Controlled evolution of three-dimensional magnetic states in strongly coupled cylindrical nanowire pairs.

Cylindrical magnetic nanowires are promising systems for the development of three-dimensional spintronic devices. Here, we simulate the evolution of magnetic states during fabrication of strongly-coupled cylindrical nanowires with varying degrees of overlap. By varying the separation between wires, the relative strength of exchange and magnetostatic coupling can be tuned. Hence, we observe the formation of six fundamental states as a function of both inter-wire separation and wire height. In particular, two complex three-dimensional magnetic states, a 3D Landau Pattern and a Helical domain wall, are observed to emerge for intermediate overlap. These two emergent states show complex spin configurations, including a modulated domain wall with both Néel and Bloch character. The competition of magnetic interactions and the parallel growth scheme we follow (growing both wires at the same time) favours the formation of these anti-parallel metastable states. This works shows how the engineering of strongly coupled 3D nanostructures with competing interactions can be used to create complex spin textures.

Accelerated cortical thinning and volume reduction over time in young people at high genetic risk for bipolar disorder.

BACKGROUND: Bipolar disorder (BD) is a familial psychiatric disorder associated with frontotemporal and subcortical brain abnormalities. It is unclear whether such abnormalities are present in relatives without BD, and little is known about structural brain trajectories in those at risk. METHOD: Neuroimaging was conducted at baseline and at 2-year follow-up interval in 90 high-risk individuals with a first-degree BD relative (HR), and 56 participants with no family history of mental illness who could have non-BD diagnoses. All 146 subjects were aged 12-30 years at baseline. We examined longitudinal change in gray and white matter volume, cortical thickness, and surface area in the frontotemporal cortex and subcortical regions. RESULTS: Compared to controls, HR participants showed accelerated cortical thinning and volume reduction in right lateralised frontal regions, including the inferior frontal gyrus, lateral orbitofrontal cortex, frontal pole and rostral middle frontal gyrus. Independent of time, the HR group had greater cortical thickness in the left caudal anterior cingulate cortex, larger volume in the right medial orbitofrontal cortex and greater area of right accumbens, compared to controls. This pattern was evident even in those without the new onset of psychopathology during the inter-scan interval. CONCLUSIONS: This study suggests that differences previously observed in BD are developing prior to the onset of the disorder. The pattern of pathological acceleration of cortical thinning is likely consistent with a disturbance of molecular mechanisms responsible for normal cortical thinning. We also demonstrate that neuroanatomical differences in HR individuals may be progressive in some regions and stable in others.

3D Echocardiography Provides Highly Accurate 3D Printed Models in Congenital Heart Disease.

Cardiac 3D printing is mainly performed from magnetic resonance imaging (MRI) and computed tomography (CT) 3D datasets, though anatomic detail of atrioventricular (AV) valves may be limited. 3D echo provides excellent visualization of AV valves. Thus, we tested the feasibility and accuracy of 3D printing from 3D echo in this pilot series of subjects with congenital heart disease (CHD), with a focus on valve anatomy. Five subjects with CHD were identified. 3D echo data were converted to 3D printable files and printed in collaboration with 3D Systems Healthcare (Golden, Colorado). A novel technique for valve modeling was utilized using commercially available software. Two readers (KM, SA) independently measured valve structures from 3D models and compared to source echo images. 3D printing was feasible for all cases. Table 1 shows measurements comparing 2D echo to 3D models. Bland Altman analysis showed close agreement and no significant bias between 2D and digital 3D models (mean difference 0.0, 95% CI 1.1 to - 1.1) or 2D vs printed 3D models, though with wider limits of agreement (mean difference - 0.3, 95% CI 1.9 to - 2.6). Accuracy of 3D models compared to 2D was within < 0.5 mm. This pilot study shows 3D echo datasets can be used to reliably print AV and semilunar valve structures in CHD. The 3D models are highly accurate compared to the source echo images. This is a novel and value-added technique that adds incremental information on cardiac anatomy over current methods.

Siblings of children with life-limiting conditions: psychological adjustment and sibling relationships.

