Publications by authors named "Jonathan Cohen"

792 Publications

Use of Machine Learning-Based Software for the Screening of Thyroid Cytopathology Whole Slide Images.

Arch Pathol Lab Med 2021 Oct 20. Epub 2021 Oct 20.

The Department of Pathology (Bell, Range), Duke University Medical Center, Durham, North Carolina.

Context.—: The use of whole slide images (WSIs) in diagnostic pathology presents special challenges for the cytopathologist. Informative areas on a direct smear from a thyroid fine-needle aspiration biopsy (FNAB) smear may be spread across a large area comprising blood and dead space. Manually navigating through these areas makes screening and evaluation of FNA smears on a digital platform time-consuming and laborious. We designed a machine learning algorithm that can identify regions of interest (ROIs) on thyroid fine-needle aspiration biopsy WSIs.

Objective.—: To evaluate the ability of the machine learning algorithm and screening software to identify and screen for a subset of informative ROIs on a thyroid FNA WSI that can be used for final diagnosis.

Design.—: A representative slide from each of 109 consecutive thyroid fine-needle aspiration biopsies was scanned. A cytopathologist reviewed each WSI and recorded a diagnosis. The machine learning algorithm screened and selected a subset of 100 ROIs from each WSI to present as an image gallery to the same cytopathologist after a washout period of 117 days.

Results.—: Concordance between the diagnoses using WSIs and those using the machine learning algorithm-generated ROI image gallery was evaluated using pairwise weighted κ statistics. Almost perfect concordance was seen between the 2 methods with a κ score of 0.924.

Conclusions.—: Our results show the potential of the screening software as an effective screening tool with the potential to reduce cytopathologist workloads.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5858/arpa.2020-0712-OADOI Listing
October 2021

Photophysiological cycles in Arctic krill are entrained by weak midday twilight during the Polar Night.

PLoS Biol 2021 Oct 19;19(10):e3001413. Epub 2021 Oct 19.

UiT, The Arctic University of Norway, Faculty for Biosciences, Fisheries and Economics, Department for Arctic and Marine Biology, Tromsø, Norway.

Light plays a fundamental role in the ecology of organisms in nearly all habitats on Earth and is central for processes such as vision and the entrainment of the circadian clock. The poles represent extreme light regimes with an annual light cycle including periods of Midnight Sun and Polar Night. The Arctic Ocean extends to the North Pole, and marine light extremes reach their maximum extent in this habitat. During the Polar Night, traditional definitions of day and night and seasonal photoperiod become irrelevant since there are only "twilight" periods defined by the sun's elevation below the horizon at midday; we term this "midday twilight." Here, we characterize light across a latitudinal gradient (76.5° N to 81° N) during Polar Night in January. Our light measurements demonstrate that the classical solar diel light cycle dominant at lower latitudes is modulated during Arctic Polar Night by lunar and auroral components. We therefore question whether this particular ambient light environment is relevant to behavioral and visual processes. We reveal from acoustic field observations that the zooplankton community is undergoing diel vertical migration (DVM) behavior. Furthermore, using electroretinogram (ERG) recording under constant darkness, we show that the main migratory species, Arctic krill (Thysanoessa inermis) show endogenous increases in visual sensitivity during the subjective night. This change in sensitivity is comparable to that under exogenous dim light acclimations, although differences in speed of vision suggest separate mechanisms. We conclude that the extremely weak midday twilight experienced by krill at high latitudes during the darkest parts of the year has physiological and ecological relevance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.3001413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525745PMC
October 2021

Description and evaluation of a pathway for unaccompanied asylum-seeking children.

Arch Dis Child 2021 Oct 16. Epub 2021 Oct 16.

Paediatric Department, University College London Hospitals NHS Foundation Trust, London, UK.

Objective: (1) To describe a novel integrated pathway for unaccompanied asylum-seeking children (UASC).(2) To evaluate a population engaged with this service.

Design: Description of the integrated pathway (objective 1) and retrospective evaluation, using data from community paediatrics, infectious diseases (IDs) screening and a sexual health (SH) service (objective 2).

Setting: Unlinked data were collected from three services across three National Health Service (NHS) trusts in London.

Patients: All Camden UASC engaged with the service from 01 January 2016 to 30 March 2019.

Interventions: A multidisciplinary approach prioritising the health needs of UASC including a childre and adolescent mental health service (CAMHS) clinican and a health improvement practitioner. There are low thresholds for onward referral and universal asymptomatic screening of UASC for ID.

