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Background The incidence of breast and colorectal cancer (CRC) in younger-than-average-age patients is rising and poorly understood. This is the largest study on patients with both cancers who are less than 60 years old and aims to characterize demographic, clinicopathologic, and genetic features and describe therapeutic dilemmas and management strategies. Materials and Methods This is a retrospective medical records review of patients at the University of California San Francisco with both primary breast and CRC before age 60. Results Fifty-one patients were identified; 41 had detailed medical records. Median age of diagnosis with breast cancer was 43 (range 27-59) and CRC was 50 (28-59). Most were Caucasian (38, 74.5%) and never smokers (23, 56.1%); about half were current alcohol consumers (20, 48.8%) and about one-third had sedentary jobs (14, 34.1%). Average BMI was 25.8 (range: 14-49), and 30% were overweight or obese. Breast was the first cancer diagnosed in 36 patients (70.6%) and 44 (86.3%) had a metachronous CRC diagnosis. Breast cancer was early stage (0-2) in 32 (78.0%) patients whereas CRC was split between early stage (1-2) in 14 (34.1%) and later stage (3-4) in 19 (46.2%). Ten patients (24.3%) had a known germline mutation, although 23 (56.1%) had a family history of cancer in a first-degree relative. Conclusion Younger patients with both breast and CRC are a unique cohort, often without known risk factors. Alcohol consumption and sedentary jobs were the most common risk factors, and about one-quarter had a known genetic predisposition. Comanagement of both cancers requires individualized, multidisciplinary care. [ABSTRACT FROM AUTHOR]

As the burden of cancers impacting low- and middle-income countries is projected to increase, formation of strategic partnerships between institutions in high-income countries and low- and middle-income country institutions may serve to accelerate cancer research, clinical care, and training. As the US National Cancer Institute and its Center for Global Health continue to encourage cancer centers to join its global mission, academic cancer centers in the United States have increased their global activities. In 2015, the Helen Diller Family Comprehensive Cancer Center at the University of California, San Francisco, responded to the call for international partnership in addressing the global cancer burden through the establishment of the Global Cancer Program as a priority initiative. In developing the Global Cancer Program, we galvanized institutional support to foster sustained, bidirectional, equitable, international partnerships in global cancer control. Our focus and intent in disseminating this commentary is to share experiences and lessons learned from the perspective of a US-based, National Cancer Institute–designated cancer center and to provide a roadmap for other high-income institutions seeking to strategically broaden their missions and address the complex challenges of global cancer control. Herein, we review the formative evaluation, governance, strategic planning, investments in career development, funding sources, program evaluation, and lessons learned. Reflecting on the evolution of our program during the first 5 years, we observed in our partners a powerful shift toward a locally driven priority setting, reduced dependency, and an increased commitment to research as a path to improve cancer outcomes in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Aims Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient's heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. Methods and results Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient's baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing–induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT's baseline MWLW-S,DT and virtual pacing–induced ΔMWLW-S,DT were both significantly associated with the real patient's reverse remodelling ΔLVESV (r = −0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = −0.34, P = 0.02). Conclusion Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery. [ABSTRACT FROM AUTHOR]

Background Autosomal dominant polycystic kidney disease (ADPKD) has occasionally been associated with lower peripheral white blood cell (WBC) counts. This study aimed to investigate the peripheral blood cell counts in a large cohort of kidney transplant recipients before and after kidney transplantation and its potential impact on post-transplant outcomes. Methods This was a retrospective study with long-term follow-up data of 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals, of whom 392 had ADPKD. Results In total, 2090 patients who underwent a first kidney transplantation in the Leuven University Hospitals were included, of whom 392 had ADPKD. Both pre- and post-transplantation, ADPKD patients had significantly lower total WBC counts, and more specifically lower neutrophil, lymphocyte and eosinophil counts compared with the non-ADPKD patients. This observation was independent of potential confounders such as level of inflammation, smoking habit, vitamins and pre-transplant medication. Overall survival and kidney transplant survival were significantly better in ADPKD vs non-ADPKD transplant recipients and a longer time to first infection was observed. However, no association between blood cell counts and outcome differences was found. Conclusions In conclusion, this large single-center study reports a strong and independent association between ADPKD and lower peripheral WBC counts both before and after kidney transplantation. Considering the role of inflammation in disease progression, further investigation into the role of WBC in ADPKD is needed. [ABSTRACT FROM AUTHOR]

