Rhesus macaques as a tractable physiological model of human ageing.
Research in the basic biology of ageing is increasingly identifying mechanisms and modifiers of ageing in short-lived organisms such as worms and mice. The ultimate goal of such work is to improve human health, particularly in the growing segment of the population surviving into old age. Thus far, few interventions have robustly transcended species boundaries in the laboratory, suggesting that changes in approach are needed to avoid costly failures in translational human research. In this review, we discuss both well-established and alternative model organisms for ageing research and outline how research in nonhuman primates is sorely needed, first, to translate findings from short-lived organisms to humans, and second, to understand key aspects of ageing that are unique to primate biology. We focus on rhesus macaques as a particularly promising model organism for ageing research owing to their social and physiological similarity to humans as well as the existence of key resources that have been developed for this species. As a case study, we compare gene regulatory signatures of ageing in the peripheral immune system between humans and rhesus macaques from a free-ranging study population in Cayo Santiago. We show that both mRNA expression and DNA methylation signatures of immune ageing are broadly shared between macaques and humans, indicating strong conservation of the trajectory of ageing in the immune system. We conclude with a review of key issues in the biology of ageing for which macaques and other nonhuman primates may uniquely contribute valuable insights, including the effects of social gradients on health and ageing. We anticipate that continuing research in rhesus macaques and other nonhuman primates will play a critical role in conjunction with the model organism and human biodemographic research in ultimately improving translational outcomes and extending health and longevity in our ageing population. This article is part of the theme issue 'Evolution of the primate ageing process'.


Communication of radiation-induced signals in vivo between DNA repair deficient and proficient medaka (Oryzias latipes).
Radiation-induced bystander effects are established consequences of exposure to ionizing radiation. The operation of this mechanism has been seen in vitro and also between fish, mammals, and plants in vive where stress signals from treated organisms induce responses in neighbors. In vitro research shows that DNA repair deficient cells produce more toxic bystander responses. To test this in vivo two strains of Japanese medaka were tested. One is a mutant, repair deficient strain (ric2) and the other, the wildtype repair proficient strain (CAB). Irradiated fish swam with unirradiated partners in a strain mix and match protocol. The data suggest that medaka produce signals, when exposed to radiation, that induce unirradiated fish ofthe same strain swimming with them to produce an altered response to that seen in bystanders to sham irradiated fish. More apoptosis was seen in bystanders to repair deficient fish. When the strains are mixed, the bystanders of either strain respond like the donor strain. Measurements of Bcl-2 and cmyc proteins in the explants confirmed these observations. A possible role for p53 was also identified in that the use of reporters with mutant p53 demonstrated that CAB signals killed all the reporter cells by apoptosis. Use of a similar but p53 wildtype cell line had no such effect. The data add to the body of knowledge showing that bystander signals operate at hierarchical levels of organization greater than the individual and may therefore have relevance in radioecology and (eco)systems biology.


How Visual Management for Continuous Improvement Might Guide and Affect Hospital Staff: A Case Study.
Visual management (VM) tools such as whiteboards, often employed in Lean thinking applications, are intended to be helpful in improving work processes in different industries including health care. It remains unclear, however, how VM is actually applied in health care Lean interventions and how it might influence the clinical staff. We therefore examined how Lean-inspired VM using whiteboards for continuous improvement efforts related to the hospital staff's work and collaboration. Within a case study design, we combined semistructured interviews, nonparticipant observations, and photography on 2 cardiology wards. The fate of VM differed between the 2 wards; in one, it was well received by the staff and enhanced continuous improvement efforts, whereas in the other ward, it was not perceived to fit in the work flow or to make enough sense in order to be sustained. Visual management may enable the staff and managers to allow communication across time and facilitate teamwork by enabling the inclusion of team members who are not present simultaneously; however, its adoption and value seem contingent on finding a good fit with the local context. A combination of continuous improvement and VM may be helpful in keeping the staff engaged in the change process in the long run.


