From empathy to caring: defining the ideal approach to a healing relationship

In recent years, “empathy” has been identified as a form of emotional engagement beneficial to patient care. Although usage varies, the term refers to sharing the feelings of another as a means of coming to a direct appreciation of the other. Defined this way, however, empathy may lead to mistaken assumptions and an absence of corrective curiosity: Once we think we understand what another is experiencing, we perceive less need to ask, listen, and learn. We propose the process of “caring” in place of “empathy” to embody the ideal emotional and behavioral approach to patient care. Caring refers to both an emotional reaction to another and the expression of that reaction in action, independent of the sharing of the other’s emotion or experience. The expression of caring in the clinical context is close observation, precise listening, and responsive questioning, in concert with committed engagement and actions directly addressing the patient’s problem, stripped of any assumptions about what the other might or might not be experiencing.     

THE USE OF ANTABUS IN THE THERAPY OF ALCOHOLIC PATIENTS

Preliminary studies on the effects of antabus (tetraethylthiuram disulfide) in the therapy of alcoholic patients indicate that it is very valuable in providing a “chemical foundation” for sobriety, even in those with a severe, long term drinking problem. In the first 30 patients treated, a favorable degree of control of the alcoholism has been effected in approximately 80 per cent. When taken regularly the drug maintains in the patient a very high degree of sensitivity to alcohol, quickly producing a number of very distressing bodily reactions whenever even very small amounts of spirits are ingested. Because of its potential dangers, antabus should be used only after thorough clinical and laboratory studies in properly staffed institutions. It is contraindicated in individuals with existing major psychosis or drug addiction and must be used only with caution in patients with diabetes mellitus, cardiovascular disease, goiter, pregnancy, epilepsy, asthma, and hepatic disease. Antabus therapy should be considered only one aspect of the total treatment program for the alcoholic patient.     

An “elite hacker”: Breast tumors exploit the normal microenvironment program to instruct their progression and biological diversity

The year 2011 marked the 40 year anniversary of Richard Nixon signing the National Cancer Act, thus declaring the beginning of the “War on Cancer” in the United States. Whereas we have made tremendous progress toward understanding the genetics of tumors in the past four decades, and in developing enabling technology to dissect the molecular underpinnings of cancer at unprecedented resolution, it is only recently that the important role of the stromal microenvironment has been studied in detail. Cancer is a tissue-specific disease, and it is becoming clear that much of what we know about breast cancer progression parallels the biology of the normal breast differentiation, of which there is still much to learn. In particular, the normal breast and breast tumors share molecular, cellular, systemic and microenvironmental influences necessary for their progression. It is therefore enticing to consider a tumor to be a “rogue hacker”—one who exploits the weaknesses of a normal program for personal benefit. Understanding normal mammary gland biology and its “security vulnerabilities” may thus leave us better equipped to target breast cancer. In this review, we will provide a brief overview of the heterotypic cellular and molecular interactions within the microenvironment of the developing mammary gland that are necessary for functional differentiation, provide evidence suggesting that similar biology—albeit imbalanced and exaggerated—is observed in breast cancer progression particularly during the transition from carcinoma in situ to invasive disease. Lastly we will present evidence suggesting that the multigene signatures currently used to model cancer heterogeneity and clinical outcome largely reflect signaling from a heterogeneous microenvironment—a recurring theme that could potentially be exploited therapeutically.     

Thyroid Nodules and Thyroid Cancer

A review of clinical and laboratory features of thyroid cancer, designed to help in a more precise selection of patients for operation, showed that factors contributing to a high index of suspicion of cancer include previous exposure to low doses of radiation, the presence of a firm, solitary thyroid nodule clearly different from the rest of the gland, a young patient, nodules that are “cold” on scan with radioiodine, and nodules that fail to regress after an adequate trial of thyroxine therapy. Factors contributing to a low index of suspicion of thyroid cancer include soft or cystic lesions, multinodular goiters, nodules that are “hot” on ¹³¹ I scan, and those that regress during thyroxine treatment.When these factors are used to select patients for surgical operation, about 30 percent are found to have thyroid cancer.Until more precise methods for preoperative diagnosis are established, it is suggested that this type of clinical selection may be very helpful in the management of patients with thyroid nodules or nontoxic goiter.     

