East Asian summer monsoon delivers large abundances of very-short-lived organic chlorine substances to the lower stratosphere.

Deep convection in the Asian summer monsoon is a significant transport process for lifting pollutants from the planetary boundary layer to the tropopause level. This process enables efficient injection into the stratosphere of reactive species such as chlorinated very-short-lived substances (Cl-VSLSs) that deplete ozone. Past studies of convective transport associated with the Asian summer monsoon have focused mostly on the south Asian summer monsoon. Airborne observations reported in this work identify the East Asian summer monsoon convection as an effective transport pathway that carried record-breaking levels of ozone-depleting Cl-VSLSs (mean organic chlorine from these VSLSs ~500 ppt) to the base of the stratosphere. These unique observations show total organic chlorine from VSLSs in the lower stratosphere over the Asian monsoon tropopause to be more than twice that previously reported over the tropical tropopause. Considering the recently observed increase in Cl-VSLS emissions and the ongoing strengthening of the East Asian summer monsoon under global warming, our results highlight that a reevaluation of the contribution of Cl-VSLS injection via the Asian monsoon to the total stratospheric chlorine budget is warranted.

Safety of direct-acting oral anticoagulant (DOAC) prescribing: OpenSAFELY-TPP analysis of 20.5 million adults' electronic health records.

BACKGROUND: During the COVID-19 pandemic many patients were switched from warfarin to DOACs which require the creatinine clearance calculated to ensure the correct dose is prescribed to avoid bleeding or reduced efficacy. AIM: To identify the study population proportion prescribed a DOAC. Of these, the proportion with recorded: weight, estimated Glomerular Filtration Rate (eGFR), creatinine, creatinine clearance (CrCl) and atrial fibrillation (AF). To analyse the proportion of patients with recorded AF and CrCl prescribed a recommended DOAC dose. DESIGN & SETTING: A retrospective cohort study of 20.5 million adult NHS patients' electronic health records (EHRs) in England in the OpenSAFELY-TPP platform (January 2018 to February 2023). METHOD: Patients on DOACs were analysed for age, sex, recorded weight, eGFR, creatinine, CrCl and AF. Prescribed DOAC doses in patients with recorded AF were compared to recommended doses for recorded CrCl and determined as either recommended, underdose or overdose. RESULTS: In February 2023, weight, eGFR, creatinine, CrCl, AF and, AF and CrCl were recorded in 72.8%; 92.4%; 94.3%; 73.5%; 73.9% of study population respectively. Both AF and CrCl were recorded for 56.7% of patients. Of these, 86.2% received the recommended and 13.8% non-recommended DOAC doses. CONCLUSIONS: CrCl is not recorded for a substantial number of patients on DOACs. We recommend that national organisations tasked with safety, collectively update guidance on the appropriate weight to use in the Cockcroft-Gault equation, clarify that CrCl is not equivalent to eGFR and work with GP clinical system suppliers to standardise the calculation of CrCl in the EHR.

Application of lidar to assess the habitat selection of an endangered small mammal in an estuarine wetland environment.

Light detection and ranging (lidar) has emerged as a valuable tool for examining the fine-scale characteristics of vegetation. However, lidar is rarely used to examine coastal wetland vegetation or the habitat selection of small mammals. Extensive anthropogenic modification has threatened the endemic species in the estuarine wetlands of the California coast, such as the endangered salt marsh harvest mouse (Reithrodontomys raviventris; SMHM). A better understanding of SMHM habitat selection could help managers better protect this species. We assessed the ability of airborne topographic lidar imagery in measuring the vegetation structure of SMHM habitats in a coastal wetland with a narrow range of vegetation heights. We also aimed to better understand the role of vegetation structure in habitat selection at different spatial scales. Habitat selection was modeled from data compiled from 15 small mammal trapping grids collected in the highly urbanized San Francisco Estuary in California, USA. Analyses were conducted at three spatial scales: microhabitat (25 m2), mesohabitat (2025 m2), and macrohabitat (~10,000 m2). A suite of structural covariates was derived from raw lidar data to examine vegetation complexity. We found that adding structural covariates to conventional habitat selection variables significantly improved our models. At the microhabitat scale in managed wetlands, SMHM preferred areas with denser and shorter vegetation and selected for proximity to levees and taller vegetation in tidal wetlands. At the mesohabitat scale, SMHM were associated with a lower percentage of bare ground and with pickleweed (Salicornia pacifica) presence. All covariates were insignificant at the macrohabitat scale. Our results suggest that SMHM preferentially selected microhabitats with access to tidal refugia and mesohabitats with consistent food sources. Our findings showed that lidar can contribute to improving our understanding of habitat selection of wildlife in coastal wetlands and help to guide future conservation of an endangered species.

