Search

Objective: To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods: On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to October 26, 2022. Randomized clinical trials and matched cohort studies investigating COVID-19 convalescent plasma transfusion compared with standard of care treatment or placebo among hospitalized patients with confirmed COVID-19 were included. The electronic search yielded 3841 unique records, of which 744 were considered for full-text screening. The selection process was performed independently by a panel of 5 reviewers. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were extracted by 5 independent reviewers in duplicate and pooled using an inverse-variance random effects model. The prespecified end point was all-cause mortality during hospitalization. Results: Thirty-nine randomized clinical trials enrolling 21,529 participants and 70 matched cohort studies enrolling 50,160 participants were included in the systematic review. Separate meta-analyses reported that transfusion of COVID-19 convalescent plasma was associated with a decrease in mortality compared with the control cohort for both randomized clinical trials (odds ratio [OR], 0.87; 95% CI, 0.76-1.00) and matched cohort studies (OR, 0.76; 95% CI, 0.66-0.88). The meta-analysis of subgroups revealed 2 important findings. First, treatment with convalescent plasma containing high antibody levels was associated with a decrease in mortality compared with convalescent plasma containing low antibody levels (OR, 0.85; 95% CI, 0.73 to 0.99). Second, earlier treatment with COVID-19 convalescent plasma was associated with a decrease in mortality compared with the later treatment cohort (OR, 0.63; 95% CI, 0.48 to 0.82). Conclusion: During COVID-19 convalescent plasma use was associated with a 13% reduced risk of mortality, implying a mortality benefit for hospitalized patients with COVID-19, particularly those treated with convalescent plasma containing high antibody levels treated earlier in the disease course.

Critical scholars contend that ‘There is no AI without Big Tech’. This study delves into the substantial role played by major technology conglomerates, including Amazon, Microsoft, and Google (Alphabet), in the ‘industrialisation of artificial intelligence’. This concept encapsulates the shift of AI technologies from the research and development stage to practical, real-world applications across diverse industry sectors, resulting in new dependencies and associated investments. We employ the term ‘Big AI’ to encapsulate the structural convergence of AI and Big Tech, characterised by the profound interdependence of AI with the infrastructure, resources, and investments of these major technology companies. Using a ‘technographic’ approach, our study scrutinises the infrastructural support and investments of Big Tech in the AI sector, focussing on corporate partnerships, acquisitions, and financial investments. Additionally, we conduct a detailed examination of the complete spectrum of cloud platform products and services offered by Amazon, Microsoft, and Google. We demonstrate that AI is not merely an abstract idea but an actual technology stack encompassing infrastructure, models, applications, and an ecosystem of applications and companies relying on this stack. Significantly, these tech giants have seamlessly integrated all three components of the stack into their cloud offerings. Furthermore, they have developed industry-focussed solutions and marketplaces aimed at attracting third-party developers and businesses, fostering the growth of a broader AI ecosystem. This analysis underscores the intricate interdependence between AI and cloud infrastructure, emphasising the industry-specific aspects of cloud AI.

The impact of trauma on the development and educational performance of school children and the benefits of trauma-informed practices have become more evident to both scientists and educators. Creating an effective and sustainable trauma-informed approach in schools, however, proves to be a challenging, time-consuming and complex process. This scoping review examined facilitators and barriers in the implementation of school-wide trauma-informed approaches and school-based trauma-specific interventions by carrying out a thematic analysis and framework synthesis based on 57 sources. The NIRN implementation drivers framework was used to guide the discussion of the findings. Five main themes were established: professional development (competency driver), implementation planning (organizational driver), leadership support, engaging stakeholders (leadership driver) and buy-in. A synthesis of these five themes helps guide the implementation process of trauma-informed approaches in schools. Findings of this review stress the need for identification and concrete operationalization of key elements and activities of trauma-informed educational approaches. Related to this, more empirical research is needed on how and to what extent implementation factors affect implementation success and effectiveness of trauma-informed educational approaches, taking into account implementation fidelity.

BackgroundA cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified.MethodsMuscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis.ResultsMuscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents.ConclusionsThis first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.

Background: This study examines participant satisfaction and effectiveness of the online mindset intervention 'The Growth Factory' (TGF) for youth with intellectual disabilities using a randomised controlled trial design. Method: Youth with mild to borderline intellectual disabilities (N = 119; 12-23 years) were randomly assigned to TGF (n = 60) or control group (n = 59). Primary outcome measures were mindsets and perseverance. Secondary outcomes were empowerment, mental health problems, self-esteem, treatment motivation, therapeutic alliance and challenge seeking. Measurements were conducted at pre-test, post-test and at 3 and 6 months follow-up. Results: TGF had positive effects on perseverance, mental health problems, self-esteem and therapeutic alliance at post-test. TGF had follow-up effects on mental health problems (3 months), mindset of intelligence (3 and 6 months) and mindset of emotion and behaviour (6 months). Conclusions: TGF offers a promising add-on intervention complementing usual care programmes accelerating improvements in mindsets and mental health in youth with intellectual disabilities.

