Elastic evolution of a self-healing ionomer observed via acoustic and ultrasonic resonant spectroscopy.

Self-healing poly (ethylene co-methacrylic acid) ionomers (EMAA) are thermoplastic materials that when punctured, cut, shot or damaged in a variety of ways, are capable of autonomously reorganizing their physical structure to heal and, in many instances, permanently seal the damaged location. However, a complete picture of the mechanisms responsible for their unusual behavior is not well understood. In this article we report the observation of time dependent acoustic and ultrasonic spectral evolution, measured using resonant acoustic and ultrasonic spectroscopy, for both pre and post-damage EMAA samples. The results provide a means to differentiate healing phases, quantify healing timescales, and potentially elucidate the composition parameters that most significantly impact healing behavior.

Using a multimedia presentation to improve patient understanding and satisfaction with informed consent for minimally invasive vascular procedures.

OBJECTIVE: As vascular procedures become more complex, patient understanding of their treatment(s) can become more difficult. We wished to evaluate the utility of multimedia presentations (MPs) to improve patient understanding of their vascular interventions. METHODS: Patients undergoing endovascular aneurysm repair (EVAR), peripheral angioplasty, Hickman catheter and peripherally inserted central catheter (PICC) insertion were randomized into a control group receiving traditional verbal consent, and a MP group that were shown a two minute simplified video of their procedure on an iPad™ computer in addition to the traditional verbal consent. After obtaining consent, all patients completed a questionnaire assessing their comprehension of the procedure, and satisfaction with the consent process. Satisfaction was rated on a 5 point Likert scale with 5 being 'very helpful' in understanding the procedure. RESULTS: Ninety-three patients were recruited for this study, 62% of which were male. The intervention significantly increased total comprehension in all procedure types controlling for procedure type (multimedia vs. control; F = 9.14, P = .003). A second ANOVA showed there was a significant main effect by intervention (F = 44.06, p < .000) with those in the intervention group showing higher overall satisfaction scores after controlling for surgery type. CONCLUSION: This study suggests that patients find the use of MP during the consent process to be helpful in patient understanding and that there is improved satisfaction. Given the rapid rate of innovation in vascular interventions, increased regular use of MPs to help patients understand their procedures would be beneficial in the care of patients undergoing vascular interventions.

Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only.

BACKGROUND: The detection rate for identifying the underlying mutation in neurocutaneous syndromes is affected by the sensitivity of the mutation test and the heterogeneity of the disease based on the diagnostic criteria. Neurofibromatosis type (NF1) has been defined for 29years by the National Institutes for Health (NIH) criteria which include ≥6 Café au Lait macules (CAL) as a defining criterion. The discovery of SPRED1 as a cause of Legius syndrome which is manifested by CAL, freckling and learning difficulties has introduced substantial heterogeneity to the NIH criteria. METHODS: We have defined the sensitivity of comprehensive RNA analysis on blood of presumed NF1 patients meeting NIH criteria with at least one nonpigmentary criterion and determined the proportion of children with ≥6 CAL and no family history that has an NF1 or SPRED1 genetic variant. RNA analysis was carried out from 04/2009-12/2015 on 361 NF1 patients. FINDINGS: A presumed causative NF1 mutation was found in 166/171 (97.08%-95% CI 94.56-99.6%) of familial cases and 182/190 (95.8%-95% CI 92.93-98.65%) sporadic de novo cases. Two of thirteen (15%) mutation negative individuals had dysembryoplastic neuroepithelial tumour (DNET) compared to 2/348 (0.6%) with an NF1 variant (p=0.007). No SPRED1 variants were found in the thirteen individuals with no NF1 variant. Of seventy-one individuals with ≥6 CAL and no non-pigmentary criterion aged 0-20years, 47 (66.2%) had an NF1 variant six (8.5%) a SPRED1 variant and 18 (25.3%) no disease causing variant. Using the 95.8% detection rate the likelihood of a child with ≥6 CAL having constitutional NF1 drops from 2/3 to 1/9 after negative RNA analysis. INTERPRETATION: RNA analysis in individuals with presumed NF1 has high sensitivity and includes a small subset with DNET without an NF1 variant. Furthermore negative analysis for NF1/SPRED1 provides strong reassurance to children with ≥6 CAL that they are unlikely to have NF1.

The BRCA2 polymorphic stop codon: stuff or nonsense?

