Robust impurity detection and tracking for tokamaks.

A robust impurity detection and tracking code, able to generate large sets of dust tracks from tokamak camera footage, is presented. This machine learning-based code is tested with cameras from the Joint European Torus, Doublet-III-D, and Magnum-PSI and is able to generate dust tracks with a 65-100% classification accuracy. Moreover, the number dust particles detected from a single camera shot can be up to the order of 1000. Several areas of improvement for the code are highlighted, such as generating more significant training data sets and accounting for selection biases. Although the code is tested with dust in single two-dimensional camera views, it could easily be applied to multiple-camera stereoscopic reconstruction or nondust impurities.

Systemic gene delivery transduces the enteric nervous system of guinea pigs and cynomolgus macaques.

Characterization of adeno-associated viral vector (AAV) mediated gene delivery to the enteric nervous system (ENS) was recently described in mice and rats. In these proof-of-concept experiments, we show that intravenous injections of clinically relevant AAVs can transduce the ENS in guinea pigs and non-human primates. Neonatal guinea pigs were given intravenous injections of either AAV8 or AAV9 vectors that contained a green fluorescent protein (GFP) expression cassette or phosphate-buffered saline. Piglets were euthanized three weeks post injection and tissues were harvested for immunofluorescent analysis. GFP expression was detected in myenteric and submucosal neurons along the length of the gastrointestinal tract in AAV8 injected guinea pigs. GFP-positive neurons were found in dorsal motor nucleus of the vagus and dorsal root ganglia. Less transduction occurred in AAV9-treated tissues. Gastrointestinal tissues were analyzed from young cynomolgus macaques that received systemic injection of AAV9 GFP. GFP expression was detected in myenteric neurons of the stomach, small and large intestine. These data demonstrate that ENS gene delivery translates to larger species. This work develops tools for the field of neurogastroenterology to explore gut physiology and anatomy using emerging technologies such as optogenetics and gene editing. It also provides a basis to develop novel therapies for chronic gut disorders.

Prognostic value of B-type natriuretic peptide in surgical palliation of children with single-ventricle congenital heart disease.

The objective of this prospective study was to assess the prognostic role of perioperative B-type natriuretic peptide (BNP) levels in infants and children with single-ventricle congenital heart disease undergoing Norwood, bidirectional cavopulmonary anastomosis (BCPA), or Fontan operation. BNP levels were measured at baseline, after cardiopulmonary bypass, 6 to 12 hours after surgery, and then daily until indwelling vascular catheters were removed. Outcome measures included length of mechanical ventilation, inotropic support, and hospital stay. Twenty subjects underwent 23 surgical procedures (13 Norwood, 5 BCPA, and 5 Fontan). BNP levels were significantly higher in patients undergoing a Norwood procedure compared with a BCPA or Fontan procedure (p < 0.01). BNP levels measured 6 to 12 hours after surgery were predictive of duration of hospitalization (p = 0.005) and inotropic support (p = 0.01). An increase in BNP level within 48 hours of extubation was observed in 92% of patients undergoing a Norwood procedure. Early postoperative BNP levels correlate significantly with the ensuing duration of inotropic support and length of hospitalization. An increase in BNP after extubation may be reflective of the degree of underlying cardiopulmonary instability. Further investigation is necessary to define this important relation.

Polemic: five proposals for a medical school admission policy.

Five proposals for admitting better applicants into medical school are discussed in this article: (1) An A level in a humanity or social science would be required, to supplement--not replace--the stringent science requirement. This would ensure that successful candidates would be better "primed" for the medical curriculum. (2) Extra points in the applicant's initial screening would be awarded for an A level in English literature. (3) There would be a minimum age of 23 for applicants, although a prior degree would not be required. This is to ensure that the applicants are mature enough to know themselves and the world better, to make a more informed and motivated choice of career, and to get more out of the humanities components of the curriculum. (4) A year's full-time experience in a healthcare or charity environment would be desirable. (5) Applicants would be given two lists of interview discussion topics to prepare: works of literature and topics in healthcare politics.

The dangers of medical ethics.

