Tumor‐cell diversification mechanisms insure that malignant neoplasms contain diversified tumor‐cell subpopulations. Because of the instability of tumor cell phenotypes, some malignant cells will evolve with the most favorable properties for their progression to highly metastatic cells. The rates of cellular phenotypic diversification vary greatly among different tumors, and they are probably modulated, in part, by genetic and chromosome defects and by epigenetic events that may vary widely depending upon the nature of the tumor cells and their microenvironments. As (...) tumor diversification and selection proceed, the most malignant cell subpopulations may eventually become dominant and gradually lose their microenvironmental responsiveness. Tumor‐cell diversification mechanisms may be similar or identical to normal, developmentally regulated diversification mechanisms that are used during embryonic cell diversification and differentiation. (shrink)

Due to advances in medicine, a malignant neoplasm is a chronic disease that can be treated for a lot of patients for many years. It may lead to profound changes in everyday life and may induce fear of life. The ability to adjust to a new situation may depend on temperamental traits and stress coping strategies. The research presented in this paper explores the relationships between quality of life, PTSD symptoms, temperamental traits, and stress coping in a sample (...) of patients diagnosed with cancer. One hundred and twenty nine participants aged 24–81 years, 69 females diagnosed with breast cancer and 60 males diagnosed with lung cancer completed Formal Characteristics of Behavior – Temperament Inventory, Coping Inventory for Stressful Situations, PTSD Inventory, and Quality of life SF-36 questionnaire. Higher level of emotional reactivity and higher level of perseveration was associated with lower emotional quality of life. Higher level of emotion oriented-coping and higher level of avoidant-distracted coping was associated with higher level of PTSD symptoms. Emotion-oriented coping and avoidant-distracted coping are ineffective in dealing with stress in the case of patients diagnosed with cancer, because they are associated with a higher level of PTSD symptoms. The significance of temperamental traits for quality of life in the situation of the patients is marginal. Control of specific factors concerned with current health and treatment status is needed the future research. (shrink)

In this work, the evolution of demographic and health patterns in a Basque rural population from Spain is analysed, as they relate to progress in demographic and epidemiological transition. For this purpose, parochial record data on 13,298 births and 9215 deaths, registered during the 19th and 20th centuries (180090) resulting from cardiovascular diseases and malignant neoplasms (post-transition causes). This last point is in contrast with observations from the first four decades of the 20th century, when infectious diseases and respiratory (...) ailments were determining factors in mortality among this population. The data provided by the study of the variation over time in demographic and health patterns indicate that reducing the risk of mortality is one of the most important preconditions for fertility decline. (shrink)

The major cause of death from cancer is the relentless growth of metastases that are resistant to conventional therapy. The pathogenesis of a metastasis is complex and requires that tumor cells complete a sequence of potentially lethal interactions with various host factors. The finding in 1973 that metastasis is selective process and the finding in 1977 that malignant neoplasms are heterogeneous and contain few preexisting metastatic subpopulations have added a new dimension to our understanding of cancer and its spread. (...) This understanding is now contributing to the design of better therapies against disseminated metastasis. (shrink)

While primary malignant brain tumors account for only two percent of all adult cancers, these neoplasms cause a disproportionate amount of cancer-related disabilities and death. The five-year survival rates for brain tumors are the third lowest among all types of cancer. Malignant gliomas comprise the most common types of primary central nervous system tumors and have a combined incidence of five to eight cases per 100,000 people. The median survival rate of conservatively treated patients with malignant gliomas (...) is 14 weeks; with surgical resection alone, 20 weeks; with surgery and radiation, 36 weeks; and with the addition of newer biochemotherapies such as temozolomide and bevacizumab, upward of 14-18 months.The profound cost of caring for terminally ill patients with primary malignant brain tumors raises ethical considerations for the American public; the stewardship of health care dollars for the population at large maintains a juxtaposed tension against a dynamic, necessary balance of hope, care, rehabilitation and research efforts for affected patients and their advocates. (shrink)

Transmissible cancers are elusive and understudied parasitic life forms caused by malignant clonal cells (nine lineages are known so far). They emerge by completing sequential steps that include breaking cell cooperation, evade anti‐cancer defences and shedding cells to infect new hosts. Transmissible cancers impair host fitness, and their importance as selective force is likely largely underestimated. It is, therefore, crucial to determine how common they might be in the wild. Here, we draw a parallel between the steps required for (...) a transmissible cancer to emerge and the steps required for an intelligent civilisation to emerge in the Milky Way using a modified Drake equation. Using numerical analyses, we estimate the potential number of extant marine and bivalve species in which transmissible cancers might exist. Our results suggest that transmissible cancers are more common than expected, and that new lineages can be found by screening a large number of species. (shrink)

