The impact of traumatic pelvic fractures on sporting activity and quality of life.

BACKGROUND: Pelvic fractures (PFX) reflect high-energy trauma with high mortality and morbidity. AIM: We attempted to determine: whether there is a decrease in levels of sporting and physical activity in patients with operatively-treated PFX; risk factors for decreased sporting activity; any correlation between sporting activity and quality of life in this group. METHODS: Retrospective demographics on mechanism of injury, fracture type, associated injury and injury severity score, as well as prospective documentation of the level and frequency of sporting activity, were collected from adult patients treated operatively for a PFX between 2007 and 2010, using a specifically designed questionnaire. Quality of life before and after injury was also recorded using the EuroQol-5D health-outcome tool. RESULTS: 80 patients without pre-existing musculoskeletal disability were enrolled. The mean age was 44.9 years (18-65). The mean follow-up was 30.5 months (12-39). A decrease in level and frequency of sporting activity was observed. It was associated with lower-extremity associated injuries, but not with injury severity score, PFX severity, PFX type, age, or timing of follow-up. Sporting activity before injury predicted higher levels of sporting participation after injury. Decreased sporting activity after injury was associated with decreased EuroQol-SD score. CONCLUSIONS: Patients should be counselled on the likelihood of a reduction in sporting activities after surgically treated PFX. A larger multi-centre study is needed to further expand on the evidence of the true impact of PFX and its associated injuries on sporting activity.

Synthesis of soluble graphite and graphene.

Because of graphene's anticipated applications in electronics and its thermal, mechanical, and optical properties, many scientists and engineers are interested in this material. Graphene is an isolated layer of the π-stacked hexagonal allotrope of carbon known as graphite. The interlayer cohesive energy of graphite, or exfoliation energy, that results from van der Waals attractions over the interlayer spacing distance of 3.34 Å (61 meV/C atom) is many times weaker than the intralayer covalent bonding. Since graphene itself does not occur naturally, scientists and engineers are still learning how to isolate and manipulate individual layers of graphene. Some researchers have relied on the physical separation of the sheets, a process that can sometimes be as simple as peeling of sheets from crystalline graphite using Scotch tape. Other researchers have taken an ensemble approach, where they exploit the chemical conversion of graphite to the individual layers. The typical intermediary state is graphite oxide, which is often produced using strong oxidants under acidic conditions. Structurally, researchers hypothesize that acidic functional groups functionalize the oxidized material at the edges and a network of epoxy groups cover the sp(2)-bonded carbon network. The exfoliated material formed under these conditions can be used to form dispersions that are usually unstable. However, more importantly, irreversible defects form in the basal plane during oxidation and remain even after reduction of graphite oxide back to graphene-like material. As part of our interest in the dissolution of carbon nanomaterials, we have explored the derivatization of graphite following the same procedures that preserve the sp(2) bonding and the associated unique physical and electronic properties in the chemical processing of single-walled carbon nanotubes. In this Account, we describe efficient routes to exfoliate graphite either into graphitic nanoparticles or into graphene without resorting to oxidation. Our exfoliation process involves the intercalation of lithium into bulk graphite to yield graphene sheets reduced by the lithium. We can alkylate the resulting graphite salt reductively using solubilizing dodecyl groups. By probe microscopy, we show that these groups are attached covalently only at the graphitic edges.

The Scottish molecular genetics consortium--15 years on.

Remarkable advances have been made in recent years in our knowledge of the human genome. Genes for disorders such as Huntington disease, cystic fibrosis and Duchenne muscular dystrophy have been mapped and mutations identified. Simple molecular tests are now available for the diagnosis of these and many other conditions. As a result, in the last 15 years the whole new field of molecular pathology has been introduced to the Health Service of the United Kingdom and now there are nearly 40 diagnostic laboratories offering tests for a wide range of genetic disease. Scotland was at the forefront in the introduction of molecular diagnostics to Clinical Genetics Services and as early as 1985 plans were made to provide laboratories in Aberdeen, Dundee, Edinburgh and Glasgow. The four laboratories, the clinical genetics staff in each centre and the officials of the National Services Division now form the Scottish Molecular Genetics Consortium the objective of which is to provide testing for a wide range of disorders, to introduce new tests as genes are identified and to carry this out in a cooperative and coordinated manner.

Conductance switching in single molecules through conformational changes.

