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PURPOSE Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease. PATIENTS AND METHODS Two hundred twenty-two women, with HER2-overexpressing metastatic breast cancer that had progressed after one or two chemotherapy regimens, were enrolled. Patients received a loading dose of 4 mg/kg intravenously, followed by a 2-mg/kg maintenance dose at weekly intervals. RESULTS Study patients had advanced metastatic disease and had received extensive prior therapy. A blinded, independent response evaluation committee identified eight complete and 26 partial responses, for an objective response rate of 15% in the intent-to-treat population (95% confidence interval, 11% to 21%). The median duration of response was 9.1 months; the median duration of survival was 13 months. The most common adverse events, which occurred in approximately 40% of patients, were infusion-associated fever and/or chills that usually occurred only during the first infusion, and were of mild to moderate severity. These symptoms were treated successfully with acetaminophen and/or diphenhydramine. The most clinically significant adverse event was cardiac dysfunction, which occurred in 4.7% of patients. Only 1% of patients discontinued the study because of treatment-related adverse events. CONCLUSION Recombinant humanized anti-HER2 monoclonal antibody, administered as a single agent, produces durable objective responses and is well tolerated by women with HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. Side effects that are commonly observed with chemotherapy, such as alopecia, mucositis, and neutropenia, are rarely seen.

Soil structure in terms of the spatial arrangement of pores and solids is highly relevant for most physical and biochemical processes in soil. While this was known for a long time, a scientific approach to quantify soil structural characteristics was also missing for a long time. This was due to its buried nature but also due to the three-dimensional complexity. During the last two decades, tools to acquire full 3D images of undisturbed soil became more and more available and a number of powerful software tools were developed to reduce the complexity to a set of meaningful numbers. However, the standardization of soil structure analysis for a better comparability of the results is not well developed and the accessibility of required computing facilities and software is still limited. At this stage, we introduce an open-access Soil Structure Library (https://structurelib.ufz.de/, last access: 22 July 2022) which offers well-defined soil structure analyses for X-ray CT (computed tomography) data sets uploaded by interested scientists. At the same time, the aim of this library is to serve as an open data source for real pore structures as developed in a wide spectrum of different soil types under different site conditions all over the globe, by making accessible the uploaded binarized 3D images. By combining pore structure metrics with essential soil information requested during upload (e.g., bulk density, texture, organic carbon content), this Soil Structure Library can be harnessed towards data mining and development of soil-structure-based pedotransfer functions. In this paper, we describe the architecture of the Soil Structure Library and the provided metrics. This is complemented by an example of how the database can be used to address new research questions.

Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data ( http://www.brainchart.io/ ). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes., R.A.I.B. was supported by a British Academy Postdoctoral fellowship and by the Autism Research Trust. J. Seidlitz was supported by NIMH T32MH019112-29 and K08MH120564. S.R.W. was funded by UKRI Medical Research Council MC_UU_00002/2 and was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). E.T.B. was supported by an NIHR Senior Investigator award and the Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network. A.F.A.-B. was supported by NIMH K08MH120564. Data were curated and analysed using a computational facility funded by an MRC research infrastructure award (MR/M009041/1) to the School of Clinical Medicine, University of Cambridge and supported by the mental health theme of the NIHR Cambridge Biomedical Research Centre.

Although paradoxes are inherent to the public sector, few attempts have been made to better understand how to manage such competing yet interrelated demands effectively. This study examines how paradoxical leadership (i.e., leaders’ sense-giving about organizational paradoxes) affects follower outcomes. Based on two-wave survey data from German district offices, structural equation modelling reveals that paradoxical leadership positively influences followers’ job satisfaction and work engagement. Role ambiguity fully mediates the relationship between paradoxical leadership and perceived performance. Our study expands the nomological network of public leadership and advances the notion that paradoxes bear potentials for leadership in ambiguous public settings.

The first millennium BCE was pivotal for the environment and for human societies in Central and Eastern Eurasia because transformations accelerated and altered natural and cultural landscapes to hitherto unknown dimensions. Among the major driving forces was the increasing use of horse riding, which extended range of movement significantly and led to the development of cavalry units as a part of large armies. Empires with enormous outreach and gravitational pull formed and disintegrated in close dependence. The wide spread of military technologies demonstrates their bonds, though mostly in the form of metal objects due to the inherent survivability of their materials. Equipment and protective clothing of organic material, albeit produced in large numbers and thus an economic and environmental factor, are rarely preserved. In Yanghai cemetery site, Turfan, the remains of one leather scale armour were discovered. In this study, the results of the AMS radiocarbon dating as well as the construction details of the Yanghai find are presented and compared with a contemporary armour of unknown origin in the Metropolitan Museum of Art New York (MET) and with finds and depictions from the Near East, the adjacent northern steppe areas and the territory of China. The armour, datable to 786–543 cal BCE (95% probability), was originally made of about 5444 smaller scales and 140 larger scales, which, together with leather laces and lining, had a total weight of ca. 4–5 kg. Our reconstruction demonstrates that it can be donned quickly and without the help of another person by wrapping the left part around the back, tying it to the right part under the right arm and fastening with thongs crosswise over the back to laces at the opposite hip parts. Fitting different statures, it is a light and highly efficient defensive garment. In age, construction details and aesthetic appearance it resembles the MET armour. The stylistic similarities but constructional differences suggest that the two armours were intended as outfits for distinct units of the same army, i.e. light cavalry and heavy infantry, respectively. As such a high level of standardization of military equipment during the 7th century BCE is only known for the Neo-Assyrian military forces, we suggest that the place of manufacture of both armours was the Neo-Assyrian Empire. If this supposition is correct, then the Yanghai armour is one of the rare actual proofs of West-East technology transfer across the Eurasian continent during the first half of the first millennium BCE, when social and economic transformation accelerated.

Research on nicotine metabolism has primarily focused on white adults. This study examined associations between nicotine metabolism, tobacco use, and demographic characteristics among Alaska Native adults who smoke cigarettes. Participants (N = 244) were Alaska Native adults who smoked and who provided a plasma sample at baseline (70.1%) or follow-up (29.9%) of a randomized controlled trial of a cardiovascular risk behavior intervention. At baseline, participants self-reported age, sex, Alaska Native heritage, cigarettes per day, time to first cigarette upon wakening, menthol use, perceived difficulty staying quit, tobacco withdrawal symptoms, and past-month tobacco product use, binge drinking, and cannabis use. At 3-, 6-, 12-, and 18-month follow-ups, participants self-reported 7-day point prevalence abstinence from smoking. Height and weight were measured to calculate body mass index (BMI). Participants' nicotine metabolite ratio (NMR), calculated as the ratio of plasma cotinine and trans-3' hydroxycotinine, was log-transformed. The sample (52.0% male, age M = 47.0 years [SD = 13.8], 60.3% of Inupiaq heritage) averaged 12.5 cigarettes per day (SD = 10.5); 64.0% smoked within 30 min of wakening. NMR was not significantly associated with age, sex, Alaska Native heritage, BMI, cigarettes per day, time to first cigarette upon wakening, menthol use, perceived difficulty staying quit, past-month dual tobacco product use, withdrawal symptoms, past-month binge drinking, past-month cannabis use, or abstinence from smoking (all p-values > .050). Characteristics that relate to NMR in Alaska Native adults may differ from those typically identified among white adults. Specifically, results may suggest that Alaska Native adults with slower nicotine metabolism do not titrate their nicotine intake when smoking. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Summary Objective To evaluate the use of psychotropic medication by family caregivers of elderly patients with and without dementia. Methodology This prospective observational study was conducted in the geriatric department of the University Hospital of Strasbourg over a period of six months. Two groups were formed: one comprising elderly patients without dementia and the other elderly patients with dementia. Semi-structured interviews were conducted with 10 caregivers of patients with dementia. Results One hundred and eighty-four “elderly patient-informal caregiver” dyads were included. Forty-three caregivers (24.3%) reported using psychotropic medication. Consumption was significantly higher among caregivers of patients with dementia (30.7% vs. 18.2%; P Conclusion Given the increase in the number of people with dementia being cared for at home, society needs to implement specific interventions to prevent the burden that informal caregivers may feel, which, in our study, translates into increased consumption of psychotropic medication.

