Science for a wilder Anthropocene: synthesis and future directions for trophic rewilding research

Trophic rewilding is an ecological restoration strategy that uses species introductions to restore top-down trophic interactions and associated trophic cascades to promote self-regulating biodiverse ecosystems. Given the importance of large animals in trophic cascades and their widespread losses and resulting trophic downgrading, it often focuses on restoring functional megafaunas. Trophic rewilding is increasingly being implemented for conservation, but remains controversial. Here, we provide a synthesis of its current scientific basis, highlighting trophic cascades as the key conceptual framework, discussing the main lessons learned from ongoing rewilding projects, systematically reviewing the current literature, and highlighting unintentional rewilding and spontaneous wildlife comebacks as underused sources of information. Together, these lines of evidence show that trophic cascades may be restored via species reintroductions and ecological replacements. It is clear, however, that megafauna effects may be affected by poorly understood trophic complexity effects and interactions with landscape settings, human activities, and other factors. Unfortunately, empirical research on trophic rewilding is still rare, fragmented, and geographically biased, with the literature dominated by essays and opinion pieces. We highlight the need for applied programs to include hypothesis testing and science-based monitoring, and outline priorities for future research, notably assessing the role of trophic complexity, interplay with landscape settings, land use, and climate change, as well as developing the global scope for rewilding and tools to optimize benefits and reduce human–wildlife conflicts. Finally, we recommend developing a decision framework for species selection, building on functional and phylogenetic information and with attention to the potential contribution from synthetic biology

Family medicine journals’ adherence to reporting guidelines and trial registration: A systematic review

Reporting guidelines have been developed as a method of mitigating inadequate reporting quality. Reporting guidelines such as the Consolidated Standards of Reporting Trials (CONSORT) for randomized control trials have shown to improve the completeness of reporting in CONSORT-endorsing journals. Additionally, requiring the registration of clinical trials and systematic reviews have similarly demonstrated a reduced risk of overall bias in comparison to trials and reviews that were not registered. To our knowledge, the rate of endorsement and requirement of the two aforementioned tools in family medicine journals has not been ascertained. Thus, our objective was to determine the frequencies of recommendation or requirement of reporting guidelines for common study types within Family Medicine journals. In addition, we also sought to assess the rate of recommendation or requirement to register clinical trials and systematic reviews. We conducted a systematic review of family medicine journals’ policies and guidelines for authors in order to examine guideline use and adherence. Using the 2021 Scopus CiteScore tool, we identified 44 active, peer-reviewed journals in the “Family Practice” subcategory as of December 2022. Prior to data collection, email correspondence to the Editors-in-Chief was sent once a week for three weeks, to determine if the journal had any unaccepted article types. In a masked, duplicate fashion, statements regarding the requirement/recommendation of reporting guidelines for popular study designs were extracted from each journal’s “instructions to authors” webpage. Statements regarding clinical trial registration were obtained in a similar manner. Our search identified 44 journals that were included for data collection. The most commonly recommended guidelines were CONSORT (29/44, 65%), PRISMA (26/44, 59%), and STROBE (26/44, 59%). The most commonly required guidelines were PRISMA (7/44, 16%) and CONSORT (6/44, 14%). The least required guidelines were SPIRIT (1/44, 2.4%), SRQR (1/44, 2.5%), ARRIVE (1/44, 2.5%), and CHEERS (1/44, 2.7%). PRISMA and STROBE guidelines were more likely to be recommended or required in journals that mentioned the EQUATOR network (p < 0.001). With respect to study registration, twenty-nine out of the forty-four (66%) journals either recommended (4/44, 9%) or required (25/44, 57%) clinical trial registration. Although CONSORT, PRISMA, and STROBE guidelines were recommended or required by more than half of our included journals, a majority of the journals did not mention many of the other reporting guidelines. Explicit endorsement or requirement of study registration, as well as appropriate reporting guidelines, is necessary to improve the quality of research published in family medicine journals. Therefore, we recommend journal editors make an effort to impose tighter instructions to prospective authors by recommending/requiring these tools

A review of the methodological features of systematic reviews in maternal medicine

Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine

Forecasting the spread of raccoon rabies using a purpose-specific group decisionmaking process

The Centers for Disease Control (CDC) and USDA Wildlife Services (WS) have been involved in an oral rabies vaccination (ORV) program for raccoons (Procyon lotor) that has slowed the westward spread of raccoon rabies. The objective of this study was to forecast the spread of the disease if an ORV zone was not maintained. A group decision-making process was designed to address the forecasting problem and was implemented using a group of 15 experts and 4 support personnel at a meeting at the USDA National Wildlife Research Center. Ten expansion regions were constructed that described the spread of disease at 2-year intervals. This forecast may provide for more accurate cost-benefit analysis of the ORV barrier