Background: Drug-related problems (DRPs) affect many patients. Many activities in general practice, hospitals, and community pharmacies have been initiated to tackle DRPs. However, recent studies exploring what DRP patients are still facing in their daily lives are scarce. Methods: Danish pharmacy staff registered DRPs in prescription encounters to understand what DRPs patients are still experiencing in daily life. They noted short descriptions of what happened in the encounter that qualified the incident as a DRP. The descriptions were subjected to an inductive content analysis. Results: A wide range of DRPs that impacted patients' daily lives practically and healthwise were identified. In total, eighteen percent of patients with prescriptions had a DRP. Three overall stages of DRPs were identified: challenges in receiving the medications, not knowing how or why to take the medications, and not experiencing satisfactory effects. Patients were emotionally affected by these problems. Conclusions: DRPs are still widespread in patients' daily lives and influence their well-being. The identified DRPs illustrated the complexity of obtaining medications to work as intended and demonstrate that health professionals must take even the basics of medication intake much more seriously. [ABSTRACT FROM AUTHOR]

Yoo and colleagues have developed an automated system called the "Banff automation system" that applies the Banff Classification rules for Kidney Allograft Pathology. The system uses logical operations to reach diagnoses based on histological information, serology, and molecular data. The tool aims to avoid misclassifications and provides a visualized decision tree to illustrate the steps of the Banff rules used. The study highlights potential problems with the Banff Classification and suggests the need for improvements, such as artificial intelligence and consensus on molecular data. The authors caution against using the Banff Classification as a prognostic tool and suggest further evaluation of simplified rules and AI-supported diagnosis. [Extracted from the article]

Background and Objectives Although it has become standard to include the views of older people when assessing their well-being, most existing methods are ill-suited to estimate the relative importance of well-being dimensions. This article investigates the potential of the factorial survey method to estimate the relative importance of six well-being dimensions (health, income, social relations, leisure, engaging activities, and religion) based on the views of older people themselves. Research Design and Methods We implemented a factorial survey in a repeated survey experiment among 800 older adults in Flanders (the Dutch-speaking northern part of Belgium). We performed several within-sample test–retests to investigate the consistency of the estimated coefficients over time (i.e. temporal reliability). In addition, we tested the feasibility of the factorial survey by studying two indicators of cognitive load: response time and response consistency. Results We estimated the relative importance of increases in six well-being dimensions. Increases from the lowest level to the highest level in the dimensions of health, income, and social relations had the highest effect on well-being—followed by leisure, engaging activities, and religion. The results proved to be consistent in most of the test–retest analyses. Furthermore, we found that respondents produced a high level of response consistency within an acceptable amount of response time. Discussion and Implications The findings suggest that the factorial survey method offers a promising way forward to elicit older people's views on well-being and, hence, in developing tailored policies that matter to them. [ABSTRACT FROM AUTHOR]

