bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence, patterns and factors associated with psychotropic use in older adults with intellectual disabilities in Ireland
Authors: O'Dwyer M. , Peklar J. , Mulryan N. , McCallion P. , McCarron M. , Henman M. C.
Published: June 2017

Background

People with intellectual disability (ID) are at increased risk of exposure to psychotropic drugs and psychotropic polypharmacy because of the higher prevalence of mental health conditions present and more controversially, the use of these agents to treat challenging behaviours. Despite the fact that many adults with ID are exposed to psychotropic polypharmacy, few studies to date have focused on the patterns of use of multiple psychotropics, or factors associated with psychotropic polypharmacy, particularly in the older population. This study aims to examine the prevalence, patterns and factors associated with psychotropic use in general and psychotropic polypharmacy in particular in a representative sample of ageing people with ID.

Methods

This was an observational cross‐sectional study from Wave 1 of Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing; a nationally representative sample of 753 persons with ID aged between 41 and 90 years. Participants/proxy reported medicines (prescription and over the counter) taken on a regular basis; medication data were available for 736 participants (98%). Participants were divided into those with no psychotropic exposure, exposure to 1 psychotropic and psychotropic polypharmacy (2+ psychotropics). Patterns of psychotropic use were analysed. A multinomial logistic regression model identified factors associated with use of 1 psychotropic and psychotropic polypharmacy.

Results

Overall, 59.1% (436) of the sample was exposed to any psychotropic; of these, 66.2% reported psychotropic polypharmacy. Antipsychotics were the most frequently reported psychotropic class by 43% of the sample. Living in a residential institution and having a history of reporting a mental health condition or sleep problems were associated with psychotropic polypharmacy after adjusting for confounders, while those with epilepsy were less likely to experience exposure to polypharmacy, but age, gender had no significant effect.

Conclusions

Psychotropic use and polypharmacy were commonplace for older adults with ID. Psychotropic use, particularly the use of psychotropic combinations, needs to be regularly reviewed for safety, efficacy and adverse effects, and rationale for use of multiple agents needs to be clear and documented.
Evaluation of the in vivo cosmetic efficacy of the MF3 blue cell serum gel. One‐ and two‐month test results
Authors: Tulina Dina , Béguin Alain , Pong Henry , Cabarbas Maria Del Mar , Klokol Dmitry , Chan Mike K.S. , Wong Michelle B.F.
Published: June 2017

Introduction

Skin is changing over time showing signs of aging: dryness, increase in visual and tactile roughness, decrease in collagen content and stiffness, and eventually formation of deep and surface wrinkles, and fine lines.

Methods

Eight‐week open experimental study was conducted to test efficacy of MF3 Blue Cell Serum Gel. Main criteria to determine product efficacy by following skin biophysical techniques were as follows: skin moisturization, firmness, epidermal and dermal density, skin surface properties and sebum level, reduction in fine lines and wrinkles. Secondary criteria were as follows: participant's opinion during study and product tolerance evaluation. Days 29 and 57 assessments included visual evaluation, skin biophysical techniques, and compliance check. The self‐assessment questionnaires completed.

Results

After week 8, obtained results showed very good hydration effect of test product, despite the fact being serum gel. Moisturizing increased continuously during study period. Important increases on skin firmness were observed which are in line with typical anti‐aging claims. Dermal density steady improvement noted especially after 4th week of study, and effect on deep skin layers was due to increase in collagen content and stiffness. Sebum regulation process was evidenced. Further significant roughness reduction in skin surface showed decrease or disappearance of fine lines and wrinkles. Products were well tolerated with no adverse events. Most of participants noticed visible improvement and increase in facial radiance, skin smoothness, and overall skin improvement.

Conclusion

Twice daily application of MF3 Blue Cell Serum Gel led to significant improvement in skin hydration, firmness, dermal density, sebum regulation, roughness reduction, decrease or disappearance of fine lines and wrinkles.
Matching Capital and Labor
Authors: BERK JONATHAN B. , van BINSBERGEN JULES H. , LIU BINYING
Published: June 2017

We establish an important role for the firm by studying capital reallocation decisions of mutual fund firms. The firm's decision to reallocate capital among its mutual fund managers adds at least $474,000 a month, which amounts to over 30% of the total value added of the industry. We provide evidence that this additional value added results from the firm's private information about the skill of its managers. The firm captures this value because investors reward the firm following a capital reallocation decision by allocating additional capital to the firm's funds.
Meeting the needs of critical care patients after discharge home: a qualitative exploratory study of patient perspectives
Authors: Allum Laura , Connolly Bronwen , McKeown Eamonn
Published: June 2017

ABSTRACT

Background

With improved survival rates in critical care, increasing focus is being placed on survivorship and how best to support patients in returning to their former activity. Little is known about what support patients themselves view as important, and this has implications for the efficacy and acceptability of services provided.

Objectives

To describe former critical care patients' perspectives on the support needed to optimize recovery.

Study design

This is a qualitative exploratory study of the experiences of support received by critical care survivors.

Research methodology

Semi‐structured interviews were undertaken with 12 critical care survivors recruited from a charity and a patient and public involvement group. The interviews were analysed using thematic analysis to describe patterns in the participants' experiences.

