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The synthesis of sterically congested amides was accomplished via Cp*Co(III)-catalyzed sequential C–H bond addition to 1,3-dienes followed by aminocarbonylation with isocyanates, a coupling partner that had never been utilized in sequential C–H bond addition reactions. A variety of C–H bond reactants, internally substituted dienes, and aromatic isocyanates provided secondary amide products incorporating α-all-carbon quaternary centers. The conversion of the amide products to other useful compound classes was also demonstrated.

A comparative experimental and computational study examining the interplay of the ancillary ligand structure and Ni oxidation state in the Ni-catalyzed C(sp2)–O cross-coupling of (hetero)aryl chlorides and primary or secondary aliphatic alcohols is presented, focusing on PAd-DalPhos (L1)-, CyPAd-DalPhos (L2)-, PAd2-DalPhos (L3)-, and DPPF (L4)-ligated [(L)NiCl]n(n= 1 or 2) and (L)Ni(o-tol)Cl precatalysts. Both L1and L2were found to outperform the other ligands examined, with the latter proving to be superior overall. While Ni(II) precatalysts generally outperformed Ni(I) species, in some instances the catalytic abilities of Ni(I) precatalysts were competitive with those of Ni(II). Density-functional theory calculations indicate the favorability of a Ni(0)/Ni(II) catalytic cycle featuring turnover-limiting C–O bond reductive elimination over a Ni(I)/Ni(III) cycle involving turnover-limiting C–Cl oxidative addition.

•We unveiled 8 lncRNAs essential for multiple myeloma (MM) cell fitness and associated with poor prognosis and high expression in patients with MM.•We identified lncRNA RP11-350G8.5 as a therapeutic target for MM and characterized its oncogenic role and molecular and structural features.

Multiple myeloma is a treatable, but currently incurable, hematological malignancy of plasma cells characterized by diverse and complex tumor genetics for which precision medicine approaches to treatment are lacking. The Multiple Myeloma Research Foundation’s Relating Clinical Outcomes in Multiple Myeloma to Personal Assessment of Genetic Profile study (NCT01454297) is a longitudinal, observational clinical study of newly diagnosed patients with multiple myeloma (n= 1,143) where tumor samples are characterized using whole-genome sequencing, whole-exome sequencing and RNA sequencing at diagnosis and progression, and clinical data are collected every 3 months. Analyses of the baseline cohort identified genes that are the target of recurrent gain-of-function and loss-of-function events. Consensus clustering identified 8 and 12 unique copy number and expression subtypes of myeloma, respectively, identifying high-risk genetic subtypes and elucidating many of the molecular underpinnings of these unique biological groups. Analysis of serial samples showed that 25.5% of patients transition to a high-risk expression subtype at progression. We observed robust expression of immunotherapy targets in this subtype, suggesting a potential therapeutic option.

Net global losses of seagrasses have accelerated efforts to understand recovery from disturbances. Stressors causing disturbances (e.g., storms, heatwaves, boating) vary temporally and spatially within meadows potentially affecting recovery. To test differential recovery, we conducted a removal experiment at sites that differed in thermal stress for a temperate seagrass (Zostera marina). We also synthesized prior studies of seagrass recovery to assess general patterns. Seagrass shoots were removed from 28.3 m2plots at edge and central sites of a meadow in South Bay, Virginia, USA. We hypothesized faster recovery for edge plots where greater oceanic exchange reduces thermal stress. Contrary to our hypothesis recovery was most rapid in the central meadow matching control site shoot density in 24 months. Recovery was incomplete at the meadow edge and estimated to require 158 months. Differences in recovery were likely due to storm‐driven sediment erosion at the edge sites. Based on data from prior recovery studies, which were primarily on monospecific meadows of Zostera, seagrasses recover across a broad range of conditions with a positive, nonlinear relationship between disturbance area and recovery time. Our experiment indicates position within a seagrass meadow affects disturbance susceptibility and length of recovery. Linking this finding to our literature synthesis suggests increased attention to spatial context will contribute to better understanding variation in recovery rates.

