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Baryon number conservation is not guaranteed by any fundamental symmetry within the standard model, and therefore has been a subject of experimental and theoretical scrutiny for decades. So far, no evidence for baryon number violation has been observed. Large underground detectors have long been used for both neutrino detection and searches for baryon number violating processes. The next generation of large neutrino detectors will seek to improve upon the limits set by past and current experiments and will cover a range of lifetimes predicted by several Grand Unified Theories. In this White Paper, we summarize theoretical motivations and experimental aspects of searches for baryon number violation in neutrino experiments.

Using data on the NBER working paper series, we show that the dissemination of economics research suffers from a congestion problem: An increase in the number of weekly released working papers on average reduces downloads, abstract views, and media attention for each paper. Subsequent publishing and citation outcomes are harmed as well. Papers written by prominent authors are not immune to this congestion effect. Finally, suggestive evidence on viewership and downloads implies that working papers substitute for the dissemination function of publication. Our results highlight how readers face time and cognitive constraints, with increased congestion in working papers leading to real impacts on how research is consumed.

To inform the vital conversation among the nation’s political leaders, elections administrators, and scholars about how to hold a safe, accessible, and fair election in November, this paper reports how a sample of 5,612 eligible American voters, surveyed April 8-10, want to see the election run during the COVID-19 crisis. We embed a randomized experiment presenting respondents with truthful summaries of the projections of two teams of scientists about the pandemic. Our descriptive findings show that four in ten eligible voters would prefer to cast their ballot by mail rather than in person this November and that a majority of respondents favor policies expanding mail voting. Our experimental findings show that respondents who read the scientific projections were more likely to prefer voting by mail, were more likely to trust that a mail ballot would be counted accurately, and were more likely to favor holding the election entirely by mail.

Are voters as polarized as political leaders when it comes to their preferences about how to cast their ballots in November 2020 and their policy positions on how elections should be run in light of the COVID-19 outbreak? Prior research has shown little party divide on voting by mail, with nearly equal percentages of voters in both parties choosing to vote this way where it is an option. Has a divide opened up this year in how voters aligned with the Democratic and Republican parties prefer to cast a ballot? We address these questions by presenting the findings of an online survey of a nationally diverse sample of 5,612 eligible voters, fielded from April 8-10, with an embedded experiment providing treated respondents with scientific projections about the COVID-19 outbreak. We find an eight-percentage point difference between Democrats and Republicans in their preference for voting by mail in the control group, but this party divide doubles in the treatment group. We also find that exposure to scientific projections about the outbreak increases support for vote-by-mail legislation and confidence in vote-by-mail election integrity for both Democrats and Republicans.

Environmental toxic pollutants and pathogens that enter the ecosystem are major global issues. Detection of these toxic chemicals/pollutants and the diagnosis of a disease is a first step in efficiently controlling their contamination and spread, respectively. Various analytical techniques are available to detect and determine toxic chemicals/pathogens, including liquid chromatography, HPLC, mass spectroscopy, and enzyme-linked immunosorbent assays. However, these sensing strategies have some drawbacks such as tedious sample pretreatment and preparation, the requirement for skilled technicians, and dependence on large laboratory-based instruments. Alternatively, biosensors, especially paper-based sensors, could be used extensively and are a cost-effective alternative to conventional laboratory testing. They can improve accessibility to testing to identify chemicals and pollutants, especially in developing countries. Due to its low cost, abundance, easy disposal (by incineration, for example) and biocompatible nature, paper is considered a versatile material for the development of environmentally friendly electrochemical/optical (bio) sensor devices. This review presents an overview of sensing platforms constructed from paper, pointing out the main merits and demerits of paper-based sensing systems, their fabrication techniques, and the different optical/electrochemical detection techniques that they exploit.

