Maternal opioid use during pregnancy is a growing national problem and can lead to newborns developing neonatal opioid withdrawal syndrome soon after birth. Recent data demonstrates that nearly every 15 min a baby is born in the United States suffering from NOWS. The primary treatment for NOWS is opioid replacement therapy, commonly oral morphine, which has neurotoxic effects on the developing brain. There is an urgent need for non-opioid treatments for NOWS. Transcutaneous auricular neurostimulation, a novel and non-invasive form of (...) electrostimulation, may serve as a promising alternative to morphine. tAN is delivered via a multichannel earpiece electrode worn on and around the left ear, targeting two cranial nerves—the vagus and trigeminal nerves. Prior research suggests that auricular neurostimulation exerts an anxiolytic effect on the body by releasing endogenous opioids and reduces withdrawal symptoms in adults actively withdrawing from opioids. In this first-in-human prospective, open-label trial, we investigated tAN as an adjuvant to morphine therapy in eight infants >33 weeks gestational age suffering from NOWS and receiving oral morphine treatment. Infants received tAN for 30 min 1 h before receiving a morphine dose. tAN was delivered at 0.1 mA below perception intensity at two different nerve targets on the ear: Region 1, the auricular branch of the vagus nerve; and Region 2, the auriculotemporal nerve. tAN was delivered up to four times daily for a maximum of 12 days. The primary outcome measures were safety [heart rate monitoring, Neonatal Infant Pain Scale, and skin irritation] and morphine length of treatment. tAN was well-tolerated and resulted in no unanticipated adverse events. Comparing to the national average of 23 days, the average oral morphine LOT was 13.3 days and the average LOT after tAN initiation was 7 days. These preliminary data suggest that tAN is safe and may serve as a promising alternative adjuvant for treating NOWS and reducing the amount of time an infant receives oral morphine. (shrink)

Tackling impaired bioenergetics in multiple sclerosis has been recently recognized as an innovative approach with therapeutic potential. Guanidinoacetic acid is an experimental nutrient that plays a significant role in high-energy phosphate metabolism. The preliminary trials suggest beneficial effects of supplemental GAA in MS, with GAA augments biomarkers of brain energy metabolism and improves patient-reported features of the disease. GAA can also impact other metabolic footprints of MS, including demyelination, oxidative stress, and GABA-glutamate imbalance. In this mini-review article, we summarize studies (...) evaluating GAA effectiveness in MS, explore mechanisms of GAA action, and discuss the challenges of using dietary GAA as an element of MS therapy. (shrink)

This paper takes part in the ongoing debate on how emotions can be dealt with by argumentation theory. Its main goal is to formulate a relationship between emotion and argumentation which differs from that usually found in most of the literature on the subject. In the “standard” conception, emotions are seen as the objects of appeals which function as adjuvants to argumentation: speakers appeal to pity, fear, shame and the like in order to enhance the cogency of an argument (...) which bears on something else—whether it be the validity of a disputable opinion or the opportunity of a course of action. According to the “alternative” conception which I propose to consider, emotions themselves may be viewed, in some cases, as the very objects of argumentation. This conception lays emphasis on the arguability of emotions. Drawing on insights from current psychological and philosophical theories, it involves a reassessment of the Aristotelian concept of pathos, as well as an in-depth critical discussion of normative and descriptive approaches to emotional appeals. (shrink)

The goal of this short note is to expand the concepts of ‘pluralism’, ‘neutrosophy’, ‘refined neutrosophy’, ‘refined neutrosophic set’, ‘multineutrosophic set’, and ‘plithogeny’ (Smarandache 2002, 2013, 2017, 2019, 2021, 2023a, 2023b, 2023c), into a larger category that I will refer to as MultiAlism (or MultiPolar). As a straightforward generalization, I propose the conceptualization of a MultiPolar System (different from a PluriPolar System), which is formed not only by multiple elements that might be random, or contradictory, or adjuvant, but also by (...) accepting features from more than one basic system (UniPolar, BiPolar, TriPolar, or PluriPolar systems). PluriAlism is a closed dynamic system without neutralities nor indeterminacies, while MultiAlism is an open dynamic system with neutralities and indeterminacies. PluriAlism is a uni-system (formed by elements from a single system), while MultiAlism is a MultiSystem (formed by elements from many systems). (shrink)