BackgroundSarcomas are a diverse group of neoplasms that vary greatly in clinical presentation and responsiveness to treatment. Given the differences in the sites of involvement, rarity, and treatment modality, a multidisciplinary approach is required. Previous literature suggests patients with sarcoma suffer from poorer quality of life especially physical and functional wellbeing. Adolescent and young adult patients are an underrepresented population in cancer research and have differing factors influencing QoL.MethodsRetrospective analysis of Young Adult patients enrolled in the Sarcoma Tissue Repository at (...) University of Iowa. QoL was assessed using the self-report FACT-G questionnaire at enrollment and 12 months post-diagnosis; overall scores and the 4 wellbeing subscales were calculated. Linear mixed effects models were used to measure the association between the rate of change in FACT-G subscale scores and baseline clinical, comorbidity, and treatment characteristics.Results49 patients were identified. 57.1% of patients had a malignancy involving an extremity. Mean FACT-G scores of overall wellbeing improved from baseline to 12 months. Social and emotional wellbeing did not differ significantly between baseline and 12 months. Physical wellbeing and functional wellbeing scores improved from baseline to 12 months. No difference was seen for FACT-G overall scores for age, sex, laterality, marital status, performance status, having children, clinical stage, limb surgery, chemotherapy, or tumor size. A difference was demonstrated in physical wellbeing scores for patients with baseline limitation compared to those with no baseline limitation. A difference was demonstrated in social wellbeing based on anatomical site.ConclusionYoung adults with sarcoma treated at a tertiary center had improvements in overall reported QoL at 12 months from diagnosis. Overall baseline QoL scores on FACT-G were lower than the general adult population for YA patients with sarcoma but at 12 months became in line with general population norms. The improvements seen merit further investigation to evaluate how these change over the continuum of care. Quality of life changes may be useful outcomes of interest in sarcoma trials. (shrink)

Variation or rearrangement of regulatory genes is responsible for cellular malignant change. These types of chromosomal variations also produce heterochrony or paedomorphic evolution at the organismal level. Analogously, neoplasia represents a cellular macroevolutionary event, and a tumour can be said to be an evolved population of cells. To understand this cellular evolution to malignancy, it may be necessary to go beyond a clonal selection (adaptationist) explanation of neoplastic alteration. In the pericellular environment natural selection consists of the organizational restraints (...) of surrounding cells as well as the host's immunological surveillance and non-specific monocyte-macrophage systems. Indirect evidence suggests that success for the neoplasm depends not upon clonal selection, but solely upon a genetic methodology—the function of which is to elude selection.The author has coined the term cellular heterochrony to illustrate analogic similarities in the molecular modes of speciation between anaplastic cancer cells and the heterochronic evolution of organisms. By reverting to a juvenile (embryonic) repertoire of cellular behaviour a tumour secures its own tenure or niche by usurping the host's armamentarium of selection forces, employing many of the same or similar methods by which implanting and invading tissues of the mammalian embryo forestall maternal detection and rejection. A number of ways by which the tumour blocks, subverts or evades selection are discussed. (shrink)

Background: Despite a gradual shift in the focus of medical care among terminally ill patients to a palliative model, studies suggest that many children with life-limiting chronic illnesses continue to die in hospital after prolonged periods of inpatient admission and mechanical ventilation.Objectives: To examine the characteristics and location of death among hospitalised children, investigate yearwise trends in these characteristics and test the hypothesis that professional ethical guidance from the UK Royal College of Paediatrics and Child Health would lead to significant (...) changes in the characteristics of death among hospitalised children.Methods: Routine administrative data from one large tertiary-level UK children’s hospital was examined over a 7-year period for children aged 0–18 years. Demographic details, location of deaths, source of admission , length of stay and final diagnoses were studied. Statistical significance was tested by the Kruskal–Wallis analysis of ranks and median test , χ2 test and Cochran–Armitage test .Results: Of the 1127 deaths occurring in hospital over the 7-year period, the majority were among infants. The main diagnoses at death included congenital malformations , perinatal diseases , cardiovascular disorders and neoplasms . Most deaths occurred in an intensive care unit environment , with a significant increase over the years . There was a clear increase in the proportion of admissions from in-hospital among the ICU cohort . Infants with congenital malformations and perinatal conditions were more likely to die in an ICU , and older children with malignancy outside the ICU . Children stayed for a median of 13 days on a hospital ward before being admitted to an ICU where they died.Conclusions: A greater proportion of hospitalised children are dying in an ICU environment. Our experience indicates that professional ethical guidance by itself may be inadequate in reversing the trends observed in this study. (shrink)

Interferons (IFNs) are a diverse group of cytokines whose potent antitumor effects have piqued the interest of scientists for decades. Some of the most sustained clinical accomplishments have been in the field of myeloproliferative neoplasms (MPNs). Here, we discuss how both historical and novel breakthroughs in our understanding of IFN function may lead to more effective therapies for MPNs. The particular relevance and importance of modulating the novel IFN‐regulated ULK1 pathway to optimize IFN responses is highlighted.