Safety of e-cigarettes and nicotine patches as stop-smoking aids in pregnancy: Secondary analysis of the Pregnancy Trial of E-cigarettes and Patches (PREP) randomized controlled trial.

AIMS: The aim of this study was to examine the safety of e-cigarettes (EC) and nicotine patches (NRT) when used to help pregnant smokers quit. DESIGN: A recent trial of EC versus NRT reported safety outcomes in the randomized arms. We conducted a further analysis based on product use. SETTING: Twenty-three hospitals in England and a stop-smoking service in Scotland took part. PARTICIPANTS: The participants comprised 1140 pregnant smokers. INTERVENTIONS: We compared women using and not using EC and NRT regularly during pregnancy. MEASUREMENTS: Measurements included nicotine intake compared with baseline, birth weight, other pregnancy outcomes, adverse events, maternal respiratory symptoms and relapse in early abstainers. FINDINGS: Use of EC was more common than use of NRT (47.3% vs 21.6%, P < 0.001). Women who stopped smoking (abstainers) and used EC at the end-of-pregnancy (EOP) reduced their salivary cotinine by 45% [49.3 ng/ml, 95% confidence interval (CI) = -79.8 to -10]. Only one abstainer used NRT at EOP. In dual users, cotinine increased by 19% (24 ng/ml, 95% CI = 3.5-68). In women reporting a reduction of at least 50% in cigarette consumption, cotinine levels increased by 10% in those using nicotine products and by 9% in those who did not. Birth weights in dual users and exclusive smokers were the same (3.1 kg). Birth weight in abstainers using either nicotine product was higher than in smokers [3.3 kg, standard deviation (SD) = 0.7] versus 3.1 kg, SD = 0.6; difference = 0.15 kg, 95% CI = 0.05-0.25) and not different from abstainers not using nicotine products (3.1 kg, SD = 0.8). Abstainers and smokers using nicotine products had no worse pregnancy outcomes or more adverse events than abstainers and smokers not using them. EC users reported more improvements than non-users in cough [adjusted relative risk (aRR) = 0.59, 95% CI = 0.37-0.93] and phlegm (aRR = 0.53, 95% CI = 0.31-0.92), controlling for smoking status. EC or NRT use had no association with relapse. CONCLUSIONS: Regular use of e-cigarettes or nicotine patches by pregnant smokers does not appear to be associated with any adverse outcomes.

Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis.

Positive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current pilot mechanistic randomized controlled trial was to test the effects of a positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis. Participants included 44 patients with a physician-confirmed diagnosis of rheumatoid arthritis (n = 29 included in functional magnetic resonance imaging (fMRI) analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre-and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Savoring significantly reduced experimental pain intensity ratings relative to rest (P < .001). Savoring also increased cerebral blood flow in the ventromedial prefrontal cortex and increased connectivity between the ventromedial prefrontal cortex and caudate during noxious thermal stimulation relative to Slow Breathing (z = 2.3 voxelwise, false discovery rate cluster corrected P = .05). Participants in the Savoring condition also reported significantly increased positive emotions (ps < .05) and reduced anhedonic symptoms (P < .01) from pre- to post-intervention. These findings suggest that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations. PERSPECTIVE: Savoring Meditation is a novel positive emotion-enhancing intervention designed for patients with chronic pain. The present findings provide preliminary evidence that Savoring Meditation is acutely analgesic, and engages neural and subjective emotional targets that are relevant to pain self-management. Future work should evaluate the clinical translation of these findings.

Nuclear environmental DNA resolves fine-scale population genetic structure in an aquatic habitat.