Chapter 49 of the Han Feizi, entitled 'Wudu', includes one of the earliest discussions in Chinese history of the concepts of gong and si: Han Fei takes si to mean 'acting in one's own interest'. Gong is simply what opposes si. 'Acting in one's own interest' is not inherently reprehensible in Han Fei's view; but a ruler must remember why ministers propose their policies: they are concerned only with enriching themselves, and look upon the ruler as nothing more than a (...) resource to be exploited in their quest for material aggrandizement. The interests of the ministers and the ruler are diametrically opposed. Ministers hope for a comfortable career; a ruler must weed out the posers in his search for those rare and invaluable adjuvants who are genuinely capable of administering the state. In short, if si is the self-interest of the minister, gong is the self-interest of the ruler. (shrink)

The revelation that data obtained for the US-based National Surgical Adjuvant Breast and Bowel Project (NSABP) from subjects enrolled at Hôpital Saint-Luc in Montreal was falsified has eroded public trust in research. Institutions can educate researchers and help prevent unethical research practices by establishing procedures to monitor research involving human subjects. Research monitoring encompasses four categories of activity: annual reviews of continuing research, monitoring of informed consent, monitoring of adherence to approved protocols and monitoring of the integrity of data. The (...) authors describe characteristics of research projects that may call for monitoring procedures in each category. The form taken by such monitoring depends on the nature of the protocol. Although appropriate research monitoring requires substantial investment of personnel and financial resources, it is required under guidelines regulating research involving human subjects in Canada. Research monitoring is a step forward in re-establishing public confidence in medical research. (shrink)

We studied changes in eligibility criteria--the largest impediment to patient accrual--in two samples of clinical trials. Trials from the NSABP (National Surgical Adjuvant Breast and Bowel Program) and POG (Pediatric Oncology Group) were analyzed. After eliminating duplications, the criteria in each protocol were enumerated and classified according to a novel schema. NSABP trials contained significantly more criteria than POG trials, and added precision criteria (making study populations homogeneous) at a faster rate than POG studies. The difference between NSABP studies (explanatory (...) trials) and POG studies (pragmatic trials) suggest that large numbers of eligibility criteria are not necessary for quality studies. We recommend that: (1) the inclusion/exclusion criteria distinction be abandoned; (2) eligibility criteria be explicitly justified; (3) the need for each criterion be assessed when new trials are planned; (4) criteria in phase III trials restricting patient accrual be minimized; and (5) further research be done to assess the impact of criteria on generalizability. (shrink)

Two types of interleukin 1 (IL‐1α and IL‐1β) have been defined by purifying the molecules from activated human peripheral blood cells, followed by cloning and expressing the molecules in Escherichia coli. Both types of IL‐1 stimulate proliferation and differentiation of T‐ and B‐lymphocytes and induce cartilage proteoglycan degradation but differ in other properties. For example, demineralization and appears to be a major mediator in the pathogenesis of joint erosion in rheumatoid arthritis. Synthetic adjuvants elicit the production of IL‐1 separate (...) from endogenous pyrogen, and this property is required for the new generation of vaccines based on antigens produced by recombinant DNA technology. (shrink)

Rationale, aims and objectives: Appropriate use of diagnostic and treatment modalities are essential for rational use of resources. The aim of this study is to evaluate the use of diagnostic modalities and different treatment options and their economic impacts following an acute ankle distortion resulting from an occupational accident. We evaluated the type-of-treatment impact on the victims' course of recovery as well as its impact on the associated accident costs. Research was carried out in Belgium. Methods: An ankle distortion victims' (...) database consisting of 200 cases of (Belgian) occupational accidents during the period 2005-2007 was analysed. Results: Patients who were prescribed immobilization or the use of adjuvant support or physical therapy (118 cases) were not employed during a period of 37 days on average, with a mean total cost of 3140.14 Euros caused by the ankle sprain. Patients without any adjuvant therapy (82 cases) were characterized by an unemployment rate of 15 days on average, and a total cost of 1077.86 Euros. Cast immobilization, although its application is not supported by evidence-based literature, was still applied in 36% of the population studied and resulted in the longest average absence of work of 42 days with an obvious significant increase in medical and total costs. Conclusions: Our results show a high rate of inappropriate use of cast immobilizations for ankle distortions. From an economic point of view and for the same clinical endpoint (being full resumption of the occupational activities), simple conventional treatment, consisting of rest, ice, compression and elevation at diagnosis with allowance of early weight bearing in the further clinical course, leads to the quickest full resumption of activities in combination with the lowest medical costs, if compared with any other kind of treatment. (shrink)

