Proposal for a Maturity Continuum Model for Open Research Data

As a contribution to the general effort in research to generalize and improve the practices of Open Research Data (ORD), we developed a model conceptualizing the degrees of maturity of a research community in terms of ORD. This model may be used to assess the ORD capacity or maturity level of a specific research community, to strengthen the use of standards with respect to ORD within this community, and to increase its ORD maturity level. We present the background and our motivations for developing such an instrument as well as the reasoning leading to its design. We present its elements in detail and discuss possible applications.&nbsp

Clinical evaluation of IDAS II, a new electronic device enabling drug adherence monitoring

Objective: The goal of this study was to evaluate clinically the acceptability of the IDAS II (Intelligent Drug Administration System), a new electronic device that enables drug adherence monitoring. Methods: IDAS II was compared to another electronic monitor, the Medication Event Monitoring System (MEMS) in a randomised two-way cross-over study involving 24 hypertensive patients treated with irbesartan. Patients used each device for 2months. The main parameter of evaluation was the patients' opinion on both devices. Rates of adherence and blood pressure were also assessed. Results: Most patients considered both devices to be reliable reminders (IDAS II: 75%;MEMS: 84%, p = ns). Ten patients (42%) preferred the MEMS, while 11 (46%) preferred the IDAS II; three (12%) expressed no preference. Patients found the MEMS device easier to use than the IDAS device (p < 0.001) but appreciated the IDAS blister packs better than the MEMS bulk packaging (p < 0.01). Over the 4-month period, the median "taking adherence” was excellent (99.2%) and comparable with both devices. However, the regularity of drug intake timing was higher with the IDAS II (p < 0.01). Conclusion: IDAS II, a new electronic device enabling drug adherence monitoring without reconditioning of the drugs appears to be a well-accepted device. Overall, practicability and acceptability of the IDAS II and the MEMS device were similar. Thus, IDAS II could be a useful tool for the management of long-term therapie

Renal perfusion evaluation with contrast-enhanced ultrasonography

Background. Contrast-enhanced ultrasonography (CEUS) is a novel imaging technique that is safe and applicable on the bedside. Recent developments seem to enable CEUS to quantify organ perfusion. We performed an exploratory study to determine the ability of CEUS to detect changes in renal perfusion and to correlate them with effective renal plasma flow. Methods. CEUS with destruction-refilling sequences was studied in 10 healthy subjects, at baseline and during infusion of angiotensin II (AngII) at low (1 ng/kg/min) and high dose (3 ng/kg/min) and 1 h after oral captopril (50 mg). Perfusion index (PI) was obtained and compared with the effective renal plasma flow (ERPF) obtained by parallel para-aminohippurate (PAH) clearance. Results. Median PI decreased from 188.6 (baseline) to 100.4 with low-dose AngII (−47%; P 0.2). These changes parallelled those observed with ERPF, which changed from a median of 672.1 mL/min (baseline) to 572.3 (low-dose AngII, −15%, P < 0.05) and to 427.2 (high-dose AngII, −36%, P < 0.001) and finally 697.1 (captopril, +4%, P < 0.02). Conclusions. This study demonstrates that CEUS is able to detect changes in human renal cortical microcirculation as induced by AngII infusion and/or captopril administration. The changes in perfusion indices parallel those in ERPF as obtained by PAH clearanc

Na Duong (northern Vietnam) – an exceptional window into Eocene ecosystems from Southeast Asia

