Acid–Base Status of Adults with Sickle-cell Anaemia

Determinations of the acid–base status of 10 adult Jamaican patients with sickle-cell anaemia during “painful crisis” and after recovery showed no evidence of metabolic acidosis in the former, in contrast to reports from elsewhere. These results could explain the failure of alkalis to abort or alter the acute painful episodes of most patients with sickle-cell anaemia.     

Blood Pressure: A Consideration of Terminology

Concepts of hypertension have changed and changes in terminology to reflect this state of affairs are suggested. Statistically, the best mortality experience is associated with blood pressure commonly regarded as subnormal, and increments of blood pressure above this level are associated with progressive increases in mortality. The terms “normal”, “benign” and “essential” in relation to blood pressure should be abandoned. “Optimal”, “acceptable” and “hypertensive” ranges of blood pressure are suggested. Hypertension is regarded as a symptom of disease, rather than as a disease in itself, and “hypertension”, when used as a diagnostic label, should be qualified always by the primary disease, if known, or by the modifying phrase, “of unknown cause”, if not known.     

“Unwarranted survivals” and “anomalous deaths” from coronary heart disease: prospective survey of general population

ObjectivesTo assess survival in people who are at apparent high risk who do not develop coronary heart disease (“unwarranted survivals”) and mortality in people at low risk who die from the disease (“anomalous deaths”) and the extent to which these outcomes are explained by other, less visible, risk factors.DesignProspective general population survey.SettingRenfrew and Paisley, Scotland.Participants6068 men aged 45-64 years at screening in 1972-6, allocated to “visible” risk groups on the basis of body mass index and smoking.ResultsVisible risk was a good predictor of mortality: 13% (45) of men at low risk and 45% (86) of men at high risk had died by age 70 years. Of these deaths, 12 (4%) and 44 (23%), respectively, were from coronary heart disease. In the group at low visible risk other less visible risk factors accounted for increased risk in 83% (10/12) of men who died from coronary heart disease and 29% (84/292) of men who survived. In the high risk group 81/107 who survived (76%) and 19/44 (43%) who died from coronary heart disease had lower risk after other factors were considered. Different risk factors modified risk (beyond smoking and body mass index) in the two groups. Among men at low visible risk, poor respiratory function, diabetes, previous coronary heart disease, and socioeconomic deprivation modified risk. Among men at high visible risk, height and cholesterol concentration modified risk.ConclusionsDifferences in survival between these extreme risk groups are dramatic. Health promotion messages would be more credible if they discussed anomalies and the limits of prediction of coronary disease at an individual level.

What is already known on this topic

People pay attention to visible risk factors, such as smoking and weight, in explaining or predicting coronary events but are aware that these behavioural risk factors fail to explain some early deaths from coronary heart disease (in those with “low risk” lifestyles) and long survival (in those with “high risk” lifestyles)Such violations to notions of coronary candidacy undermine people''s belief in the worth of modifying behavioural risk factors for coronary heart disease

What this study adds

Visible risk status was a good marker for other coronary risk factors at the extremes of the risk distributionMost men at low visible risk (slim, never smoked) who died prematurely from coronary heart disease had poorer risk profiles on other less visible risk factors; similarly, men at high visible risk (obese, heavy smokers) who survived often had more favourable profiles on other risk factors     

Survival of the Curviest: Noise-Driven Selection for Synergistic Epistasis

A major goal of human genetics is to elucidate the genetic architecture of human disease, with the goal of fueling improvements in diagnosis and the understanding of disease pathogenesis. The degree to which epistasis, or non-additive effects of risk alleles at different loci, accounts for common disease traits is hotly debated, in part because the conditions under which epistasis evolves are not well understood. Using both theory and evolutionary simulation, we show that the occurrence of common diseases (i.e. unfit phenotypes with frequencies on the order of 1%) can, under the right circumstances, be expected to be driven primarily by synergistic epistatic interactions. Conditions that are necessary, collectively, for this outcome include a strongly non-linear phenotypic landscape, strong (but not too strong) selection against the disease phenotype, and “noise” in the genotype-phenotype map that is both environmental (extrinsic, time-correlated) and developmental (intrinsic, uncorrelated) and, in both cases, neither too little nor too great. These results suggest ways in which geneticists might identify, a priori, those disease traits for which an “epistatic explanation” should be sought, and in the process better focus ongoing searches for risk alleles.     

