Recent History of Ischaemic Heart Disease and Duodenal Ulcer in Doctors

Data are presented on the incidence of ischaemic (coronary) heart disease and duodenal ulcer among the several thousand male medical practitioners aged 35–64 holding immediate sickness benefit policies with the Medical Sickness Annuity and Life Assurance Society Limited. Three periods are considered: 1947–50, 1957–60, and 1961–5.The incidence of first clinical episodes of ischaemic heart disease in the doctors altered little between 1947–50 and 1957–60 but increased in 1961–5. Comparison of the late 1940s with the early 1960s shows a 60% rise of incidence at ages 45–54 but little change at other ages. Cases first presenting as “sudden” death increased between 1947–50 and 1961–5 by 111% at 45–54, and again changed little at 55–64. In two other occupational groups that have been studied—bus conductors and insurance salesmen—the increase of incidence was greater than for the doctors at 45–54 and it occurred also over 55 years of age. The increase from 1947–50 to 1961–5 in mortality during all episodes of ischaemic heart disease was the same in the doctors as in the male population of England and Wales at 45–54, but at 55–64 it was less.The results in the doctors are not due to alterations over the period in length of sickness absence, or underwriting policy, or of the nomenclature used on the certificates.Well-documented changes in the smoking habits of doctors may be partly responsible for what appears to have been a relatively favourable experience of ischaemic heart disease from 1947–50 to 1961–5, especially at ages 55–64.Incidence of duodenal ulcer at ages 35–64 declined steadily in this population of doctors from 1947–50 to 1961–5. The decline is very likely to be real.     

Career pathways and destinations 18 years on among doctors who qualified in the United Kingdom in 1977: postal questionnaire survey

ObjectiveTo determine the career destinations, by 1995, of doctors who qualified in the United Kingdom in 1977; the relation between their destinations and early career choice; and their intentions regarding retirement age.DesignPostal questionnaire.SettingUnited Kingdom.SubjectsAll (n=3135) medical qualifiers of 1977.ResultsAfter about 12 years the distribution of respondents by type of employment, and, for women, the percentage of doctors in part time rather than full time medical work, had stabilised. Of all 2997 qualifiers from medical schools in Great Britain, 2399 (80.0% (95% confidence interval 79.5% to 80.6%)) were working in medicine in the NHS in Great Britain 18 years after qualifying. Almost half the women (318/656) worked in the NHS part time. Of 1714 doctors in the NHS, 1125 intended to work in the NHS until normal retirement age, 392 did not, and 197 were undecided. Of the 1548 doctors for whom we had sufficient information, career destinations at 18 years matched the choices made at 1, 3, and 5 years in 58.9% (912), 78.2% (1211), and 86.6% (1341) of cases respectively.ConclusionsPlanning for the medical workforce needs to be supported by information about doctors’ career plans, destinations, and whole time equivalent years of work. Postgraduate training needs to take account of doctors’ eventual choice of specialty (and the timing of this choice).

Key messages

• A large scale national study in the United Kingdom followed doctors from qualification to mid-career and beyond
• Most doctors had made their choice of eventual career—at least in terms of broadly defined specialty—within 5 years of qualifying
• Eighteen years on, 80% of the doctors were working in the NHS and nearly half of women doctors were working part time
• Almost a quarter of NHS doctors planned to retire early

     

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.”     

A warning to MDs: If you want to keep calls confidential,hang up the cordless phone

Medical professionals who use cordless telephones in the home or office may jeopardize both patient confidentiality and their personal privacy. A lengthy investigation revealed that many doctors are unaware that anyone with a radio-frequency scanner or tuneable very-high-frequency receiver can eavesdrop on conversations with patients, colleagues and business and financial advisers — anyone they talk to on a cordless phone.     