Enhanced perioperative care protocols become the standard of care in elective surgery with a significant improvement in patients outcome. The key element of the enhanced perioperative care protocol is the multimodal and interdisciplinary approach targeted to the patient, focused on a holistic approach to reduce surgical stress and improve perioperative recovery. Enhanced perioperative care in emergency general surgery is still a debated topic with little evidence available. The present position paper illustrates the existing evidence about perioperative care in emergency surgery patients with a focus on each perioperative intervention in the preoperative, intraoperative and postoperative phase. For each item was proposed and approved a statement by the WSES collaborative group.

Legal Literacies for Text Data Mining - Cross-Border (“LLTDM-X”) is a National Endowment for the Humanities Level 1 Advancement Grant project addressing legal and ethical issues faced by U.S. digital humanities (DH) practitioners whose text data mining (TDM) research and practice intersects with foreign-held or - licensed content, or involves international cooperations.LLTDM-X ​​is a collaboration between the University of California Berkeley Library and Internet Archive, and builds upon the previous NEH-sponsored institute, Building Legal Literacies for Text Data Mining (Building LLTDM). That institute provided guidance and strategies to DH TDM researchers on navigating legal literacies for text data mining (including copyright, contracts, privacy, and ethics) within a U.S. context.A common challenge highlighted during Building LLTDM was the fact that TDM practitioners encounter numerous and complex legal problems in cross-border TDM research. These occur when: (i) the materials practitioners want to mine are housed in a foreign jurisdiction, or are otherwise subject to foreign database licensing or laws; (ii) the human subjects they are studying or who created the underlying content reside in another country; or, (iii) the colleagues with whom they are collaborating reside abroad, yielding uncertainty about which country’s laws, agreements, and policies apply.We designed LLTDM-X to identify and better understand the cross-border issues that DH TDM practitioners face, with the aim of using these issues to inform prospective research and education. We also hoped that LLTDM-X would yield preliminary guidance to benefit researchers in the meantime, as instructional materials are being developed. In early 2023, we hosted a series of three online round tables with U.S.-based cross-border TDM practitioners (“Practitioners”), and law and ethics experts (“Experts”) practicing in six countries. The round table conversations were structured to illustrate the empirical issues that researchers face, and also for the Practitioners to benefit from guidance on legal and ethical challenges. Upon the completion of the round tables, the LLTDM-X project team created a robust and hypothetical case study that (i) reflects the observed cross-border LLTDM issues and (ii) contains analysis to facilitate the development of future instructional materials.

The INDDEX24 Dietary Assessment Platform (INDDEX24) was developed to facilitate the collection of 24-h dietary recall (24HR) data. Alongside validation studies in Viet Nam and Burkina Faso in 2019-2020, we conducted activity-based costing studies to estimate the cost of conducting a 24HR among women of reproductive age using INDDEX24 compared with the pen-and-paper interview (PAPI) approach. We also modelled alternative scenarios in which: (1) 25-75 % of dietary reference data were borrowed from the INDDEX24 Global Food Matters Database (FMDB); (2) all study personnel were locally based and (3) national-scale surveys. In the primary analysis, in Viet Nam, the 24HR cost US $111 004 ($755/respondent, n 147) using INDDEX24 and $120 483 ($820/respondent, n 147) using PAPI. In Burkina Faso, the 24HR cost $78 105 ($539/respondent, n 145) using INDDEX24 and $79 465 ($544/respondent, n 146) using PAPI. In modelled scenarios, borrowing dietary reference data from the FMDB decreased the cost of INDDEX24 by 17-34 % (Viet Nam) and 5-15 % (Burkina Faso). With all locally based personnel, INDDEX24 cost more than PAPI ($498 v. $448 per respondent in Viet Nam and $456 v. $410 in Burkina Faso). However, at national scales (n 4376, Viet Nam; n 6500, Burkina Faso) using all locally based personnel, INDDEX24 was more cost-efficient ($109 v. $137 per respondent in Viet Nam and $123 v. $148 in Burkina Faso). In two countries and under most circumstances, INDDEX24 was less expensive than PAPI. Higher INDDEX24 survey preparation costs (including purchasing equipment) were more than offset by higher PAPI data entry, cleaning and processing costs. INDDEX24 may facilitate cost-efficient dietary data collection.