Findings

Four themes of support were described: effective management of transfer anxiety, tailored information provision, timely access to services and a supportive social network.

Conclusion

Survivors of critical care should be equipped with information about their critical care stay, ongoing health issues and recovery and should be provided with holistic care at home. Critical care follow up was an effective way of meeting many of these needs, but this needs to be flexible to be useful to attendees. Peer support groups (face‐to‐face and online) provided information, reassurance, a social network and an avenue for those who had longer‐lasting problems than current services provide for.

Relevance to clinical practice

Whilst there are commonalities in the problems faced by critical care survivors, recovery is highly individualized, and current support services do not have sufficient flexibility to cater for this. This study shows that many survivors experience after‐effects of critical care that outlast the support they are given. These longer‐term survivors are often excluded from research studies because of fears of recall bias, resulting in poor understanding of their experiences.
Biodiversity of pollen in indoor air samples as revealed by DNA metabarcoding
Authors: Korpelainen Helena , Pietiläinen Maria
Published: June 2017

We conducted DNA metabarcoding (based on the nuclear ITS2 region) to characterize indoor pollen samples (possibly accompanied by other plant fragments) and to discover whether there are seasonal changes in their taxonomic diversity. It was shown that DNA metabarcoding has potential to allow a good discovery of taxonomic diversity. The number of spermatophyte families and genera varied greatly among sampling sites (pooled results per building) and times, between 9–40 and 10–66, respectively. Comparable Shannon's diversity indices equaled 0.33–2.76 and 0.94–3.16. The total number of spermatophyte genera found during the study was 187, of which 43.9, 39.6, 7.5 and 9.1% represented wild, garden/crop and indoor house plants, and non‐domestic fruit or other plant material, respectively. Comparable proportions of individual sequences equaled 77.4, 18.8, 2.7 and 1.1%, respectively. When comparing plant diversities and taxonomic composition among buildings or between seasons, no obvious pattern was detected, except for the second summer, when pollen coming from outdoors was highly dominant and the proportions of likely allergens, birch, grass, alder and mugwort pollen, were very high. The average pairwise values of SørensenChao indices that were used to compare similarities for taxon composition between samples among the samples from the two university buildings, two nurseries and farmhouse equaled 0.514, 0.109, 0.564, 0.865 and 0.867, respectively, while the mean similarity index for all samples was 0.524. Cleaning frequency may strongly contribute to the observed diversity. The discovery of considerable diversities, including pollen coming from outside, in both winter and summer shows that substantial amounts of pollen produced in summer enter buildings and stay there throughout the year.
Linking the degree of virilization in females with congenital adrenal hyperplasia to genotype
Authors: Gurgov Semyon , Bernabé Kerlly J. , Stites John , Cunniff Christopher M. , Lin‐Su Karen , Felsen Diane , New Maria I. , Poppas Dix P.
Published: June 2017

Mutations of CYP21A2 variably decrease 21‐hydroxylase activity and result in a spectrum of disease expressions in patients with congenital adrenal hyperplasia (CAH). We examined the association between CYP21A2 mutations and virilization (Prader score) in females with CAH. The study population included 187 CAH females with fully characterized CYP21A2 mutations. One hundred fifty‐eight patients were sorted into groups by expected enzyme activity (percent of normal activity) of the less severely affected allele: (A) null, 0%; (B) I2G, 1%; (C) I172N, 2%; and (D) V281L, >2%. We observed an inverse relationship between virilization and residual enzyme activity (P < 0.001). Subjects in group A or B had a significantly higher likelihood (unadjusted odds ratio: 16; P < 0.001) of developing severe virilization compared with those in group C. Surprisingly, 24% of group D patients, whose mutation is usually associated with nonclassical (NC) CAH, had severe virilization. Among subjects with the NC P30L mutation, 66% expressed unexpected virilization. Virilization, usually leading to extensive reconstructive surgery, is highly likely in patients with null or I2G mutations; however, NC mutations (P30L/V281L) may also lead to unexpected virilization. These findings have implications for prenatal counseling and highlight the need for additional investigations into other factors that influence virilization in CAH.
The impact of Andean Patagonian mycoflora in the search for new lead molecules
Authors: Aqueveque Pedro M. , Cespedes Carlos L. , Kubo Isao , Seigler David S. , Sterner Olov
Published: June 2017

Secondary metabolites from fungi have become a major source of chemical innovation in programs searching for lead molecules with bioactivities, especially over the last 50 years. In this review, we discuss the fundamental considerations in the discovery of molecules for agricultural and medicinal uses. This group of organisms possesses a strong potential for scientific and industrial communities. Recently, the incorporation of new technologies for the artificial cultivation of fungi and the use of better equipment to isolate and identify active metabolites has allowed the discovery of leading molecules for the design of new and safer drugs and pesticides. The geographical region including the Patagonian Andes mountains harbors a wide diversity of fungi, many of them still unknown and so far associated with Chilean–Argentinian Andean endemic forests. There have been very few chemical studies of the fungi located in this region. However, those few studies have allowed the discovery of new molecules. We argue that the richness of fungal biodiversity in this region offers an interesting source for the discovery of bioactive molecules for the basic and applied sciences.
Eosinophils in patients with lone atrial fibrillation
Authors: Chen Peng , Chen Junzhu , Xie Xudong , Zhu Junhui , Xia Liang
Published: June 2017

Background

Inflammation has been evidenced as a critical contributable mechanism for the atrial fibrillation (AF) onset and development. As the consistent inflammatory and oxidative marker, the effects of white blood cell (WBC) and its differential on lone atrial fibrillation (LAF) were investigated in the study.

