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Background: The research criteria for subjective cognitive decline (SCD) exclude mild cognitive impairment (MCI), but do not stipulate the use of specific MCI criteria. This study compared different approaches to defining (i.e., excluding) MCI during the ascertainment of SCD, focusing on the impact on dementia incidence rates in SCD., Methods: This cohort study utilized routine healthcare data collected in the Essex Memory Clinic from 1999 to 2023. Two different operationalizations of the SCD criteria were used to categorize the cohort into two SCD patient samples. One sample was based on local clinical practice - MCI was excluded according to the Winblad criteria (this sample was termed SCD Winblad ). The other sample was created via the retrospective application of the Jak/Bondi criteria for the exclusion of MCI (termed SCD Jak/Bondi ). Only patients aged ≥ 55 years at baseline with ≥ 12 months follow-up were considered for inclusion. The initial clinical/demographic characteristics of the samples were compared. Rates of incident dementia were calculated for each sample, and unadjusted and Mantel-Haenszel-adjusted incidence rate ratios were calculated to compare dementia incidence between the SCD samples., Results: The Essex Memory Clinic database included 2,233 patients in total. The SCD and study eligibility criteria were used to select SCD Winblad (n = 86) and SCD Jak/Bondi (n = 185) samples from the database. Median follow-up (3 years) did not differ between the two samples. The SCD Jak/Bondi sample was significantly older than the SCD Winblad at first assessment (median age: 74 versus 70 years) and had poorer scores on tests of global cognition, immediate and delayed verbal recall, and category fluency. Following adjustment for age, the dementia incidence rate ratio [95% confidence interval] was 3.7 [1.5 to 9.3], indicating a significantly greater rate of progression to dementia in SCD Jak/Bondi ., Conclusions: This study highlights that the approach used to ascertain SCD has important implications for both SCD phenotypes and prognosis. This underscores the importance of how MCI is operationalized within SCD studies. More broadly, the findings add to a growing body of work indicating that objective cognition should not be overlooked in SCD, and offer a potential explanation for the heterogeneity across the SCD prognostic literature., (© 2024. The Author(s).)

Background: TikTok is a popular social media site for connecting with others online where many users also access and share health-related information. Previous studies have characterized information shared about specific disabilities on TikTok, but descriptions of autism-related content are lacking. Understanding the information shared about autism on TikTok is important to understanding health communication in this space, the lived experiences of autistic people, and the role that social media platforms play in building community through connection, understanding, and inclusion., Methods: We used an open-source data scraper to identify and download videos with at least 1 million views and that used the hashtag #autism from TikTok. Using a joint inductive and deductive approach, we performed a content analysis of videos. We identified six content topics that described video content (e.g., positive social interactions and features of autism), and three categories that described video purpose (e.g., educational, experiential, and observational). We used descriptive statistics to describe characteristics of who was in the TikTok videos., Results: We analyzed n  = 678 videos. The most common content topic of TikTok videos was features of autism (39.7%), followed by marginalization (25.4%). Most videos were categorized as experiential (61.4%) or observational (31.4%) rather than educational (7.2%). Approximately 65.5% of videos featured an autistic adult and 22.6% featured an autistic child. Among videos featuring an autistic person ( n  = 594), most autistic people were perceived to be White (87.0%) with similar numbers of feminine (52.9%) and masculine (44.8%) presenting autistic people., Conclusions: Highly viewed #autism TikTok videos primarily share autistic people's individual experiences rather than providing general education about autism. However, autistic Black, Indigenous, and people of color may have difficulty finding others that represent them along both disability and racial dimensions. Future research should investigate autistic people's motivations for using TikTok, and how #autism content shapes social discourse about autism., Competing Interests: No competing financial interests exist., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Aim: Previous research using state or regional samples has shown that autistic adults have a higher prevalence of health conditions in comparison to the general population. Methods: To build upon this important previous research, we conducted a cross-sectional retrospective study of 2019-2020 healthcare claims to determine the prevalence of conditions in a US national sample of privately insured autistic adults (n = 30,258) and an age- and sex-matched population comparison (n = 60,516) group of adults without autism diagnoses. Results: Like previous studies, we found that autistic adults had significantly greater odds of most mental and physical health conditions. However, our prevalence estimates differed from previous studies for several mental and physical health conditions. For example, our sample of autistic adults had higher prevalence of anxiety disorders (55%) and attention deficit hyperactivity disorders (34%), but lower prevalence of asthma (9%) and sleep disorders (3%) than previous studies. Discussion & conclusion: Our use of a large US national sample, more recent healthcare claims data, and different methods for identifying health conditions may have contributed to these differences. Our findings alert healthcare providers and policymakers to the health conditions most common among the growing population of autistic adults. We hope these findings lead to improved screening and management of these conditions, inform initiatives to improve access to healthcare, and guide future funding.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

Background: Healthcare independence refers to an individual's ability to participate in and manage their healthcare by using specific skills like communicating with providers and scheduling appointments. Understanding healthcare independence among autistic young adults is important to designing healthcare systems that provide equitable support for autistic people throughout their lives., Objective: To quantify changes in autistic adults' healthcare independence over time and understand factors associated with change in healthcare independence., Methods: We administered a measure of healthcare skills, the Transition Readiness Assessment Questionnaire (TRAQ), to n = 27 autistic young adults who provided a self-report, and n = 21 autistic young adults who participated via proxy-report by supporters, at one autism-specialized primary care clinic. Participants completed the TRAQ at baseline, six months, and 12 months. We used repeated measures generalized linear mixed models to quantify changes in healthcare independence over time, controlling for demographic factors, executive functioning, restrictive and repetitive behaviors, and number of clinic visits. To understand factors associated with change in healthcare independence, we completed follow-up semi-structured interviews with n = 6 autistic young adults and n = 5 supporters of autistic young adults., Results: Autistic young adults who participated via self-report showed statistically significantly increases in healthcare independence between baseline and 12 months and between six months and 12 months, and significant increases on most TRAQ subdomains over time (e.g., appointment keeping, managing medications). Autistic young adults who participated via proxy-report showed no significant changes in healthcare independence over time, and significant improvement on the management of activities subdomain between baseline and 12 months. Changes in healthcare independence were associated with interactions with providers, individual health changes, consistent support needs, and community resources., Conclusions: At one autism-specialized primary care clinic, some autistic young adults may demonstrate improvements in healthcare independence, but other autistic young adults may require additional support strategies to increase healthcare independence. Future studies among larger samples are needed to obtain generalizable understanding of healthcare independence for autistic adults., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brittany N. Hand reports financial support was provided by Autism Speaks. Christopher Hanks reports a relationship with The Center for Autism Services and Transition that includes: employment. Christopher Hanks is the founder and medical director of CAST., (© 2023 The Authors.)