Many countries are facing an aging population. As people live longer, surgeons face the prospect of operating on increasingly older patients. Traditional teaching is that with older age, these patients face an increased risk of mortality and morbidity, even to a level deemed too prohibitive for surgery. However, this is not always true. An active 90-year-old patient can be much fitter than an overweight, sedentary 65-year-old patient with comorbidities. Recent literature shows that frailty-an age-related cumulative decline in multiple physiological systems, is therefore a better predictor of mortality and morbidity than chronological age alone. Despite recognition of frailty as an important tool in identifying vulnerable surgical patients, many surgeons still shun objective tools. The aim of this position paper was to perform a review of the existing literature and to provide recommendations on emergency laparotomy and in frail patients. This position paper was reviewed by an international expert panel composed of 37 experts who were asked to critically revise the manuscript and position statements. The position paper was conducted according to the WSES methodology. We shall present the derived statements upon which a consensus was reached, specifying the quality of the supporting evidence and suggesting future research directions.

Women's health care has evolved significantly since it was first acknowledged as an integral part of internal medicine training more than two decades ago. To update and clarify core competencies in sex- and gender-based women's health for general internists, the Society of General Internal Medicine (SGIM) Women and Medicine Commission prepared the following Position Paper, approved by the SGIM council in 2023. Competencies were developed using several sources, including the 2021 Accreditation Council for Graduate Medical Education Program Requirements for Internal Medicine and the 2023 American Board of Internal Medicine Certification Examination Blueprint. These competencies are relevant to the care of patients who identify as women, as well as gender-diverse individuals to whom these principles apply. They align with pivotal advances in women's health and acknowledge the changing context of patients' lives, reaffirming the role of general internal medicine physicians in providing comprehensive care to women.

The White Paper highlights selected Library activities and aligns them with UC Merced's Strategic Planning Goals; it does not showcase all Library services and contributions. Included recommendations suggest how an investment in the UC Merced Library can support the ongoing advancement of the university’s mission.

BACKGROUND: Diaphragmatic hernia (DH) presenting acutely can be a potentially life-threatening condition. Its management continues to be debatable. METHODS: A bibliographic search using major databases was performed using the terms emergency surgery diaphragmatic hernia, traumatic diaphragmatic rupture and congenital diaphragmatic hernia. GRADE methodology was used to evaluate the evidence and give recommendations. RESULTS: CT scan of the chest and abdomen is the diagnostic gold standard to evaluate complicated DH. Appropriate preoperative assessment and prompt surgical intervention are important for a clinical success. Complicated DH repair is best performed via the use of biological and bioabsorbable meshes which have proven to reduce recurrence. The laparoscopic approach is the preferred technique in hemodynamically stable patients without significant comorbidities because it facilitates early diagnosis of small diaphragmatic injuries from traumatic wounds in the thoraco-abdominal area and reduces postoperative complications. Open surgery should be reserved for situations when skills and equipment for laparoscopy are not available, where exploratory laparotomy is needed, or if the patient is hemodynamically unstable. Damage Control Surgery is an option in the management of critical and unstable patients. CONCLUSIONS: Complicated diaphragmatic hernia is a rare life-threatening condition. CT scan of the chest and abdomen is the gold standard for diagnosing the diaphragmatic hernia. Laparoscopic repair is the best treatment option for stable patients with complicated diaphragmatic hernias. Open repair is considered necessary in majority of unstable patients in whom Damage Control Surgery can be life-saving.