Cuff-based home blood pressure (BP) devices, which have been the standard for BP monitoring for decades, are limited by physical discomfort, convenience, and their ability to capture BP variability and patterns between intermittent readings. In recent years, cuffless BP devices, which do not require cuff inflation around a limb, have entered the market, offering the promise of continuous beat-to-beat measurement of BP. These devices take advantage of a variety of principles to determine BP, including (1) pulse arrival time, (2) pulse transit time, (3) pulse wave analysis, (4) volume clamping, and (5) applanation tonometry. Because BP is calculated indirectly, these devices require calibration with cuff-based devices at regular intervals. Unfortunately, the pace of regulation of these devices has failed to match the speed of innovation and direct availability to patient consumers. There is an urgent need to develop a consensus on standards by which cuffless BP devices can be tested for accuracy. In this narrative review, we describe the landscape of cuffless BP devices, summarize the current status of validation protocols, and provide recommendations for an ideal validation process for these devices.

Iron speciation is one of the most widely applied proxies used to reconstruct oxygen levels and redox conditions in past aqueous environments. The iron speciation proxy estimates proportions of different reactive iron species in fine-grained sedimentary rocks, which are mapped to redox conditions based on empirical calibrations from modern sediments. It is based on a standardized extraction technique of sequentially applying acetate, hydroxlamine-HCl, dithionite, and oxalate solutions to a powdered sample in order to dissolve iron phases and quantify the amount of iron carried by carbonates, “easily reducible” oxyhydroxides, ferric iron (oxyhydr)oxides, and magnetite, respectively. Although tested on pure minerals and mixtures, assessments of whether this sequential extraction process accurately dissolves the targeted minerals in natural sediments and sedimentary rocks are lacking. In our study, residues from each sequential extraction step were analyzed using rock magnetic and X-ray diffraction experiments to identify and quantify the iron-bearing minerals that were dissolved. The dithionite extraction robustly removes the targeted mineralogy as magnetic data show it to solubilize nearly all of the goethite. However, magnetic quantification of magnetite was orders of magnitude less than the iron measured in the oxalate extraction; X-ray diffraction data suggest that dissolution of iron-bearing clays, specifically berthierine/chamosite, could explain this disparity. Our data compilation shows higher values of iron from the oxalate extraction in Precambrian sedimentary rock samples, suggesting a significant temporal shift in iron cycling. Recognition of heterogeneity in chemical extraction efficiency and targeting is vital for holistic multiproxy interpretation of past oxygen levels and communication between disciplines.

Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization. Comparisons were made between the vitamin D3 at 5000 IU supplementation group and a non-supplemented control group. Costs of care between the groups differed but were not statistically significant. Vitamin D3 supplementation reduced healthcare utilization in four major categories: hospitalizations for any reason (rate difference: −0.19 per 1000 person-days, 95%-CI: −0.21 to −0.17 per 1000 person-days, p < 0.0001); ICU admissions for any reason (rate difference: −0.06 per 1000 person-days, 95%-CI: −0.08 to −0.04 per 1000 person-days, p < 0.0001); emergency room visits for any reason (rate difference: −0.26 per 1000 person-days, 95%-CI: −0.46 to −0.05 per 1000 person-days, p = 0.0131; and hospitalizations due to COVID-19 (rate difference: −8.47 × 10−3 per 1000 person-days, 95%-CI: −0.02 to −1.05 × 10−3 per 1000 person-days, p = 0.0253). Appropriately powered studies of longer duration are recommended for replication of these utilization findings and analysis of cost differences.

Abstract Introduction: Designing and conducting clinical trials is challenging for some institutions and researchers due to associated time and personnel requirements. We conducted recruitment, screening, informed consent, study product distribution, and data collection remotely. Our objective is to describe how to conduct a randomized clinical trial using remote and automated methods. Methods: A randomized clinical trial in healthcare workers is used as a model. A random group of workers were invited to participate in the study through email. Following an automated process, interested individuals scheduled consent/screening interviews. Enrollees received study product by mail and surveys via email. Adherence to study product and safety were monitored with survey data review and via real-time safety alerts to study staff. Results: A staff of 10 remotely screened 406 subjects and enrolled 299 over a 3-month period. Adherence to study product was 87%, and survey data completeness was 98.5% over 9 months. Participants and study staff scored the System Usability Scale 93.8% and 90%, respectively. The automated and remote methods allowed the study maintenance period to be managed by a small study team of two members, while safety monitoring was conducted by three to four team members. Conception of the trial to study completion was 21 months. Conclusions: The remote and automated methods produced efficient subject recruitment with excellent study product adherence and data completeness. These methods can improve efficiency without sacrificing safety or quality. We share our XML file for researchers to use as a template for learning purposes or designing their own clinical trials.

Methane (CH4) is a key greenhouse gas. Coastal areas account for a major proportion of marine CH4 emissions. Eutrophication and associated bottom water hypoxia enhance CH4 production in coastal sediments. Here, we assess the fate of CH4 produced in sediments at a site in a seasonally anoxic eutrophic coastal marine basin (Scharendijke, Lake Grevelingen, the Netherlands) in spring (March) and late summer (September) in 2020. Removal of CH4 in the sediment through anaerobic oxidation with sulfate (SO42-) is known to be incomplete in this system, as confirmed here by only slightly higher values of δ13C-CH4 and δD-CH4 in the porewater in the shallow sulfate-methane-transition zone (~5-15 cm sediment depth) when compared to deeper sediment layers. In March 2020, when the water column was fully oxygenated, CH4 that escaped from the sediment was at least partially removed in the bottom water through aerobic oxidation. In September 2020, when the water column was anoxic below ~35 m water depth, CH4 accumulated to high concentrations (up to 73 µmol L-1) in the waters below the oxycline. The sharp counter gradient in oxygen and CH4 concentrations at ~35 m depth and increase in δ13C-CH4 and δD-CH4 above the oxycline indicate mostly aerobic water column removal of CH4. Water column profiles of particulate and dissolved Fe and Mn suggest redox cycling of both metals at the oxycline, pointing towards a potential role of metal oxides in CH4 removal. Water column profiles of NH4+ and NO3- indicate removal of both solutes near the oxycline. Analyses of 16S rRNA gene sequences retrieved from the water column reveal the presence of aerobic CH4 oxidizing bacteria (Methylomonadaceae) and anaerobic methanotrophic archaea (Methanoperedenaceae), with the latter potentially capable of NO3- and/or metal-oxide dependent CH4 oxidation, near the oxycline. Overall, our results indicate sediment and water column removal of CH4 through a combination of aerobic and anaerobic pathways, which vary seasonally. Some of the CH4 appears to escape from the surface waters to the atmosphere, however. We conclude that eutrophication may make coastal waters a more important source of CH4 to the atmosphere than commonly assumed.