Aims TASK-1 (K2P3.1) two-pore-domain potassium channels are atrial-specific and significantly up-regulated in atrial fibrillation (AF) patients, contributing to AF-related electrical remodelling. Inhibition of TASK-1 in cardiomyocytes of AF patients was shown to counteract AF-related action potential duration shortening. Doxapram was identified as a potent inhibitor of the TASK-1 channel. In this study, we investigated the antiarrhythmic efficacy of doxapram in a porcine model of AF. Methods and results Doxapram successfully cardioverted pigs with artificially induced episodes of AF. We established a porcine model of persistent AF in domestic pigs via intermittent atrial burst stimulation using implanted pacemakers. All pigs underwent catheter-based electrophysiological investigations prior to and after 14 days of doxapram treatment. Pigs in the treatment group received intravenous administration of doxapram once per day. In doxapram-treated AF pigs, the AF burden was significantly reduced. After 14 days of treatment with doxapram, TASK-1 currents were still similar to values of sinus rhythm animals. Doxapram significantly suppressed AF episodes and normalized cellular electrophysiology by inhibition of the TASK-1 channel. Patch-clamp experiments on human atrial cardiomyocytes, isolated from patients with and without AF could reproduce the TASK-1 inhibitory effect of doxapram. Conclusion Repurposing doxapram might yield a promising new antiarrhythmic drug to treat AF in patients. [ABSTRACT FROM AUTHOR]

Background: The incidence of young-onset colorectal cancer (yoCRC) is increasing. It is unknown if there are survival differences between young and older patients with metastatic colorectal cancer (mCRC).Methods: We studied the association of age with survival in 2326 mCRC patients enrolled in the Cancer and Leukemia Group B and SWOG 80405 trial, a multicenter, randomized trial of first-line chemotherapy plus biologics. The primary and secondary outcomes of this study were overall survival (OS) and progression-free survival (PFS), respectively, which were assessed by Kaplan-Meier method and compared among younger vs older patients with the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated based on Cox proportional hazards modeling, adjusting for known prognostic variables. All statistical tests were 2-sided.Results: Of 2326 eligible subjects, 514 (22.1%) were younger than age 50 years at study entry (yoCRC cohort). The median age of yoCRC patients was 44.3 vs 62.5 years in patients aged 50 years and older. There was no statistically significant difference in OS between yoCRC vs older-onset patients (median = 27.07 vs 26.12 months; adjusted HR = 0.98, 95% CI = 0.88 to 1.10; P = .78). The median PFS was also similar in yoCRC vs older patients (10.87 vs 10.55 months) with an adjusted hazard ratio of 1.02 (95% CI = 0.92 to 1.13; P = .67). Patients younger than age 35 years had the shortest OS with median OS of 21.95 vs 26.12 months in older-onset patients with an adjusted hazard ratio of 1.08 (95% CI = 0.81 to 1.44; Ptrend = .93).Conclusion: In this large study of mCRC patients, there were no statistically significant differences in survival between patients with yoCRC and CRC patients aged 50 years and older. [ABSTRACT FROM AUTHOR]

Man does not only extract material from the Earth but increasingly uses the underground for storage and disposal purposes. One of the materials that might be disposed of this way is high-level nuclear waste. The development of safe disposal procedures, the choice of suitable host rocks, and the design of underground facilities have taken much time and money, but commissions in several countries have presented reports showing that - and how - safe geological disposal will be possible in such a way that definite isolation from the biosphere is achieved. Political views have changed in the past few years, however, and there is a strong tendency now to require that the high-level waste disposed of will be retrievable. Considering the underlying arguments for isolation from the biosphere, and also considering waste policy in general, this provides an irrational context. The development of new procedures and the design of new disposal facilities that allow retrieval will take much time again. A consequence may be that the high-active, heat-generating nuclear waste will be stored temporarily for a much longer time than objectively desirable. The delay in disposal and the counterproductive requirement of retrievability are partly due to the fact that earth-science organisations have failed to communicate in the way they should, possibly fearing public (and financial) reactions if taking a position that is (was?) considered as politically incorrect. Such an attitude should not be maintained in modem society, which has the right to be informed reliably by the scientific community. Keywords: ethics; nuclear waste; scientific reliability; The Netherlands; underground disposal

