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Abstract Depression questionnaire cutoffs are calibrated for screening accuracy and not to assess prevalence, but the Geriatric Depression Scale (GDS-15) is often used to estimate diagnostic prevalence among older adults, most commonly with scores of ≥ 5. We conducted an individual participant data meta-analysis to compare depression prevalence based on GDS-15 ≥ 5 to Structured Clinical Interview for Diagnostic and Statistical Manual (SCID) diagnoses and assessed whether an alternative cutoff could be more accurate. We used generalized linear mixed models to estimate prevalence. Data from 14 studies (3602 participants, 434 SCID major depression) were included. Pooled GDS-15 ≥ 5 prevalence was 34.2% (95% confidence interval [CI] 27.5–41.6%), and pooled SCID prevalence was 14.8% (95% CI 10.0–21.5%; difference of 17.6%, 95% CI 11.6–23.6%). GDS-15 ≥ 8 provided the closest estimate to SCID with mean difference of − 0.3% (95% prediction interval − 17.0–16.5%). Prevalence estimate differences were not associated with study or participant characteristics. In sum, GDS-15 ≥ 5 substantially overestimated depression prevalence. A cutoff of ≥ 8 was accurate overall, but heterogeneity was too high for implementation in practice. Validated diagnostic interviews should be used to estimate major depression prevalence among older adults.

Key Clinical Message Forced inspiration during mechanical ventilation risks self‐inflicted lung injury. However, controlling it with sedation or paralysis may cause polyneuropathy and myopathy. We tested bilateral phrenic nerve paralysis with local anesthetic in a patient, showing reduced inspiratory force. This offers an alternative to drug‐induced muscle paralysis. Abstract Mechanical ventilation, although a life‐saving measure, can also pose a risk of causing lung injury known as “ventilator‐induced lung injury” or VILI. Patients undergoing mechanical ventilation sometimes exhibit heightened inspiratory efforts, wherein the negative pressure generated by the respiratory muscles adds to the positive pressure generated by the ventilator. This combination of high pressures can lead to a syndrome similar to VILI, referred to as “patient self‐inflicted lung injury” or P‐SILI. Prevention of P‐SILI requires the administration of deep sedation and muscle paralysis to the patients, but both these measures can have undesired effects on their health. In this case report, we demonstrate the effect of a bilateral phrenic nerve block aiming to reduce excessive inspiratory respiratory efforts in a patient suffering from COVID‐19 pneumonitis.

Abstract The diagnostic accuracy of a screening tool is often characterized by its sensitivity and specificity. An analysis of these measures must consider their intrinsic correlation. In the context of an individual participant data meta-analysis, heterogeneity is one of the main components of the analysis. When using a random-effects meta-analytic model, prediction regions provide deeper insight into the effect of heterogeneity on the variability of estimated accuracy measures across the entire studied population, not just the average. This study aimed to investigate heterogeneity via prediction regions in an individual participant data meta-analysis of the sensitivity and specificity of the Patient Health Questionnaire-9 for screening to detect major depression. From the total number of studies in the pool, four dates were selected containing roughly 25%, 50%, 75% and 100% of the total number of participants. A bivariate random-effects model was fitted to studies up to and including each of these dates to jointly estimate sensitivity and specificity. Two-dimensional prediction regions were plotted in ROC-space. Subgroup analyses were carried out on sex and age, regardless of the date of the study. The dataset comprised 17,436 participants from 58 primary studies of which 2322 (13.3%) presented cases of major depression. Point estimates of sensitivity and specificity did not differ importantly as more studies were added to the model. However, correlation of the measures increased. As expected, standard errors of the logit pooled TPR and FPR consistently decreased as more studies were used, while standard deviations of the random-effects did not decrease monotonically. Subgroup analysis by sex did not reveal important contributions for observed heterogeneity; however, the shape of the prediction regions differed. Subgroup analysis by age did not reveal meaningful contributions to the heterogeneity and the prediction regions were similar in shape. Prediction intervals and regions reveal previously unseen trends in a dataset. In the context of a meta-analysis of diagnostic test accuracy, prediction regions can display the range of accuracy measures in different populations and settings.

