Timing of Prenatal Exposure to Trauma and Altered Placental Expressions of HPA-Axis Genes and Genes Driving Neurodevelopment

Abstract

Prenatal maternal stress increases the risk for negative developmental outcomes in offspring, however the underlying biological mechanisms remain largely unexplored. In this study, alterations in placental gene expression associated with maternal stress were examined to elucidate potential underlying epi/genetic mechanisms. Expression levels of 40 selected genes involved in regulating fetal HPA-axis and neurodevelopment were profiled in placental tissues collected from a birth cohort established around the time of Superstorm Sandy. Objective prenatal traumatic stress was defined as whether mothers were exposed to Superstorm Sandy during pregnancy. Among the 275 mother-infant dyads, 181 dyads were delivered before Superstorm Sandy (i.e., Control), 66 dyads were exposed to Superstorm Sandy during the first trimester (i.e., Early Exposure) and 28 were exposed to Superstorm Sandy during the second or third trimester (i.e., Mid-Late Exposure). Across all trimesters, expression of HSD11B2, MAOA, ZNF507, and DYRK1A was downregulated among those exposed to Superstorm Sandy during pregnancy. Furthermore, trimester specific differences were also observed: exposure during early gestation was associated with downregulation of HSD11B1 and MAOB, and upregulation of CRHBP; exposure during mid-late gestation was associated with upregulation of SRD5A3. Our findings suggest that placental gene expression may be altered in response to traumatic stress exposure during pregnancy, and the susceptibility of these genes is dependent on the time of the exposure during pregnancy. Further studies can elucidate the biological mechanisms that underlie trimester-specific exposure by evaluating the differential impact on offspring neurodevelopment later in childhood.

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Pruritic arthropod bite-like papules in T-cell large granular lymphocytic leukaemia and chronic myelomonocytic leukaemia

Summary

T-cell large granular lymphocytic leukaemia (T-LGLL) is a clinically indolent mature T-cell neoplasm characterized by a monoclonal population of CD3+ CD8+ cytotoxic T cells, which usually presents as neutropenia, anaemia and thrombocytopenia. Chronic myelomonocytic leukaemia (CMML) is a clonal haematopoietic disorder with features of both a myeloproliferative neoplasm and myelodysplastic syndrome (MDS). Patients with CMML exhibit a persistent peripheral blood monocytosis in addition to myelodysplastic features. Because of the rarity of T-LGLL, its cutaneous manifestations are poorly documented, but include vasculitis, vasculopathy, persistent ulcerations, generalized pruritus and disseminated granuloma annulare. Various types of skin lesions have been observed in patients with CMML and reportedly occur in approximately 10% of cases. We report the extraordinary case of a patient with MDS who developed T-LGLL, and subsequently the MDS progressed to CMML. The patient then developed diffuse arthropod bite-like papules and intractable pruritus.

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Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist

Summary

Background

Cannabinoids have been used for their analgesic and euphoric effects for millennia, but recently the antipruritic effects of cannabis have been discovered. Considering the similarities between pain and itch sensations, we hypothesized that cannabinoid receptors may play a role in the antipruritic effects of cannabinoids.

Aim

To analyse the role of the spinal cannabinoid receptors, CB1 and CB2, in the antipruritic effects of the cannabinoid agonist WIN 55,212-2.

Methods

Male Balb/c mice weighing 20–30 g were used. Scratching behaviour in the mice was produced by injection of serotonin 5 μg/50 μL intradermally into the nape of the neck. Scratching of the site of injection by the hind paws was video-recorded for 30 min. After testing different doses of WIN 55,212-2 [1, 3 and 10 mg/kg intraperitoneally (IP)], the effects of the CB1 receptor antagonist, AM-251 [1 μg/mouse administered intrathecally (IT)] and the CB2 receptor antagonist AM-630 (4 μg/mouse IT) on the antipruritic effects of WIN 55,212-2 were studied using a rotarod apparatus.

Results

WIN 55,212-2 (1, 3 or 10 mg/kg IP) dose-dependently decreased serotonin-induced scratches. The receptor antagonist CB1 partially reversed the effects of WIN 55,212-2 (P < 0.05); whereas CB2 had no statistically significant effect. WIN 55,212-2 impaired motor function only at the highest dose given (10 mg/kg, P < 0.05).

Conclusions

Our findings support prior researches indicating that cannabinoids exert antipruritic effects. Moreover, our results show that the antipruritic effects of cannabinoids are partially mediated by spinal CB1 receptors.

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Erythema elevatum diutinum-like vasculitis secondary to cocaine adulterated with levamisole

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Asymptomatic hyperkeratotic plaque on the vulva of a patient with lichen sclerosus

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Alternative activation of hedgehog pathway induced by ultraviolet B radiation: preliminary study

Summary

Background

There is still much ambiguity in studies of Sonic hedgehog (Shh) pathways and its dysregulation. Some studies concerning the role of the Shh pathway in basal cell carcinoma (BCC) have been conducted, but there is a lack of studies about Shh pathway dysregulation under the influence of ultraviolet (UV)B radiation.

Aim

To evaluate skin expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins in BCCs with and without the influence of UVB radiation.

Methods

In total, 34 healthy controls (HCs) and 42 patients with nodular BCC were recruited into the study. Patients were divided into five groups (A–E), depending on UVB dose received and BCC status. In all skin specimens, expression of Shh, Ptch1, Ptch2, Smo and Gli1 protein was evaluated.

Results

Comparing the BCC group with the HC group, there was significantly higher expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins. Expression of Ptch2, Smo and Gli1 was increased in response to UVB doses of 3 MED (minimal erythema dose), whereas expression of Ptch1 and Shh was unaffected.

Conclusion

The lack of change in expression of Shh and Ptch1 after exposure to UVB suggests that the Shh pathway may be activated through a noncanonical pathway under the influence of strong UVB doses.

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Caregiver and adolescent factors associated with delayed completion of the three-dose human papillomavirus vaccination series

Publication date: Available online 7 February 2018
Source:Vaccine
Author(s): Lea E. Widdice, Rebecca Hoagland, S. Todd Callahan, Jessica A. Kahn, Christopher J. Harrison, Barbara A. Pahud, Sharon E. Frey, Andrea A. Berry, Karen L. Kotloff, Kathryn M. Edwards, Mark J. Mulligan, Jon Sudman, Aya Nakamura, David I. Bernstein
BackgroundDelayed completion of human papillomavirus vaccination (4vHPV) series is common. We sought to identify factors associated with delay.MethodsThis substudy was part of a large prospective, multi-site study recruiting 9–17 year old girls at the time of their third 4vHPV dose to assess immunogenicity associated with prolonged dosing intervals. At participating sites, parents/legal guardians (caregivers) of all enrolled girls (9–17 years old) and enrolled girls aged 14–17 years were approached for participation. Caregivers completed a questionnaire measuring adolescent and caregiver sociodemographic characteristics, caregiver attitudes and beliefs about on-schedule HPV vaccination and HPV vaccine safety, adolescent's health behaviors, barriers to accessing health care, provider office vaccination practices and a Rapid Estimate of Adult Literacy in Medicine (REALM). Participating girls completed a separate questionnaire measuring their attitudes and beliefs about on-schedule HPV vaccination and HPV vaccine safety. Delay was defined as receiving the third 4vHPV dose >12 months after the first. Bivariate, multinomial logistic regression and multivariate logistic regression analyses were used to identify factors predicting delayed completion.ResultsQuestionnaires were completed by 482 caregivers and 386 adolescents; 422 caregivers completed a REALM. Delayed 4vHPV dosing occurred in most adolescents (67%). In multivariate analyses, predictors of delayed completion included caregiver demographic factors (self-reported black vs. white race and high school or less education vs. college or more) and an interaction between caregiver's inability to get an immunization appointment as soon as needed and adolescent's type of insurance.ConclusionsCaregiver's race and educational level, accessibility of immunization appointments, and adolescent's insurance type were found to be related to delays in completion of 4vHPV, but caregiver or adolescent attitudes and beliefs about on-schedule HPV vaccination or HPV vaccine safety were not. Therefore, interventions to improve adherence to recommended vaccination schedules could benefit from a focus on improving access to immunizations.ClinicalTrials.gov (NCT01030562).



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Haemophilus influenzae-protein D specific antibody correlate with protection against acute otitis media in young children

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Anthony Almudevar, Michael E. Pichichero
BackgroundHaemophilus influenzae (Hi) causes respiratory infections and pathogenesis of this microbe begins in the human nasopharynx (NP). The objective of this study was to assess the correlation of NP colonization-induced serum antibody levels to Hi protein D with risk of acute otitis media (AOM) in children <2 yr.Methods455 sera from 213 children (age 6–24 months old) were collected when they were colonized with Hi and when the children developed AOM. Presence of Hi during AOM was confirmed by culture of middle ear fluid. Quantitative ELISA was used to determine serum IgG against protein D antigen.ResultsAsymptomatic Hi NP colonization reduced the risk of future AOM infections. Higher serum IgG titers against Hi protein D were correlated with reduced future AOM risk.ConclusionColonization by Hi reduces future AOM risk. Higher antibody levels against protein D correlates with lower risk of AOM caused by Hi.