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known β and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19}  yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single β and electron capture decay ever achieved. Over all channels, the decay can be excluded for T&#95;{1/2}<0.29×10^{18}  yr.

Background: Health care resource utilization (HCRU) and costs are important metrics of health care burden, but they have rarely been explored in the setting of cardiac ion channelopathies., Hypothesis: This study tested the hypothesis that attendance-related HCRUs and costs differed between patients with Brugada syndrome (BrS) and congenital long QT syndrome (LQTS)., Methods: This was a retrospective cohort study of consecutive BrS and LQTS patients at public hospitals or clinics in Hong Kong, China. HCRUs and costs (in USD) for Accident and Emergency (A&E), inpatient, general outpatient and specialist outpatient attendances were analyzed between 2001 and 2019 at the cohort level. Comparisons were made using incidence rate ratios (IRRs [95% confidence intervals])., Results: Over the 19-year period, 516 BrS (median age of initial presentation: 51 [interquartile range: 38-61] years, 92% male) and 134 LQTS (median age of initial presentation: 21 [9-44] years, 32% male) patients were included. Compared to LQTS patients, BrS patients had lower total costs (2 008 126 [2 007 622-2 008 629] vs. 2 343 864 [2 342 828-2 344 900]; IRR: 0.857 [0.855-0.858]), higher costs for A&E attendances (83 113 [83 048-83 177] vs. 70 604 [70 487-70 721]; IRR: 1.177 [1.165-1.189]) and general outpatient services (2,176 [2,166-2,187] vs. 921 [908-935]; IRR: 2.363 [2.187-2.552]), but lower costs for inpatient stay (1 391 624 [1 391 359-1 391 889] vs. 1 713 742 [1 713 166-1 714 319]; IRR: 0.812 [0.810-0.814]) and lower costs for specialist outpatient services (531 213 [531 049-531 376] vs. 558 597 [558268-558926]; IRR: 0.951 [0.947-0.9550])., Conclusions: Overall, BrS patients consume 14% less health care resources compared to LQTS patients in terms of attendance costs. BrS patients require more A&E and general outpatient services, but less inpatient and specialist outpatient services than LQTS patients., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Soil-borne oomycetes include devastating plant pathogens that cause substantial losses in the agricultural sector. To better manage this important group of pathogens, it is critical to understand how they respond to common agricultural practices, such as tillage and crop rotation. Here, a long-term field experiment was established using a split-plot design with tillage as the main plot factor (conventional tillage (CT) vs. no till (NT), two levels) and rotation as the subplot factor (monocultures of soybean, corn, or wheat, and corn-soybean-wheat rotation, four levels). Post-harvest soil oomycete communities were characterized over three consecutive years (2016-2018) by metabarcoding the Internal Transcribed Spacer 1 (ITS1) region. The community contained 292 amplicon sequence variants (ASVs) and was dominated by Globisporangium spp. (85.1% in abundance, 203 ASV) and Pythium spp. (10.4%, 51 ASV). NT decreased diversity and community compositional structure heterogeneity, while crop rotation only affected the community structure under CT. The interaction effects of tillage and rotation on most oomycetes species accentuated the complexity of managing these pathogens. Soil and crop health represented by soybean seedling vitality was lowest in soils under CT cultivating soybean or corn, while the grain yield of the three crops responded differently to tillage and crop rotation regimes.

Self-assembled monolayers (SAMs) of perfluoroalkanethiols [CF3(CF2)xCH2CH2SH (x = 3, 5, 7, and 9)] on gold were characterized by x-ray photoelectron spectroscopy (XPS), near edge x-ray absorption fine structure (NEXAFS), and static time-of-flight secondary ion mass spectrometry (ToF-SIMS). Perfluoroalkanethiols of several chain lengths were synthesized using a known hydride reduction method for transforming commercially available perfluoroalkyliodides to corresponding perfluoroalkanethiols. This strategy provides improved product yields compared to other known routes based on hydrolysis from the common thioacetyl perfluoroalkyl intermediate. Angle-dependent XPS analysis revealed that CF3(CF2)xCH2CH2SH (x = 5, 7, and 9; F6, F8, and F10, respectively) SAMs on gold exhibited significant enrichment of the terminal CF3 group at the outer monolayer surface with the sulfur present as a metal-bound thiolate located at the monolayer-gold interface. XPS of the CF3(CF2)3CH2CH2SH (F4) monolayer revealed a thin film with a significant (>50%) amount of hydrocarbon contamination consistent with poorly organized monolayers, while the longest thiol (F10) showed XPS signals attributed to substantial ordering and anisotropy. ToF-SIMS spectra from all four SAMs contained molecular ions representative of the particular perfluorinated thiol used to prepare the monolayer. NEXAFS methods were used to determine degrees of ordering and average tilt for molecules comprising monolayers. The SAMs prepared from the longest (F10) thiols exhibited the highest degree of ordering with the molecular axis nearly perpendicular to the gold surface. The degree of ordering decreased significantly with decreasing length of the perfluorocarbon tail., (2023 Published under an exclusive license by the AVS.)

Background: The freshwater microbiome regulates aquatic ecological functionality, nutrient cycling, pathogenicity, and has the capacity to dissipate and regulate pollutants. Agricultural drainage ditches are ubiquitous in regions where field drainage is necessary for crop productivity, and as such, are first-line receptors of agricultural drainage and runoff. How bacterial communities in these systems respond to environmental and anthropogenic stressors are not well understood. In this study, we carried out a three year study in an agriculturally dominated river basin in eastern Ontario, Canada to explore the spatial and temporal dynamics of the core and conditionally rare taxa (CRT) of the instream bacterial communities using a 16S rRNA gene amplicon sequencing approach. Water samples were collected from nine stream and drainage ditch sites that represented the influence of a range of upstream land uses., Results: The cross-site core and CRT accounted for 5.6% of the total number of amplicon sequence variants (ASVs), yet represented, on average, over 60% of the heterogeneity of the overall bacterial community; hence, well reflected the spatial and temporal microbial dynamics in the water courses. The contribution of core microbiome to the overall community heterogeneity represented the community stability across all sampling sites. CRT was primarily composed of functional taxa involved in nitrogen (N) cycling and was linked to nutrient loading, water levels, and flow, particularly in the smaller agricultural drainage ditches. Both the core and the CRT were sensitive responders to changes in hydrological conditions., Conclusions: We demonstrate that core and CRT can be considered as holistic tools to explore the temporal and spatial variations of the aquatic microbial community and can be used as sensitive indicators of the health and function of agriculturally dominated water courses. This approach also reduces computational complexity in relation to analyzing the entire microbial community for such purposes., (© 2023. Crown.)