Background Our purpose is to describe the structure, function and outcomes of our multidisciplinary pediatric thyroid program and to evaluate our experience in comparison to other high-volume centers. Methods We reviewed all thyroid operations performed 10/2012 through 09/2019, and examined number of cases per year, patient demographics, procedures, final diagnoses and results. Primary outcomes were hypoparathyroidism and recurrent laryngeal nerve (RLN) injury at 12 months. Data were analyzed using descriptive statistics and univariate analyses. Results We performed 294 thyroid operations on 279 patients. Seventy-nine percent were female. Median age was 15 years (IQR: 12–17). Operations included total thyroidectomy (65%), lobectomy (30%) and completion thyroidectomy (5%). Most common diagnoses were Graves’ disease (35%), malignancy (29%), and benign nodule (20%). We developed an evidence-based clinical pathway and conducted weekly multidisciplinary meetings. A clinical data specialist reviewed process and outcome measures routinely. Overall, 6 patients (2.0%) had hypoparathyroidism and 2 (0.7%) had unilateral RLN injury at 12 months. Two of the patients with clinical suspicion of permanent hypoparathyroidism were ultimately weaned off calcium. Both patients with RLN injury had extensive locally advanced malignant disease involving the nerve. Conclusions Our multidisciplinary team achieved excellent long-term outcomes for pediatric thyroid surgery comparable to other high-volume pediatric and adult centers. Level of Evidence IV

Endovascular aneurysm repair is the standard of care for abdominal aortic aneurysm repair, however data regarding adjunctive stenting at the time of endovascular aneurysm repair (EVAR) are limited. The study aims to evaluate outcomes of patients undergoing EVAR with and without adjunctive stenting.Patients undergoing EVAR with stenting (EVAR-S) and without stenting (EVAR) (2008 - 2017) were selected from Cerner HealthFacts database using ICD-9 diagnosis and procedure codes. Chi-square analysis and multivariable logistic regression were used to evaluate the association of patient characteristics with medical and vascular outcomes.4,957 patients undergoing EVAR procedures were identified (3,816 EVAR and 1,141 EVAR-S). Demographic analysis revealed that patients who underwent EVAR-S had higher Charlson comorbidity scores (2.35 vs. 2.13, P = 0.0001). EVAR-S was associated with a greater frequency of vascular complications such as thrombolysis/percutaneous thrombectomy (0.9% vs. 0.2%; P0.0004). There were no differences seen in access complications between EVAR and EVAR-S. Multivariable analysis revealed that EVAR-S was associated with prolonged length of stay (OR 1.37, 95% CI 1.03-1.82), readmission30 days (OR 1.36, 95% CI 1.11-1.68), major adverse cardiac events (OR 1.59, 95% CI 1.09-2.32), respiratory complications (OR 1.47, 95% CI 1.16-1.88) and renal failure (OR 1.57, 95% CI 1.16-2.11).Endovascular aneurysm repair with adjunctive stenting (EVAR-S) was associated with vascular complications requiring reintervention, although the overall rate was very low. As well, readmission within 30 days, cardiac complications, respiratory problems and renal failure were more likely when compared to standard EVAR. The need for adjunctive stenting acts as a marker for an overall sicker and more complex population, not just in terms of vascular complications but across all medical complications as well. Staging the procedure may be helpful in terms of spreading out the operative risk into smaller portions. Furthermore, consideration of a non-operative strategy should be discussed with the patient if the risk of the procedure outweighs the risk of aneurysm rupture in high-risk groups.

Objectives Oncologists estimate patients' prognosis to guide care. Evidence suggests oncologists tend to overestimate life expectancy, which can lead to care with questionable benefits. Information obtained from geriatric assessment may improve prognostication for older adults. In this study, we created a geriatric assessment-based prognostic model for older adults with advanced cancer and compared its performance to alternative models. Materials and methods We conducted a secondary analysis of a trial (URCC 13070; PI: Mohile) capturing geriatric assessment and vital status up to one year for adults age ≥ 70 years with advanced cancer. Oncologists estimated life expectancy as 0–6 months, 7–12 months, and > 1 year. Three statistical models were developed: (1) a model including age, sex, cancer type, and stage (basic model), (2) basic model + Karnofsky Performance Status (≤50, 60–70, and 80+) (KPS model), and (3) basic model +16 binary indicators of geriatric assessment impairments (GA model). Cox regression was used to model one-year survival; c-indices and time-dependent c-statistics assessed model discrimination and stratified survival curves assessed model calibration. Results We included 484 participants; mean age was 75; 48% had gastrointestinal or lung cancer. Overall, 43% of patients died within one year. Oncologists classified prognosis accurately for 55% of patients, overestimated for 35%, and underestimated for 10%. C-indices were 0.61 (basic model), 0.62 (KPS model), and 0.63 (GA model). The GA model was well-calibrated. Conclusions The GA model showed moderate discrimination for survival, similar to alternative models, but calibration was improved. Further research is needed to optimize geriatric assessment-based prognostic models for use in older adults with advanced cancer.

Traumatic brain injury (TBI) and blunt thoracic aortic injury (BTAI) are the top two leading causes of death after blunt force trauma. Patients presenting with concomitant BTAI and TBI pose a specific challenge with respect to management strategy, because the optimal hemodynamic parameters are conflicting between the two pathologies. Early thoracic endovascular aortic repair (TEVAR) is often performed, even for minimal aortic injuries, to allow for the higher blood pressure parameters required for TBI management. However, the optimal timing of TEVAR for the treatment of BTAI in patients with concomitant TBI remains an active matter of controversy.The Aortic Trauma Foundation international prospective multicenter registry was used to identify all patients who had undergone TEVAR for BTAI in the setting of TBI from 2015 to 2020. The primary outcomes included delayed ischemic or hemorrhagic stroke, in-hospital mortality, and aortic-related mortality. The outcomes were examined among patients who had undergone TEVAR at emergent (6 vs ≥6 hours) or urgent (24 vs ≥24 hours) intervals.A total of 100 patients (median age, 43 years; 79% men; median injury severity score, 41) with BTAI (Society for Vascular Surgery BTAI grade 1, 3%; grade 2, 10%; grade 3, 78%; grade 4, 9%) and concomitant TBI who had undergone TEVAR were identified. Emergent repair was performed for 51 patients (51%). Comparing emergent repair (6 hours) to urgent repair (≥6 hours), no difference was found in delayed cerebral ischemic events (2.0% vs 4.1%; P = .614), in-hospital mortality (15.7% vs 22.4%; P = .389), or aortic-related mortality (2.0% vs 2.0%; P = .996) and no patient had experienced delayed hemorrhagic stroke. Likewise, repairs conducted in an urgent (24 hours) setting showed no differences compared with those completed in an emergent (≥24 hours) setting regarding delayed ischemic stroke (2.6% vs 4.3%; P = .548), in-hospital mortality (18.2% vs 21.7%; P = .764), or aortic-related mortality (1.3% vs 4.3%; P = .654), and no patient had experienced delayed hemorrhagic stroke.In contrast to prior retrospective efforts, results from the Aortic Trauma Foundation international prospective multicenter registry have demonstrated that neither emergent nor urgent TEVAR for patients with concomitant BTAI and TBI was associated with delayed stroke, in-hospital mortality, or aortic-related mortality. In these patients, the timing of TEVAR did not have an effect on the outcomes. Therefore, the decision to intervene should be guided by individual patient factors rather than surgical timing.

AIMS Socioeconomic status (SES) is an important variable that impacts healthcare outcomes. However, grouped SES data is not always representative of all members and it is difficult to obtain individual level data. A validated individual housing-based measure termed HOUSES is available, but has not been studied in diabetes. We hypothesize that patients in the lowest HOUSES quartile are associated with worse diabetic control as measured by the D5. METHODS A retrospective cohort study of 5463 patients with diabetes in 5 patient centered medical home practices in southeast Minnesota was conducted. HOUSES is a validated, standardized housing-based SES measure constructed from publicly available county assessor's office data. Diabetic control was assessed by the D5 (HgbA1c < 8, BP < 140/90, statin use, nonsmoking status, and antiplatelet therapy). RESULTS In the lowest HOUSES quartile, more patients had an uncontrolled D5 (56.4%) than any of the other quartiles (49.2%, 49.8%, 49.6% respectively, p < 0.001). A multivariate analysis shows the adjusted odds of D5 control for patients in the 2nd, 3rd or 4th HOUSES quartiles as opposed to the 1st quartile are 1.28, 1.21, and 1.20, respectively. CONCLUSION Lower SES as represented by the first quartile of HOUSES index, is associated with lower odds of D5 control and thus worse diabetic outcomes. Using the HOUSES index to identify these individuals in a patient centered medical home might prove useful in deciding where to focus diabetic control efforts.