Methods

A total of 126 patients with paroxysmal LAF who scheduled for rhythm control drug therapy and 120 age‐ and gender‐matched subjects in sinus rhythm were included sequentially. Peripheral blood sample and clinic data were collected during the first evaluation. Recurrence of AF was evaluated by outpatient clinics and telephone visits for the following 12 months.

Results

Peripheral eosinophil count, neutrophil count, and left atrial diameter (LAD) were significantly higher in LAF than control. Within a follow‐up of 12 months, 56 patients (44.4%) had developed AF recurrence. Patients with AF recurrence had higher eosinophil count and LAD. Univariable analyses showed a statistically significant relationship between eosinophil count (P = 0.042), LAD (P = 0.030), and AF recurrence. Multivariate logistic regression analysis showed that LAD (OR: 1.090 per 1 mm increase; 95% CI: 1.007–1.180; P = 0.032) and eosinophil (OR: 1.643 per 1 × 108/L increase; 95% CI: 1.047–2.578; P = 0.031) were independent predictors of AF recurrence during antiarrhythmic drug therapy.

Conclusion

Our results support the association of the WBC response and its components with the LAF. Especially, the peripheral eosinophil and LAD may play important roles in mediating inflammation and atrial remodeling in AF.
NAC transcription factor JUNGBRUNNEN1 enhances drought tolerance in tomato
Authors: Thirumalaikumar Venkatesh P. , Devkar Vikas , Mehterov Nikolay , Ali Shawkat , Ozgur Rengin , Turkan Ismail , Mueller‐Roeber Bernd , Balazadeh Salma
Published: June 2017

Water deficit (drought stress) massively restricts plant growth and the yield of crops; reducing the deleterious effects of drought is therefore of high agricultural relevance. Drought triggers diverse cellular processes including the inhibition of photosynthesis, the accumulation of cell‐damaging reactive oxygen species and gene expression reprogramming, besides others. Transcription factors (TF) are central regulators of transcriptional reprogramming and expression of many TF genes is affected by drought, including members of the NAC family. Here, we identify the NAC factor JUNGBRUNNEN1 (JUB1) as a regulator of drought tolerance in tomato (Solanum lycopersicum). Expression of tomato JUB1 (SlJUB1) is enhanced by various abiotic stresses, including drought. Inhibiting SlJUB1 by virus‐induced gene silencing drastically lowers drought tolerance concomitant with an increase in ion leakage, an elevation of hydrogen peroxide (H2O2) levels and a decrease in the expression of various drought‐responsive genes. In contrast, overexpression of AtJUB1 from Arabidopsis thaliana increases drought tolerance in tomato, alongside with a higher relative leaf water content during drought and reduced H2O2 levels. AtJUB1 was previously shown to stimulate expression of DREB2A, a TF involved in drought responses, and of the DELLA genes GAI and RGL1. We show here that SlJUB1 similarly controls the expression of the tomato orthologs SlDREB1, SlDREB2 and SlDELLA. Furthermore, AtJUB1 directly binds to the promoters of SlDREB1, SlDREB2 and SlDELLA in tomato. Our study highlights JUB1 as a transcriptional regulator of drought tolerance and suggests considerable conservation of the abiotic stress‐related gene regulatory networks controlled by this NAC factor between Arabidopsis and tomato.
In‐solution antibody harvesting with a plant‐produced hydrophobin–Protein A fusion
Authors: Kurppa Katri , Reuter Lauri J. , Ritala Anneli , Linder Markus B. , Joensuu Jussi J.
Published: June 2017

Purification is a bottleneck and a major cost factor in the production of antibodies. We set out to engineer a bifunctional fusion protein from two building blocks, Protein A and a hydrophobin, aiming at low‐cost and scalable antibody capturing in solutions. Immunoglobulin‐binding Protein A is widely used in affinity‐based purification. The hydrophobin fusion tag, on the other hand, has been shown to enable purification by two‐phase separation. Protein A was fused to two different hydrophobin tags, HFBI or II, and expressed transiently in Nicotiana benthamiana. The hydrophobins enhanced accumulation up to 35‐fold, yielding up to 25% of total soluble protein. Both fused and nonfused Protein A accumulated in protein bodies. Hence, the increased yield could not be attributed to HFB‐induced protein body formation. We also demonstrated production of HFBI–Protein A fusion protein in tobacco BY‐2 suspension cells in 30 l scale, with a yield of 35 mg/l. Efficient partitioning to the surfactant phase confirmed that the fusion proteins retained the amphipathic properties of the hydrophobin block. The reversible antibody‐binding capacity of the Protein A block was similar to the nonfused Protein A. The best‐performing fusion protein was tested in capturing antibodies from hybridoma culture supernatant with two‐phase separation. The fusion protein was able to carry target antibodies to the surfactant phase and subsequently release them back to the aqueous phase after a change in pH. This report demonstrates the potential of hydrophobin fusion proteins for novel applications, such as harvesting antibodies in solutions.
Multiplexed CRISPR/Cas9‐mediated metabolic engineering of γ‐aminobutyric acid levels in Solanum lycopersicum
Authors: Li Rui , Li Ran , Li Xindi , Fu Daqi , Zhu Benzhong , Tian Huiqin , Luo Yunbo , Zhu Hongliang
Published: June 2017