Objective The objectives were to (1) compare satisfaction with social roles and activities in a large multinational systemic sclerosis (SSc) cohort to general population normative data and (2) identify sociodemographic, lifestyle and SSc disease factors associated with satisfaction with social roles and activities.Methods Participants in the Scleroderma Patient-centered Intervention Network Cohort completed the Patient Reported Outcomes Information System Version 2 satisfaction with social roles and activities domain questionnaire. Multivariable regression was used to assess associations with sociodemographic, lifestyle and disease factors.Results Among 2385 participants, mean satisfaction with social roles and activities T-score (48.1, SD=9.9) was slightly lower than the US general population (mean=50, SD=10). Factors independently associated with satisfaction were years of education (0.54 per SD, 95% CI 0.14 to 0.93); non-White race or ethnicity (−1.13, 95% CI −2.18 to –0.08); living in Canada (−1.33, 95% CI −2.40 to –0.26 (reference USA)) or the UK (−2.49, 95% CI −3.92 to –1.06); body mass index (−1.08 per SD, 95% CI −1.47 to –0.69); gastrointestinal involvement (−3.16, 95% CI −4.27 to –2.05); digital ulcers (−1.90, 95% CI −3.05 to –0.76); moderate (−1.62, 95% CI −2.78 to –0.45) or severe (−2.26, 95% CI −3.99 to –0.52) small joint contractures; interstitial lung disease (−1.11, 95% CI −1.97 to –0.25); pulmonary arterial hypertension (−2.69, 95% CI −4.08 to –1.30); rheumatoid arthritis (−2.51, 95% CI −4.28 to –0.73); and Sjogren’s syndrome (−2.42, 95% CI −3.96 to –0.88).Conclusion Mean satisfaction with social roles and activities is slightly lower in SSc than the general population and associated with multiple sociodemographic and disease factors.

Abstract Item 10 of the Edinburgh Postnatal Depression Scale (EPDS) is intended to assess thoughts of intentional self-harm but may also elicit concerns about accidental self-harm. It does not specifically address suicide ideation but, nonetheless, is sometimes used as an indicator of suicidality. The 9-item version of the EPDS (EPDS-9), which omits item 10, is sometimes used in research due to concern about positive endorsements of item 10 and necessary follow-up. We assessed the equivalence of total score correlations and screening accuracy to detect major depression using the EPDS-9 versus full EPDS among pregnant and postpartum women. We searched Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, and Web of Science from database inception to October 3, 2018 for studies that administered the EPDS and conducted diagnostic classification for major depression based on a validated semi-structured or fully structured interview among women aged 18 or older during pregnancy or within 12 months of giving birth. We conducted an individual participant data meta-analysis. We calculated Pearson correlations with 95% prediction interval (PI) between EPDS-9 and full EPDS total scores using a random effects model. Bivariate random-effects models were fitted to assess screening accuracy. Equivalence tests were done by comparing the confidence intervals (CIs) around the pooled sensitivity and specificity differences to the equivalence margin of δ = 0.05. Individual participant data were obtained from 41 eligible studies (10,906 participants, 1407 major depression cases). The correlation between EPDS-9 and full EPDS scores was 0.998 (95% PI 0.991, 0.999). For sensitivity, the EPDS-9 and full EPDS were equivalent for cut-offs 7–12 (difference range − 0.02, 0.01) and the equivalence was indeterminate for cut-offs 13–15 (all differences − 0.04). For specificity, the EPDS-9 and full EPDS were equivalent for all cut-offs (difference range 0.00, 0.01). The EPDS-9 performs similarly to the full EPDS and can be used when there are concerns about the implications of administering EPDS item 10. Trial registration: The original IPDMA was registered in PROSPERO (CRD42015024785).

Abstract Background More people with rare diseases likely receive disease education and emotional and practical support from peer-led support groups than any other way. Most rare-disease support groups are delivered outside of the health care system by untrained leaders. Potential benefits may not be achieved and harms, such as dissemination of inaccurate information, may occur. Our primary objective was to evaluate the effects of a rare-disease support group leader education program, which was developed collaboratively by researchers, peer support group leaders, and patient organization leaders, compared to waitlist control, on peer leader self-efficacy among scleroderma support group leaders. Methods The trial was a pragmatic, two-arm partially nested randomised controlled trial with 1:1 allocation into intervention or waitlist control. Eligible participants were existing or candidate peer support group leaders affiliated with a scleroderma patient organization. Leader training was delivered in groups of 5–6 participants weekly for 13 weeks in 60–90 min sessions via the GoToMeeting® videoconferencing platform. The program included 12 general leader training modules and one module specific to scleroderma. Primary outcome was leader self-efficacy, measured by the Support Group Leader Self-efficacy Scale (SGLSS) immediately post-intervention. Secondary outcomes were leader self-efficacy 3 months post-intervention; emotional distress, leader burnout, and volunteer satisfaction post-intervention and 3 months post-intervention; and program satisfaction among intervention participants post-intervention. Results One hundred forty-eight participants were randomised to intervention (N = 74) or waitlist (N = 74). Primary outcome data were provided by 146 (99%) participants. Mean number of sessions attended was 11.4 (standard deviation = 2.6). Mean program satisfaction score (CSQ-8) was 30.3 (standard deviation = 3.0; possible range 8–32). Compared to waitlist control, leader self-efficacy was higher post-intervention [SGLSS; 16.7 points, 95% CI 11.0–22.3; standardized mean difference (SMD) 0.84] and 3 months later (15.6 points, 95% CI 10.2–21.0; SMD 0.73); leader volunteer satisfaction was significantly higher at both assessments, emotional distress was lower post-intervention but not 3 months later, and leader burnout was not significantly different at either assessment. Conclusions Peer support group leader education improved leader self-efficacy substantially. The program could be easily adapted for support group leaders in other rare diseases. Trial registration: NCT03965780 ; registered on May 29, 2019.

