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Both India and Nepal are prone to a wide range of natural and man-made disasters. Almost 85% of India’s area is vulnerable to one or more hazards, and more than 80% of the total population of Nepal is at risk of natural hazards. In terms of the number of people affected in reported disastrous events, India is in the top 10 and Nepal is in the top 20 globally. Over the last two decades, India and Nepal have taken steps to establish their respective National Disaster Management organizations, which provide essential disaster responses. However, key gaps still remain in trained clinical capacity for managing impacts from various disasters. Our review of the region has shown that large parts of the population suffer injuries, diseases, disabilities, psychosocial, and other health-related problems from disasters.
Develop disaster medicine clinical capacity to reduce morbidities and mortalities from disasters.
Independent published data and work undertaken by the lead author in various disasters in India and Nepal since 1993 formed the basis of establishing the Faculty of Disaster Medicine for South Asia. The Faculty of Disaster Medicine - India and Nepal (FDMIN) was launched from Pune in March 2015. This initiative is supported by the National Association of Primary Care (UK), Public Health England, Faculty of Pre-hospital Care of Royal College of Surgeons - Edinburgh and CRIMEDIM (Novara) - Italy.
FDMIN has international expert advisors and has outlined 16 modules training curriculum for health care professionals. FDMIN currently has partnerships for teaching disaster medicine program with 3 medical universities and 12 major health care providers. Six pilot training programmes have been conducted in Pune, Delhi, Chennai, and Kochin. Work is underway to submit an application to the Indian regulatory bodies for approval to establish a post-graduate diploma and Master’s for Disaster Medicine.
Visual hallucinations are a common symptom in dementia and Parkinson’s disease and have been associated with greater cognitive and functional decline, but optimal management strategies are unclear. We review the frequency and pathogenesis of visual hallucinations in dementia and Parkinson’s disease and examine the evidence base for their management.
We undertook a systematic review of the visual hallucinations in dementia, searching studies published between January 1980 and July 2017 using PubMed with the search terms visual hallucinations AND review AND (dementia OR parkinson*).
We found 645 articles and screened them for relevance, finally including 89 papers (11 meta-analyses, 34 randomized controlled trials, six other trials and a number of relevant review articles). Only six of the trials reported visual hallucination outcomes separately from other neuropsychiatric symptoms.
Atypical antipsychotics were frequently studied, but with the exception of clozapine in Parkinson’s disease dementia, results were equivocal. There was some evidence that acetylcholinesterase inhibitors may help visual hallucinations. Overall, effect sizes for most treatments were small and there were few studies with long term follow up. Treatments need to be carefully weighed up with the risks and reviewed often, and many patients improved without treatment. There is a lack of data regarding visual hallucinations due to the grouping of psychotic symptoms together in commonly used rating scales. The lack of a specific rating scales, or analyzable items within other scales, for visual hallucinations, limited efficacy of current and small evidence base with short follow up are important areas for future studies to address.
White matter (WM) change plays an important role in age-related cognitive decline. In this review, we consider methodological advances with particular relevance to the role of WM in age-related changes in processing speed. In this context, intra-individual variability in processing speed performance has emerged as a sensitive proxy of cognitive and neurological decline while neuroimaging techniques used to assess WM change have become increasingly more sensitive. Together with a carefully designed task protocol, we emphasize that the combined implementation of intra-individual variability and neuroimaging techniques hold promise for specifying the WM-processing speed relationship with implications for normative and clinical samples. (JINS, 2014, 20, 1–6)
Bisphenol A (BPA), a monomer of polycarbonate plastics and epoxide resin, is a high-production-volume chemical implicated in asthma pathogenesis when exposure occurs to the developing fetus. However, few studies have directly examined the effect of in utero and early-life BPA exposure on the pathogenesis of asthma in adulthood. This study examines the influence of perinatal BPA exposure through maternal diet on allergen sensitization and pulmonary inflammation in adult offspring. Two weeks before mating, BALB/c dams were randomly assigned to a control diet or diets containing 50 ng, 50 μg or 50 mg BPA/kg of rodent chow. Dams remained on the assigned diet throughout gestation and lactation until postnatal day (PND) 21 when offspring were weaned onto the control diet. Twelve-week-old offspring were sensitized to ovalbumin (OVA) and subsequently challenged with aerosolized OVA. Sera, splenocytes, bronchoalveolar lavage fluid and whole lungs were harvested to assess allergen sensitization and pulmonary inflammation after OVA challenge. Serum anti-OVA IgE levels were increased two-fold in offspring exposed to 50 μg and 50 mg BPA/kg diet, compared with control animals. In addition, production of interleukin-13 and interferon-γ were increased in OVA-stimulated splenocytes recovered from BPA-exposed mice. Pulmonary inflammation, as indicated by total and differential leukocyte counts, cytokines, chemokines and pulmonary histopathology inflammatory scores, however, was either not different or was reduced in offspring exposed to BPA. Although these data suggest that perinatal BPA exposure beginning before gestation enhances allergen sensitization by increasing serum IgE and splenocyte cytokine production, a substantial impact of BPA on OVA-induced pulmonary inflammation in adulthood was not observed.
