responses recorded via EEG.Materials and MethodsWe recorded cortical EPs in five hemispheres (four PD patients) using EEG whilst employing MICC to move the electric field from the most dorsal DBS-contact to the most ventral in 15 incremental steps.ResultsThe center of the electric field location had a significant effect on both the P3 and P10 amplitude in all hemispheres where a peak was detected (P3, detected in 4 of 5 hemispheres, p < 0.0001; P10, detected in 5 of 5 hemispheres, p < 0.0001). Post hoc analysis indicated furthermore that MICC technology can significantly refine the resolution of steering.ConclusionUsing MICC to incrementally move the center of the electric field to locations between adjacent DBS-contacts resulted in significantly different neurophysiological responses that may allow further precision of the programming of individual patients.