Nitrous Oxide Inhalation as a Fad—Dangers in Uncontrolled Sniffing for Psychedelic Effect

“LAUGHING GAS is the newest thing for kids seeking kicks,” the Stanford Daily reports. “They sniff it.”So begins a news story in the Los Angeles Times of 26 January 1967. The story continues:“It''s the latest way to travel, or so say a growing group of devotees on the campus,” the university student paper said. “It can produce much the same effects as psychedelic drugs, they claim, and it''s cheaper to obtain.”“One student said he buys the gas, nitrous oxide, from a medical supply house. `They think I am anesthetizing rats,'' he explained.“Campus medical authorities said the gas, sniffed `in sufficient amounts... could produce all the states of anesthesia, including the final stage—death.''”     

Pathological States and Criminal Responsibility

The doctor is embarrassed in court when asked to testify to the effects of illness on a defendant''s capability “of appreciating the nature and quality of an act or omission or of knowing that an act or omission is wrong”. The source of his difficulty is traced to the legal concepts of “guilt”, “crime” and “punishment” which imply a legal view of man at variance with our modern biological view. To abolish this discrepancy we need not accept a medical model for criminal law where “crime” is analogous to “disease”, and “punishment” to “treatment”. A pragmatic approach to the handling of the criminal could exclude the notions of “guilt” and “punishment” and yet fulfil the rational goals of protecting society from the criminal and of compensating his victims.     

Patients' accounts of being removed from their general practitioner's list: qualitative study

Objective To explore patients'' accounts of being removed from a general practitioner''s list.Design Qualitative analysis of semistructured interviews.Setting Patients'' homes in Leicestershire.Participants 28 patients who had recently been removed from a general practitioner''s list.Results The removed patients gave an account of themselves as having genuine illnesses needing medical care. In putting their case that their removal was unjustified, patients were concerned to show that they were “good” patients who complied with the rules that they understood to govern the doctor-patient relationship: they tried to cope with their illness and follow medical advice, used general practice services “appropriately,” were uncomplaining, and were polite with doctors. Removed patients also used their accounts to characterise the removing general practitioner as one who broke the lay rules of the doctor-patient relationship. These “bad” general practitioners were rude, impersonal, uncaring, and clinically incompetent and lied to patients. Patients felt very threatened by being removed from their general practitioner''s list; they experienced removal as an attack on their right to be an NHS patient, as deeply distressing, and as stigmatising.Conclusions Removal is an overwhelmingly negative and distressing experience for patients. Many of the problems encountered by removed patients may be remediable through general practices having an explicit policy on removal and procedures in place to help with “difficult” patients.     

Commentary: Personal Renewal

After John Gardner''s presentation on “Self-Renewal” to THE WESTERN JOURNAL OF MEDICINE Editors'' Meeting, ^* Joseph Murphy, MD, Special Editor for Wyoming, asked the former Secretary of Health, Education, and Welfare, “Where are you in your life''s cycle?” Dr Gardner, who is 80 years old, answered, “When Chief Justice Oliver Wendell Holmes, Jr, was in his 90s, he was asked a similar question and said, `I''m like a race horse cantering along after the race is over, cooling down.'' Well, I''m nowhere near cantering! I''m still in the race, pushing the world.” race, pushing the world.”John Gardner, who received his undergraduate degree from Stanford and PhD from the University of California, Berkeley, taught at the college level for several years before he joined the Carnegie Foundation. As president of Carnegie Corporation and Carnegie Foundation for the Advancement of Teaching, he began to “push the world” toward education and in 1964 received the country''s highest civilian honor, the Presidential Medal of Freedom. He has also pushed it toward political reform by founding Common Cause, toward grass-roots political action by founding the Urban Coalition, toward leadership training by founding the White House Fellows program, and toward volunteerism by founding the Independent Sector (a coalition of for-profit and not-for-profit organizations and foundations). His books, including Excellence, Self-Renewal, No Easy Victories, and On Leadership, have pushed readers to new understanding of themselves and of organizations to higher levels of creativity and energy to get important work done. His current research focuses on discovering and defining the characteristics of healthy, vital communities. His call to “keep on keeping on,” indeed, to push the world, leads to constructive change. Active people become effective people, infused with the energy and optimism that good hard work inspires. I think you will find this paper as invigorating to read as it was to hear.     

Putting the brakes on phagocytosis: “don't‐eat‐me” signaling in physiology and disease

Timely removal of dying or pathogenic cells by phagocytes is essential to maintaining host homeostasis. Phagocytes execute the clearance process with high fidelity while sparing healthy neighboring cells, and this process is at least partially regulated by the balance of “eat‐me” and “don''t‐eat‐me” signals expressed on the surface of host cells. Upon contact, eat‐me signals activate “pro‐phagocytic” receptors expressed on the phagocyte membrane and signal to promote phagocytosis. Conversely, don''t‐eat‐me signals engage “anti‐phagocytic” receptors to suppress phagocytosis. We review the current knowledge of don''t‐eat‐me signaling in normal physiology and disease contexts where aberrant don''t‐eat‐me signaling contributes to pathology.     