Background and Objectives: Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome., Findings: Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted., Conclusions: Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients., (© 2023 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

The Majorana Demonstrator searched for neutrinoless double-β decay (0νββ) of ^{76}Ge using modular arrays of high-purity Ge detectors operated in vacuum cryostats in a low-background shield. The arrays operated with up to 40.4 kg of detectors (27.2 kg enriched to ∼88% in ^{76}Ge). From these measurements, the Demonstrator has accumulated 64.5 kg yr of enriched active exposure. With a world-leading energy resolution of 2.52 keV FWHM at the 2039 keV Q&#95;{ββ} (0.12%), we set a half-life limit of 0νββ in ^{76}Ge at T&#95;{1/2}>8.3×10^{25}  yr (90% C.L.). This provides a range of upper limits on m&#95;{ββ} of (113-269) meV (90% C.L.), depending on the choice of nuclear matrix elements.

Understanding health care resource utilisation and its associated costs are important for identifying areas of improvement regarding resource allocations. However, there is limited research exploring this issue in the setting of Brugada syndrome (BrS).This was a retrospective territory-wide study of BrS patients from Hong Kong. Healthcare resource utilisation for accident and emergency (A&E), inpatient and specialist outpatient attendances were analyzed over a 19-year period, with their associated costs presented in US dollars. A total of 507 BrS patients with a mean presentation age of 49.9 ± 16.3 years old were included. Of these, 384 patients displayed spontaneous type 1 electrocardiographic (ECG) Brugada pattern and 77 patients had presented with ventricular tachycardia/ventricular fibrillation (VT/VF). At the individual patient level, the median annualized costs were $110 (52-224) at the (A&E) setting, $6812 (1982-32414) at the inpatient setting and $557 (326-1001) for specialist outpatient attendances. Patients with initial VT/VF presentation had overall greater costs in inpatient ($20161 [9147-189215] vs $5290 [1613-24937],P < 0.0001) and specialist outpatient setting ($776 [438-1076] vs $542 [293-972],P = 0.015) compared to those who did not present VT. In addition, patients without Type 1 ECG pattern had greater median costs in the specialist outpatient setting ($7036 [3136-14378] vs $4895 [2409-10554],p=0.019). There is a greater health care demand in the inpatient and specialist outpatient settings for BrS patients. The most expensive attendance type was inpatient setting stay at $6812 per year. The total median annualized cost of BrS patients without VT/VF presentation was 78% lower compared to patients with VT/VF presentation., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Left ventricular non-compaction cardiomyopathy (LVNC) is a congenital heart disease with autosomal dominant inheritance. This review aims to summarize the existing data about the predictors of fatal arrhythmias in patients with LVNC. Medline and Cochrane library databases were searched from inception to November 2021 for articles on LVNC. The reference lists of the relevant research studies as well as the relevant review studies and meta-analyses were also searched. Clinical symptoms and electrocardiogram findings such as left bundle branch block are significantly associated with ventricular arrhythmias. Other non-invasive tools such as Holter monitoring, echocardiography, and cardiac magnetic resonance (CMR) can provide additional value for risk stratification. CMR-derived left and right ventricular ejection fraction, left ventricular end-diastolic diameter, late gadolinium enhancement, and non-compacted to compacted myocardium ratio are predictive of ventricular arrhythmias. An electrophysiological study can provide additional prognostic data in patients with LVNC who are at moderate risk of ventricular arrhythmias. Risk stratification of LVNC patients with no prior history of a fatal arrhythmic event remains challenging. Symptoms assessment, electrocardiogram, Holter monitoring, and cardiac imaging should be performed on every patient, while an electrophysiological study should be performed for moderate-risk patients. Large cohort studies are needed for the construction of score models for arrhythmic risk stratification purposes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Drug-Free Macromolecular Therapeutics (DFMT) is a new paradigm in macromolecular therapeutics that induces apoptosis in target cells by crosslinking receptors without the need of low molecular weight drugs. Programmed cell death is initiated via a biomimetic receptor crosslinking strategy using a two-step approach: i) recognition of cell surface antigen by a morpholino oligonucleotide-modified antibody Fab' fragment (Fab'-MORF1), ii) followed by crosslinking with a multivalent effector motif - human serum albumin (HSA) grafted with multiple complementary morpholino oligonucleotides (HSA-(MORF2) x ). This approach is effective in vitro, in vivo, and ex vivo on cells from patients diagnosed with various B cell malignancies. We have previously demonstrated DFMT can be applied to crosslink CD20 and CD38 receptors to successfully initiate apoptosis. Herein, we show simultaneous engagement, and subsequent crosslinking of both targets ("heteroreceptor crosslinking"), can further enhance the apoptosis induction capacity of this system. To accomplish this, we incubated Raji (CD20+; CD38+) cells simultaneously with anti-CD20 and anti-CD38 Fab'-MORF1 conjugates, followed by addition of the macromolecular crosslinker, HSA-(MORF2) x to co-cluster the bound receptors. Fab' fragments from Rituximab and Obinutuzumab were employed in the synthesis of anti-CD20 bispecific engagers (Fab' RTX -MORF1 and Fab' OBN -MORF1), whereas Fab' fragments from Daratumumab and Isatuximab (Fab' DARA -MORF1 and Fab' ISA -MORF1) targeted CD38. All heteroreceptor crosslinking DFMT combinations demonstrated potent apoptosis induction and exhibited synergistic effects as determined by Chou-Talalay combination index studies (CI < 1). In vitro fluorescence resonance energy transfer (FRET) experiments confirmed the co-clustering of the two receptors on the cell surface in response to the combination treatment. The source of this synergistic therapeutic effect was further explored by evaluating the effect of combination DFMT on key apoptosis signaling events such as mitochondrial depolarization, caspase activation, lysosomal enlargement, and homotypic cell adhesion. Finally, a xenograft mouse model of CD20+/CD38+ Non Hodgkin lymphoma was employed to demonstrate in vivo the enhanced efficacy of the heteroreceptor-crosslinking DFMT design versus single-target systems., Competing Interests: Declaration of Competing Interest The authors declare the following competing financial interest(s): J.Y. and J.K. are co-inventors on a pending US patent application (PCT/US2014/023784; assigned to the University of Utah) related to this work. J.K. is Chief Scientific Advisor and J.Y. Scientific Advisor, and P.S. Chief Medical Advisor for Bastion Biologics. Otherwise, the authors declare no competing financial interests., (Copyright © 2022. Published by Elsevier B.V.)