There is considerable potential for nuclear genomic material in environmental DNA (eDNA) to inform us of population genetic structure within aquatic species. We tested if nuclear allelic composition data sourced from eDNA can resolve fine scale spatial genetic structure of the cichlid fish Astatotilapia calliptera in Lake Masoko, Tanzania. In this ∼35 m deep crater lake the species is diverging into two genetically distinguishable ecomorphs, separated by a thermo-oxycline at ∼15 m that divides biologically distinct water masses. We quantified population genetic structure along a depth transect using single nucleotide polymorphisms (SNPs) derived from genome sequencing of 530 individuals. This population genetic structure was reflected in a focal set of SNPs that were also reliably amplified from eDNA - with allele frequencies derived from eDNA reflecting those of fish within each depth zone. Thus, by targeting known genetic variation between populations within aquatic eDNA, we measured genetic structure within the focal species.

Prophylactic cyclo-oxygenase inhibitor drugs for the prevention of morbidity and mortality in extremely preterm infants: a clinical practice guideline incorporating family values and preferences.

ImportanceProphylactic cyclo-oxygenase inhibitors (COX-Is) such as indomethacin, ibuprofen and acetaminophen may prevent morbidity and mortality in extremely preterm infants (born ≤28 weeks' gestation). However, there is controversy around which COX-I, if any, is the most effective and safest, which has resulted in considerable variability in clinical practice. Our objective was to develop rigorous and transparent clinical practice guideline recommendations for the prophylactic use of COX-I drugs for the prevention of mortality and morbidity in extremely preterm infants. The Grading of Recommendations Assessment, Development and Evaluation evidence-to-decision framework for multiple comparisons was used to develop the guideline recommendations. A 12-member panel, including 5 experienced neonatal care providers, 2 methods experts, 1 pharmacist, 2 parents of former extremely preterm infants and 2 adults born extremely preterm, was convened. A rating of the most important clinical outcomes was established a priori. Evidence from a Cochrane network meta-analysis and a cross-sectional mixed-methods study exploring family values and preferences were used as the primary sources of evidence. The panel recommended that prophylaxis with intravenous indomethacin may be considered in extremely preterm infants (conditional recommendation, moderate certainty in estimate of effects). Shared decision making with parents was encouraged to evaluate their values and preferences prior to therapy. The panel recommended against routine use of ibuprofen prophylaxis in this gestational age group (conditional recommendation, low certainty in the estimate of effects). The panel strongly recommended against use of prophylactic acetaminophen (strong recommendation, very low certainty in estimate of effects) until further research evidence is available.

Helping pregnant smokers quit: a multi-centre randomised controlled trial of electronic cigarettes versus nicotine replacement therapy.

