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INTRODUCTION: Stress from negative life events may be an important risk factor for chronic cardiometabolic conditions, which are increasingly prevalent among young adults. Support from personal networks is known to buffer stress from negative life events. Yet, evidence for these relationships among both young and older adults remains unclear. METHODS: Longitudinal data came from the University of California, Berkeley Social Networks study (2015–2018), which followed young (aged 21–30 years) and late middle age adults (aged 50–70 years) over 4 years. Weighted hybrid fixed and random effects models (completed in 2020) were used to examine causal relationships among 4 negative life events, distinct forms of network support (e.g., social companionship, emergency help), and self-reported chronic cardiometabolic disease outcomes (i.e., hypertension, diabetes, or a heart condition). RESULTS: Among young adults, both the death of a close tie (Average Marginal Effect=0.10, p

Background: Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure–function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM. Methods: We performed a comprehensive multiomics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts). Results: Integrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and phosphocreatine) and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance. Conclusions: Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury.

Background: A comorbidity summary score may support early and systematic identification of women at high risk for adverse obstetric outcomes. The objective of this study was to conduct the initial development and validation of an obstetrics comorbidity risk score for automated implementation in the electronic health record (EHR) for clinical use. Methods: The score was developed and validated using EHR data for a retrospective cohort of pregnancies with delivery between 2010 and 2018 at Kaiser Permanente Northern California, an integrated health care system. The outcome used for model development consisted of adverse obstetric events from delivery hospitalization (e.g., eclampsia, hemorrhage, death). Candidate predictors included maternal age, parity, multiple gestation, and any maternal diagnoses assigned in health care encounters in the 12 months before admission for delivery. We used penalized regression for variable selection, logistic regression to fit the model, and internal validation for model evaluation. We also evaluated prenatal model performance at 18 weeks of pregnancy. Results: The development cohort (n = 227,405 pregnancies) had an outcome rate of 3.8% and the validation cohort (n = 41,683) had an outcome rate of 2.9%. Of 276 candidate predictors, 37 were included in the final model. The final model had a validation c-statistic of 0.72 (95% confidence interval [CI] 0.70-0.73). When evaluated at 18 weeks of pregnancy, discrimination was modestly diminished (c-statistic 0.68 [95% CI 0.67-0.70]). Conclusions: The obstetric comorbidity score demonstrated good discrimination for adverse obstetric outcomes. After additional appropriate validation, the score can be automated in the EHR to support early identification of high-risk women and assist efforts to ensure risk-appropriate maternal care.

BACKGROUND AND OBJECTIVESContinuous pulse oximetry (oxygen saturation [Spo2]) monitoring in hospitalized children with bronchiolitis not requiring supplemental oxygen is discouraged by national guidelines, but determining monitoring status accurately requires in-person observation. Our objective was to determine if electronic health record (EHR) data can accurately estimate the extent of actual Spo2 monitoring use in bronchiolitis.METHODSThis repeated cross-sectional study included infants aged 8 weeks through 23 months hospitalized with bronchiolitis. In the validation phase at 3 children’s hospitals, we calculated the test characteristics of the Spo2 monitor data streamed into the EHR each minute when monitoring was active compared with in-person observation of Spo2 monitoring use. In the application phase at 1 children’s hospital, we identified periods when supplemental oxygen was administered using EHR flowsheet documentation and calculated the duration of Spo2 monitoring that occurred in the absence of supplemental oxygen.RESULTSAmong 668 infants at 3 hospitals (validation phase), EHR-integrated Spo2 data from the same minute as in-person observation had a sensitivity of 90%, specificity of 98%, positive predictive value of 88%, and negative predictive value of 98% for actual Spo2 monitoring use. Using EHR-integrated data in a sample of 317 infants at 1 hospital (application phase), infants were monitored in the absence of oxygen supplementation for a median 4.1 hours (interquartile range 1.4–9.4 hours). Those who received supplemental oxygen experienced a median 5.6 hours (interquartile range 3.0–10.6 hours) of monitoring after oxygen was stopped.CONCLUSIONSEHR-integrated monitor data are a valid measure of actual Spo2 monitoring use that may help hospitals more efficiently identify opportunities to deimplement guideline-inconsistent use.

This longitudinal research describes how a 50-person management staff, led by a committed chief executive officer (CEO), was able to successfully implement a team-based structure and strategy to achieve a radical change from a non-profit hospital to a for-profit organization over a 12-year period. Many of the issues addressed and practical steps taken to establish a team-based leadership model for the new organizational template are described. Organization development models, diagnosis, intervention, and specific practices to bring about a successful transition are discussed. Seven principles are presented that contain “The Lessons Learned” from the longitudinal organizational systemic change intervention.

An 81-year-old immunocompetent patient with bronchiectasis and refractory Mycobacterium abscessus lung disease was treated for 6 months with a three-phage cocktail active against the strain. In this case study of phage to lower infectious burden, intravenous administration was safe and reduced the M. abscessus sputum load tenfold within one month. However, after two months, M. abscessus counts increased as the patient mounted a robust IgM- and IgG-mediated neutralizing antibody response to the phages, which was associated with limited therapeutic efficacy.

As rocket launch cadences increase, access to space rises dramatically - setting the stage for the next space industry surge. New, smaller, and less expensive satellites - now "nanosatellites" - can be deployed en masse to form constellations of hundreds, thousands, or even tens of thousands of devices [27, 40, 41, 16, 17, 18, 43]. A constellation of nanosatellites equipped with sensors (e.g., visual or hyperspectral cameras, particle detectors, or magnetometers) and radios provides a first-time opportunity for orbital swarm sensing to synthesize data from the unique vantage point of low-Earth orbit (LEO).

PurposeBased on social exchange theory, the study examines the influence of informational and relational internal communication on cognitive and affective responses and job engagement during organizational crises caused by the COVID-19 pandemic.Design/methodology/approachData were collected by means of an online survey among people working in organizations with a minimum of 10 employees (N = 1,033) and analyzed using structural equation modeling.FindingsResults show that informational and relational communication as organizational resources have a significant but distinct influence on how employees support their employer during the crisis. While informational communication influences employees' acceptance of managerial decisions, relational communication exerts most influence on affective commitment, which is the strongest driver of job engagement.Research limitations/implicationsThe cross-sectional design, specific crisis situation and geographic location are limitations of the study.Practical implicationsDelivering relevant information to employees quickly and reliably is important. Yet, relationship-oriented communication that demonstrates appreciation and allows for participation has even stronger effects on job engagement, which is essential to mastering challenges arising from a crisis.Social implicationsDuring the COVID-19 pandemic, organizations demanded much from their employees. In exchange, organizations should provide the resources information, status and love (Foa and Foa, 1980) by means of internal crisis communication.Originality/valueThe study demonstrates the role of different types of internal communication during organizational crises used to convey organizational resources, and it highlights the mediating role of acceptance and commitment to enhance employees' engagement at work.