Abstract In a time of rapid global change, the question of what determines patterns in species abundance distribution remains a priority for understanding the complex dynamics of ecosystems. The constrained maximization of information entropy provides a framework for the understanding of such complex systems dynamics by a quantitative analysis of important constraints via predictions using least biased probability distributions. We apply it to over two thousand hectares of Amazonian tree inventories across seven forest types and thirteen functional traits, representing major global axes of plant strategies. Results show that constraints formed by regional relative abundances of genera explain eight times more of local relative abundances than constraints based on directional selection for specific functional traits, although the latter does show clear signals of environmental dependency. These results provide a quantitative insight by inference from large-scale data using cross-disciplinary methods, furthering our understanding of ecological dynamics.

Abstract Women and gender-diverse individuals have faced disproportionate socioeconomic burden during COVID-19. There have been reports of greater negative mental health changes compared to men based on cross-sectional research that has not accounted for pre-COVID-19 differences. We compared mental health changes from pre-COVID-19 to during COVID-19 by sex or gender. MEDLINE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), EMBASE (Ovid), Web of Science Core Collection: Citation Indexes, China National Knowledge Infrastructure, Wanfang, medRxiv (preprints), and Open Science Framework Preprints (preprint server aggregator) were searched to August 30, 2021. Eligible studies included mental health symptom change data by sex or gender. 12 studies (10 unique cohorts) were included, all of which reported dichotomized sex or gender data. 9 cohorts reported results from March to June 2020, and 2 of these also reported on September or November to December 2020. One cohort included data pre-November 2020 data but did not provide dates. Continuous symptom change differences were not statistically significant for depression (standardized mean difference [SMD] = 0.12, 95% CI -0.09–0.33; 4 studies, 4,475 participants; I2 = 69.0%) and stress (SMD = − 0.10, 95% CI -0.21–0.01; 4 studies, 1,533 participants; I2 = 0.0%), but anxiety (SMD = 0.15, 95% CI 0.07–0.22; 4 studies, 4,344 participants; I2 = 3.0%) and general mental health (SMD = 0.15, 95% CI 0.12–0.18; 3 studies, 15,692 participants; I2 = 0.0%) worsened more among females/women than males/men. There were no significant differences in changes in proportions above cut-offs: anxiety (difference = − 0.05, 95% CI − 0.20–0.11; 1 study, 217 participants), depression (difference = 0.12, 95% CI -0.03–0.28; 1 study, 217 participants), general mental health (difference = − 0.03, 95% CI − 0.09–0.04; 3 studies, 18,985 participants; I2 = 94.0%), stress (difference = 0.04, 95% CI − 0.10–0.17; 1 study, 217 participants). Mental health outcomes did not differ or were worse by small amounts among women than men during early COVID-19.

Abstract Resuscitative endovascular balloon occlusion of the aorta (REBOA) for rapid hemorrhage control is increasingly being used in trauma management. Its beneficial hemodynamic effects on unstable patients beyond temporal hemostasis has led to growing interest in its use in other patient populations, such as during cardiac arrest from nontraumatic causes. The ability to insert the catheters without fluoroscopic guidance makes the technique available in the prehospital setting. However, in addition to correct positioning, challenges include reliably achieving aortic occlusion while minimizing the risk of balloon rupture. Without fluoroscopic control, inflation of the balloon relies on estimated aortic diameters and on the disappearing pulse in the contralateral femoral artery. In the case of cardiac arrest or absent palpable pulses, balloon inflation is associated with excess risk of overinflation and adverse events (vessel damage, balloon rupture). In this bench study, we examined how the pressure in the balloon is related to the surrounding blood pressure and the balloon's contact with the vessel wall in two sets of experiments, including a pulsatile circulation model. With this data, we developed a rule of thumb to guide balloon inflation of the ER-REBOA catheter with a simple disposable pressure-reading device (COMPASS). We recommend slowly filling the balloon with saline until the measured balloon pressure is 160 mmHg, or 16 mL of saline have been used. If after 16 mL the balloon pressure is still below 160 mmHg, saline should be added in 1-mL increments, which increases the pressure target about 10 mmHg at each step, until the maximum balloon pressure is reached at 240 mmHg (= 24 mL inflation volume). A balloon pressure greater than 250 mmHg indicates overinflation. With this rule and a disposable pressure-reading device (COMPASS), ER-REBOA balloons can be safely filled in austere environments where fluoroscopy is unavailable. Pressure monitoring of the balloon allows for recognition of unintended deflation or rupture of the balloon.

