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A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Deciduous dipterocarp forests throughout Asia provide crucial habitat for several globally threatened species. During the dry season water availability in these forests is primarily limited to perennial rivers and waterholes. Such water sources form an essential part of these dry forests and are used by multiple species, including large mammals and birds, but little is known regarding how waterhole characteristics affect wildlife use. We investigated waterhole utilization by six globally threatened dry forest specialists: banteng Bos javanicus, Eld's deer Rucervus eldii, giant ibis Thaumatibis gigantea, green peafowl Pavo muticus, lesser adjutant Leptoptilos javanicus and Asian woolly-necked stork Ciconia episcopus. We camera-trapped 54 waterholes in Srepok Wildlife Sanctuary, eastern Cambodia, during the dry season of December 2015–June 2016. We measured nine waterhole and landscape characteristics, including indicators of human disturbance. Waterhole depth (measured every 2 weeks) and the area of water at the start of the dry season were the main environmental factors influencing waterhole use. Additionally, waterholes further from villages were more frequently used than those nearer. Our study reaffirmed the importance of waterholes in supporting globally threatened species, especially large grazers, which are critical for maintaining these dry forest ecosystems. The results also suggested that artificially enlarging and deepening selected waterholes, particularly those further from human disturbance, could enhance available habitat for a range of species, including grazers. However, this would need to be conducted in coordination with patrolling activities to ensure waterholes are not targets for illegal hunting, which is a problem throughout South-east Asian protected areas.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Both childhood maltreatment and insecure attachment are known to be associated with depression in adulthood. The extent insecure attachment increases the risk of adult clinical depression over that of parental maltreatment among women in the general population is explored, using those at high risk because of their selection for parental maltreatment together with an unselected sample.
Semi-structured interviews and investigator-based measures are employed.
Insecure attachment is highly associated with parental maltreatment with both contributing to the risk of depression, with attachment making a substantial independent contribution. Risk of depression did not vary by type of insecure attachment, but the core pathways of the dismissive and enmeshed involved the whole life course in terms of greater experience of a mother's physical abuse and their own anger as an adult, with both related to adult depression being more often provoked by a severely threatening event involving humiliation rather than loss. By contrast, depression of the insecure fearful and withdrawn was more closely associated with both current low self-esteem and an inadequately supportive core relationship. In terms of depression taking a chronic course, insecure attachment was again a key risk factor, but with this now closely linked with the early experience of a chaotic life style but with this involving only a modest number of women.
Both insecure attachment and parental maltreatment contribute to an increased risk of depression with complex effects involving types of insecure attachment.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
Against the legal recognition of same-sex marriage, many advocates of religious liberty argue that those who adhere to “traditional” understandings of marriage should not be forced to “recognize” same-sex marriages. This includes exempting individual business owners engaged in commercial activity from anti-discrimination laws. I argue that such exemptions overreach. Equal access to the commercial arena is an essential feature of life in America’s commercial republic, which means that public accommodations should not be given exemptions on religious grounds. Yet this does not require business owners to morally approve of same-sex marriage; nor does it require them to grant same-sex marriages “equal concern and respect.” Rather, it requires simple toleration, which is compatible with moral disapproval. Indeed, I argue that this is the very sort of toleration at the foundation of religious liberty in America. Efforts to grant religious exemptions to anti-discrimination laws invite the return of religious conflict and discrimination. Prohibiting discrimination on the basis of sexual orientation in public accommodations is necessary not only for equal citizenship, but to maintain the regime of toleration that undergirds religious liberty in a pluralistic democracy.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Clozapine has proved to be an effective antipsychotic for the treatment of refractory schizophrenia – characterised by the persistence of symptoms despite optimal treatment trials with at least two different antipsychotics at adequate dose and duration – but its use is hampered by adverse effects. The development of clozapine-induced diabetes is commonly considered to arise as part of a metabolic syndrome, associated with weight gain, and thus evolves slowly. We present the case of an individual with refractory schizophrenia and metformin-controlled diabetes who developed rapid-onset insulin-dependent hyperglycaemia immediately after starting clozapine. Given the refractory nature of his illness, the decision was made to continue clozapine and manage the diabetes. This case supports the existence of a more direct mechanism by which clozapine alters glycaemic control, aside from the more routine slow development of a metabolic syndrome.
The present communication demonstrates that even if individuals are answering a pre/post survey at random, the percentage of individuals showing improvement from the pre- to the post-survey can be surprisingly high. Some simple formulas and tables are presented that will allow analysts to quickly determine the expected percentage of individuals showing improvement if participants just answered the survey at random. This benchmark percentage, in turn, defines the appropriate null hypothesis for testing if the actual percentage observed is greater than the expected random answering percentage.
The analysis is demonstrated by testing if actual improvement in a component of the US Department of Agriculture’s (USDA) Expanded Food and Nutrition Education Program is significantly different from random answering improvement.