PurposeThe purpose of this study is to explore balanced leadership behaviors, which exhibit ambidexterity, in a top management team (TMT) recognized for innovation and operational success.Design/methodology/approachAn action research case study was conducted in a single global organization in an industry requiring high levels of innovation. Operationalized as a balance of exploratory and exploitative behaviors, leadership ambidexterity was measured using the strategic-operational dimension of the Leadership Versatility Index (LVI©) which when completed included 67 assessments provided by TMT peers, supervisors and direct reports. Using quantitative and qualitative data, we examined the behaviors of six executives and the degree of flexibility they exhibit when switching opposing behaviors.FindingsThis study provides empirical evidence that TMT leaders of a highly innovative company strive to flexibly move between explorative and exploitative behaviors both as individual members and as an executive team. A high degree of exploitation–exploration versatility was also linked to the TMT effective performance.Practical implicationsFor organizational practitioners, the study offers a quantifiable measure of individual and team leadership ambidexterity. It can be used to raise awareness and suggest ambidextrous behaviors to TMT leaders and “high-management-potentials”.Originality/valueThis study measures leadership ambidexterity of individual executives and the TMT as a group using a quantitative instrument supported by 360-degree qualitative data. Access to both secondary and proprietary information allowed in depth examination of the TMT behaviors in an innovative firm, which was acquired at a premium and was recognized with multiple innovation awards.

Objective This study aimed to evaluate the performance of the California Maternal Quality Care Collaborative (CMQCC) admission risk criteria for stratifying postpartum hemorrhage risk in a large obstetrics population. Study Design Using detailed electronic health record data, we classified 261,964 delivery hospitalizations from Kaiser Permanente Northern California hospitals between 2010 and 2017 into high-, medium-, and low-risk groups based on CMQCC criteria. We used logistic regression to assess associations between CMQCC risk groups and postpartum hemorrhage using two different postpartum hemorrhage definitions, standard postpartum hemorrhage (blood loss ≥1,000 mL) and severe postpartum hemorrhage (based on transfusion, laboratory, and blood loss data). Among the low-risk group, we also evaluated associations between additional present-on-admission factors and severe postpartum hemorrhage. Results Using the standard definition, postpartum hemorrhage occurred in approximately 5% of hospitalizations (n = 13,479), with a rate of 3.2, 10.5, and 10.2% in the low-, medium-, and high-risk groups. Severe postpartum hemorrhage occurred in 824 hospitalizations (0.3%), with a rate of 0.2, 0.5, and 1.3% in the low-, medium-, and high-risk groups. For either definition, the odds of postpartum hemorrhage were significantly higher in medium- and high-risk groups compared with the low-risk group. Over 40% of postpartum hemorrhages occurred in hospitalizations that were classified as low risk. Among the low-risk group, risk factors including hypertension and diabetes were associated with higher odds of severe postpartum hemorrhage. Conclusion We found that the CMQCC admission risk assessment criteria stratified women by increasing rates of severe postpartum hemorrhage in our sample, which enables early preparation for many postpartum hemorrhages. However, the CMQCC risk factors missed a substantial proportion of postpartum hemorrhages. Efforts to improve postpartum hemorrhage risk assessment using present-on-admission risk factors should consider inclusion of other nonobstetrical factors.

ZusammenfassungSchleimhautmelanome sind seltene Formen von Melanomen mit einer ungünstigen Prognose. Bei Fehlen von therapierelevanten Mutationen und Inoperabilität stellt die Therapie mit Immuncheckpoint-Inhibitoren eine aussichtsreiche Option dar. Die Kombination aus dem PD-1-Antikörper Nivolumab und dem CTLA4-Antikörper Ipilimumab ist effektiver, jedoch auch erheblich toxischer als die Monotherapie mit PD-1-Antikörpern. Wir berichten über eine 57-jährige Patientin mit einem lymphogen metastasierten inoperablen Gingivamelanom im Stadium IIID, die mit einer Kombination aus Nivolumab und Ipilimumab behandelt wurde und hierunter multiple autoimmunvermittelte Nebenwirkungen einschließlich eines Schubs einer rheumatoiden Arthritis, einer Autoimmunkolitis, einer Autoimmunthyreoiditis und einer Autoimmunhepatitis entwickelte. Diese konnten mithilfe von systemischen Steroiden und symptomatischer Therapie beherrscht werden und es konnte eine anhaltende partielle Remission bei guter Lebensqualität erzielt werden. Unser Fall liefert ein Beispiel für den erfolgreichen Einsatz von Immuncheckpoint-Inhibitoren bei seltenen Melanom-Entitäten, veranschaulicht jedoch auch die Bedeutung von intensivem Monitoring besonders bei Patienten mit zugrunde liegenden Autoimmunerkrankungen.

Clinical alarm systems safety is a national healthcare concern in the United States. Physiologic monitors are the medical devices associated with the highest number of false and clinically insignificant alarms, producing alarm fatigue and a challenge to meet the national clinical alarm systems safety goal. Modern physiologic monitors are high-tech complex devices with multimeasurement modalities and high sensitivity for alarms. This complexity hinders safe operation of the monitors by nurses and appropriate management of associated alarms. Nurses need to integrate cognitive knowledge, psychomotor skills, and critical thinking to safely operate the monitors and support clinical decisions. Limited resources are available to support clinical education for nurses on physiologic monitor use and alarm management. This toolkit presents an educational framework for physiologic monitor use and alarm safety guided by adult learning principles. The components of the program are (1) knowledge, skills, and attitude of physiologic monitor use; (2) scenario-based learning model to support the knowledge, skills, and attitude necessary for safe monitor use; and (3) a framework for evaluating the educational program. Education should be ongoing and customized per facility to ensure safe use of complex technology and to decrease alarm fatigue, the leading cause of alarm-related sentinel events.

Antibody therapeutics can be associated with unwanted immune responses resulting in the development of anti‐drug antibodies (ADA). Optimal methods to evaluate the potential effects of ADA on clinical outcomes in oncology are not well established. In this study, we assessed efficacy and safety, based on ADA status, in patients from over 10 clinical trials that evaluated the immune checkpoint inhibitor atezolizumab as a single agent or as combination therapy for several types of advanced cancers. ADA can only be observed post randomization, and imbalances in baseline prognostic factors can confound the interpretation of ADA impact. We applied methodology to account for the confounding effects of baseline clinical characteristics and survivorship bias on efficacy. Adjusted meta‐analyses revealed that despite numerical differences in overall survival and progression‐free survival between ADA‐positive and ADA‐negative patients from some studies, ADA‐positive patients from studies with an overall treatment effect derived benefit from atezolizumab, compared with their adjusted controls. Based on large, pooled populations from atezolizumab monotherapy or combination studies, unadjusted descriptive analyses did not identify a clear relationship between ADA status and frequency or severity of adverse events. Data also suggested that any ADA impact is not driven by neutralizing activity. Collectively, this exploratory analysis suggests that the potential for ADA development should not impact treatment decisions with atezolizumab.