The Cost of Simplifying Air Travel When Modeling Disease Spread

Background

Air travel plays a key role in the spread of many pathogens. Modeling the long distance spread of infectious disease in these cases requires an air travel model. Highly detailed air transportation models can be over determined and computationally problematic. We compared the predictions of a simplified air transport model with those of a model of all routes and assessed the impact of differences on models of infectious disease.

Methodology/Principal Findings

Using U.S. ticket data from 2007, we compared a simplified “pipe” model, in which individuals flow in and out of the air transport system based on the number of arrivals and departures from a given airport, to a fully saturated model where all routes are modeled individually. We also compared the pipe model to a “gravity” model where the probability of travel is scaled by physical distance; the gravity model did not differ significantly from the pipe model. The pipe model roughly approximated actual air travel, but tended to overestimate the number of trips between small airports and underestimate travel between major east and west coast airports. For most routes, the maximum number of false (or missed) introductions of disease is small (<1 per day) but for a few routes this rate is greatly underestimated by the pipe model.

Conclusions/Significance

If our interest is in large scale regional and national effects of disease, the simplified pipe model may be adequate. If we are interested in specific effects of interventions on particular air routes or the time for the disease to reach a particular location, a more complex point-to-point model will be more accurate. For many problems a hybrid model that independently models some frequently traveled routes may be the best choice. Regardless of the model used, the effect of simplifications and sensitivity to errors in parameter estimation should be analyzed.     

Use of positive pressures to establish vulnerability curves : further support for the air-seeding hypothesis and implications for pressure-volume analysis

Loss of hydraulic conductivity occurs in stems when the water in xylem conduits is subjected to sufficiently negative pressure. According to the air-seeding hypothesis, this loss of conductivity occurs when air bubbles are sucked into water-filled conduits through micropores adjacent to air spaces in the stem. Results in this study showed that loss of hydraulic conductivity occurred in stem segments pressurized in a pressure chamber while the xylem water was under positive pressure. Vulnerability curves can be defined as a plot of percentage loss of hydraulic conductivity versus the pressure difference between xylem water and the outside air inducing the loss of conductivity. Vulnerability curves were similar whether loss of conductivity was induced by lowering the xylem water pressure or by raising the external air pressure. These results are consistent with the air-seeding hypothesis of how embolisms are nucleated, but not with the nucleation of embolisms at hydrophobic cracks because the latter requires negative xylem water pressure. The results also call into question some basic underlying assumptions used in the determination of components of tissue water potential using “pressure-volume” analysis.     

Framingham Risk Score with Cardiovascular Events in Chronic Kidney Disease

The Framingham Risk Score (FRS) was developed to predict coronary heart disease in various populations, and it tended to under-estimate the risk in chronic kidney disease (CKD) patients. Our objectives were to determine whether FRS was associated with cardiovascular events, and to evaluate the role of new risk markers and echocardiographic parameters when they were added to a FRS model. This study enrolled 439 CKD patients. The FRS is used to identify individuals categorically as “low” (<10% of 10-year risk), “intermediate” (10–20% risk) or “high” risk (≧ 20% risk). A significant improvement in model prediction was based on the −2 log likelihood ratio statistic and c-statistic. “High” risk (v.s. “low” risk) predicts cardiovascular events either without (hazard ratios [HR] 2.090, 95% confidence interval [CI] 1.144 to 3.818) or with adjustment for clinical, biochemical and echocardiographic parameters (HR 1.924, 95% CI 1.008 to 3.673). Besides, the addition of albumin, hemoglobin, estimated glomerular filtration rate, proteinuria, left atrial diameter >4.7 cm, left ventricular hypertrophy or left ventricular ejection fraction<50% to the FRS model significantly improves the predictive values for cardiovascular events. In CKD patients, “high” risk categorized by FRS predicts cardiovascular events. Novel biomarkers and echocardiographic parameters provide additional predictive values for cardiovascular events. Future study is needed to assess whether risk assessment enhanced by using these biomarkers and echocardiographic parameters might contribute to more effective prediction and better care for patients.     

