bluuebunny/crossref_metadata_2025 huggingface dataset:
Longer-term Direct and Indirect Effects of Infant Rotavirus Vaccination Across All Ages in the United States in 2000–2013: Analysis of a Large Hospital Discharge Data Set
Authors: Baker Julia M , Tate Jacqueline E , Steiner Claudia A , Haber Michael J , Parashar Umesh D , Lopman Benjamin A
Published: July 2018

Background

Rotavirus disease rates dramatically declined among children <5 years of age since the rotavirus vaccine was introduced in 2006; population-level impacts remain to be fully elucidated.

Methods

Data from the Healthcare Cost and Utilization Project State Inpatient Databases were used to conduct a time-series analysis of monthly hospital discharges across age groups for acute gastroenteritis and rotavirus from 2000 to 2013. Rate ratios were calculated comparing prevaccine and postvaccine eras.

Results

Following vaccine introduction, a decrease in rotavirus hospitalizations occurred with a shift toward biennial patterns across all ages. The 0–4-year age group experienced the largest decrease in rotavirus hospitalizations (rate ratio, 0.14; 95% confidence interval, .09–.23). The 5–19-year and 20–59-year age groups experienced significant declines in rotavirus hospitalization rates overall; the even postvaccine calendar years were characterized by progressively lower rates, and the odd postvaccine years were associated with reductions in rates that diminished over time. Those aged ≥60 years experienced the smallest change in rotavirus hospitalization rates overall, with significant reductions in even postvaccine years compared with prevaccine years (rate ratio, 0.51; 95% confidence interval, .39–.66).

Conclusions

Indirect impacts of infant rotavirus vaccination are apparent in the emergence of biennial patterns in rotavirus hospitalizations that extend to all age groups ineligible for vaccination. These observations are consistent with the notion that young children are of primary importance in disease transmission and that the initial postvaccine period of dramatic population-wide impacts will be followed by more complex incidence patterns across the age range in the long term.
Hepatitis C Guidance 2018 Update: AASLD-IDSA Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection
Authors:   AASLD-IDSA HCV Guidance Panel, Chung Raymond T , Ghany Marc G , Kim Arthur Y , Marks Kristen M , Naggie Susanna , Vargas Hugo E , Aronsohn Andrew I , Bhattacharya Debika , Broder Tina , Falade-Nwulia Oluwaseun O , Fontana Robert J , Gordon Stuart C , Heller Theo , Holmberg Scott D , Jhaveri Ravi , Jonas Maureen M , Kiser Jennifer J , Linas Benjamin P , Lo Re Vincent , Morgan Timothy R , Nahass Ronald G , Peters Marion G , Reddy K Rajender , Reynolds Andrew , Scott John D , Searson Gloria , Swan Tracy , Terrault Norah A , Trooskin Stacey B , Wong John B , Workowski Kimberly A
Published: July 2018

Recognizing the importance of timely guidance regarding the rapidly evolving field of hepatitis C management, the American Association for the Study of Liver Diseases (AASLD) and the Infectious Diseases Society of America (IDSA) developed a web-based process for the expeditious formulation and dissemination of evidence-based recommendations. Launched in 2014, the hepatitis C virus (HCV) guidance website undergoes periodic updates as necessitated by availability of new therapeutic agents and/or research data. A major update was released electronically in September 2017, prompted primarily by approval of new direct-acting antiviral agents and expansion of the guidance’s scope. This update summarizes the latest release of the HCV guidance and focuses on new or amended recommendations since the previous September 2015 print publication. The recommendations herein were developed by volunteer hepatology and infectious disease experts representing AASLD and IDSA and have been peer reviewed and approved by each society’s governing board.
Sex-specific regulation of collagen I and III expression by 17β-Estradiol in cardiac fibroblasts: role of estrogen receptors
Authors: Dworatzek Elke , Mahmoodzadeh Shokoufeh , Schriever Cindy , Kusumoto Kana , Kramer Lisa , Santos Gabriela , Fliegner Daniela , Leung Yuet-Kin , Ho Shuk-Mei , Zimmermann Wolfram-Hubertus , Lutz Susanne , Regitz-Zagrosek Vera
Published: July 2018

Aims

Sex differences in cardiac fibrosis point to the regulatory role of 17β-Estradiol (E2) in cardiac fibroblasts (CF). We, therefore, asked whether male and female CF in rodent and human models are differentially susceptible to E2, and whether this is related to sex-specific activation of estrogen receptor alpha (ERα) and beta (ERβ).

Methods and results

In female rat CF (rCF), 24 h E2-treatment (10−8  M) led to a significant down-regulation of collagen I and III expression, whereas both collagens were up-regulated in male rCF. E2-induced sex-specific collagen regulation was also detected in human CF, indicating that this regulation is conserved across species. Using specific ERα- and ERβ-agonists (10−7 M) for 24 h, we identified ERα as repressive and ERβ as inducing factor in female and male rCF, respectively. In addition, E2-induced ERα phosphorylation at Ser118 only in female rCF, whereas Ser105 phosphorylation of ERβ was exclusively found in male rCF. Further, in female rCF we found both ER bound to the collagen I and III promoters using chromatin immunoprecipitation assays. In contrast, in male rCF only ERβ bound to both promoters. In engineered connective tissues (ECT) from rCF, collagen I and III mRNA were down-regulated in female ECT and up-regulated in male ECT by E2. This was accompanied by an impaired condensation of female ECT, whereas male ECT showed an increased condensation and stiffness upon E2-treatment, analysed by rheological measurements. Finally, we confirmed the E2-effect on both collagens in an in vivo mouse model with ovariectomy for E2 depletion, E2 substitution, and pressure overload by transverse aortic constriction.