Purpose of Review: We reviewed the literature from 2017 to 2022 on autistic adults' use of mental healthcare and barriers to care. To encourage immediate improvement in mental healthcare, we provide five strategies mental health providers can use to better care for autistic adults., Recent Findings: Most autistic adults use mental healthcare and use it more often than non-autistic adults. Autistic adults' experiences with mental healthcare are characterized by (1) lack of providers knowledgeable about autism, (2) use of treatments that may not be accommodating to individual needs, and (3) difficulty navigating the complex healthcare system. These barriers contribute to prevalent unmet needs for mental healthcare. Autistic adults use mental healthcare frequently but have unmet mental health needs. As necessary systemic changes develop, providers can begin immediately to better care for autistic adults by learning about their needs and taking personalized care approaches to meet those needs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Coronavirus Disease-2019 (COVID-19) vaccination has been associated with the development of carditis, especially in children and adolescent males. However, the rates of these events in the global setting have not been explored in a systematic manner. The aim of this systematic review and meta-analysis is to investigate the rates of carditis in children and adolescents receiving COVID-19 vaccines., Methods: PubMed, Embase and several Latin American databases were searched for studies. The number of events, and where available, at-risk populations were extracted. Rate ratios were calculated and expressed as a rate per million doses received. Subgroup analysis based on the dose administered was performed. Subjects ≤ 19 years old who developed pericarditis or myocarditis following COVID-19 vaccination were included., Results: A total of 369 entries were retrieved. After screening, 39 articles were included. Our meta-analysis found that 343 patients developed carditis after the administration of 12,602,625 COVID-19 vaccination doses (pooled rate per million: 37.76; 95% confidence interval [CI] 23.57, 59.19). The rate of carditis was higher amongst male patients (pooled rate ratio: 5.04; 95% CI 1.40, 18.19) and after the second vaccination dose (pooled rate ratio: 5.60; 95% CI 1.97, 15.89). In 301 cases of carditis (281 male; mean age: 15.90 (standard deviation [SD] 1.52) years old) reported amongst the case series/reports, 261 patients were reported to have received treatment. 97.34% of the patients presented with chest pain. The common findings include ST elevation and T wave abnormalities on electrocardiography. Oedema and late gadolinium enhancement in the myocardium were frequently observed in cardiac magnetic resonance imaging (CMR). The mean length of hospital stay was 3.91 days (SD 1.75). In 298 out of 299 patients (99.67%) the carditis resolved with or without treatment., Conclusions: Carditis is a rare complication after COVID-19 vaccination across the globe, but the vast majority of episodes are self-limiting with rapid resolution of symptoms within days. Central illustration. Balancing the benefits of vaccines on COVID-19-caused carditis and post-vaccination carditis., (© 2022. The Author(s).)

Axions were originally proposed to explain the strong-CP problem in QCD. Through axion-photon coupling, the Sun could be a major source of axions, which could be measured in solid state detection experiments with enhancements due to coherent Primakoff-Bragg scattering. The Majorana Demonstrator experiment has searched for solar axions with a set of ^{76}Ge-enriched high purity germanium detectors using a 33 kg-yr exposure collected between January, 2017 and November, 2019. A temporal-energy analysis gives a new limit on the axion-photon coupling as g&#95;{aγ}<1.45×10^{-9}  GeV^{-1} (95% confidence level) for axions with mass up to 100  eV/c^{2}. This improves laboratory-based limits between about 1  eV/c^{2} and 100  eV/c^{2}.

The Majorana Demonstrator neutrinoless double-beta decay experiment comprises a 44 kg (30 kg enriched in ^{76}Ge) array of p-type, point-contact germanium detectors. With its unprecedented energy resolution and ultralow backgrounds, Majorana also searches for rare event signatures from beyond standard model physics in the low energy region below 100 keV. In this Letter, we test the continuous spontaneous localization (CSL) model, one of the mathematically well-motivated wave function collapse models aimed at solving the long-standing unresolved quantum mechanical measurement problem. While the CSL predicts the existence of a detectable radiation signature in the x-ray domain, we find no evidence of such radiation in the 19-100 keV range in a 37.5 kg-y enriched germanium exposure collected between December 31, 2015, and November 27, 2019, with the Demonstrator. We explored both the non-mass-proportional (n-m-p) and the mass-proportional (m-p) versions of the CSL with two different assumptions: that only the quasifree electrons can emit the x-ray radiation and that the nucleus can coherently emit an amplified radiation. In all cases, we set the most stringent upper limit to date for the white CSL model on the collapse rate, λ, providing a factor of 40-100 improvement in sensitivity over comparable searches. Our limit is the most stringent for large parts of the allowed parameter space. If the result is interpreted in terms of the Diòsi-Penrose gravitational wave function collapse model, the lower bound with a 95% confidence level is almost an order of magnitude improvement over the previous best limit.

Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited cardiac ion channelopathy. The present study aims to examine the clinical characteristics, genetic basis, and arrhythmic outcomes of CPVT patients from China to elucidate the difference between CPVT patients in Asia and Western countries., Methods: PubMed and Embase were systematically searched for case reports or series reporting on CPVT patients from China until 19 February 2022 using the keyword: "Catecholaminergic Polymorphic Ventricular Tachycardia" or "CPVT", with the location limited to: "China" or "Hong Kong" or "Macau" in Embase, with no language or publication-type restriction. Articles that did not state a definite diagnosis of CPVT and articles with duplicate cases found in larger cohorts were excluded. All the included publications in this review were critically appraised based on the Joanna Briggs Institute Critical Appraisal Checklist. Clinical characteristics, genetic findings, and the primary outcome of spontaneous ventricular tachycardia/ventricular fibrillation (VT/VF) were analyzed., Results: A total of 58 unique cases from 15 studies (median presentation age: 8 (5.0-11.8) years old) were included. All patients, except one, presented at or before 19 years of age. There were 56 patients (96.6%) who were initially symptomatic. Premature ventricular complexes (PVCs) were present in 44 out of 51 patients (86.3%) and VT in 52 out of 58 patients (89.7%). Genetic tests were performed on 54 patients (93.1%) with a yield of 87%. RyR2, CASQ2, TERCL, and SCN10A mutations were found in 35 (71.4%), 12 (24.5%), 1 (0.02%) patient, and 1 patient (0.02%), respectively. There were 54 patients who were treated with beta-blockers, 8 received flecainide, 5 received amiodarone, 2 received verapamil and 2 received propafenone. Sympathectomy ( n = 10), implantable cardioverter-defibrillator implantation ( n = 8) and ablation ( n = 1) were performed. On follow-up, 13 patients developed VT/VF., Conclusion: This was the first systematic review of CPVT patients from China. Most patients had symptoms on initial presentation, with syncope as the presenting complaint. RyR2 mutation accounts for more than half of the CPVT cases, followed by CASQ2, TERCL and SCN10A mutations.

Brugada syndrome (BrS) is a rare disorder characterized by coved or saddle-shaped ST-segment elevation in the right precordial leads on the electrocardiogram. Risk stratification in BrS remains challenging. A number of clinical, electrocardiographic, programmed ventricular stimulation and genetic risk factors have been identified as important predictors of future major arrhythmic events. There is a positive association between the number of risk factors and arrhythmic events. Hence, a multi-parametric approach would provide comprehensive risk assessment and more accurate risk stratification, assisting in therapeutic decisions making, including implantable cardioverter-defibrillator placement or identification of low-risk individuals. However, the extent to which each variable influences the risk and non-linear interactions between the different risk variables make risk stratification challenging. This paper aims to provide a focused review of the multi-parametric risk models for BrS risk stratification published in the literature., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The dispersion of fungal inocula such as the airborne spores of rust fungi (Pucciniales) can be monitored through metabarcoding of the internal transcribed spacer 2 (ITS2) of the rRNA gene in environmental DNAs. This method is largely dependent on a high-quality reference database (refDB) and primers with proper taxonomic coverage and specificity. For this study, a curated ITS2 reference database (named CR-ITS2-refDB) comprising representatives of the major cereal rust fungi and phylogenetically related species was compiled. Interspecific and intraspecific variation analyses suggested that the ITS2 region had reasonable discriminating power for the majority of the Puccinia species or species complexes in the database. In silico evaluation of nine forward and seven reverse ITS2 primers, including three newly designed, revealed marked variation in DNA amplification efficiency for the rusts. We validated the theoretical assessment of rust-enhanced (Rust2inv/ITS4var&#95;H) and universal fungal (ITS9F/ITS4) ITS2 primer pairs by profiling the airborne rust fungal communities from environmental samples via a metabarcoding approach. Species- or subspecies-level identification of the rusts was improved by use of CR-ITS2-refDB and the Automated Oligonucleotide Design Pipeline (AODP), which identified all mutations distinguishing highly conserved DNA markers between close relatives. A generic bioinformatics pipeline was developed, including all steps used in this study from in silico evaluation of primers to accurate identification of short metabarcodes at the level of interest for defining phytopathogens. The results highlight the importance of primer selection, refDBs that are resolved to reflect phylogenetic relationships, and the use of AODP for improving the reliability of metabarcoding in phytopathogen biosurveillance.

P-type point contact (PPC) HPGe detectors are a leading technology for rare event searches due to their excellent energy resolution, low thresholds, and multi-site event rejection capabilities. We have characterized a PPC detector's response to α particles incident on the sensitive passivated and p + surfaces, a previously poorly-understood source of background. The detector studied is identical to those in the Majorana Demonstrator experiment, a search for neutrinoless double-beta decay ( 0 ν β β ) in 76 Ge. α decays on most of the passivated surface exhibit significant energy loss due to charge trapping, with waveforms exhibiting a delayed charge recovery (DCR) signature caused by the slow collection of a fraction of the trapped charge. The DCR is found to be complementary to existing methods of α identification, reliably identifying α background events on the passivated surface of the detector. We demonstrate effective rejection of all surface α events (to within statistical uncertainty) with a loss of only 0.2% of bulk events by combining the DCR discriminator with previously-used methods. The DCR discriminator has been used to reduce the background rate in the 0 ν β β region of interest window by an order of magnitude in the Majorana Demonstrator  and will be used in the upcoming LEGEND-200 experiment., (© The Author(s) 2022.)

Immune checkpoint blockade has revolutionized the treatment of tumors with immunogenic microenvironments. However, low response rate and acquired resistance are still major challenges. Herein we used a more clinically relevant model of transgenic MMTV-PyMT tumor that more closely mimics the development of human breast cancer in an immunocompetent background to investigate a polymer-based chemo-immunotherapy. We have found that tumors acquired an increased degree of immune suppression during progression, rendering them unresponsive to anti-PD-L1 therapy. To treat large tumors at their advanced stage, we applied a combination strategy consisting of two polymer-drug conjugates that could induce immunogenic cell death (ICD) and disrupt the PD-L1/PD-1 interaction, respectively. Although ICD-inducing conjugate remodeled tumor immune microenvironment by facilitating significant CD8 + T cell infiltration, advanced tumor adapted the immune suppressive mechanism of elevating PD-L1 expression on both cancer cells and myeloid cells thereafter to enable continued tumor growth. Concurrent treatment of PD-L1 blocking conjugate not only abrogated the PD-L1 expression from the two disparate cellular sources, but also considerably reduced the number of immunosuppressive myeloid cells, thereby leading to a significant shrinkage of advanced tumors. Our data provide evidence that combinatory strategy of ICD-inducing and PD-L-blocking modalities could reverse immune suppression and establish a basis for the rational design of cancer immunotherapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The architecture of multivalent polymers exerts an amplified interaction between attached ligands and targets. In current research, we reveal that a dendronized polymer augments the efficacy of an oncolytic peptide (OP; KKWWKKWDipK) for immunotherapy by exploiting (i) "flexible" linear polymer backbone to facilitate interactions with biomembrane systems, and (ii) "rigid" dendronized side chains to enhance the membrane lytic property. We show that a dendronized N-(2-hydroxypropyl)methacrylamide (HPMA) polymer-OP conjugate (PDOP) adopts α-helix secondary structure and induces robust immunogenic cell death (ICD) in cancer cells as characterized by multiple damage-associated molecular patterns (DAMPs) which include intracellular formation of reactive oxygen species (ROS) and surface exposure of calreticulin (CRT). These events convert immunosuppressive 4T1 tumor to an immunoresponsive one by recruiting CD8+ cytotoxic T cells into tumor beds. Combination of PDOP with anti-PD-L1 immune checkpoint blockade (ICB) increases the number of effector memory T cells and completely eradicates 4T1 tumors in mice. Our findings suggest that PDOP is a promising platform for oncolytic immunotherapy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