Main Outcome Measures: Data on demographics, unmet health needs and known outcomes.

Results: Data were available for 101 UASC, 16% female, median age 16 years (range 14-17). Physical assault/abuse was reported in 67% and 13% disclosed sexual assault/abuse, including 38% of female UASC. Mental health symptoms were documented in 77%. IDs warranting treatment were identified in 41% including latent tuberculosis (25%) and schistosomiasis (13%). Interpreters were required for 97% and initial non-attendance rates at follow-up were 40% (ID) and 49% (SH).

Conclusions: These data demonstrate high rates of historical physical and sexual assault/abuse, unmet physical, mental and emotional health needs among UASC and significant barriers to engaging with services. An integrated pathway has been successfully implemented and shown to deliver appropriate, joined-up care for UASC, consistent with current recommendations, with the potential to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2021-322319DOI Listing
October 2021

All-sky camera system providing high temporal resolution annual time series of irradiance in the Arctic.

Appl Opt 2021 Aug;60(22):6456-6468

The ArcLight observatory provides hourly continuous time series of light regime data (intensity, spectral composition, and photoperiod) from the Arctic, Svalbard at 79° N. Until now, no complete annual time series of biologically relevant light has been provided from the high Arctic due to insufficient sensitivity of commercial light sensors during the Polar Night. We describe a camera system providing all-sky images and the corresponding integrated spectral irradiance () in energy or quanta units, throughout a complete annual cycle. We present hourly-diel-annual dynamics from 2017 to 2020 of irradiance and its relation to weather conditions, sun and moon trajectories.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/AO.424871DOI Listing
August 2021

Changes in consent rate, expressed deceased donation decision-making, and family interactions in Israel-a national retrospective cohort study.

Transpl Int 2021 Sep 29. Epub 2021 Sep 29.

National Transplant Center, Tel Aviv, Israel.

This study aimed to compare the consent rate for deceased organ donation in Israel over two time periods, namely 2004-2009 (2004/9) and 2016-July 2020 (2016/20). Donor and family data were collected from the Israel National Transplantation Center Registry and included donor characteristics, reasons for family consent and refusal, and a subjective assessment of donor coordinator-family interactions. The consent rate increased from 41.6% over the period 2004/9 to 61.8% for the period 2016/20 (P < 0.0001). A significant increase in the proportion of Jewish donors was noted (49.8% in 2004/9 vs. 67.5% in 2016/20, P < 0.0001), while no increase in the consent rate for the Muslim population was noted. Religious objections as a reason for refusal decreased significantly (37.6% vs. 27.3%; P = 0.02), while the proportion of families citing donating as the "right thing to do" increased significantly (7% vs. 26.6%; P < 0.0001). Finally, a significant increase in the proportion of very positive DC-family interactions (59% to 78.3%, P < 0.0001) was noted. In conclusion, the increased consent rate in 2016/20 was associated with changes in expressed decision-making and donor coordinator-donor family interactions. Additional interventions tailored to all different populations groups need to be developed and further investigated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.14126DOI Listing
September 2021

CISH attenuates homeostatic cytokine signaling to promote lung-specific macrophage programming and function.

Sci Signal 2021 Aug 31;14(698):eabe5137. Epub 2021 Aug 31.

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

[Figure: see text].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scisignal.abe5137DOI Listing
August 2021

Human inference in changing environments with temporal structure.

Psychol Rev 2021 10 13;128(5):879-912. Epub 2021 Sep 13.

Laboratoire de Physique.

To make informed decisions in natural environments that change over time, humans must update their beliefs as new observations are gathered. Studies exploring human inference as a dynamical process that unfolds in time have focused on situations in which the statistics of observations are history-independent. Yet, temporal structure is everywhere in nature and yields history-dependent observations. Do humans modify their inference processes depending on the latent temporal statistics of their observations? We investigate this question experimentally and theoretically using a change-point inference task. We show that humans adapt their inference process to fine aspects of the temporal structure in the statistics of stimuli. As such, humans behave qualitatively in a Bayesian fashion but, quantitatively, deviate away from optimality. Perhaps more importantly, humans behave suboptimally in that their responses are not deterministic, but variable. We show that this variability itself is modulated by the temporal statistics of stimuli. To elucidate the cognitive algorithm that yields this behavior, we investigate a broad array of existing and new models that characterize different sources of suboptimal deviations away from Bayesian inference. While models with "output noise" that corrupts the response-selection process are natural candidates, human behavior is best described by sampling-based inference models, in which the main ingredient is a compressed approximation of the posterior, represented through a modest set of random samples and updated over time. This result comes to complement a growing literature on sample-based representation and learning in humans. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/rev0000276DOI Listing
October 2021

Fostamatinib for the treatment of hospitalized adults with COVD-19 A randomized trial.