Conclusion

The mechanism underlying the sex-specific regulation of collagen I and III in the heart appears to involve E2-mediated differential ERα and ERβ signaling in CFs.
Same or different? Abstract relational concept use in juvenile bamboo sharks and Malawi cichlids
Authors: Fuss Theodora , John Leonie , Schluessel Vera
Published: July 2018

Sorting objects and events into categories and concepts is an important cognitive prerequisite that spares an individual the learning of every object or situation encountered in its daily life. Accordingly, specific items are classified in general groups that allow fast responses to novel situations. The present study assessed whether bamboo sharks Chiloscyllium griseum and Malawi cichlids Pseudotropheus zebra can distinguish sets of stimuli (each stimulus consisting of two abstract, geometric objects) that meet two conceptual preconditions, i.e., (1) “sameness” versus “difference” and (2) a certain spatial arrangement of both objects. In two alternative forced choice experiments, individuals were first trained to choose two different, vertically arranged objects from two different but horizontally arranged ones. Pair discriminations were followed by extensive transfer test experiments. Transfer tests using stimuli consisting of (a) black and gray circles and (b) squares with novel geometric patterns provided conflicting information with respect to the learnt rule “choose two different, vertically arranged objects”, thereby investigating (1) the individuals’ ability to transfer previously gained knowledge to novel stimuli and (2) the abstract relational concept(s) or rule(s) applied to categorize these novel objects. Present results suggest that the level of processing and usage of both abstract concepts differed considerably between bamboo sharks and Malawi cichlids. Bamboo sharks seemed to combine both concepts—although not with equal but hierarchical prominence—pointing to advanced cognitive capabilities. Conversely, Malawi cichlids had difficulties in discriminating between symbols and failed to apply the acquired training knowledge on new sets of geometric and, in particular, gray-level transfer stimuli.
Effectiveness and safety of rivaroxaban vs. warfarin in non-valvular atrial fibrillation patients with a non-sex-related CHA2DS2-VASc score of 1
Authors: Coleman Craig I , Turpie Alexander G G , Bunz Thomas J , Eriksson Daniel , Sood Nitesh A , Baker William L
Published: July 2018

Aims

To compare the effectiveness and safety of standard-dose rivaroxaban (20 mg o.d.) and warfarin in non-valvular atrial fibrillation (NVAF) patients with a non-sex-related CHA2DS2-VASc score of 1.

Methods and results

Analysis of United States Truven MarketScan claims from November 2011 to December 2016 for anticoagulant-naïve NVAF patients with a single non-sex-related stroke risk factor assigned 1-point in the CHA2DS2-VASc score and ≥12-months of continuous medical/prescription insurance coverage prior to the qualifying oral anticoagulant dispensing. Standard-dose rivaroxaban users were 1:1 propensity score-matched to warfarin users. Patients were followed until outcome occurrence, insurance disenrollment, or end of data availability. Primary outcomes included stroke or systemic embolism and major bleeding and were compared using Cox regression and reported as hazard ratios (HRs) with 95% confidence intervals (CIs). In all, 3319 rivaroxaban users were 1:1 propensity score-matched to 3319 warfarin users. Median (interquartile range) duration of follow-up was 1.6 (0.7, 2) years and the most common qualifying stroke risk factor was hypertension (n = 4532, 68.3%). Rivaroxaban was associated with a significant reduction in the 1-year stroke or systemic embolism vs. warfarin (HR 0.41, 95% CI 0.17–0.98), with no significant difference in overall major bleeding (HR 0.74, 95% CI 0.44–1.26) or major bleeding subtypes (HR ranging from 0.33 to 0.78, P > 0.05 for all). Similar results were seen after extending follow-up to 2 years.

Conclusions

Rivaroxaban may lower the rate of stroke or systemic embolism vs. warfarin in NVAF patients with a non-sex-related CHA2DS2-VASc score of 1 without impacting major bleeding.
Successful aneurysm resection and coronary artery revascularization following saphenous vein graft aneurysm rupture
Authors: Jawitz Oliver K , Keenan Jeffrey E , Perna Jennifer , Milano Carmelo A
Published: July 2018

Saphenous vein graft aneurysms after coronary artery bypass grafting (CABG) have been rarely reported. Their incidence and natural history are poorly defined. Herein, we present a patient who presented acutely with contained rupture of a large saphenous vein graft aneurysm 12 years after CABG, which was successfully managed with open aneurysm resection and regrafting.
Cardio-Oncology Services: rationale, organization, and implementation
Authors: Lancellotti Patrizio , Suter Thomas M , López-Fernández Teresa , Galderisi Maurizio , Lyon Alexander R , Van der Meer Peter , Cohen Solal Alain , Zamorano Jose-Luis , Jerusalem Guy , Moonen Marie , Aboyans Victor , Bax Jeroen J , Asteggiano Riccardo
Published: July 2018

Aims

Anticancer therapies have extended the lives of millions of patients with malignancies, but for some this benefit is tempered by adverse cardiovascular (CV) effects. Cardiotoxicity may occur early or late after treatment initiation or termination. The extent of this cardiotoxicity is variable, depending on the type of drug used, combination with other drugs, mediastinal radiotherapy, the presence of CV risk factors, and comorbidities. A recent position paper from the European Society of Cardiology addressed the management of CV monitoring and management of patients treated for cancer.

