Overshooting the critical threshold for the Greenland ice sheet.

Melting of the Greenland ice sheet (GrIS) in response to anthropogenic global warming poses a severe threat in terms of global sea-level rise (SLR)1. Modelling and palaeoclimate evidence suggest that rapidly increasing temperatures in the Arctic can trigger positive feedback mechanisms for the GrIS, leading to self-sustained melting2-4, and the GrIS has been shown to permit several stable states5. Critical transitions are expected when the global mean temperature (GMT) crosses specific thresholds, with substantial hysteresis between the stable states6. Here we use two independent ice-sheet models to investigate the impact of different overshoot scenarios with varying peak and convergence temperatures for a broad range of warming and subsequent cooling rates. Our results show that the maximum GMT and the time span of overshooting given GMT targets are critical in determining GrIS stability. We find a threshold GMT between 1.7 °C and 2.3 °C above preindustrial levels for an abrupt ice-sheet loss. GrIS loss can be substantially mitigated, even for maximum GMTs of 6 °C or more above preindustrial levels, if the GMT is subsequently reduced to less than 1.5 °C above preindustrial levels within a few centuries. However, our results also show that even temporarily overshooting the temperature threshold, without a transition to a new ice-sheet state, still leads to a peak in SLR of up to several metres.

Electromagnetic interference from left ventricular assist devices detected in patients with implantable cardioverter-defibrillators.

INTRODUCTION: Electromagnetic interference (EMI) from left ventricular assist devices (LVADs) can cause implantable cardioverter-defibrillator (ICD) oversensing. We sought to assess the frequency of inappropriate shocks/oversensing due to LVAD-related EMI and prospectively compare integrated (IB) versus dedicated bipolar (DB) sensing in patients with LVADs. METHODS: Single-center study in LVAD patients with Medtronic or Abbott ICDs between September 2017 and March 2020. We excluded patients that were pacemaker dependent. Measurements were obtained of IB and DB sensing and noise to calculate a signal-to-noise ratio (SNR). Device checks were reviewed to assess appropriate and inappropriate sensing events. RESULTS: Forty patients (age 52 ± 14 years, 75% men, 38% ischemic cardiomyopathy) were included with the median time between LVAD implantation and enrollment of 6.7 months (2.3, 11.4 months). LVAD subtypes included: HeartWare (n = 22, 55%), Heartmate II (n = 10, 25%), and Heartmate III (n = 8, 20%). Over a follow-up duration of 21.6 ± 12.9 months after LVAD implantation, 5% of patients (n = 2) had oversensing of EMI from the LVAD (both with HeartWare LVADs and Abbott ICDs) at 4 days and 10.8 months after LVAD implantation. Both patients underwent adjustment of ventricular sensing with resolution of oversensing and no further events over 5 and 15 months of further follow-up. The SNR was similar between IB and DB sensing (50 [29-67] and 57 [41-69], p = 0.89). CONCLUSION: ICD oversensing of EMI from LVADs is infrequent and can be managed with reprogramming the sensitivity. There was no significant difference in the R-wave SNR with IB versus DB ICD leads.

Impact of ultra-conservative ICD programming in patients with LVADs: Avoiding potentially unnecessary tachy-therapies.

BACKGROUND: Patients with left ventricular assist devices (LVAD) often tolerate ventricular arrhythmias (VA). We aim to assess the frequency and outcomes of ICD therapies averted by ultraconservative ICD programming (UCP) in LVAD patients. METHODS: This single center, retrospective cohort study included patients with LVADs and ICDs implanted from 2015 to 2019 that had UCP. The aim for UCP was to maximally delay VA treatments and maximize anti-tachycardia pacing (ATP) prior to ICD shocks. VA events were reviewed after UCP and evaluated under prior conservative programming to assess for potentially averted events (that would have resulted in either ATP or defibrillation with prior programming). RESULTS: Fifty patients were included in the study with follow-up of median 16 ± 10.2 months after UCP. The median time from LVAD implantation to reprogramming was 7 days (IQR 5-9 days). Fourteen patients (28%) had potentially averted VA events that would have been treated with their prior ICD programming (82 total events, median two events per patient, IQR 1-10 events). Treated VA events occurred in 15 patients (30%). Eleven of the 14 patients with potentially averted VAs had treated events as well. Only one patient reported definitive symptoms of self-limited "dizziness" during a potentially averted event that did not result in hospitalization. No patients died of complications from or needed emergent care/hospitalization due a potentially averted VA. CONCLUSIONS: UCP in LVAD patients likely prevented unnecessary VA treatments in many patients with minimal reported symptoms during these potentially averted events. Prospective studies are necessary to confirm these findings.