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Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE): A vision for the vaccines of tomorrow

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Donata Medaglini, Magdalena R. De Azero, Odile Leroy, Florence Bietrix, Philippe Denoel
A clear vision for vaccines research and development (R&D) is needed if Europe is to continue to lead the discovery of next generation vaccines. Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE) is a collaboration between leading vaccine experts to develop a roadmap setting out how Europe can best invest in the science and technology essential for vaccines innovation. This FP7 project, started in December 2013, brought together more than 130 key public and private stakeholders from academia, public health institutes, regulators, industry and small and medium-sized enterprises to determine and prioritise the gaps and challenges to be addressed to bolster innovation in vaccines and vaccination in Europe. The IPROVE consultation process was structured around seven themes: vaccine R&D, manufacturing and quality control, infrastructure, therapeutic vaccines, needs of small and medium-sized enterprises, vaccines acceptance and training needs.More than 80 recommendations were made by the consultation groups, mainly focused on the need for a multidisciplinary research approach to stimulate innovation, accelerated translation of scientific knowledge into technological innovation, and fostering of real collaboration within the European vaccine ecosystem. The consultation also reinforced the fact that vaccines are only as good as their vaccine implementation programmes, and that more must be done to understand and address vaccination hesitancy of both the general public and healthcare professionals.Bringing together a wide range of stakeholders to work on the IPROVE roadmap has increased mutual understanding of their different perspectives, needs and priorities. IPROVE is a first attempt to develop such a comprehensive view of the vaccine sector. This prioritisation effort, aims to help policy-makers and funders identify those vaccine-related areas and technologies where key investment is needed for short and medium-long term success.



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Influenza B virus reverse genetic backbones with improved growth properties in the EB66® cell line as basis for vaccine seed virus generation

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Kris M. White, Juan Ayllon, Ignacio Mena, Anna Potenski, Florian Krammer, Adolfo García-Sastre
Vaccination remains the best available prophylaxis to prevent influenza virus infections, yet current inadequacies in influenza virus vaccine manufacturing often lead to vaccine shortages at times when the vaccine is most needed, as it was the case during the last influenza virus pandemic. Novel influenza virus vaccine production systems will be crucial to improve public health and safety. Here we report the optimization of influenza B virus growth in the proprietary EB66® cell line, currently in use for human vaccine production. To this end, we collected, curated and sequenced 71 influenza B viruses selected for high diversity in date of isolation and lineage. This viral collection was tested for ability to enter and replicate within EB66® cells in a single cycle assay and appears to readily infect these cells. When the collection was tested for viral progeny production in a multi-cycle assay, we found a large variation from strain to strain. The strains with the top growth characteristics from the B/Victoria and B/Yamagata lineages were selected for vaccine backbone generation using a reverse genetics system. We then showed that these backbones maintain their desirable growth within EB66® cells when the HA and NA from poorly growing strains were substituted for the parental segments, indicating that the selected backbones are viable options for vaccine production in EB66®. Finally, we show that compounds previously reported to enhance influenza virus growth in cell culture also increase virus production in the EB66® cell line.



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Identification of suitable adjuvant for vaccine formulation with the Neospora caninum antigen NcSRS2

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Amanda Fernandes Pinheiro, Bárbara Couto Roloff, Angelita da Silveira Moreira, Maria Elisabeth Aires Berne, Renato Andreotti Silva, Fábio Pereira Leivas Leite
The parasite Neospora caninum is the main cause of abortion in cattle in many countries around the world, so a vaccine is a rational approach method for the control of the disease. An effective vaccine should be able to prevent both, the horizontal and vertical transmission of N. caninum. In this study, the immune vaccinal response of the recombinant protein rNcSRS2 of N. caninum expressed in Pichia pastoris and formulated with water-in-oil emulsion, xanthan gum, and alum hydroxide was assessed in an experimental murine model. Groups of 10 Balb/c mice were subcutaneously inoculated with two doses of prNcSRS2 twenty-one days apart. After the second immunization, four mice from each group were euthanized, and splenocytes were stimulated ex vivo with recombinant protein. The IgG dynamics were evaluated by indirect ELISA, and the splenocytes cytokines transcription by qPCR. All groups elicited specific antibodies against prNcSRS2, with the water-in-oil group showing significantly (p ≤ .05) elevated titers compared to the other groups. The prNcSRS2 protein alone did not induce a significant ex vivo splenic transcription level of IFN-γ, TNF-α, IL-4, IL-10, and IL-12 cytokines, except for IL-17A, and the adjuvant associations with the prNcSRS2 protein induced different cytokine transcription profiles. The water-in-oil emulsion modulated the expression of TNF-α; the xanthan gum modulated IL-4, IL-10, and IL-12; and alum hydroxide modulated IFN-γ, TNF-α, IL-4, IL-10, and IL-12. In conclusion, it was found that the association of the recombinant prNcSRS2 protein with different adjuvants induced different levels of specific antibody, and a distinct splenic cytokine profile in an adjuvant-dependent manner. The mechanisms of adjuvancity activity is complex, so adjuvant formulation may help in the design of efficient vaccine to control Neosporosis.



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Core pertussis transmission groups in England and Wales: A tale of two eras

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Ana I. Bento, Maria A. Riolo, Yoon H. Choi, Aaron A. King, Pejman Rohani
The recent resurgence of pertussis in England and Wales has been marked by infant deaths and rising cases in teens and adults. To understand which age cohorts are most responsible for these trends, we employed three separate statistical methods to analyze high-resolution pertussis reports from 1982 to 2012. The fine-grained nature of the time-series allowed us to describe the changes in age-specific incidence and contrast the transmission dynamics in the 1980s and during the resurgence era. Our results identified infants and school children younger than 10 years of age as a core group, prior to 2002: pertussis incidence in these populations was predictive of incidence in other age groups. After 2002, no core groups were identifiable. This conclusion is independent of methodology used. Because it is unlikely that the underlying contact patterns substantially changed over the study period, changes in predictability likely result from the introduction of more stringent diagnostics tests that may have inadvertently played a role in masking the relative contributions of core transmission groups.



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Editorial Board/Aims and Scope

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9





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Hepatitis A and hepatitis B vaccination coverage among adults with chronic liver disease

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Xin Yue, Carla L. Black, Alissa O'Halloran, Peng-Jun Lu, Walter W. Williams, Noele P. Nelson
BackgroundInfection with hepatitis A and hepatitis B virus can increase the risk of morbidity and mortality in persons with chronic liver disease (CLD). The Advisory Committee on Immunization Practices recommends hepatitis A (HepA) and hepatitis B (HepB) vaccination for persons with CLD.MethodsData from the 2014 and 2015 National Health Interview Surveys (NHIS), nationally representative, in-person interview surveys of the non-institutionalized US civilian population, were used to assess self-reported HepA (≥1 and ≥2 doses) and HepB vaccination (≥1 and ≥3 doses) coverage among adults who reported a chronic or long-term liver condition. Multivariable logistic regression was used to identify factors independently associated with HepA and HepB vaccination among adults with CLD.ResultsOverall, 19.4% and 11.5% of adults aged ≥ 18 years with CLD reported receiving ≥1 dose and ≥2 doses of HepA vaccine, respectively, compared with 14.7% and 9.1% of adults without CLD (p < .05 comparing those with and without CLD, ≥1dose). Age, education, geographic region, and international travel were associated with receipt of ≥2 doses HepA vaccine among adults with CLD. Overall, 35.7% and 29.1% of adults with CLD reported receiving ≥1 dose and ≥3 doses of HepB vaccine, respectively, compared with 30.2% and 24.7% of adults without CLD (p < .05 comparing those with and without CLD, ≥1 dose). Age, education, and receipt of influenza vaccination in the past 12 months were associated with receipt of ≥3 doses HepB vaccine among adults with CLD. Among adults with CLD and ≥10 provider visits, only 13.8% and 35.3% had received ≥2 doses HepA and ≥3 doses HepB vaccine, respectively.ConclusionsHepA and HepB vaccination among adults with CLD is suboptimal and missed opportunities to vaccinate occurred. Providers should adhere to recommendations to vaccinate persons with CLD to increase vaccination among this population.



