When I heard about the concept of immunotherapeutics, I immediately loved it. Everything I had learned about medicine, cancer biology, genetics and oncology indicated to me that this was a potent approach, and at the time, completely untapped. I figured that since we had been unable to cure most metastatic solid tumors, something completely different needed to be employed. Realistically, “magic bullets” are not easy to find and therefore something that can be combined with other therapies, for enhanced synergy without overlapping adverse events, would be appealing.
adenovirus; cancer; gene therapy; immunotherapy; oncolytic virus
Steric constraints, charged interactions and many other forces important to protein structure and function can be explored by mutagenic experiments. Research of this kind has led to a wealth of knowledge about what stabilizes proteins in their folded states. To gain a more complete picture requires that we perturb these structures in a continuous manner, something mutagenesis cannot achieve. With high pressure crystallographic methods it is now possible to explore the detailed properties of proteins while continuously varying thermodynamic parameters. In this paper, we detail the structural response of the cavity-containing mutant L99A of T4 lysozyme, as well as its pseudo wild-type (WT*) counterpart, to hydrostatic pressure. Surprisingly, the cavity has almost no effect on the pressure response: virtually the same changes are observed in WT* as in L99A under pressure. The cavity is most rigid, while other regions deform substantially. This implies that while some residues may increase the thermodynamic stability of a protein, they may also be structurally irrelevant. As recently shown, the cavity fills with water at pressures above 100 MPa while retaining its overall size. The resultant picture of the protein is one in which conformationally fluctuating side groups provide a liquid-like environment, but which also contribute to the rigidity of the peptide backbone.
The principle of respect for autonomy has shaped much of the bioethics' discourse over the last 50 years, and is now most commonly used in the meaning of respecting autonomous choice. This is probably related to the influential concept of informed consent, which originated in research ethics and was soon also applied to the field of clinical medicine. But while available choices in medical research are well defined, this is rarely the case in healthcare. Consideration of ordinary medical practice reveals that the focus on patient choice does not properly grasp the moral aspects involved in healthcare. Medical decisions are often portrayed as if doctors and patients in confidence confront specific decisions about examinations or treatment, yet the reality often involves many different participants, with decisions being made over time and space. Indeed, most of the decisions are never even presented to patients, as it would be unethical to suggest something that is not medically justifiable. The options patients do confront are somewhat arbitrarily constructed within the narrow framework of both what is deemed to be medically appropriate and how the healthcare system is organised practically. While the autonomy discourse has proven valuable, a failure to distinguish between the fields of medical research and clinical medicine has generated a focus on patient choice that does not reflect what is really at stake in healthcare settings. This is alarming, because the current discourse misrepresents medical practice in a way that actually contributes to bioethical self-delusion.
Personal autonomy; bioethics; medical ethics; professional practice; delivery of healthcare; applied and professional ethics; philosophy of medicine; informed consent
A methodology for inducing spawning in captivity of the lancelet
Branchiostoma lanceolatum has been developed recently with
animals collected at the Racou beach, in the southern coast of France. An
increasing amount of laboratories around the world are now working on the
evolution of developmental mechanisms (Evo-Devo) using amphioxus collected in
this site. Thus, today, the development of new aquaculture techniques for
keeping amphioxus in captivity is needed and the study of the natural conditions
at which amphioxus is exposed in the Racou beach during their spawning season
becomes necessary. We have investigated the amphioxus distribution, size
frequency, and population structure in the Racou beach during its natural
spawning season using multivariate methods (redundancy analysis and multiple
regression). We found a clear preference of amphioxus for sandy sites, something
that seems to be a general behaviour of different amphioxus species around the
world. We have also estimated the amphioxus growth rate and we show how the
animals are preferentially localized in shallow waters during April and
This article provides information on the origin of tobacco and its subsequent spread throughout the world. In the era of the migration of communities, tobacco use gradually gained access and subsequently migrated along with the migrants, establishing in different locations. Probably at that time people were unaware of the health hazards and were using tobacco in treating certain ailments. Much has been known and written about tobacco in the context of oral and general health hazards but little has been explored and is known to many about where from and how this plant, which is now used in various forms, and speading widely. In what form, where, and how it had been served in religious rituals and considered for treatment or remedy of certain ailments in those days could not certainly be known. In the 21st century, people are considering hazardous tobacco as beneficial for their teeth, good for concentration of mind, and something which keeps them engaged. Even many professionals, though knowing the deleterious effects, are still using tobacco and gutkha in one or the other form. This article has been designed to revive the awareness for health hazards of tobacco and similar products. A pilot project questionnaire survey comprising this subject involving the educated mass has already been started and will be produced after analysis of data in part II of this paper.