Abstract Convalescent plasma is used to treat COVID-19. There are theoretical concerns about the impact of pro-coagulant factors in convalescent plasma on the coagulation cascade particularly among patients with severe COVID-19. The aim of this study was to evaluate the coagulation profile of COVID-19 convalescent plasma. Clotting times and coagulation factor assays were compared between fresh frozen plasma, COVID-19 convalescent plasma, and pathogen-reduced COVID-19 convalescent plasma. Measurements included prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, D-dimer, von Willebrand factor activity, von Willebrand factor antigen, coagulation factors II, V, VII–XII, protein S activity, protein C antigen, and alpha-2 plasmin inhibitor. Clotting times and coagulation factor assays were not different between COVID-19 convalescent plasma and fresh frozen plasma, except for protein C antigen. When compared to fresh frozen plasma and regular convalescent plasma, pathogen reduction treatment increased activated partial thromboplastin time and thrombin time, while reducing fibrinogen, coagulation factor II, V, VIII, IX, X, XI, XII, protein S activity, and alpha-2 plasmin inhibitor. The coagulation profiles of human COVID-19 convalescent plasma and standard fresh frozen plasma are not different. Pathogen reduced COVID-19 convalescent plasma is associated with reduction of coagulation factors and a slight prolongation of coagulation times, as anticipated. A key limitation of the study is that the COVID-19 disease course of the convalesced donors was not characterized.

Regional differences in SARS-CoV-2 variants may affect treatment outcome. Here, the authors show that near-sourced convalescent plasma has higher efficacy, as defined by death within 30 days of transfusion, than plasma sourced more than 150 miles away.

Researchers, policymakers, and competition and regulation authorities worldwide recognize the utility of application programming interfaces (APIs) in powering the digital economy and driving datafication and platformization processes. However, it remains unclear how the APIs of leading social media relate to platform governance and how this relationship evolved. This article traces the evolution of Facebook’s APIs, which evolved from a relatively simple programming interface for data access into a complex layered and interconnected governance arrangement . The study draws on a large corpus of (archived) developer pages and API reference documentation to examine the history of Facebook’s API governance; that is, the governance of and by Facebook through its APIs. This historical analysis emphasizes the technical dimensions and dynamics of what, how, and whom powerful platforms seek to govern, thus highlighting the technicity of platform governance and how it evolved. Because APIs facilitate and govern the material conditions of app development and the social and economic processes they sustain, powerful platforms influence the evolution of their larger ecosystems. As such, the technicity of Facebook’s API governance represents a major source of the platform’s “infrastructural power.”

Abstract Background A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified. Methods Muscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis. Results Muscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, β, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents. Conclusions This first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.

Continental shelf sediments are a key source of trace metals to the ocean. In this study, we investigate the impact of sedimentary processes on water column concentrations of iron (Fe), manganese (Mn), cobalt (Co), and nickel (Ni) at five stations on the Louisiana continental shelf and slope, Gulf of Mexico. The highest trace metal concentrations were observed close to the seafloor at the most nearshore shelf station (water depth of 16 m), with most of the metals present in particulate form. This enrichment in the bottom water is likely the combined effect of input of trace metals in suspended matter from the Mississippi/Atchafalaya Rivers and, for Mn, Co, and Ni, benthic release from the shelf sediments. While particulate matter was the dominant carrier of Fe and Mn in bottom waters in the shelf and slope regions, Co and Ni were nearly exclusively present in dissolved form. Hence, lateral transport of Co and Ni in shelf waters is decoupled from that of Fe and Mn. Concentrations of particulate and dissolved trace metals in the water column generally decreased from the shelf to the slope, while those in the sediment increased. This suggests an increased retention of metals deposited on the sediment with distance from the coast, linked to the decrease in organic matter input and associated reductive sediment processes. The offshore decline in sediment trace metal mobilization is likely typical for river-dominated continental margins where most organic matter is deposited close to the coast.