We report the first measurement of coherent elastic neutrino-nucleus scattering (CEvNS) on argon using a liquid argon detector at the Oak Ridge National Laboratory Spallation Neutron Source. Two independent analyses prefer CEvNS over the background-only null hypothesis with greater than 3σ significance. The measured cross section, averaged over the incident neutrino flux, is (2.2±0.7)×10^{-39}  cm^{2}-consistent with the standard model prediction. The neutron-number dependence of this result, together with that from our previous measurement on CsI, confirms the existence of the CEvNS process and provides improved constraints on nonstandard neutrino interactions.

Checkpoint blockade immunotherapies harness the host's own immune system to fight cancer, but only work against tumors infiltrated by swarms of pre-existing T cells. Unfortunately, most cancers to date are immune-deserted. Here, we report a polymer-assisted combination of immunogenic chemotherapy and PD-L1 degradation for efficacious treatment in originally non-immunogenic cancer. "Priming" tumors with backbone-degradable polymer-epirubicin conjugates elicits immunogenic cell death and fosters tumor-specific CD8+ T cell response. Sequential treatment with a multivalent polymer-peptide antagonist to PD-L1 overcomes adaptive PD-L1 enrichment following chemotherapy, biases the recycling of PD-L1 to lysosome degradation via surface receptor crosslinking, and produces prolonged elimination of PD-L1 rather than the transient blocking afforded by standard anti-PD-L1 antibodies. Together, these findings established the polymer-facilitated tumor targeting of immunogenic drugs and surface crosslinking of PD-L1 as a potential new therapeutic strategy to propagate a long-term antitumor immunity, which might broaden the application of immunotherapy to immunosuppressive cancers., Competing Interests: Conflict of Interest J.K. and J.Y. are co-inventors of US Patent 9,289,510 related to KT-1; L.L., J.K., and J.Y. are co-inventors of a patent application related to combination chemo- and immunotherapy. The University of Utah licensed both to TheraTarget. Inc.

Incorporating targeting moieties that recognize cancer-specific cellular markers can enhance specificity of anticancer nanomedicines. The HER2 receptor is overexpressed on numerous cancers, making it an attractive target. However, unlike many receptors that trigger endocytosis upon ligand binding, HER2 is an internalization-resistant receptor. As most chemotherapeutics act on intracellular targets, this presents a significant challenge for exploiting HER2 overexpression for improved tumor killing. However, hyper-crosslinking of HER2 has been shown to override the receptor's native behavior and trigger internalization. This research co-opts this crosslinking-mediated internalization for efficient intracellular delivery of an anticancer nanomedicine - specifically a HPMA copolymer-based drug delivery system. This polymeric carrier was conjugated with a small (7 kDa) HER2-binding affibody peptide to produce a panel of polymer-affibody conjugates with valences from 2 to 10 peptides per polymer chain. The effect of valence on surface binding and uptake was evaluated separately. All conjugates demonstrated similar (nanomolar) binding affinity towards HER2-positive ovarian carcinoma cells, but higher-valence conjugates induced more rapid endocytosis, with over 90% of the surface-bound conjugate internalized within 4 h. Furthermore, this enhancement was sensitive to crowding - high surface loading reduced conjugates' ability to crosslink receptors. Collectively, this evidence strongly supports a crosslinking-mediated endocytosis mechanism. Lead candidates from this panel achieved high intracellular delivery even at picomolar treatment concentrations; untargeted HPMA copolymers required 1000-fold higher treatment concentrations to achieve similar levels of intracellular accumulation. This increased intracellular delivery also translated to a more potent nanomedicine against HER2-positive cells; incorporation of the chemotherapeutic paclitaxel into this targeted carrier enhanced cytotoxicity over untargeted polymer-drug conjugate., Competing Interests: Declaration of Competing Interest JY and JK are co-inventors of US patent 9,289,510 related to the technology used in the manuscript that the University of Utah licensed to TheraTarget. Otherwise, the authors declare no competing financial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Radioactive ^{129}Sb, which can be treated as a proton plus semimagic ^{128}Sn core within the particle-core coupling scheme, was studied by Coulomb excitation. Reduced electric quadrupole transition probabilities, B(E2), for the 2^{+}⊗πg&#95;{7/2} multiplet members and candidate πd&#95;{5/2} state were measured. The results indicate that the total electric quadrupole strength of ^{129}Sb is a factor of 1.39(11) larger than the ^{128}Sn core, which is in stark contrast to the expectations of the empirically successful particle-core coupling scheme. Shell-model calculations performed with two different sets of nucleon-nucleon interactions suggest that this enhanced collectivity is due to constructive quadrupole coherence in the wave functions stemming from the proton-neutron residual interactions, where adding one nucleon to a core near a double-shell closure can have a pronounced effect. The enhanced electric quadrupole strength is an early signal of the emerging nuclear collectivity that becomes dominant away from the shell closure.