Industrial process heat decarbonization through electrification could contribute significantly to climate change mitigation efforts. In the US industry, thermal processes accounted for more than two-thirds of the total final energy demand in 2021. Cross-cutting electrification technologies like industrial heat pumps are suitable for the process heat supply to several industrial unit operations in a sustainable way while also improving overall energy efficiency. This study employs a bottom-up approach to investigate the techno-enviro-economic potentials of deploying high-temperature and steam-generating heat pumps in US textile, pulp and paper, and automotive sectors in different timeframes. The results show that the annual technical potential energy and CO2 savings by electrifying heat supply are 310 PJ (or 36% of the projected energy demand) and 28 MtCO2 (or 71% of the projected CO2 emissions) in 2050 respectively, however, these incur additional costs in each sector (ranging between 5 and 18 $/GJ). The required heating capacity of industrial heat pumps is estimated at 15 GW, which translates roughly into a market of over 6000 heat pump units and an investment volume of $7 billion in the studied processes. Although there may be individual cost-effective opportunities for electrifying heat supply in specific industrial sites, the overall costs are estimated to be high in the three industrial sectors due to the large disparity between electricity and natural gas prices and low heat source temperatures. To overcome the identified techno-economic barriers, comprehensive action plans for different stakeholders are also given. This study provides novel insights that should inform policymakers’ and executives’ decisions about the electrification of the current and future US industrial heat supply in relevant industrial sectors.

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies.

Directly imaging temperate rocky planets orbiting nearby, Sun-like stars with a 6 m class IR/O/UV space telescope, recently dubbed the Habitable Worlds Observatory, is a high-priority goal of the Astro2020 Decadal Survey. To prepare for future direct imaging (DI) surveys, the list of potential targets should be thoroughly vetted to maximize efficiency and scientific yield. We present an analysis of archival radial velocity data for southern stars from the NASA/NSF Extreme Precision Radial Velocity (EPRV) Working Group’s list of high-priority target stars for future DI missions (drawn from the HabEx, LUVOIR, and Starshade Rendezvous studies). For each star, we constrain the region of companion mass and period parameter space we are already sensitive to based on the observational baseline, sampling, and precision of the archival radial velocity (RV) data. Additionally, for some of the targets, we report new estimates of magnetic activity cycle periods, rotation periods, improved orbital parameters for previously known exoplanets, and new candidate planet signals that require further vetting or observations to confirm. Our results show that for many of these stars we are not yet sensitive to even Saturn-mass planets in the habitable zone, let alone smaller planets, highlighting the need for future EPRV vetting efforts before the launch of a DI mission. We present evidence that the candidate temperate super-Earth exoplanet HD 85512b is most likely due to the star’s rotation, and report an RV acceleration for δ Pav that supports the existence of a distant giant planet previously inferred from astrometry.

Hot QCD physics studies the nuclear strong force under extreme temperatureand densities. Experimentally these conditions are achieved via high-energycollisions of heavy ions at the Relativistic Heavy Ion Collider (RHIC) and theLarge Hadron Collider (LHC). In the past decade, a unique and substantial suiteof data was collected at RHIC and the LHC, probing hydrodynamics at the nucleonscale, the temperature dependence of the transport properties of quark-gluonplasma, the phase diagram of nuclear matter, the interaction of quarks andgluons at different scales and much more. This document, as part of the 2023nuclear science long range planning process, was written to review the progressin hot QCD since the 2015 Long Range Plan for Nuclear Science, as well ashighlight the realization of previous recommendations, and presentopportunities for the next decade, building on the accomplishments andinvestments made in theoretical developments and the construction of newdetectors. Furthermore, this document provides additional context to supportthe recommendations voted on at the Joint Hot and Cold QCD Town Hall Meeting,which are reported in a separate document.

The development of highly specific biomimetic recognition material is a challenge for rapid detection of harmful residues in foodstuff. In this study, a paper-based boronate affinity metal-organic framework/molecularly imprinted polymer microfluidic chip (FZS-BA@MIP) was constructed based on the in situ construction strategy, which was also designed as a highly specific biomimetic recognition module. Here, the homogeneous zeolitic imidazole framework-8 (ZIF-8) membrane served as a great scaffold and enrichment layer. Besides, the recognition layer of MIP was prepared based on a highly oriented boronate affinity surface imprinting strategy. With the aid of the liquid flow channel, the highly specific enrichment and visual detection for antibiotic residues like kanamycin in actual products were achieved on the paper chip module of an integrated lateral flow platform. The whole analysis process could be accomplished within 30 min. In brief, this study offered a new integrated biomimetic recognition platform for visually detecting harmful veterinary residues containing cis-diols, which demonstrated promising commercial value in point-of-care testing of foodborne hazardous compounds.