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Reduced pathogenicity of fructose-1,6-bisphosphatase deficient Leishmania donovani and its use as an attenuated strain to induce protective immunogenicity

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Savita Saini, Ayan Kumar Ghosh, Sushmita Das, Ruby Singh, Kumar Abhishek, Sudha Verma, Ajay Kumar, Abhishek Mandal, Bidyut Purkait, Kislay Kumar Sinha, Pradeep Das
Currently, there is no approved vaccine for visceral leishmaniasis (VL) caused by L. donovani. The ability to manipulate Leishmania genome by eliminating or introducing genes necessary for parasites' survival considered as the powerful strategy to generate the live attenuated vaccine. In the present study fructose-1,6-bisphosphatase (LdFBPase) gene deleted L. donovani (Δfbpase) was generated using homologous gene replacement strategy. Though LdFBPase gene deletion (Δfbpase) does not affect the growth of parasite in the promastigote form but axenic amastigotes display a marked reduction in their capacity to multiply in vitro inside macrophages and in vivo in Balb/c mice. Though Δfbpase L. donovani parasite persisted in BALB/c mice up to 12 weeks but was unable to cause infection, we tested its ability to protect against a virulent L. donovani challenge. Notably, intraperitoneal immunisation with live Δfbpase parasites displayed the reduction of parasites load in mice spleen and liver post challenge. Moreover, immunised BALB/c mice showed a reversal of T cell anergy and high levels of NO production that result in the killing of the parasite. A significant, correlation was found between parasite clearance and elevated IFNγ, IL12, and IFNγ/IL10 ratio compared to IL10 and TGFβ in immunised and challenged mice. Results suggested the generation of protective Th1 type immune response which induced significant parasite clearance at 12-week, as well as 16 weeks post, challenged immunised mice, signifying sustained immunity. Therefore, we propose that Δfbpase L. donovani parasites can be a live attenuated vaccine candidate for VL and a good model to understand the correlatives of protection in visceral leishmaniasis.



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Immunogenicity and protective efficacy of recombinant fiber-2 protein in protecting SPF chickens against fowl adenovirus 4

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Li Chen, Lijuan Yin, Qingfeng Zhou, Qunhui Li, Yangyang Luo, Zhichao Xu, Yun Zhang, Chunyi Xue, Yongchang Cao
Since a novel hyper-virulent fowl adenovirus serotype 4 (FAdV-4) infection occurred in 2015, the novel FAdV-4 has been widely spreading across China, causing significant economic losses to the poultry industry. As the urgency of the issue calls for effective and efficient solutions, the present study investigated the possibility of the fiber-2 protein of the FAdV-4 to serve as a vaccine candidate against the novel FAdV-4. In the research, fiber-2 proteins were expressed in Escherichia coli, and then purified. To evaluate the immunogenicity of the recombinant fiber-2 protein, we investigated both the humoral and cellular immune responses in chickens immunized with fiber-2. The humoral immunity was assessed by detecting IgY antibodies and virus-neutralizing antibodies in chicken serum at 7, 14, 21 days post-immunization (dpi). We examined cellular immune responses by detecting CD3+CD4+ and CD3+CD8+ changes in chickens' peripheral blood through using flow cytometry at 7, 14, 21 dpi. The cytokine production in the serum of the immunized chickens was detected by ELISA at 7, 14, 21 dpi to further explore the impact of the recombinant protein on the regulation of cytokines. The protective efficacy was determined by the survival rate of the immunized chickens challenged with the novel FAdV-4. The results show that the level of IgY antibodies of the chickens immunized with fiber-2 protein was significantly higher than that of the chickens immunized with an inactivated vaccine against FAdV-4. Moreover, 7 days after immunization, the CD4+ T-cell proliferative response of the chickens immunized with fiber-2 was significantly higher than that of the chickens immunized with the inactivated vaccine. Challenge experiment showed that the fiber-2 protein could provide full protection and the inactivated vaccine could provide 90 percent protection against the FAdV-4. These results suggest that the recombinant fiber-2 protein can be an ideal candidate for subunit vaccines against the disease.



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Recipient vaccine-associated paralytic poliomyelitis in China, 2010–2015

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Wendi Wu, Huaqing Wang, Keli Li, J. Pekka Nuorti, Dawei Liu, Disha Xu, Jiakai Ye, Jingshan Zheng, Chunxiang Fan, Ning Wen, Zhijie An
IntroductionVaccine-associated paralytic poliomyelitis (VAPP) is one of the most important adverse effects of vaccines that are in current use globally. The Chinese national adverse event following immunization information system (CNAEFIS) is a passive surveillance system which collects data on VAPP.AimsTo describe the epidemiological characteristics of VAPP and estimate the risk of recipient VAPP in China.MethodsWe retrieved information from reported cases of recipient VAPP from CNAEFIS from 2010 to 2015, examined the demographic characteristics of the cases, and used administrative data on vaccination doses and the estimated number of births as denominators to calculate VAPP incidence.ResultsDuring 2010–2015, 157 cases of recipient VAPP were reported to CNAEFIS (male-to-female ratio, 8.2:1); 151 cases (96.2%) were less than six months old. All cases were associated with trivalent OPV (tOPV), and 89.8% occurred after the receipt of first dose. Of the 157 recipient VAPP cases, type II, type III, and type I poliovirus vaccine strains were isolated from 27 (17.2%) , 25 (15.9%) , and 16 (10.2%) cases, respectively. One case died and one case recovered completely; the other 155 cases had various physical disabilities, such as monolateral or bilateral limping. Using the administered doses of OPV as the denominator, the incidence of recipient VAPP during the study period was estimated at 0.4 per million doses. The estimated recipient VAPP per million births ranged from 1.0 to 2.4 during 2010–2015.ConclusionThe epidemiological characteristics of recipient VAPP cases in China, such as age distribution, were comparable to those in previous studies from other countries. The risk of recipient VAPP, using either estimated births or vaccination doses, was comparable to that in the US and Japan. We recommend using an inactive poliovirus vaccine to decrease the number of recipient VAPP cases in China.



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Vaccine failure and serologic response to live attenuated and inactivated influenza vaccines in children during the 2013–2014 season

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Jennifer P. King, Huong Q. McLean, Jennifer K. Meece, Min Z. Levine, Sarah M. Spencer, Brendan Flannery, Edward A. Belongia
BackgroundRecent observational studies in the United States indicated live attenuated influenza vaccine (LAIV) was less effective in children against clinical influenza infection caused by A(H1N1)pdm09 relative to inactivated influenza vaccine (IIV). During the 2013–2014 influenza season, we conducted an observational study among children aged 5–17 years to compare serologic responses to LAIV and IIV and explore factors associated with vaccine failure.MethodsOne hundred and sixty-one children received one dose of trivalent IIV or quadrivalent LAIV according to parental preference. Baseline and postvaccination serum samples were tested with hemagglutination inhibition (HI) assays against vaccine reference strains. Geometric mean titers (GMT), geometric mean fold rise (GMFR), seroconversion, and seroprotection (HI titer ≥ 40) were used to assess response to vaccine. Active surveillance for acute respiratory illness was conducted during the influenza season and influenza cases were confirmed by reverse transcription polymerase chain reaction (RT-PCR). Logistic regression was used to examine the association between vaccine type and vaccine failure.ResultsLAIV and IIV recipients were similar with respect to demographics and baseline GMT for each vaccine strain. RT-PCR confirmed influenza (vaccine failure) occurred in 8 (13%) of 62 LAIV recipients and 3 (3%) of 99 IIV recipients (p = .02). Postvaccination GMFR for A(H1N1)pdm09 was higher for IIV vs LAIV receipt (GMFR 3.3 vs. 0.8, p < .0001). Postvaccination titers against A(H1N1)pdm09 were ≥40 for 91% and 44% of IIV and LAIV recipients, respectively (p < .0001). Among 13 IIV and 18 LAIV recipients with seronegative baseline titer against A(H1N1pdm09), 54% and 0% seroconverted, respectively. LAIV receipt was the only factor associated with A(H1N1)pdm09 vaccine failure in the age-adjusted multivariable model (odds ratio 4.5, 95% CI 1.1–18.2).ConclusionReceipt of LAIV generated minimal HI antibody response in children, including among those seronegative at baseline. LAIV recipients had significant increased risk of A(H1N1)pdm09 infection compared to IIV recipients.