Monoclonal antibody therapy has offered treatment benefits. Nonetheless, a lack of efficacy still exists, partially because monovalent binding of antibodies to specific receptors fails to translate into an active response. Here, we report a pretargeting-postassembly approach that exploits the selective Watson-Crick base pairing properties of oligonucleotides and multivalently tethers receptor-prebound antibodies to albumin at the cell surface. We demonstrate that this two-step self-assembling strategy allows sequential actions of receptor binding and clustering that broadens and strengthens the functions of antibodies. We show that anti-CD20 obinutuzumab (OBN) modified with one morpholino oligonucleotide (OBN-MORF1) maintains the feature of naked OBN antibody upon CD20 binding, and results in actin redistribution, homotypic adhesion, and lysosome-mediated cell death. Consecutive treatment with albumin grafted with multiple copies of a complementary morpholino oligonucleotide (HSA-(MORF2) x ) hybridizes with surface-attached OBN-MORF1, manipulates CD20 clustering, and engages additional signals to induce calcium influx and caspase-related apoptosis. With the two types of different mechanisms collaborating in one system, the simple design exerted a notable survival extension of mice bearing disseminated B-cell lymphomas.

Background: A lymphedema (LE) prevention surgery (LPS) paradigm for patients undergoing axillary lymphadenectomy (ALND) was developed to protect against LE through enhanced lymphatic visualization during axillary reverse mapping (ARM) and refinement in decision making during lymphaticovenous bypass (LVB)., Methods: A retrospective analysis of a prospective database was performed evaluating patients with breast cancer who underwent ALND, ARM, and LVB from September 2016 to December 2018. Patient and tumor characteristics, oncologic and reconstructive operative details, complications and LE development were analyzed., Results: LPS was completed in 58 patients with a mean age of 51.7 years. An average of 14 lymph nodes (LN) were removed during ALND. An average of 2.1 blue lymphatic channels were visualized with an average of 1.4 LVBs performed per patient. End to end anastomosis was performed in 37 patients and a multiple lymphatic intussusception technique in 21. Patency was confirmed 96.5% of patients. Adjuvant radiation was administered to 89% of patients. Two patients developed LE with a median follow-up of 11.8 months., Conclusion: We report on our experience using a unique LPS technique. Refinements in ARM and a systematic approach to LVB allows for maximal preservation of lymphatic continuity, identification of transected lymphatics, and reestablishment of upper extremity lymphatic drainage pathways., (© 2019 Wiley Periodicals, Inc.)

Drug-free macromolecular therapeutics (DFMT) is a new paradigm for the treatment of B cell malignancies. Apoptosis is initiated by the biorecognition of complementary oligonucleotide motifs at the cell surface resulting in crosslinking of CD20 receptors. DMFT is composed from two nanoconjugates: 1) bispecific engager, Fab'-MORF1 (anti-CD20 Fab' fragment conjugated with morpholino oligonucleotide), and 2) a crosslinking (effector) component P-(MORF2) X (N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer grafted with multiple copies of complementary morpholino oligonucleotide). We evaluated this concept in 44 samples isolated from patients diagnosed with various subtypes of B cell malignancies. Apoptosis was observed in 65.9% of the samples tested. Pretreatment of cells with gemcitabine (GEM) or polymer-gemcitabine conjugate (2P-GEM) enhanced CD20 expression levels thus increasing apoptosis induced by DFMT. These positive results demonstrated that DFMT has remarkable therapeutic potential in various subtypes of B cell malignancies., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Bilateral nipple-sparing mastectomy (NSM) is a technically feasible operation and is associated with excellent cosmetic outcomes. The aim of this study was to evaluate trends in patient characteristics, indications for surgery and long-term outcomes of bilateral NSM for breast cancer risk reduction over time., Methods: A review of a single-centre experience with bilateral NSM performed between 2001 and 2017 for breast cancer risk reduction in patients without breast cancer was performed. Trends in patient characteristics and indications for surgery were evaluated over four time intervals: 2001-2005, 2006-2009, 2010-2013 and 2014-2017. Statistical analysis was performed using χ 2 tests., Results: Over the study period, 272 NSMs were performed in 136 patients; their median age was 41 years. The number of bilateral NSMs performed increased over time. The most common indication was a mutation in breast cancer-associated genes (104 patients, 76·5 per cent), which included BRCA1 (62 patients), BRCA2 (35), PTEN (2), TP53 (3) and ATM (2). Other indications were family history of breast cancer (19 patients, 14·0 per cent), lobular carcinoma in situ (10, 7·4 per cent) and a history of mantle irradiation (3, 2·2 per cent). The proportion of patients having a bilateral NSM for mutation in a breast cancer-associated gene increased over time (2001-2005: 2 of 12; 2006-2009: 9 of 17; 2010-2013: 34 of 41; 2014-2017: 61 of 66; P  < 0·001). Mean follow-up was 53 months; no breast cancers were found during follow-up., Conclusion: The use of bilateral NSM for breast cancer risk reduction is increasing and the indications have evolved over the past 16 years. These excellent long-term oncological results suggest that bilateral NSM is a good option for surgical breast cancer risk reduction.

Objectives: We aimed to compare the long-term performance of pulmonary homografts and stented bioprosthetic valves in the pulmonary position in patients aged 10-20 years., Methods: Between January 1995 and December 2015, 188 patients aged 10-20 years undergoing pulmonary valve replacement were identified retrospectively from hospital databases in both congenital cardiac centres in Brisbane. Valve performance was evaluated using previously described standard criteria. Propensity score matching was used to balance the 2 treatment groups., Results: Freedom from structural valve degeneration in homografts (n = 131) was 97%, 92% and 85% at 3, 5 and 10 years, respectively, and 91% and 53% at 3 and 5 years, respectively, in the bioprosthesis group (n = 57). Freedom from reintervention in homografts was 96%, 93% and 88% at 3, 5 and 10 years, respectively, and 93% and 68% at 3 and 5 years, respectively, in the bioprosthesis group. The unadjusted Cox regression analysis demonstrated that a bioprosthesis was at 5.64 times the risk of structural valve degeneration and 3.89 times the risk of reintervention. The Cox regression analysis performed on the propensity matched sample (45 pairs of patients) revealed that a bioprosthesis was at almost 10 times the risk of experiencing structural valve degeneration [hazard ratio (HR) = 9.18] and at more than 8 times the risk of undergoing a reintervention (HR = 8.34)., Conclusions: In our patient population, pulmonary homografts outperformed stented bioprosthetic valves within 5 years when implanted in the pulmonary position in patients aged 10-20 years. We recommend the use of a pulmonary homograft for pulmonary valve replacement in this age group in patients undergoing surgery for congenital heart disease.