One-pot syntheses and in situ ultrasonication have been optimized to generate tunable and highly hydrophobic 2,7-octadienyl-ether (ODE) cellulose nanofibrils (CNFs). Using only butadiene sulfone to serve as dual reaction medium and precursor to 1,3-butadiene (1,3-BD) for telomerization with cellulose hydroxyls, the OH-to-ODE conversion significantly improved from ca. 0.7 to 1.2, 1.8, 3.1, and 4.1 mmol of ODE/g-cellulose at 103-110 °C for 1-2 h. Ultrasonication was highly effective and versatile in the direct disintegration of ODE-cellulose (ODE-cell) in nonpolar organic solvents and plant oils into ODE-CNFs as well as pretreating cellulose for improved functionalization. Mixing 2 wt % in situ ultrasonicated 1.2 mmol of ODE/g-cell improved the modulus of polybutadiene six times and the strength of poly(styrene-b-isoprene-b-styrene) three times, whereas in situ ultrasonication of 1.8 mmol/g-cell directly with linseed oil at merely 0.07 wt % created holistic biobased hydrophobic cellulose paper to resist water penetration while also significantly improving the tensile strength. This optimized telomerization and streamlined in situ ultrasonication approach has presented a sustainable synthesis and processing strategy to generate highly hydrocarbon-compatible nanocelluloses previously unattainable.

BackgroundPrimary care practices are responding to calls to incorporate patients' social risk factors, such as housing, food, and economic insecurity, into clinical care. Healthcare likely relies on the expertise and resources of community-based organizations to improve patients' social conditions, yet little is known about the referral process.ObjectiveTo characterize referrals to community-based organizations by primary care practices.DesignQualitative study using semi-structured interviews with healthcare administrators responsible for social care efforts in their organization.ParticipantsAdministrators at 50 diverse US healthcare organizations with efforts to address patients' social risks.Main measuresApproaches used in primary care to implement social needs referral to community-based organizations.ResultsInterviewed administrators reported that social needs referrals were an essential element in their social care activities. Administrators described the ideal referral programs as placing limited burden on care teams, providing patients with customized referrals, and facilitating closed-loop referrals. We identified three key challenges organizations experience when trying to implement the ideal referrals program: (1) developing and maintaining resources lists; (2) aligning referrals with patient needs; and (3) measuring the efficacy of referrals. Collectively, these challenges led to organizations relying on staff to manually develop and update resource lists and, in most cases, provide patients with generic referrals. Administrators not only hoped that referral platforms may help overcome some of these barriers, but also reported implementation challenges with platforms including inconsistent buy-in and use across staff; integration with electronic health records; management and prioritization of resources; and alignment with other organizations in their market.Conclusion and relevanceReferrals to community-based organizations were used in primary care to improve patients' social conditions, but despite strong motivations, interviewees reported challenges providing tailored and up-to-date information to patients.

The low cost, simplicity, and ease of use of paper microfluidic devices have made them valuable medical diagnostics for applications from pregnancy testing to COVID-19 screening. Meanwhile, the increasing complexity of paper-based microfluidic devices is driving the need to produce new tools and methodologies that enable more robust biological diagnostics and potential therapeutic applications. A new design framework is being used to facilitate both research and fabrication of paper-based microfluidic biological devices to accelerate the investigative process and reduce material utilization and manpower. In this work we present a methodology for this framework to dynamically place and route microfluidic components in a nondiscrete design space where fluid volume usage, surface area utilization, and the timing required to perform specified biological assays are accounted for and optimized while also accelerating the development of potentially lifesaving new devices.