In recent years, the type II CRISPR system has become a widely used and robust technique to implement site‐directed mutagenesis in a variety of species including model and crop plants. However, few studies manipulated metabolic pathways in plants using the CRISPR system. Here, we introduced the pYLCRISPR/Cas9 system with one or two single‐site guide RNAs to target the tomato phytoene desaturase gene. An obvious albino phenotype was observed in T0 regenerated plants, and more than 61% of the desired target sites were edited. Furthermore, we manipulated the γ‐aminobutyric acid (GABA) shunt in tomatoes using a multiplex pYLCRISPR/Cas9 system that targeted five key genes. Fifty‐three genome‐edited plants were obtained following single plant transformation, and these samples represented single to quadruple mutants. The GABA accumulation in both the leaves and fruits of genomically edited lines was significantly enhanced, and the GABA content in the leaves of quadruple mutants was 19‐fold higher than that in wild‐type plants. Our data demonstrate that the multiplex CRISPR/Cas9 system can be exploited to precisely edit tomato genomic sequences and effectively create multisite knockout mutations, which could shed new light on plant metabolic engineering regulations.
RESISTANCE TO POWDERY MILDEW8.1 boosts pattern‐triggered immunity against multiple pathogens in Arabidopsis and rice
Authors: Li Yan , Zhang Yong , Wang Qing‐Xia , Wang Ting‐Ting , Cao Xiao‐Long , Zhao Zhi‐Xue , Zhao Sheng‐Li , Xu Yong‐Ju , Xiao Zhi‐Yuan , Li Jin‐Lu , Fan Jing , Yang Hui , Huang Fu , Xiao Shunyuan , Wang Wen‐Ming
Published: June 2017

The Arabidopsis gene RESISTANCE TO POWDERY MILDEW8.1 (RPW8.1) confers resistance to virulent fungal and oomycete pathogens that cause powdery mildew and downy mildew, respectively. However, the underlying mechanism remains unclear. Here, we show that ectopic expression of RPW8.1 boosts pattern‐triggered immunity (PTI) resulting in enhanced resistance against different pathogens in both Arabidopsis and rice. In Arabidopsis, transcriptome analysis revealed that ectopic expression of RPW8.1‐YFP constitutively up‐regulates expression of many pathogen‐associated molecular pattern (PAMP‐)‐inducible genes. Consistently, upon PAMP application, the transgenic line expressing RPW8.1‐YFP exhibited more pronounced PTI responses such as callose deposition, production of reactive oxygen species, expression of defence‐related genes and hypersensitive response‐like cell death. Accordingly, the growth of a virulent bacterial pathogen was significantly inhibited in the transgenic lines expressing RPW8.1‐YFP. Conversely, impairment of the PTI signalling pathway from PAMP cognition to the immediate downstream relay of phosphorylation abolished or significantly compromised RPW8.1‐boosted PTI responses. In rice, heterologous expression of RPW8.1‐YFP also led to enhanced resistance to the blast fungus Pyricularia oryzae (syn. Magnaporthe oryzae) and the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo). Taken together, our data suggest a surprising mechanistic connection between RPW8.1 function and PTI, and demonstrate the potential of RPW8.1 as a transgene for engineering disease resistance across wide taxonomic lineages of plants.
Males benefit twice—The influence of equity on affective and physical attraction in couples
Authors: QUITTSCHALLE JANINE , HERZBERG PHILIPP Y.
Published: June 2017

We examined whether relationship satisfaction mediates the association between perceptions of equity in central areas of a relationship (feelings and attractiveness) and the experience of sexuality in a sample of 93 couples. Results reveal that greater levels of an individual's own relationship satisfaction significantly predict greater levels of an individual's affective and physical sexual attraction. Furthermore, findings also provide some support for the mediating role of relationship satisfaction between an individual's own equity perceptions and an individual's own experience of sexuality within the dyad. Moreover, males benefit from the females' perception of equity in the sense that equity considerations among females significantly contribute to their partners' relationship satisfaction, which, in turn, intensifies their partners' experience of passionate and emotional sex.
Determinants of red blood cell alloantibody detection duration: analysis of multiply alloimmunized patients supports peritransfusion factors
Authors: Noiret Lorette , Slater Amy , Higgins John M.
Published: June 2017

BACKGROUND

Alloimmunization to red blood cells (RBCs) can cause serious transfusion reactions and complicate the search for compatible blood products. Alloantibodies can be detected for periods ranging from a few days to several years, yet the mechanisms controlling the duration of detectability remain unknown. We studied the detection durations in patients forming multiple antibodies to investigate whether the duration is more strongly determined by conditions present at the time of each transfusion (peritransfusion factors) or by more stable patient‐specific factors likely to persist across transfusions.

STUDY DESIGN AND METHODS

We studied retrospective medical records for alloimmunized patients at Massachusetts General Hospital and Brigham and Women's Hospital (1461 patients; 2187 antibodies).

