Co-constructing knowledge with the International Panel for Ocean Sustainability

UIDB/04666/2020 UIDP/04666/2020The efficacy of global environmental assessments in informing and shaping ocean and coastal management is hampered by recognized gaps in global science endeavours. In order to bridge these gaps, and secure inclusive and equitable knowledge co-construction by ocean stakeholders, the International Panel for Ocean Sustainability (IPOS) is emerging. Here we present the outcomes of the “Bridging Shades of Blue Workshop” held in Spain 2023. A diverse group of Ocean knowledge holders, including policymakers, small-scale fishers, marine social scientists and ocean lawyers gathered to reflect on the key features, challenges, strategies, actors to be involved, as well as pathways to balance power for advancing an inclusive and equitable IPOS. As a result, six foundational dimensions of IPOS’s institutional identity were proposed as IPOS ID cards: 1) Diversifying Ocean Knowledge Systems, 2) Widening the Range of Methods for Ocean Knowledge Production, 3) Informing Decision-making, 4) Engaging at the Interfaces of Knowledge with Decision-making, 5) Communicating, Learning, and Sharing Knowledge, 6) Measuring Progress and Evaluating Success. We conclude by emphasizing IPOS’s potential role as a beacon for inclusive, equitable, and sustainable ocean governance.publishersversionpublishe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Moments and muscle activity after high tibial osteotomy and anterior cruciate ligament reconstruction

PURPOSES: To evaluate the effects of simultaneous high tibial osteotomy (HTO) and anterior cruciate ligament (ACL) reconstruction on 1) the external knee adduction moment, 2) the external knee flexion and extension moments, and 3) the quadriceps, hamstrings, and gastrocnemius muscle activity during walking. METHODS: Twenty-one patients with varus malalignment of the lower limb, medial compartment knee osteoarthritis, and concomitant anterior cruciate ligament (ACL) deficiency were tested before and 1 yr after undergoing simultaneous medial opening wedge high tibial osteotomy (HTO) and ACL reconstruction during a single operation. Three-dimensional kinetic and kinematic data were used to calculate external coronal and sagittal moments about the knee. EMG data from the quadriceps, hamstrings, and gastrocnemius were used to determine coactivation ratio and activation patterns. RESULTS: Neutral alignment and knee stability were achieved in all patients after surgery. The peak knee adduction moment decreased from 2.88 ± 0.57 to 1.71 ± 0.56%BW×-Ht (P &lt; 0.001). The early stance knee flexion moment decreased from 1.95 ± 1.89 to 0.88 ± 1.17%BW×-Ht (P &lt; 0.01). The late stance knee extension moment increased from 1.83 ± 1.53 to 2.76 ± 1.22%BW×-Ht (P &lt; 0.001). There were no significant differences in muscle coactivation or muscle activation patterns (P &gt; 0.05). CONCLUSIONS: Improving lower limb alignment and knee stability significantly alters the coronal and the sagittal moments about the knee during walking, without apparent changes in muscle activation patterns.</p

New Short-Lived Isotope 221^{221}U and the Mass Surface Near N = 126

Two short-lived isotopes 221U and 222U were produced as evaporation residues in the fusion reaction 50Ti+176Yb at the gas-filled recoil separator TASCA. An α decay with an energy of Eα=9.31(5)  MeV and half-life T1/2=4.7(7)  μs was attributed to 222U. The new isotope 221U was identified in α-decay chains starting with Eα=9.71(5)  MeV and T1/2=0.66(14)  μs leading to known daughters. Synthesis and detection of these unstable heavy nuclei and their descendants were achieved thanks to a fast data readout system. The evolution of the N=126 shell closure and its influence on the stability of uranium isotopes are discussed within the framework of α-decay reduced width

Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases

Objective: If a gold standard is lacking in a diagnostic test accuracy study, expert diagnosis is frequently used as reference standard. However, interobserver and intraobserver agreements are imperfect. The aim of this study was to quantify the reproducibility of a panel diagnosis for pediatric infectious diseases. Study Design and Setting: Pediatricians from six countries adjudicated a diagnosis (i.e., bacterial infection, viral infection, or indeterminate)for febrile children. Diagnosis was reached when the majority of panel members came to the same diagnosis, leaving others inconclusive. We evaluated intraobserver and intrapanel agreement with 6 weeks and 3 years’ time intervals. We calculated the proportion of inconclusive diagnosis for a three-, five-, and seven-expert panel. Results: For both time intervals (i.e., 6 weeks and 3 years), intrapanel agreement was higher (kappa 0.88, 95%CI: 0.81-0.94 and 0.80, 95%CI: NA)compared to intraobserver agreement (kappa 0.77, 95%CI: 0.71-0.83 and 0.65, 95%CI: 0.52-0.78). After expanding the three-expert panel to five or seven experts, the proportion of inconclusive diagnoses (11%)remained the same. Conclusion: A panel consisting of three experts provides more reproducible diagnoses than an individual expert in children with lower respiratory tract infection or fever without source. Increasing the size of a panel beyond three experts has no major advantage for diagnosis reproducibility