The dominant conception of medical ethics being taught in British and American medical schools is at best pointless and at worst dangerous, or so it will be argued. Although it is laudable that medical schools have now given medical ethics a secure place in the curriculum, they go wrong in treating it like a scientific body of knowledge. Ethics is a unique subject matter precisely because of its widespread familiarity in all areas of life, and any teaching has to start from this shared ethical understanding and from the familiar ethical concepts of ordinary language. Otherwise there is a real risk that spurious technocratic jargon will be deployed by teacher and student alike in the futile search for intellectual respectability, culminating in a misplaced sense of having "done" the ethics module. There are no better examples of such jargon than "consequentialism", "deontology", and the "Four Principles". At best, they cannot do the work they were designed to do and, at worst, they can lead student and practitioner into ignoring their own healthy ethical intuitions and vocabulary.

B-type natriuretic peptide levels in congenital heart disease.

The objective of this study was to evaluate the potential role of B-type natriuretic peptide (BNP) levels in children with congenital heart disease undergoing cardiac catheterization. Measurement of plasma BNP concentration has been shown to be useful in the diagnosis, risk stratification, and management of adult patients with congestive heart failure, but little is known about the role of BNP in children with structural congenital heart disease. We measured plasma BNP levels using the Triage BNP test in patients with congenital heart disease referred for diagnostic or interventional cardiac catheterization. Plasma BNP concentration was measured in 96 children and 11 adults > or = 19 years old (7.9+/-8.3 years) undergoing heart catheterization for underlying congenital heart disease. BNP levels ranged from < 5 to > 1300 pg/ml, with a median BNP concentration of 19.0 pg/ml. Baseline BNP concentrations were > 100.0 pg/ml on 19 occasions in 17 patients. The pressure difference between the left ventricle and ascending aorta was 10-110 mmHg in 21 patients. BNP concentrations for this cohort ranged from < 5.0 to 1060.0 pg/ml and correlated with the degree of left ventricular outflow obstruction (correlation coefficient, 0.661; p = 0.001). This study suggests that with additional research, BNP concentration may prove to be a useful clinical tool in managing children and adults with congenital heart disease.

Adolescent girls' attitudes toward pregnancy: the importance of asking what the boyfriend wants.

OBJECTIVE: We evaluated the factors associated with attitudes toward pregnancy among girls presenting to an adolescent health clinic to better predict which girls are at the highest risk of pregnancy. STUDY DESIGN: We used a cross-sectional provider-administered survey design. POPULATION: A total 202 girls aged 13 to 18 years presenting consecutively for reproductive health services to an adolescent care clinic were interviewed about their desire for pregnancy. Girls found to be already pregnant at the initial visit (n=54) were removed from analysis. OUTCOMES: measured The main outcome measured was desire for pregnancy. Subjects were grouped by those desiring pregnancy (n=16), those desiring to avoid pregnancy (n=107), and those ambivalent about pregnancy (n=25). RESULTS: The girls who were ambivalent about pregnancy were not significantly different from the girls desiring pregnancy. In unadjusted analysis, girls desiring pregnancy or who were ambivalent about it were more likely to be Hispanic, unemployed, to not attend school, to live with neither natural parent, and to have lived away from home for more than 2 weeks. In adjusted analysis, the reported attitude of the boyfriend toward having a child was the only significant predictor of adolescent girls&rsquo attitude toward pregnancy. CONCLUSIONS: The best predictor of an adolescent girl&rsquos attitude toward pregnancy is her perception of her boyfriends&rsquo desire for a baby. Primary care providers should include boyfriends in any efforts to delay pregnancy in at-risk adolescent girls. Teenagers who are ambivalent about whether they want to be pregnant do not differ significantly from those desiring pregnancy, and should be considered just as high risk.

Transcatheter closure of fontan fenestrations using the Amplatzer septal occluder: initial experience and follow-up.