From 2011 to 2014, 364320 adults completed a standardized pre- and post-survey administered by the USDA.
For each year, the statement that the actual number of improvements is less than the expected number if the questions were just answered at random cannot be rejected. This does not mean that the pre-/post-test survey instrument is flawed, only that the data are being inappropriately evaluated.
Knowing the percentage of individuals showing improvement on a pre/post survey instrument when questions are randomly answered is an important benchmark number to determine in order to draw valid inferences about nutrition interventions. The results presented here should help analysts in determining this benchmark number for some common survey structures and avoid drawing faulty inferences about the effectiveness of an intervention.
DNA nanostructures are a set of materials with well-defined physical, chemical, and biological properties that can be used on their own or incorporated with other materials for many applications. Herein, the practical aspects of utilizing DNA nanostructures (structural or dynamic) as materials are comprehensively covered. This article first summarizes properties of DNA molecules and practical considerations and then discusses the fundamental design principles of structural DNA nanostructures. Finally, various aspects of dynamic DNA nanostructure-based actuation and computation are included.
Eddy covariance data collected over a horizontal surface on the largest ice body on Kilimanjaro, Tanzania, over 26–29 July 2005 were used to assess the uncertainty of calculating sublimation with a surface energy balance (SEB) model. Data required for input to the SEB model were obtained from an existing automatic weather station. Surface temperatures that were solved iteratively by the SEB model were used to compute emitted longwave radiation, turbulent heat fluxes using the aerodynamic bulk method and the subsurface heat flux. Roughness lengths for momentum and temperature, which were found to be the most important input parameters controlling the magnitude of modelled (bulk method) turbulent heat fluxes, were obtained using eddy covariance data. The roughness length for momentum was estimated to be 1.7×10–3 m, while the length for temperature was one order of magnitude smaller. Modelled sensible and latent heat fluxes (bulk method) compared well to eddy covariance data, with root-mean-square differences between 3.1 and 4.8 Wm–2 for both turbulent heat fluxes. Modelled sublimation accounted for about 90% of observed ablation, confirming that mass loss by melting is much less important than sublimation on the horizontal surfaces of the remaining plateau glaciers on Kilimanjaro.
We present results from a comprehensive field study carried out near Barrow, Alaska, USA, designed to characterize local- to intermediate-scale sea-ice processes in the Arctic coastal zone of central importance to the annual cycle and evolution of the coastal sea ice. Included in this are the behavior of the snow cover of the ice and adjacent tundra and lake system; concurrent studies of mass balance of the sea ice and lake ice; interaction of shortwave radiation with the shore-fast ice and the adjacent land surfaces; evolution of the area coverage and distribution of the various surface types; and the resulting regional albedo values. Maximum snow depths decreased during 2000–02 from 0.38 m to 0.26 m. Ice-melt rates in 2001 were 0.05 and 0.028md–1 at the top and bottom of the sea ice respectively, two to three times larger than observations from the central Arctic. Detailed surface results combined with aircraft photography were used to calculate regional albedos for the late spring and early summer of 2001. Values ranged from 0.8 for all cold snow-covered surfaces to approximately 0.4 for melting sea ice and lake ice vs 0.18 for bare tundra. Regional and surface-based values of cumulative shortwave radiation entering the ice were consistent, indicating that albedo sampling on a scale of 200m can provide a useful representation for regional sea-ice albedo.
Broadband radiation schemes (parameterizations) are commonly used tools in glacier mass-balance modelling, but their performance at high altitude in the tropics has not been evaluated in detail. Here we take advantage of a high-quality 2 year record of global radiation (G ) and incoming longwave radiation (L ↓) measured on Kersten Glacier, Kilimanjaro, East Africa, at 5873 m a.s.l., to optimize parameterizations of G and L ↓. We show that the two radiation terms can be related by an effective cloud-cover fraction neff , so G or L ↓ can be modelled based on neff derived from measured L ↓ or G, respectively. At neff = 1, G is reduced to 35% of clear-sky G, and L ↓ increases by 45–65% (depending on altitude) relative to clear-sky L ↓. Validation for a 1 year dataset of G and L ↓ obtained at 4850 m on Glaciar Artesonraju, Peruvian Andes, yields a satisfactory performance of the radiation scheme. Whether this performance is acceptable for mass-balance studies of tropical glaciers is explored by applying the data from Glaciar Artesonraju to a physically based mass-balance model, which requires, among others, G and L ↓ as forcing variables. Uncertainties in modelled mass balance introduced by the radiation parameterizations do not exceed those that can be caused by errors in the radiation measurements. Hence, this paper provides a tool for inclusion in spatially distributed mass-balance modelling of tropical glaciers and/or extension of radiation data when only G or L ↓ is measured.