Methods and results

The current document is focused on the basis of the Cardio-Oncology (C-O) Services, presenting their rationale, organization, and implementation. C-O Services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardiotoxicity and/or with concomitant CV diseases. These services require a multidisciplinary approach, with the aims of promoting CV health and facilitating the most effective cancer therapy.

Conclusion

The expected growing volume of patients with cancer at risk of developing/worsening CV disease, the advent of new technological opportunities to refine diagnosis, and the necessity of early recognition of cancer therapy-related toxicity mandate an integrative multidisciplinary approach and care in a specialized environment. This document from the ESC Cardio-Oncology council proposes the grounds for creating C-O Services in Europe based on expert opinion.
Peer-Based Strategies to Support Physical Activity Interventions for Older Adults: A Typology, Conceptual Framework, and Practice Guidelines
Authors: Matz-Costa Christina , Howard Elizabeth P , Castaneda-Sceppa Carmen , Diaz-Valdes Iriarte Antonia , Lachman Margie E
Published: July 2018

Despite the documented and well-publicized health and well-being benefits of regular physical activity (PA), low rates of participation have persisted among American older adults. Peer-based intervention strategies may be an important component of PA interventions, yet there is inconsistent and overlapping terminology and a lack of clear frameworks to provide a general understanding of what peer-based programs are exactly and what they aim to accomplish in the current gerontological, health promotion literature. Therefore, a group of researchers from the Boston Roybal Center for Active Lifestyle Interventions (RALI) collaborated on this paper with the goals to: (a) propose a typology of peer-based intervention strategies for use in the PA promotion literature and a variety of modifiable design characteristics, (b) situate peer-based strategies within a broader conceptual framework, and (c) provide practice guidelines for designing, implementing, and reporting peer-based PA programs with older adults. We advance clarity and a common terminology and highlight key decision points that offer guidance for researchers and practitioners in using peers in their health promotions efforts, and anticipate that it will facilitate appropriate selection, application, and reporting of relevant approaches in future research and implementation work.
Both Victim and ‘Perpetrator’: Finding a Voice before Inquiries into Historical Abuse in Out-of-Home Care
Authors: Swain Shurlee
Published: July 2018

Inquiries into historical institutional abuse have only recently come to be viewed through the lens of transitional justice. This article argues that their distinctive victim-focused approach disguises a reality that institutions in which violence was endemic blurred the line between victims and ‘perpetrators.’ Earlier inquiries often blamed residents for the prevalence of institutional violence, avoiding accusations that authorities had failed. Contemporary inquiries, intent on exposing institutional failures, draw a dichotomy between victims and perpetrators, but this makes it difficult for a victim/‘perpetrator’ to find a space in which to speak. This article explores the ways in which such people shape their understandings of their dual identity and the challenges which they pose to the unity of survivor advocacy groups in the shift from inquiry to redress. It argues that the existence of victim/‘perpetrator’ should be seen as evidence of institutional failure rather than an indication of individual culpability.
On Nonlinear Profile Decompositions and Scattering for an NLS–ODE Model
Authors: Cuccagna Scipio , Maeda Masaya
Published: July 2018

In this paper, we consider a Hamiltonian system combining a nonlinear Schrödinger equation (NLS) and an ordinary differential equation. This system is a simplified model of the NLS around soliton solutions. Following Nakanishi [33], we show scattering of $L^2$ small $H^1$ radial solutions. The proof is based on Nakanishi’s framework and Fermi Golden Rule estimates on $L^4$ in time norms.
Stable Polarized del Pezzo Surfaces
Authors: Cheltsov Ivan , Martinez-Garcia Jesus
Published: July 2018

We give a simple sufficient condition for $K$-stability of polarized del Pezzo surfaces and for the existence of a constant scalar curvature Kähler metric in the Kähler class corresponding to the polarization.
Genome-Wide Sequence Analysis of Kaposi Sarcoma-Associated Herpesvirus Shows Diversification Driven by Recombination
Authors: Sallah Neneh , Palser Anne L , Watson Simon J , Labo Nazzarena , Asiki Gershim , Marshall Vickie , Newton Robert , Whitby Denise , Kellam Paul , Barroso Inês
Published: July 2018

This study presents 45 new KSHV genomes sequenced from Uganda, a KSHV endemic region. We present new evidence for the presence of inter- and intragenic recombination across genomes contributing to the diversification of KSHV strains into at least 5 types.
Assessing information sources to elucidate diagnostic process errors in radiologic imaging — a human factors framework
Authors: Cochon Laila , Lacson Ronilda , Wang Aijia , Kapoor Neena , Ip Ivan K , Desai Sonali , Kachalia Allen , Dennerlein Jack , Benneyan James , Khorasani Ramin
Published: July 2018

Objective

To assess information sources that may elucidate errors related to radiologic diagnostic imaging, quantify the incidence of potential safety events from each source, and quantify the number of steps involved from diagnostic imaging chain and socio-technical factors.