RESULTS

Antibodies discovered simultaneously in a patient shared similar fates: 76% persisted through the last screen or first became undetectable during the same screen. Simultaneously identified antibodies were also more persistent than sequentially identified antibodies (mean, 9.2 months vs. 4.9 months; p < 10−3). Within a patient, antibodies discovered simultaneously tended to be detected for similar periods of time (mean difference, 25 days), compared to the detection period for sequentially discovered antibodies (107 days, p < 10−3).

CONCLUSIONS

The similarity in detection duration of simultaneously identified antibodies suggests that peritransfusion factors are important determinants of alloantibody detectability and duration. We also find some evidence that detection durations for sequentially identified antibodies are also more highly correlated than those for randomly selected antibodies across all patients, suggesting that patient‐specific factors also play a role in determining alloantibody persistence.
Optimal Time Allocation between Idle and Active Time
Authors: Weber Michal , Gonen Limor D. , Westreich Sara , Spiegel Uriel
Published: June 2017

Idle time is an essential and valuable factor in the production of any service. While idle time is necessary and helpful for efficient and effective utilization of time, it also has a negative effect that managers try to minimize. This paper illustrates either analytically or numerically the different effects of idle time on total net revenue. It first presents the case in which idle time is determined arbitrarily, and then shows idle time that has no direct negative effect on total revenue but a positive effect on the efficient use of active time.
Introduction to Force-Dependent Kinematics: Theory and Application to Mandible Modeling
Authors: Skipper Andersen Michael , de Zee Mark , Damsgaard Michael , Nolte Daniel , Rasmussen John
Published: June 2017

Knowledge of the muscle, ligament, and joint forces is important when planning orthopedic surgeries. Since these quantities cannot be measured in vivo under normal circumstances, the best alternative is to estimate them using musculoskeletal models. These models typically assume idealized joints, which are sufficient for general investigations but insufficient if the joint in focus is far from an idealized joint. The purpose of this study was to provide the mathematical details of a novel musculoskeletal modeling approach, called force-dependent kinematics (FDK), capable of simultaneously computing muscle, ligament, and joint forces as well as internal joint displacements governed by contact surfaces and ligament structures. The method was implemented into the anybody modeling system and used to develop a subject-specific mandible model, which was compared to a point-on-plane (POP) model and validated against joint kinematics measured with a custom-built brace during unloaded emulated chewing, open and close, and protrusion movements. Generally, both joint models estimated the joint kinematics well with the POP model performing slightly better (root-mean-square-deviation (RMSD) of less than 0.75 mm for the POP model and 1.7 mm for the FDK model). However, substantial differences were observed when comparing the estimated joint forces (RMSD up to 24.7 N), demonstrating the dependency on the joint model. Although the presented mandible model still contains room for improvements, this study shows the capabilities of the FDK methodology for creating joint models that take the geometry and joint elasticity into account.
Reliability Optimization Allocation Method for Multifunction Systems With Multistate Units Based on Goal-Oriented Methodology
Authors: Yi Xiao-jian , Dhillon B. S. , Shi Jian , Mu Hai-na , Hou Peng
Published: June 2017

This paper proposes a new reliability optimization allocation for multifunction systems with multistate units based on goal-oriented (GO) methodology. First, this optimization allocation method is expounded in terms of establishing GO model, establishing reliability optimization allocation model, and solving algorithm. Then its process is formulated. Finally, the new method is applied in reliability optimization allocation of power-shift steering transmission (PSST), whose goal is to minimize the system cost. The results analysis shows that the system costs for different operation times turn to a relatively stable value, and the allocated reliability indices of unit are satisfied with engineering requirements. All in all, this new optimization allocation method can not only obtain the reasonable allocation results quickly and effectively, but it also can overcome the disadvantages of existing reliability optimization allocation methods for complex multifunction systems efficiently. In addition, the analysis process shows that the reliability optimization allocation method based on GO method can provide a new approach for the reliability optimization allocation of multifunction systems with multistate units.
Conjugation of PspA4Pro with Capsular Streptococcus pneumoniae Polysaccharide Serotype 14 Does Not Reduce the Induction of Cross-Reactive Antibodies
Authors: da Silva Míriam A. , Converso Thiago R. , Gonçalves Viviane M. , Leite Luciana C. C. , Tanizaki Martha M. , Barazzone Giovana C.
Published: June 2017