Bidee; gutkha; naswar; paan; shisha; tobacco
In this paper, a brief, preliminary attempt is made to frame a scientific debate about how functional responses at gamma frequencies in electrophysiological recordings (EEG, MEG, ECoG, and LFP) should be classified and interpreted. In general, are all gamma responses the same, or should they be divided into different classes according to criteria such as their spectral characteristics (frequency range and/or shape), their spatial-temporal patterns of occurrence, and/or their responsiveness under different task conditions? In particular, are the responses observed in intracranial EEG at a broad range of “high gamma” frequencies (~60–200 Hz) different from gamma responses observed at lower frequencies (~30–80 Hz), typically in narrower bands? And if they are different, how should they be interpreted? Does the broad spectral shape of high gamma responses arise from the summation of many different narrow-band oscillations, or does it reflect something completely different? If we are not sure, should we refer to high gamma activity as oscillations? A variety of theories have posited a mechanistic role for gamma activity in cortical function, often assuming narrow-band oscillations. These theories continue to influence the design of experiments and the interpretation of their results. Do these theories apply to all electrophysiological responses at gamma frequencies? Although no definitive answers to these questions are immediately anticipated, this paper will attempt to review the rationale for why they are worth asking and to point to some of the possible answers that have been proposed.
Gamma band; High-gamma; Oscillations; Electrocorticography; Electroencephalography; Functional mapping; Induced responses; ERD/ERS
To develop and implement learning activities within an advanced pharmacy practice experience (APPE) to improve students' cultural competence.
During their AAPE at Community Access Pharmacy, students participated in topic discussions with faculty members, used interpreters to interview Hispanic patients, visited a Mexican grocery store, evaluated nontraditional medicine practices in the Hispanic community, and served as part of a patient care team at a homeless shelter and an HIV/AIDS clinic. The students reflected on these activities in daily logs and completed a final evaluation of their experiences.
Forty-three students completed the rotation from 2004-2007. Almost all learned something new about counseling patients with cultural/language differences (98%) and became more aware of financial barriers to health care and potential solutions to overcome them (93%). Students' reflections were positive and showed progression toward cultural competence.
A culturally diverse patient population provided opportunities for APPE students to develop the skills necessary to become culturally competent pharmacists. Future work should focus on potential evaluation tools to assess curricular cultural competency outcomes in APPE's.
experiential education; cultural competency; diversity
Comparisons between completely sequenced metazoan genomes have generally emphasized how similar their encoded protein content is, even when the comparison is between phyla. Given the manifest differences between phyla and, in particular, intuitive notions that some animals are more complex than others, this creates something of a paradox. Simplistic explanations have included arguments such as increased numbers of genes; greater numbers of protein products produced through alternative splicing; increased numbers of regulatory non-coding RNAs and increased complexity of the cis-regulatory code. An obvious value of complete genome sequences lies in their ability to provide us with inventories of such components. I examine progress being made in linking genome content to the pattern of animal evolution, and argue that the gap between genomic and phenotypic complexity can only be understood through the totality of interacting components.
comparative genomics; evolution; Metazoa; transcription factors; ultraconserved regions
The contribution of this paper is a technique that in certain circumstances allows one to avoid the removal of dynamic shadows in the visible spectrum making use of images in the infrared spectrum. This technique emerged from a real problem concerning the autonomous navigation of a vehicle in a wind farm. In this environment, the dynamic shadows cast by the wind turbines' blades make it necessary to include a shadows removal stage in the preprocessing of the visible spectrum images in order to avoid the shadows being misclassified as obstacles. In the thermal images, dynamic shadows completely disappear, something that does not always occur in the visible spectrum, even when the preprocessing is executed. Thus, a fusion on thermal and visible bands is performed.
shadow removal; road detection; thermal spectrum images
Using national survey data collected in 2004 in Burkina Faso, Ghana, Malawi, and Uganda with 12–19 year olds, we examine the prevalence of sex in exchange for money or gifts in the 12 months prior to the survey and its association with adolescents’ social and economic vulnerability and condom use. Receiving something in exchange for sex is very common among sexually active, unmarried female adolescents and there are no significant differences by household economic status, orphan status, level of schooling completed or age difference between partners. Condom use at last sex in the 12 months prior to the survey is not associated with receiving gifts or money. Qualitative data based on focus group discussions and in-depth interviews collected in 2003 with adolescents suggest that receiving money or gifts for sex is not necessarily a coercive force, but rather can be a routine aspect of dating.