Effect of Urate-Elevating Inosine on Early Parkinson Disease Progression: The SURE-PD3 Randomized Clinical Trial

Importance: Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. Objective: To determine whether sustained urate-elevating treatment with the urate precursor inosine slows early PD progression. Design, Participants, and Setting: Randomized, double-blind, placebo-controlled, phase 3 trial of oral inosine treatment in early PD. A total of 587 individuals consented, and 298 with PD not yet requiring dopaminergic medication, striatal dopamine transporter deficiency, and serum urate below the population median concentration (\u3c5.8 mg/dL) were randomized between August 2016 and December 2017 at 58 US sites, and were followed up through June 2019. Interventions: Inosine, dosed by blinded titration to increase serum urate concentrations to 7.1-8.0 mg/dL (n = 149) or matching placebo (n = 149) for up to 2 years. Main Outcomes and Measures: The primary outcome was rate of change in the Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS; parts I-III) total score (range, 0-236; higher scores indicate greater disability; minimum clinically important difference of 6.3 points) prior to dopaminergic drug therapy initiation. Secondary outcomes included serum urate to measure target engagement, adverse events to measure safety, and 29 efficacy measures of disability, quality of life, cognition, mood, autonomic function, and striatal dopamine transporter binding as a biomarker of neuronal integrity. Results: Based on a prespecified interim futility analysis, the study closed early, with 273 (92%) of the randomized participants (49% women; mean age, 63 years) completing the study. Clinical progression rates were not significantly different between participants randomized to inosine (MDS-UPDRS score, 11.1 [95% CI, 9.7-12.6] points per year) and placebo (MDS-UPDRS score, 9.9 [95% CI, 8.4-11.3] points per year; difference, 1.26 [95% CI, -0.59 to 3.11] points per year; P = .18). Sustained elevation of serum urate by 2.03 mg/dL (from a baseline level of 4.6 mg/dL; 44% increase) occurred in the inosine group vs a 0.01-mg/dL change in serum urate in the placebo group (difference, 2.02 mg/dL [95% CI, 1.85-2.19 mg/dL]; P\u3c.001). There were no significant differences for secondary efficacy outcomes including dopamine transporter binding loss. Participants randomized to inosine, compared with placebo, experienced fewer serious adverse events (7.4 vs 13.1 per 100 patient-years) but more kidney stones (7.0 vs 1.4 stones per 100 patient-years). Conclusions and Relevance: Among patients recently diagnosed as having PD, treatment with inosine, compared with placebo, did not result in a significant difference in the rate of clinical disease progression. The findings do not support the use of inosine as a treatment for early PD

Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease

This study was undertaken to determine the prevalence and correlates of cognitive impairment (CI) and neuropsychiatric symptoms (NPS) in early, untreated patients with Parkinson's disease (PD). Background: Both CI and NPS are common in PD and impact disease course and quality of life. However, limited knowledge is available about cognitive abilities and NPS. Methods: Parkinson's Progression Markers Initiative (PPMI) is a multi-site study of early, untreated PD patients and healthy controls (HCs), the latter with normal cognition. At baseline, participants were assessed with a neuropsychological battery and for symptoms of depression, anxiety, impulse control disorders (ICDs), psychosis, and apathy. Results: Baseline data of 423 PD patients and 196 HCs yielded no between-group differences in demographic characteristics. Twenty-two percent of PD patients met the PD-recommended screening cutoff for CI on the Montral Cognitive Assessment (MoCA), but only 9% met detailed neuropsychological testing criteria for mild cognitive impairment (MCI)-level impairment. The PD patients were more depressed than HCs (P<0.001), with twice as many (14% vs. 7%) meeting criteria for clinically significant depressive symptoms. The PD patients also experienced more anxiety (P<0.001) and apathy (P<0.001) than HCs. Psychosis was uncommon in PD (3%), and no between-group difference was seen in ICD symptoms (P=0.51). Conclusions: Approximately 10% of PD patients in the early, untreated disease state met traditional criteria of CI, which is a lower frequency compared with previous studies. Multiple dopaminergic-dependent NPS are also more common in these patients compared with the general population, but others associated with dopamine replacement therapy are not or are rare. Future analyses of this cohort will examine biological predictors and the course of CI and NPS