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Immunogenicity and safety of measles-mumps-rubella vaccine delivered by disposable-syringe jet injector in India: A randomized, parallel group, non-inferiority trial

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Ashish Bavdekar, Jitendra Oswal, Padmasani Venkat Ramanan, Chandrashekhar Aundhkar, P. Venugopal, Dhananjay Kapse, Tara Miller, Sarah McGray, Darin Zehrung, Prasad S. Kulkarni
BackgroundWe conducted a randomized, non-inferiority, clinical study of MMR vaccine by a disposable-syringe jet injector (DSJI) in toddlers in India in comparison with the conventional administration.MethodsMMR vaccine was administered subcutaneously by DSJI or needle-syringe (N-S) to toddlers (15–18 months) who had received a measles vaccine at 9 months. Seropositivity to measles, mumps, and rubella serum IgG antibodies was assessed 35 days after vaccination. Non-inferiority was concluded if the upper limit of the 95% CI for the difference in the percent of seropositive between groups was less than 10%. Solicited reactions were collected for 14 days after vaccination by using structured diaries.ResultsIn each study group, 170 subjects received MMR vaccine. On day 35, seropositivity for measles was 97.5% [95% CI (93.8%, 99.3%)] in the DSJI group and 98.7% [95% CI (95.5%, 99.8%)] in the N-S group; for mumps, 98.8% [95% CI (95.6%, 99.8%)] and 98.7% [95% CI (95.5%, 99.8%)]; and for rubella, 98.8% [95% CI (95.6%, 99.8%)] and 100% [95% CI (97.7%, 100.0%)]; none of the differences were significant. The day 35 post-vaccination GMTs in DSJI and N-S groups were measles: 5.48 IU/ml [95% CI (3.71, 8.11)] and 5.94 IU/ml [95% CI (3.92, 9.01)], mumps: 3.83 ISR [95% CI (3.53, 4.14)] and 3.66 ISR [95% CI (3.39, 3.95)] and rubella: 95.27 IU/ml [95% CI (70.39, 128.95)] and 107.06 IU/ml [95% CI (79.02, 145.06)]; none of the differences were significant.The DSJI group reported 173 solicited local reactions and the N-S group reported 112; most were mild grade. Of the total of 156 solicited systemic adverse events, most were mild, and incidence between the two groups was similar.ConclusionsMMR vaccination via DSJI is as immunogenic as vaccination by N-S. Safety profile of DSJI method is similar to N-S except for injection site reactions which are more with DSJI and are well-tolerated.RegistrationUS National Institutes of Health clinical trials identifier – NCT02253407.Clinical trial registry of India identifier – CTRI/2013/05/003702



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Anti-vaccination and pro-CAM attitudes both reflect magical beliefs about health

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Gabrielle M. Bryden, Matthew Browne, Matthew Rockloff, Carolyn Unsworth
We examined the relationship between complementary and alternative medicine (CAM) use and vaccination scepticism; and specifically whether a person's more general health-related worldview might explain this relationship. A cross-sectional online survey of adult Australians (N = 2697) included demographic, CAM, and vaccination measures, as well as the holistic and magical health belief scales (HHB, MHB). HHB emphasises links between mind and body health, and the impact of general 'wellness' on specific ailments or resistance to disease, whilst MHB specifically taps ontological confusions and cognitive errors about health. CAM and anti-vaccination were found to be linked primarily at the attitudinal level (r = −0.437). We did not find evidence that this was due to CAM practitioners influencing their clients. Applying a path-analytic approach, we found that individuals' health worldview (HHB and MHB) accounted for a significant proportion (43.1%) of the covariance between CAM and vaccination attitudes. MHB was by far the strongest predictor of both CAM and vaccination attitudes in regressions including demographic predictors. We conclude that vaccination scepticism reflects part of a broader health worldview that discounts scientific knowledge in favour of magical or superstitious thinking. Therefore, persuasive messages reflecting this worldview may be more effective than fact-based campaigns in influencing vaccine sceptics.



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Substance use patterns of HVTN phase I clinical trial participants: Enrollment, risk reduction counseling and retention

Publication date: 21 February 2018
Source:Vaccine, Volume 36, Issue 9
Author(s): Arame Thiam-Diouf, Barbara Metch, Cameron Sharpe, Robel Mulugeta, Michele Peake Andrasik
BackgroundThe primary objectives of HIV Vaccine Trials Network (HVTN) phase 1 preventive HIV vaccine clinical trials are to assess safety and immune response to study products. Participant alcohol and drug use may affect adherence, retention, and risk of HIV infection. Data on the effects of substance use are limited to medical care compliance and treatment adherence in HIV infected participants. To our knowledge, there are no data assessing substance use and retention in these vaccine trials.MethodsWe performed a meta-analysis on substance use and its impact on retention in HVTN phase I trials that recruited participants demonstrating lower risk profiles for HIV infection. Our analysis included data from 10 HVTN phase 1 clinical trials conducted between February 2009 and September 2014 in the Americas and Switzerland that utilized the identical interviewer-administered behavioral risk assessment questionnaire to capture participant self-report of substance use in the previous six months. Chi Square tests were used to assess statistical differences between variables.ResultsAmong the 964 participants, 170 (18%) missed a clinic visit and 78 (8%) terminated early from clinic follow-up; 75/774 (10%) on studies with multiple vaccination timepoints did not complete their vaccinations. Neither frequency of alcohol use, binge drinking, marijuana, nor other drug use reported at screening visits were associated with the three adherence/retention measures. Binge drinking was associated with higher rates of unprotected sex while drunk (p < .001).ConclusionsLight to moderate alcohol use does not negatively impact adherence or retention in phase I clinical trials. Based on these screening data and the low infection rate of participants during the trial period, the screening process for participation in HVTN phase 1 trials has largely been successful in enrolling and retaining individuals with lower risk profiles. Focusing on binge drinking and increased HIV/STI risk during risk reduction counseling may be warranted.



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The impact of immunization programs on 10 vaccine preventable diseases in Italy: 1900–2015

Publication date: Available online 7 February 2018
Source:Vaccine
Author(s): Patrizio Pezzotti, Stefania Bellino, Francesca Prestinaci, Simone Iacchini, Francesca Lucaroni, Laura Camoni, Maria Maddalena Barbieri, Walter Ricciardi, Paola Stefanelli, Giovanni Rezza
BackgroundVaccination has determined a dramatic decline in morbidity and mortality from infectious diseases over the last century. However, low perceived risk of the infectious threat and increased concern about vaccines' safety led to a reduction in vaccine coverage, with increased risk of disease outbreaks.MethodsAnnual surveillance data of nationally communicable infectious diseases in Italy between 1900 and 2015 were used to derive trends in morbidity and mortality rates before and after vaccine introduction, focusing particularly on the effect of vaccination programs. Autoregressive integrated moving average models were applied to ten vaccine-preventable diseases: diphtheria, tetanus, poliomyelitis, hepatitis B, pertussis, measles, mumps, rubella, chickenpox, and invasive meningococcal disease. Results of these models referring to data before the immunization programs were projected on the vaccination period to estimate expected cases. The difference between observed and projected cases provided estimates of cases avoided by vaccination.ResultsThe temporal trend for each disease started with high incidence rates, followed by a period of persisting reduction. After vaccine introduction, and particularly after the recommendation for universal use among children, the current rates were much lower than those forecasted without vaccination, both in the whole population and among the 0-to-4 year olds, which is, generally, the most susceptible age class. Assuming that the difference between incidence rates before and after vaccination programs was attributable only to vaccine, more than 4 million cases were prevented, and nearly 35% of them among children in the early years of life. Diphtheria was the disease with the highest number of prevented cases, followed by mumps, chickenpox and measles.ConclusionsUniversal vaccination programs represent the most effective prevention tool against infectious diseases, having a major impact on human health. Health authorities should make any effort to strengthen public confidence in vaccines, highlighting scientific evidence of vaccination benefits.



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Treatment of flat and elevated pigmented disorders with a 755-nm alexandrite picosecond laser: clinical and histological evaluation

Abstract

The novel picosecond lasers, initially developed for faster tattoo removal, have also shown great efficacy in endogenous pigmentary disorders. To describe the efficacy and safety profile of an alexandrite (755-nm) picosecond laser in a wide range of pigmented flat and elevated cutaneous lesions. A retrospective study was performed in which we collected all the clinical images of patients treated with the 755-nm alexandrite picosecond laser for 12 months (November 2016–November 2017). Clinical features were obtained from their medical charts. Patients treated for tattoo removal were excluded. All the images were analyzed by three blind physicians attending to a visual analogue scale (VAS) from 0 to 5 (0, no change; 1, 1–24% clearance; 2, 25–49% clearance; 3, 50–74% clearance; 4, 75–99% clearance; 5, complete clearance). Patient satisfaction was obtained from a subjective survey including four items: very satisfied, satisfied, non-satisfied, and totally dissatisfied. Thirty-seven patients were included (12 males; 25 females). The mean age of the study was 42.35 years. Twenty-five patients (68%) were treated for different pigmented flat disorders such as solar and mucosal lentigines (5), stasis dermatitis (4), or nevus of Ota (4), among other diagnoses. Twelve patients (32%) were treated for epidermal elevated lesions such as warts (5), epidermal nevi (2), and seborrheic keratosis (3), among other elevated lesions. Mean number of laser treatment was 3.02 sessions while mean follow-up after last laser treatment was 4.02 months. Mean VAS score of the three observers was 3.44 (61% of clearance) for pigmentary flat disorders and 3.60 (67%) for elevated lesions. Adverse effects reported were mild blistering in the first 2–5 days following laser treatment in some of the patients. Overall satisfaction among the patients included was high. The novel 755-nm picosecond alexandrite laser is effective not only for the resolution of pigmented flat lesions of different nature but also for the treatment of the more difficult elevated pigmented lesions.