Surgical resection of a primary tumour is often not sufficient to cure a patient. Even when no residual cancer can be detected at time of surgery, metastases may appear in the following years, which indicates that the primary tumour had apparently spread before surgery. Following surgery, systemic chemotherapy may be used to eradicate micro‐metastatic disease. Here we present two unconventional strategies that implement new insights into tumour biology and tumour immunology in the treatment of patients with cancer. Both experimental strategies (...) use the individual characteristics of the patient's primary tumour to optimise the control of life‐threatening micro‐metastases. We aim to modulate the patient's adaptive immune system, targeting it towards the patient's own tumour cells to eradicate residual disease following local treatment. In one approach, this is done by autologous tumour cell vaccinations as adjuvant treatment for colon cancer patients and, in a second approach, by giving chemo‐imunotherapy before local treatment to women with locally advanced breast cancer. BioEssays 25:79–86, 2003. © 2002 Wiley Periodicals, Inc. (shrink)

I will offer a conceptual analysis of different notions of structure and function of viral immunogens and of different structure-function relationships. My focus will then be on the mechanisms by which the desired immune response is induced and why strategies based on three-dimensional molecular antigen structures and their rational design are limited in their ability to induce the desired immunogenicity. I will look at the mechanisms of action of adjuvants (thus the wordplay with Janeway's "immunologist's dirty little secret"). Strategies (...) involving adjuvants and other (more successful) vaccination strategies rely on taking into account activities and functions ("what is going on"), and not just the structures involved ("who is there"), in binding in a "lock and key" fashion. Functional patterns as well as other organizational and temporal patterns, I will argue, are crucial for inducing the desired immune response and immunogenicity. The 3D structural approach by itself has its benefitsand its limits, which I want to highlight by this philosophical analysis, pointing out the importance of structure-function relationships. Different functional aspects such as antigenicity, immunogenicity, and immunity need to be kept separate and cannot be reduced to three-dimensional structures of vaccines. Taking into account different notions of structure and function and their relationships might thus advance our understanding of the immune system and rational HIV vaccine design, to which end philosophy can provide useful tools. (shrink)

The controversy over glyphosate-based herbicides, where there is extreme divergences in health and environmental assessments, is rooted in several methodological and normative factors. Foremost among them are the differences found in testing pure glyphosate compared to the testing of glyphosate formulations. The adjuvant chemicals found in formulations can be more toxic than the so-called “active ingredient.” Other factors can also account for why scientists reach different conclusions on the toxicological effects of GBH including the preconceptions and methodological choices they bring (...) into the study. Lack of consensus on the science can be problematic for policymakers. The paper argues that the toxicological science behind the GBH assessments is embedded in a normative substratum, which must be considered in policy decisions. (shrink)

Given the scarcity of educational materials (EM) to guide nutrition education strategies for phenilketonuric (PKU) patients, the goal of the present study was to develop and analyse the appearance and content validity of a EM directed to phenylketonuric children and their caregivers. The EM was evaluated by five professionals with expertise in the management of PKU. The material comprised 20 pages. All categories presented a satisfactory Index of Content Adequacy, meaning that the material was coherent, relevant and well structured. The (...) final Flesch Reading Ease Score index was 77. The ‘ABC of Phenyl’ Manual is appropriate and therefore suitable for use as an adjuvant in the management of phenylketonuria with pediatric patients. (shrink)