BACKGROUND: This study explored psychological adjustment and sibling relationships of siblings of children with life-limiting conditions (LLCs), expanding on previous research by defining LLCs using a systematic classification of these conditions. METHODS: Thirty-nine siblings participated, aged 3-16 years. Parents completed measures of siblings' emotional and behavioural difficulties, quality of life, sibling relationships and impact on families and siblings. Sibling and family adjustment and relationships were compared with population norms, where available, and to a matched comparison group of siblings of children with autistic spectrum disorder (ASD), as a comparable 'high risk' group. RESULTS: LLC siblings presented significantly higher levels of emotional and behavioural difficulties, and lower quality of life than population norms. Their difficulties were at levels comparable to siblings of children with ASD. A wider impact on the family was confirmed. Family socio-economic position, time since diagnosis, employment and accessing hospice care were factors associated with better psychological adjustment. CONCLUSIONS: Using a systematic classification of LLCs, the study supported earlier findings of increased levels of psychological difficulties in siblings of children with a LLC. The evidence is (i) highlighting the need to provide support to these siblings and their families, and (ii) that intervention approaches could be drawn from the ASD field.

A fast magnetic vector characterization method for quasi two-dimensional systems and heterostructures.

The use of magnetic vector tomography/laminography has opened a 3D experimental window to access the magnetization at the nanoscale. These methods exploit the dependence of the magnetic contrast in transmission to recover its 3D configuration. However, hundreds of different angular projections are required leading to large measurement times. Here we present a fast method to dramatically reduce the experiment time specific for quasi two-dimensional magnetic systems. The algorithm uses the Beer-Lambert equation in the framework of X-ray transmission microscopy to obtain the 3D magnetic configuration of the sample. It has been demonstrated in permalloy microstructures, reconstructing the magnetization vector field with a reduced number of angular projections obtaining quantitative results. The throughput of the methodology is × 10-× 100 times faster than conventional magnetic vector tomography, making this characterization method of general interest for the community.

Should non-anaesthetists perform pre-hospital rapid sequence induction? an observational study.

INTRODUCTION: The use of rapid sequence induction and tracheal intubation (RSI) in the pre-hospital environment is controversial. Currently, it is felt that competence to perform RSI should be defined by skills in anaesthesia not by the primary speciality of a practitioner. This aim of the study was to evaluate the tracheal intubation success rate of doctors drawn from different clinical specialities performing RSI in the pre-hospital environment. METHOD: Retrospective review of all RSI performed by doctors operating on the Warwickshire and Northamptonshire Air Ambulance over a 5-year period. Tracheal intubation failure rates were calculated and analysed for proportional differences between groups by χ(2) and, where appropriate, Fisher's exact test. RESULTS: 4362 active missions were flown. RSI was performed in 200 cases (4.6%, 3.1/month). Successful intubation occurred in 194 cases, giving a failure rate of 3% (6 cases, 95% CI 0.6 to 5.3%). While no difference in failure rate was observed between emergency department (ED) staff and anaesthetists (2.73% (3/110, 95% CI 0 to 5.7%) vs 0% (0/55, 95% CI 0 to 0%); p=0.55), a significant difference was found when non-ED, non-anaesthetic staff (GP and surgical) were compared to anaesthetists (10.34% (3/29, 95% CI 0 to 21.4%) vs 0%; p=0.04). There was no significant difference associated with seniority of practitioner (p=0.65). CONCLUSIONS: Non-anaesthetic practitioners have a higher tracheal intubation failure rate during pre-hospital RSI. This likely reflects a lack of training opportunities and infrequency of clinical experience. Strategies to improve pre-hospital airway management are required.

A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26.

Bipolar affective disorder is a heritable, relatively common, severe mood disorder with lifetime prevalence up to 4%. We report the results of a genome-wide linkage analysis conducted on a cohort of 35 Australian bipolar disorder families which identified evidence of significant linkage on chromosome 15q25-26 and suggestive evidence of linkage on chromosomes 4q, 6q and 13q. Subsequent fine-mapping of the chromosome 15q markers, using allele frequencies calculated from our cohort, gave significant results with a maximum two-point LOD score of 3.38 and multipoint LOD score of 4.58 for marker D15S130. Haplotype analysis based on pedigree-specific, identical-by-descent allele sharing, supported the location of a bipolar susceptibility gene within the Z(max-1) linkage confidence interval of 17 cM, or 6.2 Mb, between markers D15S979 and D15S816. Non-parametric and affecteds-only linkage analysis further verified the linkage signal in this region. A maximum NPL score of 3.38 (P=0.0008) obtained at 107.16 cM (near D15S130), and a maximum two-point LOD score of 2.97 obtained at marker D15S1004 (affecteds only), support the original genome-wide findings on chromosome 15q. These results are consistent with four independent positive linkage studies of mood and psychotic disorders, and raise the possibility that a common gene for susceptibility to bipolar disorder, and other psychiatric disorders may lie in this chromosome 15q25-26 region.

One hundred years (and counting) of blast-associated traumatic brain injury.