Visualization of Transepithelial Passage of the Immunogenic 33-Residue Peptide from α-2 Gliadin in Gluten-Sensitive Macaques

Background

Based on clinical, histopathological and serological similarities to human celiac disease (CD), we recently established the rhesus macaque model of gluten sensitivity. In this study, we further characterized this condition based on presence of anti-tissue transglutaminase 2 (TG2) antibodies, increased intestinal permeability and transepithelial transport of a proteolytically resistant, immunotoxic, 33-residue peptide from α₂-gliadin in the distal duodenum of gluten-sensitive macaques.

Methodology/Principal Findings

Six rhesus macaques were selected for study from a pool of 500, including two healthy controls and four gluten-sensitive animals with elevated anti-gliadin or anti-TG2 antibodies as well as history of non-infectious chronic diarrhea. Pediatric endoscope-guided pinch biopsies were collected from each animal''s distal duodenum following administration of a gluten-containing diet (GD) and again after remission by gluten-free diet (GFD). Control biopsies always showed normal villous architecture, whereas gluten-sensitive animals on GD exhibited histopathology ranging from mild lymphocytic infiltration to villous atrophy, typical of human CD. Immunofluorescent microscopic analysis of biopsies revealed IgG+ and IgA+ plasma-like cells producing antibodies that colocalized with TG2 in gluten-sensitive macaques only. Following instillation in vivo, the Cy-3-labeled 33-residue gluten peptide colocalized with the brush border protein villin in all animals. In a substantially enteropathic macaque with “leaky” duodenum, the peptide penetrated beneath the epithelium into the lamina propria.

Conclusions/Significance

The rhesus macaque model of gluten sensitivity not only resembles the histopathology of CD but it also may provide a model for studying intestinal permeability in states of epithelial integrity and disrepair.     

MANDIBULAR HERPES ZOSTER—With Report on the Use of Cortisone in a Case with Geniculate Ganglion Symptoms

Herpes zoster, an acute specific viral infection, occurs more commonly than is generally supposed. It should be differentiated from other diseases involving the ear and skin; it must be considered as a possible etiologic agent in some palsies of the facial, glossopharyngeal or vagal nerves.The type of cephalic herpes zoster should be carefully differentiated; cases involving the “geniculate zone” may be other than “Ramsay Hunt''s syndrome.” This syndrome is now defined as a herpes zoster eruption of the external ear at the “geniculate zone” with involvement of the seventh or seventh and eighth nerves.The “topognostic” method is the best for determining the level at which the facial nerve has been affected.It is questioned whether there is a single outstanding therapeutic agent for this disease. Cortisone had no apparent therapeutic effect in a case reported herein.     

Practitioner attitudes in the United States and United Kingdom toward decisions at the end of life: are medical ethicists out of touch?

Objective To assess whether UK and US health care professionals share the views of medical ethicists about medical futility, withdrawing or withholding treatment, ordinary or extraordinary interventions, and the doctrine of double effect. Design, subjects, and setting Answers to a 138-item attitudinal questionnaire completed by 469 UK nurses studying the Open University course on “Death and Dying” were compared with those of a similar questionnaire administered to 759 US nurses and 687 US physicians taking the Hastings Center course on “Decisions Near the End of Life.” Results Practitioners accept the relevance of concepts widely disparaged by bioethicists: double effect, medical futility, and the distinctions between heroic and ordinary interventions and withholding and withdrawing treatment. Within the UK nurses'' group, the responses of a “rationalist” axis of respondents who describe themselves as having “no religion” are closer to the bioethics consensus on withholding and withdrawing treatment. Conclusions Professionals'' beliefs differ substantially from the recommendations of their professional bodies and from majority opinion in bioethics. Bioethicists should be cautious about assuming that their opinions will be readily accepted by practitioners.     