Bacterial lipopolysaccharide (LPS) and its active component, lipid A, have been used either alone or as adjuvant in therapeutic anticancer vaccines. Lipid A induces various transcription factors via intracellular signaling cascades initiated by their receptor CD14-TLR4. These events lead to the synthesis of cytokines, which either have direct cytotoxic effect or stimulate the immune system. Their antitumoral effect has been demonstrated in animal models as well as clinical trials. Studies in animal models showed that their antitumoral effect relies mostly on (...) the generation of an effective immune response. In humans, the antitumoral effect was correlated with an antibody response and cell-mediated cytotoxicity. So far, some encouraging results have been achieved in phase I and II clinical trials with regards to response and stabilization of the disease, but an expansion of the studies and trials is needed to find the best conditions for their clinical application. BioEssays 24:284–289, 2002. © 2002 Wiley Periodicals, Inc.; DOI 10.1002/bies.10053. (shrink)

In the presence of heterogeneity between the randomized controlled trial (RCT) participants and the target population, evaluating the treatment effect solely based on the RCT often leads to biased quantification of the real-world treatment effect. To address the problem of lack of generalizability for the treatment effect estimated by the RCT sample, we leverage observational studies with large samples that are representative of the target population. This article concerns evaluating treatment effects on survival outcomes for a target population and considers (...) a broad class of estimands that are functionals of treatment-specific survival functions, including differences in survival probability and restricted mean survival times. Motivated by two intuitive but distinct approaches, i.e., imputation based on survival outcome regression and weighting based on inverse probability of sampling, censoring, and treatment assignment, we propose a semiparametric estimator through the guidance of the efficient influence function. The proposed estimator is doubly robust in the sense that it is consistent for the target population estimands if either the survival model or the weighting model is correctly specified and is locally efficient when both are correct. In addition, as an alternative to parametric estimation, we employ the nonparametric method of sieves for flexible and robust estimation of the nuisance functions and show that the resulting estimator retains the root- n n consistency and efficiency, the so-called rate-double robustness. Simulation studies confirm the theoretical properties of the proposed estimator and show that it outperforms competitors. We apply the proposed method to estimate the effect of adjuvant chemotherapy on survival in patients with early-stage resected non-small cell lung cancer. (shrink)

Rationale Treatment guidelines recommend a more conservative surgical approach than mastectomy for early stage breast cancer and a stronger emphasis on adjuvant therapy. Registry data at South Australian teaching hospitals have been used to monitor survivals and treatment in relation to these guidelines.Aims and objectives To use registry data to: (1) investigate trends in survival and treatment; and (2) compare treatment with guidelines.Methods Registry data from three teaching hospitals were used to analyse trends in primary courses of treatment of breast (...) cancers during 1977–2003 (n = 4671), using univariate analyses and multiple logistic regression. Disease-specific survivals were analysed using Kaplan–Meier product limit estimates and multivariable Cox proportional hazards regression.Results The 5-year survival was 79.9%, but with a secular increase, reaching 83.6% in 1997–2003. The relative risk of death (95% confidence limits) was 0.74 (0.62, 0.88) for 1997–2003, compared with previous diagnoses, after adjusting for tumour node metastasis stage, grade, age and place of residence. Treatment changes included an increase in conservative surgery (as opposed to mastectomy) from 51.7% in 1977–1990 to 76.8% in 1997–2003 for stage I (P < 0.001) and from 31.1% to 52.2% across these periods for stage II (P < 0.001). Adjuvant radiotherapy also became more common (P < 0.001), with 20.6% of patients receiving this treatment in 1977–1990 compared with 60.7% in 1997–2003. Radiotherapy generally was more prevalent when conservative surgery was provided, although also relatively common in mastectomy patients when tumour diameters exceeded 50 mm or when there were four or more involved nodes. The proportion of patients receiving chemotherapy increased (P < 0.001), from 19.6% in 1977–1990 to 36.9% in 1997–2003, and the proportion having hormone therapy also increased (P < 0.001), from 34.3% to 59.4% between these periods.Conclusions Survivals appear to be increasing and treatment trends are broadly consistent with guideline directions, and the earlier research on which these recommendations were based. (shrink)

We discuss our surgical philosophy concerning the subtle interplay between the size of the surgical margin taken and the resultant morbidity from ablative oncological. procedures, which is ever more evident in the treatment of head and neck malignancy. The extent of tissue resection is determined by the "trade off" between cancer control and the perioperative, functional and aesthetic morbidity and mortality of the surgery. We also discuss our dilemmas concerning recent minimally invasive endoscopic microsurgical. techniques for the trans-oral laser removal. (...) or co-ablation of aero-digestive tract tumours, which result in a minimal. surgical margin of oncological clearance. By a process of inductive argument as to the nature of the surgical margin, we consider whether the risks of taking a lesser margin with adjuvant therapy is justified by the attendant gain in reduced surgical morbidity and the possible costs in tumour control. (c) 2006 Elsevier Ltd. All rights reserved. (shrink)