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INCIDENCE OF VENOUS THROMBOEMBOLISM AND USE OF ANTICOAGULATION IN HEMATOLOGICAL MALIGNANCIES: CRITICAL REVIEW OF THE LITERATURE

Publication date: Available online 8 February 2018
Source:Critical Reviews in Oncology/Hematology
Author(s): Ombretta Annibali, Mariasanta Napolitano, Giuseppe Avvisati, Sergio Siragusa
Venous Thromboembolism (VTE) frequently complicates the course of hematologic malignancies (HM) and its incidence is similar to that observed in high-risk solid tumors. Despite that, pharmacologic prophylaxis and treatment of VTE in patients with HM is challenging, mainly because a severe thrombocytopenia frequently complicates the course of treatments or may be present since diagnosis, thus increasing the risk of bleeding. Therefore, in this setting, safe and effective methods of VTE prophylaxis and treatment have not been well defined and hematologists generally refer to guidelines produced for cancer patients that give indications on anticoagulation in patients with thrombocytopenia. In this review, besides to summarize the incidence and the available data on prophylaxis and treatment of VTE in HM, we give some advices on how to use antithrombotic drugs in patients with HM according to platelets count.



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Association of Low Urine pH with Insulin Resistance in Non-Diabetic Japanese Subjects

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-122943

Background Epidemiology studies have revealed that patients with obesity, hyperglycemia, or hypertension are associated with a decreased urine pH. These metabolic disorders are related to insulin resistance; however, the association between urine pH and insulin resistance remains unclear. Methods To evaluate this association while controlling for covariates, the present study was conducted in 1084 non-diabetic Japanese subjects undergoing health examination. Fasting urine pH was analyzed using an automated urine dipstick analyzer. The subjects were divided into five groups according to urine pH: those with pH <5.5, 5.5, 6.0, 6.5, and >6.5. Insulin resistance was determined using the homeostatic model assessment of insulin resistance (HOMA-IR) and divided into three categories: lower, middle, and higher tertiles of HOMA-IR. Analysis of covariance and multivariate logistic regression analysis were used to control confounding factors including serum uric acid. Results Analysis of covariance showed an increase in the mean HOMA-IR from 1.26, 1.46, 1.69, and 1.75 to 1.89 with a decrease in urine pH (p<0.001). Subjects with urine pH ≤5.5 had a significantly higher HOMA-IR than those with urine pH>6.5. Furthermore, multivariate logistic regression analysis showed that urine pH had an inverse and independent association with HOMA-IR. In subjects with urine pH 5.5 and <5.5, adjusted odds ratio (95% confidence interval) for the incidence of higher tertile of HOMA-IR was 1.34 (1.04–1.73) and 1.52 (1.09–2.13), respectively (reference, subjects with a urine pH>6.5). Conclusion Insulin resistance is independently associated with a lower urine pH, possibly via lower formation of ammonium in the kidneys.
[...]

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The Main Determinants of Serum Resistin Level in Type 2 Diabetic Patients are Renal Function and Inflammation not Presence of Microvascular Complication, Obesity and Insulin Resistance

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-121262

Aim The association of increased resistin levels in chronic kidney disease with diabetic nephropathy has not yet been clarified. Our aim was to analyze the relationship between serum resistin levels and various diabetic microvascular complications in patients. Methods A total of 83 patients were enrolled in this cross-sectional study. The subjects were divided into 3 groups: 27 patients with type 2 diabetes mellitus (T2DM) having no diabetic retinopathy (DRP) or microalbuminuria and having normal renal function were included in Group-1, 28 patients with T2DM having DRP and normal renal function in Group-2, and 28 patients with T2DM with DRP and microalbuminuria and an estimated glomerular filtration rate (eGFR) of<60 ml/min/1.73 m2 in Group-3. Serum resistin levels were analyzed by enzyme-linked immunosorbent assay. Results The mean age of the patients [46 female (55.4%)] was 54.8±9.1 years. The resistin level in Group-3 was significantly higher than in Group-1 and Group-2 (p<0.001).However the resistin level was not different between Group-1 (without microvascular complications) and Group-2 (with microvascular complications). The resistin level was found to be correlated negatively with eGFR (r=−0.459; p<0.001) and albumin (r=−0.402; p<0.001), and positively with high-sensitivity C-reactive protein (hs-CRP) (r=0.366; p=0.001). In multivariate analysis, it was observed that eGFR and hs-CRP were independent determinants of plasma resistin level. Conclusion The main determinants of resistin level in patients with T2DM are the level of renal function and inflammation rather than presence of microvascular complications, obesity and insulin resistance.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Insulin-Leptin Axis, Cardiometabolic Risk and Oxidative Stress in Elderly with Metabolic Syndrome

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-123825

Insulin and leptin have an overlapping anorexigenic action as well as opposite effects on glucose and lipid metabolism. The study focuses on the biochemical and clinical relevance of new indices of insulin-leptin axis utilized in the study of the relationships between leptinemia, insulin sensitivity and oxidative stress, in elderly subjects with metabolic syndrome. We conducted clinical studies on elderly people with metabolic syndrome versus control subjects by creating new insulin-adipogenic indices, namely Insulin-to-Leptin Ratio (ILR) and Insulin-Adipogenic Resistance index (IAR-index). Inflammation and oxidative stress biomarkers evaluated were the high-sensitivity C-reactive protein (hsCRP), the advanced oxidation protein products (AOPP), and the serum antioxidant capacity measured as ferric reducing antioxidant potential (FRAP). The metabolic syndrome group showed significantly (p<0.01) lower levels of ILR and not significant (p=0.09) higher values of IAR-index, as compared to the control group. In metabolic syndrome subjects, the IAR-index was significantly positively correlated with uric acid (r=0.313, p<0.05), FRAP (r=0.347, p<0.05) and AOPP (r=0.677, p<0.01), and negatively correlated with HDL-cholesterol (r=− 0.340, p<0.05) as well as with the ratio FRAP/uric acid (r=− 0.315, p<0.05). ILR and IAR-index reflected the biological state of adipose and pancreatic β-cells and seem to depict the adipo-insular axis status related to metabolic and oxidative stress better than individual markers. Therefore, ILR and IAR-index could represent integrated high-potential biomarkers for disease and patient stratification.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Combining Various Methods to Assess Insulin Sensitivity in Nonobese Rat after Sleeve Gastrectomy

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-125315

Background Sleeve gastrectomy (SG) procedure has been proved to improve insulin sensitivity and sustain anti-diabetic effects. Our aim is to co-use several methods to measure insulin sensitivity and investigate the effect of SG on hepatic and peripheral insulin sensitivity at early and long-term stages of postoperation. Methods Thirty 11-week-old male Goto-Kakizaki rats were divided into SG, sham-operated SG (SOSG), and control groups. They were observed before operation and for 36 weeks of postoperation. Insulin tolerance test (ITT) and homeostasis model of assessment for insulin resistance index(HOMA-IR)were used to measure insulin resistance before operations and at 2 and 36 weeks of postoperation; Pyruvate challenge test (PCT) was administrated to assess the gluconeogenesis capability in order to reflect hepatic insulin sensitivity before operation and at 2 and 36 weeks of postoperation; Hyperinsulinemic euglycemic clamps (HIEC) was conducted before operation and at 2 and 36 weeks of postoperation to calculate the endogenous hepatic glucose production (HGP) at the basal and steady-state for evaluation of hepatic insulin sensitivity, and calculate the exogenous glucose infusion rate (GIR) at the steady-state for evaluation of peripheral insulin sensitivity. Results The data showed that compared with rats in the sham and control groups, rats in SG group had 1) significantly lower AUCITT, HOMA-IR and AUC PCT values at 2 and 36 weeks of postoperation, 2) lower basal state HGP, but not steady-state GIR at 2 weeks of postoperation, and 3) significantly different basal and steady-state HGP and steady-state GIR at 36 weeks of postoperation. In addition, the basal and steady-state HGP and the steady-state GIR were significantly different between rats in SG group at 2 and 36 weeks of postoperation. Conclusions This study explored insulin sensitivity of rats after SG by jointly using a variety of techniques. The results showed that SG time-dependently improved the hepatic and peripheral insulin sensitivity.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Serum CTRP3 Level is Associated with Osteoporosis in Postmenopausal Women

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-124365

Background As a novel adipokine, CTRP3 involves in various functions of energy metabolism. Recent advance reveals a complex interaction between bone and adipose tissue via the secretion of adipokines. Aims A hospital-based case-control study was conducted to investigate the role of serum CTRP3 in osteoporosis among postmenopausal women. Methods Serum levels of CTRP3 and osteocalcin were measured. Bone mineral density (BMD) was obtained on femoral neck and lumbar spines by dual energy X-ray absorptiometry. Results Serum CTRP3 level was lower in subjects with osteoporosis (76.7±22.1 ng/ml) than it in controls (89.4±22.5 ng/ml) (P<0.001). Meanwhile, the frequency of osteoporosis presented a significant decrease (66.4%, 53.9% and 35.9%, P<0.001), in the tertiles of serum CTRP3. Furthermore, serum CTRP3 witnessed an association with a lower risk of osteoporosis (adjusted odds ratio=0.973, 95% confidence interval [0.963–0.983], P<0.001). Lastly, serum CTRP3 level was positively correlated with femoral BMD (r=0.403, P<0.001), lumbar BMD (r=0.368, P<0.001), and HDL-C (r=0.118, P=0.022), among all participants after adjustment. Meanwhile, CTRP3 presented negative correlations with HOMA-IR (r=−0.136, P=0.008) and insulin (r=−0.192, P <0.001). Conclusions It shows that a decreased serum level of CTRP3 was independently associated with osteoporosis.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