Neurite outgrowth inhibitory levels of organophosphates induce tissue transglutaminase activity in differentiating N2a cells: evidence for covalent adduct formation.

Organophosphate compounds (OPs) induce both acute and delayed neurotoxic effects, the latter of which is believed to involve their interaction with proteins other than acetylcholinesterase. However, few OP-binding proteins have been identified that may have a direct role in OP-induced delayed neurotoxicity. Given their ability to disrupt Ca2+ homeostasis, a key aim of the current work was to investigate the effects of sub-lethal neurite outgrowth inhibitory levels of OPs on the Ca2+-dependent enzyme tissue transglutaminase (TG2). At 1-10 µM, the OPs phenyl saligenin phosphate (PSP) and chlorpyrifos oxon (CPO) had no effect cell viability but induced concentration-dependent decreases in neurite outgrowth in differentiating N2a neuroblastoma cells. The activity of TG2 increased in cell lysates of differentiating cells exposed for 24 h to PSP and chlorpyrifos oxon CPO (10 µM), as determined by biotin-cadaverine incorporation assays. Exposure to both OPs (3 and/or 10 µM) also enhanced in situ incorporation of the membrane permeable substrate biotin-X-cadaverine, as indicated by Western blot analysis of treated cell lysates probed with ExtrAvidin peroxidase and fluorescence microscopy of cell monolayers incubated with FITC-streptavidin. Both OPs (10 µM) stimulated the activity of human and mouse recombinant TG2 and covalent labelling of TG2 with dansylamine-labelled PSP was demonstrated by fluorescence imaging following SDS-PAGE. A number of TG2 substrates were tentatively identified by mass spectrometry, including cytoskeletal proteins, chaperones and proteins involved protein synthesis and gene regulation. We propose that the elevated TG2 activity observed is due to the formation of a novel covalent adduct between TG2 and OPs.

Increased maternal abdominal subcutaneous fat thickness and body mass index are associated with increased cesarean delivery: A prospective cohort study.

INTRODUCTION: Early pregnancy body mass index (BMI) is known to predict adverse pregnancy outcomes but does not account for body fat distribution. This study aimed to determine prospectively whether maternal abdominal subcutaneous fat thickness (SCFT) measured by ultrasound at the fetal morphology scan is a better predictor than BMI of mode of delivery and other pregnancy outcomes. MATERIAL AND METHODS: This was a prospective cohort study of women delivering singleton neonates at a tertiary public hospital. Women were included if they had appropriate images at the routine fetal anomaly ultrasound scan and delivered in the facility. The primary outcome was mode of delivery categorized as cesarean section or vaginal delivery. The relation between maternal SCFT and BMI was described using the Pearson correlation coefficient. The association of maternal abdominal SCFT BMI at booking-in was compared with pregnancy outcomes using univariate linear and logistic regression. RESULTS: SCFT and BMI were obtained for 997 women. The median (interquartile range) SCFT was 15.3 mm (12.8-19.6) and median (interquartile range) BMI 24.3 kg/m2 (21.7-28.3). Maternal abdominal SCFT and BMI were highly correlated (R2  = 0.55). Both were significantly associated with cesarean delivery: SCFT per 5 mm (odds ratio [OR] 1.32, 95% confidence interval (CI) 1.18-1.48; BMI per 5 kg/m2 OR 1.29, 95% CI 1.15-1.44. CONCLUSIONS: Maternal abdominal SCFT and BMI were both significantly associated with cesarean delivery and other outcomes. More research is needed to define the strengths of maternal SCFT in predicting pregnancy outcomes.