Baseline patient characteristics and prognostic factors are important considerations in oncology when evaluating the impact of immunogenicity on pharmacokinetics (PK) and efficacy. Here, we assessed the impact of anti‐drug antibodies (ADA) on the PK of the immune checkpoint inhibitor atezolizumab (an anti–PD‐L1 monoclonal antibody). We evaluated data from ≈ 4500 patients from 12 clinical trials across different tumor types, treatment settings, and dosing regimens. In our dataset, ~ 30% of patients (range, 13–54%) developed treatment‐emergent ADA, and in vitro neutralizing antibodies (NAb) were seen in ~ 50% of ADA‐positive (+) patients. Pooled time course data showed a trend toward lower atezolizumab exposure in ADA+ patients, which was more pronounced in ADA+/NAb+ patients. However, the atezolizumab concentration distributions overlapped, and drug concentrations exceeded 6 µg/ml, the target concentration required for receptor saturation, in greater than 95% of patients. Patients had sufficient exposure regardless of ADA status. The dose selected to allow for dosing over effects from ADA resulted in a flat exposure‐response relationship. Analysis of study results by ADA titer showed that exposure and overall survival were not affected in a clinically meaningful way. High tumor burden, low albumin, and high CRP at baseline showed the greatest association with ADA development but not with subsequent NAb development. These imbalanced factors at baseline can confound analysis of ADA impact. ADA increases atezolizumab clearance minimally (9%), and its impact on exposure based on the totality of the clinical pharmacology assessment does not appear to be clinically meaningful.

Programs that prevent the development of severe problem behavior in young children with autism spectrum disorder (ASD) are critically needed. We describe a program designed to do this, and we report on a preliminary evaluation of its effects with four 3- and 4-year-old children with ASD. Parents served as the primary implementers, with twice-weekly coaching from a Board Certified Behavior Analyst. Direct measures and Aberrant Behavior Checklist scores reflected decreases in emerging problem behavior. Direct measures also reflected increases in child communication, social, and cooperation skills, and parents rated the process as highly acceptable. A randomized controlled trial will be required to evaluate the extent to which the program prevents the development of problem behavior in young children with ASD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40617-020-00490-3.

BACKGROUND AND OBJECTIVESPhysiologic monitor alarms occur at high rates in children’s hospitals; ≤1% are actionable. The burden of alarms has implications for patient safety and is challenging to measure directly. Nurse workload, measured by using a version of the National Aeronautics and Space Administration Task Load Index (NASA-TLX) validated among nurses, is a useful indicator of work burden that has been associated with patient outcomes. A recent study revealed that 5-point increases in the NASA-TLX score were associated with a 22% increased risk in missed nursing care. Our objective was to measure the relationship between alarm count and nurse workload by using the NASA-TLX.METHODSWe conducted a repeated cross-sectional study of pediatric nurses in a tertiary care children’s hospital to measure the association between NASA-TLX workload evaluations (using the nurse-validated scale) and alarm count in the 2 hours preceding NASA-TLX administration. Using a multivariable mixed-effects regression accounting for nurse-level clustering, we modeled the adjusted association of alarm count with workload.RESULTSThe NASA-TLX score was assessed in 26 nurses during 394 nursing shifts over a 2-month period. In adjusted regression models, experiencing >40 alarms in the preceding 2 hours was associated with a 5.5 point increase (95% confidence interval 5.2 to 5.7; P < .001) in subjective workload.CONCLUSIONAlarm count in the preceding 2 hours is associated with a significant increase in subjective nurse workload that exceeds the threshold associated with increased risk of missed nursing care and potential patient harm.

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Background The iMATRIX-atezolizumab study was a phase I/II, multicenter, open-label study designed to assess the safety and pharmacokinetics of atezolizumab in pediatric and young adult patients. We describe the pharmacokinetics (PK), exposure-safety, and immunogenicity of atezolizumab in pediatric and young adults with metastatic solid tumors or hematologic malignancies enrolled in this study. Methods Patients aged

Introduction. At a time of global economic, social, cultural and political change, it is particularly important to monitor the sustainability of socially important institutions in rapidly changing spheres. Beyond any doubt, the field of science has a special role to play in innovative transformation.The aim of the present sociological research is to establish the degree of compliance of the personal, collective and institutional levels of innovative restructuring of Russian science with the challenges of an innovative society. The consistency and integrity of functioning of these levels is one of the key conditions for the professional self-realisation of a modern scientist.Methodology and research methods. The methodological basis of the study is the integral individual-system paradigm, which considers the agent of action in the system of rules and resources, limiting the range of choice in the system. Empirical data were collected through an expert semi-formalised survey of researchers in 21 entities of the Russian Federation. The sample (N = 640) consisted of respondents engaged in technical, natural, humanitarian, social and philosophical spheres, higher education system, centres of the Russian Academy of Sciences and state management structures.Results and scientific novelty. The institutionalisation of social practices is represented as a synthesis of the field of individual intentions and rules of interaction established in the social field. At the intersection of these fields, standardised social interaction schemes are being transformed and new behaviours and actions are emerging.The present research for the first time applied a three-level model of institutionalisation of science in an innovative environment, which allowed correlating the personal, organisational and systemic factors of disclosure of the intellectual potential of the scientist. Moreover, this resulted in identifying the existing contradictions between the personal motivation of agents of scientific activity and mechanisms, which structure the work of scientific organisations and the system of indicators of their effectiveness approved by the state. The survey data demonstrated stable motivation of Russian scientists for professional self-realisation and active scientific search, based on personal responsibility, understanding of the social significance of their research, or less frequently based on the membership of a successful team. However, serious institutional barriers have been identified to optimise the working conditions of scientists. The institutional barriers include: the administrative difficulties of establishing strong professional links with production, social and power structures; the lack of opportunities to participate in global scientific discourse; the narrow functionality of scientific organisations as an intermediate link between scientists and the state; the reluctance of expert scientific community to develop the criteria and indicators of the quality of scientific activity; the non-compliance of these indicators with innovative priorities and goals, etc.Practical significance. The research results and proposals can be used to adjust the state policy of the Russian Federation and the principles of management of the organisation in accordance with the innovative priorities of the society.

Ultrasonography provides a minimally invasive method to evaluate the cervical lymph nodes in dogs as part of staging head and neck cancer; however, standardized cohesive reports of the normal lymph node size and appearance are lacking. The purpose of this prospective, descriptive, reference interval study was to characterize the ultrasonographic appearance of cervical lymph nodes in 27 clinically healthy dogs. The size, shape, echogenicity, and margination of the mandibular, medial retropharyngeal, and superficial cervical lymph nodes were evaluated and correlated with age, breed, sex, body weight, and stage of dental disease. The appearance of the lymph nodes was variable among the population. The majority were cigar or ovoid in shape with smooth margins. The echogenicity of the mandibular lymph nodes was predominantly hypoechoic whereas the medial retropharyngeal lymph nodes were predominantly isoechoic compared to the salivary glands. The superficial cervical lymph nodes were predominantly hyperechoic to the surrounding muscle bellies. Higher body weight and younger age were associated with increased size in the medial retropharyngeal and superficial cervical lymph nodes (P-values < .05). Sex and breed were not found to correlate with lymph node characteristics, and there was no trend noted in lymph node appearance associated with dental disease. These data establish normal parameters for the ultrasonographic size and appearance of cervical lymph nodes in dogs and can provide a reference of comparison for future canine cervical ultrasounds, which can be considered for routine staging procedures for head and neck cancer.