Background: Some pregnant smokers try e-cigarettes, but effectiveness and safety of such use are unknown. Objectives: To compare effectiveness and safety of nicotine patches and e-cigarettes in pregnancy. Design: A pragmatic multi-centre randomised controlled trial. Setting: Twenty-three hospitals across England, and a Stop Smoking Service in Scotland. Participants: One thousand one hundred and forty pregnant daily smokers (12-24 weeks' gestation) motivated to stop smoking, with no strong preference for using nicotine patches or e-cigarettes. Interventions: Participants in the e-cigarette arm were posted a refillable e-cigarette device with two 10 ml bottles of tobacco-flavoured e-liquid (18 mg nicotine). Participants in the nicotine patches arm were posted a 2-week supply of 15 mg/16-hour nicotine patches. Supplies were provided for up to 8 weeks. Participants sourced further supplies themselves as needed. Participants in both arms received support calls prior to their target quit date, on the quit date, and weekly for the next 4 weeks. Outcome measures: The primary outcome was validated prolonged abstinence at the end of pregnancy. Participants lost to follow-up or not providing biochemical validation were included as non-abstainers. Secondary outcomes included self-reported abstinence at different time points, treatment adherence and safety outcomes. Results: Only 55% of self-reported abstainers mailed back useable saliva samples. Due to this, validated sustained abstinence rates were low (6.8% vs. 4.4% in the e-cigarettes and nicotine patches arms, respectively, risk ratio = 1.55, 95% confidence interval 0.95 to 2.53; Bayes factor = 2.7). In a pre-specified sensitivity analysis that excluded abstainers using non-allocated products, the difference became significant (6.8% vs. 3.6%, risk ratio = 1.93, 95% confidence interval 1.14 to 3.26; Bayes factor = 10). Almost a third of the sample did not set a target quit date and the uptake of support calls was low, as was the initial product use. At end of pregnancy, 33.8% versus 5.6% of participants were using their allocated product in the e-cigarettes versus nicotine patches arm (risk ratio = 6.01, 95% confidence interval 4.21 to 8.58). Regular use of e-cigarettes in the nicotine patches arm was more common than use of nicotine replacement products in the e-cigarette arm (17.8% vs. 2.8%). Rates of adverse events and adverse birth outcomes were similar in the two study arms, apart from participants in the e-cigarette arm having fewer infants with low birthweight (<2500 g) (9.6% vs. 14.8%, risk ratio = 0.65, 95% confidence interval 0.47 to 0.90; Bayes factor = 10.3). Limitations: Low rates of validation reduced the study power. A substantial proportion of participants did not use the support on offer sufficiently to test its benefits. Sample size may have been too small to detect differences in less frequent adverse effects. Conclusions: E-cigarettes were not significantly more effective than nicotine patches in the primary analysis, but when e-cigarettes use in the nicotine patches arm was accounted for, e-cigarettes were almost twice as effective as patches in all abstinence outcomes. In pregnant smokers seeking help, compared to nicotine patches, e-cigarettes are probably more effective, do not pose more risks to birth outcomes assessed in this study and may reduce the incidence of low birthweight. Future work: Routine monitoring of smoking cessation and birth outcomes in pregnant women using nicotine patches and e-cigarettes and further studies are needed to confirm these results. Trial registration: This trial is registered as ISRCTN62025374 and Eudract 2017-001237-65. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 13. See the NIHR Journals Library website for further project information.

Like many other smokers in the UK, some pregnant smokers try to limit or stop smoking with the help of e-cigarettes. It is not known whether this helps with stopping smoking and whether using e-cigarettes has any bad effects on the baby. We recruited 1140 pregnant smokers who wanted to quit. A random half were given nicotine patches, which are commonly used to help smokers quit. The other half were given an e-cigarette. They also received six weekly phone calls to support them in stopping smoking. We then looked at how many in each group stopped smoking by the end of pregnancy. More women stopped smoking in the group that was given an e-cigarette, but the difference was small and could be due to chance. However, some of the women in the nicotine patch group who had successfully stopped smoking were using e-cigarettes rather than patches. When these (and women in the e-cigarette group who used patches) were not counted, e-cigarettes helped almost twice as many women stop smoking than patches. E-cigarettes were better than patches in preventing low birthweight (having babies who weigh less than 2.5 kg). Otherwise, women given patches and those given e-cigarettes (and their babies) had similar numbers of medical complications. For pregnant women who smoke and need help to quit, e-cigarettes are probably more helpful than nicotine patches, and do not pose any additional risks to women or their babies.

Effects of Savoring Meditation on Positive Emotions and Pain-Related Brain Function: A Mechanistic Randomized Controlled Trial in People With Rheumatoid Arthritis.

Positive emotions are a promising target for intervention in chronic pain, but mixed findings across trials to date suggest that existing interventions may not be optimized to efficiently engage the target. The aim of the current mechanistic randomized controlled trial was to test the effects of a single skill positive emotion-enhancing intervention called Savoring Meditation on pain-related neural and behavioral targets in patients with rheumatoid arthritis (RA). Participants included 44 patients with a physician-confirmed diagnosis of RA (n=29 included in fMRI analyses), who were randomized to either Savoring Meditation or a Slow Breathing control. Both meditation interventions were brief (four 20-minute sessions). Self-report measures were collected pre- and post-intervention. An fMRI task was conducted at post-intervention, during which participants practiced the meditation technique on which they had been trained while exposed to non-painful and painful thermal stimuli. Relative to Slow Breathing, Savoring significantly reduced experimental pain intensity ratings relative to rest (p<.001), increased cerebral blood flow in the ventromedial prefrontal cortex (vmPFC) and increased connectivity between the vmPFC and caudate during noxious thermal stimulation (z=2.3 voxelwise, FDR cluster corrected p=0.05). Participants in the Savoring condition also reported significantly increased positive emotions (ps<.05) and reduced anhedonic symptoms (p<.01) from pre- to post-intervention. These findings suggest that that Savoring recruits reward-enhancing corticostriatal circuits in the face of pain, and future work should extend these findings to evaluate if these mechanisms of Savoring are associated with improved clinical pain outcomes in diverse patient populations.