BACKGROUND: Despite classification of the BRCA2c.9976A>T, p.(Lys3326Ter) variant as a polymorphism, it has been associated with increased risks of pancreatic, lung, oesophageal and breast cancer. METHODS: We have noticed multiple co-occurrences of the BRCA2 c.9976A>T variant with the pathogenic BRCA2c.6275_6276delTT frameshift mutation p.(Leu2092ProfsTer7) and using a cohort study have assessed if this might account for these tumour risk associations. RESULTS: We identified 52 families with BRCA2c.6275_6276delTT, all of which occur in cis with the BRCA2c.9976A>T variant allele as demonstrated by co-segregation in all family members tested. Of 3245 breast/ovarian cancer samples sequenced for BRCA2, only 43/3245 (1.3%) carried BRCA2 c.9976A>T alone, after excluding individuals with BRCA2c.6275_6276delTT (n=22) or other BRCA1 (n=3) or BRCA2 (n=2) pathogenic mutations. The resultant frequency (1.3%) after removal of co-occurring mutations is lower than the 1.7% and 1.67% frequencies from two control populations for BRCA2 c.9976A>T, but similar to the 1.39% seen in the Exome Aggregation Consortium database. We did not identify increased frequencies of oesophageal, pancreatic or lung cancer in families with just BRCA2 c.9976A>T using person-years at risk analysis. CONCLUSIONS: It is likely that the previous associations of increased cancer risks due to BRCA2c.9976A>T represent reporting bias and are contributed to because the variant is in LD with BRCA2c.6275_6276delTT.

Rates of loss of heterozygosity and mitotic recombination in NF2 schwannomas, sporadic vestibular schwannomas and schwannomatosis schwannomas.

Biallelic inactivation of the NF2 gene occurs in the majority of schwannomas. This usually involves a combination of a point mutation or multiexon deletion, in conjunction with either a second point mutation or loss of heterozygosity (LOH). We have performed DNA sequence and dosage analysis of the NF2 gene in a panel of 239 schwannoma tumours: 97 neurofibromatosis type 2 (NF2)-related schwannomas, 104 sporadic vestibular schwannomas (VS) and 38 schwannomatosis-related schwannomas. In total, we identified germline NF2 mutations in 86 out of 97 (89%) NF2 patients and a second mutational event in 77 out of 97 (79%). LOH was by far the most common form of second hit. A combination of microsatellite analysis with either conventional comparative genomic hybridization (CGH) or multiplex ligation-dependent probe amplification (MLPA) identified mitotic recombination (MR) as the cause of LOH in 14 out of 72 (19%) total evaluable tumours. Among sporadic VS, at least one NF2 mutation was identified by sequence analysis or MLPA in 65 out of 98 (66%) tumours. LOH occurred in 54 out of 96 (56%) evaluable tumours, but MR only accounted for 5 out of 77 (6%) tested. LOH was present in 28 out of 34 (82%) schwannomatosis-related schwannomas. In all eight patients who had previously tested positive for a germline SMARCB1 mutation, this involved loss of the whole, or part of the long arm, of chromosome 22. In contrast, 5 out of 22 (23%) tumours from patients with no germline SMARCB1 mutation exhibited MR. High-resolution Affymetrix SNP6 genotyping and copy number (CN) analysis (Affymetrix, Santa Clara, CA, USA) were used to determine the chromosomal breakpoint locations in tumours with MR. A range of unique recombination sites, spanning approximately 11.4 Mb, were identified. This study shows that MR is a mechanism of LOH in NF2 and SMARCB1-negative schwannomatosis-related schwannomas, occurring less frequently in sporadic VS. We found no evidence of MR in SMARCB1-positive schwannomatosis, suggesting that susceptibility to MR varies according to the disease context.

Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis.