Selecting Essential Information for Biosurveillance—A Multi-Criteria Decision Analysis

The National Strategy for Biosurveillancedefines biosurveillance as “the process of gathering, integrating, interpreting, and communicating essential information related to all-hazards threats or disease activity affecting human, animal, or plant health to achieve early detection and warning, contribute to overall situational awareness of the health aspects of an incident, and to enable better decision-making at all levels.” However, the strategy does not specify how “essential information” is to be identified and integrated into the current biosurveillance enterprise, or what the metrics qualify information as being “essential”. Thequestion of data stream identification and selection requires a structured methodology that can systematically evaluate the tradeoffs between the many criteria that need to be taken in account. Multi-Attribute Utility Theory, a type of multi-criteria decision analysis, can provide a well-defined, structured approach that can offer solutions to this problem. While the use of Multi-Attribute Utility Theoryas a practical method to apply formal scientific decision theoretical approaches to complex, multi-criteria problems has been demonstrated in a variety of fields, this method has never been applied to decision support in biosurveillance.We have developed a formalized decision support analytic framework that can facilitate identification of “essential information” for use in biosurveillance systems or processes and we offer this framework to the global BSV community as a tool for optimizing the BSV enterprise. To demonstrate utility, we applied the framework to the problem of evaluating data streams for use in an integrated global infectious disease surveillance system.     

Prioritizing Disease Candidate Proteins in Cardiomyopathy-Specific Protein-Protein Interaction Networks Based on “Guilt by Association” Analysis

The cardiomyopathies are a group of heart muscle diseases which can be inherited (familial). Identifying potential disease-related proteins is important to understand mechanisms of cardiomyopathies. Experimental identification of cardiomyophthies is costly and labour-intensive. In contrast, bioinformatics approach has a competitive advantage over experimental method. Based on “guilt by association” analysis, we prioritized candidate proteins involving in human cardiomyopathies. We first built weighted human cardiomyopathy-specific protein-protein interaction networks for three subtypes of cardiomyopathies using the known disease proteins from Online Mendelian Inheritance in Man as seeds. We then developed a method in prioritizing disease candidate proteins to rank candidate proteins in the network based on “guilt by association” analysis. It was found that most candidate proteins with high scores shared disease-related pathways with disease seed proteins. These top ranked candidate proteins were related with the corresponding disease subtypes, and were potential disease-related proteins. Cross-validation and comparison with other methods indicated that our approach could be used for the identification of potentially novel disease proteins, which may provide insights into cardiomyopathy-related mechanisms in a more comprehensive and integrated way.     

Experiences of Community-Living Older Adults Receiving Integrated Care Based on the Chronic Care Model: A Qualitative Study

BackgroundIntegrated care models aim to solve the problem of fragmented and poorly coordinated care in current healthcare systems. These models aim to be patient-centered by providing continuous and coordinated care and by considering the needs and preferences of patients. The objective of this study was to evaluate the opinions and experiences of community-living older adults with regard to integrated care and support, along with the extent to which it meets their health and social needs.MethodsSemi-structured interviews were conducted with 23 older adults receiving integrated care and support through “Embrace,” an integrated care model for community-living older adults that is based on the Chronic Care Model and a population health management model. Embrace is currently fully operational in the northern region of the Netherlands. Data analysis was based on the grounded theory approach.ResultsResponses of participants concerned two focus areas: 1) Experiences with aging, with the themes “Struggling with health,” “Increasing dependency,” “Decreasing social interaction,” “Loss of control,” and “Fears;” and 2) Experiences with Embrace, with the themes “Relationship with the case manager,” “Interactions,” and “Feeling in control, safe, and secure”. The prospect of becoming dependent and losing control was a key concept in the lives of the older adults interviewed. Embrace reinforced the participants’ ability to stay in control, even if they were dependent on others. Furthermore, participants felt safe and secure, in contrast to the fears of increasing dependency within the standard care system.ConclusionThe results indicate that integrated care and support provided through Embrace met the health and social needs of older adults, who were coping with the consequences of aging.     