The metabolic organization of both normal and malignant prostate cellular phenotypes involves some unusual and surprising features. In particular, both conditions exhibit ratios of NADH/NAD+ and NADPH/NADP+ charactersitic of high oxidative states despite a chronic shortage of O2 in both conditions. In this paper, we observe that, in prostate cancer cells, the oxidizing power of the fatty acid synthesis (FAS) pathway is so large that redox is stabilized more favorably (more oxidized) than in normal prostate cells. This FAS‐facilitated redox (...) improvement occurs despite the fact that malignant cells are more O2 limited and therefore express more hypoxia inducible factor 1 (HIF1) and express hypoxia‐regulated genes more robustly. This unusual metabolic situation clearly separates direct regulatory effects of redox balance from secondary effects of hypoxia per se. The physiological significance of the FAS pathway is thus the harnessing of its oxidizing power for improving redox balance despite conditions of more extreme hypoxia. Similar hypoxia defense strategies are found in animal species that are unusually tolerant to oxygen lack. Our hypothesis is that the metabolic organization in the “low zinc, low citrate” phenotype reflects an hypoxia‐defense adaptation geared toward redox balance, with prostate cancer cells being relatively more oxidized, even if more hypoxic, than normal prostate cells. Recognition and understanding of these redox balancing and hypoxia defense functions may lead to new intervention strategies by developing new intracellular targets for prostate cancer therapy. BioEssays 24:749–757, 2002. © 2002 Wiley Periodicals, Inc. (shrink)

Local food systems seem virtuous in the larger context of the neoliberalization of global food systems and increasing food insecurity. However, local food systems are critiqued for reproducing neoliberalism when they prioritize niche-market consumerism over enhancing access for poor people. Advocates, in contrast, insist local food systems contribute to an equitable political economy of food if they are place-based and inclusive. Local food systems must not, according to them, be condemned monolithically in light of their neoliberal tendencies, but evaluated instead (...) on a case-by-case basis regarding their potentially innovative solutions to food insecurity. We heed this call by investigating how a regionally-renowned local food system addresses food insecurity in an impoverished corner of rural Appalachia. Specifically, we use qualitative methods, including semi-structured interviews, participant observation, and document analysis, to evaluate the local food system in Athens County, Ohio. Our findings indicate that extra-local processes under neoliberalism, including austerity and economic marginalization, create a large-scale context of malign neglect in which local food security initiatives operate. Place-based strategies for food security, in response, emphasize producer profitability and consumer responsibility as solutions to extra-local constraints. These localized processes of benign neglect, however, reproduce stifling neoliberalisms within the Athens local food system, giving it a defensive stance that fails to promote innovative modes of inclusion despite its sustainable reputation. Malign and benign forms of neglect, working in creative tension, perpetuate a problematic paradox of food insecurity amidst a seemingly robust local food system as neoliberalization operating at a variety of scales remains unchallenged. (shrink)

The problem of providing mandated medical care has become commonplace as correctional systems in the United States struggle to manage unprecedented increases in its aging prison population. This study explores older incarcerated women’s perceptions of prison health care policies and their day-to-day survival experiences. Aggregate data obtained from a sample of 327 older women residing in prison facilities in five Southern states were used to identify a baseline of health conditions and needs for this vulnerable group. With an average of (...) 4.2 chronic health conditions, frequently histories of victimization, and high rates of mental health issues, the women’s experiences of negotiating health care was particularly challenging. By incorporating the voices of older women, we expose the contradictions, dilemmas, and obstacles they experience in their attempts to obtain health care. It is clear from the personal accounts shared that, despite court mandates, penal harm practices such as delaying or denying medical treatment as well as occasional staff indifferences are common in women’s prisons. With older women having the greatest need for health care, an age- and gender-sensitive approach is recommended. (shrink)

This book tells the stories of seven people with a distinct perspective on cancer. Experts on medical ethics, personal experience showed them how little they knew about the real world of serious illness. In this book, they describe cancer's teachings on ethics, medicine, and the experience of illness.