Estradiol- and Progesterone-Associated Changes in microRNA-Induced Silencing and Reduced Antiseizure Efficacy of an Antagomir in Female Mice.

About one-third of individuals living with epilepsy have treatment-resistant seizures. Alternative therapeutic strategies are thus urgently needed. One potential novel treatment target is miRNA-induced silencing, which is differentially regulated in epilepsy. Inhibitors (antagomirs) of specific microRNAs (miRNAs) have shown therapeutic promise in preclinical epilepsy studies; however, these studies were mainly conducted in male rodent models, and research into miRNA regulation in females and by female hormones in epilepsy is scarce. This is problematic because female sex and the menstrual cycle can affect the disease course of epilepsy and may, therefore, also alter the efficacy of potential miRNA-targeted treatments. Here, we used the proconvulsant miRNA miR-324-5p and its target, the potassium channel Kv4.2, as an example to test how miRNA-induced silencing and the efficacy of antagomirs in epilepsy are altered in female mice. We showed that Kv4.2 protein is reduced after seizures in female mice similar to male mice; however, in contrast to male mice, miRNA-induced silencing of Kv4.2 is unchanged, and miR-324-5p activity, as measured by the association with the RNA-induced silencing complex, is reduced in females after seizure. Moreover, an miR-324-5p antagomir does not consistently reduce seizure frequency or increase Kv4.2 in female mice. As a possible underlying mechanism, we found that miR-324-5p activity and the silencing of Kv4.2 in the brain were differentially correlated with plasma levels of 17ß-estradiol and progesterone. Our results suggest that hormonal fluctuations in sexually mature female mice influence miRNA-induced silencing and could alter the efficacy of potential future miRNA-based treatments for epilepsy in females.

Cooperation and partner choice among Agta hunter-gatherer children: An evolutionary developmental perspective.

Examining development is essential for a full understanding of behaviour, including how individuals acquire traits and how adaptive evolutionary forces shape these processes. The present study explores the development of cooperative behaviour among the Agta, a Filipino hunter-gatherer population. A simple resource allocation game assessing both levels of cooperation (how much children shared) and patterns of partner choice (who they shared with) was played with 179 children between the ages of 3 and 18. Children were given five resources (candies) and for each was asked whether to keep it for themselves or share with someone else, and if so, who this was. Between-camp variation in children's cooperative behaviour was substantial, and the only strong predictor of children's cooperation was the average level of cooperation among adults in camp; that is, children were more cooperative in camps where adults were more cooperative. Neither age, sex, relatedness or parental levels of cooperation were strongly associated with the amount children shared. Children preferentially shared with close kin (especially siblings), although older children increasingly shared with less-related individuals. Findings are discussed in terms of their implications for understanding cross-cultural patterns of children's cooperation, and broader links with human cooperative childcare and life history evolution.

Efficacy of a Smoking Cessation Intervention for Survivors of Cervical Intraepithelial Neoplasia or Cervical Cancer: A Randomized Controlled Trial.

