Targeted mapping of Cdu1, a major locus regulating grain cadmium concentration in durum wheat (Triticum turgidum L. var durum).

Some durum wheat (Triticum turgidum L. var durum) cultivars have the genetic propensity to accumulate cadmium (Cd) in the grain. A major gene controlling grain Cd concentration designated as Cdu1 has been reported on 5B, but the genetic factor(s) conferring the low Cd phenotype are currently unknown. The objectives of this study were to saturate the chromosomal region harboring Cdu1 with newly developed PCR-based markers and to investigate the colinearity of this wheat chromosomal region with rice (Oryza sativa L.) and Brachypodium distachyon genomes. Genetic mapping of markers linked to Cdu1 in a population of recombinant inbred substitution lines revealed that the gene(s) associated with variation in Cd concentration resides in wheat bin 5BL9 between fraction breakpoints 0.76 and 0.79. Genetic mapping and quantitative trait locus (QTL) analysis of grain Cd concentration was performed in 155 doubled haploid lines from the cross W9262-260D3 (low Cd) by Kofa (high Cd) revealed two expressed sequence tag markers (ESMs) and one sequence tagged site (STS) marker that co-segregated with Cdu1 and explained >80% of the phenotypic variation in grain Cd concentration. A second, minor QTL for grain Cd concentration was also identified on 5B, 67 cM proximal to Cdu1. The Cdu1 interval spans 286 kbp of rice chromosome 3 and 282 kbp of Brachypodium chromosome 1. The markers and rice and Brachypodium colinearity described here represent tools that will assist in the positional cloning of Cdu1 and can be used to select for low Cd accumulation in durum wheat breeding programs targeting this trait. The isolation of Cdu1 will further our knowledge of Cd accumulation in cereals as well as metal accumulation in general.

"It's crucial they're treated as patients": ethical guidance and empirical evidence regarding treating doctor-patients.

Ethical guidance from the British Medical Association (BMA) about treating doctor-patients is compared and contrasted with evidence from a qualitative study of general practitioners (GPs) who have been patients. Semistructured interviews were conducted with 17 GPs who had experienced a significant illness. Their experiences were discussed and issues about both being and treating doctor-patients were revealed. Interpretative phenomenological analysis was used to evaluate the data. In this article data extracts are used to illustrate and discuss three key points that summarise the BMA ethical guidance, in order to develop a picture of how far experiences map onto guidance. The data illustrate and extend the complexities of the issues outlined by the BMA document. In particular, differences between experienced GPs and those who have recently completed their training are identified. This analysis will be useful for medical professionals both when they themselves are unwell and when they treat doctor-patients. It will also inform recommendations for professionals who educate medical students or trainees.

Abundance and distribution of iron on the moon.

The abundance and distribution of iron on the moon is derived from a near-global data set from Clementine. The determined iron content of the lunar highlands crust ( approximately 3 percent iron by weight) supports the hypothesis that much of the lunar crust was derived from a magma ocean. The iron content of lower crustal material exposed by the South Pole-Aitken impact basin on the lunar farside is higher ( approximately 7 to 8 percent by weight) and consistent with a basaltic composition. This composition supports earlier evidence that the lunar crust becomes more mafic with depth. The data also suggest that the bulk composition of the moon differs from that of the Earth's mantle. This difference excludes models for lunar origin that require the Earth and moon to have the same compositions, such as fission and coaccretion, and favors giant impact and capture.

Glue sniffing causes heart block in mice.

In mice, the inhalation of airplane glue or toluene fumes slows the sinoatrial rate, prolongs the P-R interval, and sensitizes the heart to asphyxia-induced atrioventricular block. In humans who sniff glue or solvents, similar mechanisms may be a cause of sudden death.

Automated surgical screwdriver: automated screw placement.