Aims and objectives: This study retrospectively examined patient records from the Emergency Department to investigate how nurse experience in this department affected triage decisions. Background: Triage is a crucial aspect of Emergency Department care, and studies have found that experience affects clinical decision making. The Emergency Severity Index (ESI) is a structured, well validated and widely-used tool that aims to assist triage decision making. Methods: ESI classification was compared to patients’ Emergency Department disposition at a large tertiary hospital to measure decision-making accuracy. Decisions were classified into four types: successful identification of high-urgency patients, successful identification of low-urgency patients, misidentification of high-urgency patients (under-triage), and misidentification of low-urgency patient (over-triage). Results: Analysis of 18,321 patient records demonstrated a correlation between nurses’ experience in the Emergency Department and their decisions. Pearson residuals analysis revealed that less-experienced nurses were more successful in identifying high-urgency patients, but tended to misclassify low-urgency ones (over-triage). In contrast, experienced nurses were more successful in identifying low-urgency patients, but misclassified more high-urgency ones (under-triage). Conclusion: Nurse experience is an important factor in decision making, even when using a highly-structured tool such as the ESI. The tendency of more-experienced nurses to under-triage and for less experienced nurses to over-triage highlights the need to improve triage decision making. Relevance to clinical practice: Raising awareness and providing focused feedback and continuing education may improve triage accuracy by assisting nurses to fine-tune their behavior and decision making.

Objectives To support the Zika virus (ZIKV) Individual Participant Data (IPD) Consortium’s efforts to harmonise and analyse IPD from ZIKV-related prospective cohort studies and surveillance-based studies of pregnant women and their infants and children; we developed and disseminated a metadata survey among ZIKV-IPD Meta-Analysis (MA) study participants to identify and provide a comprehensive overview of study-level heterogeneity in exposure, outcome and covariate ascertainment and definitions.Setting Cohort and surveillance studies that measured ZIKV infection during pregnancy or at birth and measured fetal, infant, or child outcomes were identified through a systematic search and consultations with ZIKV researchers and Ministries of Health from 20 countries or territories.Participants Fifty-four cohort or active surveillance studies shared deidentified data for the IPD-MA and completed the metadata survey, representing 33 061 women (11 020 with ZIKV) and 18 281 children.Primary and secondary outcome measures Study-level heterogeneity in exposure, outcome and covariate ascertainment and definitions.Results Median study sample size was 268 (IQR=100, 698). Inclusion criteria, follow-up procedures and exposure and outcome ascertainment were highly heterogenous, differing meaningfully across regions and multisite studies. Enrolment duration and follow-up for children after birth varied before and after the declaration of the Public Health Emergency of International Concern (PHEIC) and according to the type of funding received.Conclusion This work highlights the logistic and statistical challenges that must be addressed to account for the multiple sources of within-study and between-study heterogeneity when conducting IPD-MAs of data collected in the research response to emergent pathogens like ZIKV.

Background: Multiple methods have been implemented to limit the impact of radiotherapy on patients affected by mediastinal lymphoma, including breathing control techniques, image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT), although the actual diffusion of such techniques is unclear. No surveys have been published to date evaluating the techniques adopted at different centers. Methods: A survey with a dedicated questionnaire was submitted to 195 Italian radiotherapy centers, assessing items regarding the characteristics of the center and clinical practice in the treatment of mediastinal lymphomas. Results: A total of 43 centers (22%) responded, the majority of which were university hospitals (37.2%) or cancer care centers (27.9%). In 95.4% of the centers, IMRT was used in the clinical practice, and the most frequently employed techniques were VMAT (48.8% of centers) and non-rotational IMRT (31.7%). Comparison of multiple plans was performed by 66.7% of the responding centers. Dose constraints for organs at risk were consistently prescribed. IGRT techniques were adopted by 93% of the centers, while breathing control or gating techniques were routinely used by only 25.6% of the centers. A necessity to standardize OAR constraints and define guidelines was perceived by almost all participants. Conclusions: Modern radiotherapy techniques are widely used in the Italian centers, although with heterogeneous characteristics.

Previously, we described a large collection of Drosophila strains that each carry an artificial exon containing a T2AGAL4 cassette inserted in an intron of a target gene based on CRISPR-mediated homologous recombination. These alleles permit numerous applications and have proven to be very useful. Initially, the homologous recombination-based donor constructs had long homology arms (>500 bps) to promote precise integration of large constructs (>5 kb). Recently, we showed that in vivo linearization of the donor constructs enables insertion of large artificial exons in introns using short homology arms (100–200 bps). Shorter homology arms make it feasible to commercially synthesize homology donors and minimize the cloning steps for donor construct generation. Unfortunately, about 58% of Drosophila genes lack a suitable coding intron for integration of artificial exons in all of the annotated isoforms. Here, we report the development of new set of constructs that allow the replacement of the coding region of genes that lack suitable introns with a KozakGAL4 cassette, generating a knock-out/knock-in allele that expresses GAL4 similarly as the targeted gene. We also developed custom vector backbones to further facilitate and improve transgenesis. Synthesis of homology donor constructs in custom plasmid backbones that contain the target gene sgRNA obviates the need to inject a separate sgRNA plasmid and significantly increases the transgenesis efficiency. These upgrades will enable the targeting of nearly every fly gene, regardless of exon–intron structure, with a 70–80% success rate.