transactional sex; adolescents; condom use
In cognitive science and neuroscience, there have been two leading models describing how humans perceive and classify facial expressions of emotion—the continuous and the categorical model. The continuous model defines each facial expression of emotion as a feature vector in a face space. This model explains, for example, how expressions of emotion can be seen at different intensities. In contrast, the categorical model consists of C classifiers, each tuned to a specific emotion category. This model explains, among other findings, why the images in a morphing sequence between a happy and a surprise face are perceived as either happy or surprise but not something in between. While the continuous model has a more difficult time justifying this latter finding, the categorical model is not as good when it comes to explaining how expressions are recognized at different intensities or modes. Most importantly, both models have problems explaining how one can recognize combinations of emotion categories such as happily surprised versus angrily surprised versus surprise. To resolve these issues, in the past several years, we have worked on a revised model that justifies the results reported in the cognitive science and neuroscience literature. This model consists of C distinct continuous spaces. Multiple (compound) emotion categories can be recognized by linearly combining these C face spaces. The dimensions of these spaces are shown to be mostly configural. According to this model, the major task for the classification of facial expressions of emotion is precise, detailed detection of facial landmarks rather than recognition. We provide an overview of the literature justifying the model, show how the resulting model can be employed to build algorithms for the recognition of facial expression of emotion, and propose research directions in machine learning and computer vision researchers to keep pushing the state of the art in these areas. We also discuss how the model can aid in studies of human perception, social interactions and disorders.
vision; face perception; emotions; computational modeling; categorical perception; face detection
Imagination of the three-dimensional (3D) structure of cerebral vascular lesions using two-dimensional (2D) angiograms is one of the skills that neurosurgical residents should achieve during their training. Although ongoing progress in computer software and digital imaging systems has facilitated viewing and interpretation of cerebral angiograms enormously, these facilities are not always available.
We have presented the use of play dough as an adjunct to the teaching armamentarium for training in visualization of cerebral aneurysms in some cases.
The advantages of play dough are low cost, availability and simplicity of use, being more efficient and realistic in training the less experienced resident in comparison with the simple drawings and even angiographic views from different angles without the need for computers and similar equipment. The disadvantages include the psychological resistance of residents to the use of something in surgical training that usually is considered to be a toy, and not being as clean as drawings or computerized images.
Although technology and computerized software using the patients' own imaging data seems likely to become more advanced in the future, use of play dough in some complicated cerebral aneurysm cases may be helpful in 3D reconstruction of the real situation.
This paper identifies how the different ideologies of patriarchy, technology, capitalism, race and feminism shape how we see breastfeeding and the breastfeeding mother with child. Ultimately, while we can make good strong arguments for breastfeeding from the perspective of health, of outcome, of good scientific data, we need to appreciate that they are only rationalizations for a shared belief that the image of the breastfeeding woman with baby represents something precious and valuable. So while it may be important to make arguments that draw on what is valued in society, we need to think hard about what it is that we value so that as we move forward with our efforts to make breastfeeding safe, we can use but not be used by, the various ideologies or claims.
Physicians in rural Canada face much different problems than their counterparts in large cities, a recent conference for rural physicians was told. For instance, rural areas may be decimated by funding caps because "they didn't have any resources to give up in the first place," said Dr. Ken Babey. He said rural physicians don't want to create divisiveness between urban and rural doctors, "but people don't realize that when they do something that has a big impact on the doctors who practise in cities and suburban areas, it has a disastrous impact on us." Rural doctors are attempting to organize so they can present a united front; in Nova Scotia, physicians recently formed a Section of Rural Practice.
A broadly accepted definition of creativity refers to the production of something both novel and useful within a given social context. Studies of patients with neurological and psychiatric disorders and neuroimaging studies of healthy controls have each drawn attention to frontal and temporal lobe contributions to creativity. Based on previous magnetic resonance (MR) spectroscopy studies demonstrating relationships between cognitive ability and concentrations of N-acetyl-aspartate (NAA), a common neurometabolite, we hypothesized that NAA assessed in gray and white matter (from a supraventricular slab) would relate to laboratory measures of creativity. MR imaging and divergent thinking measures were obtained in a cohort of 56 healthy controls. Independent judges ranked the creative products of each participant, from which a “Composite Creativity Index” (CCI) was created. Different patterns of correlations between NAA and CCI were found in higher verbal ability versus lower verbal ability participants, providing neurobiological support for a critical “threshold” regarding the relationship between intelligence and creativity. To our knowledge, this is the first report assessing the relationship between brain chemistry and creative cognition, as measured with divergent thinking, in a cohort comprised exclusively of normal, healthy participants.