We propose an infinite-dimensional adjoint-based inexact Gauss-Newton method for the solution of inverse problems governed by Stokes models of ice sheet flow with nonlinear rheology and sliding law. The method is applied to infer the basal sliding coefficient and the rheological exponent parameter fields from surface velocities. The inverse problem is formulated as a nonlinear least-squares optimization problem whose cost functional is the misfit between surface velocity observations and model predictions. A Tikhonov regularization term is added to the cost functional to render the problem well-posed and account for observational error. Our findings show that the inexact Newton method is significantly more efficient than the nonlinear conjugate gradient method and that the number of Stokes solutions required to solve the inverse problem is insensitive to the number of inversion parameters. The results also show that the reconstructions of the basal sliding coefficient converge to the exact sliding coefficient as the observation error (here, the noise added to synthetic observations) decreases, and that a nonlinear rheology makes the reconstruction of the basal sliding coefficient more difficult. For the inversion of the rheology exponent field, we find that horizontally constant or smoothly varying parameter fields can be reconstructed satisfactorily from noisy observations.
OBJECTIVES/SPECIFIC AIMS: The goal of this research is to use circulating tumor cells (CTC) enumeration and characterization to monitor anticancer treatment response. Emerging evidence strongly suggests the implications that epithelial-to-mesenchymal transition may have in cancer metastasis. Consequently, we hope to elucidate the significance of mesenchymal and stem-like CTCs in the peripheral blood of metastatic pancreatic cancer patients by analyzing the prevalence and frequency trends of CD133+ CTCs, as they relate to clinical events. We also hope to determine if there is a correlation between EpCAM+ CTCs and CD133+ CTCs numbers with tumor size, disease stage, and patient clinical outcome. METHODS/STUDY POPULATION: Blood samples of patients with metastatic pancreatic cancer (stage IV) were obtained from the University of Florida Health Cancer Center after informed consent through an IRB-approved protocol. CTC capture, characterization, and enumeration was performed on the blood of these cancer patients during their anticancer treatment. Patients had blood drawn for this purpose at time points aligned with clinical phlebotomy (every 2 weeks). CTC capture was performed by introducing treated patient blood samples into antibody-functionalized microdevices. The PDMS devices were functionalized by immobilizing either anti-EpCAM or anti-CD133, through an avidin-biotin complex. After capture, cells were fixated and permeabilized with 4% paraformaldehyde and 0.2% Triton X-100, respectively. Three-color immunocytochemistry (anti-cytokeratin-FITC, anti-CD45-PE, and DAPI) was performed to identify CTCs from nonspecifically captured blood cells. To be counted as a CTC, based on the FDA-approved technical definition, a cell with the appropriate cell size and morphology must be nucleated (DAPI+), express cytokeratin (CK+), and lack the leukocytic CD45 marker (CD45−). RESULTS/ANTICIPATED RESULTS: We tested the clinical utility of the device for monitoring the response of patients with advanced pancreatic cancer to a chemotherapy treatment consisting of anticancer drugs including 5-fluorouracil, leucovorin, oxaliplatin, and dasatinib. We have detected EpCAM+ CTCs in 47/47 (100%) and CD133+ CTCs in 41/47 (87.2%) of blood samples, coming from a cohort of 16 patients. We studied the correlation between the CTC numbers and the clinical result of patients in the study. We found that the size and changes in the size of the primary tumor (confirmed by CT scans) correlated with the frequency and increase/decrease trends in the number of CTCs detected. We expect to find some relationship between the number of detected CD133+ CTCs, or rather stem-like CTCs, and the clinical outcome of patients (eg, disease progression leading to withdrawal from study). DISCUSSION/SIGNIFICANCE OF IMPACT: Enumeration of patient CTCs and stem-like CTCs at different stages of a patient’s treatment may correlate with disease stage and prognosis, and prove useful in monitoring early recurrence, patient-specific treatment response, and newly acquired resistances; all of which would aid in providing guidance for the next step in clinical intervention. This type of liquid biopsy technology has great potential to make an impact in the future of personalized medicine and point-of-care diagnostics, as well as become a sturdy tool for translational research.
This article examines ambivalence—the simultaneous holding of two or more conflicting values or beliefs about a political issue—among Indonesian citizens’ attitudes about vote buying. Using an original survey taken during the 2014 Indonesian elections, we analyse the factors related both to citizens’ normative views about vote buying and their willingness to accept gifts from candidates. A large number of citizens demonstrate ambivalence by viewing the practice as unjustified or corrupt and yet expressing willingness to accept money from candidates. We also examine the differential effects of education and income on these attitudes. Consistent with “demand side” theories of vote buying, low income creates economic pressure to accept money but does not influence normative attitudes about vote buying. Education, however, has a broader effect by influencing both normative attitudes and willingness to accept money. We consider implications of these results for Indonesian officials focused on reducing vote-buying behavior.
Objectives: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. Methods: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. Results: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. Conclusions: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104–112)