Current pneumococcal vaccines are composed of bacterial polysaccharides as antigens, plain or conjugated to carrier proteins. While efficacious against vaccine serotypes, epidemiologic data show an increasing incidence of infections caused by nonvaccine serotypes ofStreptococcus pneumoniae. The use of pneumococcal surface protein A (PspA) as a carrier protein in a conjugate vaccine could help prevent serotype replacement by increasing vaccine coverage and reducing selective pressure ofS. pneumoniaeserotypes. PspA is present in all pneumococcal strains, is highly immunogenic, and is known to induce protective antibodies. Based on its sequence, PspA has been classified into three families and six clades. A PspA fragment derived from family 2, clade 4 (PspA4Pro), was shown to generate antibodies with a broad range of cross-reactivity, across clades and families. Here, PspA4Pro was modified and conjugated to capsular polysaccharide serotype 14 (PS14). We investigated the impact of conjugation on the immune response induced to PspA4Pro and PS14. Mice immunized with the PS14-mPspA4Pro conjugate produced higher titers of anti-PS14 antibodies than the animals that received coadministered antigens. The conjugate induced antibodies with opsonophagocytic activity against PS14-carrying strains, as well as against a panel of strains bearing PspAs from five clades (encompassing families 1 and 2) bearing a non-PS14 serotype. Furthermore, mice immunized with PS14-mPspA4Pro were protected against nasal colonization with a nonrelatedS. pneumoniaestrain bearing PspA from clade 1, serotype 6B. These results demonstrate that the cross-reactivity mediated by PspA4Pro is retained following conjugation, supporting the use of PspA4 as a carrier protein in order to enhance pneumococcal vaccine coverage and encourage its further investigation as a candidate in future vaccine designs.
Bioactive Immune Components of Anti-Diarrheagenic Enterotoxigenic Escherichia coli Hyperimmune Bovine Colostrum Products
Authors: Sears Khandra T. , Tennant Sharon M. , Reymann Mardi K. , Simon Raphael , Konstantopoulos Nicky , Blackwelder William C. , Barry Eileen M. , Pasetti Marcela F.
Published: June 2017

Diarrhea is a common illness among travelers to resource-limited countries, the most prevalent attributable agent being enterotoxigenic
Escherichia coli
(ETEC). At this time, there are no vaccines licensed specifically for the prevention of ETEC-induced traveler's diarrhea (TD), and this has propelled investigation of alternative preventive methods. Colostrum, the first milk expressed after birthing, is rich in immunoglobulins and innate immune components for protection of newborns against infectious agents. Hyperimmune bovine colostrum (HBC) produced by immunization of cows during gestation (and containing high levels of specific antibodies) is a practical and effective prophylactic tool against gastrointestinal illnesses. A commercial HBC product, Travelan, is available for prevention of ETEC-induced diarrhea. Despite its demonstrated clinical efficacy, the underlying immune components and antimicrobial activity that contribute to protection remain undefined. We investigated innate and adaptive immune components of several commercial HBC products formulated to reduce the risk of ETEC-induced diarrhea, including Travelan and IMM-124E, a newer product that has broader gastrointestinal health benefits. The immune components measured included total and ETEC-specific IgG, total IgA, cytokines, growth factors, and lactoferrin. HBC products contained high levels of IgG specific for multiple ETEC antigens, including O-polysaccharide 78 and colonization factor antigen I (CFA/I) present in the administered vaccines. Antimicrobial activity was measured
in vitro
using novel functional assays. HBC greatly reduced ETEC motility in soft agar and exhibited bactericidal activity in the presence of complement. We have identified immune components and antimicrobial activity potentially involved in the prevention of ETEC infection by HBC
in vivo
.
Cross-sectional surveillance study to phenotype lorry drivers’ sedentary behaviours, physical activity and cardio-metabolic health
Authors: Varela-Mato Veronica , O’Shea Orlagh , King James A , Yates Thomas , Stensel David J , Biddle Stuart JH , Nimmo Myra A , Clemes Stacy A
Published: June 2017

Objectives

Elevated risk factors for a number of chronic diseases have been identified in lorry drivers. Unhealthy lifestyle behaviours such as a lack of physical activity (PA) and high levels of sedentary behaviour (sitting) likely contribute to this elevated risk. This study behaviourally phenotyped UK lorry drivers’ sedentary and non-sedentary behaviours during workdays and non-workdays and examined markers of drivers cardio-metabolic health.

Setting

A transport company from the East Midlands, UK.

Participants

A sample of 159 male heavy goods vehicle drivers (91% white European; (median (range)) age: 50 (24, 67) years) completed the health assessments. 87 (age: 50.0 (25.0, 65.0); body mass index (BMI): 27.7 (19.6, 43.4) kg/m2) provided objective information on sedentary and non-sedentary time.

Outcomes

Participants self-reported their sociodemographic information. Primary outcomes: sedentary behaviour and PA, assessed over 7 days using an activPAL3 inclinometer. Cardio-metabolic markers included: blood pressure (BP), heart rate, waist circumference (WC), hip circumference, body composition and fasted capillary blood glucose, triglycerides, high-density lipopreotein cholesterol, low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels. These cardio-metabolic markers were treated as secondary outcomes.

Results

Lorry drivers presented an unhealthy cardio-metabolic health profile (median (IQR) systolic BP: 129 (108.5, 164) mm Hg; diastolic BP: 81 (63, 104) mm Hg; BMI: 29 (20, 47) kg/m2; WC: 102 (77.5, 146.5) cm; LDL-C: 3 (1, 6) mmol/L; TC: 4.9 (3, 7.5) mmol/L). 84% were overweight or obese, 43% had type 2 diabetes or prediabetes and 34% had the metabolic syndrome. The subsample of lorry drivers with objective postural data (n=87) accumulated 13 hours/day and 8 hours/day of sedentary behaviour on workdays and non-workdays (p<0.001), respectively. On average, drivers accrued 12 min/day on workdays and 6 min/day on non-workdays of moderate-to-vigorous PA (MVPA).