Characteristics of consultants who hold distinction awards in England and Wales: database analysis with particular reference to sex and ethnicity

Objective To determine whether women, ethnic minorities, and particular specialties are discriminated against in the receipt of NHS distinction awards.Design Analysis of database of consultants eligible for distinction awards.Setting England and Wales, 2002.Main outcome measures Holding of B, A, and Aplus distinction awards, analysed for all awards, irrespective of when made, and for awards made in the last five years studied.Results Women and doctors from ethnic minorities were substantially under-represented among award holders when no account was taken of potential confounding factors. Differences diminished after multivariate analysis, but some remained significant. For example, the adjusted odds ratio of women holding awards compared with men was 0.69 (95% confidence interval 0.59 to 0.82) for any award and 1.37 (0.86 to 2.20) for Aplus awards; the odds ratio for any award for non-white doctors trained abroad compared with white doctors trained in the United Kingdom was 0.45 (0.37 to 0.56). In the last five years studied the adjusted ratio of women to men was 0.94 (0.79 to 1.10) for B awards and 1.54 (0.85 to 2.83) for Aplus awards. The adjusted ratio for non-white British trained consultants was 0.86 (0.62 to 1.17) for B awards and 1.20 (0.37 to 3.87) for Aplus awards; for non-white consultants trained abroad it was 0.68 (0.54 to 0.85) for B awards and 0.69 (0.15 to 3.10) for Aplus awards; and for white consultants trained abroad it was 0.70 (0.54 to 0.91) for B awards and 0.90 (0.38 to 2.15) for Aplus awards.Conclusion Historical under-representation in award holding by women and doctors from ethnic minorities was partly explained by time spent as a consultant. Recent awards showed no under-representation of women and no appreciable under-representation of ethnic minorities overall. However, doctors who trained abroad—both white and non-white—remained under-represented for B awards.     

Nutritional biology: a neglected basic discipline of nutritional science

On the basis of a scientific-philosophical analysis, this paper tries to show that the approaches in current nutritional science—including its subdisciplines which focus on molecular aspects—are predominantly application-oriented. This becomes particularly evident through a number of conceptual problems characterized by the triad of ‘dearth of theoretical foundation,’ ‘particularist research questions,’ and ‘reductionist understanding of nutrition.’ The thesis presented here is that an interpretive framework based on nutritional biology is able to shed constructive light on the fundamental problems of nutritional science. In this context, the establishment of ‘nutritional biology’ as a basic discipline in research and education would be a first step toward recognizing the phenomenon of ‘nutrition’ as an oecic process as a special case of an organism–environment interaction. Modern nutritional science should be substantively grounded on ecological—and therefore systems biology as well as organismic—principles. The aim of nutritional biology, then, should be to develop near-universal ‘law statements’ in nutritional science—a task which presents a major challenge for the current science system.     

Placebo Trends across the Border: US versus Canada

Background

Physicians around the world report to using placebos in a variety of situations and with varying degrees of frequency. Inconsistent methodologies, however, complicate interpretation and prevent direct comparisons across studies. While US- and Canada-based physicians share similar professional standards, Canada harbours a less-litigious universal healthcare model with no formal placebo-related policy—factors that may impact how physicians view and use placebos.

Methods

To compare American and Canadian data, we circulated an online survey to academic physicians practicing in Canada, collected anonymous responses, and extracted those of internists and rheumatologists for comparison to US data obtained through parallel methodologies.

Results

Whereas our data show overall concordance across the border—from definitions to ethical limitations and therapeutic potential—differences between American- and Canadian-based placebo practices merit acknowledgement. For example, compared to 45%-80% among US-based respondents, only 23±7% of Canada-based respondents reported using placebos in clinical practice. However, 79±7% of Canada-respondents—a figure comparable to US data—professed to prescribing at least one form of treatment without proven or expected efficacy. Placebo interventions including unwarranted vitamins and herbal supplements (impure placebos) as well as sugar pills and saline injections (pure placebos) appear more common in Canada, where more doctors described placebos as “placebos” (rather than “medications”) and used them as a “diagnostic” tool (rather than a means of placating patient demands for treatment).

Interpretation

Cross-border variation in the use of clinical placebos appears minor despite substantial differences in health care delivery system, malpractice climate, and placebo-related policy. The prevalence of impure placebos in both Canadian and US clinics raises ethical and practical questions currently unaddressed by policy and warranting investigation.     

Constraints and variation in food web link-species space

Predicting food web structure in future climates is a pressing goal of ecology. These predictions may be impossible without a solid understanding of the factors that structure current food webs. The most fundamental aspect of food web structure—the relationship between the number of links and species—is still poorly understood. Some species interactions may be physically or physiologically ‘forbidden''—like consumption by non-consumer species—with possible consequences for food web structure. We show that accounting for these ‘forbidden interactions'' constrains the feasible link-species space, in tight agreement with empirical data. Rather than following one particular scaling relationship, food webs are distributed throughout this space according to shared biotic and abiotic features. Our study provides new insights into the long-standing question of which factors determine this fundamental aspect of food web structure.     