The use of power screwdrivers and drills for tapping and screw insertion in surgery is becoming more common. It has been established from clinical observations that the use of a small air drill for inserting self-tapping screws provides improved coaxial alignment and precision, and that the drill should be stopped before the screw head is completely seated on the plate, presumably to reduce the risk of over-tightening. The risk of overrun and over-tightening during tapping and screw insertion is increased with the use of power tools. Prevention of over-tightening is dependent upon when the surgeon detects the onset of tightening, both visually and from the feel of the rapid increase in torque. If detection is too late, then over-tightening or stripping can occur. This study is concerned with using a mechatronic screwdriver to control the tapping depth and to prevent the over-tightening of screws. The effects of various parameters upon the torque profile during tapping and screw insertion have been investigated in synthetic bone and sheep tibia. An automated system is proposed for preventing over-tightening of pre-tapped and self-tapping screws when attaching a surgical plate to a sheep tibia in vitro. The system was used to attach a plate to a sheep tibia using self-tapping screws. The mean torque of the screws inserted using the automated system was 35 per cent of the stripping torque.

Ventricular arrhythmias induced in monkeys by the inhalation of aerosol propellants.

After inhaling fluoroalkane gases, which are used as aerosol propellants, some people have died suddently and unexpectedly. Seeking an explanation, we had 14 monkeys inhale these gases. All developed ventricular premature beats, bigeminy, or tachycardia, which began at an average of 39 (SE +/-4.2) sec. Fluoroalkanes were present in blood, but arterial hypoxemia or hypercapnia was absent, and arterial pressure was reduced only slightly. In contrast, without fluoroalkanes, 3 min of asphyxia or anoxia caused arrhythmias in only one monkey whose arterial oxygen tension had fallen to 16 mm Hg. The ventricular arrhythmias caused in well oxygenated monkeys by fluoroalkane gases may either be mediated through beta adrenergic receptors, since propranolol abolished these arrhythmias, or result from a nonadrenergic, direct, toxic effect of these gases on the heart. These results suggest that some deaths after propellant inhalation may be caused by ventricular tachycardia or fibrillation.

Brief exposure of 0.05% chlorhexidine does not impair non-osteoarthritic human cartilage metabolism.

Jet lavage with chlorhexidine 0.05% is an effective means of wound decontamination with 99% of bacteria removed or killed after 1min. Reports of chondrolysis following exposure to concentrations of >0.05% or prolonged exposure to chlorhexidine have curtailed its use in orthopaedic practice. Using radiolabelled sulphur uptake to measure cartilage metabolism, we quantitatively assessed the in-vitro effect of osteoarthritic and non-osteoarthritic human cartilage exposure to chlorhexidine 0.05% for 1min and 1h. The metabolism of non-osteoarthritic cartilage was not significantly affected by a 1min exposure to chlorhexidine 0.05% whereas that of osteoarthritic cartilage was markedly impaired. Prolonged exposure for 1h markedly affected both types of cartilage. These results are encouraging in that 0.05% chlorhexidine may have a role in the decontamination of contaminated open joint injuries in patients with no signs of osteoarthritis. Until there is further understanding of the mechanism underlying reported incidents of chondrolysis following its use, however, it cannot be recommended for the irrigation of 'clean' articular cartilage.

X-ray-based machine vision system for distal locking of intramedullary nails.

In surgical procedures for femoral shaft fracture treatment, current techniques for locking the distal end of intramedullary nails, using two screws, rely heavily on the use of two-dimensional X-ray images to guide three-dimensional bone drilling processes. Therefore, a large number of X-ray images are required, as the surgeon uses his/her skills and experience to locate the distal hole axes on the intramedullary nail. The long-term effects of X-ray radiation and their relation to different types of cancer still remain uncertain. Therefore, there is a need to develop a surgical technique that can limit the use of X-rays during the distal locking procedure. A robotic-assisted orthopaedic surgery system has been developed at Loughborough University to assist orthopaedic surgeons by reducing the irradiation involved in such operations. The system simplifies the current approach as it uses only two near-orthogonal X-ray images to determine the drilling trajectory of the distal locking holes, thereby considerably reducing irradiation to both the surgeon and patient. Furthermore, the system uses robust machine vision features to reduce the surgeon's interaction with the system, thus reducing the overall operating time. Laboratory test results have shown that the proposed system is very robust in the presence of variable noise and contrast in the X-ray images.