Introduction: Advantageous effects of biological motion detection, a low-perceptual mechanism that allows the rapid recognition and understanding of spatiotemporal characteristics of movement via salient kinematics information, can be amplified when combined with motor imagery, i.e., the mental simulation of motor acts. According to Jeannerod’s neurostimulation theory, asynchronous firing and reduction of mu and beta rhythm oscillations, referred to as suppression over the sensorimotor area, are sensitive to both MI and action observation of BM. Yet, not many studies investigated the use (...) of BM stimuli using combined AO-MI tasks. In this study, we assessed the neural response in the form of event-related synchronization and desynchronization patterns following the observation of point-light-walkers and concordant MI, as compared to MI alone.Methods: Twenty right-handed healthy participants accomplished the experimental task by observing BM stimuli and subsequently performing the same movement using kinesthetic MI. We recorded an electroencephalogram with 32 channels and performed time-frequency analysis on alpha and beta frequency bands during the MI task. A two-way repeated-measures ANOVA was performed to test statistical significance among conditions and electrodes of interest.Results: The results revealed significant ERD/S patterns in the alpha frequency band between conditions and electrode positions. Post hoc comparisons showed significant differences between condition 1 and condition 3 over the left primary motor cortex. For the beta band, a significantly less difference in ERD patterns was detected only between condition 3 and condition 4.Discussion: Our results confirmed that the observation of BM combined with MI elicits a neural suppression, although just in the case of jumping. This is in line with previous findings of AO and MI eliciting a neural suppression for simulated whole-body movements. In the last years, increasing evidence started to support the integration of AOMI training as an adjuvant neurorehabilitation tool in Parkinson’s disease.Conclusion: We concluded that using BM stimuli in AOMI training could be promising, as it promotes attention to kinematic features and imitative motor learning. (shrink)

Objective: To review the principles and practice of the use of conscious sedation for IVF.Design: The pertinent literature was reviewed and recommendations are provided.Result(s): Conscious sedation appears to be the most commonly used method of pain relief for transvaginal retrieval of oocytes. Conscious sedation does not require the presence of an anesthesiologist and can be done in freestanding clinics. Agents commonly used include opioids in combination with benzodiazepines. This combination minimizes pain, decreases anxiety, and provides sedation and some amnesia (...) class='Hi'>Adjuvants such as promethazine and hydroxyzine can also be used but often are not needed. Conscious sedation is well tolerated by patients and does not require highly specialized equipment. However, there are specific safeguards that should be followed. Only a few toxicity studies have been performed, but they are reassuring because they have not found significant effects on fertilization or cleavage.Conclusion(s): Conscious sedation appears to be a safe and cost-effective method of providing analgesia and anesthesia for transvaginal retrieval of oocytes. (shrink)

Biomedical ethics requires that clinical trial participants be accurately informed of the potential risks associated with investigational medical products. We found that the vaccine manufacturer Merck made false statements to the trial participants about the safety of Gardasil in its Future II HPV vaccine trial in Denmark. The clinical study protocol specified that safety testing was one of the trial’s primary objectives, but the recruitment brochure given to trial participants stated this was not the case, as allegedly the vaccine had (...) already been proven safe in previous trials. The advertising material for the trial and the informed consent forms stated that the comparator was saline or an inactive substance, when, in fact, it contained Merck’s proprietary aluminum adjuvant which is highly immunogenic. Several trial participants experienced long-term disabling symptoms during the trial, also some randomized to the adjuvant “placebo” control group. In all cases, their serious adverse events were dismissed as unrelated to the study treatment by Merck’s clinical investigators. We demonstrate that Merck’s published statements about the safety of their proprietary aluminum adjuvant is contradicted by the research evidence. The use of adjuvants as “placebos” in vaccine clinical trials is unethical as it makes it difficult to discover serious vaccine harms. (shrink)