Background Pediatric nonmalignant lymphoproliferative disorders (PLPDs) are clinically and genetically heterogeneous. Long-standing immune dysregulation and lymphoproliferation in children may be life-threatening, and a paucity of data exists to guide evaluation and treatment of children with PLPD. Objective The primary objective of this study was to ascertain the spectrum of genomic immunologic defects in PLPD. Secondary objectives included characterization of clinical outcomes and associations between genetic diagnoses and those outcomes. Methods PLPD was defined by persistent lymphadenopathy, lymph organ involvement, or lymphocytic infiltration for more than 3 months, with or without chronic or significant Epstein-Barr virus (EBV) infection. Fifty-one subjects from 47 different families with PLPD were analyzed using whole exome sequencing. Results Whole exome sequencing identified likely genetic errors of immunity in 51% to 62% of families (53% to 65% of affected children). Presence of a genetic etiology was associated with younger age and hemophagocytic lymphohistiocytosis. Ten-year survival for the cohort was 72.4%, and patients with viable genetic diagnoses had a higher survival rate (82%) compared to children without a genetic explanation (48%, P = .03). Survival outcomes for individuals with EBV-associated disease and no genetic explanation were particularly worse than outcomes for subjects with EBV-associated disease and a genetic explanation (17% vs 90%; P = .002). Ascertainment of a molecular diagnosis provided targetable treatment options for up to 18 individuals and led to active management changes for 12 patients. Conclusions PLPD defines children at high risk for mortality, and whole exome sequencing informs clinical risks and therapeutic opportunities for this diagnosis.

Cash and voucher assistance (CVA) has become a widespread humanitarian tool to support people affected by conflicts, displacement, and disasters. It promises improved ways to meet the diverse needs of aid beneficiaries. Current policy and academic debates mainly centre on technocratic questions concerning economy, effectiveness, and equity, and, to a lesser extent, the effects on individual recipients and households. This paper challenges the assumption of CVA as a linear process and argues that the shift to CVA is more than changing the aid delivery platform. It contends that scholarship and practice have so far overlooked the social meaning of money, and therefore its broader implications for humanitarian aid and local markets. The paper presents evidence that CVA impacts on social relations and risks creating new, or exacerbating existing, conflicts in already fragile contexts. It highlights less explored areas of CVA and outlines a multidimensional research agenda that emphasises its potential social and socioeconomic consequences.أصبحت المساعدات النقدية والقسائم، أداة إنسانية واسعة الانتشار لدعم الأشخاص المتضررين من النزاعات والنزوح والكوارث. وتعد بوسائل محسنة لتلبية الاحتياجات المتنوعة للمستفيدين من المساعدات. تركز المناقشات السياسية والأكاديمية الحالية حتى الآن بشكلٍ أساسي على الأسئلة المناصرة للتقنية حول الاقتصاد والفعالية والاقتصاد والإنصاف وبدرجة أقل، التأثير على المتلقين الأفراد والأسر. تتصدي هذه المقالة لافتراض CVA كعملية خطية وتناقش بأن التحول إلى CVA هو أكثر من مجرد نظام لتقديم المساعدة. وتناقش بأن الدراسة والممارسة حتى الآن تتغاضيان عن المعنى الاجتماعي للمال وبناءً عليه الآثار الشاملة للمساعدات الإنسانية والأسواق المحلية. تقدم المقالة دليلاً على أن CVA تؤثر على العلاقات الاجتماعية وتخاطر بخلق صراعات جديدة أو تفاقم النزاعات القائمة في سياقات هشة بالفعل. يُسلط الضوء على المجالات الأقل استكشافًا في CVA ويحدد جدول أعمال بحثي متعدد الأبعاد يؤكد على آثاره الاجتماعية والاقتصادية الاجتماعية المحتملة. الكلمات الدليلية: المساعدات، الصراع، النزوح، الاقتصاد اليومي، العمل الإنساني، المساعدات النقدية الإنسانية.现金和代金券援助 (CVA) 已成为普遍用于帮助遭受灾难、冲突，流离失所的人们的人道主义工具。CVA承诺，会改进帮助方法，满足受援助者的不同需求。迄今为止，政策和学术辩论主要围绕CVA在经济、有效性、经济、公平等技术层面上的问题，对个人接受者和家庭的影响问题的讨论要少一点。本文挑战将CVA作为线性过程的假设，认为向CVA的转变不仅仅是改变援助的交付平台。本文认为，迄今为止的学术和实践忽视了金钱的社会意义，因此忽视了金钱对人道主义援助和当地市场的更广泛影响。本文提供的证据表明，CVA会影响社会关系，并有可能让脆弱的环境中产生新的冲突或加剧现有冲突。本文呈现了CVA较少探索的领域，并概述了一个多维研究议程，强调CVA对社会和社会经济的潜在影响。 关键词： 援助、冲突、流离失所、日常经济、人道主义、人道主义现金援助.

Item does not contain fulltext BACKGROUND: The aim of this study was to analyze the stoma-related reinterventions, complications and readmissions after an anterior resection for rectal cancer, based on a cross-sectional nationwide cohort study with 3-year follow-up. METHODS: Rectal cancer patients who underwent a resection with either a functional anastomosis, a defunctioned anastomosis, or Hartmann's procedure (HP) with an end colostomy in 2011 in 71 Dutch hospitals were included. The primary outcome was number of stoma-related reinterventions. RESULTS: Of the 2095 patients with rectal cancer, 1400 patients received an anterior resection and were included in this study; 257 received an initially functional anastomosis, 741 a defunctioned anastomosis, and 402 patients a HP. Of the 1400 included patients, 62% were males, 38% were females and the mean age was 67 years (SD 11.1). Following a primary functional anastomosis, 48 (19%) patients received a secondary stoma. Stoma-related complications occurred in six (2%) patients, requiring reintervention in one (0.4%) case. In the defunctioned anastomosis group, stoma-related complications were present in 92 (12%) patients, and required reintervention in 23 (3%) patients, in 10 (1%) of these more than 1 year after initial resection. Stoma-related complications occurred in 92 (23%) patients after a HP, and required reintervention in 39 (10%) patients in 17 (4%) of cases more than 1 year after initial resection. The permanent stoma rate was 11% and 20%, in the functional anastomosis and the defuctioned anastomosis group, respectively. The end colostomy in the HP group was reversed in 4% of cases. CONCLUSIONS: Construction of a stoma after resection for rectal cancer with preservation of the sphincter is accompanied with long-term stoma-related morbidity. Stoma complications are more frequent after a HP. Even after 1 year, a significant number of reinterventions are required.

Early low socioeconomic status (SES) is associated with poor outcomes in childhood, many of which endure into adulthood. It is critical to determine how early low SES relates to trajectories of brain development and whether these mediate relationships to poor outcomes. We use data from a unique 17-year longitudinal study with five waves of structural brain imaging to prospectively examine relationships between preschool SES and cognitive, social, academic, and psychiatric outcomes in early adulthood.Children (n = 216, 50% female, 47.2% non-White) were recruited from a study of early onset depression and followed approximately annually. Family income-to-needs ratios (SES) were assessed when children were ages 3 to 5 years. Volumes of cortical gray and white matter and subcortical gray matter collected across five scan waves were processed using the FreeSurfer Longitudinal pipeline. When youth were ages 16+ years, cognitive function was assessed using the NIH Toolbox, and psychiatric diagnoses, high-risk behaviors, educational function, and social function were assessed using clinician administered and parent/youth report measures.Lower preschool SES related to worse cognitive, high-risk, educational, and social outcomes (|standardized B| = 0.20-0.31, p values.003). Lower SES was associated with overall lower cortical (standardized B = 0.12, p.0001) and subcortical gray matter (standardized B = 0.17, p.0001) volumes, as well as a shallower slope of subcortical gray matter growth over time (standardized B = 0.04, p = .012). Subcortical gray matter mediated the relationship of preschool SES to cognition and high-risk behaviors.These novel longitudinal data underscore the key role of brain development in understanding the long-lasting relations of early low SES to outcomes in children.