We examined performance on a self-referenced memory (SRM) task for higher functioning children with autism (HFA) and a matched comparison group. SRM performance was examined in relation to symptom severity and social cognitive tests of mentalizing.
Sixty-two children (31 HFA, 31 comparison; 8–16 years) completed a SRM task in which they read a list of words and decided whether the word described something about them, something about Harry Potter, or contained a certain number of letters. They then identified words that were familiar from a longer list. Dependent measures were memory performance (d′) in each of the three encoding conditions as well as a self-memory bias score (d′ self-d′ other). Children completed The Strange Stories Task and The Children’s Eyes Test as measures of social cognition. Parents completed the SCQ and ASSQ as measures of symptom severity.
Children in the comparison sample showed the standard SRM effect in which they recognized significantly more self-referenced words relative to words in the other-referenced and letter conditions. In contrast, HFA children showed comparable rates of recognition for self- and other-referenced words. For all children, SRM performance improved with age and enhanced SRM performance was related to lower levels of social problems. These associations were not accounted for by performance on the mentalizing tasks.
Children with HFA did not show the standard enhanced processing of self- vs. other-relevant information. Individual differences in the tendency to preferentially process self-relevant information may be associated with social cognitive processes that serve to modify the expression of social symptoms in children with autism.
In industry, hospital, clinic, laboratory or office, professionals are continually faced with “all size” of problems which can be successfully answered by using investigative scientific methods.
The recognition and formulation of an existing problem followed by the desire to seek an answer are the first major steps. Collecting and analyzing data, followed by valid scientific conclusion completes the picture.
Professional success means knowing most about something, not something about most. Investigation-research is a particular pattern in weaving, made of organized curiosity, skillful analysis, inventive thinking and professional objectivity.
The purpose of the article remains to identify fundamental questions which emerge from clinical observations and practice, to identify and project needed research and to guide the finding of scientific answers.
Rehabilitation is an essential and integral part of burn treatment. It is not something which takes place following healing of skin grafts or discharge from hospital; instead it is a process that starts from day one of admission and continues for months and sometimes years after the initial event. Burns rehabilitation is not something which is completed by one or two individuals but should be a team approach, incorporating the patient and when appropriate, their family. The term ‘Burns Rehabilitation’ incorporates the physical, psychological and social aspects of care and it is common for burn patients to experience difficulties in one or all of these areas following a burn injury. Burns can leave a patient with severely debilitating and deforming contractures, which can lead to significant disability when left untreated. The aims of burn rehabilitation are to minimise the adverse effects caused by the injury in terms of maintaining range of movement, minimising contracture development and impact of scarring, maximising functional ability, maximising psychological wellbeing, maximising social integration
Burn rehabilitation; splintage; range of movements; post burn physiotherapy
Cancer treatments are complex, involving multiple clinicians, toxic therapies, and uncertain outcomes. Consequently, patients are vulnerable when breakdowns in care occur. This study explored cancer patients' perceptions of preventable, harmful events; the impact of these events; and interactions with clinicians after such events.
Patients and Methods
In-depth telephone interviews were conducted with cancer patients from three clinical sites. Patients were eligible if they believed: something “went wrong” during their cancer care; the event could have been prevented; and the event caused, or could have caused, significant harm. Interviews focused on patients' perceptions of the event, its impact, and clinicians' responses to the event.
Ninety-three of 416 patients queried believed something had gone wrong in their care that was preventable and caused or could have caused harm. Seventy-eight patients completed interviews. Of those interviewed, 28% described a problem with medical care, such as a delay in diagnosis or treatment; 47% described a communication problem, including problems with information exchange or manner; and 24% described problems with both medical care and communication. Perceived harms included physical and emotional harm, disruption of life, effect on family members, damaged physician-patient relationship, and financial expense. Few clinicians initiated discussion of the problematic events. Most patients did not formally report their concerns.
Cancer patients who believe they experienced a preventable, harmful event during their cancer diagnosis or care often do not formally report their concerns. Systems are needed to encourage patients to report such events and to help physicians and health care systems respond effectively.