The Past and Future of Tuberculosis Research

Renewed efforts in tuberculosis (TB) research have led to important new insights into the biology and epidemiology of this devastating disease. Yet, in the face of the modern epidemics of HIV/AIDS, diabetes, and multidrug resistance—all of which contribute to susceptibility to TB—global control of the disease will remain a formidable challenge for years to come. New high-throughput genomics technologies are already contributing to studies of TB''s epidemiology, comparative genomics, evolution, and host–pathogen interaction. We argue here, however, that new multidisciplinary approaches—especially the integration of epidemiology with systems biology in what we call “systems epidemiology”—will be required to eliminate TB.     

Patients' assessment of out of hours care in general practice

A sample of 177 patients drawn from 13 north London practices were interviewed shortly after they had sought help from their practice outside normal surgery hours. Patients were asked to describe the process and outcome of their out of hours call, to comment on specific aspects of the consultation, and to access their overall satisfaction with the encounter.Parents seeking consultations for children were least satisfied with the consultation; those aged over 60 responded most positively. Visits from general practitioners were more acceptable than visits from deputising doctors for patients aged under 60, but for patients aged over 60 visits from general practitioners and deputising doctors were equally acceptable.Monitoring of patients'' views of out of hours consultations is feasible, and the findings of this study suggest that practices should regularly review the organisation of their out of hours care and discuss strategies for minimising conflict in out of hours calls—particularly those concerning children.     

Variations in Sulfhydryl, Disulfide, and Protein Content during Synchronous and Asynchronous Growth of HeLa Cells

The cellular contents of protein-bound and nonprotein sulfhydry (—SH) and disulfide (—SS—) groups were measured in both asynchronous and synchronous HeLa S3 cultures. About 90% of these groups are associated with proteins, the majority in the —SH form. The content of protein-bound groups, and hence the total content of —SH and —SS— groups (28 × 10^-15 moles/cell, or 1.1 × 10^-6 moles/g protein on average), changes in parallel with the protein content (which varies between 2 and 4 × 10^-10 g/cell) as asynchronous populations pass from the lag through the exponential to the stationary phase of growth. The concentration of nonprotein —SH groups, in contrast, increases 10-fold during lag phase and decreases in stationary phase; it follows the protein concentration closely during the exponential phase, at a level of about 2.8 × 10^-15 moles/cell. In synchronous cultures the protein content doubles during the cell cycle, possibly in an exponential fashion. The total —SH and —SS— content also doubles, but the rate of increase appears to fluctuate. The concentrations of the protein-bound groups show 2- to 3-fold fluctuations per unit protein: protein-bound —SH groups and mixed —SS— linkages rise to maxima while protein-bound —SS— groups fall to a minimum at the G₁/S transition, and fluctuations in these groups occur again during G₂. In addition, the protein-bound —SH concentration falls continuously during the S phase. The nonprotein —SH concentration undergoes the largest (relative) fluctuations, dropping from 4 × 10^-15moles/cell in early G₁ to about 0.4 × 10^-15 moles/cell (of standard protein content) at the end of G₁, and then rising to 30 times this value by the end of S.     

Reconciling competing mechanisms posited to underlie auditory verbal hallucinations

Perception is not the passive registration of incoming sensory data. Rather, it involves some analysis by synthesis, based on past experiences and context. One adaptive consequence of this arrangement is imagination—the ability to richly simulate sensory experiences, interrogate and manipulate those simulations, in service of action and decision making. In this paper, we will discuss one possible cost of this adaptation, namely hallucinations—perceptions without sensory stimulation, which characterize serious mental illnesses like schizophrenia, but which also occur in neurological illnesses, and—crucially for the present piece—are common also in the non-treatment-seeking population. We will draw upon a framework for imagination that distinguishes voluntary from non-voluntary experiences and explore the extent to which the varieties and features of hallucinations map onto this distinction, with a focus on auditory-verbal hallucinations (AVHs)—colloquially, hearing voices. We will propose that sense of agency for the act of imagining is key to meaningfully dissecting different forms and features of AVHs, and we will outline the neural, cognitive and phenomenological sequelae of this sense. We will conclude that a compelling unifying framework for action, perception and belief—predictive processing—can incorporate observations regarding sense of agency, imagination and hallucination.This article is part of the theme issue ‘Offline perception: voluntary and spontaneous perceptual experiences without matching external stimulation’.     