BackgroundAmblyopia is the interocular visual acuity difference of two lines or more with the best correction in both eyes. It is treated with ocular occlusion therapy, but its success depends on neuroplasticity, and thus is effective in children but not adults. Transcranial Direct Current Stimulation (tDCS) is suggested to increase neuroplasticity.ObjectiveTo determine if combined intervention of bilateral tDCS and ocular occlusion improves visual function in adults with amblyopia.MethodsA double-blind randomized, controlled pilot trial was conducted in 10 volunteers with amblyopia. While applying ocular occlusion and performing a reading task, participants received bilateral tDCS (n= 5) or sham stimulation (n= 5), with the anodal tDCS electrode in the contralateral visual cortex and the cathodal in the ipsilateral visual cortex in relation to the amblyopic eye. Visual function (through visual acuity, stereopsis, and contrast sensitivity tests) and visual evoked potential (with checkerboard pattern stimuli presentation) were evaluated immediately after.ResultsA total of 30 min after treatment with bilateral tDCS, visual acuity improved by 0.16 (± 0.025) LogMAR in the treatment group compared with no improvement (–0.02 ± 0.02) in five controls (p= 0.0079), along with a significant increase in the amplitude of visual evoked potentials of the amblyopic eye response (p= 0.0286). No significant changes were observed in stereopsis and contrast sensitivity. No volunteer reported any harm derived from the intervention.ConclusionOur study is the first to combine anodal and cathodal tDCS for the treatment of amblyopia, showing transient improved visual acuity in amblyopic adults.

Despite standardization efforts, vendors still use specific proprietary software algorithms for echocardiographic strain measurements, which result in high inter-vendor variability. Using vendor-independent software could be one solution. Little is known, however, how vendor specific image characteristics can influence tracking results of such software. We therefore investigated the reproducibility, accuracy, and scar detection ability of strain measurements on images from different vendors by using a vendor-independent software. A vendor-independent software (TomTec Image Arena) was used to analyse datasets of 63 patients which were obtained on machines from four different ultrasound machine vendors (GE, Philips, Siemens, Toshiba). We measured the tracking feasibility, inter-vendor bias, the relative test-re-test variability and scar discrimination ability of strain measurements. Cardiac magnetic resonance delayed enhancement images were used as the reference standard of scar definition. Tracking feasibility on vendor datasets were significantly different (p < 0.001). Variability of global longitudinal strain (GLS) measurements was similar among the vendors whereas variability of segmental longitudinal strain (SLS) showed modest difference. Relative test-re-test variability of GLS and SLS showed no relevant differences. No significant difference in scar detection capability was observed. Average GLS and SLS values were similar among vendors. Reproducibility of GLS measurements showed no difference among vendors and was in acceptable range. SLS reproducibility was high but similar for all vendors. No relevant difference was found for identifying regional dysfunction. Tracking feasibility showed a substantial difference among images from different vendors. Our findings demonstrate that tracking results depend mainly on the software used and show little influence from vendor specific image characteristics.

Chronic hepatitis B virus (HBV) infection is the major aetiology of hepatocellular carcinoma (HCC). The optimal goal of therapy, hepatitis B surface antigen (HBsAg) loss and anti-HBs production, is achieved rarely and HBsAg-associated HCC risk is well recognized. Here we review the role of HBsAg in HCC, the link between HBsAg and HCC recurrence post-liver transplantation or resection, and the implications for therapy. HBV-associated carcinogenesis is a multifactorial process. The observation that HBV-related HCC can occur in the absence of cirrhosis is compatible with a direct oncogenic effect of the virus, which may occur via multiple mechanisms, including those mediated by both mutated and unmutated HBsAg. HCC recurrence in HBsAg-positive patients post-liver transplantation has been reported in 10%-15% of patients and is likely to be because of expansion of residual HCC tumour cell populations containing integrated HBV DNA, which expand and independently replicate HBV, leading to the recurrence of both HCC and HBV. The direct role of HBsAg in HCC recurrence post-liver resection is less clear. Cirrhosis is the most important risk factor for HCC development, and precancerous cirrhotic liver remains after resection, with the potential to undergo malignant transformation regardless of the existence of HBV-derived oncogenic drivers. The role of HBsAg in the development of HCC and its recurrence post-surgical intervention has multiple implications for therapy and suggests a potential role for immunotherapy in the future management of HCC, in particular post-liver transplantation. Use of hepatitis B immunoglobulins that target HBsAg directly, alongside immune-oncology therapies, may be relevant in this setting.

BACKGROUND: Pharmacological pain management options can relieve women's pain during labour and birth. Trials of these interventions have used a wide variety of outcomes, complicating meaningful comparisons of their effects. To facilitate better assessment of the effectiveness of labour pain management in trials and meta-analyses, consensus about key outcomes and the development of a core outcome set is essential. OBJECTIVE: To identify all outcomes used in studies of pharmacological pain management interventions during labour and birth. DESIGN: A review of systematic reviews and their included randomised controlled trials was undertaken. SEARCH STRATEGY: Cochrane CENTRAL was searched to identify all Cochrane systematic reviews describing pharmacological pain management options for labour and birth. Search terms included 'pain management', 'labour' and variants, with no limits on year of publication or language. SELECTION CRITERIA: Cochrane reviews and randomised controlled trials contained within these reviews were included, provided they compared a pharmacological intervention with other pain management options, placebo or no treatment. DATA COLLECTION AND ANALYSIS: All outcomes reported by reviews or trials were extracted and tabulated, with frequencies of individual outcomes reported. MAIN RESULTS: Nine Cochrane reviews and 227 unique trials were included. In total, 146 unique outcomes were identified and categorised into maternal, fetal, neonatal, child, health service, provider's perspective or economic outcome domains. CONCLUSIONS: Outcomes of pharmacological pain management interventions during labour and birth vary widely between trials. The standardisation of trial outcomes would permit the assessment of meta-analyses for best clinical practice. TWEETABLE ABSTRACT: Outcomes to measure pharmacological pain management options during labour are highly variable and require standardisation.

BACKGROUND AND AIMS Consensus guidelines recommend high-dose corticosteroids (1-2 mg/kg/day methylprednisolone equivalents) for treating grade ≥3 immune checkpoint inhibitor (ICI) hepatitis. We examined the effect of corticosteroid dosing on time to alanine aminotransferase (ALT) normalization, need for additional immunosuppression, and steroid-related complications. APPROACH AND RESULTS We conducted a retrospective cohort study of 215 ICI-treated patients from 2010-2020 who developed grade ≥3 (ALT>200 U/L) ICI hepatitis. Patients were grouped by initial corticosteroid dose (≥1.5 mg/kg or

Background: Autobiographical memory (AM) is a personal form of memory that becomes impaired in the early, clinical stages of Alzheimer’s disease (AD). In the “preclinical” phase of AD, neuropathological hallmarks are present (especially in a brain network underpinning AM), but performance on standardized neuropsychological tests is normal. Even so, some patients have subjective cognitive decline (SCD). Objective: The aim was to 1) investigate AM performance on two tests with different approaches in SCD, and in prodromal and mild AD, and 2) examine the association between the AM tests. Methods: We included 17 SCD patients with heightened risk of AD, 17 amnestic mild cognitive impairment (aMCI) patients, 17 patients with mild dementia due to AD, and 30 healthy controls. Patients were diagnosed according to international criteria, and all participants had MMSE scores≥24. AM was assessed using the Columbia Autobiographical Memory Interview-Short Form (CAMI-SF) and the Three Events Test. These tests measure the production of contextual details. Results: Significant group effects were found for the Three Events Test and the CAMI-SF. All patient groups produced significantly fewer contextual details than the controls on the Three Events Test. On CAMI-SF, the aMCI and mild AD groups were able to answer fewer questions or gave significantly less detailed answers than the other groups. The SCD patients performed below the controls on CAMI-SF, but the difference was not significant. Conclusion: AM may be impaired in very early AD, even in the phases where standardized episodic memory tests show no decline.