Air pollution contributes to poor respiratory and cardiovascular health. Susceptible individuals may be advised to mitigate effects of air pollution through actions such as reducing outdoor physical activity on days with high pollution. Our analysis identifies the extent to which susceptible individuals changed activities due to bad air quality. This cross-sectional study included 10,898 adults from the National Health and Nutrition Examination Survey (NHANES) 2007–2010. Participants reported if they did something differently when air quality was bad. Susceptible categories included respiratory conditions, cardiovascular conditions and older age (≥65 years). Analyses accounted for complex survey design; logistic regression models controlled for gender, race, education, smoking, and body mass index. 1305 individuals reported doing something differently (12.0%, 95% confidence interval (CI): 10.9, 13.1). This percentage was 14.2% (95% CI: 11.6, 16.8), 25.1% (95% CI: 21.7, 28.6), and 15.5% (95% CI: 12.2, 18.9) among older adults, those with a respiratory condition, and those with a cardiovascular condition, respectively. In adjusted regression models the following were significantly more likely to have changed activity compared to those who did not belong to any susceptible group: respiratory conditions (adjusted odds ratio (aOR): 2.61, 95% CI: 2.03, 3.35); respiratory and cardiovascular conditions (aOR: 4.36, 95% CI: 2.47, 7.69); respiratory conditions and older age (aOR: 3.83; 95% CI: 2.47, 5.96); or all three groups (aOR: 3.52; 95% CI: (2.33, 5.32). Having cardiovascular conditions alone was not statistically significant. Some individuals, especially those with a respiratory condition, reported changing activities due to poor air quality. However, efforts should continue to educate the public about air quality and health.
We have set up a study that can make a contribution to our knowledge of the effect of the present oral contraceptive agents. We may also learn something about the characteristics of women who chose the pill and about those who reject it. Perhaps our results will provide a more secure base from which research for a better product can begin.
It may be, however, that we have demonstrated something of greater importance: that meaningful large-scale morbidity statistics can be accurately collected from the point at which the greatest information is available-the records of the family physician.
There has been an increased interest in the role of a human rights framework to mobilize resources for health.
This paper argues that the human rights framework does provide us with an appropriate understanding of what values should guide a nation's health policy, and a potentially powerful means of moving the health agenda forward. It also, however, argues that appeals to human rights may not necessarily be effective at mobilizing resources for specific health problems one might want to do something about. Specifically, it is not possible to argue that a particular allocation of scarce health care resources should be changed to a different allocation, benefiting other groups. Lack of access to health care services by some people only shows that something has to be done, but not what should be done.
The somewhat weak claim identified above together with the obligation to realize progressively a right to health can be used to mobilize resources for health.
How does one design something that is complex? Or something that is simple? Why should one try to reduce or increase complexity? What is complexity? There are a large number of different uses of the word, including many in mathematics and physics. Most of these are not useful in attempting to fit the word to the problems of the design of systems and devices for medicine. In this paper the concept has been defined to apply to health care, which has led to some conclusions about the future development of medical systems and devices.
complexity; design; patient safety
The current study presented 1,933 adolescents from 13 schools with a scenario about a hypothetical peer's plan to “do something dangerous” at school and asked how likely they would be to respond with four different actions: intervene directly, tell a teacher or principal, discuss it with a friend but not an adult, and do nothing. High school students were less likely than those in middle school to say they would approach the peer directly or confide in a teacher or principal. Students were most likely to favor taking action on their own over all of the other response strategies. Students with positive perceptions of their schools were more likely to say they would do something rather than ignore their peer's dangerous intentions. These relationships were mediated by students’ beliefs that confiding in a teacher may have unfavorable consequences. Findings from this study support the important role schools play in creating a culture where students take responsibility for one another.
school climate; adolescents; teachers; intervention; peers
It is common to refer to all sorts of clear-cut differences between the sexes as something that is biologically almost inevitable. Although this does not reflect the status of evolutionary theory on sex determination and sexual dimorphism, it is probably a common view among evolutionary biologists as well, because of the impact of sexual selection theory. To get away from thinking about biological sex and traits associated with a particular sex as something static, it should be recognized that in an evolutionary perspective sex can be viewed as a reaction norm, with sex attributes being phenotypically plastic. Sex determination itself is fundamentally plastic, even when it is termed “genetic”. The phenotypic expression of traits that are statistically associated with a particular sex always has a plastic component. This plasticity allows for much more variation in the expression of traits according to sex and more overlap between the sexes than is typically acknowledged. Here we review the variation and frequency of evolutionary changes in sex, sex determination and sex roles and conclude that sex in an evolutionary time-frame is extremely variable. We draw on recent findings in sex determination mechanisms, empirical findings of morphology and behaviour as well as genetic and developmental models to explore the concept of sex as a reaction norm. From this point of view, sexual differences are not expected to generally fall into neat, discrete, pre-determined classes. It is important to acknowledge this variability in order to increase objectivity in evolutionary research.
Phenotypic plasticity; Sexual selection; Sex determination; Sex change; Sex role reversal; Gender bias