Dans les Esquisses pyrrhoniennes, Sextus Empiricus entreprend de réfuter le sunèmmenon, qui correspond en logique à notre « implication ». Sa réfutation procède circulairement, chacun des quatre critères proposés se voyant réfuté par le critère qui lui succède, de sorte que la dernière réfutation marque implicitement le retour à la première. Une telle situation est exemplaire parce qu’elle trouve un étrange écho dans la controverse qui oppose les logiciens du xx e siècle : savoir si la conséquence logique peut être (...) réduite à la validité du conditionnel matériel ou si elle n’exige pas plutôt ce que les logiciens appellent la « pertinence ». Envisagée dans cette perspective, la batterie des réfutations sceptiques se réduit au rôle d’adjuvant dans une controverse qui la dépasse, comme si la logique elle-même devenait sceptique lorsqu’elle se heurte à une aporie constitutive. (shrink)

There is an increasing emphasis on clear disclosure of conflict of interest in medical communities, following repeated scientific frauds in clinical trials. However, incomplete COI statements continue to be prevalent in the medical community, as appears to have occurred in the Capecitabine for Residual Cancer as Adjuvant Therapy trial, which was recently published in the New England Journal of Medicine. The authors of the article did not clearly report the roles of the Japan Breast Cancer Research Group, a sponsor and (...) funder of the study, although a majority of the Japanese authors served in important positions in the organization. Furthermore, the conflict of interest related to Chugai Pharmaceutical Company, a Japanese distributor of capecitabine, was not correctly disclosed. More transparent statements of conflict of interest and clarification of sponsors and funders’ roles, as well as rigorous review by academic journals are required to fairly interpret the findings of clinical trials, including and beyond the single case of the CREATE-X trial. (shrink)

Cet article propose l’analyse de quelques chapitres du Monologion d’Anselme de Canterbury (1033-1109) qui traitent de la création ex nihilo. L’auteur y démontre que le Dieu créateur est une cause uniquement efficiente, et non matérielle, de sa création ; il n’y a donc pas de cause autre qu’efficiente au passage du non-être à l’être, le devenir n’a pas de cause matérielle. La création n’est pas un engendrement, ni l’action conjointe de deux principes (la puissance et la matière, par exemple), mais (...) l’acte efficient d’un être qui n’a besoin d’aucune autre cause que lui-même pour créer son autre. La théorie anselmienne de la création est ensuite située dans l’histoire générale de la causalité ; ignorant la quadripartition aristotélicienne des causes, Anselme développe, pour les besoins de la compréhension théologique, une théorie binaire fondée sur l’efficience et ses adjuvants. Or il semble que cette conception de la causalité puisse trouver sa source dans le stoïcisme cicéronien. Par ailleurs, elle a pu elle-même constituer un modèle ontologique pour la conception mécaniste de la cause à l’âge classique, en définissant la cause comme ce qui est au principe de l’existence de l’effet, plutôt qu’un principe explicatif formel ou final. (shrink)