Materials and Methods

This retrospective, Institutional Review Board-approved study was conducted at the ambulatory healthcare facilities associated with a large academic hospital. Five information sources were evaluated: an electronic safety reporting system (ESRS), alert notification for critical result (ANCR) system, picture archive and communication system (PACS)-based quality assurance (QA) tool, imaging peer-review system, and an imaging computerized physician order entry (CPOE) and scheduling system. Data from these sources (January-December 2015 for ESRS, ANCR, QA tool, and the peer-review system; January-October 2016 for the imaging ordering system) were collected to quantify the incidence of potential safety events. Reviewers classified events by the step(s) in the diagnostic process they could elucidate, and their socio-technical factors contributors per the Systems Engineering Initiative for Patient Safety (SEIPS) framework.

Results

Potential safety events ranged from 0.5% to 62.1% of events collected from each source. Each of the information sources contributed to elucidating diagnostic process errors in various steps of the diagnostic imaging chain and contributing socio-technical factors, primarily Person, Tasks, and Tools and Technology.

Discussion

Various information sources can differentially inform understanding diagnostic process errors related to radiologic diagnostic imaging.

Conclusion

Information sources elucidate errors in various steps within the diagnostic imaging workflow and can provide insight into socio-technical factors that impact patient safety in the diagnostic process.
Influence of simulation on electronic health record use patterns among pediatric residents
Authors: Orenstein Evan W , Rasooly Irit R , Mai Mark V , Dziorny Adam C , Phillips Wanczyk , Utidjian Levon , Luberti Anthony , Posner Jill , Tenney-Soeiro Rebecca , Bonafide Chris P
Published: July 2018

Objective

Electronic health record (EHR) simulation with realistic test patients has improved recognition of safety concerns in test environments. We assessed if simulation affects EHR use patterns in real clinical settings.

Materials and Methods

We created a 1-hour educational intervention of a simulated admission for pediatric interns. Data visualization and information retrieval tools were introduced to facilitate recognition of the patient’s clinical status. Using EHR audit logs, we assessed the frequency with which these tools were accessed by residents prior to simulation exposure (intervention group, pre-simulation), after simulation exposure (intervention group, post-simulation), and among residents who never participated in simulation (control group).

Results

From July 2015 to February 2017, 57 pediatric residents participated in a simulation and 82 did not. Residents were more likely to use the data visualization tool after simulation (73% in post-simulation weeks vs 47% of combined pre-simulation and control weeks, P <. 0001) as well as the information retrieval tool (85% vs 36%, P < .0001). After adjusting for residents’ experiences measured in previously completed inpatient weeks of service, simulation remained a significant predictor of using the data visualization (OR 2.8, CI: 2.1-3.9) and information retrieval tools (OR 3.0, CI: 2.0-4.5). Tool use did not decrease in interrupted time-series analysis over a median of 19 (IQR: 8-32) weeks of post-simulation follow-up.

Discussion

Simulation was associated with persistent changes to EHR use patterns among pediatric residents.

Conclusion

EHR simulation is an effective educational method that can change participants’ use patterns in real clinical settings.
Cross-fostering as a conservation tool to augment endangered carnivore populations
Authors: Gese Eric M , Waddell William T , Terletzky Patricia A , Lucash Chris F , McLellan Scott R , Behrns Susan K
Published: July 2018

Cross-fostering offspring with nonbiological parents could prove useful to augment populations of endangered carnivores. We used cross-fostering to augment captive-born and wild-born litters for the endangered red wolf (Canis rufus). Between 1987 and 2016, 23 cross-fostering events occurred involving captive-born pups fostered into captive litters (n = 8 events) and captive-born pups fostered into wild recipient litters (n = 15 events). Percentage of pups surviving 3 and 12 months was 91.7% for captive-born pups fostered into captive recipient litters. For pups fostered into wild litters, percentage of pups surviving 5 months was > 94% among fostered pups (pups fostered into a wild red wolf litter or replaced a hybrid litter), pups in recipient litters (wild-born litters receiving fostered pups), and pups in control litters (wild-born litters not in a fostering event) when using pups with known fates. Including pups with unknown fates as deaths, percentage of pups surviving 5 months was > 54% among fostered pups, pups in recipient litters, and pups in control litters. Among wild litters, percentage of pups surviving 12 months was > 82% among fostered pups, pups in recipient litters, and pups in control litters when using pups with known fates. Including pups with unknown fates as deaths, percentage of pups surviving 12 months was > 48% among fostered pups, pups in recipient litters, and pups in control litters. Although survival to 12 months was similar among the groups, average life span was different with pups in control litters living 3.3 years, pups in recipient litters living 4.6 years, and fostered pups living 5.6 years. Of fostered pups surviving > 12 months in the wild, 9 animals whelped or sired 26 litters. Cross-fostering was successful at augmenting litter size for red wolves without any deleterious effects on recipient litters, illustrating fostering as a tool for increasing populations of endangered carnivores.
Prometastatic Molecular Profiles in Breast Tumors From Socially Isolated Women
Authors: Bower Julienne E , Shiao Stephen L , Sullivan Peggy , Lamkin Donald M , Atienza Robert , Mercado Fernando , Arevalo Jesusa , Asher Arash , Ganz Patricia A , Cole Steve W
Published: July 2018