Reconstructing the last interglacial at Summit, Greenland: Insights from GISP2.

The Eemian (last interglacial, 130-115 ka) was likely the warmest of all interglacials of the last 800 ka, with summer Arctic temperatures 3-5 °C above present. Here, we present improved Eemian climate records from central Greenland, reconstructed from the base of the Greenland Ice Sheet Project 2 (GISP2) ice core. Our record comes from clean, stratigraphically disturbed, and isotopically warm ice from 2,750 to 3,040 m depth. The age of this ice is constrained by measuring CH4 and δ(18)O of O2, and comparing with the historical record of these properties from the North Greenland Ice Core Project (NGRIP) and North Greenland Eemian Ice Drilling (NEEM) ice cores. The δ(18)Oice, δ(15)N of N2, and total air content for samples dating discontinuously from 128 to 115 ka indicate a warming of ∼6 °C between 127-121 ka, and a similar elevation history between GISP2 and NEEM. The reconstructed climate and elevation histories are compared with an ensemble of coupled climate-ice-sheet model simulations of the Greenland ice sheet. Those most consistent with the reconstructed temperatures indicate that the Greenland ice sheet contributed 5.1 m (4.1-6.2 m, 95% credible interval) to global eustatic sea level toward the end of the Eemian. Greenland likely did not contribute to anomalously high sea levels at ∼127 ka, or to a rapid jump in sea level at ∼120 ka. However, several unexplained discrepancies remain between the inferred and simulated histories of temperature and accumulation rate at GISP2 and NEEM, as well as between the climatic reconstructions themselves.

Future sea level rise constrained by observations and long-term commitment.

Sea level has been steadily rising over the past century, predominantly due to anthropogenic climate change. The rate of sea level rise will keep increasing with continued global warming, and, even if temperatures are stabilized through the phasing out of greenhouse gas emissions, sea level is still expected to rise for centuries. This will affect coastal areas worldwide, and robust projections are needed to assess mitigation options and guide adaptation measures. Here we combine the equilibrium response of the main sea level rise contributions with their last century's observed contribution to constrain projections of future sea level rise. Our model is calibrated to a set of observations for each contribution, and the observational and climate uncertainties are combined to produce uncertainty ranges for 21st century sea level rise. We project anthropogenic sea level rise of 28-56 cm, 37-77 cm, and 57-131 cm in 2100 for the greenhouse gas concentration scenarios RCP26, RCP45, and RCP85, respectively. Our uncertainty ranges for total sea level rise overlap with the process-based estimates of the Intergovernmental Panel on Climate Change. The "constrained extrapolation" approach generalizes earlier global semiempirical models and may therefore lead to a better understanding of the discrepancies with process-based projections.

Cardiopulmonary Arrest and Extracorporeal Membrane Oxygenation: Case Report and Review.

National trends suggest that less than one in four patients experiencing in-hospital cardiac arrest (IHCA) in the United States survive to discharge. This is especially relevant as the rates of IHCA are expected to rise in the years to come. Only a modest upward trend in survival to discharge among patients with IHCA over the past decade warrants evaluation of novel ideas to improve outcomes postcardiopulmonary resuscitation. One such idea is that the use of veno-arterial-extracorporeal membrane oxygenation (VA-ECMO) to augment standard advanced cardiac life support algorithm in patients with an identifiable and reversible cause of cardiac arrest would improve survival to discharge. Here, we present the case of a patient with refractory ventricular fibrillation arrest who was transitioned to VA-ECMO immediately following cardiac catheterization for an IHCA.

A case of disseminated Mycobacterium bovis 2 years post-intravesicular Bacillus Calmette-Guérin therapy for superficial urinary bladder cancer.

