Structure of the moiré exciton captured by imaging its electron and hole.

Interlayer excitons (ILXs) - electron-hole pairs bound across two atomically thin layered semiconductors - have emerged as attractive platforms to study exciton condensation1-4, single-photon emission and other quantum information applications5-7. Yet, despite extensive optical spectroscopic investigations8-12, critical information about their size, valley configuration and the influence of the moiré potential remains unknown. Here, in a WSe2/MoS2 heterostructure, we captured images of the time-resolved and momentum-resolved distribution of both of the particles that bind to form the ILX: the electron and the hole. We thereby obtain a direct measurement of both the ILX diameter of around 5.2 nm, comparable with the moiré-unit-cell length of 6.1 nm, and the localization of its centre of mass. Surprisingly, this large ILX is found pinned to a region of only 1.8 nm diameter within the moiré cell, smaller than the size of the exciton itself. This high degree of localization of the ILX is backed by Bethe-Salpeter equation calculations and demonstrates that the ILX can be localized within small moiré unit cells. Unlike large moiré cells, these are uniform over large regions, allowing the formation of extended arrays of localized excitations for quantum technology.

Temporal Outcomes of Patients Diagnosed With Transthyretin Cardiac Amyloidosis.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is increasingly recognized. Clinical outcomes have evolved over time amid changes in the diagnostic pathway and advances in therapeutics. We sought to evaluate clinical outcomes over time of patients with ATTR-CA with access to disease-modifying therapy. METHODS AND RESULTS: This is a retrospective cohort study of 419 patients diagnosed with ATTR-CA during 2001-2021, comparing clinical characteristics across eras. The primary end point was composite all-cause mortality or orthotopic heart transplantation (OHT). Time-to-event analysis was performed using Cox proportional hazard modeling controlling for differences among cohorts. Patients diagnosed in the more recent years had higher median age (2017-2021, 78 years; 2014-2016, 75 years; 2001-2013, 74 years) and more often had wild-type ATTR (81.9% vs 82.5% vs 56.4%), but less severe phenotypes as evidenced by more individuals with Columbia stage I disease (47.6% vs 35.9% vs 22.4%), owing to lower biomarkers, more patients in New York Heart Association functional classes I and II (68.9% vs 47.6% vs 43.6%), and lower use of loop diuretics (67.0% vs 78.6% vs 89.1%). Over time, patients were treated more frequently with tafamidis (74% vs 37% vs 32%). On multivariable analysis, greater Columbia score (hazard ratio 1.42, 95% confidence interval 1.30-1.54, P < .001) was predictive of death or OHT, whereas tafamidis (hazard ratio 0.31, 95% confidence interval 0.22-0.44, P < .001) was associated with greater survival and freedom from OHT. CONCLUSIONS: Patients recently diagnosed with ATTR-CA have earlier stage disease and substantially lower mortality. Tafamidis is associated with significantly improved survival and freedom from OHT.

Psychometric properties of health-related quality of life instruments used in survivors of critical illness: a systematic review.

BACKGROUND AND OBJECTIVES: Health-related quality of life (HRQoL) is a patient-reported measure of health status. However, research on the psychometric properties of HRQoL instruments used post-critical care is less common. We conducted a systematic review assessing the psychometric properties of HRQoL instruments used in adult survivors following critical illness. METHODS: Three databases were systematically searched between 1990 and June 2022. Screening articles for eligibility, we selected either development studies for new tools or studies that evaluated psychometric properties, and whose target population represented adult survivors following critical illness. Methodological quality was assessed using the COnsensus-Based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The results of each psychometric property were then assessed for criteria of good psychometric properties (sufficient, insufficient or indeterminate) and qualitatively summarised. Finally, we graded the quality of the evidence using a modified GRADE approach. RESULTS: We retrieved 13 eligible studies from 2,983 records identifying 10 HRQoL instruments used post-critical illness. While high-quality evidence for the considered PROMs was limited primarily due to risk of bias, seven instruments demonstrated sufficient levels of reliability, four instruments presented sufficient hypothesis testing, and two instruments showed sufficient responsiveness. Except the Short Form-36, evidence for psychometric properties of other individual measures was limited to a few studies. CONCLUSION: There was limited evidence demonstrated for the psychometric properties of the included PROMs evaluating HRQoL. Further research is warranted to evaluate the psychometric properties of HRQoL measures, strengthening the evidence for administering these instruments in survivors following critical illness.