PURPOSE: Women who smoke and have a history of cervical intraepithelial neoplasia (CIN) or cervical cancer represent a vulnerable subgroup at elevated risk for recurrence, poorer cancer treatment outcomes, and decreased quality of life. The purpose of this study was to evaluate the long-term efficacy of Motivation And Problem Solving (MAPS), a novel treatment well-suited to meeting the smoking cessation needs of this population. METHODS: Women who were with a history of CIN or cervical cancer, age 18 years and older, spoke English or Spanish, and reported current smoking (≥100 lifetime cigarettes plus any smoking in the past 30 days) were eligible. Participants (N = 202) were recruited in clinic in Oklahoma City and online nationally and randomly assigned to (1) standard treatment (ST) or (2) MAPS. ST consisted of repeated referrals to a tobacco cessation quitline, self-help materials, and combination nicotine replacement therapy (patch plus lozenge). MAPS comprised all ST components plus up to six proactive telephone counseling sessions over 12 months. Logistic regression and generalized estimating equations evaluated the intervention. The primary outcome was self-reported 7-day point prevalence abstinence from tobacco at 18 months, with abstinence at 3, 6, and 12 months and biochemically confirmed abstinence as secondary outcomes. RESULTS: There was no significant effect for MAPS over ST at 18 months (14.2% v 12.9%, P = .79). However, there was a significant condition × assessment interaction (P = .015). Follow-up analyses found that MAPS (v ST) abstinence rates were significantly greater at 12 months (26.4% v 11.9%, P = .017; estimated OR, 2.60; 95% CI, 1.19 to 5.89). CONCLUSION: MAPS led to a greater than two-fold increase in smoking abstinence among survivors of CIN and cervical cancer at 12 months. At 18 months, abstinence in MAPS declined to match the control condition and the treatment effect was no longer significant.

Hospital bed replacement for acute care of children at home during the COVID-19 pandemic through a Hospital-in-the-Home programme.

OBJECTIVES: During the COVID-19 pandemic, we expanded our Hospital-in-the-Home (HITH) programme to increase capacity and manage COVID-19-positive children. We aimed to assess impact on overall HITH activity and COVID-19-positive outcomes. DESIGN: Prospective comparative cohort study. SETTING: The largest paediatric HITH in Australasia, at The Royal Children's Hospital Melbourne. PATIENTS: Children 0-18 years admitted to HITH during the pandemic. INTERVENTION: We developed a COVID-19 responsive service, and a guideline for COVID-19-positive patients. We compared overall activity prior to and during the pandemic, and COVID-19-positive admissions with different variants. MAIN OUTCOMES: We compared outcomes for all HITH patients before and during the pandemic, and for COVID-19-positive patients admitted first to hospital versus directly to HITH. RESULTS: HITH managed 7319 patients from March 2020 to March 2022, a 21% increase to previously, with a 132% telehealth increase. 421 COVID-19-positive patients (3 days-18.9 years) were admitted to HITH, predominantly high risk (63%) or moderately unwell (33%). Rates of childhood infection in Victoria, with proportion admitted to HITH were: original/alpha variant-3/100 000/month, 0.7%; delta-92/100 000/month, 0.8%; omicron-593/100 000/month, 0.3%. Eligible parents of only 29 of 71 (41%) high-risk children were vaccinated. COVID-19-positive children admitted directly to HITH were less likely to receive COVID-19-specific treatment than those admitted to hospital first (14 of 113 (12%) vs 33 of 46 (72%), p<0.001), reflecting more severe respiratory, but not other features in inpatients. 15 of 159 (10%) were readmitted to hospital, but none deteriorated rapidly. CONCLUSIONS: COVID-19-positive children at high risk or with moderate symptoms can be managed safely via HITH at home, the ideal place for children during the pandemic.

Twenty-One Flavors of Type 1 Innate Lymphoid Cells with PD-1 (Programmed Cell Death-1 Receptor) Sprinkles.

Innate lymphoid cells (ILCs) are tissue-resident immune cells that have been recently implicated in initiating and driving anti-tumor responses. ILCs are classified into three main groups, namely type 1 ILCs (ILC1), type 2 ILCs, and type 3 ILCs. All three groups have been implicated in either eliciting pro or anti-tumor immune responses in different cancer subtypes with the consensus that ILCs cannot be overlooked within the field of anti-tumor immune responses. In this review, we will specifically expand on the knowledge on ILC1, their characterization, function, and plasticity in anti-cancer immune responses. Within this premise, we will discuss caveats of ILC1 characterization, and expand on the expression and function of immune checkpoint receptors within ILC1 subsets, specifically focusing on the role of programmed cell death-1 receptor in controlling specific ILC1 responses. We summarize that ILC1s are a vital component in initiating anti-tumor responses and can be boosted by checkpoint receptors.

Moving beyond response times with accessible measures of manual dynamics.