Abstract Tyrosine kinase inhibitors (TKIs) targeting FLT3 have shown activity but when used alone have achieved limited success in clinical trials, suggesting the need for combination with other drugs. We investigated the combination of FLT3 TKIs (Gilteritinib or Sorafenib), with Venetoclax, a BCL-2 selective inhibitor (BCL-2i), on FLT3/ITD leukemia cells. The combination of a FLT3 TKI and a BCL-2i synergistically reduced cell proliferation and enhanced apoptosis/cell death in FLT3/ITD cell lines and primary AML samples. Venetoclax also re-sensitized FLT3 TKI-resistant cells to Gilteritinib or Sorafenib treatment, mediated through MAPK pathway inhibition. Gilteritinib treatment alone dissociated BIM from MCL-1 but increased the binding of BIM to BCL-2. Venetoclax treatment enhanced the binding of BIM to MCL-1 but dissociated BIM from BCL-2. Treatment with the drugs together resulted in dissociation of BIM from both BCL-2 and MCL-1, with an increased binding of BIM to the cell death mediator BAX, leading to increased apoptosis. These findings suggest that Venetoclax mitigates the unintended pro-survival effects of FLT3 TKI mainly through the dissociation of BIM and BCL-2 and also decreased BIM expression. This study provides evidence that the addition of BCL-2i enhances the effect of FLT3 TKI therapy in FLT3/ITD AML treatment.

Abstract Objective Standard rodent sepsis models as cecal ligation and puncture models (CLP) or cecal ligation and incision models (CLI) are frequently not suited experiments, mainly because they lack surgical repair, and they are difficult to control for severity. The colon ascendens stent peritonitis model (CASP) overcomes some of these limitations. Result Here we present our modification of the rodent CASP model, where severity of sepsis can be controlled by timing of surgical repair and treatment, and by diameter of the stent. Further, basic hemodynamic monitoring (blood pressure and heart rate) and frequent blood sampling can be achieved, which might guide further treatment.

[This corrects the article DOI: 10.1371/journal.pone.0235819.].

BackgroundTransrectal ultrasound (TRUS) guided biopsy for prostate cancer is prone to random and systemic error and has been shown to have a negative predictive value of 70%. PRECISION and PRECISE are among the first randomised studies to evaluate the new MRI-targeted biopsy (MRI-TB) pathway with a non-paired design to detect clinically significant prostate cancer and avoid unnecessary treatment. The trials' results individually demonstrated non-inferiority of MRI-TB compared to TRUS biopsy. An individual patient data (IPD) meta-analysis was planned from the outset of the two trials in parallel and this IPD meta-analysis aims to further elucidate the utility of MRI-TB as the optimal diagnostic pathway for prostate cancer.Methods and materialsThis study is registered on PROSPERO (CRD42021249263). A search of Medline, Embase, Cochrane Central Register of Registered Trials (CENTRAL), Web of Science, and ClinicalTrials.gov was performed up until 4th February 2021. Only randomised controlled trials (PRECISE, PRECISION and other eligible trials) comparing the MRI-targeted biopsy pathway and traditional TRUS biopsy pathway will be included. The primary outcome of the review is the proportion of men diagnosed with clinically significant prostate cancer in each arm (Gleason ≥ 3+4 = 7). IPD and study-level data and characteristics will be sought from eligible studies. Analyses will be done primarily using an intention-to-treat approach, and a one-step IPD meta-analysis will be performed using generalised linear mixed models. A non-inferiority margin of 5 percentage points will be used. Heterogeneity will be quantified using the variance parameters from the mixed model. If there is sufficient data, we will investigate heterogeneity by exploring the effect of the different conducts of MRIs, learning curves of MRI reporting and MRI targeted biopsies.Trial registrationThis systematic review is registered on PROSPERO (CRD42021249263).

RESUMEN Introducción: Los profesionales de la salud están constantemente expuestos a situaciones estresantes. Particularmente, las enfermeras dedicadas al cuidado del paciente crítico resultan más afectadas por el estrés laboral lo que impacta negativamente en su salud mental y predispone a infecciones. Ello evidencia la estrecha interrelación psiconeuroinmunendocrina. Objetivo: Describir las consecuencias clínicas e inmunológicas del estrés laboral crónico en una enfermera intensivista. Presentación del caso: La paciente de 39 años presentó infecciones recurrentes por varicela zoster, así como forunculosis cutánea, infecciones urinarias, neumonía y candidiasis vaginal en un año. Se constató neutropenia marcada, monocitopenia e hipogammaglobulinemia. La citometría de flujo evidenció disminución de los linfocitos T cooperadores CD4+ y los B CD19+. Se diagnosticó inmunodeficiencia secundaria al estrés laboral crónico y depresión severa. La terapia inmunomoduladora con factor de transferencia (Hebertrans) subcutáneo y vitaminoterapia mejoró su inmunidad. Conclusiones: En trabajadores de la salud inmunocompetentes expuestos a altos niveles de estrés, la presencia de infecciones recurrentes o múltiples de etiología variada en breve tiempo puede estar asociado a inmunodeficiencia potencialmente reversible de controlarse o eliminar la causa.