Maternal and Fetal Radiation-Induced Cancer Risk From Computed Tomography Pulmonary Angiography During Pregnancy: A Retrospective Cohort Study Across a Multihospital Integrated Health Care Network.

OBJECTIVE: Computed tomography pulmonary angiogram (CTPA) is important to evaluate suspected pulmonary embolism in pregnancy but has maternal/fetal radiation risks. The objective of this study was to estimate maternal and fetal radiation-induced cancer risk from CTPA during pregnancy. METHODS: Simulation modeling via the National Cancer Institute's Radiation Risk Assessment Tool was used to estimate excess cancer risks from 17 organ doses from CTPA during pregnancy, with doses determined by a radiation dose indexing monitoring system. Organ doses were obtained from a radiation dose indexing monitoring system. Maternal and fetal cancer risks per 100,000 were calculated for male and female fetuses and several maternal ages. RESULTS: The 534 CTPA examinations had top 3 maternal organ doses to the breast, lung, and stomach of 17.34, 15.53, and 9.43 mSv, respectively, with a mean uterine dose of 0.21 mSv. The total maternal excess risks of developing cancer per 100,000 were 181, 151, 121, 107, 94.5, 84, and 74.4, respectively, for a 20-, 25-, 30-, 35-, 40-, 45-, and 50-year-old woman undergoing CTPA, compared with baseline cancer risks of 41,408 for 20-year-old patients. The total fetal excess risks of developing cancer per 100,000 were 12.3 and 7.3 for female and male fetuses, respectively, when compared with baseline cancer risks of 41,227 and 48,291. DISCUSSION: Excess risk of developing cancer from CTPA was small relative to baseline cancer risk for pregnant patients and fetuses, decreased for pregnant patients with increasing maternal age, and was greater for female fetuses than male fetuses.

Anticoagulation after pulmonary vein isolation for atrial fibrillation: Associations with CHA2DS2-VASc score, sex, and rhythm.

Guidelines recommend using the CHA2DS2-VASc score to determine anticoagulation decisions in atrial fibrillation (AF) patients, including those who undergo pulmonary vein isolation (PVI), however this may not consistently occur in the real-world setting because of other clinical factors. We sought to evaluate the anticoagulation prescription rates patterns in AF patients 1 year PVI at our institution. Consecutive AF patients undergoing PVI in our prospective registry during 2014-2018 who were alive at 1-year post-PVI were studied. Anticoagulation prescription rates at this time-point were adjudicated, and correlated to CHA2DS2-VASc score, sex, and heart rhythm status at 1 year. Amongst 4596 patients undergoing PVI, mean age was 64.2 ± 10.0 years, 1328 (28.9%) were female, and based on CHA2DS2-VASc score anticoagulation was not indicated, can be considered and indicated in 872 (19.0%), 1183 (25.7%), and 2541 (55.3%) patients, respectively. At 1-year after PVI, 3504 (76.2%) patients were on anticoagulation, and 792 (17.2%) had recurrence of AF. Anticoagulation was continued in over half of AF patients without classic CHA2DS2-VASc indication particularly in those with AF recurrence and women, while they were mildly under-prescribed in those with indication, especially for those without AF recurrence and men. In a large real world cohort of patients after PVI, anticoagulation prescription is not solely depending on the CHA2DS2-VASc score and sex, but also heart rhythm status and other clinical or imaging factors.

Prevalence and significance of extracardiac uptake on pyrophosphate imaging in the SCAN-MP study: the first 379 cases.