Clin Infect Dis 2021 Sep 1. Epub 2021 Sep 1.

National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA.

Background: Coronavirus Disease 2019 (Covid-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response and immunothrombosis. Fostamatinib, is a novel spleen tyrosine kinase inhibitor we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response.

Methods: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with Covid-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29.

Results: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared to 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ± 0.3 vs. -2.6 ± 0.4, P = .035) and the median length in the ICU was 3 days in the fostamatinib group vs. 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs. 28, P = .027). There were trends towards more rapid reductions in C-reactive protein, D-dimer, fibrinogen and ferritin levels in the fostamatinib group.

Conclusion: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared to placebo. These results warrant further validation in larger confirmatory trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab732DOI Listing
September 2021

Molecular basis of cholesterol efflux via ABCG subfamily transporters.

Proc Natl Acad Sci U S A 2021 Aug;118(34)

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390;

The ABCG1 homodimer (G1) and ABCG5-ABCG8 heterodimer (G5G8), two members of the adenosine triphosphate (ATP)-binding cassette (ABC) transporter G family, are required for maintenance of cellular cholesterol levels. G5G8 mediates secretion of neutral sterols into bile and the gut lumen, whereas G1 transports cholesterol from macrophages to high-density lipoproteins (HDLs). The mechanisms used by G5G8 and G1 to recognize and export sterols remain unclear. Here, we report cryoelectron microscopy (cryo-EM) structures of human G5G8 in sterol-bound and human G1 in cholesterol- and ATP-bound states. Both transporters have a sterol-binding site that is accessible from the cytosolic leaflet. A second site is present midway through the transmembrane domains of G5G8. The Walker A motif of G8 adopts a unique conformation that accounts for the marked asymmetry in ATPase activities between the two nucleotide-binding sites of G5G8. These structures, along with functional validation studies, provide a mechanistic framework for understanding cholesterol efflux via ABC transporters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2110483118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403869PMC
August 2021

The temporal dynamics of opportunity costs: A normative account of cognitive fatigue and boredom.

Psychol Rev 2021 Aug 12. Epub 2021 Aug 12.

Department of Psychology.

Cognitive fatigue and boredom are two phenomenological states that reflect overt task disengagement. In this article, we present a rational analysis of the temporal structure of controlled behavior, which provides a formal account of these phenomena. We suggest that in controlling behavior, the brain faces competing behavioral and computational imperatives, and must balance them by tracking their opportunity costs over time. We use this analysis to flesh out previous suggestions that feelings associated with subjective effort, like cognitive fatigue and boredom, are the phenomenological counterparts of these opportunity cost measures, instead of reflecting the depletion of resources as has often been assumed. Specifically, we propose that both fatigue and boredom reflect the competing value of particular options that require foregoing immediate reward but can improve future performance: Fatigue reflects the value of offline computation (internal to the organism) to improve future decisions, while boredom signals the value of exploration (external in the world). We demonstrate that these accounts provide a mechanistically explicit and parsimonious account for a wide array of findings related to cognitive control, integrating and reimagining them under a single, formally rigorous framework. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1037/rev0000309DOI Listing
August 2021

SweetPea: A standard language for factorial experimental design.

Behav Res Methods 2021 Aug 6. Epub 2021 Aug 6.

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, 08544, USA.

Experimental design is a key ingredient of reproducible empirical research. Yet, given the increasing complexity of experimental designs, researchers often struggle to implement ones that allow them to measure their variables of interest without confounds. SweetPea ( https://sweetpea-org.github.io/ ) is an open-source declarative language in Python, in which researchers can describe their desired experiment as a set of factors and constraints. The language leverages advances in areas of computer science to sample experiment sequences in an unbiased way. In this article, we provide an overview of SweetPea's capabilities, and demonstrate its application to the design of psychological experiments. Finally, we discuss current limitations of SweetPea, as well as potential applications to other domains of empirical research, such as neuroscience and machine learning.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3758/s13428-021-01598-2DOI Listing
August 2021

Rationalizing constraints on the capacity for cognitive control.