BACKGROUND: Schwannomatosis is a rare condition characterised by multiple schwannomas and lack of involvement of the vestibular nerve. A recent report identified bi-allelic mutations in the SMARCB1/INI1 gene in a single family with schwannomatosis. We aimed to establish the contribution of the SMARCB1 and the NF2 genes to sporadic and familial schwannomatosis in our cohort. METHODS: We performed DNA sequence and dosage analysis of SMARCB1 and NF2 in 28 sporadic cases and 15 families with schwannomatosis. RESULTS: We identified germline mutations in SMARCB1 in 5 of 15 (33.3%) families with schwannomatosis and 2 of 28 (7.1%) individuals with sporadic schwannomatosis. In all individuals with a germline mutation in SMARCB1 in whom tumour tissue was available, we detected a second hit with loss of SMARCB1. In addition, in all affected individuals with SMARCB1 mutations and available tumour tissue, we detected bi-allelic somatic inactivation of the NF2 gene. SMARCB1 mutations were associated with a higher number of spinal tumours in patients with a positive family history (p = 0.004). CONCLUSION: In contrast to the recent report where no NF2 mutations were identified in a schwannomatosis family with SMARCB1 mutations, in our cohort, a four hit model with mutations in both SMARCB1 and NF2 define a subset of patients with schwannomatosis.

Should NF2 mutation screening be undertaken in patients with an apparently isolated vestibular schwannoma?

Early onset of vestibular schwannoma (VS) is associated with the inherited condition neurofibromatosis type 2 (NF2). However, the majority of NF2 presents bilaterally and the proportion of early-onset apparent sporadic unilateral VS because of NF2 remains to be determined. We have determined the risk by studying NF2 risk in a population-based set of VS, looking at the mode of presentation in a large NF2 data set and the outcome of NF2 mutation analysis in 148 sporadic unilateral VS. The risk of NF2 in an apparently sporadic case of unilateral VS is small apart from in the very youngest age group (<20 years). NF2 germ line mutation testing is unlikely to reveal a mutation except <20 years as a result of the low risk and high rates of mosaicism. Germ line mutation testing is probably only justified in sporadic unilateral VS <20 years unless other features of NF2 are present. Ideally mutation testing should start with the original tumour specimen.

Mosaicism in neurofibromatosis type 2: an update of risk based on uni/bilaterality of vestibular schwannoma at presentation and sensitive mutation analysis including multiple ligation-dependent probe amplification.

BACKGROUND: Neurofibromatosis type 2 (NF2) is almost unique among inherited disorders in the frequency of mosaicism in the first affected generation. However, the implications of this on transmission risks have not been fully elucidated. METHODS: The expanded database of 460 families with NF2 and 704 affected individuals was analysed for mosaicism and transmission risks to offspring. RESULTS: 64 mosaic patients, with a projected mosaicism rate of 33% for sporadic classical NF2 with bilateral vestibular schwannoma at presentation and 60% for those presenting unilaterally, were identified. Offspring risks can be radically reduced on the basis of a sensitive mutation analysis of blood DNA including multiple ligation-dependent probe amplification (MLPA, which detects 15% of all mutations), but even MLPA cannot detect high levels of mosaicism. CONCLUSION: The chances of mosaicism in NF2 and the resultant risks of transmission of the mutation to offspring in a number of different clinical situations have been further delineated. The use of MLPA in this large NF2 series is also reported for the first time.

Overexpression of aurora B kinase (AURKB) in primary non-small cell lung carcinoma is frequent, generally driven from one allele, and correlates with the level of genetic instability.

Aurora kinases are key regulators of chromosome segregation during mitosis. We have previously shown by microarray analysis of primary lung carcinomas and matched normal tissue that AURKB (22 out of 37) and AURKA (15 out of 37) transcripts are frequently over-represented in these tumours. We now confirm these observations in a second series of 44 carcinomas and also show that aurora B kinase protein levels are raised in the tumours compared to normal tissue. Elevated levels of expression in tumours are not a consequence of high-level amplification of the AURKB gene. Using a coding sequence polymorphism we show that in most cases (seven out of nine) tumour expression is predominantly driven from one AURKB allele. Given the function of aurora B kinase, we examined whether there was an association between expression levels and genetic instability. We defined two groups of high and low AURKB expression. Using a panel of 10 microsatellite markers, we found that the group showing the higher level of expression had a higher frequency of allelic imbalance (P=0.0012). Analysis of a number of other genes that are strongly and specifically expressed in tumour over normal lung, including SERPINB5, TERT and PRAME, showed marked allelic expression imbalances in the tumour tissue in the context of balanced or only marginally imbalanced relative allelic copy numbers. Our data support a model of early carcinogenesis wherein defects in the process of inactivation of lung stem-cell associated genes during differentiation, contributes to the development of carcinogenesis.

The use of allelic expression differences to ascertain functional polymorphisms acting in cis: analysis of MMP1 transcripts in normal lung tissue.