CYTOLOGIC DETECTION OF CERVICAL CANCER—Four Years' Experience with Routine Smear Examination in Private Practice

Simplified Papanicolaou smear techniques appear to be adaptable to private clinical practice when experienced cytodetection laboratory facilities are available. A private physician''s office seems potentially an efficient, economical and practical place for detection of cervical cancer by use of the smear technique as a routine part of examination of patients.In a series here reported upon, examination of 11,207 cervical smears taken at the first examination of patients of all ages led to diagnosis of unsuspected malignant disease in 80 cases—in all instances at a stage when it should be easily curable. Cancer was not detected in examination of 6,060 smears taken later from women who had had a “negative” smear at the time of first examination, which seems to indicate that the first screening was reasonably accurate.In a few cases, early cancer was detected when smears were reported as “atypical” or “suspicious.” Such reports demand as careful follow-up as do “positive” reports.There are dangers and limitations in wide-spread clinical application of screening by this method. Care must be observed in the development of programs for its use lest the potential benefits in early detection be outweighed by the dangers from misuse.     

Molecular Diagnostics of Fine Needle Aspiration for the Presurgical Screening of Thyroid Nodules

“The incidence of thyroid cancer, the most common endocrine malignancy, is rising. The two most common types of thyroid cancer are papillary and follicular” thyroid carcinomas. “Fine-needle aspiration (FNA) of thyroid nodules” can permit to detect many genetic mutations and other molecular alterations, including RAS and BRAF point mutations, PAX8/peroxisome proliferator-activated receptor (PPAR)γ and “RET/PTC rearrangements, occurring in thyroid papillary and follicular carcinomas” (more than 70% of cases), which can be used successfully to improve the diagnosis “and the management of patients with thyroid nodules”. The most extensive experience has been accumulated with “the diagnostic use of BRAF mutation”, which is highly specific for malignancy. “Testing FNA samples for a panel of mutations” that typically includes RAS, BRAF, PAX8/PPARγ and RET/PTC could permit to achieve the biggest diagnostic impact. “The accuracy of cancer diagnosis in thyroid nodules could be improved significantly using these and other emerging molecular markers”.     

Quantitative Risk Stratification of Oral Leukoplakia with Exfoliative Cytology

Exfoliative cytology has been widely used for early diagnosis of oral squamous cell carcinoma (OSCC). Test outcome is reported as “negative”, “atypical” (defined as abnormal epithelial changes of uncertain diagnostic significance), and “positive” (defined as definitive cellular evidence of epithelial dysplasia or carcinoma). The major challenge is how to properly manage the “atypical” patients in order to diagnose OSCC early and prevent OSCC. In this study, we collected exfoliative cytology data, histopathology data, and clinical data of normal subjects (n=102), oral leukoplakia (OLK) patients (n=82), and OSCC patients (n=93), and developed a data analysis procedure for quantitative risk stratification of OLK patients. This procedure involving a step called expert-guided data transformation and reconstruction (EdTAR) which allows automatic data processing and reconstruction and reveals informative signals for subsequent risk stratification. Modern machine learning techniques were utilized to build statistical prediction models on the reconstructed data. Among the several models tested using resampling methods for parameter pruning and performance evaluation, Support Vector Machine (SVM) was found to be optimal with a high sensitivity (median>0.98) and specificity (median>0.99). With the SVM model, we constructed an oral cancer risk index (OCRI) which may potentially guide clinical follow-up of OLK patients. One OLK patient with an initial OCRI of 0.88 developed OSCC after 40 months of follow-up. In conclusion, we have developed a statistical method for qualitative risk stratification of OLK patients. This method may potentially improve cost-effectiveness of clinical follow-up of OLK patients, and help design clinical chemoprevention trial for high-risk populations.     