Coastal systems can act as filters for anthropogenic nutrient input into marine environments. Here, we assess the processes controlling the removal of phosphorus (P) and nitrogen (N) for four sites in the eutrophic Stockholm archipelago. Bottom water concentrations of oxygen (O2) and P are inversely correlated. This is attributed to the seasonal release of P from iron-oxide-bound (Fe-oxide-bound) P in surface sediments and from degrading organic matter. The abundant presence of sulfide in the pore water and its high upward flux towards the sediment surface (∼4 to 8 mmol m−2 d−1), linked to prior deposition of organic-rich sediments in a low-O2 setting (“legacy of hypoxia”), hinder the formation of a larger Fe-oxide-bound P pool in winter. This is most pronounced at sites where water column mixing is naturally relatively low and where low bottom water O2 concentrations prevail in summer. Burial rates of P are high at all sites (0.03–0.3 mol m−2 yr−1), a combined result of high sedimentation rates (0.5 to 3.5 cm yr−1) and high sedimentary P at depth (∼30 to 50 µmol g−1). Sedimentary P is dominated by Fe-bound P and organic P at the sediment surface and by organic P, authigenic Ca-P and detrital P at depth. Apart from one site in the inner archipelago, where a vivianite-type Fe(II)-P mineral is likely present at depth, there is little evidence for sink switching of organic or Fe-oxide-bound P to authigenic P minerals. Denitrification is the major benthic nitrate-reducing process at all sites (0.09 to 1.7 mmol m−2 d−1) with rates decreasing seaward from the inner to outer archipelago. Our results explain how sediments in this eutrophic coastal system can remove P through burial at a relatively high rate, regardless of whether the bottom waters are oxic or (frequently) hypoxic. Our results suggest that benthic N processes undergo annual cycles of removal and recycling in response to hypoxic conditions. Further nutrient load reductions are expected to contribute to the recovery of the eutrophic Stockholm archipelago from hypoxia. Based on the dominant pathways of P and N removal identified in this study, it is expected that the sediments will continue to remove part of the P and N loads.

BackgroundThe United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma.Methods and findingsMayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (ConclusionsThese results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease.Trial registrationClinicalTrials.gov NCT#: NCT04338360.

Vitamin D supplementation has been shown to reduce the incidence of acute respiratory infections in populations at risk. The COVID-19 pandemic has highlighted the importance of preventing viral infections in healthcare workers. The aim of this study was to assess the hypothesis that vitamin D3 supplementation at 5000 IU daily reduces influenza-like illness (ILI), including COVID-19, in healthcare workers. We conducted a prospective, controlled trial at a tertiary university hospital. A random group of healthcare workers was invited to receive 5000 IU daily vitamin D3 supplementation for nine months, while other random healthcare system workers served as controls. All healthcare workers were required to self-monitor and report to employee health for COVID-19 testing when experiencing symptoms of ILI. COVID-19 test results were retrieved. Incidence rates were compared between the vitamin D and control groups. Workers in the intervention group were included in the analysis if they completed at least 2 months of supplementation to ensure adequate vitamin D levels. The primary analysis compared the incidence rate of all ILI, while secondary analyses examined incidence rates of COVID-19 ILI and non-COVID-19 ILI. Between October 2020 and November 2021, 255 healthcare workers (age 47 ± 12 years, 199 women) completed at least two months of vitamin D3 supplementation. The control group consisted of 2827 workers. Vitamin D3 5000 IU supplementation was associated with a lower risk of ILI (incidence rate difference: −1.7 × 10−4/person-day, 95%-CI: −3.0 × 10−4 to −3.3 × 10−5/person-day, p = 0.015) and a lower incidence rate for non-COVID-19 ILI (incidence rate difference: −1.3 × 10−4/person-day, 95%-CI −2.5 × 10−4 to −7.1 × 10−6/person-day, p = 0.038). COVID-19 ILI incidence was not statistically different (incidence rate difference: −4.2 × 10−5/person-day, 95%-CI: −10.0 × 10−5 to 1.5 × 10−5/person-day, p = 0.152). Daily supplementation with 5000 IU vitamin D3 reduces influenza-like illness in healthcare workers.

Convalescent plasma has been used worldwide to treat patients hospitalized with coronavirus disease 2019 (COVID-19) and prevent disease progression. Despite global usage, uncertainty remains regarding plasma efficacy, as randomized controlled trials (RCTs) have provided divergent evidence regarding the survival benefit of convalescent plasma. Here, we argue that during a global health emergency, the mosaic of evidence originating from multiple levels of the epistemic hierarchy should inform contemporary policy and healthcare decisions. Indeed, worldwide matched-control studies have generally found convalescent plasma to improve COVID-19 patient survival, and RCTs have demonstrated a survival benefit when transfused early in the disease course but limited or no benefit later in the disease course when patients required greater supportive therapies. RCTs have also revealed that convalescent plasma transfusion contributes to improved symptomatology and viral clearance. To further investigate the effect of convalescent plasma on patient mortality, we performed a meta-analytical approach to pool daily survival data from all controlled studies that reported Kaplan–Meier survival plots. Qualitative inspection of all available Kaplan–Meier survival data and an aggregate Kaplan–Meier survival plot revealed a directionally consistent pattern among studies arising from multiple levels of the epistemic hierarchy, whereby convalescent plasma transfusion was generally associated with greater patient survival. Given that convalescent plasma has a similar safety profile as standard plasma, convalescent plasma should be implemented within weeks of the onset of future infectious disease outbreaks.

Social media platforms’ digital advertising revenues depend considerably on partnerships. Business partnerships are endemic and essential to the business of platforms, yet their role remains relatively underexplored in the literature on platformisation and platform power. This article considers the significance of partnerships in the social media ecosystem to better understand how industry platforms, and the infrastructure they build, mediate and shape platform power and governance. We argue that partners contribute to ‘platformisation’ through their collective development of business-to-business platform infrastructures. Specifically, we examine how partners have integrated social media platforms with what we call the audience economy – an exceptionally complex global and interconnected marketplace of intermediaries involved in the creation, commodification, analysis, and circulation of data audiences for purposes including but not limited to digital advertising and marketing. We determined which relationships are involved, which are exclusive or shared, and identified key ecosystem partners. Further, we found that partners build and integrate extensive infrastructures for data-sourcing and media distribution, surfacing infrastructural and strategic sources and locations, or ‘nodes’, of power in this ecosystem. The empirical findings thus highlight the significance of partnerships and partner integrations and draw attention to the powerful industry players and intermediaries that remain largely invisible.