Conclusion

Lorry drivers demonstrate a high-risk cardio-metabolic profile and are highly sedentary and physically inactive. Interventions to reduce sitting and increase MVPA during breaks and leisure time to improve cardio-metabolic health are urgently needed. Educational programmes to raise awareness about diet and exercise are recommended.
Filling the gaps in SARDs research: collection and linkage of administrative health data and self-reported survey data for a general population-based cohort of individuals with and without diagnoses of systemic autoimmune rheumatic disease (SARDs) from British Columbia, Canada
Authors: McCormick Natalie , Reimer Kathryn , Famouri Ali , Marra Carlo A , Aviña-Zubieta J. Antonio
Published: June 2017

Purpose

Systemic autoimmune rheumatic diseases (SARDs) are a group of debilitating autoimmune diseases, including systemic lupus erythematosus and related disorders. Assessing the healthcare and economic burden of SARDs has been challenging: while administrative databases can be used to determine healthcare utilisation and costs with minimal selection and recall bias, other health, sociodemographic and economic data have typically been sourced from highly selected, clinic-based cohorts. To address these gaps, we are collecting self-reported survey data from a general population-based cohort of individuals with and without SARDs and linking it to their longitudinal administrative health data.

Participants

Using administrative data from the province of British Columbia (BC), Canada, we established a population-based cohort of all BC adults receiving care for SARDs during 1996–2010 (n=20 729) and non-SARD individuals randomly selected from the general population. BC Ministry of Health granted us contact information for 12 000 SARD and non-SARD individuals, who were recruited to complete the surveys by mail or online.

Findings to date

Four hundred individuals were initially invited to participate, with 135 (34%) consenting and 127 (94%) submitting the first survey (72% completed online). Sixty-three (49.6%) reported ≥1 SARD diagnosis. The non-SARDs group (n=64) was 92% female with mean age 57.0±11.6 years. The SARDs group (n=63) was 94% female with mean age 56.5±13.1 years. Forty-eight per cent of those with SARDs were current-or-former smokers (mean 10.6±16.2 pack-years), and 33% were overweight or obese (mean body mass index of 24.4±5.3).

Future plans

Health and productivity data collected from the surveys will be linked to participants’ administrative health data from the years 1990–2013, allowing us to determine the healthcare and lost productivity costs of SARDs, and assess the impact of patient-reported variables on utilisation, costs, disability and clinical outcomes. Findings will be disseminated through scientific conferences and peer-reviewed journals.
Incidence of diabetes-related complications in Chinese patients with type 1 diabetes: a population-based longitudinal cohort study in Taiwan
Authors: Ou Huang-Tz , Lee Tsung-Ying , Li Chung-Yi , Wu Jin-Shang , Sun Zih-Jie
Published: June 2017

Objective

To estimate the incidence densities and cumulative incidence of diabetes-related complications in patients with type 1 diabetes for a maximum of 15-year follow-up. The estimations were further stratified by gender and age at diagnosis (ie, early onset: 0–12 years, late onset:≥13 years).

Design

A population-based retrospective longitudinal cohort study.

Setting

Taiwan’s National Health Insurance medical claims.

Participants

4007 patients newly diagnosed with type 1 diabetes were identified during 1999–2012.

Outcome measures

Acute complications included diabetic ketoacidosis (DKA) and hypoglycaemia. Chronic complications were cardiovascular diseases (CVD), retinopathy, neuropathy and nephropathy.

Results

The incidence density of retinopathy was greatest (97.74 per 1000 person-years), followed by those of nephropathy (31.36), neuropathy (23.93) and CVD (4.39). Among acute complications, the incidence density of DKA was greatest (121.11 per 1000 person-years). The cumulative incidences of acute complications after 12 years following diagnosis were estimated to be 52.1%, 36.1% and 4.1% for DKA, outpatient hypoglycaemia and hospitalised hypoglycaemia, respectively. For chronic complications, the cumulative incidence of retinopathy after 12 years following diagnosis was greatest (65.2%), followed by those of nephropathy (30.2%), neuropathy (23.7%) and CVD (4.1%). Females with late-onset diabetes were greatly affected by advanced retinopathy (ie, sight-threatening diabetic retinopathy) and hospitalised hypoglycaemia, whereas those with early-onset diabetes were more vulnerable to DKA. Chronic complications were more commonly seen in late-onset diabetes, whereas early-onset diabetes were most affected by acute complications.

Conclusions

Ethnic Chinese patients with type 1 diabetes were greatly affected by DKA and retinopathy. The incidence of diabetes-related complications differed by age at diagnosis and sex.
The impact of the asylum process on mental health: a longitudinal study of unaccompanied refugee minors in Norway
Authors: Jakobsen Marianne , Meyer DeMott Melinda Ashley , Wentzel-Larsen Tore , Heir Trond
Published: June 2017

Objectives

To examine the mental health of unaccompanied refugee minors prospectively during the asylum-seeking process, with a focus on specific stages in the asylum process, such as age assessment, placement in a supportive or non-supportive facility and final decision on the asylum applications.

Design

This was a2½ year follow-up study of unaccompanied minors (UM) seeking asylum in Norway. Data were collected within three weeks (n=138) and at 4 months (n=101), 15 months (n=84) and 26 months (n=69) after arrival.