THE GEOTROPIC REACTION OF RODLESS MICE IN LIGHT AND IN DARKNESS

"Black—short ears—kinky tail—rodless" mice, controlled by "pink eyed—dilute—brown" mice, were tested on an inclined plane in order to determine if they are photically sensitive, and, if so, to get a quantitative expression for their visual receptivity. Rodless and control animals were tested in the dark to obtain an expression for normal geotropic orientation. Light was then introduced to modify these reactions if possible. Under light, the controls failed to orient, whereas the rodless gave reactions almost identical with those in the dark. This test has failed in this experiment to suggest sight in the rodless mouse.     

BASE: A novel workflow to integrate nonubiquitous genes in comparative genomics analyses for selection

Inferring the selective forces that orthologous genes underwent across different lineages can help us understand the evolutionary processes that have shaped their extant diversity and the phenotypes they underlie. The most widespread metric to estimate the selection regimes of coding genes—across sites and phylogenies—is the ratio of nonsynonymous to synonymous substitutions (dN/dS, also known as ω). Nowadays, modern sequencing technologies and the large amount of already available sequence data allow the retrieval of thousands of orthologous genes across large numbers of species. Nonetheless, the tools available to explore selection regimes are not designed to automatically process all genes, and their practical usage is often restricted to the single‐copy ones which are found across all species considered (i.e., ubiquitous genes). This approach limits the scale of the analysis to a fraction of single‐copy genes, which can be as low as an order of magnitude in respect to those which are not consistently found in all species considered (i.e., nonubiquitous genes). Here, we present a workflow named BASE that—leveraging the CodeML framework—eases the inference and interpretation of gene selection regimes in the context of comparative genomics. Although a number of bioinformatics tools have already been developed to facilitate this kind of analyses, BASE is the first to be specifically designed to allow the integration of nonubiquitous genes in a straightforward and reproducible manner. The workflow—along with all relevant documentation—is available at github.com/for‐giobbe/BASE.     

Science vs Conspiracy: Collective Narratives in the Age of Misinformation

The large availability of user provided contents on online social media facilitates people aggregation around shared beliefs, interests, worldviews and narratives. In spite of the enthusiastic rhetoric about the so called collective intelligence unsubstantiated rumors and conspiracy theories—e.g., chemtrails, reptilians or the Illuminati—are pervasive in online social networks (OSN). In this work we study, on a sample of 1.2 million of individuals, how information related to very distinct narratives—i.e. main stream scientific and conspiracy news—are consumed and shape communities on Facebook. Our results show that polarized communities emerge around distinct types of contents and usual consumers of conspiracy news result to be more focused and self-contained on their specific contents. To test potential biases induced by the continued exposure to unsubstantiated rumors on users’ content selection, we conclude our analysis measuring how users respond to 4,709 troll information—i.e. parodistic and sarcastic imitation of conspiracy theories. We find that 77.92% of likes and 80.86% of comments are from users usually interacting with conspiracy stories.     

Towards an evolutionary theory of the origin of life based on kinetics and thermodynamics

A sudden transition in a system from an inanimate state to the living state—defined on the basis of present day living organisms—would constitute a highly unlikely event hardly predictable from physical laws. From this uncontroversial idea, a self-consistent representation of the origin of life process is built up, which is based on the possibility of a series of intermediate stages. This approach requires a particular kind of stability for these stages—dynamic kinetic stability (DKS)—which is not usually observed in regular chemistry, and which is reflected in the persistence of entities capable of self-reproduction. The necessary connection of this kinetic behaviour with far-from-equilibrium thermodynamic conditions is emphasized and this leads to an evolutionary view for the origin of life in which multiplying entities must be associated with the dissipation of free energy. Any kind of entity involved in this process has to pay the energetic cost of irreversibility, but, by doing so, the contingent emergence of new functions is made feasible. The consequences of these views on the studies of processes by which life can emerge are inferred.     