Abstract Background Adolescents with intellectual disabilities have an increased risk of developing academic, social, and psychological problems compared with non-disabled peers. These difficulties might have an impact on the implicit theories—or so called mindset—of these youth. Youth with a fixed mindset believe that their attributes are static while youth with a growth mindset believe their attributes are malleable. A growth mindset can positively affect the academic and psychosocial development of youth and can be stimulated by so called ‘mindset interventions’. Nevertheless, mindset interventions specifically adapted to adolescents with intellectual disabilities are non-existing. Methods/design The aim of the present study is to conduct a randomized controlled trial (RCT) to test the effectiveness of the online mindset intervention “The Growth Factory” aimed to teach adolescents with intellectual disabilities a growth mindset and thereby positively impacting their psychosocial development. The RCT targets adolescents (12–23 years) with mild to borderline intellectual disabilities (IQ 50–85) admitted to residential care or special education. Participants will be individually randomized to the intervention (n = 60) or control (n = 60) group. The intervention group will individually participate in the six sessions of “The Growth Factory” and the control group will receive care as usual. Primary outcome will be mindset. Empowerment, behavior problems, self-esteem, treatment motivation, therapeutic alliance, challenge seeking, and the impact of social exclusion will be included as secondary outcome measures. Moreover, moderation (i.e., intervention satisfaction, IQ, age, baseline mindset, gender) and mediation effects will be investigated. Self-reported and mentor assessments will be administrated at baseline, post-test and at three (except mentor assessment) and six months follow-up. Discussion This paper describes the design of a RCT examining the effectiveness of the online mindset intervention “The Growth Factory” aimed to empower adolescents with intellectual disabilities. If effective, “The Growth Factory” makes an important contribution to the treatment and psychosocial development of adolescents with intellectual disabilities in residential care and special education. Due to the online approach, implementation will be efficient and cost-effective and therefore the intervention “The Growth Factory” can be used on large scale. Trial registration Dutch Trial Register NTR5460. Registered 2 October 2015.

Estuarine sediments are key sites for removal of phosphorus (P) from rivers and the open sea. Vivianite, an Fe(II)-P mineral, can act as a major sink for P in Fe-rich coastal sediments. In this study, we investigate the burial of P in the Öre Estuary in the northern Baltic Sea. We find much higher rates of P burial at our five study sites (up to ∼ 0.145 mol m−2 yr−1) when compared to more southern coastal areas in the Baltic Sea with similar rates of sedimentation. Detailed study of the sediment P forms at our site with the highest rate of sedimentation reveals a major role for P associated with Fe and the presence of vivianite crystals below the sulfate methane transition zone. By applying a reactive transport model to sediment and porewater profiles for this site, we show that vivianite may account for up to ∼ 40 % of total P burial. With the model, we demonstrate that vivianite formation is promoted in sediments with a low bottom water salinity and high rates of sedimentation and Fe oxide input. While high rates of organic matter input are also required, there is an optimum rate above which vivianite formation declines. Distinct enrichments in sediment Fe and sulfur at depth in the sediment are attributed to short periods of enhanced input of riverine Fe and organic matter. These periods of enhanced input are linked to variations in rainfall on land and follow dry periods. Most of the P associated with the Fe in the sediment is likely imported from the adjacent eutrophic Baltic Proper. Our work demonstrates that variations in land-to-sea transfer of Fe may act as a key control on burial of P in coastal sediments. Ongoing climate change is expected to lead to a decrease in bottom water salinity and contribute to continued high inputs of Fe oxides from land, further promoting P burial as vivianite in the coastal zone of the northern Baltic Sea. This may enhance the role of this oligotrophic area as a sink for P imported from eutrophic parts of the Baltic Sea.

BackgroundSeveral pain management guidelines recommend regular urine drug testing (UDT) in patients who are being treated with chronic opioid analgesic therapy (COAT) to monitor compliance and improve safety. Guidelines also recommend more frequent testing in patients who are at high risk of adverse events related to COAT; however, there is no consensus on how to identify high-risk patients or on the testing frequency that should be used. Using previously described clinical risk factors for UDT results that are inconsistent with the prescribed COAT, we developed a web-based tool to adjust drug testing frequency in patients treated with COAT. ObjectiveThe objective of this study was to evaluate a risk stratification tool, the UDT Randomizer, to adjust UDT frequency in patients treated with COAT. MethodsPatients were stratified using an algorithm based on readily available clinical risk factors into categories of presumed low, moderate, high, and high+ risk of presenting with UDT results inconsistent with the prescribed COAT. The algorithm was integrated in a website to facilitate adoption across practice sites. To test the performance of this algorithm, we performed a retrospective analysis of patients treated with COAT between June 2016 and June 2017. The primary outcome was compliance with the prescribed COAT as defined by UDT results consistent with the prescribed COAT. Results979 drug tests (867 UDT, 88.6%; 112 oral fluid testing, 11.4%) were performed in 320 patients. An inconsistent drug test result was registered in 76/979 tests (7.8%). The incidences of inconsistent test results across the risk tool categories were 7/160 (4.4%) in the low risk category, 32/349 (9.2%) in the moderate risk category, 28/338 (8.3%) in the high risk category, and 9/132 (6.8%) in the high+ risk category. Generalized estimating equation analysis demonstrated that the moderate risk (odds ratio (OR) 2.1, 95% CI 0.9-5.0; P=.10), high risk (OR 2.0, 95% CI 0.8-5.0; P=.14), and high risk+ (OR 2.0, 95% CI 0.7-5.6; P=.20) categories were associated with a nonsignificantly increased risk of inconsistency vs the low risk category. ConclusionsThe developed tool stratified patients during individual visits into risk categories of presenting with drug testing results inconsistent with the prescribed COAT; the higher risk categories showed nonsignificantly higher risk compared to the low risk category. Further development of the tool with additional risk factors in a larger cohort may further clarify and enhance its performance.