INTRODUCTION Studies have shown the benefit of intensive care unit (ICU) bundled protocols; however, they are primarily derived from medical patients. We hypothesized that patients and their medication profiles are different between critically ill medical, surgical, and trauma patients. METHODS The Pediatric Health Information System 2017 dataset was used to perform a retrospective cohort study of critically ill children. The pediatric medical, surgical, and trauma cohorts were separated based on ICD-10 codes. Data collected included demographics, secondary diagnoses, outcomes, and medication data. Medications were grouped as opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, paralytics, and "other" sedatives. A non-parametric Kolmogorov-Smirnov test (KS test) and odds ratios (reference group: medical cohort) were calculated to compare medication administration between the study cohorts for the first 30 ICU days. RESULTS A total of 4488 critically ill children (medical 2078, surgical 1650, and trauma 760) were identified. The trauma cohort had increased incidence of delirium (medical 10.8%, surgical 11.5%, trauma 13.8%; p 50% received GABA-agonists on ICU days 0-30. With the KS test, there was a significant difference in administration of opiates, GABA-agonists, alpha-2 agonists, anti-psychotics, and "other" sedatives over the first 30 days in the ICU. Relative to medical patients, trauma patients had significantly higher odds of receiving anti-psychotics on ICU days 10-20 and 22-24. CONCLUSION Critically ill pediatric trauma, medical, and surgical patients are distinctly different patient populations with differing pharmacologic profiles for analgesia, sedation, and delirium. LEVEL OF EVIDENCE Level III (Retrospective Comparative Study).

Objectives Physician assistants (PAs) and NPs are essential to quality care delivery. The need to demonstrate value and optimize PA and NP roles in neurology subspecialty clinics is unmet. We outline the development of a PA- and NP-led neuro-oncology procedural clinic and provide metrics to support the institutional and clinician value added. Methods We designed a PA- and NP-led Geisinger Ommaya Clinic (GOC) to manage leptomeningeal carcinomatosis (LMC) with defined clinician roles and the GOC treatment protocol. A retrospective review of 135 patients (2012-2019) compared survival outcomes for patients treated on the protocol compared with those treated off the protocol. Results Centralized care in the GOCs minimized shared physician encounters and improved PA and NP autonomy and utility. LMC therapy as part of the GOC protocol improved care continuity and survival outcomes. Conclusions PA- and NP-led procedural clinics optimize use of these clinicians and open physician availability for nonprocedural duties. This research highlights the institutional patient and financial benefit while demonstrating the operational and leadership growth potential for PAs and NPs.

Resume Le reninome, ou tumeur a cellules de l’appareil juxta-glomerulaire, est une tumeur renale rare, generalement benigne, secretant de la renine. Nous rapportons ici le cas d’une jeune femme âgee de 18 ans, sans antecedents medicaux notables, qui a ete referee aux urgences de notre hopital pour un œdeme papillaire bilateral. Le bilan ophtalmologique a ete fait en ambulatoire en raison de l’apparition progressive d’un flou visuel bilateral depuis une semaine, associe a des cephalees en casque. L’IRM cerebrale et la ponction lombaire demandees par l’ophtalmologue et le neurologue permettent d’exclure une hypertension intracrânienne. La patiente presente une hypertension arterielle severe. Le bilan biologique montre une hypokaliemie, une alcalose metabolique compensee et une microalbuminurie. Lors du sejour, apparait egalement une insuffisance renale aigue AKIN 1. L’ultrason revele une lesion tissulo-kystique du pole superieur renal droit. L’IRM abdominale confirme cette lesion et evoque un carcinome renal a cellules claires, sans invasion calicielle ni vasculaire. Le dosage de la renine plasmatique est superieur a 500 mUI/L, avec un dosage de l’aldosterone dans les normes. La biopsie renale est compatible avec une tumeur de l’appareil juxta-glomerulaire. Apres un traitement agressif initial, l’hypertension arterielle est bien controlee sous spironolactone seule, permettant finalement un sevrage complet des traitements antihypertenseurs. Une nephrectomie partielle par laparoscopie robot-assistee est effectuee. L’analyse de la piece operatoire confirme le diagnostic de reninome benin. Le suivi clinique montre une resolution totale des parametres clinico-biologiques.

As part of the EUREC4A (Elucidating the role of cloud–circulation coupling in climate) field campaign, the German research aircraft HALO (High Altitude and Long Range Research Aircraft), configured as a cloud observatory, conducted 15 research flights in the trade-wind region east of Barbados in January and February 2020. Narrative text, aircraft state data, and metadata describing HALO's operation during the campaign are provided. Each HALO research flight is segmented by timestamp intervals into standard elements to aid the consistent analysis of the flight data. Photographs from HALO's cabin and animated satellite images synchronized with flight tracks are provided to visually document flight conditions. As a comprehensive product from the remote sensing observations, a multi-sensor cloud mask product is derived and quantifies the incidence of clouds observed during the flights. In addition, to lower the threshold for new users of HALO's data, a collection of use cases is compiled into an online book, How to EUREC4A, included as an asset with this paper. This online book provides easy access to most of EUREC4A's HALO data through an intake catalogue. Code and data are freely available at the locations specified in Table 6.

The integration of trauma-informed care practices into the care of obstetric patients requires an understanding of psychological trauma, its impact on this population, and how trauma-informed care can be adapted to improve outcomes for those patients with a previous history of trauma or for those that experience peripartum trauma. System-based changes to policies, protocols, and practices are needed to achieve sustainable change. Maternal morbidity and mortality that result from trauma-related and other mental health conditions in the peripartum period are significant. Innovative approaches to the prevention of negative birth experiences and retraumatization during labor and delivery are needed.

This study investigates methods of data gathering and management, along with the relationship of lifespan and older adults’ activity. Community-dwelling older adults (n = 47, 81.7 ± 3.6 years) completed the Lifetime Leisure Physical Activity Questionnaire. Current activity was assessed by use of accelerometers. The data were converted to the metabolic equivalent of task hours. Correlations between the main outcomes (metabolic equivalent of task/hour, Lifetime Leisure Physical Activity Questionnaire), as well as individual estimation errors for data adjustments, were computed. The accelerometer and Lifetime Leisure Physical Activity Questionnaire data for the last 12 months’ activity were associated (r = .31, p = .033). The average overestimation in the self-reported data was 176%. The adapted data on lifetime physical activity reveals correlations between older adults’ activity and the activity levels of three 15-year episodes (r = .354; r = .336; r = .323; each p T2 = 45–164; p ≤ .002). Our findings indicate a relationship between lifetime and older adults’ activity and provide further support for lifelong engagement in physical activity.

Background and aims Messenger RNA (mRNA)-based therapeutics are rapidly progressing to the clinic and hold tremendous potential for benefiting millions of people worldwide. Therapeutic targeting of injuries that require transient restoration of proteins by mRNA delivery is an attractive aspect, however until recently, it has remained poorly explored. In this study, we examined for the first time, the therapeutic utility of mRNA delivery in liver fibrosis and cirrhosis, which contributes to millions of deaths, annually. Here, we aimed to demonstrate therapeutic efficacy of the human transcription factor hepatocyte nuclear factor alpha (HNF4A) encoding mRNA in chronically injured murine liver leading to fibrosis and cirrhosis. Methods We investigated restoration of hepatocyte functions by HNF4A mRNA transfection in vitro, and analyzed the attenuation of liver fibrosis and cirrhosis in multiple mouse models, by delivering hepatocyte-targeted biodegradable lipid nanoparticles (LNP) encapsulating HNF4A mRNA. To identify potential mechanisms, we performed microarray-based gene expression profiling, single cell RNA sequencing, and chromatin immunoprecipitation. We used primary liver cells and human liver buds for additional functional validation. Results Expression of HNF4A encoding mRNA led to restoration of metabolic activity of fibrotic primary murine and human hepatocytes in vitro. Repeated in vivo delivery of HNF4A mRNA encapsulated-LNP induced a robust inhibition of fibrogenesis in four independent mouse models of hepatotoxin- and cholestasis-induced liver fibrosis. Mechanistically, we discovered that paraoxonase 1 is a direct target of HNF4A and it contributes to HNF4A-mediated attenuation of liver fibrosis via modulation of liver macrophages and hepatic stellate cells. Conclusion Collectively, our findings provide the first direct preclinical evidence of the applicability of HNF4A mRNA therapeutics for the treatment of fibrosis in the liver. Lay summary Liver fibrosis and cirrhosis remain unmet medical needs and contribute to high mortality, worldwide. Herein, we take advantage of a promising, emerging mRNA therapy approach to treat liver fibrosis and cirrhosis. We demonstrate that restoration of a key gene, HNF4A, via mRNA encapsulated in lipid nanoparticles decreased injury in multiple mouse models of fibrosis and cirrhosis. Our study provides the proof-of-concept that mRNA therapy would be a promising strategy for reversing liver fibrosis and cirrhosis.