Disseminated Mycobacterium bovis is an uncommon side-effect of intravesical Bacillus Calmette-Guérin (BCG) therapy that may be mediated through Mycobacteraemia. This case report, of a 77-year-old man with a history of intravesical BCG therapy and recent cardiac surgery, highlights the need for patients with similar features on history, presenting with generalised symptoms, to have mycobacterial cultures included in their workup.

Iceberg discharges of the last glacial period driven by oceanic circulation changes.

Proxy data reveal the existence of episodes of increased deposition of ice-rafted detritus in the North Atlantic Ocean during the last glacial period interpreted as massive iceberg discharges from the Laurentide Ice Sheet. Although these have long been attributed to self-sustained ice sheet oscillations, growing evidence of the crucial role that the ocean plays both for past and future behavior of the cryosphere suggests a climatic control of these ice surges. Here, we present simulations of the last glacial period carried out with a hybrid ice sheet-ice shelf model forced by an oceanic warming index derived from proxy data that accounts for the impact of past ocean circulation changes on ocean temperatures. The model generates a time series of iceberg discharge that closely agrees with ice-rafted debris records over the past 80 ka, indicating that oceanic circulation variations were responsible for the enigmatic ice purges of the last ice age.

The multimillennial sea-level commitment of global warming.

Global mean sea level has been steadily rising over the last century, is projected to increase by the end of this century, and will continue to rise beyond the year 2100 unless the current global mean temperature trend is reversed. Inertia in the climate and global carbon system, however, causes the global mean temperature to decline slowly even after greenhouse gas emissions have ceased, raising the question of how much sea-level commitment is expected for different levels of global mean temperature increase above preindustrial levels. Although sea-level rise over the last century has been dominated by ocean warming and loss of glaciers, the sensitivity suggested from records of past sea levels indicates important contributions should also be expected from the Greenland and Antarctic Ice Sheets. Uncertainties in the paleo-reconstructions, however, necessitate additional strategies to better constrain the sea-level commitment. Here we combine paleo-evidence with simulations from physical models to estimate the future sea-level commitment on a multimillennial time scale and compute associated regional sea-level patterns. Oceanic thermal expansion and the Antarctic Ice Sheet contribute quasi-linearly, with 0.4 m °C(-1) and 1.2 m °C(-1) of warming, respectively. The saturation of the contribution from glaciers is overcompensated by the nonlinear response of the Greenland Ice Sheet. As a consequence we are committed to a sea-level rise of approximately 2.3 m °C(-1) within the next 2,000 y. Considering the lifetime of anthropogenic greenhouse gases, this imposes the need for fundamental adaptation strategies on multicentennial time scales.

Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor.

Among the biological phenomena that fall within the emerging field of "quantum biology" is the suggestion that magnetically sensitive chemical reactions are responsible for the magnetic compass of migratory birds. It has been proposed that transient radical pairs are formed by photo-induced electron transfer reactions in cryptochrome proteins and that their coherent spin dynamics are influenced by the geomagnetic field leading to changes in the quantum yield of the signaling state of the protein. Despite a variety of supporting evidence, it is still not clear whether cryptochromes have the properties required to respond to magnetic interactions orders of magnitude weaker than the thermal energy, k(B)T. Here we demonstrate that the kinetics and quantum yields of photo-induced flavin-tryptophan radical pairs in cryptochrome are indeed magnetically sensitive. The mechanistic origin of the magnetic field effect is clarified, its dependence on the strength of the magnetic field measured, and the rates of relevant spin-dependent, spin-independent, and spin-decoherence processes determined. We argue that cryptochrome is fit for purpose as a chemical magnetoreceptor.

"My religion picked my birth control": the influence of religion on contraceptive use.

This research investigates the influence of religious preference and practice on the use of contraception. Much of earlier research examines the level of religiosity on sexual activity. This research extends this reasoning by suggesting that peer group effects create a willingness to mask the level of sexuality through the use of contraception. While it is understood that certain religions, that is, Catholicism does not condone the use of contraceptives, this research finds that Catholics are more likely to use certain methods of contraception than other religious groups. With data on contraceptive use from the Center for Disease Control's Family Growth Survey, a likelihood probability model is employed to investigate the impact religious affiliation on contraception use. Findings suggest a preference for methods that ensure non-pregnancy while preventing feelings of shame and condemnation in their religious communities.