AbstractAntipermeation and anticorrosion coatings are being developed to reduce tritium permeation from liquid metal [LiPb of the water-cooled lithium-lead breeding blanket and Pb for lead-cooled fast reactors (LFRs)] to primary heat transfer systems. The facility APRIL (Alumina-coating for tritium Permeation Reduction for Innovative LFR) was designed and installed at ENEA Brasimone R.C. to characterize the permeation reduction factor (PRF) of the candidate coatings in static conditions.In the current configuration, APRIL is composed of three pipes, closed at one end, that simulate the heat exchangers of the ALFRED LFR. Two of the pipes are coated with 3 µm of alumina with pulsed laser deposition techniques, the reference method for a fission reactor. The third pipe is uncoated. During the tests, all the pipes are filled with pressurized steam at 100 bar and 480°C, the steam generator condition of the ALFRED LFR. The tests are made in the gas phase; indeed, the three pipes are installed in a chamber filled with helium with a known concentration of deuterium that simulates tritium. Deuterium permeates inside the pipes, allowing for the evaluation of the PRF by means of the ratio between the measured permeated flux in the uncoated pipe and in the coated ones. A first test with 0.5% of deuterium was carried out and the evaluated PRF was about 13.5.

Objectives: Primary objective: describe rates of 30-days unplanned readmission following outpatient resection of oral cavity cancer. Secondary objective: evaluate for patient and treatment factors associated with readmission.Methods: Retrospective, dual-institution cohort study of 2 tertiary care referral centers involving adult patients undergoing resection of oral cavity cancer with plans for same-day discharge. Consecutive sample of 77 patients included. Primary outcome was unplanned readmission to emergency room or inpatient stay in the 30 days following surgery. Comparison testing was used between return and non-return groups.Results: Among 77 patients treated with outpatient surgery for oral cavity cancer, 19 (25%) returned to the hospital within 30 days. Among the reasons for return, 16 (80%) were directly related to surgery, and 4 (20%) were related to perioperative medical complications not directly related to a surgical site. Among the 25 patients also undergoing sentinel lymph node biopsy with their oral cavity resection, none returned to the hospital for neck-related complications. While most patients could be safely observed and discharged after return to the hospital, 8 patients (10%) required inpatient readmission. No significant differences between return and non-return groups were identified, although there was a trend toward shorter driving distance from hospital for the return group (47.6 miles vs. 69.5 miles, P= 0.097).Conclusion: Unplanned return to the hospital following outpatient oral cavity resection is prevalent and primarily driven by postoperative primary resection site concerns. Among patients selected for same day discharge, no definite population at highest risk of unplanned return was identified.

ABSTRACTIn response to challenges emerging in society, universities are searching for ways to innovate their courses through novel institutional educational policies and practices. Those efforts, however, are often not informed by knowledge about course innovation characteristics university-wide, and are often not supported by processes of reflection questioning the ‘who’, ‘how’ and ‘for what’ of course innovations. This study applied the multifaceted analytical Course Innovation Framework (CIF) in order to explore characteristics of a large set of intended course innovations in a higher education institution in the Netherlands. The application of the CIF enabled a descriptive analysis of multiple characteristics of the intended course innovations. This analysis unveiled university-wide course innovation trends, upon which university stakeholders reflected in order to responsibly guide and transform policy and practices. The study findings show how the application of the CIF helps to gather situated knowledge on university-wide innovation trends, and how reflection on these trends empowers stakeholders to deliberate the culture and values of educational innovation they wish to promote within their institution.