Objectives: This study examines the early and midterm safety, efficacy, and durability of mitral valve repair for primary mitral regurgitation (MR) using the ChordArt device (CoreMedic) for chordal replacement. Methods: Five patients with symptomatic severe primary degenerative MR due to isolated central posterior leaflet prolapse/flail were treated with the ChordArt device in a transseptal surgical approach and followed prospectively with periodical clinical and echocardiographic assessments for 2 years. Results: Reduction of MR immediately after the implantation of artificial chords was achieved in all patients showing no or trace MR (

Objectives We established reference intervals for serum concentrations of hormones from healthy pediatric subjects and investigated their associations with gender, body mass index (BMI), puberty and oral contraceptives (oC). Methods We calculated reference intervals for the thyroid parameters thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and calcitonin (Ct); the bone markers osteocalcin, procolagen type 1 N-propeptide, and carboxy-terminal cross-linking telopeptide of type 1 collagen; the calciotropic hormones 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone and the steroids cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone, estradiol, dehydroepiandrosterone sulfate and aldosterone. Up to 10,002 blood serum samples from 3,229 healthy children and adolescents (age interval: 3 months to 20 years) were measured. To investigate the associations between the hormone levels with age, sex, weight status and the role of puberty-based changes, the measurement and BMI values were transformed into standard deviation scores. Results Most of the hormones depended on age- and gender. Puberty was linked to a, in part, temporary decrease in TSH, FT3 (for females), FT4, Ct, cortisol (for girls) and aldosterone (for boys) and peak in the bone marker and calciotropic hormones (excluding 25(OH)D) and nearly all remaining steroids. BMI had effects on the thyroid, bone, and calciotropic parameters, whereas oC led to increased cortisol, suppressed progesterone and estradiol values. Conclusions Age- and gender-specific reference intervals are essential for the interpretation of pediatric patients’ hormone measurements. Influencing factors as puberty, BMI, or oC should be taken into consideration for diagnosis and treatment monitoring.

Background and purpose Supporting clinician mental health and well-being must start in the learning environment, especially as health profession students have been shown to have higher rates of mental illness than their peers pursuing other careers. This project aimed to support positive mental health in pharmacy students through small changes that faculty implemented both inside and outside of the classroom. Educational activity and setting In partnership with the Counseling and Mental Health Center, faculty received training, resources, and (in some cases) classroom observation and feedback on how to incorporate small changes that support student well-being. Assessments were performed each semester beginning in spring 2018 and ending in spring 2020. These included the Mental Health Continuum – Short Form (measuring positive mental health and well-being), the Theories of Intelligence Scale – Self Form for Adults (measuring growth mindset), the Sense of Belonging Scale (measuring five domains of social connectedness), and the Brief Resilience Scale (measuring resilience). Participating faculty were surveyed regarding how frequently selected activities were incorporated into their practice and how comfortable they felt supporting student mental health. Findings Positive trends were seen throughout the project on the scales assessing growth mindset and sense of belonging. Summary Supporting positive mental health in pharmacy students in the learning environment is important for both students and the quality and safety of the health care system. Future efforts should expand on this work by refining the measurements used, identifying more interventions, and evaluating the impact these efforts have as students become pharmacists.

This work was partially supported by intramural funds of the University of Pisa, DKFZ, and University Hospital of Southern Jutland, Denmark, and by a grant of the French National Cancer Institute (INCA). The authors wish to thank Dr. Dominic Edelmann (Division of Biostatistics, DKFZ) for helpful advice about data analysis., There is overwhelming epidemiologic evidence that the risk of multiple myeloma (MM) has a solid genetic background. Genome-wide association studies (GWAS) have identified 23 risk loci that contribute to the genetic susceptibility of MM, but have low individual penetrance. Combining the SNPs in a polygenic risk score (PRS) is a possible approach to improve their usefulness. Using 2361 MM cases and 1415 controls from the International Multiple Myeloma rESEarch (IMMEnSE) consortium, we computed a weighted and an unweighted PRS. We observed associations with MM risk with OR = 3.44, 95% CI 2.53-4.69, p = 3.55 x 10(-15) for the highest vs. lowest quintile of the weighted score, and OR = 3.18, 95% CI 2.1 = 34-4.33, p = 1.62 x 10(-13) for the highest vs. lowest quintile of the unweighted score. We found a convincing association of a PRS generated with 23 SNPs and risk of MM. Our work provides additional validation of previously discovered MM risk variants and of their combination into a PRS, which is a first step towards the use of genetics for risk stratification in the general population., University of Pisa, DKFZ, University Hospital of Southern Jutland, Denmark, Institut National du Cancer (INCA) France

Excessive tissue–instrument interaction forces during robotic surgery have the potential for causing iatrogenic tissue damages. The current in vivo study seeks to assess whether tactile feedback could reduce intraoperative tissue–instrument interaction forces during robotic-assisted total mesorectal excision. Five subjects, including three experts and two novices, used the da Vinci robot to perform total mesorectum excision in four pigs. The grip force in the left arm, used for retraction, and the pushing force in the right arm, used for blunt pelvic dissection around the rectum, were recorded. Tissue–instrument interaction forces were compared between trials done with and without tactile feedback. The mean force exerted on the tissue was consistently higher in the retracting arm than the dissecting arm (3.72 ± 1.19 vs 0.32 ± 0.36 N, p

Controller design and their software implementations are usually done in isolated design spaces using respective COTS design tools. However, this separation of concerns can lead to long debugging and integration phases. This is because assumptions made about the implementation platform during the design phase—e.g., related to timing—might not hold in practice, thereby leading to unacceptable control performance. In order to address this, several control/architecture co-design techniques have been proposed in the literature. However, their adoption in practice has been hampered by the lack of design flows using commercial tools. To the best of our knowledge, this is the first article that implements such a co-design method using commercially available design tools in an automotive setting, with the aim of minimally disrupting existing design flows practiced in the industry. The goal of such co-design is to jointly determine controller and platform parameters in order to avoid any design-implementation gap , thereby minimizing implementation time testing and debugging. Our setting involves distributed implementations of control algorithms on automotive electronic control units ( ECUs ) communicating via a FlexRay bus. The co-design and the associated toolchain Co-Flex jointly determines controller and FlexRay parameters (that impact signal delays) in order to optimize specified design metrics. Co-Flex seamlessly integrates the modeling and analysis of control systems in MATLAB/Simulink with platform modeling and configuration in SIMTOOLS/SIMTARGET that is used for configuring FlexRay bus parameters. It automates the generation of multiple Pareto-optimal design options with respect to the quality of control and the resource usage, that an engineer can choose from. In this article, we outline a step-by-step software development process based on Co-Flex tools for distributed control applications. While our exposition is automotive specific, this design flow can easily be extended to other domains.

Purpose Telehealth may remain an integral part of cancer survivorship care after the SARS-CoV-2 pandemic. While telehealth may reduce travel/waiting times and costs for many patients, it may also create new barriers that could exacerbate care disparities in historically underserved populations, manifesting as differences in overall care participation, and in differential video versus phone use for telehealth. Methods We reviewed visits by cancer survivors between January and December 2020 at a designated cancer center in Minnesota. We used descriptive statistics, data visualization, and generalized estimating equation logistic regression models to compare visit modalities and trends over time by age, urban/rural status, and race/ethnicity. Results Among 159,301 visits, including 33,242 telehealth visits, older and rural-dwelling individuals were underrepresented in telehealth compared with in-person care. Non-Hispanic White individuals, those aged 18–69 years, and urban residents used video for > 50% of their telehealth visits. In contrast, those aged ≥ 70 years, rural residents, and most patient groups of color used video for only 33–43% of their telehealth visits. Video use increased with time for everyone, but relative differences in telehealth modalities persisted. Visits of Black/African American patients temporarily fell in spring/summer 2020. Conclusions Our findings underscore reduced uptake of telehealth, especially video, among potentially vulnerable patient populations. Future research should evaluate reasons for differential telehealth utilization and whether visit modality (in-person versus video versus phone) affects cancer outcomes. Implications for Cancer Survivors A long-term cancer care model with integrated telehealth elements needs to account for specific barriers for vulnerable populations. Supplementary Information The online version contains supplementary material available at 10.1007/s11764-021-01133-4.