Purpose When in the Summer of 2015 unprecedented numbers of refugees traveled through Austria, not only public and governmental authorities were challenged to provide support, but also the business sector. Various companies responded to the challenge by organizing relief actions, among them Austrian Federal Railways (OEBB). The purpose of this paper is to analyze the effects of this initiative on stakeholder perceptions and behavior. Design/methodology/approach The case of OEBB served as the research context. Data were collected by means of an online survey in May of 2016, about eight months after the initiative. Findings Almost half of the participants mentioned OEBB’s activities for refugees in an unaided recall task. Unaided corporate social responsibility (CSR) awareness is related to people’s issue involvement and reminiscence of specific activities and communication measures. People unaidedly recalling the initiative expressed a significantly better CSR image and identification with the company; they also expressed a stronger intention to speak positively (positive word of mouth) about the company’s CSR activities. CSR image and attitude toward the initiative mediates this effect. Research limitations/implications The study stresses the importance of CSR awareness and communication. The non-representative sample does not allow general inferences. Originality/value This research uses an actual case to test the effectiveness of CSR activities and communication in the context of a highly critical situation, and sheds light on the mediating processes that drive the effects. The study extends existing knowledge from experimental studies.

Spirometry plays an important role in the diagnosis and management of obstructive and restrictive lung disease [1–4]. To help ensure the accuracy of spirometry testing the American Thoracic Society (ATS)/European Respiratory Society (ERS) recommend that the calibration of spirometers be verified daily with a 3-L syringe and the recorded value should be 3 L ±3.5% [5]. This recommendation is based on expert opinion, not evidence. The following case describes a situation where a significant spirometer malfunction was not detected by the ATS/ERS spirometer calibration limits and offers an alternative approach to spirometer quality control., The ATS/ERS spirometer calibration standards may not be adequate http://ow.ly/Pqdq30nwAmb

Until we have more comprehensive data from all regions in the world, we must be careful not to apply GLI equations indiscriminatelyhttps://bit.ly/3g1r9Q5

The treatment of diseases with biologic agents can result in the formation of anti-drug antibodies (ADA). The occurrence of ADA were reported for atezolizumab, an anti-PD-L1 monoclonal antibody widely used as immunotherapeutic treatment in cancer patients. Although drivers for ADA formation are unknown, a role for antigen presentation is likely, and variation in human leukocyte antigen (HLA) genes has been shown to be associated with occurrence of ADA for several biologics. Here, we performed an HLA-wide association study in 1,982 patients treated with atezolizumab across 8 clinical trials. On average, 29.8% of patients were ADA positive (N = 591, range of 13.5% -38.4%), and 14.6% of patients were positive for ADA that were neutralizingin vitro(NAb, N = 278, range of 6.4% - 21.9%). We found statistically significant associations between HLA class II alleles and ADA status. The top-associated alleles wereHLA-DRB1*01:01for all ADA (p = 3.4*10−5, odds ratio = 1.96), andHLA-DQA1*01:01when considering NAb only (p = 2.8 x 10−7, OR = 2.31). Both alleles occur together on a common HLA haplotype, and the ADA association was explained by the NAb subset. In conclusion, our study showed that HLA class II genotype contributes to the risk of developing ADA, and specifically NAb, in patients treated with atezolizumab, but suggests that genetic factors are not sufficient as clinically meaningful predictors.

Purpose The purpose of this study was to evaluate the safety, efficacy, and efficiency of a Descemet membrane endothelial keratoplasty (DMEK) graft preparation device, DescePrep, through measurement of graft viability, yield, and preparation time in both healthy and diabetic (high-risk) donor eyes. Methods Twenty nondiabetic and 10 diabetic donor corneas were processed using DescePrep, which standardizes the liquid bubble technique. Corneas were stained with trypan blue and then processed. Cell counts through specular microscopy, optical coherence tomography imaging, and slit-lamp analysis were used for the evaluation of graft separation and viability in 5 nondiabetic corneas. The remaining 25 corneas (15 nondiabetic and 10 diabetic) were evaluated for preparation success rate and processing time. Ten corneas (5 nondiabetic and 5 diabetic) were randomly selected for further evaluation of global cell loss through staining. Results Ninety-seven percent of corneas (29 of 30) were prepared successfully with DescePrep. The average preparation time was 2.83 ± 1.8 minutes. There was no significant difference in the time of preparation between the nondiabetic and diabetic groups (P = 0.077). The overall average cell death after processing was 7.9% ± 3.7% for all corneas. There was no significant difference in cell viability between diabetic and nondiabetic tissues after DescePrep processing (P = 0.769). Conclusions DescePrep is a new DMEK preparation technique that can process both nondiabetic and diabetic donor corneas at high yields in minutes. High-yield preparation of diabetic corneas may offer eye banks access to a larger donor , which is important because the demand for DMEK grafts continues to rise worldwide.

Background E-cigarette use, or vaping, is known to be associated with potentially life-threatening lung injury, with the Centers for Disease Control and Prevention reporting 2,807 hospitalizations and 68 deaths in the United States due to e-cigarette or vaping-associated lung injury. Vaping is also a risk factor for and is implicated in the spreading of COVID-19. Despite the consequences of vaping, the views and training of medical students regarding vaping is unclear. This study sought to investigate the knowledge and perception of vaping amongst future health care providers. Methods An anonymous, online survey was administered to 259 first through fourth year medical students at Nova Southeastern University Dr. Kiran C. Patel College of Osteopathic Medicine via a secure website link in October 2019 and January 2020. The survey consisted of two sections. All participants answered section one, involving nine questions. This first section addressed sociodemographic characteristics, personal views on vaping, rating and impact of vaping medical education, and whether students had ever tried vaping. If students had ever vaped, they proceeded to section two of the survey including nine additional questions. Students that reported no past vaping use ended the survey and did not proceed to section two. Section two focused on evaluating vaping habits of users by questioning age of first usage, use frequency and nature, reasons for first trying and/or continuing to use, plans for quitting, personal impact of use, and current use. Data was analyzed with frequency and percentage distributions. Results Most respondents were of age 18-25 years (66.8%) and female (60.2%). Almost all students (96.5%) were aware of the negative health consequences of vaping. More than two thirds of students (68.7%) rated their vaping medical education as inadequate and the majority (76.1%) indicated their medical school curriculum did not impact their view on the matter. Most students (71.0%) reported a more negative stance on vaping due to recent news and media. Of the respondents, over two thirds (37.5%) vaped at least once and were labeled "vapers." The most commonly stated reason for first trying vaping was recreational (60.8%). Half of vapers (50.5%) admitted to vaping in the past year and most vapers (90.6%) did not think their vaping impacted others. Current vaping use was reported in almost one-third of vapers (32.3%) despite knowing its dangers, and several (6.3%) did not consider vaping dangerous. Conclusion The findings from this pilot study conducted at a single medical school indicate possible deficiencies in vaping education, at least as perceived by the respondents and demonstrated by their vaping-related actions. It is unknown if the stated vaping views and practices of these medical students would be positively impacted by better vaping education or if these practices are generalizable to other students. However, the data suggests there is a need to consider more extensive analyses of medical school curriculums with respect to vaping education and training of students in these and related areas. Recommendations to enhance medical school curriculums include vaping-focused respiratory and gastrointestinal lectures, problem-based case studies on vaping, standardized patient encounters, and a community education program taught by medical students.