Abstract Background Depression symptom questionnaires are commonly used to assess symptom severity and as screening tools to identify patients who may have depression. They are not designed to ascertain diagnostic status and, based on published sensitivity and specificity estimates, would theoretically be expected to overestimate prevalence. Meta-analyses sometimes estimate depression prevalence based on primary studies that used screening tools or rating scales rather than validated diagnostic interviews. Our objectives were to determine classification methods used in primary studies included in depression prevalence meta-analyses, if pooled prevalence differs by primary study classification methods as would be predicted, whether meta-analysis abstracts accurately describe primary study classification methods, and how meta-analyses describe prevalence estimates in abstracts. Methods We searched PubMed (January 2008–December 2017) for meta-analyses that reported pooled depression prevalence in the abstract. For each meta-analysis, we included up to one pooled prevalence for each of three depression classification method categories: (1) diagnostic interviews only, (2) screening or rating tools, and (3) a combination of methods. Results In 69 included meta-analyses (81 prevalence estimates), eight prevalence estimates (10%) were based on diagnostic interviews, 36 (44%) on screening or rating tools, and 37 (46%) on combinations. Prevalence was 31% based on screening or rating tools, 22% for combinations, and 17% for diagnostic interviews. Among 2094 primary studies in 81 pooled prevalence estimates, 277 (13%) used validated diagnostic interviews, 1604 (77%) used screening or rating tools, and 213 (10%) used other methods (e.g., unstructured interviews, medical records). Classification methods pooled were accurately described in meta-analysis abstracts for 17 of 81 (21%) prevalence estimates. In 73 meta-analyses based on screening or rating tools or on combined methods, 52 (71%) described the prevalence as being for “depression” or “depressive disorders.” Results were similar for meta-analyses in journals with impact factor ≥ 10. Conclusions Most meta-analyses combined estimates from studies that used screening tools or rating scales instead of diagnostic interviews, did not disclose this in abstracts, and described the prevalence as being for “depression” or “depressive disorders ” even though disorders were not assessed. Users of meta-analyses of depression prevalence should be cautious when interpreting results because reported prevalence may exceed actual prevalence.

In this paper, we use a Delphi approach to investigate whether, and to what extent, blockchain-based applications might affect firms’ organizations, innovations, and strategies by 2030, and, consequently, which societal areas may be mainly affected. We provide a deep understanding of how the adoption of this technology could lead to changes in Europe over multiple dimensions, ranging from business to culture and society, policy and regulation, economy, and technology. From the projections that reached a significant consensus and were given a high probability of occurrence by the experts, we derive four scenarios built around two main dimensions: the digitization of assets and the change in business models.

Plants have been used in Amazonian forests for millennia and some of these plants are disproportionally abundant (hyperdominant). At local scales, people generally use the most abundant plants, which may be abundant as the result of management of indigenous peoples and local communities. However, it is unknown whether plant use is also associated with abundance at larger scales. We used the population sizes of 4,454 arboreal species (trees and palms) estimated from 1946 forest plots and compiled information about uses from 29 Amazonian ethnobotany books and articles published between 1926 and 2013 to investigate the relationship between species usefulness and their population sizes, and how this relationship is influenced by the degree of domestication of arboreal species across Amazonia. We found that half of the arboreal species (2,253) are useful to humans, which represents 84% of the estimated individuals in Amazonian forests. Useful species have mean populations sizes six times larger than non-useful species, and their abundance is related with the probability of usefulness. Incipiently domesticated species are the most abundant. Population size was weakly related to specific uses, but strongly related with the multiplicity of uses. This study highlights the enormous usefulness of Amazonian arboreal species for local peoples. Our findings support the hypothesis that the most abundant plant species have a greater chance to be useful at both local and larger scales, and suggest that although people use the most abundant plants, indigenous people and local communities have contributed to plant abundance through long-term management.

Comatose patients admitted to the intensive care unit (ICU) after out-of-hospital cardiac arrest frequently die after withdrawal of life support. Guidelines recommend scheduling prognostication no sooner than 96 hours after cardiac arrest, and strict withdrawal criteria leave many patients waiting for improvement for days without ever reaching a favourable outcome. In clinical practice, physicians are frequently confronted with vague living wills expressed by next of kin or an imprecise advance care directive soon after cardiac arrest. Often a decision to admit a patient to an ICU or limiting ICU treatment in terms of time or intensity is made early, based on the patient’s preferences. The Target Temperature Management (TTM) risk score is an imperfect measure that predicts outcome early, at the time of ICU admission. It was developed on a data set of 939 patients included in the TTM Trial, a study in which unconscious patients after cardiac arrest were randomised into two temperature management arms. Patient selection in that trial might impede generalisability. We aimed to validate the TTM risk score with 100 consecutive patients treated in our ICU. Although we had different survival rates, reflecting a different patient population, we were able to confirm the score’s albeit imperfect ability to predict outcome early after cardiac arrest. The suggested cut-off values of 10 and 16 can be used as a basis for discussion with the family; in particular, a risk score value below 10 predicts a favourable outcome and might guide early discussion. As in the original study, the outcome of an individual patient cannot be predicted. (ClinicalTrials.gov Identifier: NCT02722460)