Alzheimer's disease (AD) is considered to be a disorder predominantly affecting memory. It is increasingly recognized that the cognitive profile may be heterogeneous. We hypothesized that it would be possible to define distinct “cognitive phenotypes” in older people with AD.
Participants from three individual studies were included, consisting of 109 patients with a diagnosis of probable AD, and 91 age- and gender-matched control participants. All had demographic and cognitive assessment data available, including the Cambridge Cognitive Examination of the Elderly (CAMCOG). The CAMCOG scores and sub-scores were further analyzed using hierarchical cluster analysis and factor analysis.
Three clusters were identified. The scores loaded onto three factors representing the domains of attention, praxis, calculation, and perception; memory; and language comprehension and executive function. The main difference between the clusters related to degree of memory impairment. The composite score for memory between the clusters remained significantly different despite adjustment for illness duration and age of onset (p < 0.001).
These data suggest clinical heterogeneity within an older group of people with AD. This may have implications for diagnosis, prognosis, response to currently available treatments, and the development of novel therapies.
Depression is a common and costly comorbidity in dementia. There are very few data on the cost-effectiveness of antidepressants for depression in dementia and their effects on carer outcomes.
To evaluate the cost-effectiveness of sertraline and mirtazapine compared with placebo for depression in dementia.
A pragmatic, multicentre, randomised placebo-controlled trial with a parallel cost-effectiveness analysis (trial registration: ISRCTN88882979 and EudraCT 2006-000105-38). The primary cost-effectiveness analysis compared differences in treatment costs for patients receiving sertraline, mirtazapine or placebo with differences in effectiveness measured by the primary outcome, total Cornell Scale for Depression in Dementia (CSDD) score, over two time periods: 0–13 weeks and 0–39 weeks. The secondary evaluation was a cost-utility analysis using quality-adjusted life years (QALYs) computed from the Euro-Qual (EQ-5D) and societal weights over those same periods.
There were 339 participants randomised and 326 with costs data (111 placebo, 107 sertraline, 108 mirtazapine). For the primary outcome, decrease in depression, mirtazapine and sertraline were not cost-effective compared with placebo. However, examining secondary outcomes, the time spent by unpaid carers caring for participants in the mirtazapine group was almost half that for patients receiving placebo (6.74 v. 12.27 hours per week) or sertraline (6.74 v. 12.32 hours per week). Informal care costs over 39 weeks were £1510 and £1522 less for the mirtazapine group compared with placebo and sertraline respectively.
In terms of reducing depression, mirtazapine and sertraline were not cost-effective for treating depression in dementia. However, mirtazapine does appear likely to have been cost-effective if costing includes the impact on unpaid carers and with quality of life included in the outcome. Unpaid (family) carer costs were lower with mirtazapine than sertraline or placebo. This may have been mediated via the putative ability of mirtazapine to ameliorate sleep disturbances and anxiety. Given the priority and the potential value of supporting family carers of people with dementia, further research is warranted to investigate the potential of mirtazapine to help with behavioural and psychological symptoms in dementia and in supporting carers.
Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear.
To investigate the relationship between baseline and incident depression and progression of white matter changes.
In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale.
Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline.
Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.
The flexibility and cost advantages of the wire bumping process are making it increasingly attractive as an alternative bumping method for low I/O flip chip technologies. In this study, electrical measurements from DC to 8.1 GHz and die shear experiments are used to assess the thermo-mechanical integrity of Au/2%Pd wire bumped GaAs/Al2O3 flip chip modules. Finite Element Modeling results for in-process and in-service temperature cycling indicated that the maximum stress of the flip chip module is well below the failure stresses for GaAs, Al2O3 and the Au interconnect. These results are validated by data from thermal cycling experiments. Average shear strength after thermal cycle, thermal shock, and thermal aging (MIL-STD-883C, Condition C) was 64 grams/bump. Electrical characterization (from 45 MHz to 8.1 GHz) using a coplanar waveguide flip chip test structure showed no thermal stress-induced microwave energy losses.
Nanophosphors correspond to nanostructured inorganic insulator materials that emit light under particle or electromagnetic radiation excitation. In this work we investigate the structure and luminescent properties of Ce-doped Lu2SiO5 (LSO) nanophosphors prepared by solution combustion synthesis with the Ce content 0.1 to 12 at. %. Samples were characterized by transmission electron microscopy (TEM), line scan electron energy-loss spectroscopy (EELS), x-ray diffraction (XRD), and electron paramagnetic resonance (EPR) spectroscopy. Photoluminescence excitation and emission spectra are composed of two major bands centered at 360 and 430 nm, respectively. These results reveal a red-shift and enhanced Stokes shift for the nanophosphors when compared to bulk. Ce content was also found to affect photoluminescence emission intensity and fluorescent lifetime. The nanophosphor concentration quenching curve presents a broad maximum centered at 1 at.%. Lifetime measurements show a continuous decrease from 34 to 21 ns as Ce content is increased.
Due to the increasing prevalence of resistance of bacteria to antibiotics and antiseptic methods, new strategies to prevent colonization of biomaterials are needed. Due to its high antimicrobial activity and relatively low toxicity to human cells, we are evaluating silver (Ag) releasing plasma polymers as a strategy to prevent bacterial colonization. Such Ag/plasma polymer nanocomposite materials, consisting of nano-scaled metal clusters embedded within a plasma-polymer matrix can be deposited using a mixed, plasma polymerization /sputtering process. For example, Ag containing plasma polymer nanocomposites are deposited employing an Ag cathode, an appropriate monomer to yield the desired material properties of the matrix (biocompatibility) and an asymmetric reactor design. The focus of this paper is a new development at Empa: a multi-functional Ag/amino-hydrocarbon (Ag/a-C:H:N) nanocomposite that can enhance cell growth and simultaneously prevent bacterial colonization at surfaces. Ag/a-C:H:N coatings containing 4.0% Ag have been demonstrated to reduce bacterial adhesion of E. coli by up to 95%, as compared to an external polyester fabric control in a static assay. Likewise, these coatings demonstrated a bacterial toxic effect both at the surface and in the surrounding media due to the release of Ag ions. XPS characterization of various nanocomposites has shown that the Ag quantity and matrix characteristics of the films can be tailored to specific requirements by altering deposition parameters such as power input, pressure and gas feed ratio. Although the surface chemistry has been characterized, open questions remain to the amount and the kinetics of the release of Ag and the subsequent effect on bacteria and cells. Since Ag release profiles will ultimately determine the antimicrobial efficacy of the coatings, as well as duration of the effect, these dosing issues must be quantified and clarified. Ag release kinetics of the various Ag/a-C:H:N as measured by atomic absorption spectroscopy has been evaluated and the relationships to biological assays, including bacterial and cellular adhesion are clarified. A range of Ag/a-C:H:N coatings having various Ag content are tested in two biological assays, bacterial toxicity and cytoxicity. Bacterial growth tests using the pathogen, P. aeruginosa wild type (PAO1), were performed according to the method of Tiller et al. The method is based on the bacterial deposition from aerosols, thus, it mimics bacterial exposure through airways such as intubation tubes. Secondly, cytotoxicity assays of the nanocomposites has been performed using a murine fibroblast cell line 3T3 testing protocol, and the proliferation of the cultures was measured taking the DNA amount per well as an index (Bruinink 2001). We will answer questions regarding what is the fundamental Ag content and Ag release profile under static bacterial testing environments which allow a maximum bacterial-toxic effect with a minimum amount of Ag.