The Mitochondrial Unfoldase-Peptidase Complex ClpXP Controls Bioenergetics Stress and Metastasis

Mitochondria must buffer the risk of proteotoxic stress to preserve bioenergetics, but the role of these mechanisms in disease is poorly understood. Using a proteomics screen, we now show that the mitochondrial unfoldase-peptidase complex ClpXP associates with the oncoprotein survivin and the respiratory chain Complex II subunit succinate dehydrogenase B (SDHB) in mitochondria of tumor cells. Knockdown of ClpXP subunits ClpP or ClpX induces the accumulation of misfolded SDHB, impairing oxidative phosphorylation and ATP production while activating “stress” signals of 5′ adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and autophagy. Deregulated mitochondrial respiration induced by ClpXP targeting causes oxidative stress, which in turn reduces tumor cell proliferation, suppresses cell motility, and abolishes metastatic dissemination in vivo. ClpP is universally overexpressed in primary and metastatic human cancer, correlating with shortened patient survival. Therefore, tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. This pathway may provide a “drugable” therapeutic target in cancer.     

Using the “reverse Warburg effect” to identify high-risk breast cancer patients: Stromal MCT4 predicts poor clinical outcome in triple-negative breast cancers

We have recently proposed a new model of cancer metabolism to explain the role of aerobic glycolysis and L-lactate production in fueling tumor growth and metastasis. In this model, cancer cells secrete hydrogen peroxide (H₂O₂), initiating oxidative stress and aerobic glycolysis in the tumor stroma. This, in turn, drives L-lactate secretion from cancer-associated fibroblasts. Secreted L-lactate then fuels oxidative mitochondrial metabolism (OXPHOS) in epithelial cancer cells, by acting as a paracrine onco-metabolite. We have previously termed this type of two-compartment tumor metabolism the “reverse Warburg effect,” as aerobic glycolysis takes place in stromal fibroblasts, rather than epithelial cancer cells. Here, we used MCT4 immunostaining of human breast cancer tissue microarrays (TMAs; >180 triple-negative patients) to directly assess the prognostic value of the “reverse Warburg effect.” MCT4 expression is a functional marker of hypoxia, oxidative stress, aerobic glycolysis and L-lactate efflux. Remarkably, high stromal MCT4 levels (score = 2) were specifically associated with decreased overall survival (<18% survival at 10 years post-diagnosis). In contrast, patients with absent stromal MCT4 expression (score = 0), had 10-year survival rates of ∼97% (p-value < 10⁻³²). High stromal levels of MCT4 were strictly correlated with a loss of stromal Cav-1 (p-value < 10⁻¹⁴), a known marker of early tumor recurrence and metastasis. In fact, the combined use of stromal Cav-1 and stromal MCT4 allowed us to more precisely identify high-risk triple-negative breast cancer patients, consistent with the goal of individualized risk-assessment and personalized cancer treatment. However, epithelial MCT4 staining had no prognostic value, indicating that the “conventional” Warburg effect does not predict clinical outcome. Thus, the “reverse Warburg effect” or “parasitic” energy-transfer is a key determinant of poor overall patient survival. As MCT4 is a druggable target, MCT4 inhibitors should be developed for the treatment of aggressive breast cancers, and possibly other types of human cancers. Similarly, we discuss how stromal MCT4 could be used as a biomarker for identifying high-risk cancer patients that could likely benefit from treatment with FDA-approved drugs or existing MCT-inhibitors (such as, AR-C155858, AR-C117977 and AZD-3965).Key words: caveolin-1, oxidative stress, pseudohypoxia, lactate shuttle, MCT4, metabolic coupling, tumor stroma, predictive biomarker, SLC16A3, monocarboxylic acid transporter, two-compartment tumor metabolism     

Unlocking Patients with Mental Disorders Who Were in Restraints at Home: A National Follow-Up Study of China’s New Public Mental Health Initiatives

Background

In 2005, China implemented a demonstration program known as “686” to scale-up nation-wide basic mental health services designed to improve access to evidence-based care and to promote human rights for people with severe mental disorders. As part of the 686 Program, teams “unlocked” and provided continuous mental health care to people with severe mental disorders who were found in restraints and largely untreated in their family homes. We implemented a nation-wide two-stage follow-up study to measure the effectiveness and sustainability of the “unlocking and treatment” intervention and its impact on the well-being of patients’ families.