VEGF inhibition in gastric cancer has a proven benefit in the second line setting. Pazopanib, an oral tyrosine kinase inhibitor, selectively inhibits VEGFR-1, -2 and -3, c-kit and PDGF-R resulting in inhibition of angiogenesis. This open-label randomized phase II trial (2:1) investigated the efficacy of combining pazopanib with FLO (5-fluorouracil, oxaliplatin) vs FLO alone (internal control arm) as first-line treatment in patients with advanced adenocarcinoma of the stomach and gastroesophageal junction (GEJ). Eighty-seven patients were randomized and 78 patients were eligible and evaluable (PaFLO arm 51 patients, FLO arm 27 patients). The PFS rate at 6 months (primary endpoint) was 34% in the PaFLO arm vs 30% in the FLO arm. Comparing PaFLO with FLO median PFS was 4.66 months (95% confidence interval [CI] 2.87-6.46) vs 4.47 months (95% CI 1.79-7.14) (95% CI, hazard ratio [HR] 0.96 (0.60-1.55), P = .882 [exploratory]); median OS was 10.19 months (95% CI 5.46-14.92) vs 7.33 months (95% CI 4.93-9.73), (95% CI HR 1.01 [0.62-1.65], P = .953, exploratory), disease control rate was 72% vs 59%. PaFLO was well tolerable, toxicities were slightly higher in the PaFLO arm. Major adverse events were loss of appetite, nausea, fatigue, diarrhea, neutropenia and thrombocytopenia. Adding pazopanib to chemotherapy shows signs of efficacy but no major improvement in this randomized phase 2 trial. The PFS at 6 months in both arms was lower than expected from the literature. Biomarkers identifying subgroups who benefit and novel combinations are needed. ClinicalTrials.gov: NCT01503372.

BACKGROUND Dysphagia is a major clinical concern in multiple system atrophy (MSA). A detailed evaluation of its major endoscopic features compared with Parkinson's disease (PD) is lacking. OBJECTIVE This study systematically assessed dysphagia in MSA compared with PD and correlated subjective dysphagia to objective endoscopic findings. METHODS Fifty-seven patients with MSA (median, 64 [interquartile range (IQR): 59-71] years; 35 women) underwent flexible endoscopic evaluation of swallowing using a specific MSA-flexible endoscopic evaluation of swallowing task protocol. Findings were compared with an age-matched cohort of 57 patients with PD (median, 67 [interquartile range: 60-73] years; 28 women). In a subcohort, subjective dysphagia was assessed using the Swallowing Disturbance Questionnaire and correlated to endoscopy findings. RESULTS Patients with MSA predominantly showed symptoms suggestive of oral-phase disturbance (premature spillage, 75.4%, piecemeal deglutition, 75.4%). Pharyngeal-phase symptoms occurred less often (pharyngeal residues, 50.9%; penetration/aspiration, 28.1%). In contrast, pharyngeal symptoms were the most common finding in PD (pharyngeal residues, 47.4%). Oral symptoms occurred less frequently in PD (premature spillage, 15.8%, P

We propose a style of hand postures to trigger commands on a laptop. The key idea is to perform hand-postures while keeping the hands on, beside, or below the keyboard, to align with natural laptop usage. 36 hand-posture variations are explored considering three resting locations, left or right hand, open or closed hand, and three wrist rotation angles. A 30-participant formative study measures posture preferences and generates a dataset of nearly 350K images under different lighting conditions and backgrounds. A deep learning recognizer achieves over 97% accuracy when classifying all 36 postures with 2 additional non-posture classes for typing and non-typing. A second experiment with 20 participants validates the recognizer under real-time usage and compares posture invocation time with keyboard shortcuts. Results find low error rates and fast formation time, indicating postures are close to current typing and pointing postures. Finally, practical use case demonstrations are presented, and further extensions discussed.

We propose CursorTap, an extension of Forlines et al.'s mixed, absolute and relative "HybridPointing" to large wall-sized multitouch displays. Our technique uses a relative pointing quasimode activated with one hand, while the other hand controls a distant cursor similar to a large touchpad. A controlled experiment compares the technique to standard absolute touch input as a baseline and a whole-display "Drag" technique representing a common alternate approach. Results show CursorTap is fastest for the common usage scenario of reaching distant targets and then returning to nearby targets. Overall, median selection times across distances are similar with CursorTap, but linearly increase with the other techniques. As further validation, a second study explore show people use CursorTap in a two-person game. The results found just over half of the participants choose to use CursorTap for half of the primary interactions where "enemies" are eliminated using a tap, drag, or lasso "tool".

Objective Assessment of vessel walls is an integral part in diagnosis and disease monitoring of vascular diseases such as vasculitis. Vessel wall imaging (VWI), in particular of intracranial arteries, is the domain of Magnetic Resonance Imaging (MRI) – but still remains a challenge. The tortuous anatomy of intracranial arteries and the need for high resolution within clinically acceptable scan times require special technical conditions regarding the hardware and software environments. Materials and methods In this work a dedicated framework for intracranial VWI is presented offering an optimized, black-blood 3D T1-weighted post-contrast Compressed Sensing (CS)-accelerated MRI sequence prototype combined with dedicated 3D-GUI supported post-processing tool for the CPR visualization of tortuous arbitrary vessel structures. Results Using CS accelerated MRI sequence, the scanning time for high-resolution 3D black-blood CS-space data could be reduced to under 10 min. These data are adequate for a further processing to extract straightened visualizations (curved planar reformats – CPR). First patient data sets could be acquired in clinical environment. Conclusion A highly versatile framework for VWI visualization was demonstrated utilizing a post-processing tool to extract CPR reformats from high-resolution 3D black-blood CS-SPACE data, enabling simplified and optimized assessment of intracranial arteries in intracranial vascular disorders, especially in suspected intracranial vasculitis, by stretching their tortuous course. The processing time from about 15–20 min per patient (data acquisition and further processing) allows the integration into clinical routine.

Morale research over the past several years documents a crisis in the library profession and a 2021 report by Ithaka S + R reveals a confidence deficit in library administrators around work toward ...

Background Home-based rehabilitation of arm function is a significant gap in service provision for adult stroke. The EDNA-22 tablet is a portable virtual rehabilitation-based system that provides a viable option for home-based rehabilitation using a suite of tailored movement tasks, and performance monitoring via cloud computing data storage. The study reported here aimed to compare use of the EDNA system with an active control (Graded Repetitive Arm Supplementary Program—GRASP training) group using a parallel RCT design. Methods Of 19 originally randomized, 17 acute-care patients with upper-extremity dysfunction following unilateral stroke completed training in either the treatment (n = 10) or active control groups (n = 7), each receiving 8-weeks of in-home training involving 30-min sessions scheduled 3–4 times weekly. Performance was assessed across motor, cognitive and functional behaviour in the home. Primary motor measures, collected by a blinded assessor, were the Box and Blocks Task (BBT) and 9-Hole Pegboard Test (9HPT), and for cognition the Montreal Cognitive Assessment (MoCA). Functional behaviour was assessed using the Stroke Impact Scale (SIS) and Neurobehavioural Functioning Inventory (NFI). Results One participant from each group withdrew for personal reasons. No adverse events were reported. Results showed a significant and large improvement in performance on the BBT for the more-affected hand in the EDNA training group, only (g = 0.90). There was a mild-to-moderate effect of training on the 9HPT for EDNA (g = 0.55) and control (g = 0.42) groups, again for the more affected hand. In relation to cognition, performance on the MoCA improved for the EDNA group (g = 0.70). Finally, the EDNA group showed moderate (but non-significant) improvement in functional behaviour on the SIS (g = 0.57) and NFI (g = 0.49). Conclusion A short course of home-based training using the EDNA-22 system can yield significant gains in motor and cognitive performance, over and above an active control training that also targets upper-limb function. Intriguingly, these changes in performance were corroborated only tentatively in the reports of caregivers. We suggest that future research consider how the implementation of home-based rehabilitation technology can be optimized. We contend that self-administered digitally-enhanced training needs to become part of the health literacy of all stakeholders who are impacted by stroke and other acquired brain injuries. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) Number: ACTRN12619001557123. Registered 12 November 2019, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378298&isReview=true

This paper presents a numerical study of the effects of blade roughness on wind turbine performance and annual energy production and how these effects may be partially mitigated through improved control. Three rotors are designed using the NACA4415, S801 and S810 airfoils, and blade element momentum theory is used to model wind turbine behaviour. The aerodynamic lift and drag data for the clean and roughened airfoils are taken from previous experimental work. These show that surface roughness leads to a decreased airfoil lift coefficient and an increased drag coefficient across an angle of attack range typical for large wind turbines, which will clearly lead to decreased turbine performance. Three separate control methods are considered for wind turbines with roughened blades operating at each of four candidate wind sites with different wind speed distributions. Results show that, compared to clean rotor blades, the roughened blades lead to a performance drop in the range of 2.9–8.6% for a torque based control strategy. A control-based performance recovery strategy, in which the controller gain coefficient is re-optimised, increased roughened rotor annual energy production by 0.1–1.0%.

