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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.
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.
As a follow-up to the development of astrometric detectors of sufficient accuracy to detect extrasolar planetary systems, the Allegheny Observatory is modernizing their 30-inch Thaw Refractor. Changes include a new objective lens and the transition of the observational bandpass from blue light to red. The new system will have sufficient accuracy to detect jovian planets orbiting any of several dozen of the Sun's nearest stellar neighbors.
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.
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.
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.
The U.S. Army uses universal preventives interventions for several negative outcomes (e.g. suicide, violence, sexual assault) with especially high risks in the early years of service. More intensive interventions exist, but would be cost-effective only if targeted at high-risk soldiers. We report results of efforts to develop models for such targeting from self-report surveys administered at the beginning of Army service.
21 832 new soldiers completed a self-administered questionnaire (SAQ) in 2011–2012 and consented to link administrative data to SAQ responses. Penalized regression models were developed for 12 administratively-recorded outcomes occurring by December 2013: suicide attempt, mental hospitalization, positive drug test, traumatic brain injury (TBI), other severe injury, several types of violence perpetration and victimization, demotion, and attrition.
The best-performing models were for TBI (AUC = 0.80), major physical violence perpetration (AUC = 0.78), sexual assault perpetration (AUC = 0.78), and suicide attempt (AUC = 0.74). Although predicted risk scores were significantly correlated across outcomes, prediction was not improved by including risk scores for other outcomes in models. Of particular note: 40.5% of suicide attempts occurred among the 10% of new soldiers with highest predicted risk, 57.2% of male sexual assault perpetrations among the 15% with highest predicted risk, and 35.5% of female sexual assault victimizations among the 10% with highest predicted risk.
Data collected at the beginning of service in self-report surveys could be used to develop risk models that define small proportions of new soldiers accounting for high proportions of negative outcomes over the first few years of service.
The drilled Inter-Continental Drilling Project core at the deeps of the Dead Sea reveals thick sequences of halite deposits from the last interglacial period, reflecting prevailing arid conditions in the lake’s watershed. Here, we examine sequences of intercalating evaporates (halite or gypsum) and fine-detritus laminae and apply petrographic, micro-X-ray fluorescence, and statistical tools to establish in high-temporal resolution the hydroclimatic controls on the sedimentation in the last interglacial Dead Sea. The time series of the thickness of the best-recovered core sections of the layered halite, detritus, and gypsum reveals periodicities of ~11, 7–8, and 4–5 yr, pointing to a North Atlantic control and possibly solar influence on the hydrology of the Dead Sea watershed during the regionally arid period of the last interglacial period. Similar periodicities were detected in the last glacial and modern sedimentary sequences of the Dead Sea and other archives of the central Levant, indicating a persistent impact of the solar cycles on regional hydrology, possibly through the effects of the North Atlantic Oscillation.
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.
Fourteen members of the committee have failed to respond to correspondence; nearly all of the others have expressed the definite opinion that non-responsive members should be dropped from committee membership when a new list is prepared a few correspondents indicating however, that the policy should be adopted for Commission 27 only if generally adopted for all commissions of the Union.
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.
Nutrient deficiencies have been implicated in anti-social behaviour in schoolchildren; hence, correcting them may improve sociability. We therefore tested the effects of vitamin, mineral and n-3 supplementation on behaviour in a 12-week double-blind randomised placebo-controlled trial in typically developing UK adolescents aged 13–16 years (n 196). Changes in erythrocyte n-3 and 6 fatty acids and some mineral and vitamin levels were measured and compared with behavioural changes, using Conners’ teacher ratings and school disciplinary records. At baseline, the children’s PUFA (n-3 and n-6), vitamin and mineral levels were low, but they improved significantly in the group treated with n-3, vitamins and minerals (P=0·0005). On the Conners disruptive behaviour scale, the group given the active supplements improved, whereas the placebo group worsened (F=5·555, d=0·35; P=0·02). The general level of disciplinary infringements was low, thus making it difficult to obtain improvements. However, throughout the school term school disciplinary infringements increased significantly (by 25 %; Bayes factor=115) in both the treated and untreated groups. However, when the subjects were split into high and low baseline infringements, the low subset increased their offences, whereas the high-misbehaviour subset appeared to improve after treatment. But it was not possible to determine whether this was merely a statistical artifact. Thus, when assessed using the validated and standardised Conners teacher tests (but less clearly when using school discipline records in a school where misbehaviour was infrequent), supplementary nutrition might have a protective effect against worsening behaviour.
To determine the association between household food security and infant complementary feeding practices in rural Bangladesh.
Prospective, cohort study using structured home interviews during pregnancy and 3 and 9 months after delivery. We used two indicators of household food security at 3-months’ follow-up: maternal Food Composition Score (FCS), calculated via the World Food Programme method, and an HHFS index created from an eleven-item food security questionnaire. Infant feeding practices were characterized using WHO definitions.
Two rural sub-districts of Kishoreganj, Bangladesh.
Mother–child dyads (n 2073) who completed the 9-months’ follow-up.
Complementary feeding was initiated at age ≤4 months for 7 %, at 5–6 months for 49 % and at ≥7 months for 44 % of infants. Based on 24 h dietary recall, 98 % of infants were still breast-feeding at age 9 months, and 16 % received ≥4 food groups and ≥4 meals (minimally acceptable diet) in addition to breast milk. Mothers’ diet was more diverse than infants’. The odds of receiving a minimally acceptable diet for infants living in most food-secure households were three times those for infants living in least food-secure households (adjusted OR=3·0; 95 % CI 2·1, 4·3). Socio-economic status, maternal age, literacy, parity and infant sex were not associated with infant diet.
HHFS and maternal FCS were significant predictors of subsequent infant feeding practices. Nevertheless, even the more food-secure households had poor infant diet. Interventions aimed at improving infant nutritional status need to focus on both complementary food provision and education.
Considerable research has documented that exposure to traumatic events has negative effects on physical and mental health. Much less research has examined the predictors of traumatic event exposure. Increased understanding of risk factors for exposure to traumatic events could be of considerable value in targeting preventive interventions and anticipating service needs.
General population surveys in 24 countries with a combined sample of 68 894 adult respondents across six continents assessed exposure to 29 traumatic event types. Differences in prevalence were examined with cross-tabulations. Exploratory factor analysis was conducted to determine whether traumatic event types clustered into interpretable factors. Survival analysis was carried out to examine associations of sociodemographic characteristics and prior traumatic events with subsequent exposure.
Over 70% of respondents reported a traumatic event; 30.5% were exposed to four or more. Five types – witnessing death or serious injury, the unexpected death of a loved one, being mugged, being in a life-threatening automobile accident, and experiencing a life-threatening illness or injury – accounted for over half of all exposures. Exposure varied by country, sociodemographics and history of prior traumatic events. Being married was the most consistent protective factor. Exposure to interpersonal violence had the strongest associations with subsequent traumatic events.
Given the near ubiquity of exposure, limited resources may best be dedicated to those that are more likely to be further exposed such as victims of interpersonal violence. Identifying mechanisms that account for the associations of prior interpersonal violence with subsequent trauma is critical to develop interventions to prevent revictimization.
Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood.
Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated.
Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71–7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers.
Maternal D&A is associated with persistent D&A during the daughter's transition to adulthood. Intervention strategies should consider the mother's mental health.
Although interventions exist to reduce violent crime, optimal implementation requires accurate targeting. We report the results of an attempt to develop an actuarial model using machine learning methods to predict future violent crimes among US Army soldiers.
A consolidated administrative database for all 975 057 soldiers in the US Army in 2004–2009 was created in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). Of these soldiers, 5771 committed a first founded major physical violent crime (murder-manslaughter, kidnapping, aggravated arson, aggravated assault, robbery) over that time period. Temporally prior administrative records measuring socio-demographic, Army career, criminal justice, medical/pharmacy, and contextual variables were used to build an actuarial model for these crimes separately among men and women using machine learning methods (cross-validated stepwise regression, random forests, penalized regressions). The model was then validated in an independent 2011–2013 sample.
Key predictors were indicators of disadvantaged social/socioeconomic status, early career stage, prior crime, and mental disorder treatment. Area under the receiver-operating characteristic curve was 0.80–0.82 in 2004–2009 and 0.77 in the 2011–2013 validation sample. Of all administratively recorded crimes, 36.2–33.1% (male-female) were committed by the 5% of soldiers having the highest predicted risk in 2004–2009 and an even higher proportion (50.5%) in the 2011–2013 validation sample.
Although these results suggest that the models could be used to target soldiers at high risk of violent crime perpetration for preventive interventions, final implementation decisions would require further validation and weighing of predicted effectiveness against intervention costs and competing risks.
An estimated 200 million children worldwide fail to meet their development potential due to poverty, poor health and unstimulating environments. Missing developmental milestones has lasting effects on adult human capital. Africa has a large burden of risk factors for poor child development. The objective of this paper is to identify scope for improvement at the country level in three domains – nutrition, environment, and mother–child interactions. We used nationally representative data from large-scale surveys, data repositories and country reports from 2000 to 2014. Overall, there was heterogeneity in performance across domains, suggesting that each country faces distinct challenges in addressing risk factors for poor child development. Data were lacking for many indicators, especially in the mother–child interaction domain. There is a clear need to improve routine collection of high-quality, country-level indicators relevant to child development to assess risk and track progress.