Purpose: The relationship between axial surface rotation (ASR) measured by surface topography (ST) and axial vertebral rotation (AVR) measured by radiography in the transverse plane is not well defined. This study aimed to: (1) quantify ASR and AVR patterns and their magnitudes from T1 to L5; (2) determine the correlation or agreement between the ASR and AVR; and (3) investigate the relationship between axial rotation differences (ASR–AVR) and major Cobb angle. Methods: This is a retrospective study evaluating patients (age 8–18) with IS or spinal asymmetry with both radiographic and ST measurements. Demographics, descriptive analysis, and correlations and agreements between ASR and AVR were evaluated. A piecewise linear regression model was further created to relate rotational differences to Cobb angle. Results: Fifty-two subjects met inclusion criteria. Mean age was 14.1 ± 1.7 and 39 (75%) were female. Looking at patterns, AVR had maximal rotation at T8, while ASR had maximal rotation at T11 (r= 0.35, P= .006). Cobb angle was 24.1° ± 13.3° with AVR of − 1° ± 4.6° and scoliotic angle was 20.9° ± 11.5° with ASR of − 2.3° ± 6.6°. (ASR–AVR) vs Cobb angle was found to be very weakly correlated with a curve of less than 38.8° (r= 0.15, P= .001). Conclusion: Our preliminary findings support that ASR measured by ST has a weak correlation with estimation of AVR by 3D radiographic reconstruction. This correlation may further help us to understand the application of transverse rotation in some clinical scenarios such as specific casting manipulation, padding mechanism in brace, and surgical correction of rib deformity.

Sex-based differences in the prevalence of autism spectrum disorder (ASD) are well-documented, with a male-to-female ratio of approximately 4:1. The clinical presentation of the core symptoms of ASD can also vary between sexes. Previously, positron emission tomography (PET) studies have identified alterations in the in vivo levels of translocator protein (TSPO)—a mitochondrial protein—in primarily or only male adults with ASD, with our group reporting lower TSPO relative to whole brain mean in males with ASD. However, whether in vivo TSPO levels are altered in females with ASD, specifically, is unknown. This is the first pilot study to measure in vivo TSPO in the brain in adult females with ASD using [11C]PBR28 PET-magnetic resonance imaging (MRI). Twelve adult females with ASD and 10 age- and TSPO genotype-matched controls (CON) completed one or two [11C]PBR28 PET–MRI scans. Females with ASD exhibited elevated [11C]PBR28 standardized uptake value ratio (SUVR) in the midcingulate cortex and splenium of the corpus callosum compared to CON. No brain area showed lower [11C]PBR28 SUVR in females with ASD compared to CON. Test-retest over several months showed stable [11C]PBR28 SUVR across time in both groups. Elevated regional [11C]PBR28 SUVR in females with ASD stand in stark contrast to our previous findings of lower regional [11C]PBR28 SUVR in males with ASD. Preliminary evidence of regionally elevated mitochondrial protein TSPO relative to whole brain mean in ASD females may reflect neuroimmuno-metabolic alterations specific to females with ASD.

The most advanced antiviral molecules addressing major SARS-CoV-2 targets (Main protease, Spike protein, and RNA polymerase), compared with proteins of other human pathogenic coronaviruses, may have a short-lasting clinical efficacy. Accumulating knowledge on the mechanisms underlying the target structural basis, its mutational progression, and the related biological significance to virus replication allows envisaging the development of better-targeted therapies in the context of COVID-19 epidemic and future coronavirus outbreaks. The identification of evolutionary patterns based solely on sequence information analysis for those targets can provide meaningful insights into the molecular basis of host–pathogen interactions and adaptation, leading to drug resistance phenomena. Herein, we will explore how the study of observed and predicted mutations may offer valuable suggestions for the application of the so-called “synthetic lethal” strategy to SARS-CoV-2 Main protease and Spike protein. The synergy between genetics evidence and drug discovery may prioritize the development of novel long-lasting antiviral agents.

•MIR17HG produces a long noncoding RNA that acts as a chromatin scaffold for protein interaction and tumor cell growth.•Targeting this long noncoding RNA with optimized antisense oligonucleotides has potent antimyeloma activity in preclinical models.

Long noncoding RNAs (lncRNAs) can drive tumorigenesis and are susceptible to therapeutic intervention. Here, we used a large-scale CRISPR interference viability screen to interrogate cell-growth dependency to lncRNA genes in multiple myeloma (MM) and identified a prominent role for the miR-17-92 cluster host gene (MIR17HG). We show that an MIR17HG-derived lncRNA, named lnc-17-92, is the main mediator of cell-growth dependency acting in a microRNA- and DROSHA-independent manner. Lnc-17-92 provides a chromatin scaffold for the functional interaction between c-MYC and WDR82, thus promoting the expression of ACACA, which encodes the rate-limiting enzyme of de novo lipogenesis acetyl-coA carboxylase 1. Targeting MIR17HG pre-RNA with clinically applicable antisense molecules disrupts the transcriptional and functional activities of lnc-17-92, causing potent antitumor effects both in vitro and in vivo in 3 preclinical animal models, including a clinically relevant patient-derived xenograft NSG mouse model. This study establishes a novel oncogenic function of MIR17HG and provides potent inhibitors for translation to clinical trials.