We tracked over time the conductance switching of single and bundled phenylene ethynylene oligomers isolated in matrices of alkanethiolate monolayers. The persistence times for isolated and bundled molecules in either the ON or OFF switch state range from seconds to tens of hours. When the surrounding matrix is well ordered, the rate at which the inserted molecules switch is low. Conversely, when the surrounding matrix is poorly ordered, the inserted molecules switch more often. We conclude that the switching is a result of conformational changes in the molecules or bundles, rather than electrostatic effects of charge transfer.

No excess of factor V:Q506 genotype but high prevalence of anticardiolipin antibodies without antiendothelial cell antibodies in retinal vein occlusion in young patients.

Factor V:Q506 (factor V Leiden) is associated with venous thrombosis and has been reported to be a risk factor for retinal vein occlusion (RVO). Anticardiolipin antibodies (ACA), also associated with RVO, are a marker for the prothrombotic condition antiphospholipid syndrome, in which antiendothelial antibodies (AECA) are also frequently present. This study reviewed 45 younger patients 10 GPL units); in 6 of these, the titre was >20 GPL units (population reference range = 0-10 GPL units). No patient had antiendothelial cell reactivity. The low-titre ACA may therefore represent a non-specific response to vascular injury.

From the cover: nanoscale imaging of chemical interactions: fluorine on graphite.

Using C60-functionalized scanning tunneling microscope tips, we have investigated the adsorption of fluorine on graphite. Based on characteristics of the accompanying electron standing waves, we are able to distinguish the fluorine adatoms that have bonded ionically to the graphite surface from those that have formed covalent bonds with the surface. This result permits determination of the ratio of ionic to covalent C-F bonds on graphite obtained by gas phase fluorination, which seems to be temperature-independent between 200 and 300 degrees C under the reaction conditions used.

Fragile X syndrome with FMR1 and FMR2 deletion.

We report a 13 year old boy with fragile X syndrome resulting from a de novo deletion of the FMR1 and FMR2 genes extending from (and including) DXS7536 proximally to FMR2 distally. The patient has severe developmental delay, epilepsy, and behavioural difficulties, including autistic features. He has epicanthic folds, in addition to facial features typical of fragile X syndrome, and marked joint hypermobility. We compare our patient to the three other cases reported in which both FMR1 and FMR2 are deleted. This case has the smallest deletion reported to date. All four patients have epilepsy and a more severe degree of mental retardation than is usual in fragile X syndrome resulting from FMR1 triplet repeat expansion. Three of the patients have joint laxity and two have epicanthic folds. We suggest that these features, in particular severe developmental delay and epilepsy, may form part of the characteristic phenotype resulting from deletion of both FMR1 and FMR2 genes. The diagnosis in this case was delayed because routine cytogenetics showed no abnormality and standard molecular tests for FMR1 triplet repeat expansion (PCR and Southern blotting) failed. Further DNA studies should be undertaken to investigate for a deletion where clinical suspicion of fragile X syndrome is strong and routine laboratory tests fail.

Thrombosis, markers of thrombotic risk, indwelling central venous catheters and antithrombotic prophylaxis using low-dose warfarin in subjects with malignant disease.

Markers of thrombotic risk--fibrinogen, factor VIII and immunoglobulin G (IgG) anticardiolipin titres--were measured, and the presence of lupus anticoagulant and factor V Leiden were assessed in 84 patients with a solid or haematological malignancy. These patients were monitored, following the insertion of an indwelling venous catheter, for thrombosis. Fifty-five were given prophylactic low-dose warfarin. Over a mean of 15 weeks there were 10 (12%) thrombotic events in 10 patients. Seven were on warfarin. Haemorrhagic problems occurred in three (5%), all on warfarin. Of the 84 patients, 86% had raised fibrinogen levels, 37% elevated factor VIII and 44% raised anticardiolipin levels. Lupus anticoagulant was present in five and three were heterozygous for factor V Leiden. A high prevalence of a range of prothrombotic changes was confirmed and the frequent presence of low-titre anticardiolipin antibody in subjects with malignancy demonstrated. However, none of these parameters predicted the development of thrombosis (P > 0.05).

Rapid diagnosis and identification of cross-over sites in patients with glucocorticoid remediable aldosteronism.