Trends Cogn Sci 2021 09 28;25(9):757-775. Epub 2021 Jul 28.

Princeton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USA; Department of Psychology, Princeton University, Princeton, NJ 08544, USA.

Humans are remarkably limited in: (i) how many control-dependent tasks they can execute simultaneously, and (ii) how intensely they can focus on a single task. These limitations are universal assumptions of most theories of cognition. Yet, a rationale for why humans are subject to these constraints remains elusive. This feature review draws on recent insights from psychology, neuroscience, and machine learning, to suggest that constraints on cognitive control may result from a rational adaptation to fundamental, computational dilemmas in neural architectures. The reviewed literature implies that limitations in multitasking may result from a trade-off between learning efficacy and processing efficiency and that limitations in the intensity of commitment to a single task may reflect a trade-off between cognitive stability and flexibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tics.2021.06.001DOI Listing
September 2021

Pelagic organisms avoid white, blue, and red artificial light from scientific instruments.

Sci Rep 2021 07 22;11(1):14941. Epub 2021 Jul 22.

Department of Arctic and Marine Biology, UiT the Arctic University of Norway, Tromsø, Norway.

In situ observations of pelagic fish and zooplankton with optical instruments usually rely on external light sources. However, artificial light may attract or repulse marine organisms, which results in biased measurements. It is often assumed that most pelagic organisms do not perceive the red part of the visible spectrum and that red light can be used for underwater optical measurements of biological processes. Using hull-mounted echosounders above an acoustic probe or a baited video camera, each equipped with light sources of different colours (white, blue and red), we demonstrate that pelagic organisms in Arctic and temperate regions strongly avoid artificial light, including visible red light (575-700 nm), from instruments lowered in the water column. The density of organisms decreased by up to 99% when exposed to artificial light and the distance of avoidance varied from 23 to 94 m from the light source, depending on colours, irradiance levels and, possibly, species communities. We conclude that observations from optical and acoustic instruments, including baited cameras, using light sources with broad spectral composition in the 400-700 nm wavelengths do not capture the real state of the ecosystem and that they cannot be used alone for reliable abundance estimates or behavioural studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-94355-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298562PMC
July 2021

The Successful Anesthesia Patient Safety Officer.

Anesth Analg 2021 09;133(3):816-820

From the Department of Anesthesiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ANE.0000000000005637DOI Listing
September 2021

Missense variant in insulin receptor (Y1355H) segregates in family with fatty liver disease.

Mol Metab 2021 Jul 13;53:101299. Epub 2021 Jul 13.

The Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA. Electronic address:

A missense variant in the cytoplasmic domain of the insulin receptor (INSR) was identified by exome sequencing in affected members of a four-generation family with fatty liver disease (FLD). The variant (rs766457461, c.4063T>C, p.Y1355H) results in the substitution of histidine for a tyrosine that undergoes autophosphorylation in response to insulin stimulation in vitro. Because insulin promotes lipogenesis in hepatocytes, we hypothesized that the variant was causally linked to FLD in the family. To test this hypothesis, we used CRISPR/Cas9 technology to replace the corresponding tyrosine in mouse INSR with histidine (Y1345H). No significant differences were found in hepatic insulin signaling, as assessed by phosphorylation of INSR or AKT levels or in activation of the insulin-responsive transcription factor SREBP-1c. Glucose tolerance and hepatic triglyceride (TG) content in Insr mice fed a chow diet or diets rich in fat, sucrose or fructose did not differ significantly from WT littermates. Thus, our studies in mice failed to support the notion that INSR (Y1355H) is causally related to FLD in the family or that phosphorylation of this residue alters hepatic TG metabolism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molmet.2021.101299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371211PMC
July 2021

Inflammatory Responses with Left Ventricular Compromise after Induction of Myocardial Infarcts in Sheep (Ovis .

Comp Med 2021 06 3;71(3):240-246. Epub 2021 Jun 3.

Center for Comparative Medicine and Surgery, Icahn School of Medicine at Mt. Sinai, New York, New York.