INTRODUCTION: Technetium-labeled bone-avid radiotracers can be used to diagnose transthyretin cardiac amyloidosis (ATTR-CA). Extracardiac uptake of technetium pyrophosphate (Tc-99m PYP) in this context has not been extensively explored and its significance is not well characterized. We assessed extracardiac Tc-99m PYP uptake in individuals undergoing nuclear scintigraphy and the extent of clinically actionable findings. METHODS: The Screening for Cardiac Amyloidosis with Nuclear Imaging in Minority Populations (SCAN-MP) study utilizes Tc-99m PYP imaging to identify ATTR-CA in self-identified Black and Caribbean Hispanic participants ≥ 60 years old with heart failure. We characterized the distribution of extracardiac uptake, including stratification of findings by timing of scan (1 hour vs 3 hours after Tc-99m PYP administration) and noted any additional testing in these subjects. RESULTS: Of 379 participants, 195 (51%) were male, 306 (81%) Black race, and 120 (32%) Hispanic ethnicity; mean age was 73 years. Extracardiac Tc-99m PYP uptake was found in 42 subjects (11.1%): 21 with renal uptake only, 14 with bone uptake only, 4 with both renal and bone uptake, 2 with breast uptake, and 1 with thyroid uptake. Extracardiac uptake was more common in subjects with Tc-99m PYP scans at 1 hour (23.8%) than at 3 hours (6.2%). Overall, four individuals (1.1%) had clinically actionable findings. CONCLUSION: Extracardiac Tc-99m PYP uptake manifested in about 1 in 9 SCAN-MP subjects but was clinically actionable in only 1.1% of cases.

Prior oral proton-pump inhibitor use is associated with reduced severity of aspirin-related upper gastrointestinal bleeding in older people.

Low-dose aspirin is commonly used for primary or secondary prophylaxis against cardiovascular disease in older people. However, the potential risk of upper gastrointestinal (UGI) ulceration and bleeding associated with low-dose aspirin use is often not appreciated by prescribers and older consumers. Among 133 serial patients with UGI bleeding, aspirin-users aged ≥70 years had a ninefold increased likelihood of overt UGI bleeding compared with non-users, reducing by 90% in regular proton-pump inhibitor users (adjusted odds ratio 0.10). We recommend risk-versus-benefit discussions when recommending aspirin to older people.

Crosslinked Polypeptide Films via RAFT-Mediated Continuous Assembly of Polymers.

Polypeptide coatings are a cornerstone in the field of surface modification due to their widespread biological potential. As their properties are dictated by their structural features, subsequent control thereof using unique fabrication strategies is important. Herein, we report a facile method of precisely creating densely crosslinked polypeptide films with unusually high random coil content through continuous assembly polymerization via reversible addition-fragmentation chain transfer (CAP-RAFT). CAP-RAFT was fundamentally investigated using methacrylated poly-l-lysine (PLLMA) and methacrylated poly-l-glutamic acid (PLGMA). Careful technique refinement resulted in films up to 36.1±1.1 nm thick which could be increased to 94.9±8.2 nm after using this strategy multiple times. PLLMA and PLGMA films were found to have 30-50 % random coil conformations. Degradation by enzymes present during wound healing reveals potential for applications in drug delivery and tissue engineering.

Incorporating coronary calcification by computed tomography into CHA2DS2-VASc score: impact on cardiovascular outcomes in patients with atrial fibrillation.

AIMS: CHA2DS2-VASc score is widely utilized for risk stratification and guiding anticoagulation in patients with atrial fibrillation (AF). Cardiac computed tomography (CCT) routinely performed for pulmonary vein isolation (PVI) can also identify coronary artery calcifications (CAC). We evaluated the frequency and outcomes of incorporating CAC into the CHA2DS2-VASc score in AF patients undergoing PVI. METHODS AND RESULTS: Consecutive patients in a prospective PVI registry during 2014-18 having CCT within 1 year of PVI were studied. Reclassification of CHA2DS2-VASc score and associations between CAC as a binary variable detected on CCT with clinical characteristics, stroke as primary endpoint, death, myocardial infarction, and major adverse cardiovascular events (MACE) were analysed. Amongst 3604 AF patients, 2238 (62.1%) had CAC detected on CCT and was associated with most traditional cardiovascular risk factors. Coronary artery calcification was independently associated with all pre-specified endpoints adjusting for clinical parameters in multivariable analysis. Adjusting for CHA2DS2-VASc score, CAC was associated with stroke (hazards ratio 3.64, 95% confidence interval 1.25-10.6, P = 0.018), death (2.26, 1.29-3.98, P = 0.006), and MACE (2.08, 1.36-3.16, P = 0.001) during 2.8 ± 1.6-year follow-up. Incorporating CAC as a vascular disease parameter of CHA2DS2-VASc score, anticoagulation decision-making would be revised in 723 (20.1%) patients, including an additional 488 (13.5%) patients where anticoagulation would be now indicated. CONCLUSION: Coronary artery calcification is prevalent in AF patients undergoing PVI and independently associated stroke, death and MACE even when adjusted for traditional CHA2DS2-VASc score. Adding CAC as vascular component to the CHA2DS2-VASc score requires further research as it potentially modified the anticoagulation management in 20% of our AF cohort.