X-Ray Solution Scattering of Squid Heavy Meromyosin: Strengthening the Evidence for an Ancient Compact off State

The overall conformations of regulated myosins or heavy meromyosins from chicken/turkey, scallop, tarantula, limulus, and scorpion sources have been studied by a number of techniques, including electron microscopy, sedimentation, and pulsed electron paramagnetic resonance. These studies have indicated that the binding of regulatory ions changes the conformation of the molecule from a compact shape found in the “off” state of the muscle to extended relationships between the tail and independently mobile heads that predominate in the “on” state. Here we strengthen the argument for the generality of this conformational change by using small angle X-ray scattering on heavy meromyosin from squid. Small angle X-ray scattering allows the protein to be visualized in solution under mild and relatively physiological conditions, and squid differs from the other species studied by at least 500 million years of evolution. Analysis of the data indicates that upon addition of Ca²⁺ the radius of gyration increases. Differences in the squid “on” and “off” states are clearly distinguishable as bimodal and unimodal pair distance distribution functions respectively. These observations are consistent with a Ca²⁺-free squid heavy meromyosin that is compact, but which becomes extended when Ca²⁺ is bound. Further, the scattering profile derived from the current model of tarantula heavy meromyosin in the “off” state is in excellent agreement with the measured “off” state scattering profile for squid heavy meromyosin. The previous and current studies together provide significant evidence that regulated myosin''s compact off-state conformation is an ancient trait, inherited from a common ancestor during divergent evolution.     

Doctor,you're in tobacco sales!

The director of British Columbia''s Doctors'' Stop-Smoking Project says that, whether they recognize it or not, doctors have the best and most competitive position within the tobacco industry because they have the best product line. Dr. Frederic Bass says physicians'' products—health and freedom from addiction—will win against the competition, which can offer only smoke, addiction to nicotine and ill health. “We offer the better deal,” he says, “but are we selling like we could? That''s the issue.”     

Computer-Assisted Diagnosis of Abdominal Pain using “Estimates” Provided by Clinicians

This paper reports a comparison between two modes of computer-aided diagnosis in a real-time prospective trial involving 472 patients with acute abdominal pain. In the first mode the computer-aided system analysed each of the 472 patients by referring to data previously collated from a large series of 600 real-life patients. In the second mode the system used as a basis for its analysis “estimates” of probability provided by a group of six clinicians. The accuracy and reliability of both modes were compared with the performance of unaided clinicians.Using “real-life” data the computer system was significantly more effective than the unaided clinician. By contrast, when using the clinicians'' own estimates the computer-aided system was often less effective than the unaided clinician—especially when diagnosing less common disorders. It seems, firstly, that future systems for computer-aided diagnosis should employ data from real-life and not clinicians'' estimates, and, secondly, that clinicians themselves cannot analyse cases in a probabilistic fashion, since often they have little idea of what the “true” probabilities are.     

When a Text Is Translated Does the Complexity of Its Vocabulary Change? Translations and Target Readerships

In linguistic studies, the academic level of the vocabulary in a text can be described in terms of statistical physics by using a “temperature” concept related to the text''s word-frequency distribution. We propose a “comparative thermo-linguistic” technique to analyze the vocabulary of a text to determine its academic level and its target readership in any given language. We apply this technique to a large number of books by several authors and examine how the vocabulary of a text changes when it is translated from one language to another. Unlike the uniform results produced using the Zipf law, using our “word energy” distribution technique we find variations in the power-law behavior. We also examine some common features that span across languages and identify some intriguing questions concerning how to determine when a text is suitable for its intended readership.     

Plant intelligence: Why,why not or where?

The concept of plant intelligence, as proposed by Anthony Trewavas, has raised considerable discussion. However, plant intelligence remains loosely defined; often it is either perceived as practically synonymous to Darwinian fitness, or reduced to a mere decorative metaphor. A more strict view can be taken, emphasizing necessary prerequisites such as memory and learning, which requires clarifying the definition of memory itself. To qualify as memories, traces of past events have to be not only stored, but also actively accessed. We propose a criterion for eliminating false candidates of possible plant intelligence phenomena in this stricter sense: an “intelligent” behavior must involve a component that can be approximated by a plausible algorithmic model involving recourse to stored information about past states of the individual or its environment. Re-evaluation of previously presented examples of plant intelligence shows that only some of them pass our test.

“You were hurt?” Kumiko said, looking at the scar.Sally looked down. “Yeah.”“Why didn''t you have it removed?”“Sometimes it''s good to remember.”“Being hurt?”“Being stupid.”—(W. Gibson: Mona Lisa Overdrive)

Key words: intelligence, memory, learning, plant development, mathematical models, plant neurobiology, definition of terms     

Division of Labor Regulates Precision Rescue Behavior in Sand-Dwelling Cataglyphis cursor Ants: To Give Is to Receive