Background

Social isolation is associated with accelerated breast cancer progression and increased disease recurrence and mortality, but the underlying biological mechanisms remain poorly understood. In preclinical models, beta-adrenergic signaling from fight-or-flight stress responses can stimulate prometastatic processes in the tumor microenvironment including upregulation of M2 macrophages, epithelial–mesenchymal transition (EMT), and lymphovascular invasion. This study examines whether the same pathways are upregulated in breast tumors from socially isolated cancer patients.

Methods

EMT and M1/M2 macrophage gene expression programs were analyzed by genome-wide transcriptional profiling, and lymphatic and vascular density were assessed by immunohistochemistry in primary tumors from 56 early-stage breast cancer patients who were part of the UCLA RISE study. Social isolation was quantified by the Social Provisions Scale, and disease characteristics were assessed by medical record review. General linear models were used to quantify differential gene expression across risk factor groups. Linear regression models were used to examine associations between social isolation and lymphovascular invasion.

Results

Tumors from socially isolated patients showed upregulated expression of genes involved in EMT (average score difference = +0.080 log2 mRNA abundance ± 0.034 standard error) and M2 macrophage polarization (+0.033 ± 0.014) as well as increased density of lymphatic vessels (β= –.29) but no difference in blood vessel density. TELiS promoter–based bioinformatics analyses indicated activation of CREB family transcription factors that mediate the gene-regulatory effects of β-adrenergic signaling (log2 fold-difference in promoter binding site prevalence: mean ± standard error = +0.49 ± 0.19).

Conclusions

Primary breast tumors from socially isolated patients show multiple prometastatic molecular alterations, providing a plausible biological pathway through which poor social support may accelerate breast cancer progression and defining new targets for intervention.
Elements of disturbance that affect epiphyte vitality in a temperate rainforest: an experimental approach
Authors: Nadkarni Nalini M , Kohl Kevin D
Published: July 2018

Aims

Epiphytes are an abundant and diverse component of many wet temperate forests and have significant roles in ecosystem processes. Little is known about the processes and rates of their death and decomposition when they fall from the canopy, which limits our understanding of their role in forest carbon sequestration and nutrient cycling. In the temperate rainforest of the Quinault River Valley, Washington State, our aim was to test hypotheses regarding four elements of disturbance that might contribute to their decline.

Methods

We established set of experiments in which we placed samples of canopy epiphytes and their branch segments: (i) in the canopy versus forest floor microenvironment (stratum); (ii) attached to live versus dead branch substrates; (iii) subjected to physical disruption and ‘jarring’; and (iv) in direct versus indirect contact with the forest floor. Over the 2-year study, we assigned a non-destructive ‘vitality index’ (based on color and apparent mortality and dryness) to each sample every 2–3 months to compare effects of the experimental treatments and analyzed with a statistical model and post hoc pairwise comparisons of treatments.

Important Findings

The canopy versus ground stratum and live/dead branch status significantly affected epiphyte vitality. Effects of physical disruption and ground contact were not significant. There were seasonal effects (low vitality during the sampling times in the summer, revitalization upon sampling times in the winter) for all treatments except samples in contact with the ground. One implication of these results relates to effects of climate change, which is predicted to shift to hotter, drier summers and wetter winters. Climate change may affect forest dynamics and nutrient cycling in unpredictable ways. Results also point to future experiments to understand biotic and abiotic effects on epiphyte disturbance and dynamics.
Approach to the patient with metabolic acidosis or alkalosis
Authors: Halperin Mitchell L. , Kamel Kamel S.
Published: July 2018

The pathophysiology, clinical approach, and management of the common causes of metabolic acidosis and alkalosis are discussed.
In metabolic acidosis, a quantitative estimate of the extracellular volume (ECFV) is required to determine its content of bicarbonate in a patient with ECFV contraction. Buffering of H+ must occur by the bicarbonate buffer system in muscle to avoid binding to intracellular proteins, this requires low muscle capillary PCO2; acid gain type of metabolic acidosis is detected by the finding of new anions in blood and/or urine. The urine osmolal gap is the best indirect test to assess [NH4+] in urine.
In metabolic alkalosis, Cl− depletion alkalosis is misleading. Deficits must be defined as HCl, KCl, and/or NaCl. A quantitative assessment of ECFV helps determine the contribution of individual deficits of Cl− salts. There is no tubular maximum for HCO3− reabsorption. Angiotensin II and the usual pH in proximal convoluted tubule cells, the two major stimuli for NaHCO3 reabsorption, must be removed/ changed for NaHCO3 to be excreted.
Cancer and metabolism
Authors: Snell Cameron , Gatter Kevin C. , Harris Adrian L. , Pezzella Francesco
Published: July 2018