Ring opening polymerization of α-amino acids: advances in synthesis, architecture and applications of polypeptides and their hybrids.

Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and tunable cytocompatibility. Macromolecular design in conjunction with rational monomer composition can direct architecture, self-assembly and chemical behavior, ultimately guiding the choice of appropriate application within the biomedical field. This review focuses on the applications of polypeptides alongside the synthetic advances in the ring opening polymerization of α-amino acid N-carboxyanhydrides achieved in the past five years. Key architectures obtained through NCA ROP or in combination with other polymerization methods are reviewed, as these play an important role in the wide range of applications towards which polypeptides have been applied.

A systematic review and meta-analysis of surgical versus endovascular thrombectomy of thrombosed arteriovenous grafts in hemodialysis patients.

BACKGROUND: The major pitfall of arteriovenous grafts (AVGs) for hemodialysis patients is thrombosis and occlusion. Prompt intervention with either surgical or endovascular therapy to salvage the vascular access is crucial in maintaining effective hemodialysis. The purpose of this systematic review and meta-analysis was to assess and compare the efficacy of open surgical vs wholly endovascular therapy for the treatment of thrombosed AVGs. METHODS: This review was conducted according to the PRISMA guidelines. Relative risks **(RRs) and pooled proportions for both primary and secondary outcomes were calculated. RESULTS: A total of eight randomized, controlled trials and two retrospective cohort studies were included, comprising 806 (63%) and 466 (37%) participants in the surgical and wholly endovascular treatment arms respectively. There were no significant differences between endovascular and surgical therapy in the 30-, 60-, and 90-day primary nonpatency rates. However, endovascular therapy reported a significantly higher 1-year primary nonpatency rate (rate ratio [RR], 1.22; 95% confidence interval [CI], 1.13-1.33; P < .01) and the 2-year primary nonpatency rate (RR, 1.26; 95% CI, 1.10-1.45; P < .01) as compared with surgical therapy. Similarly, the endovascular arm had a higher pooled proportion of primary nonpatency of 87.7% (95% CI, 81.5%-92.9%; P = .297), as compared with the surgical arm (72.1%; 95% CI, 66.4%-77.4%; P = .289). In terms of secondary nonpatency rates, there were no significant differences between endovascular and surgical procedures at 30, 60, and 90 days. Endovascular procedures reported a significantly higher technical failure rate as compared with surgical thrombectomy (RR, 1.58; 95% CI, 1.06-2.37; P = .03). There was no significant difference in terms of minor and major complications. CONCLUSIONS: Our data suggest that, for thrombectomy of AVGs, wholly endovascular therapy seems to be inferior to open surgery plus adjuncts based on the long-term patency and technical failure rates. However, further research in the form of a well-conducted randomized trial is warranted to establish a firmer conclusion.

Incidental LAD stenosis identified on non-gated chest CTA.

A 57-year-old male former smoker presented to the Emergency Department (ED) with blurry vision, headache, and generalized weakness. He was hypoxic on room air and ECG showed sinus tachycardia. A CT pulmonary angiogram was ordered in the ED and revealed no pulmonary embolism but incidentally noted a likely significant stenosis in the proximal LAD. Subsequent cardiac catheterization revealed a 90% stenotic lesion with percutaneous coronary intervention leading to symptom resolution. Unlike coronary CTA, CTPA is performed with non-ECG gated helical scanning and generates motion artifacts associated with myocardial contraction. However, the timing of vascular contrast opacification during CTPA often allows for at least partial evaluation of the coronary arteries, especially ostial and proximal segments. Physicians ordering and evaluating noncardiac-focused CT chest studies, particularly in the ED, should remain cognizant of the radiographic appearance of underlying CAD, particularly life-threatening incidental coronary pathologies to allow for timely management and intervention.

Morphospaces of functionally analogous traits show ecological separation between birds and pterosaurs.