The increase in global energy consumption urges the exploitation of known energy resources in the most efficient way. The oil and gas industry seems well capable, but politics may hamper optimum recovery, even though politicians advocate that the laws and regulations laid upon the industry are meant to promote a sustainable society and to diminish environmental pollution. Lack of geological insight sometimes plays a role, which implies that an attitude of effectively wringing out the Earth is not sufficient: more attention for earth-scientific education may turn out to be even more important. This does not affect, however, the need for ever more effective technologies for wringing out the Earth. Keywords: energy policy; mineral exploitation; natural gas; oil

Earth sciences, however sophisticated present-day models may be, are based essentially on field data. Such data must not only be collected, but also analyzed and communicated. This was done during the past few centuries primarily in the form of printed material. An era of new ways to disseminate scientific knowledge seems ahead. There will be new media for distribution, but the classical way of handling manuscripts (in particular the refereeing, editing and distribution) will change as well. This will have great impact on the infrastructure of the scientific community. The new generation of editors should be aware that profound knowledge of the technological and social developments is essential for an optimum transfer of information. For the purpose, they should join organizations that deal with these aspects in a professional way. Earth scientists involved in editing a journal (or in some related activity) have the possibility to join the Association of Earth Science Editors (AESE). Members of this organization met in Washington last year, at a conference organized jointly with the European Association of Science Editors (EASE) and the Council of Biology Editors (CBE). The topics discussed at the meeting provide a glimpse of a new era in (earth) science communication. Keywords: Editing: Electronic publishing; Professionalization; Scientific information transfer; Superdatabase

Some palaeoclimatic changes - and consequently also some environmental changes - were geologically abrupt, sometimes even fairly abrupt from a human point of view. One might question whether such abrupt changes in the global (or regional) climate are reflected, in one way or another, in the sedimentary record. It seems to be a simple and logical question, but it was never asked explicitly by geologists - until June 1998, when a conference at Stockholm University was devoted to the topic. One of the points discussed was: what does 'abrupt' mean in a geological context? Keywords: abruptness; palaeoclimatic change: environmental change

Large changes in the wintertime atmospheric circulation have occurred over the past two decades over the ocean basins of the Northern Hemisphere, and these changes have had a profound effect on regional distributions of surface temperature and precipitation. The changes over the North Pacific have been well documented and have contributed to increases in temperatures across Alaska and much of western North America and to decreases in sea surface temperatures over the central North Pacific. The variations over the North Atlantic are related to changes in the North Atlantic Oscillation (NAO). Over the past 130 years, the NAO has exhibited considerable variability at quasibiennial and quasi-decadal time scales, and the latter have become especially pronounced the second half of this century. Since 1980, the NAO has tended to remain in one extreme phase and has accounted for a substantial part of the observed wintertime surface warming over Europe and downstream over Eurasia and cooling in the northwest Atlantic. Anomalies in precipitation, including dry wintertime conditions over southern Europe and the Mediterranean and wetter-than-normal conditions over northern Europe and Scandinavia since 1980, are also linked to the behavior of the NAO. Changes in the monthly mean flow over the Atlantic are accompanied by a northward shift in the storm tracks and associated synoptic eddy activity, and these changes help to reinforce and maintain the anomalous mean circulation in the upper troposphere. It is important that studies of trends in local climate records, such as those from high elevation sites, recognize the presence of strong regional patterns of change associated with phenomena like the NAO.

Malindi-Watamu reefs in Kenya reveal a strong correlation between the terrigenous sediment load and consequent combined coral stress response. Coral stress response is a combination of the proportion of injured colonies, cover of soft corals and rocky substrate unsuited for corals. Coral stress response is advantageous as it is a means of bio-monitoring.

Data from a Statewide Migration Telephone Survey done in Utah in Oct 1988 were gathered to analyze the effect of cognitive factors on migration intentions. Results show that residents from both metropolitan and non-metropolitan areas are unlikely to migrate regardless of community size preference status if they are contented with local economic means and public services. In addition, metropolitan and non-metropolitan residents fom the largest communities planning to relocate to a different size class are more likely to leave in the short-term than those migrants planning to transfer to large communities.