This chapter covers the relationship between cancer and metabolism. It discusses the role of angiogenesis and metabolic reprogramming in influencing tumour growth. The transcription factors that orchestrate the metabolic switch are discussed. The chapter presents an overview of the contribution of tumour suppressors to increased glycolysis. The metabolic changes that support uncontrolled proliferation such as lactate and pH levels, hypoxia, and reactive oxygen species are discussed. The chapter also covers the contribution of metabolic genes with oncogenic or tumour suppressor activity to metabolic transformation, the upregulation of lipid biosynthesis in cancer, and glycogen synthesis in cancer. The chapter concludes with a description of the potential strategies for targeting metabolic transformation.
Smoking and cancer
Authors: Samet Jonathan M.
Published: July 2018

Worldwide, there are more than one billion users of tobacco products, including about 750,000 people who smoke cigarettes regularly. The resulting burden of premature mortality, about six million deaths in 2011, makes tobacco use the world’s leading cause of avoidable premature mortality. Of the six million deaths, an estimated 2.12 million (33%) are from cancer. This chapter provides a perspective on tobacco smoking as a cause of cancer, summarizing the evidence from epidemiological studies and reviewing a now extensive literature. Active smoking causally increases risk for multiple cancer sites. Secondhand smoke inhaled by never smokers has also been causally linked to various cancers, including lung cancer. Tobacco control provides a tremendous opportunity for cancer prevention. For oncologists, emerging evidence points to clinical implications of smoking with regard to therapy and outcomes in cancer. As for all clinical encounters, smoking needs to be assessed routinely and cessation counselled vigorously.
Chemical carcinogens
Authors: Oliveira Paula A.
Published: July 2018

The development of cancer associated with exposure to chemical carcinogens is a reality and existing knowledge of these cancers is based on epidemiological, in vivo, and in vitro studies. Chemical carcinogens are present virtually everywhere and humans can be exposed to these compounds in food, air, water, their environment, or their workplace. This chapter is concerned with the main types of exogenous chemical carcinogens, how they are classified and their modes of action, absorption, and metabolism, as well as the principal tests available for evaluating their carcinogenicity. Only exogenous chemicals are considered in this chapter, since exogenous chemical carcinogens may be the major contributors to human cancer.
Aetiology and progression of cancer
Authors: van Duijnhoven Fränzel J.B. , Kampman Ellen
Published: July 2018

Worldwide, there is a large difference in cancer rates. These rates may change over generations when people move from one part of the world to another. This occurs because these generations adapt their lifestyle to that of the host country, indicating that lifestyle factors are important in the aetiology of cancer. In this chapter an overview of established associations between body fatness, physical activity, diet, and other lifestyle factors and the development of cancer is given. About one-third of all cancers worldwide are caused by an unhealthy lifestyle. Evidence-based recommendations for the general population to decrease their risk of cancer have been set. Guidelines for individuals who are diagnosed with cancer, however, are lacking, due to limited evidence on the role of lifestyle during and after cancer treatment. Research should now be directed towards the role of body fatness, physical activity, diet, and other lifestyle factors in cancer progression.
Practice points for radiation oncology
Authors: Seidlitz Annekatrin , Combs Stephanie E. , Debus Jürgen , Baumann Michael
Published: July 2018

Radiotherapy is an indispensable treatment modality in modern oncology with curative potential in applying ionizing radiation in a wide spectrum of malignancies. Radiotherapy is often combined in multidisciplinary concepts with surgery or cytostatic drugs, and increasingly also with molecular-targeted therapies. The aim of radiotherapy is to achieve uncomplicated local or locoregional tumour control, that is to permanently inactivate all cancer cells in the irradiated volume without inducing severe normal tissue reactions. This aim can be reached for a substantial proportion of patients with modern high-precision radiation treatment planning and application technologies. Clinical and radiobiological principles guide the radiation oncologist in time-dose volume prescription of radiotherapy and in selection of the optimal radiation treatment plan for the individual patient. The scope of this chapter is to summarize important basic biological, physical, and clinical principles and practice points of radiotherapy of relevance for the non-radiation oncologist.
Cancer prevention
Authors: Goltz Sarah E.B. , Lob-Levyt Julian
Published: July 2018

This chapter describes the increasingly critical role of cancer vaccines in preventing, and potentially even treating, cancers in all resource settings. At this time, there are three cancer vaccines, two of which protect against cancer-causing viruses—hepatitis B virus (HBV) and the human papillomavirus (HPV); the third is an immunostimulant treatment virus for late-stage prostate cancer. Few advances in medicine and public health have had as substantial an impact on morbidity and mortality worldwide as vaccines. The potential public health impact of cancer vaccines is particularly significant in developing countries, where limited resources make prevention, screening, and disease management especially challenging. Numerous strategies are being employed to improve access to cancer vaccines in low- and middle-income settings. These efforts are beginning to demonstrate impact on cancer rates, indicating how innovative mechanisms may be used to expand access to HPV and other future cancer vaccines in the decades to come.
Oesophageal cancer
Authors: Dirix Piet , Weytjens Reinhilde , Vanderkam Sabine , Haustermans Karin , Cutsem Eric Van , Sagaert Xavier , Deroose Christophe M. , Nafteux Philippe , Prenen Hans , Lerut Toni
Published: July 2018