Methods

266 patients unlocked from 2005 in “686” demonstration sites across China were recruited in Stage One of the study in 2009. In 2012, 230 of the 266 cases were re-interviewed (the Stage Two study). Outcome measures included the patient medication adherence and social functioning, family burden ratings, and relocking rate. We utilized pre-post tests to analyze the changes over time following the unlocking efforts.

Results

96% of patients were diagnosed with schizophrenia. Prior to unlocking, their total time locked ranged from two weeks to 28 years, with 32% having been locked multiple times. The number of persons regularly taking medicines increased from one person at the time of unlocking to 74% in 2009 and 76% in 2012. Pre-post tests showed sustained improvement in patient social functioning and significant reductions in family burden. Over 92% of patients remained free of restraints in 2012.

Conclusion

Practice-based evidence from our study suggests an important model for protecting the human rights of people with mental disorders and keeping them free of restraints can be achieved by providing accessible, community based mental health services with continuity of care. China’s “686” Program can inform similar efforts in low-resource settings where community locking of patients is practiced.     

2009 Society for Medical Anthropology Conference: Training,Communication, and Competence: The Making of Health Care Professionals

The role of medical anthropology in tackling the problems and challenges at the intersections of public health, medicine, and technology was addressed during the 2009 Society for Medical Anthropology Conference at Yale University in an interdisciplinary panel session entitled Training, Communication, and Competence: The Making of Health Care Professionals.The discipline of medical anthropology is not very formalized in the health setting. Although medical anthropologists work across a number of health organizations, including schools of public health, at the Centers for Disease Control (CDC), and at non-governmental organizations (NGOs), there is an emerging demand for an influential applied medical anthropology that contributes both pragmatically and theoretically to the health care field.The role of anthropology at the intersections of public health, medicine, and technology was addressed during the 2009 Society for Medical Anthropology Conference at Yale University in September. In a conference session entitled Training, Communication, and Competence: The Making of Health Care Professionals, health professional career issues, including training and education, medical entrepreneurship, and the maintenance of clinical relationships with patients were examined. The presentations encompassed macro approaches to institutional reform in training, education, and health care delivery, as well as micro studies of practitioner-patient interaction. Seemingly disparate methodological, disciplinary, and theoretical orientations were united to assess the increasing relevance of medically oriented anthropology in addressing the challenges of health care delivery, health education, and training.Margaret Bentley, a professor of public health at the University of North Carolina, Chapel Hill, spoke about the increasing “epidemic of global health” in universities, noting a doubling of global health majors within the past three years. Despite this expansion of the field, a common discipline of global health continues to be developed. In September, the Association of Schools of Public Health (ASPH) and the University of Minnesota hosted a Global Health Core Competency Development Consensus Conference with the initiative to explore “workforce needs, practice settings, and to identify core constructs, competency domains, and a preliminary global health competency model”¹. Given the current variability in training, Bentley believes medical anthropology is uniquely suited to inform training in global health because of its offerings in the way of interdisciplinary methods and team-based applied field experience.Anthropologists Carl Kendall of Tulane University and Laetitia Atlani of Université de Paris X Nanterre have seen medical anthropologists examine models of health strictly within a clinical experience. Understanding of the social determinants of epidemiology, methodological issues of population health, and survey research is crucial. However, training individuals through a more formalized program (currently in development in Europe) will allow anthropologists to better understand context, explain complex models, humanize aggregate statistics, and articulate methods of the multidimensional “social field” of health outside of the clinical experience.The social field of health, however, as Robert Like of the University of Medicine and Dentistry of New Jersey explained, shares an uncomfortable interface with