Aims: Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease, characterized by life-threatening ventricular arrhythmias and progressive cardiac dysfunction. The aim of this study is to use computer simulations to non-invasively estimate the individual patient's myocardial tissue substrates underlying regional right ventricular (RV) deformation abnormalities in a cohort of AC mutation carriers.Methods and Results: In 68 AC mutation carriers and 20 control subjects, regional longitudinal deformation patterns of the RV free wall (RVfw), interventricular septum (IVS), and left ventricular free wall (LVfw) were obtained using speckle-tracking echocardiography. We developed and used a patient-specific parameter estimation protocol based on the multi-scale CircAdapt cardiovascular system model to create virtual AC subjects. Using the individual's deformation data as model input, this protocol automatically estimated regional RVfw and global IVS and LVfw tissue properties. The computational model was able to reproduce clinically measured regional deformation patterns for all subjects, with highly reproducible parameter estimations. Simulations revealed that regional RVfw heterogeneity of both contractile function and compliance were increased in subjects with clinically advanced disease compared to mutation carriers without clinically established disease (17 ± 13% vs. 8 ± 4%, P = 0.01 and 18 ± 11% vs. 10 ± 7%, P < 0.01, respectively). No significant difference in activation delay was found.Conclusion: Regional RV deformation abnormalities in AC mutation carriers were related to reduced regional contractile function and tissue compliance. In clinically advanced disease stages, a characteristic apex-to-base heterogeneity of tissue abnormalities was present in the majority of the subjects, with most pronounced disease in the basal region of the RVfw. [ABSTRACT FROM AUTHOR]

Introduction Comparative embryology of the various body plans, and an understanding of the molecular regulation of the establishment of these body plans, are powerful tools that can help us reconstruct [...]

Background Recently a peripheral blood 8-gene expression assay was developed for non-invasive detection of antibody-mediated rejection (ABMR) after kidney transplantation. Its value has not yet been evaluated in detail in clinical scenarios with different baseline disease probability [human leucocyte antigen donor-specific antibodies (HLA-DSA)-positive versus HLA-DSA-negative cases at the time of stable graft function versus graft dysfunction]. Methods Here we investigated the diagnostic accuracy of the 8-gene expression assay for histology of ABMR (ABMRh) with or without HLA-DSA in a cross-sectional cohort study of 387 blood samples with a concomitant graft biopsy. Results In patients with HLA-DSA (n  = 64), the 8-gene expression assay discriminated DSA-positive ABMRh (DSAposABMRh) cases (n  = 16) with good diagnostic performance {area under the receiver operating characteristic curve [AUROC] 83.1% [95% confidence interval (CI) 70.8–95.3]}. Also, in HLA-DSA-negative samples (n  = 323), a clinically relevant diagnostic performance for DSAnegABMRh cases was found (n  = 30) with an AUROC of 75.8% (95% CI 67.4–84.4). The 8-gene assay did not discriminate DSAposABMRh cases from DSAnegABMRh cases. There was a net benefit for clinical decision-making when adding the 8-gene expression assay to a clinical model consisting of estimated glomerular filtration rate, proteinuria, HLA-DSA and age. Conclusion The 8-gene expression assay shows great potential for implementation in the clinical follow-up of high-risk HLA-DSA-positive patients and clinical relevance in HLA-DSA-negative cases. [ABSTRACT FROM AUTHOR]