Glucocorticoid remediable aldosteronism (GRA) is an autosomal dominant cause of primary aldosteronism and high blood pressure resulting from a chimeric 11beta-hydroxylase/aldosterone synthase gene. Abnormal expression of aldosterone synthase causes primary aldosteronism, which can be inhibited by glucocorticoids. Diagnosis of GRA has depended on the identification of a restriction enzyme product in genomic DNA of affected individuals. Recently, a two-tube long PCR method was described that allowed diagnosis of GRA in a kindred in Australia. A similar long PCR method confirmed the diagnosis of GRA in members of five northeastern Scotland families previously identified by Southern blotting and detected affected members of five GRA families previously identified in Glasgow. A multiplex PCR protocol is described here that allows the control aldosterone synthase amplification and chimeric gene amplification to be carried out in the same tube. We describe the regions of cross-over in each of 10 kindreds identified in Scotland. To identify cross-over regions in each of the kindreds, the chimeric long PCR product was cloned and sequenced. Five cross-over sites were identified ranging from intron 2 to exon 4, indicating the reliability of the method in identifying chimeric genes resulting from different sites of cross-over.

Antenatal screening for carriers of cystic fibrosis: randomised trial of stepwise v couple screening.

OBJECTIVE: To perform a rigorous comparative evaluation of stepwise and couple approaches to antenatal carrier screening for cystic fibrosis. DESIGN: Pragmatic randomised trial. SETTING: Hospital antenatal clinic serving a regional population. SUBJECTS: 2002 women (couples) attending for booking antenatal visit at less than 17 weeks' gestation with no family history of cystic fibrosis. INTERVENTIONS: Offering counselling and carrier testing for cystic fibrosis, either to women in the first instance (stepwise) or to couples (couple screening). MAIN OUTCOME MEASURES: Uptake rates; anxiety; knowledge of cystic fibrosis and carrier status (both partners); attitudes to health, pregnancy, the baby, and screening (both partners); and uptake of carrier testing by relatives. RESULTS: Uptake of screening was the same for both approaches (90%). After delivery most women remembered test results and their meaning, but 53/253 (21%) of those with negative results of couple testing had forgotten that repeat testing would be advisable if they had a pregnancy with a new partner. With stepwise screening women identified as carriers had high levels of anxiety when results were received (mean anxiety score 52.3). This dissipated with a reassuring partner's result (carriers' mean anxiety score 36.1) to levels similar to those receiving negative results from couple screening. Of those receiving negative results, women who had stepwise screening were significantly less anxious than those who had couple screening (mean score with result 32.1 v 35.4, 95% confidence interval for difference -4.7 to -2.1). CONCLUSIONS: Couple screening allows carriers to avoid transient high levels of anxiety, but is associated with more anxiety and false reassurance among most screenees who will test negative. Stepwise screening gives carriers and their relatives genetic information and is, in our opinion, the better method.

Evaluation of laboratory methods for cystic fibrosis carrier screening: reliability, sensitivity, specificity, and costs.

We report a comparative evaluation of three different laboratory methods for screening large numbers of mouthwash DNA samples for common cystic fibrosis mutations. Sensitivity, specificity, and costs of ARMS (allele refractory mutation detection system), dot blotting, and a deletion/digest/PAGE method (multiplex PCR of exons 10 and 11, digest with HincII followed by polyacrylamide gel electrophoresis (PAGE)) were assessed. ARMS was the most reliable and sensitive method and so was considered more suitable than the cheaper deletion/digest/PAGE. As well as being less reliable than ARMS, the dot blotting method assessed was considerably more costly. ARMS was the best laboratory method for CF screening tested.

p53 mutation is a common genetic event in ovarian carcinoma.