Small-scale density variations in the lunar crust revealed by GRAIL.

Data from the Gravity Recovery and Interior Laboratory (GRAIL) mission have revealed that ~98% of the power of the gravity signal of the Moon at high spherical harmonic degrees correlates with the topography. The remaining 2% of the signal, which cannot be explained by topography, contains information about density variations within the crust. These high-degree Bouguer gravity anomalies are likely caused by small-scale (10's of km) shallow density variations. Here we use gravity inversions to model the small-scale three-dimensional variations in the density of the lunar crust. Inversion results from three non-descript areas yield shallow density variations in the range of 100-200 kg/m3. Three end-member scenarios of variations in porosity, intrusions into the crust, and variations in bulk crustal composition were tested as possible sources of the density variations. We find that the density anomalies can be caused entirely by changes in porosity. Characteristics of density anomalies in the South Pole-Aitken basin also support porosity as a primary source of these variations. Mafic intrusions into the crust could explain many, but not all of the anomalies. Additionally, variations in crustal composition revealed by spectral data could only explain a small fraction of the density anomalies. Nevertheless, all three sources of density variations likely contribute. Collectively, results from this study of GRAIL gravity data, combined with other studies of remote sensing data and lunar samples, show that the lunar crust exhibits variations in density by ±10% over scales ranging from centimeters to 100's of kilometers.

Comparative cost of myocardial revascularization: percutaneous transluminal angioplasty and coronary artery bypass surgery.

A consecutive series of 78 patients having percutaneous transluminal coronary angioplasty for single vessel coronary artery disease and 85 patients having single vessel coronary artery bypass graft surgery were followed up prospectively for 1 year. Days in hospital and angiographic and revascularization procedures were counted in the two groups of patients and total cost of care for 12 months was calculated using current billing levels. Angioplasty was initially successful in 74% of patients; because of initial failure in 26% and late restenosis in 18%, bypass surgery was ultimately needed in 23 of 78 patients having coronary angioplasty. Nevertheless, total cost of care per patient was 43% lower for those having angioplasty as an initial procedure for single vessel coronary artery disease.

Prospective assessment of regional myocardial perfusion before and after coronary revascularization surgery by quantitative thallium-201 scintigraphy.

Because thallium-201 uptake relates directly to the amount of viable myocardium and nutrient blood flow, the potential for exercise scintigraphy to predict response to coronary revascularization surgery was investigated in 47 consecutive patients. All patients underwent thallium-201 scintigraphy and coronary angiography at a mean (+/- standard deviation) of 4.3 +/- 3.1 weeks before and 7.5 +/- 1.6 weeks after surgery. Thallium uptake and washout were computer-quantified and each of six segments was defined as normal, showing total or partial redistribution or a persistent defect. Persistent defects were further classified according to the percent reduction in regional thallium activity; PD25-50 denoted a 25 to 50% constant reduction in relative thallium activity and PD greater than 50 denoted a greater than 50% reduction. Of 82 segments with total redistribution before surgery, 76 (93%) showed normal thallium uptake and washout postoperatively, versus only 16 (73%) of 22 with partial redistribution (probability [p] = 0.01). Preoperative ventriculography revealed that 95% of the segments with total redistribution had preserved wall motion, versus only 74% of those with partial redistribution (p = 0.01). Of 42 persistent defects thought to represent myocardial scar before surgery, 19 (45%) demonstrated normal perfusion postoperatively. Of the persistent defects that showed improved thallium perfusion postoperatively, 75% had normal or hypokinetic wall motion before surgery, versus only 14% of those without improvement (p less than 0.001). Whereas 57% of the persistent defects that showed a 25 to 50% decrease in myocardial activity demonstrated normal thallium uptake and washout postoperatively, only 21% of the persistent defects with a decrease in myocardial activity greater than 50% demonstrated improved perfusion after surgery (p = 0.02). Thus, preoperative quantitative thallium-201 scintigraphy appears useful in predicting response to revascularization surgery, and some persistent defects may revert to normal thallium uptake after surgery. Importantly, the preoperative distinction between viable and nonviable myocardium can be reasonably established by quantitating the amount of persistent reduction in thallium uptake and correlating this with preoperative wall motion.