Odors and Sensations of Humidity and Dryness in Relation to Sick Building Syndrome and Home Environment in Chongqing,China

The prevalence of perceptions of odors and sensations of air humidity and sick building syndrome symptoms in domestic environments were studied using responses to a questionnaire on the home environment. Parents of 4530 1–8 year old children from randomly selected kindergartens in Chongqing, China participated. Stuffy odor, unpleasant odor, pungent odor, mold odor, tobacco smoke odor, humid air and dry air in the last three month (weekly or sometimes) was reported by 31.4%, 26.5%, 16.1%, 10.6%, 33.0%, 32.1% and 37.2% of the parents, respectively. The prevalence of parents’ SBS symptoms (weekly or sometimes) were: 78.7% for general symptoms, 74.3% for mucosal symptoms and 47.5% for skin symptoms. Multi-nominal regression analyses for associations between odors/sensations of air humidity and SBS symptoms showed that the odds ratio for “weekly” SBS symptoms were consistently higher than for “sometimes” SBS symptoms. Living near a main road or highway, redecoration, and new furniture were risk factors for perceptions of odors and sensations of humid air and dry air. Dampness related problems (mold spots, damp stains, water damage and condensation) were all risk factors for perceptions of odors and sensations of humid air and dry air, as was the presence of cockroaches, rats, and mosquitoes/flies, use of mosquito-repellent incense and incense. Protective factors included cleaning the child’s bedroom every day and frequently exposing bedding to sunshine. In conclusion, adults’ perceptions of odors and sensations of humid air and dry air are related to factors of the home environment and SBS symptoms are related to odor perceptions.     

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.     

Network Effects of Risk Behavior Change Following Prophylactic Interventions

We formulated a network-based model to understand how risk behavior change in conjunction with failure of prophylactic interventions can lead to unintended outcomes where “less (intervention) is more (effective).” Our model captures the distinction between one- and two-sided risk behavior change. In one-sided situations (e.g. influenza/H1N1) it is sufficient for either individual in an interaction to exhibit risk behavior change whereas in two-sided situations (e.g. AIDS/HIV) it is necessary for both individuals in the interaction to exhibit risk behavior change, for a potential transmission of the disease. A central discovery is that this phenomenon occurs at differing levels of intervention coverage depending upon the “sidedness” of the interaction. We find that for one-sided interactions, sufficiently high vaccination coverage is necessary for mitigating the effects of risk behavior; for two-sided interactions, it is essential to combine prophylactic treatments with programs aimed at reducing risky behavior. Furthermore, again dependent on the “sidedness,” targeting highly connected nodes can be strictly worse than uniformly random interventions at the same level of coverage.     

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.     

Passive smoking and lung cancer: a publication bias?

To assess the likelihood of publication bias in a recent review of the effect of passive smoking on lung cancer the evidence from the reviewed papers was visualised on a “funnel” plot. In such a plot if the relative risks from various studies are plotted according to sample size they should scatter round some underlying true value, the scatter being greatest where the studies have the lowest statistical power—thus showing a “funnel” pattern. If there is publication bias and studies with non-significant results are not being published there should be a “gap” in the plot. The logarithm of the relative risks was plotted against the standard error of the logarithm of the relative risk (which was used instead of sample size as a measure of statistical uncertainty). The resulting plot was compatible with a publication bias but only in studies on men.Further studies of passive smoking and lung cancer in men seem to be warranted.     