Setting

Initially in an observation and orientation centre for unaccompanied asylum-seeking adolescents, and subsequently wherever the UM were located in other refugee facilities in Norway.

Participants

Male UM from Afghanistan, Somalia, Algeria and Iran.

Main outcome measures

Mental health symptoms assessed by Hopkins Symptom Checklist-25 and Harvard Trauma Questionnaire.

Results

At the group level, the young asylum seekers reported high levels of psychological distress on arrival and symptom levels that stayed relatively unchanged over time. According to age-assessment procedures, 56% of the population were not recognised as minors. Subsequent placement in a low-support facility was associated with higher levels of psychological distress in the follow-up period. Those who were placed in a reception centre for adults had higher levels of psychological distress symptoms both after 15 months and 26 months compared with the remaining participants who were placed in reception centres for youth. Refusal of asylum was highly associated with higher levels of psychological distress.

Conclusion

Mental health trajectory of young asylum seekers appears to be negatively affected by low support and refusal of asylum.
Outpatient percutaneous native renal biopsy: safety profile in a large monocentric cohort
Authors: Roccatello Dario , Sciascia Savino , Rossi Daniela , Naretto Carla , Bazzan Mario , Solfietti Laura , Baldovino Simone , Menegatti Elisa
Published: June 2017

Objectives

We aim to evaluate the safety of performing percutaneous native kidney biopsy (PKB) as an outpatient procedure (implying an observation period of 6 hours) compared with the traditional inpatient policy.

Design, setting, participants and measurements

Group I, in whom PKB was performed in the outpatient department (2012–2016) and followed by 6 hours’ observation period and then by regular outpatient visits and group II, in whom PKB was performed and followed by at least 1 day hospital admission. Group II included retrospectively retrieved patients who underwent PKB in our Institution between January 2000 and November 2012 as an inpatient procedure. All biopsies were performed by a single nephrologist following a structured protocol.

Results

462 biopsies were reviewed, 210 (45.5%) of patients were women and the mean age was 54.7±17.9 years. One hundred and twenty-nine (27.9%) of these biopsies were performed in outpatients. A total of 36 (7.8%) of patients developed a complication, and of those, 9 (1.9%) suffered for a major complication (arteriovenous fistula (six cases, 1.2%), ischaemic stroke (2; 0.4%), thromboembolic pulmonary embolism (1; 0.2%)) and 27 (5.8%) for minor(macroscopic haematuria (12 cases, 2.6%), haematomas on sonography not requiring intervention (15 cases, 3.2%)). When comparing the complication rate between groups I and II, no statical difference was observed. When analysing together both groups, after multivariate analysis, serum creatinine >3 mg/dL (OR 2.03, 95% CI 1.18 to 6.81) and known severe hypertension (OR 2.01, 95% CI 1.2 to 4.7) were found to be independent risk factors for minor and major complications, respectively. Conversely, we found no association of risk with the number of biopsy passes, gender, age, diagnosis, presence of haematuria before the kidney biopsy nor the degree of proteinuria.

Conclusions

Outpatient biopsy could be a valuable, safe and perhaps cost-effective method of obtaining diagnostic renal tissue in the majority of patients.
The CLOSED trial; CLOnidine compared with midazolam for SEDation of paediatric patients in the intensive care unit: study protocol for a multicentre randomised controlled trial
Authors: Neubert Antje , Baarslag Manuel Alberto , Dijk Monique van , Rosmalen Joost van , Standing Joseph F , Sheng Yucheng , Rascher Wolfgang , Roberts Deborah , Winslade Jackie , Rawcliffe Louise , Hanning Sara M , Metsvaht Tuuli , Giannuzzi Viviana , Larsson Peter , Pokorná Pavla , Simonetti Alessandra , Tibboel Dick
Published: June 2017

Introduction

Sedation is an essential part of paediatric critical care. Midazolam, often in combination with opioids, is the current gold standard drug. However, as it is a far-from-ideal agent, clonidine is increasingly being used in children. This drug is prescribed off-label for this indication, as many drugs in paediatrics are. Therefore, the CLOSED trial aims to provide data on the pharmacokinetics, safety and efficacy of clonidine for the sedation of mechanically ventilated patients in order to obtain a paediatric-use marketing authorisation.

Methods and analysis

The CLOSED study is a multicentre, double-blind, randomised, active-controlled non-inferiority trial with a 1:1 randomisation between clonidine and midazolam. Both treatment groups are stratified according to age in three groups with the same size: <28 days (n=100), 28 days to <2 years (n=100) and 2–18 years (n=100). The primary end point is defined as the occurrence of sedation failure within the study period. Secondary end points include a pharmacokinetic/pharmacodynamic relationship, pharmacogenetics, occurrence of delirium and withdrawal syndrome, opioid consumption and neurodevelopment in the neonatal age group. Logistic regression will be used for the primary end point, appropriate statistics will be used for the secondary end points.

Ethics

Written informed consent will be obtained from the parents/caregivers. Verbal or deferred consent will be used in the sites where national legislation allows. The study has institutional review board approval at recruiting sites. The results will be published in a peer-reviewed journal and shared with the worldwide medical community.

Trial Registration

EudraCT: 2014-003582-24; Clinicaltrials.gov:NCT02509273; pre-results.