Objective To (1) investigate the extent to which recently published meta-analyses report trial funding, author–industry financial ties and author–industry employment from included randomised controlled trials (RCTs), comparing Cochrane and non-Cochrane meta-analyses; (2) examine characteristics of meta-analyses independently associated with reporting funding sources of included RCTs; and (3) compare reporting among recently published Cochrane meta-analyses to Cochrane reviews published in 2010.Design Review of consecutive sample of recently published meta-analyses.Data sources MEDLINE database via PubMed searched on 19 October 2018.Eligibility criteria for selecting articles We selected the 250 most recent meta-analyses listed in PubMed that included a documented search of at least one database, statistically combined results from ≥2 RCTs and evaluated the effects of a drug or class of drugs.Results 90 of 107 (84%) Cochrane meta-analyses reported funding sources for some or all included trials compared with 21 of 143 (15%) non-Cochrane meta-analyses, a difference of 69% (95% CI 59% to 77%). Percent reporting was also higher for Cochrane meta-analyses compared with non-Cochrane meta-analyses for trial author–industry financial ties (44% versus 1%; 95% CI for difference 33% to 52%) and employment (17% versus 1%; 95% CI for difference 9% to 24%). In multivariable analysis, compared with Cochrane meta-analyses, the odds ratio (OR) for reporting trial funding was ≤0.11 for all other journal category and impact factor combinations. Compared with Cochrane reviews from 2010, reporting of funding sources of included RCTs among recently published Cochrane meta-analyses improved by 54% (95% CI 42% to 63%), and reporting of trial author–industry financial ties and employment improved by 37% (95% CI 26% to 47%) and 10% (95% CI 2% to 19%).Conclusions Reporting of trial funding sources, trial author–industry financial ties and trial author–industry employment in Cochrane meta-analyses has improved since 2010 and is higher than in non-Cochrane meta-analyses.

Past human societies have left persistent marks on forests worldwide. However, the degree to which pre-colonial Amerindian societies have affected forest structure is still not fully understood, especially in southern Brazil. This study investigated the influence of two distinct Amerindian groups (Southern-Jê and Guarani) over tree composition of forest fragments in the State of Santa Catarina. Vegetation data was obtained from the Santa Catarina Forest and Floristic Inventory (SCFFI): a statewide systematic vegetation sampling project. Archaeological data was collated from literature reviews as well as existing databases for archaeological sites occupied by Guarani and Southern-Jê groups. Using these sites of known Amerindian occupation, and corresponding environmental variables, ecological niche models were developed for each Amerindian group, predicting potential archaeological sites occupied by these groups across southern Brazil. Maps of these potential occupation sites of pre-colonial Amerindian groups were compared with 417 corresponding floristic inventory plots. Redundancy analysis (RDA) was used to identify floristic composition patterns linked to areas with a high probability of Southern-Jê or Guarani presence. Southern-Jê and Guarani pre-colonial occupations overlapped near main rivers; however, Southern-Jê groups generally occupied elevated areas whereas Guarani occupied mostly coastal areas. We observed differences in forest composition associated with the predicted occurrence of these pre-colonial Amerindian groups. Based on these results, we argue there is a relationship between tree species distribution and pre-colonial human occupation by these two Amerindian groups.

Abstract Yield-phenology relation is a critical issue affecting rainfed maize field productivity in semiarid east African Plateau (EAP). We first introduced Chinese ridge-furrow mulching (RFM) system to EAP, using three maize cultivars with early-, mid- and late-maturing traits as test materials. A two-year field experiment was conducted in a semiarid farm of Kenya from 2012 to 2013. Three treatments were designed: alternative ridge and furrow with transparent plastic mulching (FT), with black plastic mulching (FB) and without mulching (CK). We found that FT and FB significantly increased soil moisture and accelerated crop maturity across two growing seasons. Leaf area and shoot biomass were increased by 30.2% and 67.5% in FT, 35.2% and 73.5% in FB, respectively, compared with CK. Grain yield, water use efficiency and economic output were increased by 55.6%, 57.5% and 26.7% in FT, and 50.8%, 53.3% and 19.8% in FB, respectively. Optimal yield and economic benefit were observed in late-maturing cultivar due to increased topsoil temperature in FT in 2012 (cool), and in early-maturing cultivar owing to cooling effect in FB in 2013 (warm). Our study suggested RFM system, combined with crop phenology selection, be a promising strategy to boost maize productivity and profitability in semiarid EAP.