Prognostic cardiac catheterization variables in survivors of acute myocardial infarction: a five year prospective study.

The prognostic variables from predischarge coronary angiography and left ventriculography in survivors of acute myocardial infarction during the years 1974 to 1978 were evaluated in 143 patients (less than or equal to 66 years of age) with documented myocardial infarction who were then followed up prospectively for 5 years. One half of the study population had triple vessel coronary disease (greater than or equal to 50% stenosis). However, only 7% of patients had severely depressed left ventricular function with an ejection fraction less than or equal to 29%. Evaluation of the contribution of many clinical and angiographic variables to a first cardiac event (death, nonfatal reinfarction or coronary artery bypass surgery) was considered with Kaplan-Meier actuarial curves and multivariate Cox's hazard function analysis. A risk segment was defined as an area of contracting myocardium supplied by a coronary artery with a greater than 50% stenosis. Multivariate analysis demonstrated that right plus left anterior descending coronary artery stenoses (p less than 0.01), ejection fraction (p less than 0.01) and the presence of risk segments (p less than 0.05) were significant predictors of outcome. Furthermore, on separate multivariate analyses, the angiographic variables added significantly to the clinical variables to predict cardiac events over 5 years of follow-up. Therefore, in survivors of acute myocardial infarction who undergo cardiac catheterization, additive prognostic information is obtained that can be used to stratify risk over 5 years.

Induction of Microsomal Membrane Proteins in Roots of an Aluminum-Resistant Cultivar of Triticum aestivum L. under Conditions of Aluminum Stress.

Three-day-old seedlings of an Al-sensitive (Neepawa) and an Al-resistant (PT741) cultivar of Triticum aestivum were subjected to Al concentrations ranging from 0 to 100 [mu]M for 72 h. At 25 [mu]M Al, growth of roots was inhibited by 57% in the Al-sensitive cultivar, whereas root growth in the Al-resistant cultivar was unaffected. A concentration of 100 [mu]M Al was required to inhibit root growth of the Al-resistant cultivar by 50% and resulted in almost total inhibition of root growth in the sensitive cultivar. Cytoplasmic and microsomal membrane fractions were isolated from root tips (first 5 mm) and the adjacent 2-cm region of roots of both cultivars. When root cytoplasmic proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, no changes in polypeptide patterns were observed in response to Al stress. Analysis of microsomal membrane proteins revealed a band with an apparent molecular mass of 51 kD, which showed significant accumulation in the resistant cultivar following Al exposure. Two-dimensional gel analysis revealed that this band comprises two polypeptides, each of which is induced by exposure to Al. The response of the 51-kD band to a variety of experimental conditions was characterized to determine whether its pattern of accumulation was consistent with a possible role in Al resistance. Accumulation was significantly greater in root tips when compared to the rest of the root. When seedlings were subjected to Al concentrations ranging from 0 to 150 [mu]M, the proteins were evident at 25 [mu]M and were fully accumulated at 100 [mu]M. Time-course studies from 0 to 96 h indicated that full accumulation of the 51-kD band occurred within 24 h of initiation of Al stress. With subsequent removal of stress, the polypeptides gradually disappeared and were no longer visible after 72 h. When protein synthesis was inhibited by cycloheximide, the 51-kD band disappeared even when seedlings were maintained in Al-containing media. Other metals, including Cu, Zn, and Mn, failed to induce this band, and Cd and Ni resulted in its partial accumulation. These results indicate that synthesis of the 51-kD microsomal membrane proteins is specifically induced and maintained during Al stress in the Al-resistant cultivar, PT741.