Ischemic myocardial disease is a major cause of death among humans worldwide; it results in scarring and pallor of the myocardium and triggers an inflammatory response that contributes to impaired left ventricular function. This response includes and is evidenced by the production of several inflammatory cytokines including TNFα, IL1β, IL4, IFNγ, IL10 and IL6. In the current study, myocardial infarcts were induced in 6 mo old male castrated sheep by ligation of the left circumflex obtuse marginal arteries (OM 1 and 2). MRI was used to measure parameters of left ventricular function that include EDV, ESV, EF, SVI, dp/dt max and dp/dt min at baseline and at 4 wk and 3 mo after infarct induction. We also measured serum concentrations of an array of cytokines. Postmortem histologic findings corroborate the existence of left ventricular myocardial injury and deterioration. Our data show a correlation between serum cytokine concentrations and the development of myocardial damage and left ventricular functional compromise.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.30802/AALAS-CM-21-000005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223870PMC
June 2021

Donor Factors Associated with Familial Consent for Organ Donation among Trauma Casualties: a 10-Year Retrospective Study.

Isr Med Assoc J 2021 May;23(5):286-290

Department of General Surgery, Rabin Medical Center (Beilinson Campus), Petah Tikva, Israel.

Background: Consent rates for organ donation remain one of the most important factors determining the number of organs available for transplantation. Trauma casualties constitute a substantial part of the deceased organ donor pool and have unique characteristics that distinguish them from the general donor population. However, this group has not been extensively studied.

Objectives: To identify donor factors associated with positive familial consent for solid organ donation among trauma casualties.

Methods: This retrospective study included all trauma casualties who were admitted to the Rabin Medical Center, Beilinson hospital, during the period from January 2008 to December 2017, who were potential organ donors. Data collected included demographic features, the nature of the injury, surgical interventions, and which organs were donated. Data was collected from the Rabin Medical Center Trauma Registry.

Results: During the study period 24,504 trauma patients were admitted and 556 died over their hospital course. Of these 76 were potential donors, of whom 32 became actual donors and donated their organs. Two factors showed a statistically significant correlation to donation, namely female gender (P = 0.018) and Jewish religion of the deceased (P = 0.032).

Conclusions: Only a small group of in hospital trauma deaths were potential solid organ donors (13.7%) and less than half of these became actual donors. Consent rates were higher when the deceased was female or Jewish.
View Article and Find Full Text PDF

Download full-text PDF

Source
May 2021

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors.

Invest New Drugs 2021 10 14;39(5):1284-1297. Epub 2021 Apr 14.

Eli Lilly and Company, Indianapolis, IN, USA.

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W. ClinicalTrials.gov ID: NCT02718911 (Registration Date: May 3, 2011).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10637-021-01088-4DOI Listing
October 2021

Keep Calm and Stay Safe: The Relationship between Anxiety and Other Psychological Factors, Media Exposure and Compliance with COVID-19 Regulations.

Int J Environ Res Public Health 2021 03 11;18(6). Epub 2021 Mar 11.

Department of Psychological Medicine, Schneider Children's Medical Center of Israel, Petah Tikva 4920235, Israel.

The COVID-19 pandemic has led many countries to employ public health regulations to achieve behavioral change and stop the transmission of the virus. The factors influencing compliance with these regulations may differ from "classic" predictors for medical compliance. This study attempted to assess the effect of social communication and psychological factors on intention to comply. A cross-sectional online survey was conducted on healthy adults living in Israel ( = 697). The survey assessed the intention to comply with the state COVID-19 regulations and explored possible correlations with demographic and psychosocial factors. Data were collected during May 2020 using a Qualtrics online survey. Data were analyzed to find correlations between anxiety, uncertainty, media exposure and other variables and the level of intention to comply as self-reported. Moderation and mediation effects were studied by an integrative model of influencing factors. We found that media exposure change, trust in responsible agencies and anxiety were positively correlated with compliance, while uncertainty was correlated with noncompliance. The effect of media exposure on compliance had two components. First, media exposure was positively correlated with compliance. On the other hand, media exposure was positively correlated with uncertainty, and uncertainty was negatively correlated with compliance. Interestingly, anxiety, which was positively correlated with media exposure, also moderated the negative correlation between uncertainty and compliance. Our results highlight the important role of uncertainty and anxiety as moderators between media exposure and compliance. To increase public compliance with COVID-19 regulations, efforts should be directed at decreasing uncertainty and anxiety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph18062852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999992PMC
March 2021

Our Postpandemic World: What Will It Take to Build a Better Future for People and Planet?

Milbank Q 2021 06 30;99(2):467-502. Epub 2021 Mar 30.

Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine.