Aptamer-based multiplexed proteomic technology for biomarker discovery

Interrogation of the human proteome in a highly multiplexed and efficient manner remains a coveted and challenging goal in biology. We present a new aptamer-based proteomic technology for biomarker discovery capable of simultaneously measuring thousands of proteins from small sample volumes (15 [mu]L of serum or plasma). Our current assay allows us to measure ~800 proteins with very low limits of detection (1 pM average), 7 logs of overall dynamic range, and 5% average coefficient of variation. This technology is enabled by a new generation of aptamers that contain chemically modified nucleotides, which greatly expand the physicochemical diversity of the large randomized nucleic acid libraries from which the aptamers are selected. Proteins in complex matrices such as plasma are measured with a process that transforms a signature of protein concentrations into a corresponding DNA aptamer concentration signature, which is then quantified with a DNA microarray. In essence, our assay takes advantage of the dual nature of aptamers as both folded binding entities with defined shapes and unique sequences recognizable by specific hybridization probes. To demonstrate the utility of our proteomics biomarker discovery technology, we applied it to a clinical study of chronic kidney disease (CKD). We identified two well known CKD biomarkers as well as an additional 58 potential CKD biomarkers. These results demonstrate the potential utility of our technology to discover unique protein signatures characteristic of various disease states. More generally, we describe a versatile and powerful tool that allows large-scale comparison of proteome profiles among discrete populations. This unbiased and highly multiplexed search engine will enable the discovery of novel biomarkers in a manner that is unencumbered by our incomplete knowledge of biology, thereby helping to advance the next generation of evidence-based medicine

Stress, Depressive Symptoms, and Maternal Self-Efficacy in First-Time Mothers: Modelling and Predicting Change across the First Six Months of Motherhood

Background: First-time mothers commonly experience stress and depressive symptoms in the postpartum period. Maternal self-efficacy has been shown to be an important protective factor against these experiences; however, research on the dynamic nature of stress, depressive symptoms, and maternal self-efficacy is limited. The aim of this study was to document changes in these psychological factors among first-time mothers, and determine how early maternal self-efficacy perceptions may predict change in stress and depressive symptoms over the first 6 months postpartum. Methods: Sixty first-time Australian mothers were recruited during their third trimester of pregnancy. Participants completed a baseline survey during the third trimester of pregnancy (M = 32.87 weeks, SD = 2.62 weeks), and subsequently reported stress, depressive symptoms, and maternal self-efficacy every 3 weeks postpartum for 6 months. Latent growth curve modelling was used to estimate participants’ change over time for stress and depressive symptoms. Results: First-time mothers’ stress and depressive symptoms peaked, and maternal self-efficacy was weakest, at 3 weeks postpartum. Maternal self-efficacy at 3 weeks postpartum was a significant (negative) predictor of 3-week levels of, and also (positively) predicted later reductions in, stress. Conclusion: Future interventions aimed at bolstering early maternal self-efficacy may protect against postpartum stress for first-time mothers

Lung diffusing capacity for nitric oxide and carbon monoxide in relation to morphological changes as assessed by computed tomography in patients with cystic fibrosis

Background Due to large-scale destruction, changes in membrane diffusion (Dm) may occur in cystic fibrosis (CF), in correspondence to alterations observed by computed tomography (CT). Dm can be easily quantified via the diffusing capacity for nitric oxide (DLNO), as opposed to the conventional diffusing capacity for carbon monoxide (DLCO). We thus studied the relationship between DLNO as well as DLCO and a CF-specific CT score in patients with stable CF. Methods Simultaneous single-breath determinations of DLNO and DLCO were performed in 21 CF patients (mean ± SD age 35 ± 9 y, FEV1 66 ± 28%pred). Patients also underwent spirometry and bodyplethysmography. CT scans were evaluated via the Brody score and rank correlations (rS) with z-scores of functional measures were computed. Results CT scores correlated best with DLNO (rS = -0.83; p < 0.001). Scores were also related to the volume-specific NO transfer coefficient (KNO; rS = -0.63; p < 0.01) and to DLCO (rS = -0.79; p < 0.001) but not KCO. Z-scores for DLNO were significantly lower than for DLCO (p < 0.001). Correlations with spirometric (e.g., FEV1, IVC) or bodyplethysmographic (e.g., SRaw, RV/TLC) indices were weaker than for DLNO or DLCO but most of them were also significant (p < 0.05 each). Conclusion In this cross sectional study in patients with CF, DLNO and DLCO reflected CT-morphological alterations of the lung better than other measures. Thus the combined diffusing capacity for NO and CO may play a future role for the non-invasive, functional assessment of structural alterations of the lung in CF

Neutrophils incite and macrophages avert electrical storm after myocardial infarction

Sudden cardiac death, arising from abnormal electrical conduction, occurs frequently in patients with coronary heart disease. Myocardial ischemia simultaneously induces arrhythmia and massive myocardial leukocyte changes. In this study, we optimized a mouse model in which hypokalemia combined with myocardial infarction triggered spontaneous ventricular tachycardia in ambulatory mice, and we showed that major leukocyte subsets have opposing effects on cardiac conduction. Neutrophils increased ventricular tachycardia via lipocalin-2 in mice, whereas neutrophilia associated with ventricular tachycardia in patients. In contrast, macrophages protected against arrhythmia. Depleting recruited macrophages in Ccr2−/− mice or all macrophage subsets with Csf1 receptor inhibition increased both ventricular tachycardia and fibrillation. Higher arrhythmia burden and mortality in Cd36−/− and Mertk−/− mice, viewed together with reduced mitochondrial integrity and accelerated cardiomyocyte death in the absence of macrophages, indicated that receptor-mediated phagocytosis protects against lethal electrical storm. Thus, modulation of leukocyte function provides a potential therapeutic pathway for reducing the risk of sudden cardiac death

Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains unknown, depletion of surface heparan sulfates block H522 infection. Temporally resolved transcriptomic and proteomic profiling reveal alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type I interferon signaling. These findings establish an alternative SARS-CoV-2 host cell receptor for the E484D SARS-CoV-2 variant, which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis