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This is a copy of the slides presented at the meeting but not formally written up for the volume.
Cerium oxide (ceria) can be considered as one of the most important rare earth oxides. In conjunction with the benefits of nanotechnology, it has found enormous applications in catalysis, sensors and biomedical applications. These applications stem from its ability to switch oxidation states between +3 and +4 depending on ambient conditions. Nanoceria has been shown to impart protection to cells against the reactive oxygen species (ROS) by our group. We have also established a preferential protection of the normal cells against radiation damage as compared to the tumor cells. These stimulating properties of nanoceria make it imperative to stabilize it in various aqueous and non-aqueous solvents for practical applications. Systematic engineering of nanoceria in media like poly (ethylene glycol) (PEG), dextran and glucose can be of great importance in biological applications. Dextran and PEG have been used extensively to stabilize nanoparticles in solution. Biocompatibility of these media can be exploited to disperse nanoceria inside the body to provide cell protection. Unlike most of the reported work, where a two step synthesis and re-dispersion strategy is used, nanoceria prepared under room temperature wet chemical synthesis shows active switching of oxidation states. In the present work we report the successful synthesis of nanoceria in glucose, dextran and their effect on stability of nanoparticles in acidic and basic media. The role of polyhydroxyl group in complexing ceria and their subsequent oxidation/hydrolysis is monitored using UV-VIS spectroscopy. The nanoparticle characterization using high resolution transmission electron microscopy (HRTEM) for structure and morphology and X-ray Photoelectron Spectroscopy (XPS) for oxidation states will be reported. An effort will be made to present the quantitative analysis of various results.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
As in vivo cellular imaging becomes the necessary norm for understanding cancer and other diseases, new non-toxic nanoprobes are going to be required to replace the high quality cadmium based nanoprobes in use today. We are developing less toxic probes based on two types of luminescent ceramic nanoparticles: naturally occurring fluorescent (NOF) mimics and Ln-based ceramic oxide materials. The NOF minerals of interest and that have demonstrated initial luminosity of sufficient brightness for use in cellular studies that include sphalerite, scheelite, manganoan and perovskite nanoparticles. For Ln-based materials we have shown that Ln-doped zincite will also luminesce enough to allow for quantification in cellular activity. Once formed, these probes are functionalized such that they can be delivered to desired cellular targets. Probe derivatization has focused on surface capping with functionalized poly(ethyleneglycol) molecules/lipids to yield water soluble NCs and polyarginine-based transporters for transmembrane delivery. The probes are being evaluated for their luminescent properties, as well as their non-toxicity and ability to report on cell-signaling events with various cell lines using multi-spectral, confocal microscopy, and other techniques. Preliminary interdisciplinary studies have validated the basic approaches for the synthesis of NOF nanoprobes and the bio-delivery and imaging of nanoparticles. Work to optimize the design, delivery, and imaging of these new nanoprobes is expected to achieve the NIH directed goal of increasing in the sensitivity and specificity of molecular probes for imaging. Details of the synthesis, functionalization and biological imaging using these probes will be presented. This work partially supported by the United States Department of Energy under contract number DE-AC04-94AL85000. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the United States Department of Energy and by the National Institutes of health through the NIH Roadmap for Medical Research, Grant #1 R21 EB005365-01. Information on this RFA (Innovation in Molecular Imaging Probes) can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-021.html.
Our purpose was to describe the clinical, epidemiological and laboratory characteristics of patients hospitalised with acute Q fever in an endemic area of Israel. We conducted a historical cohort study of all patients hospitalised with a definite diagnosis of acute Q fever, and compared them to patients suspected to have acute Q fever, but diagnosis was ruled out. A total of 38 patients had a definitive diagnosis, 47% occurred during the autumn and winter seasons, only 18% lived in rural regions. Leucopaenia and thrombocytopaenia were uncommon (16% and 18%, respectively), but mild hepatitis was common (mean aspartate aminotransferase 76 U/l, mean alanine aminotransferase 81 U/l). We compared them with 74 patients in which acute Q fever was ruled out, and found that these parameters were not significantly different. Patients with acute Q fever had a shorter hospitalisation and they were treated more often with doxycycline than those without acute Q fever (6.4 vs. 14 days, P = 0.007, 71% vs. 38%, P = 0.001, respectively). In conclusion, acute Q fever can manifest as an unspecified febrile illness, with no seasonality. We suggest that in endemic areas, Q fever should be considered in the differential diagnosis in any febrile patient with risk factors for a persistent infection.
Let K be a convex body (compact, convex set with interior points) in n-dimensional Euclidean space En, and let V(K) denote the volume of K. Let K′ be a centrally symmetric body of maximum volume contained in K (in fact, K′ is unique; see 2 or 9), and define
Single-phase Fe-Nb and Co-Nb Laves phase alloys were produced by arc melting and levitation melting. By casting the levitation melted alloys in a preheated mould and subsequent slow cooling to room temperature, solid rods of 15 mm in diameter and about 100 mm length of the brittle Laves phases were obtained. Within the extended homogeneity ranges of the NbFe2 and NbCo2 Laves phases, the Vickers hardness was measured in dependence on composition. The results show that the hardness has a maximum at the stoichiometric composition in both systems, indicating defect softening. Nanoindentation measurements on a Co-Nb diffusion couple confirm the dependence of the hardness on composition. In addition, these measurements indicate that the crystal structure of the Laves phase polytype – cubic or hexagonal – seems to have no effect on the hardness. Indentation fracture toughness KIC-IF data for the different polytypes of the Laves phases were evaluated from the Palmquist cracks originating from the edges of the Vickers indentations.
Many studies have identified changes in the brain associated with obsessive–compulsive disorder (OCD), but few have examined the relationship between genetic determinants of OCD and brain variation.
We present the first genome-wide investigation of overlapping genetic risk for OCD and genetic influences on subcortical brain structures.
Using single nucleotide polymorphism effect concordance analysis, we measured genetic overlap between the first genome-wide association study (GWAS) of OCD (1465 participants with OCD, 5557 controls) and recent GWASs of eight subcortical brain volumes (13 171 participants).
We found evidence of significant positive concordance between OCD risk variants and variants associated with greater nucleus accumbens and putamen volumes. When conditioning OCD risk variants on brain volume, variants influencing putamen, amygdala and thalamus volumes were associated with risk for OCD.
These results are consistent with current OCD neurocircuitry models. Further evidence will clarify the relationship between putamen volume and OCD risk, and the roles of the detected variants in this disorder.
Declaration of interest
The authors have declared that no competing interests exist.
Research on post-traumatic stress disorder (PTSD) course finds a substantial proportion of cases remit within 6 months, a majority within 2 years, and a substantial minority persists for many years. Results are inconsistent about pre-trauma predictors.
The WHO World Mental Health surveys assessed lifetime DSM-IV PTSD presence-course after one randomly-selected trauma, allowing retrospective estimates of PTSD duration. Prior traumas, childhood adversities (CAs), and other lifetime DSM-IV mental disorders were examined as predictors using discrete-time person-month survival analysis among the 1575 respondents with lifetime PTSD.
20%, 27%, and 50% of cases recovered within 3, 6, and 24 months and 77% within 10 years (the longest duration allowing stable estimates). Time-related recall bias was found largely for recoveries after 24 months. Recovery was weakly related to most trauma types other than very low [odds-ratio (OR) 0.2–0.3] early-recovery (within 24 months) associated with purposefully injuring/torturing/killing and witnessing atrocities and very low later-recovery (25+ months) associated with being kidnapped. The significant ORs for prior traumas, CAs, and mental disorders were generally inconsistent between early- and later-recovery models. Cross-validated versions of final models nonetheless discriminated significantly between the 50% of respondents with highest and lowest predicted probabilities of both early-recovery (66–55% v. 43%) and later-recovery (75–68% v. 39%).
We found PTSD recovery trajectories similar to those in previous studies. The weak associations of pre-trauma factors with recovery, also consistent with previous studies, presumably are due to stronger influences of post-trauma factors.
Sexual assault is a global concern with post-traumatic stress disorder (PTSD), one of the common sequelae. Early intervention can help prevent PTSD, making identification of those at high risk for the disorder a priority. Lack of representative sampling of both sexual assault survivors and sexual assaults in prior studies might have reduced the ability to develop accurate prediction models for early identification of high-risk sexual assault survivors.
Data come from 12 face-to-face, cross-sectional surveys of community-dwelling adults conducted in 11 countries. Analysis was based on the data from the 411 women from these surveys for whom sexual assault was the randomly selected lifetime traumatic event (TE). Seven classes of predictors were assessed: socio-demographics, characteristics of the assault, the respondent's retrospective perception that she could have prevented the assault, other prior lifetime TEs, exposure to childhood family adversities and prior mental disorders.
Prevalence of Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) PTSD associated with randomly selected sexual assaults was 20.2%. PTSD was more common for repeated than single-occurrence victimization and positively associated with prior TEs and childhood adversities. Respondent's perception that she could have prevented the assault interacted with history of mental disorder such that it reduced odds of PTSD, but only among women without prior disorders (odds ratio 0.2, 95% confidence interval 0.1–0.9). The final model estimated that 40.3% of women with PTSD would be found among the 10% with the highest predicted risk.
Whether counterfactual preventability cognitions are adaptive may depend on mental health history. Predictive modelling may be useful in targeting high-risk women for preventive interventions.
Background: The surgical risk factors and neuro-imaging characteristics associated with cerebellar mutism (CM) remain unclear and require further investigation. We aimed to examine surgical and MRI findings associated with CM in children following posterior fossa tumor resection. Methods: Using our data registry, we retrospectively collected data from pediatric patients who acquired CM and were matched based on age and pathology type with patients not acquiring CM after posterior fossa surgery. The strength of association between surgical and MRI variables and CM were examined using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results: A total of 22 patients were included. Medulloblastoma was the most common pathology among CM patients (91%). Tumor attachment to the floor of the fourth ventricle (OR, 6; 95% CI, 0.7-276), calcification/hemosiderin deposition (OR 7; 95% CI 0.9-315.5), and post-operative peri-ventricular ischemia on MRI (OR, 5; 95% CI, 0.5-236.5) were found to have the highest association with CM. Conclusions: Our results may suggest that tumor attachment to the floor of the fourth ventricle, pathological calcification, and post-operative ischemia are relatively more prevalent in patients with CM. Collectively, our work calls for a larger multi-institutional study of CM patients to further investigate the determinants and management of CM to potentially minimize its development and predict onset.
The suicide rate has increased significantly among US Army soldiers over the past decade. Here we report the first results from a large psychological autopsy study using two control groups designed to reveal risk factors for suicide death among soldiers beyond known sociodemographic factors and the presence of suicide ideation.
Informants were next-of-kin and Army supervisors for: 135 suicide cases, 137 control soldiers propensity-score-matched on known sociodemographic risk factors for suicide and Army history variables, and 118 control soldiers who reported suicide ideation in the past year.
Results revealed that most (79.3%) soldiers who died by suicide have a prior mental disorder; mental disorders in the prior 30-days were especially strong risk factors for suicide death. Approximately half of suicide decedents tell someone that they are considering suicide. Virtually all of the risk factors identified in this study differed between suicide cases and propensity-score-matched controls, but did not significantly differ between suicide cases and suicide ideators. The most striking difference between suicides and ideators was the presence in the former of an internalizing disorder (especially depression) and multi-morbidity (i.e. 3+ disorders) in the past 30 days.
Most soldiers who die by suicide have identifiable mental disorders shortly before their death and tell others about their suicidal thinking, suggesting that there are opportunities for prevention and intervention. However, few risk factors distinguish between suicide ideators and decedents, pointing to an important direction for future research.
Introduction: The Canadian Triage and Acuity Scale (CTAS) is the standard used in all Canadian (and many international) emergency departments (EDs) for establishing the priority by which patients should be assessed. In addition to its clinical utility, CTAS has become an important administrative metric used by governments to estimate patient care requirements, ED funding and workload models. Despite its importance, the process by which CTAS scores are derived is highly variable. Emphasis on ED wait times has also drawn attention to the length of time the triage process takes. The primary objective of this study was to determine the interrater agreement of CTAS in current clinical practice. The secondary objective was to determine the time it takes to triage in a variety of ED settings. Methods: This was a prospective, observational study conducted in 7 hospital EDs, selected to represent a mix of triage processes (electronic vs. manual), documentation practices (electronic vs. paper), hospital types (rural, community and teaching) and patient volumes (annual ED census ranged from 38,000 to 136,000). An expert CTAS auditor observed on-duty triage nurses in the ED and assigned independent CTAS in real time. Research assistants not involved in the triage process independently recorded the triage time. Interrater agreement was estimated using unweighted and quadratic-weighted kappa statistics with 95% confidence intervals (CIs). Results: 738 consecutive patient CTAS assessments were audited over 21 seven-hour triage shifts. Exact modal agreement was achieved for 554 (75.0%) patients. Using the auditor’s CTAS score as the reference standard, on-duty triage nurses over-triaged 89 (12.1%) and under-triaged 95 (12.9%) patients. Interrater agreement was “good” with an unweighted kappa of 0.63 (95% CI: 0.58, 0.67) and quadratic-weighted kappa of 0.79 (95% CI: 0.67, 0.90). Research assistants captured triage time for 3808 patients over 69 shifts at 7 different EDs. Median (IQR) triage time was 5.2 (3.8, 7.3) minutes and ranged from 3.9 (3.1, 4.8) minutes to 7.5 (5.8, 10.8) minutes. Conclusion: Variability in the accuracy, and length of time taken to perform CTAS assessments suggest that a standardized approach to performing CTAS assessments would improve both clinical decision making, and administrative data accuracy.
The stress sensitization theory hypothesizes that individuals exposed to childhood adversity will be more vulnerable to mental disorders from proximal stressors. We aimed to test this theory with respect to risk of 30-day major depressive episode (MDE) and generalized anxiety disorder (GAD) among new US Army soldiers.
The sample consisted of 30 436 new soldier recruits in the Army Study to Assess Risk and Resilience (Army STARRS). Generalized linear models were constructed, and additive interactions between childhood maltreatment profiles and level of 12-month stressful experiences on the risk of 30-day MDE and GAD were analyzed.
Stress sensitization was observed in models of past 30-day MDE (χ28 = 17.6, p = 0.025) and GAD (χ28 = 26.8, p = 0.001). This sensitization only occurred at high (3+) levels of reported 12-month stressful experiences. In pairwise comparisons for the risk of 30-day MDE, the risk difference between 3+ stressful experiences and no stressful experiences was significantly greater for all maltreatment profiles relative to No Maltreatment. Similar results were found with the risk for 30-day GAD with the exception of the risk difference for Episodic Emotional and Sexual Abuse, which did not differ statistically from No Maltreatment.
New soldiers are at an increased risk of 30-day MDE or GAD following recent stressful experiences if they were exposed to childhood maltreatment. Particularly in the military with an abundance of unique stressors, attempts to identify this population and improve stress management may be useful in the effort to reduce the risk of mental disorders.
Traumatic events are common globally; however, comprehensive population-based cross-national data on the epidemiology of posttraumatic stress disorder (PTSD), the paradigmatic trauma-related mental disorder, are lacking.
Data were analyzed from 26 population surveys in the World Health Organization World Mental Health Surveys. A total of 71 083 respondents ages 18+ participated. The Composite International Diagnostic Interview assessed exposure to traumatic events as well as 30-day, 12-month, and lifetime PTSD. Respondents were also assessed for treatment in the 12 months preceding the survey. Age of onset distributions were examined by country income level. Associations of PTSD were examined with country income, world region, and respondent demographics.
The cross-national lifetime prevalence of PTSD was 3.9% in the total sample and 5.6% among the trauma exposed. Half of respondents with PTSD reported persistent symptoms. Treatment seeking in high-income countries (53.5%) was roughly double that in low-lower middle income (22.8%) and upper-middle income (28.7%) countries. Social disadvantage, including younger age, female sex, being unmarried, being less educated, having lower household income, and being unemployed, was associated with increased risk of lifetime PTSD among the trauma exposed.
PTSD is prevalent cross-nationally, with half of all global cases being persistent. Only half of those with severe PTSD report receiving any treatment and only a minority receive specialty mental health care. Striking disparities in PTSD treatment exist by country income level. Increasing access to effective treatment, especially in low- and middle-income countries, remains critical for reducing the population burden of PTSD.
This is the first cross-national study of intermittent explosive disorder (IED).
A total of 17 face-to-face cross-sectional household surveys of adults were conducted in 16 countries (n = 88 063) as part of the World Mental Health Surveys initiative. The World Health Organization Composite International Diagnostic Interview (CIDI 3.0) assessed DSM-IV IED, using a conservative definition.
Lifetime prevalence of IED ranged across countries from 0.1 to 2.7% with a weighted average of 0.8%; 0.4 and 0.3% met criteria for 12-month and 30-day prevalence, respectively. Sociodemographic correlates of lifetime risk of IED were being male, young, unemployed, divorced or separated, and having less education. The median age of onset of IED was 17 years with an interquartile range across countries of 13–23 years. The vast majority (81.7%) of those with lifetime IED met criteria for at least one other lifetime disorder; co-morbidity was highest with alcohol abuse and depression. Of those with 12-month IED, 39% reported severe impairment in at least one domain, most commonly social or relationship functioning. Prior traumatic experiences involving physical (non-combat) or sexual violence were associated with increased risk of IED onset.
Conservatively defined, IED is a low prevalence disorder but this belies the true societal costs of IED in terms of the effects of explosive anger attacks on families and relationships. IED is more common among males, the young, the socially disadvantaged and among those with prior exposure to violence, especially in childhood.
Most systematic tables of data associated to ranks of elliptic curves order the curves by conductor. Recent developments, led by work of Bhargava and Shankar studying the average sizes of
-Selmer groups, have given new upper bounds on the average algebraic rank in families of elliptic curves over
, ordered by height. We describe databases of elliptic curves over
, ordered by height, in which we compute ranks and
-Selmer group sizes, the distributions of which may also be compared to these theoretical results. A striking new phenomenon that we observe in our database is that the average rank eventually decreases as height increases.
A high-resolution atmospheric radiocarbon record has been obtained for the interval of 17–36 kyr from U/Th-dated aragonite sediment of Lake Lisan. Reservoir age corrections were applied with reservoir ages of 200, 1250, and 2000 yr, which correlate with the different water levels of the lake. The present 14C record for Lake Lisan shows near resemblance with that of Lake Suigetsu: both converge to the value of Δ14C ∼0‰ at 32 kyr cal BP. Both also show significant differences compared to other reported high-resolution 14C records (e.g. Iceland Sea, Cariaco basin, and Bahamas speleothem). This inconsistency should be addressed by re-assessment of the basic assumptions behind the determination of calendar ages of the various records.
The Commission again subscribes to a number of the good resolutions it has made in the past, for example, to follow the almost universal practice of counting the observed times, either in decimals of a day or in hours and minutes, from Greenwich mean noon, even though one is convinced that the rest of the world should adopt U.T.; and to prepare a chart, identifying the variable and the comparison stars, to form a part of the discovery announcement of a variable which cannot be easily identified through a Durchmusterung number and which is bright enough to invite further observation.