Metallo-β-lactamases (MBLs) contribute to the resistance of Gram-negative bacteria to carbapenems, last-resort antibiotics at hospital, and MBL inhibitors are urgently needed to preserve these important antibacterial drugs. Here, we describe a series of 1,2,4-triazole-3-thione-based inhibitors displaying an α-amino acid substituent, which amine was mono- or disubstituted by (hetero)aryl groups. Compounds disubstituted by certain nitrogen-containing heterocycles showed submicromolar activities against VIM-type enzymes and strong NDM-1 inhibition (Ki= 10–30 nM). Equilibrium dialysis, native mass spectrometry, isothermal calorimetry (ITC), and X-ray crystallography showed that the compounds inhibited both VIM-2 and NDM-1 at least partially by stripping the catalytic zinc ions. These inhibitors also displayed a very potent synergistic activity with meropenem (16- to 1000-fold minimum inhibitory concentration (MIC) reduction) against VIM-type- and NDM-1-producing ultraresistant clinical isolates, including Enterobacteralesand Pseudomonas aeruginosa. Furthermore, selected compounds exhibited no or moderate toxicity toward HeLa cells, favorable absorption, distribution, metabolism, excretion (ADME) properties, and no or modest inhibition of several mammalian metalloenzymes.

ABSTRACTThis paper presents a multi-faceted analytical Course Innovation Framework (CIF) that can help institutes of higher education analyze multiple aspects of course innovation. The CIF was constructed by integrating insights from literature, policy documentation and course-innovation practices at Wageningen University and Research in the Netherlands. The resulting CIF considers multiple stages of course innovation – intended, implemented and attained – along with multiple innovation processes organized into the following five clusters: Rationale for the Innovation; Nature of the Innovation; Innovation in Teaching and Learning; Evaluation and Dissemination Strategy; and Consistency and Reflection. University stakeholders experienced the CIF as usable and relevant. This study is intended to generate a multi-faceted understanding of course innovation and to provide university policy-makers and educators with inspiration or even guidance in their efforts to analyze, map and decide upon their course-innovation practices.

IMPORTANCE: Studies comparing perioperative outcomes of fibula free flaps (FFFs), osteocutaneous radial forearm free flaps (OCRFFFs), and scapula free flaps (SFFs) have been limited by insufficient sample size. OBJECTIVE: To compare the perioperative outcomes of patients who underwent FFFs, OCRFFFs, and SFFs. DESIGN, SETTING, AND PARTICIPANTS: This cohort study assessed the outcomes of 1022 patients who underwent FFFs, OCRFFFs, or SFFs for head and neck reconstruction performed at 1 of 6 academic medical centers between January 2005 and December 2019. Data were analyzed from September 17, 2021, to June 9, 2022. MAIN OUTCOMES AND MEASURES: Patients were stratified based on the flap performed. Evaluated perioperative outcomes included complications (overall acute wound complications, acute surgical site infection [SSI], fistula, hematoma, and flap failure), 30-day readmissions, operative time, and prolonged hospital length of stay (75th percentile, >13 days). Patients were excluded if data on flap type or clinical demographic characteristics were missing. Associations between flap type and perioperative outcomes were analyzed using logistic regression, after controlling for other clinically relevant variables. Adjusted odds ratios (aORs) with 95% CIs were generated. RESULTS: Perioperative outcomes of 1022 patients (mean [SD] age, 60.7 [14.5] years; 676 [66.1%] men) who underwent major osseous head and neck reconstruction were analyzed; 510 FFFs (49.9%), 376 OCRFFFs (36.8%), and 136 SFFs (13.3%) were performed. Median (IQR) operative time differed among flap types (OCRFFF, 527 [467-591] minutes; FFF, 592 [507-714] minutes; SFF, 691 [610-816] minutes). When controlling for SSI, FFFs (aOR, 2.47; 95% CI, 1.36-4.51) and SFFs (aOR, 2.95; 95% CI, 1.37-6.34) were associated with a higher risk of flap loss than OCRFFFs. Compared with OCRFFFs, FFFs (aOR, 1.77; 95% CI, 1.07-2.91) were associated with a greater risk of fistula after controlling for the number of bone segments and SSI. Both FFFs (aOR, 1.77; 95% CI, 1.27-2.46) and SFFs (aOR, 1.68; 95% CI, 1.05-2.69) were associated with an increased risk of 30-day readmission compared with OCRFFFs after controlling for Charlson-Deyo comorbidity score and acute wound complications. Compared with OCRFFFs, FFFs (aOR, 1.78; 95% CI, 1.25-2.54) and SFFs (aOR, 1.96; 95% CI, 1.22-3.13) were associated with a higher risk of prolonged hospital length of stay after controlling for age and flap loss. CONCLUSIONS AND RELEVANCE: Findings of this cohort study suggest that perioperative outcomes associated with OCRFFFs compare favorably with those of FFFs and SFFs, with shorter operative times and lower rates of flap loss, 30-day readmissions, and prolonged hospital length of stay. However, patients undergoing SFFs represented a more medically and surgically complex population than those undergoing OCRFFFs or FFFs.