Policy Points Despite the pandemic's ongoing devastating impacts, it also offers the opportunity and lessons for building a better, fairer, and sustainable world. Transformational change will require new ways of working, challenging powerful individuals and industries who worsened the crisis, will act to exploit it for personal gain, and will work to ensure that the future aligns with their interests. A flourishing world needs strong and equitable structures and systems, including strengthened democratic, research, and educational institutions, supported by ideas and discourses that are free of opaque and conflicted influence and that challenge the status quo and inequitable distribution of power.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1468-0009.12508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241272PMC
June 2021

Unexplained recurrent implantation failures: Predictive factors of pregnancy and therapeutic management from a French multicentre study.

J Reprod Immunol 2021 06 22;145:103313. Epub 2021 Mar 22.

Sorbonne Université, APHP, Service de Médecine Interne, Département Hospitalo-Universitaire Inflammation-Immunopathologie-Biotherapie (DMU i3), F-75012, Paris, France. Electronic address:

Introduction: Recurrent implantation failure is defined as the absence of pregnancy after at least three transfers of good-quality embryos after in vitro fecundation/intracytoplasic sperm injection.

Aim: The aim of this study was to describe a multicentre cohort of women with unexplained RIF, to analyse the factors associated with clinical pregnancy and to evaluate the immunomodulatory therapies efficacy.

Methods: Women were consecutively recruited from university departments with unexplained RIF.

Results: Sixty-four women were enrolled with mean age 36 ± 3 years. The rates of clinical pregnancy in 64 women were compared in untreated and treated cycles and according to therapies used during the last prospectively followed embryo transfer. A clinical pregnancy after the transfer was noted in 56 % pregnancies on intralipids and in 50 % on prednisone, versus 5 % in untreated ones (p < 0.001). The 340 embryo transfers of these 64 women resulted in 68 clinical pregnancies and 18 live births. Clinical pregnancies were significantly more frequent in treated versus untreated embryo transfers (44 % vs 9 %; p < 0.001) with odds ratio at 8.13 (95 % CI 4.49-14.72, p < 0.0001). Cumulative pregnancy rates were higher for steroid-treated transfers than for untreated transfers when considering overall transfers before and after using steroids and also only those under steroids. Cumulative pregnancy rates were not different from steroid- and intralipid-treated embryo transfers CONCLUSIONS: In this multicentre study of women with unexplained RIF, use of immunomodulatory treatments before embryo transfer resulted in higher clinical pregnancy. Randomised, well-designed studies in well-defined population of RIF women are necessary to confirm our preliminary data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jri.2021.103313DOI Listing
June 2021

Unexplained recurrent miscarriages: predictive value of immune biomarkers and immunomodulatory therapies for live birth.

Am J Reprod Immunol 2021 08 12;86(2):e13425. Epub 2021 Apr 12.

Sorbonne Université Service de Gynécologie Obstétrique, Hôpital Armand-Trousseau, Paris, France.

Introduction: Recurrent miscarriages are defined as three or more early miscarriages before 12 weeks of gestation. The aim of this study was to describe a cohort of women with unexplained recurrent miscarriages, evaluate several potential biomarkers of immune origin, and describe the outcome of pregnancies under immunomodulatory therapies.

Methods: Women having a history of at least 3 early miscarriages without any etiology were recruited from 3 university hospitals.

Results: Among 101 women with recurrent miscarriages, overall, 652 pregnancies have been included in the analysis. Women which experienced miscarriages were older (33.3 ± 5.4 versus 31.9 ± 6.7; p = 0.03), with history of more pregnancies (4 (2-6) versus 3.5 (1-5.75); p 0.0008), and less frequently the same partner (406 (74%) versus 79 (86%); p=0.01). There was no difference in the level and frequencies of biomarkers of immune origin (NK, lymphocyte, gamma globulins and blood cytokine levels and endometrial uNK activation status), except the higher rates of positive antinuclear antibodies in women with live birth (12 (13%) versus 36 (7%); p=0.03). Among the 652 pregnancies, 215 (33%) have been treated and received either aspirin/low weighted molecular heparin (LMWH) and/or combined to different lines of immunomodulatory treatment. Patients with pregnancy under treatment had a significantly higher rate of cumulative live birth rate than those with untreated ones (43.0% vs 34.8%; p = 0.04). When compared to patients with untreated pregnancies, patients with steroids during the pregnancy had twice more chances to obtain live birth (OR 2.0, CI95% 1.1 - 3.7, p = 0.02).

Conclusions: Unexplained recurrent miscarriages could have improved obstetrical outcome under immunomodulatory therapies and in particular steroids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.13425DOI Listing
August 2021

Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis.