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Impact of Depression and Psychosocial Treatment on Heart Rate Variability in Patients with Type 2 Diabetes Mellitus: An Exploratory Analysis Based on the HEIDIS Trial

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-125445

Objectives To explore the impact of depression on heart rate (HR) and heart rate variability (HRV) as a marker of autonomic nervous system (ANS) impairment in depressed and non-depressed patients with advanced type 2 diabetes mellitus (T2DM) and to explore possible effects of an acceptance- and mindfulness-based group intervention (MBSR) on HR and HRV. Methods Alongside a prospective clinical trial, we collected demographic, psychosocial and clinical data from 113 chronic T2DM patients in a standardized setting. At baseline and after one year, depressive mood was assessed with the Patient Health Questionnaire (PHQ-9), and autonomic function was determined by measuring HR and HRV markers. A subsample was randomly assigned to take part in eight MBSR sessions. Results Of the 113 T2DM patients (77.9% men; mean age=58.8±7.0 years; diabetes duration 11.5±7.0 years), 33 showed clinically relevant depressive symptoms at baseline. In cross-sectional analysis, we found no association between depression and HR/HRV (all comparisons p>0.05). In prospective regression analysis depression did not predict follow-up scores of HRV. The patients who participated in the MBSR intervention showed a tendency toward improved parasympathetic control (RMSSD, CV, E-I-Ratio) with small-to-moderate effect sizes (d≤0.38). Conclusions Depression was not directly associated with cardiac autonomic control in this sample, but MBSR training may have positively influenced HR and HRV. In advanced diabetes, somatic and behavioral parameters seem to be more predictive than depression for the course of autonomic functioning, but the pathways remain unclear.
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© Georg Thieme Verlag KG Stuttgart · New York

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Effects of the Reactive Metabolite Methylglyoxal on Cellular Signalling, Insulin Action and Metabolism – What We Know in Mammals and What We Can Learn From Yeast

Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-122382

Levels of reactive metabolites such as reactive carbonyl and oxygen species are increased in patients with diabetes mellitus. The most important reactive dicarbonyl species, methylglyoxal (MG), formed as by-product during glucose metabolism, is more and more recognized as a trigger for the development and progression of diabetic complications. Although it is clear that MG provokes toxic effects, it is currently not well understood what cellular changes MG induces on a molecular level that may lead to pathophysiological conditions found in long-term diabetic complications. Here we review the current knowledge about the molecular effects that MG can induce in a cell. Within the mammalian system, we will focus mostly on the metabolic effects MG exerts when applied systemically to rodents or when applied in vitro to pancreatic β-cells and adipocytes. Due to the common limitations associated with complex model organisms, we then summarize how yeast as a very simple model organism can help to gain valuable comprehensive information on general defence pathways cells exert in response to MG stress. Pioneering studies in additional rather simple eukaryotic model organisms suggest that many cellular reactions in response to MG are highly conserved throughout evolution.
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© Georg Thieme Verlag KG Stuttgart · New York

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Assessment of progeny concentrations of 222 Rn/ 220 Rn and their related doses using deposition-based direct progeny sensors

Abstract

Indoor radon and thoron concentrations in the domestic environment result in natural radiation exposure to the public due to the inhalation of their short-lived decay products. Keeping this in view, the annual effective dose and other radiation risks due to radon/thoron progenies have been calculated. In this study, newly developed time deposition-based progeny sensors (DTPS/DRPS) were used for long-term passive determination of progeny concentrations in the environment of Jammu and Kashmir, Himalayas, India. The total equilibrium equivalent radon (EECR_A + U) and thoron (EECT_A + U) concentrations ("A" and "U" referring to attached and unattached fractions) were found to vary from 5 to 38 Bq m⁻³ with an average value of 18 Bq m⁻³ and from 0.48 to 5.49 Bq m⁻³ with an average value of 1.69 Bq m⁻³, respectively. The aerosol concentration, equilibrium factors, and unattached fractions for radon and thoron progeny have been estimated in normal living conditions and their dependence on each others have also been studied. The annual equilibrium factor for radon and thoron progeny has been determined from the calculated data. The estimated annual effective dose due to radon progeny (0.34 to 2.42 mSv y⁻¹) and thoron progeny (0.13 to 1.54 mSv y⁻¹) is found to be below the world's recommended level. Based on measurements of mean values of the unattached fraction, dose conversion factors (DCFs) in units of mSv per working level month (WLM) has been calculated and the average calculated values of DCFs are 24, 10, and 13 mSv WLM⁻¹. The variability of equilibrium factor and radon/thoron progeny with different seasons, ventilation conditions, and types of houses were also analyzed.

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Treatment of soak liquor and bioelectricity generation in dual chamber microbial fuel cell

Abstract

The discharge of untreated soak liquor from tannery industry causes severe environmental pollution. This study is characterizing the soak liquor as a substrate in the microbial fuel cell (MFC) for remediation along with electricity generation. The dual chamber MFC was constructed and operated. Potassium permanganate was used as cathode solution and carbon felt electrode as anodic and cathodic material, respectively. The soak liquor was characterized by electrochemical studies viz., cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and polarization studies, respectively. The removal percentage of protein, lipid, and chemical oxygen demand (COD) were measured before and after treatment with MFC. The results of MFC showed a highest current density of 300 mA/cm² and a power density of 92 mW/m². The removal of COD, protein, and lipid were noted as 96, 81, and 97% respectively during MFC process. This MFC can be used in tannery industries for treating soak liquor and simultaneous electricity generation.

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Probing the toxic mechanism of bisphenol A with acid phosphatase at the molecular level

Abstract

As an endocrine-disrupting chemical, bisphenol A (BPA), can affect normal endocrine function of hormone. This paper studied the toxic effect of BPA on acid phosphatase at the molecular level by multi-spectroscopic measurements, molecular docking, and enzyme activity experiment. BPA could enhance the fluorescence intensity, change the structure, and cause an increased hydrophobicity of acid phosphatase. Hydrogen bond interaction and van der Waals forces were the main forces to generate the BPA-acid phosphatase complex on account of the negative ΔH (− 36.92 kJ mol⁻¹) and ΔS (− 50.78 J mol⁻¹ K⁻¹). BPA led to the loosening and unfolding of protein structure and extending the peptide strands, as revealed by UV-vis absorption and CD spectra. Based on the enzyme activity experiment, BPA could decrease the activity of the acid phosphatase by entering the active site of the enzyme. The molecular docking model showed that BPA could bind into the cavity of acid phosphatase and interact with Tyr A252 and a hydrogen bond (1.47 Å) was formed in the binding process. This work suggested the structures and functions of acid phosphatase were both affected by BPA.

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Occurrence and molecular characterization of Giardia duodenalis cysts and Cryptosporidium oocysts in raw water samples from the Rímac River, Peru

Abstract

Giardia and Cryptosporidium are potentially pathogenic protozoa which are ubiquitous in ambient surface water. The present study included 60 samples of surface water from three sampling sites from the Rímac River, Lima and Callao, Peru, to detect the occurrence of Giardia spp. and Cryptosporidium spp. and to perform molecular characterization of specimens found. Water samples were concentrated using the membrane filtration technique, and following elution, cysts and oocysts were visualized by direct immunofluorescence assay (IFA). For molecular characterization, tpi and bg gene fragments and 18S rRNA were amplified by nested PCR for Giardia and Cryptosporidium, respectively, followed by sequencing and phylogenetic analysis. Giardia cysts were found in 93.3% of the analyzed samples, whereas Cryptosporidium oocysts were detected in 15%. The positivity of the Giardia cysts was 86.6% (n = 26) in 2014, while Cryptosporidium oocysts were not detected. In 2015, both protozoa were found in raw water samples, with all 30 samples collected positive for Giardia cysts (100.0%) and 9 positive for Cryptosporidium oocysts (30.0%). Oocysts were detected in 20.0% of water samples from sites 1 (mean 5.25 oocysts/L) and 2 (mean 52.3 oocysts/L), while at site 3, oocysts were detected in 50.0% of raw water samples (mean 193.6 oocysts/L). The presence of Giardia duodenalis assemblage A was confirmed in several samples by the phylogenetic positioning of the bg and tpi genes, and the sub-assemblage AII was predominant (8/9). Sequencing for Cryptosporidium resulted in profiles compatible with Cryptosporidium hominis, Cryptosporidium meleagridis, and Cryptosporidium baileyi. This is the first time that the presence of G. duodenalis assemblage A/sub-assemblage AII and Cryptosporidium species has been reported in surface water samples in Peru. These Cryptosporidium species and the Giardia duodenalis assemblage are associated with human disease which highlights the potential risk to public health and the need to increase environmental monitoring measures to protect this water body.