Background: In middle-income countries, the burden of colorectal cancer (CRC) is increasing in parallel with resources for diagnosis and treatment. There is a potential benefit of CRC screening programs in Mexico.Objective: Since there are no organized screening programs in the country, we explored the willingness of individuals to complete a faecal immunochemical testing (FIT) based CRC screening program and its potential benefit in Mexico.Methods: We conducted a CRC screening program pilot in Veracruz, Mexico, during 2015-16 using FIT. Individuals with FIT results >100 ng of haemoglobin/ml buffer were referred for diagnostic colonoscopy.Results: Of 473 FIT kits distributed to adults aged 50-75, 85.8% (406) were completed by participants and analysed in the laboratory. Of these, 5.9% (24/406) of test results showed >100 ng haemoglobin/ml. Twenty-one participants completed colonoscopy. The positive predictive value of FIT >100 ng haemoglobin/ml for premalignant lesions was 33%.Conclusion: These results provide preliminary evidence of the willingness of individuals to complete FIT-based CRC screening program in Mexico. However, further evaluation of health systems resources will be needed prior to large-scale implementation of CRC screening programs. [ABSTRACT FROM AUTHOR]

Background: The recently developed Social Exclusion Index for Health Surveys (SEI-HS) revealed particularly strong social exclusion in non-Western immigrant groups compared to the native Dutch population. To qualify such results, cross-cultural validation of the SEI-HS in non-Western immigrant groups is called for. Methods: A sequential explanatory mixed methods design was used, employing quantitative data from the Netherlands Public Health Monitor along with qualitative interviews. Data from 1,803 adults aged 19 years or older of Surinamese, 1,009 of Moroccan and 1,164 of Turkish background and 19,318 native Dutch living in the four largest cities in the Netherlands were used to test the factorial structure of the SEI-HS and differential item functioning across immigrant groups. Additionally, 52 respondents with a high score on the SEI-HS and from different background were interviewed on the item content of the SEI-HS and subjective feelings of exclusion. For each SEI-HS item the semantic, conceptual and contextual connotations were coded and compared between the immigrant groups and native Dutch. Results: High levels of social exclusion were found in 20.0% of the urban population of Surinamese origin, 20.9% of Moroccan, 28.7% of Turkish and 4.2% of native Dutch origin. The 4-factor structure of the SEI-HS was confirmed in all three immigrant groups. None of the items demonstrated substantial differential item functioning in relation to immigration background. The interviews uncovered some methodological shortcomings, but these did not substantially impact the observed excess of social exclusion in immigrant groups. Conclusions: The present study provides evidence in support of the validity of the SEI-HS in adults of Surinamese, Moroccan and Turkish background and confirms the major social exclusion of these immigrant groups in the main cities in the Netherlands. Policy measures to enhance social inclusion and reduce exclusion are urgently needed. [ABSTRACT FROM AUTHOR]

A study evaluated the effects of cellulose degradation products on the sorption of radioactive waste in a cementitious low- and intermediate-level radioactive waste (L/ILW) repository. A high portion of L/ILW is composed of cellulosic materials, which when subjected to the alkaline conditions can form water-soluble, low molecular weight compounds. Isosaccharinic acid is the primary product of cellulose degradation in the Ca2+ environment of cementitious radioactive waste repositories and can form stable complexes with tri- and tetravalent radionuclides, reducing the sorption of these radioactive wastes in the cement phase.

Actual surveys in kindergartens on SARS-CoV-2 infections are rare. At the beginning of the second pandemic wave, we screened 12 randomly selected kindergartens in Berlin, Germany. A total of 720 participants (pre-school children, staff and connected household members) were briefly examined and interviewed, and SARS-CoV-2 infections and anti-SARS-Cov-2 IgG antibodies were assessed. About a quarter of the participants showed common cold-resembling symptoms. However, no SARS-CoV-2 infection was detected, and only one childcare worker showed IgG seroreactivity. Against a backdrop of increased pandemic activity in the community, this cross-sectional study does not suggest that kindergartens are silent transmission reservoirs. [ABSTRACT FROM AUTHOR]

A study was conducted to show that most of the strains that possess enzymes related to CYP153A1 and CYP153A6, cytochrome P450 enzymes that were characterized as alkane hydroxylases, using PCR. Result provided evidence that the newly cloned P450s are indeed alkane hydroxylases.