clinical medicine. Recent efforts by the New Jersey Board of Examiners to incorporate cultural competency legislation have been robustly criticized. Evaluations of six-hour training sessions on cultural competency training have revealed health professionals’ frustration with the health care system’s inability to deal with “culturally different” individuals. In fact, the majority of health professionals who were required to complete the training believe cultural competency to be an area of study that is a “waste of time.”This opposition to cross-cultural education and the value of “cultural competence” training also has been a topic of great debate among anthropologists and health researchers. Despite the ubiquitous use of the term among research and health professionals, cultural competency is a term that cannot be defined precisely enough to operationalize.In “Anthropology in the Clinic: The Problem of Cultural Competency and How to Fix It,” Arthur Kleinman and Peter Benson asserted that the static notion of culture in the medical field “suggests that a culture can be reduced to a technical skill for which clinicians can be trained to develop expertise” [1]. T.S. Harvey, a linguistic and medical anthropologist at the University of California, Riverside, expounded on Kleinman’s opposition to competence as an acquired “technical skill” [1] and suggested reconceptualizing the approach to competence as communication. Although Kleinman’s explanatory models approach [2] provides a health care professional with what to ask the patient, Harvey pulls from Dell Hymes’ communicative competence [3] to understand how to ask it. Harvey recommended viewing competence as a “sociolinguistic acquisition … like a foreign language” where competencies are rule-governed and communication and speech events are formulaic.Harvey also noted that the “onus of cultural competency” is too often placed on the practitioner. Inevitably, there is an asymmetry in every clinical encounter, whereby the “would-be patient” is perpetually considered the “passive receptor.” Patients also share a stake in their health and, as such, should be taught communicative competence as well.Harvey also noted that the “onus of cultural competency” is too often placed on the practitioner. Inevitably, there is an asymmetry in every clinical encounter, whereby the “would-be patient” is perpetually considered the “passive receptor.” Patients also share a stake in their health and, as such, should be taught communicative competence as well.The role of the patient is made ever more complex by the power relationship that exists in the patient-provider context. Through ethnographic research, Sylvie Fainzang, director of research in the Inserm (Cermes), examines how doctors and patients lie. She argues that lying, in the context of secrecy, is an indication of a power relationship [4]. Fainzaing’s further research on the relationship between doctors and patients has yielded additional information on how patients learn about their diagnoses and how they will react to these diagnoses. Though a clinical encounter between a doctor and patient is expected to be one of informed consent, doctors often judge patients upon their ability to “intellectually understand” [4] and assess who is “psychologically ready” [4] to bear the information. This leads to manipulated, misinformed, and “resigned consent” [4]. This sort of social training of obligation of a subject to medical authority provides the patient with the choice either to conform or overthrow the rules as defined by society.Collectively, this interdisciplinary panel worked to inform the discussion on how medical anthropology can address training, communication, and competence at the intersections of medicine, public health, and education. By reviewing health professionals’ growing interest in public health, training in health education and competence, and the patient-provider relationship, medical anthropology can be seen as both relevant and necessary to addressing the challenges faced by the medical and health community today.     

THE MANAGEMENT OF CANCER OF THE BREAST

Radical mastectomy is excellent only for cases of operable breast cancer in which the tumor is limited to the breast or to the nodes in the axilla. That there is metastasis to the internal mammary lymph nodes in a high proportion of cases has been “overlooked” for many years. Also it is probable that metastasis occurs to the supraclavicular lymph nodes more often than is suspected. Hence the extended radical mastectomy operation leaves much to be desired. There has been no significant improvement in recent years in the mortality rate of mammary cancer.Simple mastectomy and thorough adequate postoperative radiation therapy have much to offer.Treatment of “operable” breast cancer should be a cooperative effort of surgeon, radiation therapist and pathologist.     