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Health care expenditures of overweight and obese U.S. adults with intellectual and developmental disabilities

Publication date: April 2018
Source:Research in Developmental Disabilities, Volume 75
Author(s): Henan Li, Glenn Fujiura, Sandra Magaña, Susan Parish
BackgroundU.S. adults with intellectual and developmental disabilities (IDD) have poorer health status and greater risks for being overweight and obese, which are major drivers of health care expenditures in the general population. Health care expenditures and IDD have not been studied using nationally representative samples, and the impact of overweight and obesity have not been examined.AimUsing nationally representative data, we aimed to compare the health care expenditures of not-overweight, overweight and obese U.S. adults with IDD, and calculate model-adjusted expenditures.Methods and proceduresPooled data from the 2002–2011 Medical Expenditure Panel Survey linked to National Health Interview Survey (n = 1224) were analyzed. Two-part model regressions were conducted, with covariates being year of survey, age, sex, race/ethnicity, household income status, geographical region, urban/rural, marital status, insurance coverage, perceived health status, and perceived mental health status.Outcomes and resultsOverall, obese adults with intellectual and developmental disabilities had higher expenditures than their non-obese peers. Being obese was associated with an estimated additional $2516 in mean expenditures and $1200 in median expenditures compared with the reference group, who were neither overweight nor obese.Conclusions and implicationsObesity is an important predictor of higher health care costs among community-living adults with IDD Finding effective strategies and interventions to address obesity in this population has great financial and policy significance.



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Polymorph formation for a zeolitic imidazolate framework composition - Zn(Im)2

Publication date: 15 July 2018
Source:Microporous and Mesoporous Materials, Volume 265
Author(s): Chao Zhou, Malwina Stepniewska, Jens Martin Sørensen, Luca Scarpa, Giuliana Magnacca, Vittorio Boffa, Thomas D. Bennett, Yuanzheng Yue
We study the effect of synthesis time and temperature on the crystal formation, morphology and size of zeolitic imidazolate frameworks (ZIFs) with the Zn(Im)2 composition by using the solution mixing method. The crystal structure, morphology and thermodynamic properties of the ZIFs were characterized by powder X-ray diffraction, scanning electron microscopy and nitrogen sorption isotherms. Our results indicate that the synthesis time significantly influences the structure and topology of crystal products. The crystal structure transforms from ZIF-coi to the progressively denser polymorphs (ZIF-zec, ZIF-nog and ZIF-zni) upon increasing synthesis time from 18 to 120 hours at 10 °C, in accordance with Ostwald's step rule. Increasing synthesis temperature does not change the formation of the ZIF-zec crystals but affects their morphologies and porosities. Both ZIF-nog and ZIF-zec exhibit relatively large surface areas (>500 m²/g). Furthermore, heating ZIF-nog and ZIF-zec causes recrystallization to ZIF-zni and subsequent melting. Quenching the MOF-liquid results in Zn(Im)2 glass. This work helps to understand and control the crystal formation of ZIFs, and reveals two new MOF glass formers.



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Penaeus vannamei protease stabilizing process of ZnS nanoparticles

Publication date: June 2018
Source:International Journal of Biological Macromolecules, Volume 112
Author(s): Mozhgan Razzaghi, Ahmad Homaei, Elaheh Mosaddegh
The protease enzyme purified from the Penaeus vannamei shrimp has unique properties, so improving the stability of this enzyme can improve their practical applications. In this study, ZnS nanoparticles, which have special properties for enzyme immobilization, were synthesized using a chemical precipitation method, and Penaeus vannamei protease was successfully immobilized on them. The size, structure, and morphology of the ZnS nanoparticles, and the immobilization of the protease were studied, using Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FT-IR) spectroscopy, UV–Vis spectroscopy and Dynamic Light Scattering (DLS) analysis. We show that the immobilized enzyme has improved functionality at high temperatures, extreme pH conditions (pH3 and 12), and during storage. Immobilization increased the optimum temperature range of the enzyme, but did not change the pH optimum, which remained at pH7. Immobilization of P. vannamei protease enzyme increased the Km and decreased kcat/Km. These results indicate that P. vannamei protease immobilized on ZnS nanoparticles, has improved properties due to its high stability and unique properties, can be used for biotechnology applications.



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Attitudes to climate change, perceptions of disaster risk, and mitigation and adaptation behavior in Yunlin County, Taiwan

Abstract

Issues that are associated with climate change have global importance. Most related studies take a national or regional perspective on the impact of climate change. Taiwan is constrained by its geographical conditions, which increase its vulnerability to climate change, especially in its western coastal areas. The county that is most affected by climate change is Yunlin. In 2013–2014, projects that were sponsored by Taiwan's government analyzed the relationship among synthesized vulnerability, ecological footprint (EF) and adaptation to climate change and proposed 15 categories of synthesized vulnerability and EF values. This study further examines the relationship between vulnerability and EF values and examines how residents of four townships—Linnei, Sihu, Mailiao, and Huwei—cope with the effects of climate change. This study investigates whether the residents of the four townships vary in their attitudes to climate change, their perceptions of disaster risk, and their behavioral intentions with respect to coping with climate change. The structural equation model (SEM) is used to examine the relationships among attitudes to climate change, perceptions of disaster risk, and the behavioral intentions of residents in townships with various vulnerabilities to climate change. The results that are obtained using the SEM reveal that climate change mitigation/adaptation behavior is affected by attitudes to climate change and perceptions of disaster risk. However, the effects of attitudes and perceptions on mitigation and adaptation that are mediated by place attachment are not statistically significant.

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Assessment of atrazine toxicity to the estuarine phytoplankter, Dunaliella tertiolecta (Chlorophyta), under varying nutrient conditions

Abstract

Anthropogenic inputs of chemical environmental contaminants are frequently associated with developing harmful algal blooms, but little is known about how estuarine phytoplankton assemblages respond to multiple, co-occurring chemical stressors in chronically disturbed habitats. The goals of this research were to establish a robust protocol for testing the effects of atrazine on estuarine phytoplankton, and then to use that protocol to compare the effects of atrazine exposure with and without nutrient enrichment on a cosmopolitan estuarine/marine alga, Dunaliella tertiolecta (Chlorophyta). Atrazine sensitivity in nutrient-replete media (96-h growth inhibition \( \overline{x} \) ) was 159.16 μg l⁻¹, but sensitivity was influenced by exposure duration, and inhibitory effects of herbicide on algal growth decreased under imbalanced nutrient regimes and low nitrogen and phosphorus supplies. These findings advance knowledge about how nutrient regimes and herbicides interact to control estuarine phytoplankton population dynamics.

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Efficacy and Safety of Sym004 in Refractory Metastatic Colorectal Cancer

This phase 2 randomized clinical trial evaluates the efficacy and safety of Sym004 (a mixture of futuximab and modotuximab) for the treatment of refractory metastatic colorectal cancer with acquired resistance to anti-EGFR therapy.

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Trend Analysis on Reoperation After Lumpectomy for Breast Cancer—Reply

In Reply We concur with Yang et al that our study design cannot definitively address causality, and this limitation was noted in our article. However, a substantial body of evidence strongly suggests that there is a relationship between the margin guideline publication and increased use of less-extensive surgery. Long-term secular trends in the use of breast-conserving surgery documented prior to our study (and publication of the margins guideline) showed decreased use of breast-conserving surgery and a concomitant increased use of mastectomy. Furthermore, a study examining reoperation rates after initial lumpectomy in patients treated prior to publication of the guidelines (2004 through 2010) found only a 2.9% decrease in additional surgery. By contrast, we observed a marked increase in breast-conserving surgery—the result of a substantial decrease in reoperations after lumpectomy. Additionally, we demonstrated that the observed decrease in second surgery after lumpectomy was associated with a high rate of surgeon endorsement of a margin of no ink on tumor. High acceptance rates of margins of no ink on tumor were not observed in earlier studies performed prior to publication of the margin guidelines. Finally, we noted no change in the use of second surgery in the patients with ductal carcinoma in situ, a group not included in the margin guideline, who were sampled during the same period.