Epidemiologic data highlight sex differences in melanoma outcome. A putative role of sex hormones is still under investigation. Very few laboratory investigations have focused on the level of expression of estrogen receptors in melanoma. We evaluated the presence of estrogen receptors alpha (ERα) and beta (ERβ) in melanoma specimens from female patients with a previous history of breast carcinoma (BC). Moreover, another group of female patients undergoing ovarian stimulation (OS) were also compared to two control groups matched for age and melanoma staging. The study was performed at the IRCCS Policlinico di Sant’Orsola Hospital’s Melanoma Unit from January 2017 to December 2019. The nuclear and cytoplasmatic immunohistochemical staining was evaluated and scored by the percentage of stained tumour cells: 0 (≤20%), 1 (21–50%) or 2 (≥50%). Twenty-eight specimens were analysed. ERβ nuclear presence was detected in all cases of women with a history of breast cancer. Cytoplasmatic ERβ was clearly expressed with a score of 2 in seven cases. In the respective control group, nuclear and cytoplasmatic ERβ expression was much lower. A cytoplasmatic ERα positivity was also detected in almost all cases. In the second group of women who experienced ovarian stimulation for Assisted Reproductive Technology (ART), a lower abundance of nuclear ERs was detected. Conversely, cytoplasmatic ERβ and α expression ranged widely. Melanoma of women treated with anti-estrogen therapy is generally more prone to express estrogen receptors compared with women of the same age and CM staging but also compared with women in fertile age with and without a history of OS.

Electronic transport models for conducting polymers (CPs) and blends focus on the arrangement of conjugated chains, while the contributions of the nominally insulating components to transport are largely ignored. In this work, an archetypal CP blend is used to demonstrate that the chemical structure of the non-conductive component has a substantial effect on charge carrier mobility. Upon diluting a CP with excess insulator, blends with as high as 97.4 wt % insulator can display carrier mobilities comparable to some pure CPs such as polyaniline and low regioregularity P3HT. In this work, we develop a single, multiscale transport model based on the microstructure of the CP blends, which describes the transport properties for all dilutions tested. The results show that the high carrier mobility of primarily insulator blends results from the inclusion of aromatic rings, which facilitate long-range tunneling (up to ca.3 nm) between isolated CP chains. This tunneling mechanism calls into question the current paradigm used to design CPs, where the solubilizing or ionically conducting component is considered electronically inert. Indeed, optimizing the participation of the nominally insulating component in electronic transport may lead to enhanced electronic mobility and overall better performance in CPs.