We have recently used the Amplatzer septal occluder to close Fontan fenestrations. Between June 1998 and December 1999, 13 patients underwent transcatheter occlusion of their Fontan fenestrations. Systemic blood flow decreased significantly without a concomitant decrease in pulmonary blood flow. All residual shunts detectable by oximetry were at sites separate from those into which occlusion devices were implanted. One patient developed severe tricuspid regurgitation following the procedure requiring surgical removal of the device. At the last follow-up, all patients were doing well clinically. There were no shunts detectable through or around the devices by echocardiography. Our experience indicates that the location of the fenestration within the Fontan baffle is critical to avoiding device interference with other intracardiac structures. The Amplatzer septal occluder offers an effective means of transcatheter closure of Fontan baffle fenestrations. Although more experience is needed, our current follow-up data suggest that long-term outcomes will be favorable. Cathet. Cardiovasc. Intervent. 51:301-304, 2000.

Interventional cardiac catheterization advances in nonsurgical approaches to congenital heart disease.

Interventional cardiac catheterization offers increased therapeutic options to many patients with congenital heart disease. Over the past year encouraging results have been reported in hundreds of patients with interatrial communications, patent ductus arteriosus, and pulmonary artery stenosis requiring stenting. The Amplatzer (AGA Medical Corporation, Golden Valley, MN, USA) family of atrial septal, ventricular septal, and ductus occluding devices shows particular promise. Other studies support the efficacy and safety of established procedures such as balloon valvuloplasty and coarctation angioplasty. In some areas, such as transcatheter perforation of atretic pulmonary valves and endovascular stenting for coarctation of the aorta, our technical abilities may be advancing faster than our understanding of the ultimate clinical impact of our treatment. As interventional cardiac catheterization procedures continue to develop, they must be evaluated carefully against alternative treatments.

Snare-assisted vascular access: a new technique.

Access to the central circulation can be difficult in small infants, particularly when normal anatomic landmarks have been altered. We describe a new technique that utilizes any existing central catheter to establish additional sites of vascular access. A 4 Fr end hole catheter is advanced under fluoroscopic guidance to the desired site of new vascular access. A 10-mm Amplatz snare catheter is advanced through the end hole catheter and the loop opened within the target vessel lumen. The snare is then used to guide percutaneous placement of a Cope wire through a 21-gauge needle and then to pull the wire into the central circulation. New access is then achieved by introducing an additional catheter over the guidewire. This technique has now been successfully utilized 16 times in 13 patients. Snare assistance is a safe and effective technique that provides a reliable means of establishing additional secure vascular access. Cathet. Cardiovasc. Intervent. 47:315-318, 1999.

Treatment of infected left ventricular assist device using antibiotic-impregnated beads.

There is no well-established therapy for treating infections of heart-assist or artificial heart devices, a serious problem with life-threatening consequences. We used a promising new approach in which antibiotic-impregnated polymethylmethacrylate beads were placed around an implanted left ventricular assist device to control an external blood pump infection in a bridge-to-transplant patient. In this case report, we describe the potential of antimicrobial-impregnated polymethylmethacrylate beads for in situ control of infections involving external surfaces of cardiovascular devices.

Exon-intron organization of the human type 2 desmocollin gene (DSC2): desmocollin gene structure is closer to "classical" cadherins than to desmogleins.

The cadherins are a superfamily of calcium-dependent glycoproteins that are cell adhesion molecules. Two families of cadherins, the desmocollins (Dsc) and desmogleins (Dsg), are found only in the desmosome type of cell-cell junction. They are each present in at least three different isoforms with differing spatial and temporal distributions and are specified by two clusters of closely linked genes on human chromosome 18q12.1. The human DSC2 gene, coding for the most widely distributed form of the desmocollins, has been found to consist of more than 32 kb of DNA. By using PCR we have determined the exon-intron organization. The gene is arranged into 17 exons ranging in size from 46 to 258 bp; exon 16 is alternatively spliced, giving rise to the a and b forms of the protein. This has revealed a remarkable degree of conservation of intron position with other cadherins. The desmocollin exon-intron organization is more similar to the so-called classical cadherins than to the desmogleins, especially in the cytoplasmic domain. Intron 1 is the largest in DSC2, as it is in the desmogleins, in contrast to the classical cadherins, where intron 2 is extremely large; this latter intron is missing from the desmogleins.