Using the single-strand conformational polymorphism technique, we have screened 66 malignant ovarian tumors for p53 mutation in exons 5 to 8. Thirty-four of the tumors demonstrated a single-strand conformational polymorphism band shift in this region of the gene, including 6 in exon 5, 7 in exon 6, 12 in exon 7, and 10 in exon 8 (one of the tumors showed a shift for exons 7 and 8). All of the single-strand conformational polymorphism shifts have been further characterized by DNA sequencing, and 31 of 35 have been shown to represent genuine DNA alterations. These include 27 point mutations (23 missense, 2 nonsense, and 2 silent mutations), 3 deletions (a 2-base pair deletion introducing, by frameshift, a stop codon further downstream; a 3-base pair deletion; and an unusual 6-base pair deletion made up of separate 2-base pair and 4-base pair deletions), and a 4-base pair insertion (introducing a stop codon downstream). In total, 29 of the 66 (44%) carcinomas analyzed had mutations affecting the primary sequence of the p53 protein. p53 mutation was found in tumors of all International Federation of Gynecologists and Obstetricians stages, suggesting that it might be an earlier genetic event in the progression of epithelial ovarian tumors than previously thought. A significantly greater number of p53 mutations were seen in high-grade serous carcinomas than in those of endometrioid and mucinous types (0.02 > P > 0.01). Analysis of the distribution of point mutations showed no preference for any particular mutation type.

Prevalence of cystic fibrosis mutations in the Grampian region of Scotland.

We have identified all known sufferers of cystic fibrosis (CF) alive in the Grampian region, north east Scotland, on 1 January 1989. DNA samples were obtained for a prevalence study of the common mutations with near to complete ascertainment. A relatively high prevalence of the delta F508 mutation was found (82%), with one of four mutations being present on 92% of CF chromosomes. The high prevalence of these four easily detectable mutations in Grampian has local implications for genetic counselling, the efficacy of population carrier screening, and the usefulness of mutation analysis in cases where the diagnosis of CF is in doubt.

Linkage studies with 17q and 18q markers in a breast/ovarian cancer family.

Genes on chromosomes 17q and 18q have been shown to code for putative tumor suppressors. By a combination of allele-loss studies on sporadic ovarian carcinomas and linkage analysis on a breast/ovarian cancer family, we have investigated the involvement of such genes in these diseases. Allele loss occurred in sporadic tumors from both chromosome 17p, in 18/26 (69%) cases, and chromosome 17q, in 15/22 (68%) cases. In the three familial tumors studied, allele loss also occurred on chromosome 17 (in 2/3 cases for 17p markers and in 2/2 cases for a 17q allele). Allele loss on chromosome 18q, at the DCC (deleted in colorectal carcinomas) locus, was not as common (6/16 cases [38%]) in sporadic ovarian tumors but had occurred in all three familial tumors. The results of linkage analysis on the breast/ovarian cancer family suggested linkage between the disease locus and 17q markers, with a maximum lod score of 1.507 obtained with Mfd188 (D17S579) polymorphism at 5% recombination. The maximum lod score for DCC was 0.323 at 0.1% recombination. In this family our results are consistent with a predisposing gene for breast/ovarian cancer being located at chromosome 17q21.

Prenatal diagnosis for the cystic fibrosis mutation 1717-1, G-->A using arms.

A family carrying two cystic fibrosis mutations, delta F508 and 1717-1, G-->A, requested prenatal diagnosis. In order to eliminate the need for labelling of allele-specific oligonucleotides and to simplify the analysis, 1717-1, G-->A was detected using an ARMS (amplification refractory mutation system) method (Newton et al., 1989). Fetal DNA was obtained by chorionic villus sampling (CVS) and the ARMS technique was used to exclude the 1717-1, G-->A mutation. The fetus was found to be heterozygous for the delta F508 mutation. ARMS is a simple, quick, non-radioactive method suitable for detecting DNA mutations in various clinical situations.

Prenatal diagnosis for dystrophia myotonica using the polymerase chain reaction.

The polymerase chain reaction has been used to detect an abundant class of short repeat DNA families of the form (dC-dA)n.(dG-dT)n, known as microsatellites. These units are found throughout the human genome and have been characterized for several loci including APOC2 on chromosome 19q12-q13.2. The locus APOC2 is linked to the gene for dystrophia myotonica and a microsatellite within this locus was used to derive polymorphisms in a family to predict the inheritance of the disease. Chorionic villus sampling (CVS) was performed at 15 1/2 weeks' gestation. Following DNA extraction from the CVS material and parental blood samples, microsatellite analysis was carried out by the polymerase chain reaction.

Biliary-jejunal drainage for failed biliary-duodenal drainage.

Percutaneous biliary drainage, as palliation for malignant biliary obstruction, is subject to complications, particularly blockage of the drainage tube. Blockage may occur because of duodenal tumour involvement. In nine patients with blockage of the biliary-duodenal drainage tube, conversion to biliary-jejunal drainage allowed continued internal drainage of bile.