Optical spatial tracking using coherent detection in the pupil plane.
Design considerations for a heterodyne spatial tracking system utilizing pupil plane processing techniques and its advantages over traditional focal plane processing are described. Noise performance bounds, optimal and suboptimal local oscillator distributions, pull-in performance, and applications other than spatial tracking are discussed. Experimental verification of a one-axis closed-loop tracking system is presented.


Repair of the inferior vena cava with autogenous peritoneo-fascial patch graft following abdominal trauma: a case report.
Abdominal vascular injuries are among the most challenging and lethal injuries in traumatized patients. Inferior vena cava is the most frequently injured vein during the blunt or penetrating trauma. The primary repair, end to end anastomosis, endovascular stenting, or graft interposition with autogenous or synthetic materials should be considered in selected cases. However, in cases the synthetic graft was preferred, intestinal contaminations due to small or large bowel perforation accompanying the trauma have been cited as a limiting factor for the use of such grafts as in the current case. However, a previous history of lower leg variceal surgery prevents the use of great saphenous vein as a graft. So in the present case, the authors report a patient with inferior vena cava injury repaired with autogenous peritoneo-fascial graft. The authors have used APF graft in traumatic inferior vena cava injury for the first time.


[Hyperphosphatemic pseudotumoral calcinosis due to FGF23 mutation with secondary amyloidosis].
A 44 years old man was admitted for nephrotic syndrome and rapidly progressive renal failure. Two firm, tumour-like masses were localized around the left shoulder and the right hip joint. Since the age of 8 years old, the patient had a history of metastatic calcification of the soft tissues suggesting hyperphosphatemic pseudotumoral calcinosis. Despite treatment for a long time with phosphate binders the metastatic calcinosis had to be removed with several surgeries. The patient had also a history of recurrent fever associated with pain localized toward the two masses and underwent multiple antibiotic courses. Laboratory findings at admission confirmed nephrotic syndrome. S-creatinine was 2.8 mg/dl. Calcium was 8.4 mg/dl, Phosphorus 8.2 mg/dl, PTH 80 pg/ml, 25 (OH)VitD 8 ng/ml. Serum amyloid A was slightly increased. We performed renal biopsy and we found AA amyloid deposits involving the mesangium and the tubules. The bone marrow biopsy revealed the presence of AA amyloid in the vascular walls. During the next two months renal failure rapidly progressed and the patient started hemodialysis treatment. We performed genetic analysis that confirmed homozygous mutation of the FGF23 gene. After 14 months on hemodialysis, the patient's lesions are remarkably and significantly reduced in dimension. The current phosphate binder therapy is based on sevelamer and lanthanum carbonate. Serum amyloid A is persistently slightly increased as well as C reactive protein. Proteinuria is in the nephrotic range without nephrotic syndrome.


Filtration kinetics of chitosan separation by electrofiltration.
Downstream processing of chitosan requires several technological steps that contribute to the total production costs. Precipitation and especially evaporation are energy-consuming processes, resulting in higher costs and limiting industrial scale production. This study investigated the filtration kinetics of chitosan derived from cell walls of fungi and from exoskeletons of arthropods by electrofiltration, an alternative method, thus reducing the downstream processing steps and costs. Experiments with different voltages and pressures were conducted in order to demonstrate the effect of both parameters on filtration kinetics. The concentration of the biopolymer was obtained by the average factor of 40 by applying an electric field of 4 V/mm and pressure of 4 bars. A series of analytical experiments demonstrated the lack of structural and functional changes in chitosan molecules after electrofiltration. These results, combined with the reduction of energy and processing time, define the investigated method as a promising downstream step in the chitosan production technology.