Phosphorus (P) resource availability and quality is declining and recycling P-fertilizers from waste materials are becoming increasingly important. One important secondary P resource is sewage sludge (SSL) where P is often bound as aluminum phosphate (Al-P), iron phosphate (Fe-P) and polyphosphate (poly-P), respectively. Thermal treatment in different ways is a promising way in P recycling to produce highly plant-available P-fertilizers. To investigate mechanisms behind transformation of hardly available P-species toward plant-available P forms we treated a model SSL containing different kinds of defined P sources by low-temperature conversion (LTC) at 500 ��C and subsequent thermochemical treatment of the LTC product with Na additives (TCT) at 950 ��C, respectively. Pot experiments with ryegrass were carried out to determine the plant availability of P of the different treatments. The poly-P (here pyrophosphates) based fertilizers had a very high plant availability after both thermal treatments. During LTC treatment the plant availability of the Fe-P and Al-P variants increased because of the formation of Fe(II)-phosphates and/or pyro-/polyphosphates. Especially the formation of Al-polyphosphate shows a high plant availability. The subsequent TCT further increased strongly the plant availability of the Fe-P variants because of the formation of highly plant-available CaNaPO4. Thus, a direct TCT without prior LTC probably also produce CaNaPO4 and is recommended for Fe-P based SSL. However, a molar Ca/P ratio of ���1 in the fertilizer is favorable for CaNaPO4 formation. Thus, the knowledge on the source of primary P in SSL is essential for choosing the accurate thermal treatment method to produce highly plant-available P-fertilizers from SSL.

Astronomical intensity interferometry enables quantitative measurements of the source geometry by measuring the photon fluxes in individual telescopes and correlating them, rather than correlating the electromagnetic waves’ amplitudes. This simplifies the realization of large telescope baselines and high angular resolutions. Imaging Atmospheric Cherenkov Telescopes (IACTs), intended to detect the optical emission of γ-ray-induced air showers, are excellent candidates to perform intensity correlations in the optical at reasonable signal-to-noise ratios. The detected coherence time is on the scale of (10−12)–(10−15) s – depending on the optical bandwidth of the measurement – which challenges the detection system to work in a stable and accurate way. We developed an intensity interferometry set-up applicable to IACTs, which measures the photocurrents from photomultipliers and correlates them offline, and as such is designed to handle the very large photon rates provided by the telescopes. We present measurements in the lab simulating starlight using a xenon lamp and measured at different degrees of temporal and spatial coherence. Necessary calibration procedures are described with the goal of understanding the measurements quantitatively. Measured coherence times between $5\,$femtoseconds (corresponding signal-to-background ratio 5 × 10−7) and $110\,$femtoseconds (signal-to-background ratio 10−5) are in good agreement with expectations, and so are the noise levels in the correlations, reaching down to 6 × 10−8, after measurements between $30\,$min and $1\,$h.

Zusammenfassung Hintergrund Für das fortgeschrittene hepatozelluläre Karzinom steht uns seit Kurzem ein deutlich erweitertes Spektrum an systemischen Therapieoptionen zur Verfügung. Insbesondere mit den immunonkologischen Kombinationstherapien können mittlerweile beeindruckende Ansprechraten und ein deutlich verlängertes Überleben bei insgesamt guter Verträglichkeit erreicht werden. Dabei werden diese Immun-Onkologie (IO)-basierten Kombinationen nicht nur zur Therapie des fortgeschrittenen HCC geprüft, sondern zunehmend auch in früheren Stadien im Sinne von periinterventionellen Therapiekonzepten und auch zum down-sizing zu lokalen Therapien. Im Kontext der Lebertransplantation (LTx) muss allerdings eine besonders kritische Nutzen-Risiko-Abwägung vor Einsatz von Immuntherapeutika im Rahmen multimodaler Konzepte erfolgen, da durch die Immuntherapie das Risiko einer potenziell letalen Abstoßung signifikant gesteigert werden kann. Methode Diese Übersichtsarbeit basiert auf einer selektiven Literaturrecherche, die zwischen Dezember 2020 und April 2021 in den Datenbanken PubMed und Cochrane Library durchgeführt wurde. Leitlinien, Expertenmeinungen und Empfehlungen von Fachgesellschaften wurden besonders berücksichtigt. Ergebnisse Fast jede fünfte LTx in Deutschland erfolgt aufgrund eines HCC (DSO Jahresbericht 2019). Die LTx ist dabei eine kurative Therapieoption nicht nur für die zugrunde liegende Lebererkrankung, sondern auch für den malignen Tumor. Einzelfallbeschreibungen weisen darauf hin, dass auch eine IO-Therapie vor einer LTx das Risiko einer Abstoßung bzw. eines Leberversagens bei einer nachfolgenden LTx erhöhen kann. Seit ca. 2015 werden Immuntherapeutika vielfach auch zur Tumortherapie bei Patienten nach einer LTx eingesetzt. In kleinen Fallserien wurden dabei Abstoßungsraten von 36%, die mit einer abstoßungsbedingten Mortalität von 20% der behandelten Patienten einhergingen, beschrieben. Eine ähnliche Inzidenz von Abstoßungsreaktionen wurde auch nach dem Einsatz von Immuntherapeutika bei Patienten nach anderen Organtransplantationen beschrieben. Schlussfolgerung Im Zusammenhang mit einer Organtransplantation besteht durch eine IO-Therapie das Risiko einer Transplantatabstoßung, welches zum Verlust des Transplantates und auch zum Tod des Patienten führen kann. Unter Abwägung der oben dargelegten Überlegungen kann aber nach unserer sorgfältigen Nutzen-Risiko-Abwägung aus heutiger Sicht ein Einsatz einer IO-basierten Therapie im Kontext der Organtransplantation erfolgen.

Objective: Since 2018 imaging and histopathology are incorporated in the International Federation of Gynecology and Obstetrics (FIGO) staging system of cervical cancer. The aim of this study was to assess the positive predictive value (PPV) and negative predictive value (NPV) of 2-[18F] fluoro-2-deoxy-D-glucose [18F] FDG-PET/CT ([18F] FDG-PET/CT) for lymph node involvement in patients with cervical cancer and to review the literature. Methods: First, PPV and NPV were calculated in a retrospective study including 98 patients with stage ≥IB1 cervical cancer that underwent a [18F] FDG-PET/CT before surgery. Second, the literature was reviewed on PPV and NPV of PET/CT in cervical cancer. Twenty-one studies were included and analyzed using the Spearman's rank correlation coefficient. Results: In the retrospective study 63 patients (64%) were treated with a radical hysterectomy and complete pelvic lymph node dissection, and 35 patients (36%) underwent a lymph node debulking followed by chemoradiation. The PPV was 79% (inconclusive PET/CT interpreted as suspicious) or 89% (inconclusive PET/CT interpreted as non-suspicious) and the NPV was 81% or 80% respectively. The PPV in the subgroup of 63 patients treated with pelvic node dissection was 56% or 70% respectively. The NPV was 81% for both strategies. Literature results showed a positive correlation (R = 0.354) between the percentage of patients with positive nodes and the PPV of PET/CT. Conclusion: [18F] FDG-PET/CT overestimates the incidence of lymph node metastases, especially in early stage cervical cancer. This may cause a shift of the treatment regime from surgery to radiotherapy. Therefore, histopathological confirmation of [18F] FDG-PET/CT-positive nodes is essential to guide therapy decisions.