BackgroundNew consumer health devices are being developed to easily monitor multiple physiological parameters on a regular basis. Many of these vital sign measurement devices have yet to be formally studied in a clinical setting but have already spread widely throughout the consumer market. ObjectiveThe aim of this study was to investigate the accuracy and precision of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen saturation (SpO2) measurements of 2 novel all-in-one monitoring devices, the BodiMetrics Performance Monitor and the Everlast smartwatch. MethodsWe enrolled 127 patients (>18 years) from the Thomas Jefferson University Hospital Preadmission Testing Center. SBP and HR were measured by both investigational devices. In addition, the Everlast watch was utilized to measure DBP, and the BodiMetrics Performance Monitor was utilized to measure SpO2. After 5 min of quiet sitting, four hospital-grade standard and three investigational vital sign measurements were taken, with 60 seconds in between each measurement. The reference vital sign measurements were calculated by determining the average of the two standard measurements that bounded each investigational measurement. Using this method, we determined three comparison pairs for each investigational device in each subject. After excluding data from 42 individuals because of excessive variation in sequential standard measurements per prespecified dropping rules, data from 85 subjects were used for final analysis. ResultsOf 85 participants, 36 (42%) were women, and the mean age was 53 (SD 21) years. The accuracy guidelines were only met for the HR measurements in both devices. SBP measurements deviated 16.9 (SD 13.5) mm Hg and 5.3 (SD 4.7) mm Hg from the reference values for the Everlast and BodiMetrics devices, respectively. The mean absolute difference in DBP measurements for the Everlast smartwatch was 8.3 (SD 6.1) mm Hg. The mean absolute difference between BodiMetrics and reference SpO2 measurements was 3.02%. ConclusionsBoth devices we investigated met accuracy guidelines for HR measurements, but they failed to meet the predefined accuracy guidelines for other vital sign measurements. Continued sale of consumer physiological monitors without prior validation and approval procedures is a public health concern.

We assess the disputed phase relations between forcing and climatic response in the early Pleistocene with a spliced Gelasian (∼ 2.6–1.8 Ma) multi-proxy record from the southern North Sea basin. The cored sections couple climate evolution on both land and sea during the intensification of Northern Hemisphere glaciation (NHG) in NW Europe, providing the first well-constrained stratigraphic sequence of the classic terrestrial Praetiglian stage. Terrestrial signals were derived from the Eridanos paleoriver, a major fluvial system that contributed a large amount of freshwater to the northeast Atlantic. Due to its latitudinal position, the Eridanos catchment was likely affected by early Pleistocene NHG, leading to intermittent shutdown and reactivation of river flow and sediment transport. Here we apply organic geochemistry, palynology, carbonate isotope geochemistry, and seismostratigraphy to document both vegetation changes in the Eridanos catchment and regional surface water conditions and relate them to early Pleistocene glacial–interglacial cycles and relative sea level changes. Paleomagnetic and palynological data provide a solid integrated timeframe that ties the obliquity cycles, expressed in the borehole geophysical logs, to Marine Isotope Stages (MIS) 103 to 92, independently confirmed by a local benthic oxygen isotope record. Marine and terrestrial palynological and organic geochemical records provide high-resolution reconstructions of relative terrestrial and sea surface temperature (TT and SST), vegetation, relative sea level, and coastal influence.During the prominent cold stages MIS 98 and 96, as well as 94, the record indicates increased non-arboreal vegetation, low SST and TT, and low relative sea level. During the warm stages MIS 99, 97, and 95 we infer increased stratification of the water column together with a higher percentage of arboreal vegetation, high SST, and relative sea level maxima. The early Pleistocene distinct warm–cold alterations are synchronous between land and sea, but lead the relative sea level change by 3000–8000 years. The record provides evidence for a dominantly Northern Hemisphere-driven cooling that leads the glacial buildup and varies on the obliquity timescale. Southward migration of Arctic surface water masses during glacials, indicated by cool-water dinoflagellate cyst assemblages, is furthermore relevant for the discussion on the relation between the intensity of the Atlantic meridional overturning circulation and ice sheet growth.