Blast-associated traumatic brain injury (TBI) has become one of the signature issues of modern warfare and is increasingly a concern in the civilian population due to a rise in terrorist attacks. Despite being a recognised feature of combat since the introduction of high explosives in conventional warfare over a century ago, only recently has there been interest in understanding the biology and pathology of blast TBI and the potential long-term consequences. Progress made has been slow and there remain remarkably few robust human neuropathology studies in this field. This article provides a broad overview of the history of blast TBI and reviews the pathology described in the limitedscientific studies found in the literature.

Genome-wide analysis implicates microRNAs and their target genes in the development of bipolar disorder.

Bipolar disorder (BD) is a severe and highly heritable neuropsychiatric disorder with a lifetime prevalence of 1%. Molecular genetic studies have identified the first BD susceptibility genes. However, the disease pathways remain largely unknown. Accumulating evidence suggests that microRNAs, a class of small noncoding RNAs, contribute to basic mechanisms underlying brain development and plasticity, suggesting their possible involvement in the pathogenesis of several psychiatric disorders, including BD. In the present study, gene-based analyses were performed for all known autosomal microRNAs using the largest genome-wide association data set of BD to date (9747 patients and 14 278 controls). Associated and brain-expressed microRNAs were then investigated in target gene and pathway analyses. Functional analyses of miR-499 and miR-708 were performed in rat hippocampal neurons. Ninety-eight of the six hundred nine investigated microRNAs showed nominally significant P-values, suggesting that BD-associated microRNAs might be enriched within known microRNA loci. After correction for multiple testing, nine microRNAs showed a significant association with BD. The most promising were miR-499, miR-708 and miR-1908. Target gene and pathway analyses revealed 18 significant canonical pathways, including brain development and neuron projection. For miR-499, four Bonferroni-corrected significant target genes were identified, including the genome-wide risk gene for psychiatric disorder CACNB2. First results of functional analyses in rat hippocampal neurons neither revealed nor excluded a major contribution of miR-499 or miR-708 to dendritic spine morphogenesis. The present results suggest that research is warranted to elucidate the precise involvement of microRNAs and their downstream pathways in BD.

Design and synthesis of thrombin inhibitors: analogues of MD-805 with reduced stereogenicity and improved potency.

Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibitors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3, 3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, P2-FEP, and P1-arginine (45g) had a K(i) of 6 nM (MD-805 K(i) = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

Effect of normal MSAFP screening on maternal age for genetic amniocentesis.

Routine maternal serum alpha-fetoprotein (MSAFP) screening for neural tube defects is considered by many to be standard obstetrical care, and recently many have encouraged this test to screen for Trisomy-21 (Down's syndrome). We questioned whether, after a normal MSAFP screen, the risk of Trisomy-21 decreases enough to warrant modifying the recommended age for genetic amniocentesis for Down's syndrome. A logistic regression was developed which, using reported values for sensitivity and specificity for MSAFP detection of Trisomy-21 and assuming a constant threshold risk in opting for amniocentesis, indicates that genetic amniocentesis for Trisomy-21 may be deferred in some women who have a normal MSAFP screening. Sensitivity analysis of varying thresholds for a normal MSAFP demonstrates that a 37 year old woman with a median MSAFP level has the same risk for Trisomy-21 as an unscreened women who is 4.5 years younger. An abnormal MSAFP is useful in screening for neural tube defects and possibly for Trisomy-21. A normal MSAFP may allow for delaying the potentially risky amniocentesis in otherwise low-risk pregnancies.

Attitudes of beginning medical students toward older persons: a five-campus study. The University of California Academic Geriatric Resource Program Student Survey Research Group.

OBJECTIVE: To examine the attitudes of beginning medical students toward older persons and their medical care. DESIGN: Cross-sectional survey. SETTING: Five University of California medical schools. PARTICIPANTS: Beginning medical school students from the Class of 1994. MEASUREMENTS: Demographic characteristics, personal contacts with older persons, and previous coursework or research experience with older persons were assessed. Knowledge with regard to aging was measured with a group of 10 questions, which were modified from the Facts on Aging Quiz. The attitudes of students toward older persons were assessed using the Aging Semantic Differential (ASD), the Maxwell-Sullivan Attitude Scale (MSAS), and two case scenarios. RESULTS: Ninety-two percent of the participants (554 of 603) responded; 93% of these responses were usable. Students were much less likely to admit an acutely ill 85-year-old woman to an intensive care unit, intubate her, and treat her aggressively than they were to treat an acutely ill 10-year-old girl with underlying chronic leukemia. In multivariate models, male gender and younger student age were both independently predictive of less favorable attitudes regarding a 70-year-old person on the ASD Instrumental-Ineffective subscale. Asian-Americans and males had less favorable attitudes on the Autonomous-Dependent and the Personal Acceptability-Unacceptability subscales. More knowledge with regard to aging was predictive of more favorable attitudes on the Autonomous-Dependent and Personal Acceptability-Unacceptability subscales. Male gender and Asian-American ethnicity were significantly associated with less favorable attitudes on the two scales derived from the MSASs. Students who had previously visited a long-term care facility were more likely to disagree that it takes too much time to care for older persons. CONCLUSION: Beginning medical students have already formed some unfavorable attitudes about older persons. Few independent predictors (either sociodemographic or students' previous experiences) of student attitudes could be identified that would help in the selection of students who had more favorable attitudes toward older persons. Hence, attempts to generate physicians with good attitudes must rely on curricular efforts during medical school and residency training.