Low-dose dual-source computed tomography (DSCT) protocols for the evaluation of lung diseases in children and adolescents are of importance since this age group is particularly prone to radiation damage. The aim of this study was to evaluate image quality of low-dose DSCT of the lung and to assess the potential of radiation dose reduction compared to digital radiographs (DR). Three groups, each consisting of 19 patients, were examined with different DSCT protocols using tin prefiltration (Sn96/64/32 ref. mAs at 100 kV). Different strengths of iterative reconstruction were applied (ADMIRE 2/3/4). DSCT groups were compared to 19 matched patients examined with posterior–anterior DR. Diagnostic confidence, detectability of anatomical structures and small lung lesions were evaluated on a 4-point Likert scale (LS 1 = unacceptable, 4 = fully acceptable, a value ≥ 3 was considered acceptable). Effective dose (ED) was 31-/21-/9-fold higher in Sn96/Sn64/Sn32 compared to DR. Diagnostic confidence was sufficient in Sn96/Sn64 (LS 3.4/3.2), reduced in Sn32 (LS 2.7) and the worst in DR (LS 2.4). In DSCT, detectability of small anatomical structures was always superior to DR (p &lt, 0.05). Mean lesion size ranged from 5.1–7 mm, detectability was acceptable in all DSCT groups (LS 3.0–3.4) and superior to DR (LS 1.9, p &lt, 0.05). Substantial dose lowering in DSCT of the pediatric lung enables acceptable detectability of small lung lesions with a radiation dose being about 10-fold higher compared to DR.

Clothing value chain is fundamental to Mar del Plata (Argentina) as it holds a high rate of industrial added-value, is rooted in local history, and has shaped relationships and institutions. This means sustainable clothing practices are interwoven with Mar del Plata’s social and economic development. However, fashion entrepreneurs must overcome many difficulties when talking about sustainable design. To begin with, some aspects of international labels and certifications are unsuitable for textile industry in a developing country. Due to the absence of measure tools, companies lack information about their production and cannot afford improvements. Furthermore, there is a gap between academic knowledge production and industrial production. Therefore, the following questions arise: How to engage firms in assessment processes to work on a sustainable culture? How to enrich relationships between companies and research groups? The Sustainable Design Research Group (GIDSu) belonging to Universidad Nacional de Mar del Plata, Argentina, has been working for local industries for more than ten years. GIDSu has been able to design a tool to evaluate sustainable design and management in local fashion and textile firms, which finally took the name of CeDiS (Spanish acronym of sustainable design certification). CeDiS was developed in order to offer a tailored solution for small and medium companies. It works as an ecolabel, based on self-declared claims from the firms and audited by the research group (GIDSu). The aim of this tool was to acquire information about each enterprise, detect problems to display it to managers and suggest sustainable changes for continuous improvement. In addition, it worked as a way to close the gap between private companies and public science. To design the CeDiS, researchers based on present methods and standards (D4S, LIDs Wheel, ISO 14006, ISO 14021) as well as field tests and interviews. As a result, the tool includes an interview protocol, a process matrix; a result display (wheel matrix); and a diagnosis and suggestions sheet. Finally, during September 2019, GIDSu verified the CeDiS, employing it over 20 textile and fashion firms from Mar del Plata, supported by a national program for local clusters (called Programa de Apoyo a la Competitividad or PAC in Spanish). The aim of this paper is dual. First, it describes the process of adapting and designing sustainable assessment methods for industries in a developing country. Second, it shows the positive impact of this tools in local development. Through the CeDiS study, we share a possible blueprint for fashion and textile value chain (including businesspeople, scientists, politicians, consumers, and workers) to face sustainable development in complex—and often uncertain—settings.

In this paper, we present a multimodal mobile teleoperation system that consists of a novel vision-based hand pose regression network (Transteleop) and an IMU (inertial measurement units)-based arm tracking method. Transteleop observes the human hand through a low-cost depth camera and generates not only joint angles but also depth images of paired robot hand poses through an image-to-image translation process. A keypoint-based reconstruction loss explores the resemblance in appearance and anatomy between human and robotic hands and enriches the local features of reconstructed images. A wearable camera holder enables simultaneous hand-arm control and facilitates the mobility of the whole teleoperation system. Network evaluation results on a test dataset and a variety of complex manipulation tasks that go beyond simple pick-and-place operations show the efficiency and stability of our multimodal teleoperation system.

Robotic manipulation systems frequently utilize RGB-D cameras based on infrared projection to perceive three-dimensional environments. Unfortunately, this technique often fails on transparent objects such as glasses, bottles and plastic containers. We present methods to exploit the perceived infrared camera images to detect and reconstruct volumetric shapes of arbitrary transparent objects. Our reconstruction pipeline first segments transparent surfaces based on pattern scattering and absorption, followed by optimization-based multi-view reconstruction of volumetric object models. Outputs from the segmentation stage can also be utilized for single-view transparent object detection. The presented methods improve on previous work by analyzing infrared camera images directly and by successfully reconstructing cavities in objects such as drinking glasses. A dataset of recorded transparent objects, autonomously gathered by a robotic camera-in-hand setup, is published together with this work.

This study provides an understanding of how employees’ perception of organizational transparency during the long-lasting situation of the COVID-19 pandemic engendered their job engagement as well as job disengagement. Data were collected by means of an online survey among 410 employees in Austria during March 2021. Results show that employees’ perception of their organization’s approach to transparency directly influenced their job engagement and disengagement. Importantly, the relationship between transparency and job engagement was also mediated through organizational trust, and job-specific state anxiety mediated the relationship between transparency and job disengagement. The results imply the importance of transparency during times of great uncertainty and emphasize the necessity to closely consider employees’ emotional states and worries during a crisis.