The low cost, simplicity, and ease of use of paper microfluidic devices have made them valuable medical diagnostics for applications from pregnancy testing to COVID-19 screening. Meanwhile, the increasing complexity of paper-based microfluidic devices is driving the need to produce new tools and methodologies that enable more robust biological diagnostics and potential therapeutic applications. A new design framework is being used to facilitate both research and fabrication of paper-based microfluidic biological devices to accelerate the investigative process and reduce material utilization and manpower. In this work we present a methodology for this framework to dynamically place and route microfluidic components in a nondiscrete design space where fluid volume usage, surface area utilization, and the timing required to perform specified biological assays are accounted for and optimized while also accelerating the development of potentially lifesaving new devices.

Effective nutrition policies require timely, accurate individual dietary consumption data; collection of such information has been hampered by cost and complexity of dietary surveys and lag in producing results. The objective of this work was to assess accuracy and cost-effectiveness of a streamlined, tablet-based dietary data collection platform for 24-hour individual dietary recalls (24HR) administered using INDDEX24 platform v. a pen-and-paper interview(PAPI) questionnaire, with weighed food record (WFR) as a benchmark. This cross-sectional comparative study included women 18-49 years old from rural Burkina Faso (n 116 INDDEX24; n 115 PAPI). A WFR was conducted; the following day, a 24HR was administered by different interviewers. Food consumption data were converted into nutrient intakes. Validity of 24HR estimates of nutrient and food group consumption was based on comparison with WFR using equivalence tests (group level) and percentages of participants within ranges of percentage error (individual level). Both modalities performed comparably estimating consumption of macro- and micronutrients, food groups and quantities (modalities' divergence from WFR not significantly different). Accuracy of both modalities was acceptable (equivalence to WFR significant at P < 0·05) at group level for macronutrients, less so for micronutrients and individual-level consumption (percentage within ±20 % for WFR, 17-45 % for macronutrients, 5-17 % for micronutrients). INDDEX24 was more cost-effective than PAPI based on superior accuracy of a composite nutrient intake measure (but not gram amount or item count) due to lower time and personnel costs. INDDEX24 for 24HR dietary surveys linked to dietary reference data shows comparable accuracy to PAPI at lower cost.

In late fall-early winter 2021 the Institute for Diversity, Equity, and Advancement (IDEA) in the UC Davis Office of Diversity, Equity and Inclusion partnered with the UCD-based non-profit Sacramento Area Youth Speaks (SAYS) to design the COVID Diaries research project. It was implemented in March – June 2022 at eight middle and high schools (6 - 12th grades) served by SAYS in Sacramento County and Yolo County. To learn more about the project’s findings, see the COVID Diaries White Paper on eScholarship.

BACKGROUND: A crisis in pain management persists, as does the epidemic of opioid overdose deaths, addiction, and diversion. Pain medicine is meeting these challenges by returning to its origins: the Bonica model of multidisciplinary pain care. The 2018 Academic Consortium White Paper detailed the historical context and magnitude of the pain crisis and the evidence base for nonpharmacologic strategies. More than 50% of chronic opioid use begins in the acute pain care setting. Acupuncture may be able to reduce this risk. OBJECTIVE: This article updates the evidence base for acupuncture therapy for acute pain with a review of systematic reviews and meta-analyses on postsurgical/perioperative pain with opioid sparing and acute nonsurgical/trauma pain, including acute pain in the emergency department. METHODS: To update reviews cited in the 2018 White Paper, electronic searches were conducted in PubMed, MEDLINE, CINAHL, and the Cochrane Central Register of Controlled Trials for acupuncture and acupuncture therapy and acute pain, surgery, peri-operative, trauma, emergency department, urgent care, review(s) , systematic review, meta-analysis, with additional manual review of titles, links, and reference lists. RESULTS: There are 22 systematic reviews, 17 with meta-analyses of acupuncture in acute pain settings, and a review for acute pain in the intensive care unit. There are additional studies of acupuncture in acute pain settings. CONCLUSION: The majority of reviews found acupuncture therapy to be an efficacious strategy for acute pain, with potential to avoid or reduce opioid reliance. Future multicenter trials are needed to clarify the dosage and generalizability of acupuncture for acute pain in the emergency department. With an extremely low risk profile, acupuncture therapy is an important strategy in comprehensive acute pain care.