Prior to availability of an effective vaccine, an estimated 4 million cases of varicella occurred annually in the United States, resulting in 10,000 hospitalizations and over 100 deaths. With the increased usage of a two-dose varicella vaccine (as recommended by the ACIP), approval of other VZV-containing products and the adoption of varicella vaccination in additional countries, the demand for VZV-containing vaccines has increased. This study (NCT02062502) evaluated the safety, tolerability, and immunogenicity of VARIVAX™ (VAR, varicella vaccine live) manufactured using a new seed manufacturing process (VARNSP) compared to the currently licensed VAR. Healthy children 12–23 months were randomized (1:1) into Group 1 (2 doses of VARNSP given concomitantly with M-M-R™ II, ∼3 months apart) versus Group 2 (2 doses of VAR given concomitantly with M-M-R™ II, ∼3 months apart). Serum samples collected prior to vaccination on Day 1 and 6 weeks Postdose 1 were tested for antibody to VZV using a glycoprotein enzyme-linked immunosorbent assay (gpELISA). Safety was assessed Days 1 to 42 following each vaccination. Six weeks Postdose 1, the response rate (percent of subjects with VZV antibody titer ≥5 gpELISA units/mL) of VARNSP was non-inferior compared to VAR. Vaccine-related adverse events (AEs) were comparable with the exception of measles-like rash, where a greater number of rashes were observed with VAR than VARNSP. The 2 vaccination groups were comparable with incidence rates of AEs, injection-site AEs, vaccine-related AEs, systemic AEs, and serious AEs. This new process is an important innovation for the extreme demand of sustaining sufficient supplies of varicella vaccine to protect our communities against diseases caused by VZV.

Sediment records recovered from the Baltic Sea during Integrated Ocean Drilling Program Expedition 347 provide a unique opportunity to study paleoenvironmental and climate change in central and northern Europe. Such studies contribute to a better understanding of how environmental parameters change in continental shelf seas and enclosed basins. Here we present a multi-proxy-based reconstruction of paleotemperature (both marine and terrestrial), paleosalinity, and paleoecosystem changes from the Little Belt (Site M0059) over the past ∼ 8000 years and evaluate the applicability of inorganic- and organic-based proxies in this particular setting. All salinity proxies (diatoms, aquatic palynomorphs, ostracods, diol index) show that lacustrine conditions occurred in the Little Belt until ∼ 7400 cal yr BP. A connection to the Kattegat at this time can thus be excluded, but a direct connection to the Baltic Proper may have existed. The transition to the brackish–marine conditions of the Littorina Sea stage (more saline and warmer) occurred within ∼ 200 years when the connection to the Kattegat became established after ∼ 7400 cal yr BP. The different salinity proxies used here generally show similar trends in relative changes in salinity, but often do not allow quantitative estimates of salinity. The reconstruction of water temperatures is associated with particularly large uncertainties and variations in absolute values by up to 8 °C for bottom waters and up to 16 °C for surface waters. Concerning the reconstruction of temperature using foraminiferal Mg  /  Ca ratios, contamination by authigenic coatings in the deeper intervals may have led to an overestimation of temperatures. Differences in results based on the lipid paleothermometers (long chain diol index and TEXL86) can partly be explained by the application of modern-day proxy calibrations to intervals that experienced significant changes in depositional settings: in the case of our study, the change from freshwater to marine conditions. Our study shows that particular caution has to be taken when applying and interpreting proxies in coastal environments and marginal seas, where water mass conditions can experience more rapid and larger changes than in open ocean settings. Approaches using a multitude of independent proxies may thus allow a more robust paleoenvironmental assessment.

Introduction: Research on communication in maternity care gives little attention to opinions of parents and focuses on the barriers rather than the facilitators of communication (1). To understand how parents and professionals in Dutch maternity care establish and preserve constructive collaboration we examined the way things are actually done on the unit, learning from ‘good practice’, and actively including parents and professionals as co-researchers. Methods: We used video-reflexive ethnographic methods (2) to study the collaboration of parents and professionals in 9 midwifery practices and 2 obstetric wards in the Netherlands (2013-2015). By filming in situ everyday practices, editing footage, and using clips for co-analysis in reflexivity-sessions we helped professionals and parents to see, relive, and experience things they forgot, took for granted, or ceased to see. Our co-researchers were 26 parents, 24 primary care midwives, 3 secondary care midwives, 11 obstetric nurses, 17 obstetricians, and 7 medical assistants who participated in at least one of 24 reflexivity-meetings. We used inductive content analysis for analyzing transcripts of reflexivity-meetings and fieldwork notes. Findings: We identified the informal ways of talking and acting that facilitate connectedness. We found that small talk, humor, being familiar with each other, using different senses and taking different positions, e.g., standing, sitting, varying distances, are highly effective for bonding and reducing the stress of caregiving and care receiving. Our colleagues were aware of the pitfalls in communication and collaboration as well, and expressed the need to be sincere and to be sensitive to context, to the values and feelings of others, and to the timing of care. Discussion: These balancing and sensing competencies turn maternity care into a ‘paradoxical care’, expressed in oxymorons: acts of “regulated spontaneity” and “informal formalities” that must be used in the right dose at the right time and place. Paradoxical care is about concurrent acts based on non-stop probing and fine-tuning, requiring high levels of social sensitivity and self-reflection. Conclusions: Our study of the actual practice of effective communicating and collaborating with and between all parties in maternity care revealed the use of different informal strategies to establish not just ‘doing’ things together, but ‘being’ together. These strategies require social and self-reflective competencies. Lessons learned: Different professionals hesitated about the value of video-reflexivity for practice improvement, because they are used to learning from what goes wrong. Use of the method, however, positively influenced their reflecting and collaborating work. Parents appreciated being taken seriously and seeing the dedication of professionals to improving communication and collaboration. Our research underlines the importance of ‘paradoxical care’ – ‘regulated spontaneity’ and ‘informal formalities’ – and the competencies required of professionals to use these to promote good collaboration. Limitations: Our research focus did not allow us to study explicit factors or barriers for communication and collaboration that also play a crucial role. Suggestions for future research: Video-reflexivity research on the interactions between informal strategies and contextual factors of maternity care, e.g., architecture and time, will deepen our understanding of the drivers of good collaboration in health care.