Dieser Artikel ist eine Antwort auf Dr. J. G. Cottinghams The Role of the Malignant Demon. Ich stelle die folgenden Behauptungen von Dr. Cottingham in Frage: 1) daß die Sätze der Logik und Mathematik in der ersten Meditation nur nebenbei behandelt werden; 2) daß Descartes glaubt, daß die Sätze der Mathematik keine Existenzbedeutung haben; 3) daß „parum curant“ bedeutet „sie kümmern sich wenig um“; 4) daß die Hypothese des bösen Dämons nur eine subsidiäre Rolle spiele.

A politically oriented study of the thought of the founders of the main schools of contemporary academic philosophy, those which dominate nearly all universities throughout the world. It concentrates on four key masters: Wittgenstein, who founded both Logical Positivism and the so-called Common Language or Analytic school; Heidegger, the acknowledged master of Hermeneutic Philosophy or the so-called Continental school; Lukacs, the founder of Hegelian Marxism and the leading Communist philosopher of the Soviet period; and, finally, the now lesser-known Gentile, the (...) Hegelian Idealist. (shrink)

Thomas Urquhart (1611–1660), celebrated for his English translation of Rabelais’ Gargantua et Pantagruel, has earned some notoriety for his eccentric, putatively incomprehensible early book on trigonometry The Trissotetras (1645). The Trissotetras was too impractical to succeed in its own day as a textbook, since it lacked both trigonometric tables and sample calculations. But its current bad reputation is based on literary authors’ amplifications of the verdict prefaced to its 19th century reprinting by one mathematician, William Wallace, who lacked the background (...) to appreciate the book’s historical context. Considering that context (including seventeenth century ‘copious’ prose, and medieval logic and ‘art of memory’), the bad reputation is undeserved: the book is mathematically clear, clever (e.g. in superimposing 16 problems into one diagram), and complete. The Trissotetras may thus be viewed as simply one more of Urquhart’s polymathic projects and involvements – which included education, rise of the middle class, religious and class conflicts, development of science and mathematics, search for patronage, universal language construction, and development of English prose – which serve to make him a lively and instructive intellectual Everyman for his time. (shrink)

This paper is about the ontology of a cancer diagnosis at high-end hospitals in Colombia. Drawing on a seventeen-month ethnographic fieldwork study in this country, it pays attention to how dermatologists, pathologists, and oncologists looked at my partner’s skin during a routine medical checkup and enacted two seemingly contradictory diagnoses: a lethal melanoma and a benign dysplastic nevus—commonly known as mole. Because their differences under the microscope or through dermatology goggles may be subtle, physicians often disagree on what they see. (...) When medical services are not unrelated to the economic possibilities of patients to pay for them, what emerges through a microscope might be different. With neoliberal medical reforms in Colombia as background, this paper focuses on the ontological indeterminacy of cancer and its relationship to high-end hospitals and a patient who could, albeit not without effort, pay for the treatment. Thus, I argue that how physicians saw was not unrelated to what they saw and therefore to their practices of medicine in neoliberal Colombia. How do medical practices and ways of seeing in Colombia enter into composition with the bodies they study? Could the same skin tissue simultaneously be cancerous and noncancerous? (shrink)

Cancers often express hundreds of genes otherwise specific to germ cells, the germline/cancer (GC) genes. Here, we present and discuss the hypothesis that activation of a “germline program” promotes cancer cell malignancy. We do so by proposing four hallmark processes of the germline: meiosis, epigenetic plasticity, migration, and metabolic plasticity. Together, these hallmarks enable replicative immortality of germ cells as well as cancer cells. Especially meiotic genes are frequently expressed in cancer, implying that genes unique to meiosis may play a (...) role in oncogenesis. Because GC genes are not expressed in healthy somatic tissues, they form an appealing source of specific treatment targets with limited side effects besides infertility. Although it is still unclear why germ cell specific genes are so abundantly expressed in cancer, from our hypothesis it follows that the germline's reproductive program is intrinsic to cancer development. (shrink)

* Editor’s Note: This paper won the Young Epistemologist Prize for the Rutgers Epistemology conference held in 2003.