Cell 2021 04 24;184(8):2151-2166.e16. Epub 2021 Mar 24.

Department of Dermatology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15261, USA. Electronic address:

Cutaneous mast cells mediate numerous skin inflammatory processes and have anatomical and functional associations with sensory afferent neurons. We reveal that epidermal nerve endings from a subset of sensory nonpeptidergic neurons expressing MrgprD are reduced by the absence of Langerhans cells. Loss of epidermal innervation or ablation of MrgprD-expressing neurons increased expression of a mast cell gene module, including the activating receptor, Mrgprb2, resulting in increased mast cell degranulation and cutaneous inflammation in multiple disease models. Agonism of MrgprD-expressing neurons reduced expression of module genes and suppressed mast cell responses. MrgprD-expressing neurons released glutamate which was increased by MrgprD agonism. Inhibiting glutamate release or glutamate receptor binding yielded hyperresponsive mast cells with a genomic state similar to that in mice lacking MrgprD-expressing neurons. These data demonstrate that MrgprD-expressing neurons suppress mast cell hyperresponsiveness and skin inflammation via glutamate release, thereby revealing an unexpected neuroimmune mechanism maintaining cutaneous immune homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cell.2021.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052305PMC
April 2021

Alternative Splicing of the Inhibitory Immune Checkpoint Receptor SLAMF6 Generates a Dominant Positive Form, Boosting T-cell Effector Functions.

Cancer Immunol Res 2021 06 24;9(6):637-650. Epub 2021 Mar 24.

Sharett Institute of Oncology, Hadassah Hebrew University Hospital, Jerusalem, Israel.

SLAMF6 is a homotypic receptor of the Ig-superfamily associated with progenitor-exhausted T cells. Here we show that in humans, SLAMF6 has three splice isoforms involving its V-domain. Although the canonical receptor inhibited T-cell activation through SAP recruitment, the short isoform SLAMF6 had a strong agonistic effect. The costimulatory action depended on protein phosphatase SHP1 and led to a cytotoxic molecular profile mediated by the expression of TBX21 and RUNX3. Patients treated with immune checkpoint blockade showed a shift toward SLAMF6 in peripheral blood T cells. We developed splice-switching antisense oligonucleotides (ASO) designed to target the relevant SLAMF6 splice junction. Our ASOs enhanced SLAMF6 expression in human tumor-infiltrating lymphocytes and improved their capacity to inhibit human melanoma in mice. The yin-yang relationship of SLAMF6 splice isoforms may represent a balancing mechanism that could be exploited to improve cancer immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/2326-6066.CIR-20-0800DOI Listing
June 2021

COVID-19 vaccine as a cause for unilateral lymphadenopathy detected by 18F-FDG PET/CT in a patient affected by melanoma.

Eur J Nucl Med Mol Imaging 2021 07 6;48(8):2659-2660. Epub 2021 Mar 6.

Sharett Institute of Oncology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00259-021-05278-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936232PMC
July 2021

A marine zooplankton community vertically structured by light across diel to interannual timescales.

Biol Lett 2021 02 24;17(2):20200810. Epub 2021 Feb 24.

Department of Biological Sciences, University of Bergen, 5020 Bergen, Norway.

The predation risk of many aquatic taxa is dominated by visually searching predators, commonly a function of ambient light. Several studies propose that changes in visual predation will become a major climate-change impact on polar marine ecosystems. The High Arctic experiences extreme seasonality in the light environment, from 24 h light to 24 h darkness, and therefore provides a natural laboratory for studying light and predation risk over diel to seasonal timescales. Here, we show that zooplankton (observed using acoustics) in an Arctic fjord position themselves vertically in relation to light. A single isolume (depth-varying line of constant light intensity, the value of which is set at the lower limit of photobehaviour reponses of spp. and krill) forms a ceiling on zooplankton distribution. The vertical distribution is structured by light across timescales, from the deepening of zooplankton populations at midday as the sun rises in spring, to the depth to which zooplankton ascend to feed during diel vertical migration. These results suggest that zooplankton might already follow a foraging strategy that will keep visual predation risk roughly constant under changing light conditions, such as those caused by the reduction of sea ice, but likely with energetic costs such as lost feeding opportunities as a result of altered habitat use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1098/rsbl.2020.0810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086989PMC
February 2021

Genetic and Metabolic Determinants of Plasma Levels of ANGPTL8.