Outcomes of intended home births in nurse-midwifery practice: a prospective descriptive study.

OBJECTIVE: To describe the outcomes of intended home birth in the practices of certified nurse-midwives. METHODS: Twenty-nine US nurse-midwifery practices were recruited for the study in 1994. Women presenting for intended home birth in these practices were enrolled in the study from late 1994 to late 1995. Outcomes for all enrolled women were ascertained. Validity and reliability of submitted data were established. RESULTS: Of 1404 enrolled women intending home births, 6% miscarried, terminated the pregnancy or changed plans. Another 7.4% became ineligible for home birth prior to the onset of labor at term due to the development of perinatal problems and were referred for planned hospital birth. Of those women beginning labor with the intention of delivering at home, 102 (8.3%) were transferred to the hospital during labor. Ten mothers (0.8%) were transferred to the hospital after delivery, and 14 infants (1.1%) were transferred after birth. Overall intrapartal fetal and neonatal mortality for women beginning labor with the intention of delivering at home was 2.5 per 1000. For women actually delivering at home, intrapartal fetal and neonatal mortality was 1.8 per 1000. CONCLUSION: Home birth can be accomplished with good outcomes under the care of qualified practitioners and within a system that facilitates transfer to hospital care when necessary. Intrapartal mortality during intended home birth is concentrated in postdates pregnancies with evidence of meconium passage.

Effective strategies that enhance adherence to breast cancer screening guidelines.

Mammography has long been recognized as the most effective cancer screening modality. Nevertheless, substantial numbers of women either do not utilize mammography or do not do so in compliance with recommended screening guidelines. A substantial body of literature has been published that discusses strategies likely to be effective in increasing mammography screening. Health care provider recommendation for a mammogram is the single most effective intervention. This paper reviews the more recent literature to highlight a selection of the additional strategies that are most likely to be effective among all women, and among women of various vulnerable cultural and population subgroups. African American, Hispanic, Pacific Asian, and Native American communities are included in the discussion. The paper also addresses other communities with special needs, such as those who are lesbians, elderly, low users of health services, and those who are physically or mentally challenged.

Relationships of cortisol, perceived stress, genitourinary infections, and fetal fibronectin to gestational age at birth.

The authors investigated the role of stress and cortisol with patients having preterm labor (PTL) and preterm birth (PTB). The relationships of maternal cortisol, perceived stress, fetal fibronectin (fFN), and genitourinary infections to PTL and PTB were studied. A prospective, longitudinal, observational study (n = 78) was conducted in a private practice in central Texas. Subjects had 4 blood draws for cortisol measurements grouped by 15-19, 20-22, 23-26, 27-30, and 31-35 weeks of gestation. Subjects had 2 vaginal swabs forfFN, chlamydia, and bacterial vaginosis screens at 23-26 and 27-30 weeks with assessment of psychosocial stress at 23-26 and 31-35 weeks. Statistical analysis was by analysis of variance, Pearson correlations, Fisher exact test, and logistic regression. There were no significant differences between the PTB, PTL, and term groups on cortisol levels at any of the gestational periods. Cortisol concentrations at any gestational stage did not correlate with gestational age at birth. A relationship of cortisol to race was observed when comparing Caucasians to other ethnic groups. A correlation (r = 0.42, P < 0.001) between the change in Perceived Stress Scale (PSS) score and gestational age was observed. The greater the decrease in PSS scores, the longer was the gestational age. A significant increase in cortisol at 19-21 weeks (P < 0.04), 23-26 weeks (P < 0.05), and 31-35 weeks (P < 0.01) was observed in patients having genitourinary infection. PTL was also significantly increased in subjects having positive genitourinary infections at either 23-26 weeks or 27-30 weeks (P < 0.01). The sensitivity of fFN to predict PTL collected at 27-30 weeks was 40%, specificity 86%, positive predictive value 55%, and negative predictive value 83%. These results indicate that cortisol is a poor predictor of either PTL or PTB. A decrease in perceived stress during the 2nd trimester was associated with an increase in length of gestation, suggesting the possibility of stress reduction as an appropriate intervention for lengthening gestational age.