The batch-foaming behavior of multiphase polymer blends and block copolymers was systematically investigated using carbon dioxide as a blowing agent. Three different polymer systems were evaluated: (i) nanostructured triblock terpolymers, (ii) microstructured polymer blends, and (iii) nanostructured polymer blends. In order to obtain nanostructured blends, immis-cible blends of poly(2,6-dimethyl-1,4-phenylene ether)/poly(styrene-co-acrylonitrile) (PPE/SAN) were melt-compatibilised via polystyrene-b-polybutadiene-b-poly(methyl methacry-late) triblock terpolymers. Due to the specific interaction between the respective components, a nanostructured interphase between PPE and SAN was observed. With regard to neat block co-polymers, the self-assembly of solvent-cast SBM triblock terpolymers was exploited in order to produce nanostructured morphologies. In each case, the resulting foam morphology was charac-terized by evaluating the foam density as well as the cell size. Combined with the multiphase structure of the non-foamed material and its thermal as well as physical behavior, relationships between the foaming characteristics and the cellular morphology were established. As an exam-ple for the foaming results, submicro-cellular structures were observed by foaming nanostruc-tured polymer blends, while the cell walls still revealed the nanostructured morphology. In con-trast, batch-foaming of neat triblock terpolymers led to the formation of microcellular foams; however, as highlighted by scanning electron microscopy, the cell walls did undergo some fur-ther expansion and formed additional nano-sized cells. In the light of these results, new routes for preparing cellular polymers are derived by systematically exploiting the multiphase charac-teristics of polymer blends and block copolymers.
Formation of carbon nanospheres is typically relegated to two costly methods. Chemical vapor deposition produces uniform spheres safely anchored to a substrate but at the cost of being slow and expensive to run. Arc discharge of a carbon target produces soot containing a low density of random spheres that must be laboriously sorted. An alternative approach is to fabricate carbon nanospheres through the pyrolysis of organic feedstock. This paper presents the findings from an investigation into using pectin as a pre-cursor material for pyrolysis. The pectin is combined with different saccharides - sucrose, dextrose, and fructose and processed in aqueous solution until a gel set. The gel is then thermally processed in a nitrogen environment at 500 °C. The resultant carbon material is examined under SEM. Images confirm the formation of nanospheres and other microscale and nanoscale structures. The pectin, a naturally derived product from plant materials, is a renewable source of materials which can be used to form nanotechnologies for many energy-related applications.
Isothermal titration calorimetry (ITC) has gained wide acceptance in drug discovery and development laboratories throughout the world. Every major pharmaceutical company and most biopharmaceutical companies and major research institutions now use ITC. Modern, highly sensitive ITC instruments are being applied in the drug discovery and development process for applications such as: (a) selection of small-molecule “hits” following primary and secondary screening of chemical libraries against protein targets of interest, (b) optimization of smallmolecule leads based on elucidation of the binding mechanism and binding characteristics and development of structure–activity relationships (SAR) used in the optimization process, and (c) selection and optimization of therapeutic protein variants.
Because ITC directly measures the heat released or absorbed during a biomolecular binding event, it is the only technique that allows simultaneous determination of all thermodynamic binding parameters (n, KA, ΔH and ΔS) in a single experiment. The ITC technique provides this unique capability in an experimental environment that is label-free, in solution, and that does not require immobilization of either the target macromolecule or ligand. Modern instruments are highly sensitive, accurate, and reproducible, and unlike spectroscopic methods, the degree of optical clarity of the solutions is unimportant. As modern ITC instrumentation has evolved, these instruments have become more sensitive, faster, and easier to use. Binding parameters determined by ITC are often referred to as “gold standard” values and are frequently used as reference standard values for other techniques.