This article discusses how existential phenomenology may serve as a frame in a mixed‐methods study of changes in weight and body composition among women in adjuvant treatment for breast cancer. In accordance with ontologically and epistemologically fundamental assumptions in nursing, we link mixed‐methods and existential phenomenology from the perspective of the French philosopher Maurice Merleau‐Ponty and his notion of a unified body subject. Letting this perspective permeate our philosophy, methodology and issues at the method level in mixed‐method research undermines the (...) distinction between first‐ and third‐person perspective when applying and integrating different data sources in a mixed‐methods study. Applying Merleau‐Ponty's third way, the women's bodily experiences appear as gestalt; a ‘figure’ against a ground of existential threats that are grasped through insight from data integrating in joint displays, which revealed the women's experiences on a deep existential level. Existential phenomenology as a frame in mixed‐method studies can speak not only to nurses but also to a multidisciplinary audience in a shared attempt to deepen the understanding of a patient's healthcare problem. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Moral Distress in Academic Medicine: My Brother’s Keeper?Lauren B. SmithAs a member of the hospital ethics committee, I’ve become the go–to person for any ethical issues that arise in our Department. Being a pathologist who is interested in ethics, I’m a rare bird. In this role, I get the occasional curbside consult when anyone has a question or concern. Shortly after an ethics lecture to our trainees, one of (...) the junior residents approached me and asked to speak privately. We headed to the cafeteria and found a private table where we could talk. She hesitated, running her fingers through her hair and gazing around the room before speaking.She told me that the trainees were concerned because they had noticed that the pathologists at another institution were not grading one type of cancer the way that they had learned to do this at our hospital. This type of cancer grading is a surrogate for aggressiveness, and, while somewhat flawed, it often determines the staging and adjuvant therapy that the patient will receive. The resident argued that at this hospital, patients were getting assigned cancer grades that were higher than the ones they would receive at our institution. Therefore, a cancer presenting at the other hospital would be considered more aggressive by the clinicians treating the patient.The resident and many of her colleagues had tried to broach this subject with the pathologists. [End Page E18] Many had been brave enough to voice their confusion and concern over the practices. Their efforts, she explained, had been rebuffed. The pathologists assured the residents that they were grading their cases correctly and cited a reference that they used for this purpose. Due to the hierarchical nature of medicine, it is understandably difficult for trainees to confront attending physicians when they have concerns about their clinical cases and diagnostic acumen. Residents and fellows often do not express their concerns for fear of overstepping their roles. In spite of this, many trainees felt that their concerns for the patient made them set aside their own best interest and they spoke up. Moral distress and genuine concern trumped self–interest in this case, which was admirable.At the time of our meeting, I wondered what I could do to help. I am a hematopathologist who specializes in diagnosing leukemias and lymphomas. I know very little about solid tumor diagnosis and treatment. I have not looked at many solid tumors since I was a trainee six years ago. I do not read the literature in that area and I’m not up–to–date on any controversies regarding grading. In summary, I am far from an expert.However, the problem, on a broader scale, was familiar. As pathologists, we may disagree with or question the diagnoses of our colleagues. What is the appropriate course of action when this occurs? This question is an interesting and infinitely complex issue in the realm of pathological diagnosis. If you aren’t a pathologist or a physician, it may be difficult to grasp why there isn’t a right answer in every case. Diagnosing cancer, in many ways, is truly an art as much as a science. Many intersecting variables are at play, including the size and quality of the sample, the experience and training of the pathologist, and the clinical information available at the time of the diagnosis. Some areas are fraught with subjectivity and inter–observer reliability. Some pathologists are more skilled than others. These are realities that no one wishes to freely admit.It is important, however, to differentiate between systematic and random errors. There are many errors that are difficult to predict or avoid. However, systematic errors are the ones that we most want to uncover as they can be fixed with education and awareness. This case appeared to represent a systematic error in which the pathologists at the other hospital were all performing grading in a way that differed from usual practice.I wondered if it would be overstepping my role to speak to the pathologists. I ran the situation by some of the senior pathologists that I know. Many understood my concern but subtly discouraged any action. Many felt... (shrink)

Est-ce bien la nature elle-même qui doit être comprise comme la cause proprement productrice des corps naturels et de leurs changements, ou bien le régime de production dévolu à la causalité naturelle n’est-il qu’un adjuvant : l’instrument par lequel agit une causalité d’un tout autre ordre? Dans le monumental Commentaire à la Physique d’Aristote que rédigea vers 540 le néoplatonicien Simplicius de Cilicie, cette question gouverne la partie consacrée aux trois premiers chapitres du livre II....

... We will turn our attention to the current state of pain relief technology and the ethical questions surrounding the use of advanced technology, otherwise referred to as "high-tech," pain relief. It is obvious that pain may decrease the quality of life for cancer patients. The availability of long-acting narcotics, such as MS Contin or methadone, affords cancer patients long-duration pain relief at minimal cost. The use of adjuvant medications may also be important. Clinical examples of the effective use of (...) adjuvant medications include the addition of a nonsteroidal, anti-inflammatory agent to help patients cope with bone pain and the use of a serotonin blocking agent to reduce the transmission of pain impulses in the spinal cord. Only a small percentage of patients are good candidates for high-tech delivery systems for narcotic administration. In our pain management clinic, all patients are initially placed on oral medications. When the side effects of oral medications become excessive, or the patient becomes unable to take oral medications, high-tech modalities are considered for use. (shrink)