Introducción. El virus de la coriomeningitis linfocítica es un arenavirus del Viejo Mundo que se hospeda en el ratón casero (Mus musculus), y puede causar infecciones congénitas, hidrocefalia, coriorretinitis y falla orgánica múltiple en pacientes receptores de trasplantes. En Colombia aún no se ha reportado la enfermedad mediante diagnóstico clínico, pero en estudios serológicos se ha detectado la infección por el virus Pichindé en roedores en los departamentos del Cauca y Valle del Cauca, y por el virus Guanarito, en roedores en Córdoba. Objetivo. Detectar el virus de la coriomeningitis linfocítica en M. musculus en el municipio de Sincelejo. Materiales y métodos. Se evaluaron 80 muestras de plasma mediante la prueba ELISA usando antígeno del virus de la coriomeningitis linfocítica. Además, se empleó la reacción en cadena de la polimerasa con transcriptasa inversa (RT-PCR) anidada en muestras de animales seropositivos y seronegativos para la detección del segmento S. Resultados. Se encontró una seroprevalencia de 10% (8/80) y se detectó el genoma viral en 16 muestras de cerebro; el alineamiento (en la Basic Local Alignment Search Tool, BLAST) y el análisis filogenético (mediante el programa MrBayes, versión 3.2.2) confirmaron que correspondía al virus de la coriomeningitis linfocítica. Conclusión. Los resultados indicaron que la infección por el virus de la coriomeningitis linfocítica en humanos podría ocurrir en el área urbana de Sincelejo, aunque hasta la fecha no se hayan reportado casos.

The Brazil nut tree (Bertholletia excelsa) is an iconic and economically valuable species that dominates vast swathes of the Amazon Basin. This species seems to have been an important part of human subsistence strategies in the region from at least the Early Holocene, and its current distribution may be a legacy of past human settlement. Because B. excelsa is a long-lived pioneer tree it requires natural or human disturbances to increase light availability in the understory for a successful establishment. However, it remains unclear how the long-term population dynamics of this species have been shaped by pre-colonial and post-colonial human practices. Here, we use tree-ring analyses to look at changes in growing conditions over the past 400 years in a Brazil nut tree population in Central Amazonia. We identify changes in tree recruitment and growth rates associated not only with regional climatic variability, but also major political and socio-economic activities recorded by historical documents in the vicinity of Manaus. We demonstrate that the expansion of a post-colonial political center (Manaus) from the middle of the 18th century onwards coincided with a reduction in recruitment of B. excelsa. We argue that this hiatus suggests the interruption of indigenous management practices, probably due to the collapse of pre-Columbian societies. A second recruitment pulse, and unprecedented cycles of growth release and suppression, aligns with a shift to modern exploitation of the forest into the 20th century. Our findings shed light on how past histories of human-forest interactions can be revealed by the growth rings of trees in Amazonia. Future interdisciplinary analysis of these trees should enable more detailed investigation of how human forest management has changed in this part of the world, through pre-colonial, colonial, and industrial periods of human activity, with potential implications for conservation.

We generated a library of ~1000 Drosophila stocks in which we inserted a construct in the intron of genes allowing expression of GAL4 under control of endogenous promoters while arresting transcription with a polyadenylation signal 3’ of the GAL4. This allows numerous applications. First, ~90% of insertions in essential genes cause a severe loss-of-function phenotype, an effective way to mutagenize genes. Interestingly, 12/14 chromosomes engineered through CRISPR do not carry second-site lethal mutations. Second, 26/36 (70%) of lethal insertions tested are rescued with a single UAS-cDNA construct. Third, loss-of-function phenotypes associated with many GAL4 insertions can be reverted by excision with UAS-flippase. Fourth, GAL4 driven UAS-GFP/RFP reports tissue and cell-type specificity of gene expression with high sensitivity. We report the expression of hundreds of genes not previously reported. Finally, inserted cassettes can be replaced with GFP or any DNA. These stocks comprise a powerful resource for assessing gene function.

The Argentine hemorrhagic fever (AHF) is a severe acute viral disease caused by the Junin virus of the Arenaviridae family. The AHF endemic area coincides geographically with the largest grain export agro-industrial complex of the country [Argentina]. Since the implementation of vaccination with the Candid #1 vaccine, a significant reduction in incidence was achieved and risk patterns were modified. A previous study allowed characterizing these changes and identifying three transmission scenarios: classic, emergent-reemergent, and traveler. The latter scenario includes seasonal migrant workers who move each year, mainly from the province of Santiago del Estero, the endemic area to work in the detasseling of maize. With the objective of protecting this group of workers, a prevention campaign was initiated which included: capacity building of health personnel in the province, health education, and immunization with the vaccine Candid #1. 3,021 workers were vaccinated. Prior to vaccination, serum samples were taken from a group of 104 volunteers. Tests for neutralizing antibodies specific to the Junin virus were performed and 6 (5.76%) tested positive. The unexpected finding of a high percentage of workers with antibodies suggests the need to evaluate several hypotheses: a) that the result is the product of non-probabilistic sampling; b) that it could be people who fell ill in previous travels, c) or who were vaccinated in previous travels; or d) consider this region as an emerging scenario.