Evidence points to the impact of chronic musculoskeletal pain conditions on sexual function, yet there is little systematic appraisal and synthesis of evidence examining these associations across noninflammatory conditions. We aimed to systematically review evidence surrounding the association between chronic primary and chronic secondary musculoskeletal pain with intimate relationships and sexual function. Four electronic databases were searched from January 1, 1990 to September 5, 2019 for cross‐sectional or prospective epidemiologic and qualitative studies among cohorts with chronic primary or secondary noninflammatory musculoskeletal pain, defined by International Classification of Diseases, Eleventh Revision classification criteria. Fifty‐one eligible studies were included (46 quantitative, 3 qualitative, 2 mixed‐methods designs). Sample sizes ranged from 13 to 12,377 and mean age from 32.6 to 69.2 years. Cross‐sectional controlled cohort studies consistently reported poorer sexual function outcomes among cohorts with pain relative to comparison groups. Of 15 studies reporting outcomes for the Female Sexual Function Index, 14 demonstrated mean scores of ≤26.55 for the pain group, indicating sexual dysfunction. In 4 studies reporting the International Index of Erectile Function, the pain cohorts demonstrated consistently lower mean subscale scores and the erectile function subscale scores were ≤25.0, indicating erectile dysfunction. Three key themes emerged from a meta‐synthesis of qualitative studies: impaired sexual function; compromised intimate relationships; and impacts of pain on sexual identity, body image, and self‐worth. Sexual dysfunction and negative impacts on intimate relationships are highly prevalent among people with chronic noninflammatory musculoskeletal pain. Consideration of these associations is relevant to the delivery of holistic, person‐centered musculoskeletal pain care.

Background: Direct comparisons between [18F]FDG PET/CT findings and clinical occurrence of immune-related adverse events (irAEs) based on independent assessments of clinical and imaging features in patients receiving immune checkpoint inhibitors (ICIs) are missing. Our aim was to estimate sites, frequency, and timing of immune-related PET findings during ICIs treatment in patients with melanoma and NSCLC, and to assess their correlation with clinical irAEs. Prognostic implications of immune-related events were also investigated. Methods: Fifty-one patients with melanoma (47%) or NSCLC (53%) undergoing multiple PET examinations during anti-PD1/PDL1 treatment were retrospectively included. Clinical irAEs were graded according to CTCAE v.5.0. Abnormal PET findings suggestive of immune activation were described by two readers blinded to the clinical data. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method in patients stratified according to the presence of irAEs, immune-related PET findings or both. Results: Twenty-one patients showed clinical irAEs only (n= 6), immune-related PET findings only (n= 6), or both (n= 9). In patients whose imaging findings corresponded to clinical irAEs (n= 7), a positive correlation between SUVmaxand the severity of the clinical event was observed (rs=0.763, p= 0.046). Clinical irAEs occurred more frequently in patients without macroscopic disease than in metastatic patients (55% vs. 23%, p= 0.039). Patients who developed clinical irAEs had a significantly longer PFS than patients who remained clinically asymptomatic, both in the overall cohort (p= 0.011) and in the subgroup of (n= 35) patients with metastatic disease (p= 0.019). The occurrence of immune-related PET findings significantly stratified PFS in the overall cohort (p= 0.040), and slightly missed statistical significance in patients with metastatic disease (p= 0.08). The best stratification of PFS was achieved when all patients who developed immune-related events, either clinically relevant or detected by PET only, were grouped together both in the overall cohort (p= 0.002) and in patients with metastatic disease (p= 0.004). In the whole sample, OS was longer in patients who developed any immune-related events (p= 0.032). Conclusion: Patients with melanoma or NSCLC under ICI treatment can develop clinical irAEs, immune-related PET findings, or both. The occurrence of immune-related events has a prognostic impact. Combining clinical information with PET assessment improved outcome stratification.

Depression and obesity are highly comorbid conditions with shared biological mechanisms. It remains unclear how depressive symptoms and body mass index (BMI) interact in relation to inflammation. This cross-sectional study investigated the independent associations of depressive symptoms and BMI with high sensitivity C-reactive protein (hs-CRP), as well as the moderating role of BMI on the depressive symptoms-hs-CRP association.