Summary Aberrant expression of matrix metalloproteinase 1 (MMP1) has been implicated in a number of pathological conditions of the lung. In vitro results and analysis of tumours and cell lines suggest that an insertion/deletion polymorphism at position -1607 in the promoter of the gene can influence expression levels. However, whether this polymorphism is associated with differences in expression in normal lung tissue remains to be established. Polymorphisms affecting expression in cis will lead to alleles with different expression levels and will result in unequal expression of both alleles in heterozygous individuals (allelic expression imbalance, AEI). This can be detected using a transcribed marker. Here we follow a new approach and use AEI to ascertain that the -1607 polymorphism is associated with allelic expression differences of MMP1 in normal lung tissue. This approach could be used to map the sites associated with inter-individual expression differences in other genes. This is of particular interest since such sites allow prediction of expression levels, and can be used to test whether genetically determined differences in expression influence inter-individual differences of a phenotype of interest, such as disease predisposition.

Prenatal care and multiple pregnancy.

Prenatal care of multiple pregnancy presents a variety of nursing challenges. Specialized care, beginning in early pregnancy, can have a significant impact on the outcome for mothers and neonates. Dramatically increasing roles for advanced technology in the care of multifetal pregnancies must be balanced with families' needs for education and support.

Intrapartum care for women with multiple pregnancy.

Intrapartum management of multiple pregnancy presents many challenges for obstetric nurses. Optimal care often is complicated by prematurity, low and very low birth weights, and the unique circumstances of the delivery of multiple neonates. Higher perinatal mortality for multiple pregnancies continues to complicate delivery outcome. Nurses need special knowledge and skills to provide care for women with a variety of high-risk conditions in rapidly changing situations.

The multiple birth explosion: implications for nursing practice.

An explosion in multiple birth rates has generated record numbers of multiple pregnancies and infants. Obstetric and neonatal nurses and those in related practice areas, such as reproductive endocrinology, perinatal education, home health, and lactation services, need special knowledge and resources to provide optimal care for these high-risk families. Multiple birth families have a number of unique health care problems that require directed nursing interventions throughout the perinatal continuum.

Intra- and interspecific mitochondrial DNA sequence variation within two species of rock-dwelling cichlids (Teleostei: Cichlidae) from Lake Malawi, Africa.

Difficulties in interpreting the evolutionary significance of Lake Malawi cichlid morphologies led us to examine molecular techniques for resolving relationships among closely related species. Mitochondrial DNA (mtDNA) sequence variation in the first half of the control region (445 bp) was examined within and between two species of Melanochromis, a genus of rock-dwelling cichlids from Lake Malawi, Africa. The mean number of pairwise differences observed within Melanochromis auratus (Boulenger) and Melanochromis heterochromis Bowers and Stauffer mtDNA haplotypes was 2.0 (0.45%) and 5.0 (1.13%), respectively, and a mean of 4.9 (1.11%) pairwise differences between the two species was observed. Mean pairwise differences between Melanochromis species and Pseudotropheus zebra (Boulenger), another species of rock-dwelling cichlid and Tramitichromis cf. liturus, a sand-dwelling genus, were 11.2 (2.52%) and 21.9 (4.93%), respectively. Species divergence and radiation within the genus Melanochromis appears to have occurred rapidly and recently. Mitochondrial DNA sequence variation within this genus was sufficient for generating hypotheses concerning the evolutionary relationships within the genus and for examining generic-level relationships within and among the major cichlid lineages in Lake Malawi.

Medical, family, and scholastic conditions in urban delinquents.

Effects of medical, family, and scholastic conditions were evaluated for the number and type of offenses and test score performances in 1,962 urban delinquents. Conditions were evaluated using multivariate followed by univariate analysis of variance with post-hoc tests. There were subgroup differences in the number and type of offenses and test score performances. Also, interactions of medical, family, and scholastic conditions changed the number and type of offenses and lowered test scores. Findings supported a developmental biopsychosocial model of delinquency that emphasized the predominance of medical/scholastic conditions. Orphaned or one-parent delinquents with nervous system or neonatal conditions, retardation, or hyperactivity committed assault.

Early pregnancy loss in the infertile couple.

The infertile couple invests tremendous amounts of time, money, and physical and emotional energy in attempting to conceive. When these couples experience early pregnancy loss, their grief can be profound. The emotional aspects of such pregnancy losses and specific nursing interventions are presented.