This article discusses methodological approaches to app studies, focusing on their embeddedness and situatedness within multiple infrastructural settings. Our approach involves close attention to the multivalent affordances of apps as software packages, particularly their capacity to enter into diverse groupings and relations depending on different infrastructural situations. The changing situations they evoke and participate in, accordingly, make apps visible and accountable in a variety of unique ways. Therefore, engaging with and even staging these situations allows for political-economic, social, and cultural dynamics associated with apps and their infrastructures to be investigated through a style of research we describe as multi-situated app studies. This article offers an overview of four different entry points of enquiry that are exemplary of this multi-situated approach, focusing on app stores, app interfaces, app packages, and app connections. We conclude with nine propositions that develop out of these studies as prompts for further research.

Blood pressure telemonitoring (BPT) is a telemedicine strategy that uses a patient's self-measured blood pressure (BP) and transmits this information to healthcare providers, typically over the internet. BPT has been shown to improve BP control compared to usual care without remote monitoring. Traditionally, a cuff-based monitor with data communication capabilities has been used for BPT; however, cuff-based measurements are inconvenient and cause discomfort, which has prevented the widespread use of cuff-based monitors for BPT. The development of new technologies which allow for remote BP monitoring without the use of a cuff may aid in more extensive adoption of BPT. This would enhance patient autonomy while providing physicians with a more complete picture of their patient's BP profile, potentially leading to improved BP control and better long-term clinical outcomes. This mini-review article aims to: (1) describe the fundamentals of current techniques in cuff-less BP measurement; (2) present examples of commercially available cuff-less technologies for BPT; (3) outline challenges with current methodologies; and (4) describe potential future directions in cuff-less BPT development.

Oceanic Anoxic Event 2 (OAE2), a ∼ 600 kyr episode close to the Cenomanian–Turonian boundary (ca. 94 Ma), is characterized by relatively widespread marine anoxia and ranks amongst the warmest intervals of the Phanerozoic. The early stages of OAE2 are, however, marked by an episode of widespread transient cooling and bottom water oxygenation: the Plenus Cold Event. This cold spell has been linked to a decline in atmospheric pCO2, resulting from enhanced global organic carbon burial. To investigate the response of phytoplankton to this marked and rapid climate shift we examined the biogeographical response of dinoflagellates to the Plenus Cold Event. Our study is based on a newly generated geochemical and palynological data set from a high-latitude Northern Hemisphere site, Pratts Landing (western Alberta, Canada). We combine these data with a semi-quantitative global compilation of the stratigraphic distribution of dinoflagellate cyst taxa. The data show that dinoflagellate cysts grouped in the Cyclonephelium compactum–membraniphorum morphological plexus migrated from high to mid-latitudes during the Plenus Cold Event, making it the sole widely found (micro)fossil to mark this cold spell. In addition to earlier reports from regional metazoan migrations during the Plenus Cold Event, our findings illustrate the effect of rapid climate change on the global biogeographical dispersion of phytoplankton.

Coccydynia can be difficult to resolve with conventional treatment options. Dorsal root ganglion (DRG) stimulation has recently emerged as a treatment for chronic pain, but its application has not been described in the context of coccydynia. We used DRG stimulation treatment in a patient suffering from intractable coccyx pain. At long-term follow-up, the patient experienced a decrease in pain intensity and improvement in function, without any complications. DRG stimulation may be a treatment modality for coccydynia refractory to other approaches.

Global warming, changes in the hydrological cycle and enhanced marine primary productivity all have been invoked as having contributed to the occurrence of widespread ocean anoxia during the Cenomanian–Turonian oceanic anoxic event (OAE2; ~94 Ma), but disentangling these factors on a regional scale has remained problematic. In an attempt to separate these forcing factors, we generated palynological and organic geochemical records using a core spanning the OAE2 from Wunstorf, Lower Saxony Basin (LSB; northern Germany), which exhibits cyclic black shale–marl alternations related to the orbital precession cycle. Despite the widely varying depositional conditions complicating the interpretation of the obtained records, TEX86H indicates that sea-surface temperature (SST) evolution in the LSB during OAE2 resembles that of previously studied sites throughout the proto-North Atlantic. Cooling during the so-called Plenus Cold Event interrupted black shale deposition during the early stages of OAE2. However, TEX86 does not vary significantly across black shale–marl alternations, suggesting that temperature variations did not force the formation of the cyclic black shale horizons. Relative (i.e., with respect to marine palynomorphs) and absolute abundances of pollen and spores are elevated during phases of black shale deposition, indicative of enhanced precipitation and run-off. High abundances of cysts from inferred heterotrophic and euryhaline dinoflagellates supports high run-off, which likely introduced additional nutrients to the epicontinental shelf resulting in elevated marine primary productivity. We conclude that orbitally forced enhanced precipitation and run-off, in tandem with elevated marine primary productivity, were critical in cyclic black shale formation on the northern European epicontinental shelf and potentially for other OAE2 sections in the proto-Atlantic and Western Interior Seaway at similar latitudes as well.