Background Electrocardiographic telemetry monitors are ubiquitous in hospitals. Dedicated monitor watchers, either on the unit or in a centralized location, are often responsible for observing telemetry monitors and responding to their alarms. The impact of use of monitor watchers is not known. Objectives To evaluate the association of monitor-watcher use with (1) nurses’ knowledge of electrocardiographic (ECG) monitoring and (2) accuracy of arrhythmia detection. Methods Baseline data from 37 non–intensive care unit cardiac patient care areas in 17 hospitals in the Practical Use of the Latest Standards for Electrocardiography trial were analyzed. Nurses’ knowledge (n = 1136 nurses) was measured using a validated, 20-item online test. Accuracy of arrhythmia detection (n = 1189 patients) was assessed for 5 consecutive days by comparing arrhythmias stored in the monitor with nurses’ documentation. Multiple regression was used to evaluate the association of use of monitor watchers with scores on the ECG-monitoring knowledge test. The association of monitor-watcher use with accuracy of arrhythmia detection was examined by χ2 analysis. Results Of the 37 units, 13 (35%) had monitor watchers. Use of monitor watchers was not independently associated with ECG-monitoring knowledge (P = .08). The presence of monitor watchers also was not significantly associated with the accuracy of arrhythmia detection (P = .94). Conclusion Although the use of monitor watchers was not associated with diminished nurses’ knowledge of ECG monitoring, it also was not associated with more accurate arrhythmia detection. If implementing a monitor-watcher program, critical safety points, such as ensuring closed-loop communication, must be considered.

Background Sleep is an important, restorative behavior for health, yet many adults report troubled sleep. The existence of a support network may be beneficial for sleep quality, including as a buffer for stressful events, yet few studies have examined these relationships longitudinally. Purpose To examine the causal effect of changes in personal network support on sleep quality both directly and as a buffer of negative life events among young and older adults. Methods The UC Berkeley Social Network survey collected data from young (21–30 year old, n = 475) and late middle-age (50–70 year old, n = 637) adults across three waves between 2015 and 2018. Participants reported on personal network characteristics, negative life events, and number of nights with trouble falling and staying asleep. Fixed effects models are used to examine causal relationships among each age cohort. Results Direct effects of network support on sleep quality were observed among older adults. Insufficient practical support predicted higher rates of trouble falling asleep (incident rate ratio [IRR] = 1.40, p < .01), while a desire for more social companions predicted lower rates of trouble staying asleep (IRR = 0.81, p < .01). Buffering effects of network support on sleep quality were observed among young adults. Changes in partnership status buffer the negative effects of the death of a close tie on trouble falling asleep (IRR = 0.75, p < .01) and persistent difficulties paying bills on trouble staying asleep (IRR = 0.45, p < 0.001) among young adults. Conclusions This study provides evidence for the direct and buffering role of network support on sleep quality. Our results indicate that efforts to improve sleep quality should address personal networks and the support they provide, perhaps especially during times of stress for younger adults.

Significance Using mouse models that recapitulate key genetic abnormalities accumulating during colorectal cancer (CRC) tumorigenesis, we report that chemically induced colitis promoted development of colon tumors that were largely resistant to anti-VEGF antibody treatment. Serum G-CSF levels were markedly elevated after induction of colitis. Inhibition of G-CSF or Bv8/PROK2 increased the efficacy of anti-VEGF antibody and prevented onset of resistance. To verify the potential clinical relevance of these findings, we examined a series of CRC specimens and found that tumor-infiltrating neutrophils strongly expressed Bv8/PROK2. CRC patients had significantly higher plasma Bv8/PROK2 levels than healthy volunteers and high plasma Bv8/PROK2 levels were inversely correlated with overall survival. These findings establish Bv8/PROK2 as a translational target in CRC, in combination with anti-VEGF agents., We tested cis-ApcΔ716/Smad4+/− and cis-ApcΔ716/Smad4+/− KrasG12D mice, which recapitulate key genetic abnormalities accumulating during colorectal cancer (CRC) tumorigenesis in humans, for responsiveness to anti-VEGF therapy. We found that even tumors in cis-ApcΔ716/Smad4+/− KrasG12D mice, although highly aggressive, were suppressed by anti-VEGF treatment. We tested the hypothesis that inflammation, a major risk factor and trigger for CRC, may affect responsiveness to anti-VEGF. Chemically induced colitis (CIC) in cis-ApcΔ716/Smad4+/− and cis-ApcΔ716/Smad4+/− KrasG12D mice promoted development of colon tumors that were largely resistant to anti-VEGF treatment. The myeloid growth factor G-CSF was markedly increased in the serum after induction of colitis. Antibodies blocking G-CSF, or its target Bv8/PROK2, suppressed tumor progression and myeloid cell infiltration when combined with anti-VEGF in CIC-associated CRC and in anti-VEGF-resistant CRC liver metastasis models. In a series of CRC specimens, tumor-infiltrating neutrophils strongly expressed Bv8/PROK2. CRC patients had significantly higher plasma Bv8/PROK2 levels than healthy volunteers and high plasma Bv8/PROK2 levels were inversely correlated with overall survival. Our findings establish Bv8/PROK2 as a translational target in CRC, in combination with anti-VEGF agents.

Hypertrophic cardiomyopathy (HCM) is a complex disease, the phenotypes of which are only partly explained by the biomechanical effects of individual genetic variants. At the cellular level, HCM sarcomeric mutations generally enhance maximal force production ultimately leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure-function relationships, there is limited knowledge on the link between altered cardiac energetics and HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics are a common pathway leading to the clinical pathophysiological phenotypes of HCM. We performed a comprehensive multi-omic study of the molecular, ultrastructural, and functional features of HCM energetics using septal myectomy samples from 27 HCM patients and 13 normal controls (donor hearts). Combined mass spectrometry and RNA-Seq revealed dramatic alterations in multiple metabolic pathways,with major dysregulation in fatty acid metabolism leading to reduced acylcarnitines and accumulation of free fatty acids. Additionally, HCM hearts showed clear signs of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and PCr) and reduction in several mitochondrial genes involved in creatine kinase and ATP synthesis machinery. Quantitative electron microscopy showed a marked increase in severely damaged mitochondria with reduced cristae density, affecting 10-12% of total mitochondria, coinciding with reduced citrate synthase (CS) activity and mitochondrial respiration. These mitochondrial abnormalities were associated with elevated ROS and reduced antioxidant defenses along with insufficient mitophagic clearance. Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in HCM. A central role for compromised energetics in HCM could also help explain the delayed age of onset of the clinical phenotype and present novel drug targets for attenuation of the clinical disease through reducing mitochondrial injury and improving function.

Planar pushing remains a challenging research topic, where building the dynamic model of the interaction is the core issue. Even an accurate analytical dynamic model is inherently unstable because physics parameters such as inertia and friction can only be approximated. Data-driven models usually rely on large amounts of training data, but data collection is time consuming when working with real robots. In this paper, we collect all training data in a physics simulator and build an LSTM-based model to fit the pushing dynamics. Domain Randomization is applied to capture the pushing trajectories of a generalized class of objects. When executed on the real robot, the trained recursive model adapts to the tracked object's real dynamics within a few steps. We propose the algorithm \emph{Recurrent} Model Predictive Path Integral (RMPPI) as a variation of the original MPPI approach, employing state-dependent recurrent models. As a comparison, we also train a Deep Deterministic Policy Gradient (DDPG) network as a model-free baseline, which is also used as the action generator in the data collection phase. During policy training, Hindsight Experience Replay is used to improve exploration efficiency. Pushing experiments on our UR5 platform demonstrate the model's adaptability and the effectiveness of the proposed framework.