A YAC contig joining the desmocollin and desmoglein loci on human chromosome 18 and ordering of the desmocollin genes.

The desmocollins and desmogleins are members of the cadherin family of adhesive proteins present in the desmosome type of cell-cell junction. All of the known desmoglein and desmocollin isoforms, which have differing tissue and developmental distributions, are coded by very closely linked genes at 18q12.1. We have previously described YAC clones carrying all three known desmoglein (DSG) genes. We have now isolated YAC clones that carry all three known desmocollin genes (DSC1, 2, and 3) from two libraries and also isolated clones that join the DSC locus to the DSG locus, forming a complete contig for the region. Absence of chimeric ends for some of the YACs was confirmed by isolating Vectorette PCR products for the YAC ends and mapping the derived DNA sequences back to other YACs from CEPH. The whole DSC/DSG gene complex occupies no more than about 700 kb, and the genes are arranged in the order cen-3'-DSC3-DSC2-DSC1-5'-5'-DSG1-DSG3-D SG2-3'-tel, so that the two gene clusters are transcribed outward from the interlocus region. A P1 clone carrying part of DSC2 and DSC3 confirmed the relative orientation of transcription of these two genes. The conservation of close genetic linkage may be of trivial importance related to the recent duplication of these genes or may be because there is a region within the locus that is involved in coordinating the expression of the desmoglein and desmocollin genes.

Clinical and postmortem outcome of "no-reflow' phenomenon in a patient treated with rotational atherectomy.

In the 77-year-old woman described, atherectomy of a circumflex artery with the Rotablator device was complicated by "no reflow." Ten days later, a 75% right coronary artery stenosis was successfully managed by balloon angioplasty. On the following day, acute closure of this vessel resulted in death. Gross examination of the heart showed features of recent posterior infarction, and microscopic study revealed atheroemboli in myocardial arterioles. We conclude that high-speed pulverization of atherosclerotic plaque can cause clinically significant emboli.

Intracardiac yolk sac tumor: echocardiographic evaluation.

To our knowledge, this case of an abdominal yolk sac tumor with extensive cardiac involvement is the first to be reported in a pediatric patient. The report describes the echocardiographic findings of the tumor and the role of echocardiography in providing important information for patient management decisions.

The absence of ongoing immunoglobulin gene hypermutation suggests a distinct mechanism for c-myc mutation in endemic Burkitt's lymphoma.

PURPOSE: Burkitt's lymphoma is a malignancy of mature, immunoglobulin (Ig)-bearing B cells characterized by translocation between c-myc and Ig gene loci. A role for the juxtaposed Ig genes in the mutation and deregulation of c-myc expression typical of endemic Burkitt's lymphoma (eBL) has been proposed, but never proven. Our objective was to determine whether Ig gene hypermutation is ongoing in eBL. METHODS: We isolated Ig heavy-chain sequences from K962 eBL tumor cells using reverse transcription and polymerase chain reaction (PCR) amplification. The PCR product was ligated into Bluescript II vectors. Multiple subclones were sequenced and the variable regions were compared for evidence of ongoing Ig hypermutation. RESULTS: Six total single base substitutions were observed within four of the nine subclones studied. Four substitutions resulted in amino acid changes and two were silent. There was no clustering of mutations in hypervariable regions, or a high incidence of amino acid replacement or link substitutions, all of which are characteristic of Ig hypermutation. The observed mutations occurred at a rate consistent with Taq polymerase error. CONCLUSIONS: Our data indicate that in the eBL tumor sample K962, the mechanism underlying c-myc mutation is distinct from that which gives rise to Ig hypermutation.

Sinus node dysfunction in tuberous sclerosis.

Tuberous sclerosis is an autosomal dominant disease with potential for involvement of the skin, brain, lungs, kidneys, and heart. A case of prolonged sinus node pause and episodes of unresponsiveness in a 21-week-old infant with tuberous sclerosis is described. The infant subsequently underwent placement of an epicardial pacemaker. This case illustrates the importance of electrocardiographic studies in infants with tuberous sclerosis and seizure-like episodes.