J Clin Endocrinol Metab 2021 05;106(6):1649-1667

Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Context: ANGPTL8 (A8) plays a key role in determining the tissue fate of circulating triglycerides (TGs). Plasma A8 levels are associated with several parameters of glucose and TG metabolism, but the causality of these relationships and the contribution of genetic variants to differences in A8 levels have not been explored.

Objective: To characterize the frequency distribution of plasma A8 levels in a diverse population using a newly-developed enzyme-linked immunosorbent assay (ELISA) and to identify genetic factors contributing to differences in plasma A8 levels.

Methods: We studied a population-based sample of Dallas County, comprising individuals in the Dallas Heart Study (DHS-1, n = 3538; DHS-2, n = 3283), including 2131 individuals with repeated measurements 7 to 9 years apart (age 18-85 years; >55% female; 52% Black; 29% White; 17% Hispanic; and 2% other). The main outcome measures were associations of A8 levels with body mass index (BMI), plasma levels of glucose, insulin, lipids, and hepatic TGs, as well as DNA variants identified by exome-wide sequencing.

Results: A8 levels varied over a 150-fold range (2.1-318 ng/mL; median, 13.3 ng/mL) and differed between racial/ethnic groups (Blacks > Hispanics > Whites). A8 levels correlated with BMI, fasting glucose, insulin, and TG levels. A variant in A8, R59W, accounted for 17% of the interindividual variation in A8 levels but was not associated with the metabolic parameters correlated with plasma A8 concentrations.

Conclusions: A8 levels were strongly associated with indices of glucose and TG metabolism, but the lack of association of genetic variants at the A8 locus that impact A8 levels with these parameters indicates that differences in A8 levels are not causally related to the associated metabolic phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8118582PMC
May 2021

Is Activity Silent Working Memory Simply Episodic Memory?

Trends Cogn Sci 2021 04 4;25(4):284-293. Epub 2021 Feb 4.

Department of Psychology, Princeton University, Princeton, NJ, USA; Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Working memory (WM) maintains task-relevant information in a state ready for processing. While traditional theories assume that sustained neuronal activity is responsible for WM, the Activity Silent WM (ASWM) account proposes that maintenance can also be supported by short-term synaptic weight changes. Here, we argue that the evidence for ASWM can be explained more parsimoniously by the involvement of episodic memory (EM) in WM tasks. Like ASWM, EM relies on rapid synaptic modification that is also activity silent; however, while ASWM posits transient synaptic modifications, EM traces persist over longer time periods. We discuss how, despite this difference, well-established EM mechanisms can account for the key findings attributed to ASWM, and describe predictions of this account.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tics.2021.01.003DOI Listing
April 2021

Is conservation based on best available science creating an ecological trap for an imperiled lagomorph?

Ecol Evol 2021 Jan 19;11(2):912-930. Epub 2020 Dec 19.

Department of Environmental and Forest Biology SUNY College of Environmental Science and Forestry Syracuse NY USA.

Habitat quality regulates fitness and population density, making it a key driver of population size. Hence, increasing habitat quality is often a primary goal of species conservation. Yet, assessments of fitness and density are difficult and costly to obtain. Therefore, species conservation often uses "best available science," extending inferences across taxa, space, or time, and inferring habitat quality from studies of habitat selection. However, there are scenarios where habitat selection is not reflective of habitat quality, and this can lead to maladaptive management strategies. The New England cottontail () is an imperiled shrubland obligate lagomorph whose successful recovery hinges on creation of suitable habitat. Recovery of this species is also negatively impacted by the non-native eastern cottontail (), which can competitively exclude New England cottontails from preferred habitat. Herein, we evaluate habitat quality for adult and juvenile New England and eastern cottontails using survival and density as indicators. Our findings did not support selection following an ideal free distribution by New England cottontails. Instead, selected resources, which are a target of habitat management, were associated with low survival and density and pointed to a complex trade-off between density, survival, habitat, and the presence of eastern cottontails. Further, movement distance was inversely correlated with survival in both species, suggesting that habitat fragmentation limits the ability of cottontails to freely distribute based on habitat quality. While habitat did not directly regulate survival of juvenile cottontails, tick burden had a strong negative impact on juvenile cottontails in poor body condition. Given the complex interactions among New England cottontails, eastern cottontails, and habitat, directly assessing and accounting for factors that limit New England cottontail habitat quality in management plans is vital to their recovery. Our study demonstrates an example of management for possible ecological trap conditions via the application of incomplete knowledge.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ece3.7104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820145PMC
January 2021
-->