Button-press measures of response time (RT) and accuracy have long served a central role in psychological research. However, RT and accuracy provide limited insight into how cognitive processes unfold over time. To address this limitation, researchers have used hand-tracking techniques to investigate how cognitive processes unfold over the course of a response, are modulated by recent experience, and function across the lifespan. Despite the efficacy of these techniques for investigating a wide range of psychological phenomena, widespread adoption of hand-tracking techniques within the field is hindered by a range of factors, including equipment costs and the use of specialized software. Here, we demonstrate that the behavioral dynamics previously observed with specialized motion-tracking equipment in an Eriksen flanker task can be captured with an affordable, portable, and easy-to-assemble response box. Six-to-eight-year-olds and adults (N = 90) completed a computerized version of the flanker task by pressing and holding a central button until a stimulus array appeared. Participants then responded by releasing the central button and reaching to press one of two response buttons. This method allowed RT to be separated into initiation time (when the central button was released) and movement time (time elapsed between initiation and completion of the response). Consistent with previous research using motion-tracking techniques, initiation times and movement times revealed distinct patterns of effects across trials and between age groups, indicating that the method used in the current study presents a simple solution for researchers from across the psychological and brain sciences looking to move beyond RTs.

Comparison of accuracy and reproducibility of colposcopic impression based on a single image versus a two-minute time series of colposcopic images.

OBJECTIVE: Colposcopy is an important part of cervical screening/management programs. Colposcopic appearance is often classified, for teaching and telemedicine, based on static images that do not reveal the dynamics of acetowhitening. We compared the accuracy and reproducibility of colposcopic impression based on a single image at one minute after application of acetic acid versus a time-series of 17 sequential images over two minutes. METHODS: Approximately 5000 colposcopic examinations conducted with the DYSIS colposcopic system were divided into 10 random sets, each assigned to a separate expert colposcopist. Colposcopists first classified single two-dimensional images at one minute and then a time-series of 17 sequential images as 'normal,' 'indeterminate,' 'high grade,' or 'cancer'. Ratings were compared to histologic diagnoses. Additionally, 5 colposcopists reviewed a subset of 200 single images and 200 time series to estimate intra- and inter-rater reliability. RESULTS: Of 4640 patients with adequate images, only 24.4% were correctly categorized by single image visual assessment (11% of 64 cancers; 31% of 605 CIN3; 22.4% of 558 CIN2; 23.9% of 3412 < CIN2). Individual colposcopist accuracy was low; Youden indices (sensitivity plus specificity minus one) ranged from 0.07 to 0.24. Use of the time-series increased the proportion of images classified as normal, regardless of histology. Intra-rater reliability was substantial (weighted kappa = 0.64); inter-rater reliability was fair ( weighted kappa = 0.26). CONCLUSION: Substantial variation exists in visual assessment of colposcopic images, even when a 17-image time series showing the two-minute process of acetowhitening is presented. We are currently evaluating whether deep-learning image evaluation can assist classification.

The antimicrobial peptide cathelicidin drives development of experimental autoimmune encephalomyelitis in mice by affecting Th17 differentiation.

Multiple sclerosis (MS) is a highly prevalent demyelinating autoimmune condition; the mechanisms regulating its severity and progression are unclear. The IL-17-producing Th17 subset of T cells has been widely implicated in MS and in the mouse model, experimental autoimmune encephalomyelitis (EAE). However, the differentiation and regulation of Th17 cells during EAE remain incompletely understood. Although evidence is mounting that the antimicrobial peptide cathelicidin profoundly affects early T cell differentiation, no studies have looked at its role in longer-term T cell responses. Now, we report that cathelicidin drives severe EAE disease. It is released from neutrophils, microglia, and endothelial cells throughout disease; its interaction with T cells potentiates Th17 differentiation in lymph nodes and Th17 to exTh17 plasticity and IFN-γ production in the spinal cord. As a consequence, mice lacking cathelicidin are protected from severe EAE. In addition, we show that cathelicidin is produced by the same cell types in the active brain lesions in human MS disease. We propose that cathelicidin exposure results in highly activated, cytokine-producing T cells, which drive autoimmunity; this is a mechanism through which neutrophils amplify inflammation in the central nervous system.