Aerosolization of Respirable Droplets from a Domestic Spa Pool and the Use of MS-2 Coliphage and Pseudomonas aeruginosa as Markers for Legionella pneumophila

Legionnaires'' disease can result when droplets or aerosols containing legionella bacteria are inhaled and deposited in the lungs. A number of outbreaks have been associated with the use of a spa pool where aeration, a high water temperature, and a large and variable organic load make disinfectant levels difficult to maintain. Spa pool ownership is increasing, and the aim of this study, using two surrogate organisms (MS-2 coliphage and Pseudomonas aeruginosa [a natural contaminant]), was to assess the potential risk to domestic users when disinfection fails. A representative “entry level” domestic spa pool was installed in an outdoor courtyard. The manufacturer''s instructions for spa pool maintenance were not followed. A cyclone sampler was used to sample the aerosols released from the spa pool with and without activation of the air injection system. Samples were taken at increasing heights and distances from the pool. An aerodynamic particle sizer was used to measure the water droplet size distribution at each sample point. When the air injection system was inactivated, neither surrogate organism was recovered from the air. On activation of the air injection system, the mean mass of droplets within the respirable range (10 cm above the water line) was 36.8 μg cm⁻³. This corresponded to a mean air concentration of P. aeruginosa of 350 CFU m⁻³. From extrapolation from animal data, the estimated risk of infection from aerosols contaminated with similar concentrations of Legionella pneumophila was 0.76 (males) and 0.65 (females). At 1 m above and/or beyond the pool, the mean aerosol mass decreased to 0.04 μg cm⁻³ and corresponded to a 100-fold reduction in mean microbial air concentration. The estimated risk of infection at this distance was negligible.     

The changing pattern of ischemic heart disease

Male and female death rates from all the major forms of cardiovascular disease were approximately equal until about 1920. Since that time the male:female ratio in fatal ischemic heart disease (IHD) has risen dramatically, but some closely related diseases such as cerebrovascular disease and uncomplicated angina pectoris have maintained sex ratios close to unity. It is difficult to reconcile this divergent trend in the sex ratio of IHD with a simple stenotic-thrombotic view of myocardial infarction (MI) and it is suggested that the modern epidemic of MI in men may be the result of a disorder of muscle metabolism (“vulnerable myocardium”) superimposed on a relatively stable background of stenotic-thrombotic arterial disease. The proposed mechanism would also help to explain the selective action of some modern “coronary risk factors” (such as cigarette smoking and physical inactivity) which increase the risk of MI but have little or no effect on the risk of developing cerebrovascular disease or uncomplicated angina pectoris.     

The Association of 5-HT2A, 5-HTT,and LEPR Polymorphisms with Obstructive Sleep Apnea Syndrome: A Systematic Review and Meta-Analysis

Objective

A consensus has not been reached regarding the association of several different gene polymorphisms and susceptibility to obstructive sleep apnea syndrome (OSAS). We performed a meta-analysis to better evaluate the associations between 5-HT2A, 5-HTT, and LEPR polymorphisms, and OSAS.

Method

5-HT2A, 5-HTT, and LEPR polymorphisms and OSAS were identified in PubMed and EMBASE. The pooled odd rates (ORs) with 95%CIs were estimated using a fixed-effect or random-effect models. The associations between these polymorphisms and OSAS risk were assessed using dominant, recessive and additive models.