Worldwide, oesophageal cancer, including cancer of the gastro-oesophageal junction (GEJ), is the sixth leading cause of death from cancer. Despite recent advances, treatment of oesophageal cancer remains challenging and is best approached by an experienced multidisciplinary team. Surgery alone is the treatment of choice in early stage carcinoma although in superficial cancers (T1a) endoscopic resection is to be preferred. In locally advanced tumors induction therapy followed by surgery is the preferred treatment. In selected cases definitive chemoradiotherapy could be considered as a valuable alternative The role of adjuvant chemotherapy is unclear, but could be considered for selected GEJ adenocarcinoma patients. Adjuvant chemoradiotherapy should be considered in all patients with advanced disease or positive margins who did not receive neo-adjuvant radiotherapy. For metastatic disease, the goal is to prolong and maximize quality of life. Regarding the palliative treatment of dysphagia, brachytherapy was shown to be more effective than stenting.
Rectal cancer and systemic therapy of colorectal cancer
Authors: Beets-Tan Regina , Glimelius Bengt
Published: July 2018

In rectal cancer treatment, surgery is most important. Dissection outside the mesorectal fascia, total mesorectal excision is required for cure in most cases; a local procedure is possible in the earliest tumours. Appropriate staging is required prior to treatment decision to stratify patients into risk groups. In early tumours surgery alone is sufficient whereas in intermediate cancers local recurrence rates are too high and preoperative radiotherapy is indicated. A short-course schedule is convenient, low toxic, although some prefer long-course chemoradiotherapy. The addition of a fluoropyrimidine enhances the radiotherapy. In locally advanced tumours preoperative chemoradiotherapy is required. The value of adjuvant chemotherapy in rectal cancer is controversial, particularly if preoperative chemoradiotherapy was used. Palliative chemotherapy prolongs life and improves well-being in patients with metastatic disease. Targeted drugs further improves the results to some extent. In some patients, chemotherapy may convert non-readily resectable metastases to resectable, and result in long-term cure.
Colorectal cancer
Authors: Boussioutas Alex , Fox Stephen , Nagtegaal Iris , Heriot Alexander , Knowles Jonathan , Michael Michael , Ngan Sam , Field Kathryn , Zalcberg John
Published: July 2018

This chapter covers colorectal cancer, and includes information on epidemiology, risk factors (chronic inflammation/inflammatory bowel disease, radiation, diet and lifestyle, post cholecystectomy, diabetes, obesity and insulin resistance, cigarette smoking, alcohol, ureterocolic anastamosis, and genetic risk factors, screening, and chemoprevention (aspirin, and NSAIDS), the molecular biology and pathology of colorectal cancer, colorectal carcinoma (location, pathologic prognostic markers, and predictive markers), surgical management (colonic cancer and inflammatory bowel disease, hereditary non-polyposis colonic cancer or HNPCC, presenting as an emergency, treatment of polyp or early cancers, liver and lung metastasis, peritoneal disease, results of surgery and treatment for colon cancer, medical management of early stage disease, adjuvant chemotherapy for stage III disease (T1-4, N1-2M0), adjuvant therapy of patients with resected stage II colon cancer, radiotherapy, multidisciplinary care and special groups, the role of allied teams, and surveillance and follow-up.
Peritoneal mesothelioma
Authors: Richard Alexander H. , Baratti Dario , Chua Terence C. , Deraco Marcello , Hassan Raffit , Pennati Marzia , Perrone Federica , Sugarbaker Paul H. , Thomas Anish , Turner Keli , Yan Tristan D. , Zaffaroni Nadia
Published: July 2018

Malignant peritoneal mesothelioma (MPM) is a rare malignancy arising from the serosa of the abdominal cavity; its natural history is hallmarked by intra-abdominal disease progression. Peritoneal mesothelioma patients generally present with abdominal pain and/or ascites. Pathologically, a positive immunostain for calretinin has markedly increased the accuracy of diagnosis. A new staging system combining extent of tumour burden measured by the peritoneal cancer index (PCI), abdominal nodal status and extra-abdominal metastases has been demonstrated to reliably stratify patient outcomes after cytoreductive surgery (CRS) and hyperthermic perioperative chemotherapy (HIPEC). Over the past decade, the management of these patients has evolved as a multimodality treatment similar to ovarian cancer treatment and now involves CRS and HIPEC.
Cancer of unknown primary site
Authors: Pavlidis Nicholas , Pentheroudakis George
Published: July 2018

This chapter covers cancer of unknown primary site (CUP), and includes information on epidemiology, molecular biology, pathology, and multidisciplinary management of clinicopathological subsets. Previously, these tumours were diagnosed and treated based on clinical presentation, light microscopy and clinical intuition. Today, the majority of cancers of unknown primary site are becoming less unknown, more accurately classified, and appropriately treated by the use of multiplex or genome-wide expression profiling platforms. These techniques allow for precise and correct knowledge of the true tumour origin, leading to more rational and effective treatment. However, there also may be genetic signatures that are primary-independent, pro-metastatic, and possibly CUP-specific.
Primary prevention: principles and practice
Authors: Vannuzzo Diego , Giampaoli Simona
Published: July 2018