Differential Exudation of Polypeptides by Roots of Aluminum-Resistant and Aluminum-Sensitive Cultivars of Triticum aestivum L. in Response to Aluminum Stress.

Cultivars of Triticum aestivum differing in resistance to Al were grown under aseptic conditions in the presence and absence of Al and polypeptides present in root exudates were collected, concentrated, and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Upon exposure to 100 and 200 [mu]M Al, root elongation in Al-sensitive cultivars was reduced by 30 and 65%, respectively, whereas root elongation in resistant cultivars was reduced by only 15 and 30%. Accumulation of polypeptides in the growth medium increased with time for 96 to 120 h, with little additional accumulation thereafter. This pattern of exudation was virtually unaffected by exposure to 100 [mu]M Al in the Al-resistant cultivars Atlas 66 and Maringa, whereas total accumulation was reduced in sensitive cultivars. Changes in exudation were consistent with alterations in root elongation. Al-induced or Al-enhanced polypeptide bands were detected in Atlas 66 and Maringa after 72 h of exposure to Al. Increased accumulation of 12-, 22-, and 33-kD bands was observed at 75 [mu]M Al in Atlas 66 and 12-, 23-, and 43.5-kD bands started to appear at 50 [mu]M Al in Maringa. In the Al-sensitive cultivars Roblin and Katepwa, no significant effect on polypeptide profiles was observed at values up to 100 [mu]M Al. When root exudates were separated by ultrafiltration and the Al content was measured in both high molecular mass (HMM; >10 kD) and ultrafiltrate (<10 kD) fractions, approximately 2 times more Al was detected in HMM fractions from Al-resistant cultivars than from Al-sensitive cultivars. Dialysis of HMM fractions against water did not release this bound Al;digestion with protease released between 62 and 73% of total Al, with twice as much released from exudates of Al-resistant than of Al-sensitive cultivars. When plants were grown in the presence of 0 to 200 [mu]M Al, saturation of the Al-binding capacity of HMM exudates occurred at 50 [mu]M Al in Al-sensitive cultivars. Saturation was not achieved in resistant cultivars. Differences in exudation of total polypeptides in response to Al stress, enhanced accumulation of specific polypeptides, and the greater association of Al with HMM fractions from Al-resistant cultivars suggest that root exudate polypeptides may play a role in plant response to Al.

Accumulation of Al in Root Mucilage of an Al-Resistant and an Al-Sensitive Cultivar of Wheat.

To estimate rates of Al accumulation within the symplasm, all apoplastic pools of Al need to be eliminated or accounted for. We have developed a revised kinetic protocol that allows us to estimate the contribution of mucilage-bound Al to total, nonexchangeable Al, and to eliminate the mucilage as an apoplastic pool of Al. By comparing the Al content of excised root tips (2 cm) of wheat (Triticum aestivum L.) with and without the removal of the mucilage (using a 10-min wash in 1 M NH4Cl), we found that Al bound to the mucilage accounted for approximately 25 to 35% of Al remaining after desorption in citric acid. The kinetics of Al uptake into mucilage were biphasic, with a rapid phase occurring in the first 30 min of uptake, followed by a linear phase occurring in the remainder of the experimental period (180 min). By adopting a step for removal of mucilage into our existing kinetic protocol, we have been able to isolate a linear phase of uptake with only a slight deviation from linearity in the first 5 min. Although we cannot unambiguously identify this phase of uptake as uptake into the symplasm, we believe this new protocol provides us with the most accurate quantitative estimate of symplastic Al yet available.

Al-Induced, 51-Kilodalton, Membrane-Bound Proteins Are Associated with Resistance to Al in a Segregating Population of Wheat.