Hormone replacement therapy and Alzheimer's disease.
There is ample evidence to show the beneficial effect of estrogen on the risk and course of Alzheimer's disease (AD). Estrogen may play a role in the pathophysiology of AD through improvement of cerebral blood flow, stimulation of the neuron or gliacyte and interaction with genetic factors. Most etiological studies of estrogen replacement therapy and AD have been retrospective studies. In these studies, the history of estrogen use was obtained from an informant, limiting the validity of the findings. Of the three follow-up studies conducted to date, one has failed to show a protective effect. There is some evidence for a synergistic effect between estrogen and the genetic factors involved in AD. However, up until now, studies of estrogen replacement therapy have generally been too small and of low validity. Large scale, long-term population studies may clarify the role of estrogen replacement therapy in the prevention and therapy of AD.


Biological Diversity and Evolution of Type IV Secretion Systems.
The bacterial type IV secretion systems (T4SSs) are a highly functionally and structurally diverse superfamily of secretion systems found in many species of Gram-negative and -positive bacteria. Collectively, the T4SSs can translocate DNA and monomeric and multimeric protein substrates to a variety of bacterial and eukaryotic cell types. Detailed phylogenomics analyses have established that the T4SSs evolved from ancient conjugation machines whose original functions were to disseminate mobile DNA elements within and between bacterial species. How members of the T4SS superfamily evolved to recognize and translocate specific substrate repertoires to prokaryotic or eukaryotic target cells is a fascinating question from evolutionary, biological, and structural perspectives. In this chapter, we will summarize recent findings that have shaped our current view of the biological diversity of the T4SSs. We focus mainly on two subtypes, designated as the types IVA (T4ASS) and IVB (T4BSS) systems that respectively are represented by the paradigmatic Agrobacterium tumefaciens VirB/VirD4 and Legionella pneumophila Dot/Icm T4SSs. We present current information about the composition and architectures of these representative systems. We also describe how these and a few related T4ASS and T4BSS members evolved as specialized nanomachines through acquisition of novel domains or subunits, a process that ultimately generated extensive genetic and structural mosaicism among this secretion superfamily. Finally, we present new phylogenomics information establishing that the T4BSSs are much more broadly distributed than initially envisioned.


Institutional review board approval: why it matters.
The modern institutional review boards originated in the 1970s. They exist to protect human subjects participating in research from potential harm. The Belmont Report provided the ethical principles (respect for persons, beneficence, and justice) that should be observed while conducting research on human subjects. Compliance with the ethical principles of the Belmont Report is a first step in successful submissions to an institutional review board. Regulations regarding conflict of interest represent an attempt to ensure that research is not biased by financial or other interest and to maintain public trust.


Honey and metformin ameliorated diabetes-induced damages in testes of rat; correlation with hormonal changes.
The global prevalence of diabetes mellitus is on rise. Diabetes-induced oxidative stress has been known to affect liver, pancreas, kidney and reproductive organs pathologically. Honey is a natural product of bee with antioxidant properties. Current study aimed to analyze the protective effects of Metformin (MF) alone and MF+ natural honey co-administration on diabetes-induced histological derangements in testis of rats. Thirty six, mature male Wistar rats were randomly divided into six groups including; control, honey-dosed non-diabetic, diabetes-induced (65 mg/kg, single dose), honey-administrated diabetic (1.0 g/kg/day), Metformin-received diabetic (100 mg/kg/day), Metformin and honey-co-treated diabetic which were followed 40 days. The animals were anesthetized by diethyl ether and the blood samples were collected. The serum levels of testosterone, Insulin, LH and FSH analyzed using antibody enzyme immunoassay method. The testicular tissues were dissected out and underwent to histological analyses. The biochemical analyses revealed that the diabetes resulted in significantly reduced testosterone (p<0.01), LH and FSH (P<0.01, 0.001) levels in serum. Light microscopic analyses showed remarkable (p<0.01) reduction in seminiferous tubules diameter (STD), spermiogenesis index (SPI) and thickness of the epithelium in the diabetic group versus control and co-treated groups. Simultaneous administration of the honey with MF could fairly up-regulate testosterone, LH and FSH levels. The animals in metformin and honey-treated group exhibited with improved tubules atrophy, elevated spermiogenesis index and germinal epithelium thickness. Our data indicated that co-administration of Metformin and honey could inhibit the diabetes-induced damages in testicular tissue. Moreover, the simultaneous administration of metformin and honey up-regulated the diabetes-reduced insulin, LH, FSH and testosterone levels. This article extracted from M.Sc. thesis. (Ozra Nasrolahi).