Results

Twelve publications were included in this study. The -1438 “A” allele of 5-HT2A was identified as a candidate genetic risk factor for OSAS (OR: 2.33, 95%CI 1.49–3.66). Individuals carrying the -1438 “G” allele had a nearly 70% reduced risk of OSAS when compared with AA homozygotes (OR: 0.30, 95%CI 0.23–0.40). There was no significant association between 5-HT2A 102C/T and OSAS risk, using any model. The “S” allele of 5-HTTLPR conferred protection against OSAS (OR: 0.80, 95%CI 0.67–0.95), while the “10” allele of 5-HTTVNTR contributed to the risk of OSAS (OR: 2.08, 95%CI: 1.58–2.73). The “GG” genotype of LEPR was associated with a reduced risk of OSAS (OR: 0.39, 95%CI 0.17–0.88).

Conclusion

The meta-analysis demonstrated that 5-HTR-1438 “A” and 5-HTTVNTR “10” alleles were significantly associated with OSAS. The “S” allele of 5-HTTLPR and the “GG” genotype of LEPR conferred protection against OSAS. Further studies, such as Genome-Wide Association study (GWAS), should be conducted in a large cohort of OSAS patients to confirm our findings.     

The Epidemiologist's Dilemma: A Position Paper on the Role of Epidemiology in Canadian Research

Canadian epidemiology is currently in transition from being primarily interested in infectious disease to becoming active in investigating causes of non-infectious disease. Generally, epidemiologists limit their work to “field”, “basic”, or “theoretical” epidemiology. In all three fields there appears to be a shortage of qualified personnel which is likely to become even more acute because of new roles that epidemiologists will probably play in the future. A minimum of 40 full-time epidemiologists is currently required in Canada.Departments other than departments of preventive medicine at medical schools and teaching hospitals are currently spending 79.5% of all funds allocated for non-microbiological epidemiological research in Canada. Since epidemiology is by its very nature population orientated, rather than clinically orientated, clinicians require consultative advice from epidemiologists at many stages of their research. Epidemiological facilities in departments of preventive medicine should therefore be strengthened in order to provide research training and didactic courses needed as the numbers of physicians, nurses and paramedical persons are increased.     

Temporal Characteristics of Online Syntactic Sentence Planning: An Event-Related Potential Study

During sentence production, linguistic information (semantics, syntax, phonology) of words is retrieved and assembled into a meaningful utterance. There is still debate on how we assemble single words into more complex syntactic structures such as noun phrases or sentences. In the present study, event-related potentials (ERPs) were used to investigate the time course of syntactic planning. Thirty-three volunteers described visually animated scenes using naming formats varying in syntactic complexity: from simple words (‘W’, e.g., “triangle”, “red”, “square”, “green”, “to fly towards”), to noun phrases (‘NP’, e.g., “the red triangle”, “the green square”, “to fly towards”), to a sentence (‘S’, e.g., “The red triangle flies towards the green square.”). Behaviourally, we observed an increase in errors and corrections with increasing syntactic complexity, indicating a successful experimental manipulation. In the ERPs following scene onset, syntactic complexity variations were found in a P300-like component (‘S’/‘NP’>‘W’) and a fronto-central negativity (linear increase with syntactic complexity). In addition, the scene could display two actions - unpredictable for the participant, as the disambiguation occurred only later in the animation. Time-locked to the moment of visual disambiguation of the action and thus the verb, we observed another P300 component (‘S’>‘NP’/‘W’). The data show for the first time evidence of sensitivity to syntactic planning within the P300 time window, time-locked to visual events critical of syntactic planning. We discuss the findings in the light of current syntactic planning views.     

Screening for Hepatocellular Carcinoma: Review and Perspective

In patients with hepatocellular carcinoma, early diagnosis offers the only hope for resection and cure. Data from Asia, where it is closely associated with viral hepatitis, indicate that serum α-fetoprotein assay and abdominal ultrasonography are the most effective and feasible screening tests. These data may not be applicable in America, where most patients at risk for hepatocellular carcinoma have underlying alcoholic cirrhosis. Also, it is unclear whether resecting “curable” lesions prolongs survival, particularly in patients with cirrhosis. Screening trials are indicated to answer these questions. Preventing risk factors, however, especially hepatitis B viral disease, is of paramount importance throughout the world.