Attenuation of leukocyte recruitment via CXCR1/2 inhibition stops the progression of PAH in mice with genetic ablation of endothelial BMPR-II.

Previous studies from our group have demonstrated that bone morphogenetic protein receptor-II (BMPR-II), expressed on pulmonary artery endothelial cells, imparts profound anti-inflammatory effects by regulating the release of proinflammatory cytokines and promoting barrier function by suppressing the transmigration of leukocytes into the pulmonary vessel wall. Here we demonstrate that, in mice with endothelial-specific loss of BMPR-II expression (L1Cre(+);Bmpr2(f/f)), reduction in barrier function and the resultant pulmonary hypertension observed in vivo are the result of increased leukocyte recruitment through increased CXCR1/2 signaling. Loss of endothelial expressed BMPR-II leads to elevated plasma levels of a wide range of soluble mediators important in regulating leukocyte migration and extravasation, including the CXCR1/2 ligand, KC. Treatment of L1Cre(+);Bmpr2(f/f) mice with the CXCR1/2 antagonist SCH527123 inhibits leukocyte transmigration into lung and subsequently reverses the pulmonary hypertension. Our data have uncovered a previously unrecognized regulatory function of BMPR-II, which acts to regulate the expression of CXCR2 on endothelial cells, suggesting that increased CXCR2 signaling may also be a feature of the human pathology and that CXCR1/2 pathway antagonists may represent a novel therapeutic approach for treating pulmonary hypertension because of defects in BMPR-II expression.

When Precision Meets Penmanship: ChatGPT and Surgery Documentation.

ChatGPT (Chatbot Generative Pre-Trained Transformer) is an artificial intelligence with several potential applications in the field of medicine. As a large language model, it is particularly good at generating text. This study investigates the use of ChatGPT in constructing operation notes for laparoscopic appendicectomy, one of the most common surgical procedures in the UK. We prompted ChatGPT-4, the latest generation of ChatGPT, to produce operation notes for laparoscopic appendicectomy, which were then evaluated against 'Getting It Right First Time' (GIRFT) recommendations. GIRFT is an organisation that has collaborated with the National Health Service (NHS) to improve surgical documentation guidelines. Excluding certain items documented elsewhere in patient records, the generated notes were assessed against 30 key points in GIRFT recommendations. This process was repeated three times to obtain an average score. Our results showed that ChatGPT generated operation notes in seconds, with an average coverage of 78.8% (23.66 out of 30 points) of the GIRFT guidelines, surpassing average compliance with similar guidelines from the Royal College of Surgeons (RCS). However, the quality of ChatGPT's output was found to be dependent on the quality of the prompt, highlighting the need for verification of the generated content. Additionally, secure integration with electronic health records is required before ChatGPT can be adopted into the NHS.

Time-scale synchronisation of oscillatory responses can lead to non-monotonous R-tipping.

Rate-induced tipping (R-tipping) describes the fact that, for multistable dynamic systems, an abrupt transition can take place not only because of the forcing magnitude, but also because of the forcing rate. In the present work, we demonstrate through the case study of a piecewise-linear oscillator (PLO), that increasing the rate of forcing can make the system tip in some cases but might also prevent it from tipping in others. This counterintuitive effect is further called non-monotonous R-tipping (NMRT) and has already been observed in recent studies. We show that, in the present case, the reason for NMRT is the peak synchronisation of oscillatory responses operating on different time scales. We further illustrate that NMRT can be observed even in the presence of additive white noise of intermediate amplitude. Finally, NMRT is also observed on a van-der-Pol oscillator with an unstable limit cycle, suggesting that this effect is not limited to systems with a discontinuous right-hand side such as the PLO. This insight might be highly valuable, as the current research on tipping elements is shifting from an equilibrium to a dynamic perspective while using models of increasing complexity, in which NMRT might be observed but hard to understand.