Pineoblastoma in a cockatiel.

Pineoblastoma, a primitive neoplasm of pineal gland origin, was diagnosed in a cockatiel based on gross, histopathological, and electron-microscopic findings.

Provision of comprehensive perinatal services through rural outreach: a model program.

A university-based program of perinatal care was extended to serve a spectrum of underserved populations through both urban and rural outreach. The program centered on the use of a multidisciplinary health care team comprised of a physician, nurse-midwife, health educator, social worker, nutritionist, pediatric nurse-practitioner, and patient case manager for health service delivery. It emphasized a decentralized service model with central referral and management of high-risk problems. The program has become a model for perinatal access and is reflected in current state legislation. The implementation of this program in four geographically rural communities is presented. Selected indices of perinatal outcome are presented, with San Diego County, CA, and national statistics as comparisons.

Task analysis in education and evaluation: an application among midwives in the Republic of Yemen.

The political union between the countries of North and South Yemen prompted nurse-midwife educators to re-examine the midwifery curricula of both countries and define the roles midwives play as members of the health team, based on the unique circumstance in which Yemeni midwives operate within the health care system. The faculty of the Health and Manpower Institute (HMI), the main educational institution for the education of midwives, recognised that the delineation of tasks attributed to the practice of midwifery varied widely within Yemen, and between Yemen and other countries, despite the existing international definition of the role. In 1992, the Agency for International Development (AID) funded a workshop for the HMI faculty. Nineteen midwives, nurses and other health care professionals used task analysis techniques to define key knowledge, skills and attitudes that a midwife should be taught in Yemen. Task analysis, a psychometric (test development) technique, is a process that can be used to develop specific role delineations. This article describes in detail the process of task analysis in identifying key skills, knowledge and attitudes to be taught to student midwives in Yemen, clarifying the role of midwives and identifying the usefulness of a derived task listing in educational development and student evaluations.

PIP: With the political union of North and South Yemen, Health and Manpower Institute (HMI) faculty noted a need to define tasks related to the practice of midwifery since these tasks differed greatly within Yemen and between Yemen and other countries. In 1992, USAID provided funds to the Family Health Training Project to put on a 3 day workshop in basic evaluation skills for 19 midwife teachers, nurses, and X-ray technicians. The workshop facilitators had the participants use the process of task analysis to define key knowledge, skills, and attitudes that a midwife should learn in Yemen. Task analysis is a psychometric (test development) technique. The steps of task analysis are data collection, development of a comprehensive document of the tasks, and evaluation of the task document. When task analysis is used as an evaluation methodology, the first step is making a detailed list of expected competencies (i.e., task statements) which are used to guide curriculum development. Program managers can use norm-referenced evaluation methods (i.e., comparing the pefformance of 1 midwife student or practitioner to that of others in the same or similar group) and/or criterion-referenced evaluation methods (i.e., an expected and predetermined standard of competent performance). The task statements can also be used for practicing midwives to perform self-assessment of their competency. The task list can also be used in more global evaluation strategies (e.g., licensure exams). HMI faculty learned and used task analysis during the workshop to identify core clinical competencies and to set goals and objectives (e.g., competency checklist aimed to improve midwifery instruction and improve quality of care). At the end of the workshop, the 2 groups built a consensus and finalized a Performance Assessment Instrument. Faculty members of midwifery schools throughout Yemen have field tested the instrument for validity.

Scoring and setting pass/fail standards for an essay certification examination in nurse-midwifery.

Examination for certification or licensure of health professionals (credentialing) in the United States is almost exclusively of the multiple choice format. The certification examination for entry into the practice of the profession of nurse-midwifery has, however, used a modified essay format throughout its twenty-year history. The examination has recently undergone a revision in the method for score interpretation and for pass/fail decision-making. The revised method, described in this paper, has important implications for all health professional credentialing agencies which use modified essay, oral or practical methods of competency assessment. This paper describes criterion-referenced scoring, the process of constructing the essay items, the methods for assuring validity and reliability for the examination, and the manner of standard setting. In addition, two alternative methods for increasing the validity of the pass/fail decision are evaluated, and the rationale for decision-making about marginal candidates is described.