Incorporation of 35S into protein is reduced by exposure to Al in wheat (Triticum aestivum), but the effects are genotype-specific. Exposure to 10 to 75 [mu]M Al had little effect on 35S incorporation into total protein, nuclear and mitochondrial protein, microsomal protein, and cytosolic protein in the Al-resistant cultivar PT741. In contrast, 10 [mu]M Al reduced incorporation by 21 to 38% in the Al-sensitive cultivar Katepwa, with effects becoming more pronounced (31-62%) as concentrations of Al increased. We previously reported that a pair of 51-kD membrane-bound proteins accumulated in root tips of PT741 under conditions of Al stress. We now report that the 51-kD band is labeled with 35S after 24 h of exposure to 75 [mu]M Al. The specific induction of the 51-kD band in PT741 suggested a potential role of one or both of these proteins in mediating resistance to Al. Therefore, we analyzed their expression in single plants from an F2 population arising from a cross between the PT741 and Katepwa cultivars. Accumulation of 1,3-[beta]-glucans (callose) in root tips after 24 h of exposure to 100 [mu]M Al indicated that this population segregated for Al resistance in about a 3:1 ratio. A close correlation between resistance to Al (low callose content of root tips) and accumulation of the 51-kD band was observed, indicating that at least one of these proteins cosegregates with the Al-resistance phenotype. As a first step in identifying a possible function, we have demonstrated that the 51-kD band is most clearly associated with the tonoplast. Whereas Al has been reported to stimulate the activity of the tonoplast H+-ATPase and H+-PPase, antibodies raised against these proteins did not cross-react with the 51-kD band. Efforts are now under way to purify this protein from tonoplast-enriched fractions.

Traumatic pericardiocentesis: two-dimensional echocardiographic visualization of an unfortunate event.

Two-dimensional echocardiography was performed simultaneously with pericardiocentesis in an attempt to visualize the pericardiocentesis needle. Rapid penetration of the right ventricular myocardium by the pericardiocentesis needle occurred and was only appreciated in a slow-motion analysis of the two-dimensional echocardiogram videotape. Development of an intrapericardial thrombus was clearly detected by the two-dimensional echocardiogram videotape. Development of an intrapericardial thrombus was clearly detected by the two-dimensional echocardiogram within 24 hours following this traumatic pericardiocentesis. While two-dimensional echocardiography may offer the possibility for seeing the pericardiocentesis needle, technical considerations may limit the easy visualization of the pericardiocentesis needle and accurate localization of its tip. However, two-dimensional echocardiography may be useful in identifying consequences of suspected or proved traumatic pericardiocentesis procedures.

Left ventricular mural thrombus in a patient with thrombocytosis and agnogenic myeloid metaplasia.

The two factors responsible for the development of left ventricular mural thrombi are endocardial injury secondary to old or recent anterior myocardial infarction and left ventricular dysfunction. Endothelial damage also is thought to be the initial event in the development of arterial thrombi. However, arterial thrombi may develop in patients with thrombocytosis secondary to myeloproliferative disorders in the absence of endothelial injury. A patient had thrombocytosis secondary to agnogenic myeloid metaplasia and a left ventricular mural thrombus developed in the absence of clinical or laboratory evidence of old or coronary angiogram and left ventricular function. To our knowledge, this is the first such case reported.

Alexithymia: concept, measurement, and implications for treatment.

Alexithymia refers to a specific disturbance in psychic functioning characterized by difficulties in the capacity to verbalize affect and to elaborate fantasies. Although initially described in the context of psychosomatic illness, alexithymic characteristics may be observed in patients with a wide range of medical and psychiatric disorders. The author reviews the concept of alexithymia, including its historical background, clinical and demographic features, and possible etiology. He critically evaluates the different methods used to measure alexithymia and discusses the important implications it has for medical and psychiatric treatment.

A preliminary investigation of alexithymia in men with psychoactive substance dependence.

The prevalence of alexithymia in a group of newly abstinent male substance abusers (N = 44) was 50%. The alexithymic patients had significantly less ego strength and repressive defensive behavior and significantly higher levels of somatic complaints and general dysphoria.