Cardiovascular primary prevention is a coordinated set of actions at community and individual level aimed at eradicating, eliminating, or compressing at later ages the impact of cardiovascular diseases and their related disability. Its aim is healthy ageing. Cardiovascular epidemiology has elucidated the role of cardiovascular risk factors, forming the basis of strategies to reduce cardiovascular risk and subsequent disease. There is evidence that cardiovascular primary prevention works if three strategies are implemented together: a population strategy (particularly through a widespread adoption of healthy lifestyles) which aims to keep everyone at low risk from infancy and reduces the cardiovascular risk profile of the whole community; an individualized high-risk strategy through lifestyle changes also prophylactic evidence-based drugs if necessary; and an individualized intermediate-risk strategy which may benefit from non-invasive assessment of subclinical disease and end organ damage.
Behaviour and motivation
Authors: Albus Christian , Herrmann-Lingen Christoph
Published: July 2018

Changing one’s lifestyle is difficult and adherence to medication in people at high cardiovascular risk and established cardiovascular disease is low. Lifestyle is usually based on longstanding patterns and is highly determined by social environment and socioeconomic status. Additional factors such as chronic stress, cognitive impairment, and negative emotions (e.g. depression, anxiety) further impede the ability to adopt a healthy lifestyle, as does complex or confusing advice by medical caregivers. In clinical practice, increased awareness of these factors will facilitate empathetic counselling and the provision of simple and explicit advice. Established cognitive-behavioural strategies are important tools to help with behaviour change and medication adherence. Specialized healthcare professionals (e.g. nurses, dieticians, psychologists) should be involved whenever necessary and feasible. Reducing dosage demands to the lowest applicable level is the single most effective means for enhancing adherence to medication.
Glucose intolerance and diabetes
Authors: Jarnert Christina , Mellbin Linda , Rydén Lars , Tuomilehto Jaakko
Published: July 2018

Diabetes dramatically increases the risk of cardiovascular diseases (CVD). Diabetes is defined by elevated glucose in blood circulation. The level of glycaemia has a graded relation with CVD risk and diabetes is very frequent in people with CVD. In the general population half of the people with type 2 diabetes are undiagnosed, yet efficient methods for population screening exist. Despite considerable improvements in the management of CVD, patients with disturbed glucose metabolism have not benefited to the same extent as those without diabetes. Primary and secondary prevention of CVD in people with diabetes and other disturbances in glucose metabolism must be multifactorial and treatment targets stricter than for patients without glucose aberrations. Increased collaboration between different therapeutic disciplines including diabetologists, cardiologists, general practitioners, and dieticians is key to improved management for this large and high-risk population. Some important aspects of these issues are presented in this chapter.
Ambulatory preventive care: outpatient clinics and primary care
Authors: Schmid Jean-Paul , Saner Hugo , Dendale Paul , Frederix Ines
Published: July 2018

Cardiac rehabilitation (CR) services aim to restore the physical, psychosocial, and vocational status of cardiac patients. The role of these services has evolved due to the progress of interventional cardiology with its prompt and effective treatment of acute coronary syndromes. The focus has moved from the restoration of a patient’s health following an acute event towards a more pronounced long-term targeted secondary prevention intervention. As a consequence, CR services have also expanded their indication in order to include not only patients after myocardial infarction or surgery but also a variety of ’non-acuteʼ cardiovascular disease (CVD) states like stable coronary heart disease and peripheral obstructive artery disease as well as asymptomatic patients with no history of CVD but with a constellation of cardiovascular risk factors, especially metabolic syndrome or diabetes mellitus. This chapter provides a wide-ranging summary of the issues concerning outpatients and primary care.
Evaluation of preventive cardiology
Authors: Kotseva Kornelia , Oldridge Neil , Piepoli Massimo F.
Published: July 2018

The Joint European Societies guidelines on cardiovascular disease (CVD) prevention define lifestyle and risk factor targets for patients with coronary or other atherosclerotic disease and people at high risk of developing CVD. However, several surveys in Europe and the United States showed inadequate lifestyle and risk factor management and under-use of prophylactic drug therapies in primary and secondary CVD prevention. Various professional associations have developed core components, standards, and outcome measures to evaluate quality of care and provide guidelines for identifying opportunities for improvements. Optimal control of cardiovascular risk factors is one of the most effective methods for reducing vascular events in patients with atherosclerotic disease or high cardiovascular risk. Improving treatment adherence is also very important. Health-related quality of life (HRQL) is considered as an outcome measure in research studies and in clinical practice. HRQL measures can help in improving patient-clinician communication, screening, monitoring, and continuous assessment of quality of care.
Technology to enhance locomotor function
Authors: Rupp Rüdiger , Schließmann Daniel , Schuld Christian , Weidner Norbert
Published: July 2018

Technology plays an important role in the rehabilitation of patients with impairments of the lower extremity due to disease or trauma of the central nervous system. In gait rehabilitation compensatory or restorative strategies are applied depending on the time after trauma and the level of impairment. Over the last 20 years advances in the understanding of the intrinsic capacity of the central nervous system for plasticity and recovery led to the establishment of task-oriented restorative therapies: body weight supported treadmill training, either manually assisted or with robotic devices. The effectiveness of robotic locomotion systems will only improve by consequent implementation of principles of motor learning. For enhancement of mobility in individuals with severe sensorimotor impairment of the lower extremities compensatory strategies including the implementation of wheelchairs and more recently active exoskeletons need to be considered.