Descartes nimmt in Anspruch, daß sein Argument des Deus malignus über die Einwände der Skeptiker hinausgehe. Was fügt es dem Traumargument hinzu? Die verbreitete Ansicht, der Dämon stelle die Erkenntnis mathematischer und logischer Wahrheiten in Frage, wird im folgenden diskutiert und zurückgewiesen. Die richtige Interpretation lautet: Die Annahme des Dämons unterstützt den Skeptizismus und verstärkt die Zweifel an der Existenz äußerer Objekte. Es werden drei Einwände gegen diese Interpretation erörtert und zurückgewiesen. Eine andere Auffassung vertritt Frankfurt: Die Rolle des Traumarguments (...) sei wesentlich begrenzt; die durch den Dämon aufgeworfenen Zweifel seien umfassender. Eine genaue Analyse der Entwicklung des Traumarguments in der Ersten Meditation führt zur Widerlegung dieser Interpretation. (shrink)

Th is discussion review appeals to a minimal militant comradeship across struggles. Theory is also a struggle, and solidarity is always key. It agrees with Slavoj Žižek’s main argument: the critique of Eurocentrism cannot sustain itself without acknowledging the positive influence of the Enlightenment radical tradition. It also underlines that particular emancipatory projects set against universalism fail to properly problematise political subjectivity. This is not to coalesce with certain Western/European metropolitan intellectual and political inclinations, not least in the Left, particularly (...) prone to lay down the correct and rightful terms of anybody else’s struggles. Various examples from different historic and contemporary contexts illustrate and clarify this point. In the process, some hints are also given on possible theoretical and political reconciliations between Decolonial Theory and the Idea of Communism or between Žižek’s “possibilism” and Alain Badiou’s politics of the impossibl e. (shrink)

Background and Purpose The decision to perform decompressive craniectomy for patients with malignant MCA syndrome can be ethically complex. We investigated factors that clinicians consider in this decision-making process. Methods A survey including clinical vignettes and attitudes questions surrounding the use of hemicraniectomy in malignant MCA syndrome was distributed to 203 neurosurgeons, neurologists, staff and residents, and nurses and allied health members specializing in the care of neurological patients. These were practicing health care providers situated in an urban (...) setting in Canada where access to health care is covered by national policy and is a human right. Results Eighty-eight participants responded to survey. All participants unanimously supported the procedure for young and healthy patients. Advanced age, the presence of aphasia, comorbid medical conditions, and poor baseline functional status were dominant factors associated with increasing reluctance to offer surgical decompression. Patients’ previously expressed wishes were also an important consideration. Eighty-six percent of respondents agreed that withholding surgery is ethically justified if the outcome is perceived as futile. Conclusions Health care providers use similar factors to determine if aggressive management is justified given anticipated burden on patient quality of life and extended impact on society. This convergence can be harnessed beneficially for the transparent communication of medical options in the ethically complex setting of decompressive hemicraniectomy post-stroke. (shrink)

Russell's objections to object-theory have been refuted by the proofs of the consistency of Meinong's system given by various writers. These proofs exploit technical distinctions that Meinong apparently uses very little if at all. Instead, Meinong introduces a theoretical postulate called the modal moment. I describe this postulate and its place in Meinong's system, and I argue that it has been much under-rated by Meinong's logician expositors.

In "Remarks on the Foundations of Mathematics" Wittgenstein discusses an argument that goes from Gödel’s incompleteness result to the conclusion that some truths of mathematics are unprovable. Wittgenstein takes issue with this argument. Wittgenstein’s remarks in this connection have received very negative reaction from some very prominent people, for example, Gödel and Dummett. The paper is a defense of what Wittgenstein has to say about the argument in question.

Russell's objections to object-theory have been refuted by the proofs of the consistency of Meinong's system given by various writers. These proofs exploit technical distinctions that Meinong apparently uses very little if at all. Instead, Meinong introduces a theoretical postulate called the modal moment. I describe this postulate and its place in Meinong's system, and I argue that it has been much under-rated by Meinong's logician expositors.

Gilles de la Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterised by the presence of motor and vocal tics. Patients with malignant TS experience severe disease sequelae; risking morbidity and mortality due to tics, self-harm, psychiatric comorbidities and suicide. By definition, those cases termed ‘malignant’ are refractory to all conventional psychiatric and pharmacological regimens. In these instances, deep brain stimulation (DBS) may be efficacious. Current 2015 guidelines recommend a 6-month period absent of suicidal ideation before DBS is (...) offered to patients with TS. We therefore wondered whether it may be ethically justifiable to offer DBS to a minor with malignant TS. We begin with a discussion of non-maleficence and beneficence. New evidence suggests that suicide risk in young patients with TS has been underestimated. In turn, DBS may represent an invaluable opportunity for children with malignant TS to secure future safety, independence and fulfilment. Postponing treatment is associated with additional risks. Ultimately, we assert this unique risk-benefit calculus justifies offering DBS to paediatric patients with malignant TS. A multidisciplinary team of clinicians must determine whether DBS is in the best interest of their individual patients. We conclude with a suggestion for future TS-DBS guidelines regarding suicidal ideation. The importance of informed consent and assent is underscored. (shrink)