Proportionality: A Valid Alternative to Correlation for Relative Data

In the life sciences, many measurement methods yield only the relative abundances of different components in a sample. With such relative—or compositional—data, differential expression needs careful interpretation, and correlation—a statistical workhorse for analyzing pairwise relationships—is an inappropriate measure of association. Using yeast gene expression data we show how correlation can be misleading and present proportionality as a valid alternative for relative data. We show how the strength of proportionality between two variables can be meaningfully and interpretably described by a new statistic ϕ which can be used instead of correlation as the basis of familiar analyses and visualisation methods, including co-expression networks and clustered heatmaps. While the main aim of this study is to present proportionality as a means to analyse relative data, it also raises intriguing questions about the molecular mechanisms underlying the proportional regulation of a range of yeast genes.     

Characteristics of the process of enzyme release from secretory plant cells

Secretion—the outward movement of molecules across the plasmalemma—of α-amylase by barley (Hordeum vulgare L. cv. Himalaya) aleurone layers is an energy-dependent process that is not directly dependent upon protein synthesis or RNA synthesis and does not appear to be under the direct control of gibberellic acid or abscisic acid. Release—the movement of the secreted α-amylase molecules through the walls into the surrounding medium—is apparently diffusion limited and is markedly dependent upon the presence of ions.     

Beyond the white coat ceremony

Note from Anna B. Reisman, Co-Director, Yale Internal Medicine Residency Writers’ Workshop, Assistant Professor, Department of Internal Medicine, Yale University School of Medicine and VA Connecticut Health Care System: This issue inaugurates a new feature: selected writings from the Yale Internal Medicine Residency Program’s Writers’ Workshop. The annual workshop began in 2003. Abraham Verghese and Richard Selzer, among the best known physician-writers in the United States, have served as workshop leaders, teaching the craft of writing to more than 35 residents. In designing the workshop with my co-director, Dr. Asghar Rastegar, our aim was to make participants better physicians by providing a creative outlet for reflection. The tempo of a resident’s day is typically furious — one patient dies, perhaps, another sickens, a third refuses a necessary procedure, a fourth’s wife cries inconsolably at the bedside — with no time in between to ponder what happened, much less what it meant to the patient or to the resident and how it might shape the way the resident practices medicine in the future. Without time to muse about the experience, many residents take the easy road: They emotionally detach. Writing, we believe, can be an antidote to this tendency. The exercise of writing not only makes us empathic; it also sharpens our diagnostic skills. One of the keys to compelling writing is attention to detail: the nervous twitch of an old man’s eye muscles or the decayed front teeth of a young woman, a former crack addict. Such details not only make our writing come alive but also sensitize us to our patients’ plights and sharpen our diagnostic skills. The stories and essays written by the Writers’ Workshop participants present a range of experiences, real and imagined, and take us deep into the minds of young doctors trying to make sense of what they do.     

Modeling the Effect of APC Truncation on Destruction Complex Function in Colorectal Cancer Cells

In colorectal cancer cells, APC, a tumor suppressor protein, is commonly expressed in truncated form. Truncation of APC is believed to disrupt degradation of β—catenin, which is regulated by a multiprotein complex called the destruction complex. The destruction complex comprises APC, Axin, β—catenin, serine/threonine kinases, and other proteins. The kinases and , which are recruited by Axin, mediate phosphorylation of β—catenin, which initiates its ubiquitination and proteosomal degradation. The mechanism of regulation of β—catenin degradation by the destruction complex and the role of truncation of APC in colorectal cancer are not entirely understood. Through formulation and analysis of a rule-based computational model, we investigated the regulation of β—catenin phosphorylation and degradation by APC and the effect of APC truncation on function of the destruction complex. The model integrates available mechanistic knowledge about site-specific interactions and phosphorylation of destruction complex components and is consistent with an array of published data. We find that the phosphorylated truncated form of APC can outcompete Axin for binding to β—catenin, provided that Axin is limiting, and thereby sequester β—catenin away from Axin and the Axin-recruited kinases and . Full-length APC also competes with Axin for binding to β—catenin; however, full-length APC is able, through its SAMP repeats, which bind Axin and which are missing in truncated oncogenic forms of APC, to bring β—catenin into indirect association with Axin and Axin-recruited kinases. Because our model indicates that the positive effects of truncated APC on β—catenin levels depend on phosphorylation of APC, at the first 20-amino acid repeat, and because phosphorylation of this site is mediated by , we suggest that is a potential target for therapeutic intervention in colorectal cancer. Specific inhibition of is predicted to limit binding of β—catenin to truncated APC and thereby to reverse the effect of APC truncation.