Despite the fundamental advantages of this technique and the advances in instrumentation, use of ITC in the early, critical decision-making stages of drug discovery is often limited.
Studies investigating the cognitive effects of serotonin depletion, using the technique of acute tryptophan depletion (ATD) by dietary means, have generally suggested that ATD impairs delayed verbal recall and recognition. In two previous studies in the elderly, this result has not been replicated and ATD impaired working memory. These results may be susceptible to type II error but a similar testing schedule in the individual studies allows data to be pooled in a larger analysis.
Data from two separate double-blind placebo-controlled studies of the effects of ATD on cognitive function in the elderly were combined. In one study, a low dose and in the other a high dose of amino acids was used. In a repeated measures analysis of variance, the effects of ATD and the interaction of this with the other factors (age, gender and dose) on cognitive measures was examined.
Data from 31 healthy subjects aged between 60 and 81 years were analysed. There were no main effects of ATD or consistent interactions between ATD and age, gender or dose. There were significant interactions between ATD, gender and dose. When tryptophan depleted, females having the higher dose drink had reduced scores on Digit span and immediate recall on the Rey Auditory Verbal Learning Test.
The enlarged data set did not confirm an overall effect of ATD on working memory or on delayed word recall but does suggest an effect of ATD on encoding or registration in the subgroup of females receiving a higher strength drink.
Recently, conservation estate in South Africa's Eastern Cape Province has increased 10-fold resulting in large predators being increasingly reintroduced to restore ecological integrity and maximize tourism. We describe the reintroductions of large carnivores (>10 kg) that have occurred in the Eastern Cape and use various criteria to assess their success. Lion Panthera leo reintroduction has been highly successful with a population of 56 currently extant in the region and problems of overpopulation arising. The African wild dog Lycaon pictus population has increased to 24 from a founder population of 11. Preliminary results for spotted hyaenas Crocuta crocuta also indicate success. Wild populations of leopards Panthera pardus exist on several reserves and have been supplemented by translocated individuals, although deaths of known individuals have occurred and no estimate of reproduction is available. Cheetah Acinonyx jubatus reintroduction has also been less successful with 36 individuals reintroduced and 23 cubs being born but only 41 individuals surviving in 2005. Criteria for assessing the success of reintroductions of species that naturally occur in low densities, such as top predators, generally have limited value. Carrying capacity for large predators is unknown and continued monitoring and intensive management will be necessary in enclosed, and possibly all, conservation areas in the Eastern Cape to ensure conservation success.
This study investigates the distribution of pulsed-field gel electrophoresis (PFGE) profiles within Salmonella enterica serotype Enteritidis phage type (PT) 4 and S. Typhimurium definitive phage type (DT) 104, from cases of human infection in nine European countries from 2000 to 2004. Isolates were subtyped using standardized methods and gel images submitted by each participating country to the coordinating centre (Health Protection Agency Centre for Infections, London, UK), where they were entered into a central database, developed within BioNumerics software, and designated using an agreed nomenclature. S. Enteritidis PT4 (n=3637) was differentiated into 38 different profiles. Simpson's index of diversity (D) of profiles ranged from 0·2 to 0·4. Profile SENTXB.0001 represented at least 80% of all profiles in each country. S. Typhimurium DT104 (n=1202) was differentiated into 28 different profile types. Simpson's D was at least 0·6 in all countries except in Austria and Italy. In both these countries over 74% of S. Typhimurium DT104 profiles were STYMXB.0013. Profile STYMXB.0061, was predominant in Denmark, Spain, Finland and England & Wales where it represented between 36% and 45% of profiles. Profile STYMXB.0001 represented nearly half of all profiles in Scotland and 23% in England & Wales. PFGE is proving useful for further discrimination within S. Enteritidis PT4 and S. Typhimurium DT104. Ascertainment of international outbreaks involving common serotypes and phage types may be increased by the timely pooling of PFGE profiles within a central database readily accessible to all participating countries.