Division of labor, an adaptation in which individuals specialize in performing tasks necessary to the colony, such as nest defense and foraging, is believed key to eusocial insects'' remarkable ecological success. Here we report, for the first time, a completely novel specialization in a eusocial insect, namely the ability of Cataglyphis cursor ants to rescue a trapped nestmate using precisely targeted behavior. Labeled “precision rescue”, this behavior involves the ability of rescuers not only to detect what, exactly, holds the victim in place, but also to direct specific actions to this obstacle. Individual ants, sampled from each of C. cursor''s three castes, namely foragers, nurses and inactives, were experimentally ensnared (the “victim”) and exposed to a caste-specific group of potential “rescuers.” The data reveal that foragers were able to administer, and obtain, the most help while members of the youngest, inactive caste not only failed to respond to victims, but also received virtually no help from potential rescuers, regardless of caste. Nurses performed intermediate levels of aid, mirroring their intermediate caste status. Our results demonstrate that division of labor, which controls foraging, defense and brood care in C. cursor, also regulates a newly discovered behavior in this species, namely a sophisticated form of rescue, a highly adaptive specialization that is finely tuned to a caste member''s probability of becoming, or encountering, a victim in need of rescue.     

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.”     

Intention Understanding in Autism

When we observe a motor act (e.g. grasping a cup) done by another individual, we extract, according to how the motor act is performed and its context, two types of information: the goal (grasping) and the intention underlying it (e.g. grasping for drinking). Here we examined whether children with autistic spectrum disorder (ASD) are able to understand these two aspects of motor acts. Two experiments were carried out. In the first, one group of high-functioning children with ASD and one of typically developing (TD) children were presented with pictures showing hand-object interactions and asked what the individual was doing and why. In half of the “why” trials the observed grip was congruent with the function of the object (“why-use” trials), in the other half it corresponded to the grip typically used to move that object (“why-place” trials). The results showed that children with ASD have no difficulties in reporting the goals of individual motor acts. In contrast they made several errors in the why task with all errors occurring in the “why-place” trials. In the second experiment the same two groups of children saw pictures showing a hand-grip congruent with the object use, but within a context suggesting either the use of the object or its placement into a container. Here children with ASD performed as TD children, correctly indicating the agent''s intention. In conclusion, our data show that understanding others'' intentions can occur in two ways: by relying on motor information derived from the hand-object interaction, and by using functional information derived from the object''s standard use. Children with ASD have no deficit in the second type of understanding, while they have difficulties in understanding others'' intentions when they have to rely exclusively on motor cues.     

Do Pressures to Publish Increase Scientists' Bias? An Empirical Support from US States Data

The growing competition and “publish or perish” culture in academia might conflict with the objectivity and integrity of research, because it forces scientists to produce “publishable” results at all costs. Papers are less likely to be published and to be cited if they report “negative” results (results that fail to support the tested hypothesis). Therefore, if publication pressures increase scientific bias, the frequency of “positive” results in the literature should be higher in the more competitive and “productive” academic environments. This study verified this hypothesis by measuring the frequency of positive results in a large random sample of papers with a corresponding author based in the US. Across all disciplines, papers were more likely to support a tested hypothesis if their corresponding authors were working in states that, according to NSF data, produced more academic papers per capita. The size of this effect increased when controlling for state''s per capita R&D expenditure and for study characteristics that previous research showed to correlate with the frequency of positive results, including discipline and methodology. Although the confounding effect of institutions'' prestige could not be excluded (researchers in the more productive universities could be the most clever and successful in their experiments), these results support the hypothesis that competitive academic environments increase not only scientists'' productivity but also their bias. The same phenomenon might be observed in other countries where academic competition and pressures to publish are high.     

The Cultivation of Bt Corn Producing Cry1Ac Toxins Does Not Adversely Affect Non-Target Arthropods

Transgenic corn producing Cry1Ac toxins from Bacillus thuringiensis (Bt) provides effective control of Asian corn borer, Ostrinia furnacalis (Guenée), and thus reduces insecticide applications. However, whether Bt corn exerts undesirable effects on non-target arthropods (NTAs) is still controversial. We conducted a 2-yr study in Shangzhuang Agricultural Experiment Station to assess the potential impact of Bt corn on field population density, biodiversity, community composition and structure of NTAs. On each sampling date, the total abundance, Shannon''s diversity index, Pielou''s evenness index and Simpson''s diversity index were not significantly affected by Bt corn as compared to non-Bt corn. The “sampling dates” had a significant effect on these indices, but no clear tendencies related to “Bt corn” or “sampling dates X corn variety” interaction were recorded. Principal response curve analysis of variance indicated that Bt corn did not alter the distribution of NTAs communities. Bray-Curtis dissimilarity and distance analysis showed that Cry1Ac toxin exposure did not increase community dissimilarities between Bt and non-Bt corn plots and that the evolution of non-target arthropod community was similar on the two corn varieties. The cultivation of Bt corn failed to show any detrimental evidence on the density of non-target herbivores, predators and parasitoids. The composition of herbivores, predators and parasitoids was identical in Bt and non-Bt corn plots. Taken together, results from the present work support that Bt corn producing Cry1Ac toxins does not adversely affect NTAs.