Today, the continental ecosystems of Southeast Asia represent a global biodiversity hotspot. From a deep-time perspective, however, very little is known about the formation of this hotspot. In particular, the evolutionary and biogeographic roots of numerous terrestrial biota are unknown, and ecosystemic information, especially for the Paleogene, is unavailable. The Na Duong Basin in northern Vietnam has yielded a remarkable diversity of Paleogene vertebrate, invertebrate, and plant fossils, and is thus one of the few localities in Southeast Asia allowing for multi-focused investigation of this period. We present stratigraphic, paleontologic, and paleoecologic results from the 220 m thick Na Duong section derived from magnetostratigraphy, biochronology, vertebrate, invertebrate, and plant taxonomy, and biomarker analysis. Only the upper 40 m of the section show the original magnetization, prohibiting any further magnetostratigraphic interpretation. The affinities of two newly described mammal species, Bakalovia orientalis nov. sp. (Anthracotheriidae) and Epiaceratherium naduongense nov. sp. (Rhinocerotidae), suggest an Eocene, late Bartonian to Priabonian age (39–35 Ma). High biodiversity is recorded for unionid mussels (five species), freshwater fishes (nine taxa, including Planktophaga minuta nov. gen. et sp.), turtles (five to six taxa), and crocodiles (three taxa), and long-term stability of Southeast Asian unionid and fish faunas is demonstrated. Fossil leaves, wood and resin document azonal and zonal vegetation; dipterocarp trees were identified from resin exudate spectroscopy. In-situ tree-stump horizons allow for calculation of tree density (600 specimens/ha) and maximum canopy height (35m); both values resemble those of recent Southeast Asian peat swamp forests. Environment changed abruptly from a swamp forest to a tropical to warm sub-tropical lake of fluctuating water depth. The strong biogeographic link between the Eocene mammal faunas from Na Duong and Europe highlights the importance of Southeast Asia as a source region for trans-continental mammal dispersal along the northern Tethys margin.Heutige kontinentale Ökosysteme Südost Asiens sind ein Hotspot der globalen Biodiversität, über dessen geohistorische Entstehung jedoch sehr wenig bekannt ist. So sind die evolutionären und biogeographischen Wurzeln der meisten terrestrischen Lebensformen unbekannt und Daten zu Ökosystemen, speziell aus dem Paläogen, fehlen. Das Becken von Na Duong im nördlichen Vietnam beherbergt bemerkenswert diverse Biota fossiler Pflanzen, Mollusken und Wirbeltiere und stellt für das Paläogen eine der wenigen Regionen Südost Asiens dar, welche einen multi-disziplinären Untersuchungsansatz erlauben. Auf der Grundlage von Paläomagnetik, Biochronologie, Wirbeltier-, Mollusken- und Pflanzen-Taxonomie, sowie der Analyse von Biomarkern präsentieren wir hier unsere stratigraphischen, paläontologischen und paläo-ökologischen Ergebnisse eines 220 m mächtigen Profils der Braunkohlengrube Na Duong. Nur die hangenden 40 m der Sektion zeigen die ursprüngliche Magnetisierung, wodurch eine magnetostratigraphische Interpretation verhindert wird. Die Verwandschaftsverhältnisse von zwei neu beschriebenen Säugetierarten, Bakalovia orientalis nov. sp. (Anthracotheriidae) und Epiaceratherium naduongense nov. sp. (Rhinocerotidae), verweisen auf ein eozänes Alter (oberes Bartonium bis Priabonium, 39-35 Ma). Starke biogeographische Bezüge beider Säugetiere aus Na Duong zu europäischen Arten unterstreichen die Bedeutung Südost Asiens als eine Quellregion paläogener transkontinentaler Säugetier Ausbreitungen entlang des nördlichen Randes der Tethys. Hohe Diversitäten werden für unionide Muscheln (fünf Arten), Süßwasserfische (9 Taxa, darunter Planktophaga minuta nov. gen. et sp.), Schildkröten (fünf bis sechs Taxa) und Krokodile (drei Taxa) belegt, wobei eine taxonomische Langzeit-Stabilität der Unioniden- und Fisch-Faunen Südost Asiens belegt wird. Fossile Blätter, Hölzer und Harze dokumentieren die azonale und zonale Vegetation, letztere repräsentiert durch spektroskopisch an Harzen belegte Zweiflügelfrucht-Gewächse (Dipterocarpaceae). In-situ Baumstubben-Horizonte erlauben die Berechnung der Baum-Dichte (600 per ha) und der maximalen Kronendach-Höhe (35 m), welches in guter Übereinstimmung zu heutigen südostasiatischen Sumpfwäldern steht. Die Umwelt veränderte sich abrupt von einem Sumpfwald zu einem tropisch bis warm-subtropischen See mit fluktuierender Wassertiefe