Small Molecule Metabolite Extraction Strategy for Improving LC/MS Detection of Cancer Cell Metabolome

Metabolomics is the comprehensive assessment of endogenous metabolites of a biological system. “Oncometabolomics” is a rapidly emerging field with potential for developing specific biomarkers for early detection, diagnosis, and disease prognosis. Given the power of this technology, the availability of standardized sample preparation methods for immortalized human cancer cell lines is critical toward augmenting research in this direction. Using MCF-7 cells as a model system, we describe an approach for intracellular metabolite extraction from cell cultures for reproducible and comprehensive metabolite extraction. The samples, when injected onto a reverse-phase 50 × 2.1 mm Acquity 1.7-μm C18 column, using an ultra performance liquid chromatography system (UPLC) coupled with electrospray ionization-quadrupole-time-of-flight-mass spectrometry (ESI-Q-TOF-MS) in positive and negative modes, yielded a data matrix with a total of 2600 features. This method, when compared with a water-extraction procedure described earlier, was found to yield significantly higher coverage and detection of molecular features. Finally, we successfully tested the performance of this method for an array of human cancer cell lines used widely in the cancer research field.     

INITIAL CARE OF ACUTE BACK INJURIES

The mechanism of injury to the back should be obtained with the utmost accuracy and set down in the history as a separate paragraph under that heading. This is usually best obtained by questioning and requestioning the patient during the course of the examination. A history of any previous back affections should also be obtained at the first visit.The detailed examination of the back is not complete without a general physical examination.X-ray studies should be done immediately in all cases in which the injury has been caused by direct violence or forceful indirect violence (as in “jackknife” injury).Terms such as “disc disease,” “ruptured intervertebral disc” and various others that convey a similar meaning should not be used as the initial diagnosis and should be withheld until such a diagnosis is definitely established.The plan of treatment may include a period in hospital or of rest at home, or it may be carried out with the patient ambulatory. Corsets and braces should be prescribed only when they are to serve a definite function and the same can be said of physiotherapy.     

What can experience add to early medical education? Consensus survey

Objective To provide a rationale for integrating experience into early medical education (“early experience”).Design Small group discussions to obtain stakeholders'' views. Grounded theory analysis with respondent, internal, and external validation.Setting Problem based, undergraduate medical curriculum that is not vertically integrated.Participants A purposive sample of 64 students, staff, and curriculum leaders from three university medical schools in the United Kingdom.Results Without early experience, the curriculum was socially isolating and divorced from clinical practice. The abruptness of students'' transition to the clinical environment in year 3 generated positive and negative emotions. The rationale for early experience would be to ease the transition; orientate the curriculum towards the social context of practice; make students more confident to approach patients; motivate them; increase their awareness of themselves and others; strengthen, deepen, and contextualise their theoretical knowledge; teach intellectual skills; strengthen learning of behavioural and social sciences; and teach them about the role of health professionals.Conclusion A rationale for early experience would be to strengthen and deepen cognitively, broaden affectively, contextualise, and integrate medical education. This is partly a process of professional socialisation that should start earlier to avoid an abrupt transition. “Experience” can be defined as “authentic human contact in a social or clinical context that enhances learning of health, illness or disease, and the role of the health professional.”     

PathAct: a novel method for pathway analysis using gene expression profiles

We developed PathAct, a novel method for pathway analysis to investigate the biological and clinical implications of the gene expression profiles. The advantage of PathAct in comparison with the conventional pathway analysis methods is that it can estimate pathway activity levels for individual patient quantitatively in the form of a pathway-by-sample matrix. This matrix can be used for further analysis such as hierarchical clustering and other analysis methods. To evaluate the feasibility of PathAct, comparison with frequently used gene-enrichment analysis methods was conducted using two public microarray datasets. The dataset #1 was that of breast cancer patients, and we investigated pathways associated with triple-negative breast cancer by PathAct, compared with those obtained by gene set enrichment analysis (GSEA). The dataset #2 was another breast cancer dataset with disease-free survival (DFS) of each patient. Contribution by each pathway to prognosis was investigated by our method as well as the Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis. In the dataset #1, four out of the six pathways that satisfied p < 0.05 and FDR < 0.30 by GSEA were also included in those obtained by the PathAct method. For the dataset #2, two pathways (“Cell Cycle” and “DNA replication”) out of four pathways by PathAct were commonly identified by DAVID analysis. Thus, we confirmed a good degree of agreement among PathAct and conventional methods. Moreover, several applications of further statistical analyses such as hierarchical cluster analysis by pathway activity, correlation analysis and survival analysis between pathways were conducted.