A therapeutic platform-drug-free macromolecular therapeutics (DFMT)-that induces apoptosis in B cells by cross-linking of CD20 receptors, without the need for low molecular weight cytotoxic drug, is developed. In this report, a DFMT system is synthesized and evaluated based on human serum albumin (HSA) and two complementary coiled-coil forming peptides, CCE and CCK. Fab' fragment of anti-CD20 monoclonal antibody rituximab is attached to CCE (Fab'-CCE); multiple grafts of CCK are conjugated to HSA (HSA-(CCK) 7 ). The colocalization of both nanoconjugates at the surface of non-Hodgkin's lymphoma (NHL) Raji cells is demonstrated by confocal fluorescence microscopy. The colocalization leads to coiled-coil formation, CD20 cross-linking, and apoptosis induction. The apoptotic levels are evaluated by Annexin V, Caspase 3, and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Selective surface binding of DFMT to CD20+ cells is validated in experiments on a coculture of CD20+ (Raji) and CD20-(DG-75) cells. It is found that DFMT can trigger calcium influx only in Raji cells, but not in DG-75 cells. A highly specific treatment for NHL and other B cell malignancies with considerable translational potential is presented by HSA-based DFMT system., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

With the alarming proliferation of antibiotic resistance, it is important to understand the de novo development of bacterial adaptation to antibiotics in formerly susceptible lineages, in the absence of external genetic input from existing resistance pools. A strain of ceftiofur susceptible Salmonella enterica serovar Enteritidis ABB07-SB3071 (MIC = 1.0 μg/ml) was successively exposed to sub-MIC of ceftiofur to allow its adaptation for tolerance to a concentration of 2.0 μg/ml of this antibiotic. Genomic and proteomic comparative analyses of the parental strain and induced tolerant derived lineages were performed to characterize underlying mechanisms of de novo adaptation (tolerance). Expression and localization of specific drug-, heme-, sugar-, amino acid-, and sulfate-transporters were altered, as was the localization of the cell membrane stabilizing protein OsmY in the tolerant strains adapted to 2.0 μg/ml compared to the parental isolate lines. This redistribution of existing transporters acts to minimize the concentrations of ceftiofur in the periplasm, by decreasing facilitated import and increasing active efflux and cytosolic sequestration as determined by high performance liquid chromatography quantification of residual total and extracellular ceftiofur after growth. Genetic, subcellular localization, and abundance changes of specific regulators of transcription, translation, and post-translational dynamics in the derived ceftiofur tolerant lineages decrease metabolic strain on cell walls and enhance periplasmic envelop stability against stress. This produces slower growing, more tolerant populations, which deplete free ceftiofur concentrations significantly more than susceptible parental populations ( P < 0.05), as measured by recoverable levels of ceftiofur from cultures of equivalent cellular density incubated with equal ceftiofur concentrations. Genetic and abundance changes to specific carbon and nitrogen metabolism enzymes, not traditionally associated with beta-lactam metabolism, establish an enzymatic framework with the potential to detoxify/degrade ceftiofur, while mutations and changes in subcellular localization in specific cell surface factors enhance the stability of the Gram-negative cell envelop despite the compromising effect of ceftiofur. The observed changes highlight generalizable mechanisms of de novo tolerance without horizontal gene transfer, and thus can inform policies to combat antibiotic tolerance and minimize induction of de novo tolerance.

We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast-conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I-III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET-alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET-alone based on the CALGB 9343/PRIME-II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC-ESTRO trial/ASTRO guidelines/ABS guidelines/GEC-ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET-alone. This analysis shows that a large proportion of patients with node-negative breast cancer are eligible for HFRT, APBI and/or ET-alone after breast-conserving surgery., (© 2018 Wiley Periodicals, Inc.)

Introduction: This study aimed to explore United Kingdom (UK) and Australian (Aus) dental hygiene and dental therapy students' (DHDTS) perception of stress and well-being during their undergraduate education. Upon qualification, DHDTS in the UK register as dental therapists (DT), and in Australia, they register as Oral Health Therapists (OHT)., Materials and Methods: A questionnaire was distributed to years 1, 2 and 3 DHDTS at the University of Portsmouth Dental Academy (UPDA) in the UK and La Trobe Rural Health School in Australia. The questionnaire consisted of 5 well-used measurement instruments which included the following: Dental Environment Stress questionnaire (DES); Depression Anxiety Stress Scales (DASS-21); Scales of Psychological Well-Being (SPWB); Valuing Questionnaire (VQ); and the Adult Hope Scale (AHS) to collect data on students' perception of levels of stress and well-being., Results: A response rate of 58% (UK) and 55% (Australia) was achieved. Clinical factors and academic work were perceived as stressful for DHDTS in both the UK and Australia. The Australian DHDTS-perceived stress in the educational environment was significantly higher (P < .002) than the UK DHDTS. The majority of respondents reported levels of depression, anxiety and stress to be within the normal-to-moderate range. All students reported high levels of positive well-being, with no significant differences between the 2 groups., Conclusions: DHDTS in the UK and Australia identified sources of stress within their undergraduate education, but also perceived themselves as positively functioning individuals., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Removable partial dentures (RPDs) are still a very important treatment modality in general dentistry to replace missing teeth. With the increase in popularity of implants, RPDs are sometimes seen as an 'old-fashioned' treatment option and if not carefully designed can be damaging to oral tissue and aesthetically less favourable. However, there is still a significantly large cohort of patients for whom RPDs are the best option for replacement of teeth either due to a failing dentition, inappropriate anatomy or financial considerations. This article explores the importance of effective three way communication with the patient, the laboratory and the dental nurse to support the provision of reliable and predictable prosthodontic outcomes.

The Majorana Demonstrator is an ultralow-background experiment searching for neutrinoless double-beta decay in ^{76}Ge. The heavily shielded array of germanium detectors, placed nearly a mile underground at the Sanford Underground Research Facility in Lead, South Dakota, also allows searches for new exotic physics. Free, relativistic, lightly ionizing particles with an electrical charge less than e are forbidden by the standard model but predicted by some of its extensions. If such particles exist, they might be detected in the Majorana Demonstrator by searching for multiple-detector events with individual-detector energy depositions down to 1 keV. This search is background-free, and no candidate events have been found in 285 days of data taking. New direct-detection limits are set for the flux of lightly ionizing particles for charges as low as e/1000.