Birds originated and radiated in the presence of another group of flying vertebrates, the pterosaurs. Opinion is divided as to whether birds competitively displaced pterosaurs from small-body size niches or whether the two groups coexisted with little competition. Previous studies of Mesozoic birds and pterosaurs compared measurements of homologous limb bones to test these hypotheses. However, these characters probably reflect differing ancestries rather than ecologies. Here, competition and ecological separation were tested for using multivariate analyses of functionally equivalent morphological characters. As well as using characters from the fore- and hindlimbs, these analyses also included measurements of the lower jaw. The results of this study indicate that pterosaurs had relatively longer jaws, shorter metatarsals and shorter brachial regions compared with birds of similar size. Contrary to the results of previous studies, the distal wing was not important for separating the two clades in morphospace owing to the inclusion of the primary feathers in this unit. The differences found here indicate ecological separation based on differences in size, locomotory features and feeding adaptations. Thus, instead of one group displacing the other, birds and pterosaurs appear to have adopted distinctive ecological strategies throughout their period of coexistence.

Tip convolution on HOPG surfaces measured in AM-AFM and interpreted using a combined experimental and simulation approach.

Amplitude modulated atomic force microscopy (AM-AFM) was used to examine the influence of the size of the AFM tip apex on the measured surface topography of single highly oriented pyrolytic graphite (HOPG) atomic steps. Experimental measurements were complemented by molecular dynamics simulations of AM-AFM and the results from both were evaluated by comparison of the measured or simulated width of the topography at the step to that predicted using simple rigid-body geometry. The results showed that the step width, which is a reflection of the resolution of the measurement, increased with tip size, as expected, but also that the difference between the measured/simulated step width and the geometric calculation was tip size dependent. The simulations suggested that this may be due to the deformation of the bodies and the effect of that deformation on the interaction force and oscillation amplitude. Overall, this study showed that the resolution of AM-AFM measurements of atomic steps can be correlated to tip size and that this relationship is affected by the deformation of the system.

Macroporous Hydrogels Composed Entirely of Synthetic Polypeptides: Biocompatible and Enzyme Biodegradable 3D Cellular Scaffolds.

Synthetic polypeptides are a class of bioinspired polymers with well demonstrated biocompatibility, enzyme biodegradability, and cell adhesive properties, making them promising materials for the preparation of macroporous hydrogels as 3D cellular scaffolds. Three-dimensional macroporous hydrogels composed entirely of biocompatible and enzyme biodegradable synthetic polypeptides have thus been prepared. Under cryoconditions, macroporous hydrogels in the form of macroporous cryogels were prepared using a single copolymer component through direct EDC/sulfo-NHS zero-length cross-linking between poly(l-glutamic acid) (PLG) and poly(l-lysine) (PLL) residues on a PLG-r-PLL random copolypeptide chain. The resulting macroporous cryogels were found to contain large interconnected pores (≥100 µm) highly suitable for tissue engineering applications. Tuning the relative ratios of the amino acid components could result in cryogels with very different pore structures, swelling, and mechanical properties, suitable for developing gels for a range of possible soft tissue engineering applications. These cryogels were shown to be enzymatically biodegradable and demonstrated excellent biocompatibility, cell attachment and cell proliferation profiles with mammalian fibroblast (NIH-3T3) cells, demonstrating the appeal of these novel cryogels as highly suitable cellular scaffolds.

High prevalence of HPV59 in cytologically abnormal cervical samples.

BACKGROUND: Cervical cancer is the second most common form of cancer among women. There are over 100 different types of human papillomavirus (HPV), 40 of which are frequently detected in anogenital mucosa. HPV is the primary etiological agent of cervical cancer and is present predominantly in cervical cancers. Thirteen commonly recognized high-risk genotypes have oncogenic potential. The most common high-risk HPV (hrHPV) genotypes in cervical cancer are HPV16 and HPV18, which have the greatest malignancies. The objective of this study was to determine the distribution of hrHPV types in patient samples received at the Mount Sinai Medical Center for routine cytology and HPV testing. In addition, the study compared the sensitivity of the Hybrid Capture 2 (HC2) and Roche Linear Array HPV Genotyping assays. METHODS: Cytology specimens with abnormal diagnoses were tested for HPV by the Roche Linear Array HPV Genotyping and Digene Hybrid Capture 2 molecular systems. RESULTS: The Roche Linear Array HPV Genotyping Assay was more sensitive than HC2. Additionally, specimens exhibited higher rates of HPV16, HPV51, and HPV59 infections than HPV16 and HPV18 infections. CONCLUSION: The results demonstrate that geographical distribution of HPV genotypes may play an important role in clinical management of HPV infection, particularly when treating cervical dysplasia and recommending HPV vaccination.