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Concurrent Chemoradiotherapy for Stage IIIB Cervical Cancer

Of the 500 000 new cervical cancer cases annually, most (85%) locally advanced cervical cancer (LACC) occurs in low- and middle-income countries (LMICs), where sufficient resources are not always readily available for treatment. For almost 2 decades, the optimal management for all LACC in the United States has included concurrent chemoradiotherapy (CRT). A National Cancer Institute alert was released in 1999, after the publication of multiple randomized clinical trials demonstrated improved survival rates with concurrent CRT compared with radiotherapy (RT) alone. In particular, the Radiation Therapy Oncology Group (RTOG) 90-01 trial showed a 5-year absolute survival benefit of 21% for all stages of cervical cancer with CRT. However, an unplanned and inadequately powered subgroup analysis of patients with stage III to IVA disease showed an overall survival (OS) advantage of 14% (P = .06), disease-free survival (DFS) benefit of 17% (P = .05), and locoregional control benefit of 15% (P = .065). A 2010 meta-analysis demonstrated a 5-year absolute OS benefit of 6% for all stages of cervical cancer treated with concurrent CRT compared with RT alone; however, the survival benefit was only 3% for women with stage III to IVA cervical cancer. Nevertheless, due to the lack of statistical significance in the patient subgroup with stage IIIB to IVA disease in RTOG 90-01, combined with issues of cost and access, some LMICs chose not to standardize CRT for all patients with LACC.

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Circulating Tumor DNA and Anti–PD-1 Pseudoprogression in Melanoma

This cohort study assesses whether baseline and early therapy circulating tumor DNA measurements differentiate pseudoprogression from true progression in patients with metastatic melanoma treated with anti–programmed cell death 1 antibodies.

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Participation by Black Men in Prostate Cancer Clinical Trials

This study examines the lack of race-adjusted measurements for renal function in eligibility criteria for participation of black men in prostate cancer trials.

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Cisplatin Chemoradiotherapy vs Radiotherapy in FIGO Stage IIIB SCC of the Uterine Cervix

This randomized clinical trial investigates the benefit of concurrent chemoradiotherapy vs radiotherapy alone in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIIB squamous cell carcinoma of the uterine cervix.

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Trend Analysis on Reoperation After Lumpectomy for Breast Cancer

To the Editor We read with great interest the article by Morrow et al. It highlights an important issue of overtreatment in breast surgery. Despite its scientific rigor and novelty, we believe that there are 3 limitations that the authors may have considered but did not address in the article.

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Effect of Sulindac and Erlotinib vs Placebo for Colorectal Neoplasia in Familial Adenomatous Polyposis

This secondary analysis of data from the the FAP Erlotinib-Sulindac Trial (FAPEST) trial examines the effect of sulindac and erlotinib on colorectal adenoma formation and regression in patients with familial adenomatous polyposis.

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Atezolizumab Monotherapy for Patients With Metastatic Urothelial Cancer

This cohort study of an ongoing phase 1 trial reports long-term clinical outcomes with atezolizumab therapy for patients with metastatic urothelial carcinoma.

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Issue Information

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Evaluation of T lymphocyte subpopulations in Actinic Keratosis, In Situ and Invasive Squamous Cell Carcinoma of the Skin

Abstract

Background

Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing two semi-quantitative scoring systems, and assesses the presence of regulatory T-cells (Tregs) in these lesions.

Methods

Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semi-quantitative Klintrup-Mäkinen score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification.

Results

An increase of all TIL subpolulations from precursor lesions towards inSCC was shown by both scoring systems. Treg counts progressively increased from normal skin to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes.

Conclusions

T-cells and cytotoxic T-cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K-M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC.

http://ift.tt/2EOrhzo

Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time

Abstract

Purpose

To describe the course of growth hormone response to growth hormone releasing hormone (GHRH) plus arginine provocative test in children with idiopathic short stature (ISS) and to evaluate the role of peak time.

Methods

A retrospective study was performed analyzing 344 GHRH plus arginine provocative tests performed in children and adolescents with short stature. Serum GH levels were measured at four-time points (T0′, T30′, T45′ and T60′) and GH peak was defined as the maximum value at any time point. Mean (T30′–T60′) GH value and area under the curve (AUC) were calculated.

Results

When analyzing the time of peak at the provocative test, the most frequent peak time was T45′ (53.8%) in the ISS group, with no differences in gender, age, and pubertal stage. Analyzing GHD subjects, the most frequent time of peak was T30 (50%). Analyzing the whole population, the GH T0′ levels were significantly lower in subjects with the GH peak at T45′ than those with the GH peak at T30′ (1.7 ± 2.0 vs. 3.2 ± 4.0, p < 0.001). In subjects with GH peak at T45′, the value of GH peak, AUC and mean GH were significantly higher than in those with GH peak at T30′ and T60′. A direct correlation was found between the value of GH peak and growth velocity SDS (r = 0.127, p = 0.04) and a negative one between GH peak and GH level at T0′ (r = − 0.111, p = 0.04), even when adjusted for gender, age, pubertal stage and BMI Z score.

Conclusions

The time peak at 45 min seems to be associated with a better response to the test considering GH peak, mean and AUC. Patients with a GH peak at 30 min more probably could have a derangement in GH secretion showing worst growth pattern and/or a GH deficiency and should be carefully observed.

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Radiotherapy With Double Checkpoint Blockade of Locally Advanced HNSCC

Condition:   Locally Advanced Head and Neck Squamous Cell Carcinoma
Intervention:   Combination Product: Durvalumab + Tremelimumab + RT
Sponsor:   University of Erlangen-Nürnberg Medical School
Not yet recruiting

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Divers Alert Network Annual Diving Reports.

Fatalities and serious diving injuries are rare and often seem to be associated with unsafe behaviors or hazardous conditions, but they can occur without apparent cause.

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Acute Antiobesity Effects of Intracerebroventricular 11β-HSD1 Inhibitor Administration in Diet-induced obese mice

Abstract

Hypothalamus is the regulatory center of both appetite and energy balance, and endoplasmic reticulum (ER) stress in the hypothalamus is involved in the pathogenesis of obesity. Recently, inhibition of 11 β hydroxysteroid dehydrogenase type1 (11β-HSD1) was reported to have an anti-obesity effect by reducing fat mass. However, link between the role of 11β-HSD1 in hypothalamus and obesity has yet to be elucidated. In this study, embryonal primary hypothalamic neurons and high fat diet (HFD) fed mice were used to investigate the anorexigenic effects of 11β-HSD1 inhibitors in in vitro and in vivo. In hypothalamic neurons, carbenoxolone (a non selecitve 11β-HSD inhibitor) alleviated ER stress and ER stress-induced neuropeptide alterations. In HFD mice, intracerebroventricular (ICV) administrations of carbenoxolone or KR67500 (non-selective and selective 11β-HSD1 inhibitors, respectively) were associated with less weight gain than controls for 24 hours after the treatment, presumably by reducing food intake. Furthermore, glucose regulated protein(Grp78), spliced X-box binding protein(Xbp-1s), c/EBP homologous protein (chop), and ER DnaJ homolog protein(Erdj4) expressions were decreased in the hypothalami of mice administrated 11β-HSD1inhibitors as compared with controls. Conversely the phosphorylations of protein kinase B (PKB/Akt), signal transducers and activators transcription 3 (Stat3), mitogen activated protein kinase (MAPK/ERK), S6 kinase1 (S6K1) in hypothalamus were more induced in mice treated using the same regimes. In conclusion, acute11β-HSD1 inhibition in hypothalamus could reduce food intake by decreasing ER stress and increasing insulin, leptin, and mammalian target of rapamycin complex 1(mTORC1) signaling.

This article is protected by copyright. All rights reserved.

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Scholar : These new articles for Cogent Geoscience are available online

The online platform for Taylor & Francis Online content New for Cogent Geoscience and online now on Taylor & Francis Online: Research Article The use of Terrestrial Laser Scanning in Monitoring and Analyses of Erosion Phenomena in Natural and Anthropogenically Transformed Areas | Paweł B. Dąbek, Ciechosław Patrzałek, Bartłomiej Ćmielewski & Romuald Żmuda | Louis-Noel Moresi Reviewing Editor 1437684 | DOI: 10.1080/23312041.2018.1437684This is the author accepted version which has not been proofed or edited Browse papers on image & data fusion, GIS, LiDAR & more in the International Journal of Image and Data Fusion's exclusive Editor's Choice collection. To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Creative Industries Journal are available online

The online platform for Taylor & Francis Online content New for Creative Industries Journal and online now on Taylor & Francis Online: Original Articles 'Oh Joy, Oh Rapture': The Oily Chart Opera Company reflects the enduring charm of Gilbert and Sullivan in South Africa Roy Page-Shipp, Dawn Joseph & Caroline van Niekerk Pages: 1-16 | DOI: 10.1080/17510694.2018.1434360 Browse this free access collection on Communication, Media and Culture in Asia: http://bit.ly/cmc-in-asia To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Standards for Reporting EMG Data

Publication date: February 2018
Source:Journal of Electromyography and Kinesiology, Volume 38





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Scholar : These new articles for Critique: Studies in Contemporary Fiction are available online

The online platform for Taylor & Francis Online content New for Critique: Studies in Contemporary Fiction and online now on Taylor & Francis Online: Original Articles "Everything has to be qualified": Reading as Misreading in John Banville and Paul de Man Elke D'hoker Pages: 1-11 | DOI: 10.1080/00111619.2018.1427546 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.