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin-associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3-5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)-what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real-world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step-by-step patient-centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long-term compliance with lipid-lowering therapy.

Loop-mediated isothermal amplification (LAMP) has been widely used to detect many infectious diseases. However, minor inconveniences during the steps of adding reaction ingredients and lack of simple color results hinder point-of-care detection. We therefore invented a fluorometric paper-based LAMP by incorporating LAMP reagents, including a biotinylated primer, onto a cellulose membrane paper, with a simple DNA fluorescent dye incubation that demonstrated rapid and accurate results parallel to quantitative polymerase chain reaction (qPCR) methods. This technology allows for instant paper strip detection of methicillin-resistant Staphylococcus aureus (MRSA) in the laboratory and clinical samples. MRSA represents a major public health problem as it can cause infections in different parts of the human body and yet is resistant to commonly used antibiotics. In this study, we optimized LAMP reaction ingredients and incubation conditions following a central composite design (CCD) that yielded the shortest reaction time with high sensitivity. These CCD components and conditions were used to construct the paper-based LAMP reaction by immobilizing the biotinylated primer and the rest of the LAMP reagents to produce the ready-to-use MRSA diagnostic device. Our paper-based LAMP device could detect as low as 10 ag (equivalent to 1 copy) of the MRSA gene mecA within 36-43 min, was evaluated using both laboratory (individual cultures of MRSA and non-MRSA bacteria) and clinical blood samples to be 100% specific and sensitive compared to qPCR results, and had 35 day stability under 25 °C storage. Furthermore, the color readout allows for quantitation of MRSA copies. Hence, this device is applicable for point-of-care MRSA detection.

Loop-mediated isothermal amplification (LAMP) has been widely used to detect many infectious diseases. However, minor inconveniences during the steps of adding reaction ingredients and lack of simple color results hinder point-of-care detection. We therefore invented a fluorometric paper-based LAMP by incorporating LAMP reagents, including a biotinylated primer, onto a cellulose membrane paper, with a simple DNA fluorescent dye incubation that demonstrated rapid and accurate results parallel to quantitative polymerase chain reaction (qPCR) methods. This technology allows for instant paper strip detection of methicillin-resistant Staphylococcus aureus (MRSA) in the laboratory and clinical samples. MRSA represents a major public health problem as it can cause infections in different parts of the human body and yet is resistant to commonly used antibiotics. In this study, we optimized LAMP reaction ingredients and incubation conditions following a central composite design (CCD) that yielded the shortest reaction time with high sensitivity. These CCD components and conditions were used to construct the paper-based LAMP reaction by immobilizing the biotinylated primer and the rest of the LAMP reagents to produce the ready-to-use MRSA diagnostic device. Our paper-based LAMP device could detect as low as 10 ag (equivalent to 1 copy) of the MRSA gene mecA within 36-43 min, was evaluated using both laboratory (individual cultures of MRSA and non-MRSA bacteria) and clinical blood samples to be 100% specific and sensitive compared to qPCR results, and had 35 day stability under 25 °C storage. Furthermore, the color readout allows for quantitation of MRSA copies. Hence, this device is applicable for point-of-care MRSA detection.

In simple dyadic games such as rock, paper, scissors (RPS), people exhibit peculiar sequential dependencies across repeated interactions with a stable opponent. These regularities seem to arise from a mutually adversarial process of trying to outwit their opponent. What underlies this process, and what are its limits? Here, we offer a novel framework for formally describing and quantifying human adversarial reasoning in the rock, paper, scissors game. We first show that this framework enables a precise characterization of the complexity of patterned behaviors that people exhibit themselves, and appear to exploit in others. This combination allows for a quantitative understanding of human opponent modeling abilities. We apply these tools to an experiment in which people played 300 rounds of RPS in stable dyads. We find that although people exhibit very complex move dependencies, they cannot exploit these dependencies in their opponents, indicating a fundamental limitation in people’s capacity for adversarial reasoning. Taken together, the results presented here show how the rock, paper, scissors game allows for precise formalization of human adaptive reasoning abilities.