Gas hydrates have received considerable attention due to their important role in flow assurance for the oil and gas industry, their extensive natural occurrence on Earth and extraterrestrial planets, and their significant applications in sustainable technologies including but not limited to gas and energy storage, gas separation, and water desalination. Given not only their inherent structural flexibility depending on the type of guest gas molecules and formation conditions, but also the synthetic effects of a wide range of chemical additives on their properties, these variabilities could be exploited to optimise the role of gas hydrates. This includes increasing their industrial applications, understanding and utilising their role in Nature, identifying potential methods for safely extracting natural gases stored in naturally occurring hydrates within the Earth, and for developing green technologies. This review summarizes the different properties of gas hydrates as well as their formation and dissociation kinetics and then reviews the fast-growing literature reporting their role and applications in the aforementioned fields, mainly concentrating on advances during the last decade. Challenges, limitations, and future perspectives of each field are briefly discussed. The overall objective of this review is to provide readers with an extensive overview of gas hydrates that we hope will stimulate further work on this riveting field.

Introduction Research on disparities in health and health care has demonstrated that social, economic, and political factors are key drivers of poor health outcomes. Yet the role of such structural forces on health and health care has been incorporated unevenly into medical training. The framework of structural competency offers a paradigm for training health professionals to recognize and respond to the impact of upstream, structural factors on patient health and health care. Methods We report on a brief, interprofessional structural competency curriculum implemented in 32 distinct instances between 2015 and 2017 throughout the San Francisco Bay Area. In consultation with medical and interprofessional education experts, we developed open-ended, written-response surveys to qualitatively evaluate this curriculum's impact on participants. Qualitative data from 15 iterations were analyzed via directed thematic analysis, coding language, and concepts to identify key themes. Results Three core themes emerged from analysis of participants' comments. First, participants valued the curriculum's focus on the application of the structural competency framework in real-world clinical, community, and policy contexts. Second, participants with clinical experience (residents, fellows, and faculty) reported that the curriculum helped them reframe how they thought about patients. Third, participants reported feeling reconnected to their original motivations for entering the health professions. Discussion This structural competency curriculum fills a gap in health professional education by equipping learners to understand and respond to the role that social, economic, and political structural factors play in patient and community health.

Predicted values for pulmonary function tests differ significantly from the reference values used for many other diagnostic tests. Historically, simple equations using age, height, and sex were used to "predict" normal lung function. However, these multiple factors interact in complex ways to determine what the expected lung function values are in healthy subjects. Healthy individuals exhibit a wide range of variability for most pulmonary function variables, and this variability is not consistent across all age ranges. Recent analysis of large groups of healthy subjects has allowed the development of sophisticated prediction models that take into account not only variability but also skew that occurs as the lungs develop and mature. These modern reference equations provide uninterrupted expected values from early childhood, through adolescence and adulthood, and extending into the ninth decade. Modern equations use upper and lower limits of normal to offer a statistically robust means of defining who is within normal limits. Despite these advances, interpretation of pulmonary function test results has not been highly standardized, largely because interpretation depends on the reference equations used and, more importantly, how they are applied. This review discusses the strengths and limitations of using reference equations to interpret pulmonary function data in the context of research and clinical practice.

This cross-sectional study uses data from a large integrated health care system to assess search patterns and practices among electronic health record users., Key Points Question What are the electronic health record search patterns and practices among electronic health record users? Findings In this cross-sectional study of 12 313 047 patient electronic health record search activities, physicians and pharmacists conducted the most searches, with statin, colonoscopy, and pft being the most frequently searched terms. Search term networks revealed how users bridged together data across various domains relevant to a single clinical interaction. Meaning Our results suggest that opportunities exist for improving the clinical use of the electronic health record by identifying potential areas to customize information retrieval based on diverse user roles and linked search approaches., Importance The electronic health record (EHR) is a source of practitioner dissatisfaction in part because of challenges with information retrieval. To improve data accessibility, a better understanding of practitioners’ information needs within individual patient records is needed. Objective To assess EHR users’ searches using data from a large integrated health care system. Design, Setting, and Participants This retrospective cross-sectional analysis used EHR search data from Kaiser Permanente Northern California, an integrated health care delivery system with more than 4.4 million members. Users’ EHR search activity data were obtained from April 1, 2018, to May 15, 2019. Main Outcomes and Measures Search term frequency was grouped by user and practitioner types. Network analyses were performed of co-occurring search terms within a single search episode, and centrality measures for search terms (degree and betweenness centrality) were calculated. Results A total of 12 313 047 search activities (including 4 328 330 searches and 7 984 717 result views) conducted by 34 735 unique users within 977 160 unique patient EHRs were identified. In aggregate, users searched for 208 374 unique search terms and conducted a median of 4 searches (interquartile range, 1-28 searches). Of all 97 367 active EHR users, 34 735 (35.7%) conducted at least 1 search. However, of all 12 968 active EHR physician users, 9801 (75.6%) conducted at least 1 search, and of all 1908 active pharmacist users, 1402 (73.5%) conducted at least 1 search. The top 3 most commonly searched terms were statin (75 017 searches [1.7%]), colonoscopy (73 545 [1.7%]), and pft (54 990 [1.3%]). However, wide variation in top searches were noted across practitioner groups. Terms searched most often with another term in a single linked search episode included statin, lisinopril, colonoscopy, gabapentin, and aspirin. Conclusions and Relevance Although physicians and pharmacists were the most active users of EHR searches, search volume and frequently searched terms varied considerably by and within user role. Further customization of the EHR interface may help leverage users’ search content and patterns to improve targeted information retrieval.