With the scaling of lateral dimensions in advanced transistors, an increased gate capacitance is desirable both to retain the control of the gate electrode over the channel and to reduce the operating voltage1. This led to a fundamental change in the gate stack in 2008, the incorporation of high-dielectric-constant HfO2(ref. 2), which remains the material of choice to date. Here we report HfO2–ZrO2superlattice heterostructures as a gate stack, stabilized with mixed ferroelectric–antiferroelectric order, directly integrated onto Si transistors, and scaled down to approximately 20 ångströms, the same gate oxide thickness required for high-performance transistors. The overall equivalent oxide thickness in metal–oxide–semiconductor capacitors is equivalent to an effective SiO2thickness of approximately 6.5 ångströms. Such a low effective oxide thickness and the resulting large capacitance cannot be achieved in conventional HfO2-based high-dielectric-constant gate stacks without scavenging the interfacial SiO2, which has adverse effects on the electron transport and gate leakage current3. Accordingly, our gate stacks, which do not require such scavenging, provide substantially lower leakage current and no mobility degradation. This work demonstrates that ultrathin ferroic HfO2–ZrO2multilayers, stabilized with competing ferroelectric–antiferroelectric order in the two-nanometre-thickness regime, provide a path towards advanced gate oxide stacks in electronic devices beyond conventional HfO2-based high-dielectric-constant materials.

Aliphatic polyamides, or nylons, are typically highly crystalline and thermally robust polymers used in high-performance applications. Nylon 6, a high-ceiling-temperature (HCT) polyamide from ε-caprolactam, lacks expedient chemical recyclability, while low-ceiling temperature (LCT) nylon 4 from pyrrolidone exhibits complete chemical recyclability, but it is thermally unstable and not melt-processable. Here, we introduce a hybrid nylon, nylon 4/6, based on a bicyclic lactam composed of both HCT ε-caprolactam and LCT pyrrolidone motifs in a hybridized offspring structure. Hybrid nylon 4/6 overcomes trade-offs in (de)polymerizability and performance properties of the parent nylons, exhibiting both excellent polymerization and facile depolymerization characteristics. This stereoregular polyamide forms nanocrystalline domains, allowing optical clarity and high thermal stability, however, without displaying a melting transition before decomposition. Of a series of statistical copolymers comprising nylon 4/6 and nylon 4, a 50/50 copolymer achieves the greatest synergy in both reactivity and polymer properties of each homopolymer, offering an amorphous nylon with favorable properties, including optical clarity, a high glass transition temperature, melt processability, and full chemical recyclability.

AbstractObjective:To determine whether cascade reporting is associated with a change in meropenem and fluoroquinolone consumption.Design:A quasi-experimental study was conducted using an interrupted time series to compare antimicrobial consumption before and after the implementation of cascade reporting.Setting:A 399-bed, tertiary-care, Veterans’ Affairs medical center.Participants:Antimicrobial consumption data across 8 inpatient units were extracted from the Center for Disease Control and Prevention (CDC) National Health Safety Network (NHSN) antimicrobial use (AU) module from April 2017 through March 2019, reported as antimicrobial days of therapy (DOT) per 1,000 days present (DP).Intervention:Cascade reporting is a strategy of reporting antimicrobial susceptibility test results in which secondary agents are only reported if an organism is resistant to primary, narrow-spectrum agents. A multidisciplinary team developed cascade reporting algorithms for gram-negative bacteria based on local antibiogram and infectious diseases practice guidelines, aimed at restricting the use of fluoroquinolones and carbapenems. The algorithms were implemented in March 2018.Results:Following the implementation of cascade reporting, mean monthly meropenem (P=.005) and piperacillin/tazobactam (P= .002) consumption decreased and cefepime consumption increased (P< .001). Ciprofloxacin consumption decreased by 2.16 DOT per 1,000 DP per month (SE, 0.25; P< .001). Clostridioides difficilerates did not significantly change.Conclusion:Ciprofloxacin consumption significantly decreased after the implementation of cascade reporting. Mean meropenem consumption decreased after cascade reporting was implemented, but we observed no significant change in the slope of consumption. cascade reporting may be a useful strategy to optimize antimicrobial prescribing.