The differential impact of a 6-versus 12-month pharmacist-led interprofessional medication adherence program on medication adherence in patients with diabetic kidney disease: the randomized PANDIA-IRIS study

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention.Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases.Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons.Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated.Clinical Trial Registration:Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS

Biochronological and palaeobiogeographical significance of the earliest Miocene mammal fauna from Northern Vietnam

Current scientific knowledge of Tertiary fossils from south of the Ailao Shan-Red River shear zone is extremely poor, in sharp contrast with the situation nowadays, as the area of Laos and Vietnam is regarded as a global hotspot of biodiversity. In this context, the few localities that yielded fossil assemblages are of first importance for the understanding of Cenozoic palaeobiogeography and the tectonic and palaeogeographical evolution of the region. Hang Mon 1 (Son La Province, Northern Vietnam) was the first site that provided evidence of Tertiary mammals, but its age remained very controversial, interpretations ranging from Oligocene to Late Miocene. Herein, we re-investigate the mammal fauna of the locality based on newly collected material and previously published fossil mammals. A new outcrop, Hang Mon 2, provides evidence of the rhinoceroses Pleuroceros blanfordi and Bugtirhinus sp. Together with the earlier finds of uncommonly small-sized Protaceratherium, these fossils allow a correlation to the earliest Miocene (most probably ranging from ~23 to ~21 Ma; Aquitanian) based on faunal comparison with the Sulaiman Province of Pakistan. The revision of the mammals from Hang Mon 1 is in agreement with this stratigraphic proposal. In addition, the discoveries from Vietnam (the rhinocerotid assemblage and Hyotherium) further support the hypothesis of strong biogeographical and environmental affinities between Europe, the Indian Subcontinent and Southeast Asia (Vietnam) during the Aquitanian

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals

Background: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. Methods: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. Findings: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). Interpretation: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution

Inflammatory Monocytes and Neutrophils Are Licensed to Kill during Memory Responses In Vivo

Immunological memory is a hallmark of B and T lymphocytes that have undergone a previous encounter with a given antigen. It is assumed that memory cells mediate better protection of the host upon re-infection because of improved effector functions such as antibody production, cytotoxic activity and cytokine secretion. In contrast to cells of the adaptive immune system, innate immune cells are believed to exhibit a comparable functional effector response each time the same pathogen is encountered. Here, using mice infected by the intracellular bacterium Listeria monocytogenes, we show that during a recall bacterial infection, the chemokine CCL3 secreted by memory CD8+ T cells drives drastic modifications of the functional properties of several populations of phagocytes. We found that inflammatory ly6C+ monocytes and neutrophils largely mediated memory CD8+ T cell bacteriocidal activity by producing increased levels of reactive oxygen species (ROS), augmenting the pH of their phagosomes and inducing antimicrobial autophagy. These events allowed an extremely rapid control of bacterial growth in vivo and accounted for protective immunity. Therefore, our results provide evidence that cytotoxic memory CD8+ T cells can license distinct antimicrobial effector mechanisms of innate cells to efficiently clear pathogens

A muon-track reconstruction exploiting stochastic losses for large-scale Cherenkov detectors

IceCube is a cubic-kilometer Cherenkov telescope operating at the South Pole. The main goal of IceCube is the detection of astrophysical neutrinos and the identification of their sources. High-energy muon neutrinos are observed via the secondary muons produced in charge current interactions with nuclei in the ice. Currently, the best performing muon track directional reconstruction is based on a maximum likelihood method using the arrival time distribution of Cherenkov photons registered by the experiment\u27s photomultipliers. A known systematic shortcoming of the prevailing method is to assume a continuous energy loss along the muon track. However at energies >1 TeV the light yield from muons is dominated by stochastic showers. This paper discusses a generalized ansatz where the expected arrival time distribution is parametrized by a stochastic muon energy loss pattern. This more realistic parametrization of the loss profile leads to an improvement of the muon angular resolution of up to 20% for through-going tracks and up to a factor 2 for starting tracks over existing algorithms. Additionally, the procedure to estimate the directional reconstruction uncertainty has been improved to be more robust against numerical errors