For decades, those working in hospitals normalised the incessant alarms from medical devices as a necessary, almost comforting, reality of a high tech industry. While nurses drowned in excessive, frequently uninformative alarms, other members of the healthcare team often paid little attention. Fortunately, times are changing and managing alarm fatigue is now a key patient safety priority in acute care environments.1 Adverse patient events from alarm fatigue, particularly related to excessive physiological monitor alarms, have received widespread attention over the last decade, including from the news media.2–5 In the USA, hospitals redoubled alarm safety efforts following the 2013 Joint Commission Sentinel Event Alert and subsequent National Patient Safety Goals on alarm safety.1 2 6 We are now beginning to understand how to reduce excessive non-actionable alarms (including invalid alarms as well as those that are valid but not actionable or informative),7 8 better manage alarm notifications and ultimately improve patient safety. Alarm data are readily available and measuring alarm response time during patient care is possible.7 9 Yet we have few high-quality reports describing clear improvement to clinical alarm burden, and most published interventions are of limited scope, duration or both.10 11 To demonstrate value in alarm quality improvement (QI) efforts moving forward, we need more rigorous evidence for interventions and more meaningful outcome measures. In this issue of BMJ Quality and Safety, Pater et al 12 report the results of a comprehensive multidisciplinary alarm management QI project executed over 3½ years in a 17-bed paediatric acute care cardiology unit. The primary project goal was to reduce alarm notifications from continuous bedside monitoring. Although limited to a single unit, the project is an important contribution to the scant literature on alarm …

Background Among other factors, the patients’ consultation reasons and GPs’ spectrum of services determine the process and outcome of the medical treatment. So far, however, there has been little information on differences in reasons for consultation and GPs’ services between urban and rural areas. Our study’s goal was thus to investigate these factors in relation to the regional location of GPs’ practices. Methods We conducted a cross-sectional observational study based on standardised GP interviews in a quota sampling design. All counties and independent cities within a radius of 120 km around Hamburg were divided into three regional categories (urban area, environs, rural area) and stratified proportionally to the population size. Differences in the number of reasons for consultation and services were analysed by multivariate linear regressions in mixed models adjusted for random effects on the levels of the German federal states and administrative districts. Differences in individual consultation reasons and services were identified by logistic regression via stepwise forward and backward selection. Results Primary care practices in 34 of the 37 selected administrative districts (91.9%) were represented in the dataset. In total, 211 GPs were personally interviewed. On average, GPs saw 344 patients per month with a slightly higher number of patients in rural areas. They reported 59.1 ± 15.4 different reasons for consultation and 30.3 ± 3.9 different services. There was no statistically significant regional variation in the number of different consultation reasons, but there was a broader service spectrum by rural GPs (ß = − 1.42; 95% confidence interval − 2.75/− 0.08; p = 0.038) which was statistically explained by a higher level of medical training. Additionally, there were differences in the frequency of individual consultation reasons and services between rural and urban areas. Conclusion GPs in rural areas performed more frequently services usually provided by medical specialists in urban areas. This might be caused by a low availability of specialists in rural areas. The association between medical training and service spectrum might imply that GPs compensate the specific needs of their patients by completing advanced medical training before or after setting up a medical practice. Trial registration The study was registered in ClinicalTrials.gov (NCT02558322).

The 6-minute walk test (6MWT) is not intended to document oxygen (O2) desaturation during exertion but is often used for this purpose. Because of this, it only has modest reproducibility in determining the need for ambulatory O2 therapy in patients with cardiopulmonary disease. The diagnostic and prognostic value of detecting exertional O2 desaturation is still unknown. The aims of this study were to estimate the prevalence of O2 desaturation during a 6MWT based on pulse oximetry measurements at the beginning and end of a 6MWT in a clinical population of patients with suspected cardiopulmonary disease and to determine whether the pulmonary function test (PFT) can predict exercise-induced desaturation during a 6MWT. This retrospective cohort study reviewed the results of the 6MWT and the PFT (i.e., spirometry, lung volumes, and diffusion capacity) of all patients who were evaluated for suspected cardiopulmonary disease at an academic medical center during a 5-year study period. The patients were categorized into three groups based on the change in O2 saturation by pulse oximetry (SpO2) from start to end of the 6MWT: (1) SpO2 decreased by &ge, 3%, (2) SpO2 unchanged (&minus, 2 &le, &Delta, &le, 0%), and (3) SpO2 increased by &ge, 1%. Demographic, anthropometric, and lung function measurements were analyzed to determine which factors predicted O2 desaturation during the 6MWT. Of the 319 patients who underwent the 6MWT and the PFT from November 2005 until December 2010 (mean age = 54 &plusmn, 0.78 years, 63% women, 58% Whites, body mass index = 29.63 &plusmn, 8.10 kg/m2), 113 (35%) had a decreased SpO2, 146 (46%) had no change, and 60 (19%) had an increased SpO2 from the start to end of test. Our bivariate analysis found age, spirometric measures, and diffusion capacity for carbon monoxide (DLCO) had statistically significant inverse associations with the SpO2 change category (p &lt, 0.001). Both a 3% and 4% drop in SpO2 during the 6MWT were statistically significantly associated with an older age, a higher prevalence of obstruction, and reduced forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC, DLCO and 6-minute walk distance (6MWD). Multivariable logistic regression analyses revealed that only DLCO was a significant independent predictor of the change in SpO2 and a &ge, 4% O2 desaturation during a 6MWT. Receiver operating curve analysis indicates DLCO cut-off of 45% is 82% sensitive and 40% specific in identifying &ge, 4% O2 desaturators, with an area under the curve of 0.788 &plusmn, 0.039 (p &lt, 0.001). The prevalence of a &ge, 3% oxygen desaturation via pulse oximetry during a 6MWT in our clinical population of patients with suspected cardiopulmonary disease was 35%. Although age, spirometric lung volumes, and DLCO had statistically significant unadjusted inverse associations with the change in SpO2 during a 6MWT, the DLCO is the only significant independent predictor of both the magnitude of the change in SpO2 and the occurrence of O2 desaturation of at least 4%, respectively, during the test. Clinical Implications: A DLCO cut-off of 45% may be useful in identifying patients at risk for exertional hypoxemia during a 6MWT.

This paper reviews applications of acoustic wave devices in mobile communication. After a general and historical introduction to bulk acoustic wave (BAW) and surface acoustic wave (SAW) devices, a review is given on the architectures where acoustic wave devices are applied driving the requirements on the SAW and BAW components. Following this, we discuss the progress in technology important materials. Next, an overview on the modeling and characterization of SAW and BAW at high power levels is given. Finally an overview of packaging technologies and an outlook to future developments is provided. Finally, an outlook to future developments is provided.

Das Merkelzellkarzinom ist ein seltenes, aggressiv verlaufendes neuroendokrines Karzinom der Haut. In der Ara der Chemotherapie war die Prognose bei Fernmetastasierung nahezu infaust — mit Einfuhrung der Immuncheckpointinhibitoren wurde das Spektrum der Therapieoptionen wesentlich erweitert.

Background Customizing monitor alarm settings to individual patients can reduce alarm fatigue in intensive care units (ICUs), but has not been widely studied. Objectives To understand ICU nurses' approaches to customization of electrocardiographic (ECG) monitor alarms. Methods A convergent mixed methods study was conducted in 3 ICUs in 1 hospital. Data on the type and frequency of ECG alarm customization were collected from patient monitors (n=298). Nurses' customization clinical reasoning was explored through semi-structured interviews (n=27). Results Of the 298 patients, 58.7% had ≥1 alarm(s) customized. Heart rate limits, irregular heart rate, and atrial fibrillation were the most commonly customized alarms. Interviews revealed that customization practices varied widely and were influenced by factors including clinical expertise, lack of customization education, and negative experiences. Conclusion Alarm customization is nuanced and requires adequate support to develop safe and effective practices. The challenges identified can inform development of strategies to improve alarm customization.