Radiolabeled iododeoxyuridine: safety evaluation.
The emphasis of radiolabeled iododeoxyuridine (*IUdR) research at our institution to date has been to assess its safety as a potential therapeutic agent. Toward this goal, we have performed preclinical and clinical studies, using various routes of administration, to detect adverse changes in normal tissues in both humans and animals. As IUdR is rapidly dehalogenated by the liver, the intravenous route is unlikely to be successful in therapeutic efforts. We have therefore focused our attention on more "protected" routes: intra-arterial and intravesicular administration. Studies were performed in farm pigs after multiple administrations of [125I]IUdR into the aorta, carotid artery and bladder. IUdR and metabolites were measured in venous blood samples at appropriate time intervals after administration, after which histologic examination of tissues was performed. Studies in human have been performed after intra-arterial administration of [123I]IUdR in patients with liver metastases and intravesicular administration in patients with bladder carcinoma, initially using [123I]IUdR and currently using both [123I]IUdR and [125I]IUdR. Blood samples for pharmacokinetics and metabolite analysis and tissue for autoradiography (when feasible) have been obtained. To date, no evidence of adverse effects on normal tissue or alteration of hematologic or metabolic indices have been seen in pigs or humans. When instilled in the bladder, there is little leakage of IUdR in the circulation. When [125I]IUdR is used as a therapeutic agent, we anticipate little or no effect on normal tissues.


Utilizing genotype imputation for the augmentation of sequence data.
In recent years, capabilities for genotyping large sets of single nucleotide polymorphisms (SNPs) has increased considerably with the ability to genotype over 1 million SNP markers across the genome. This advancement in technology has led to an increase in the number of genome-wide association studies (GWAS) for various complex traits. These GWAS have resulted in the implication of over 1500 SNPs associated with disease traits. However, the SNPs identified from these GWAS are not necessarily the functional variants. Therefore, the next phase in GWAS will involve the refining of these putative loci. A next step for GWAS would be to catalog all variants, especially rarer variants, within the detected loci, followed by the association analysis of the detected variants with the disease trait. However, sequencing a locus in a large number of subjects is still relatively expensive. A more cost effective approach would be to sequence a portion of the individuals, followed by the application of genotype imputation methods for imputing markers in the remaining individuals. A potentially attractive alternative option would be to impute based on the 1000 Genomes Project; however, this has the drawbacks of using a reference population that does not necessarily match the disease status and LD pattern of the study population. We explored a variety of approaches for carrying out the imputation using a reference panel consisting of sequence data for a fraction of the study participants using data from both a candidate gene sequencing study and the 1000 Genomes Project. Imputation of genetic variation based on a proportion of sequenced samples is feasible. Our results indicate the following sequencing study design guidelines which take advantage of the recent advances in genotype imputation methodology: Select the largest and most diverse reference panel for sequencing and genotype as many "anchor" markers as possible.


Effect of intra-articular administration of superparamagnetic iron oxide nanoparticles (SPIONs) for MRI assessment of the cartilage barrier in a large animal model.
Early diagnosis of cartilage disease at a time when changes are limited to depletion of extracellular matrix components represents an important diagnostic target to reduce patient morbidity. This report is to present proof of concept for nanoparticle dependent cartilage barrier imaging in a large animal model including the use of clinical magnetic resonance imaging (MRI). Conditioned (following matrix depletion) and unconditioned porcine metacarpophalangeal cartilage was evaluated on the basis of fluorophore conjugated 30 nm and 80 nm spherical gold nanoparticle permeation and multiphoton laser scanning and bright field microscopy after autometallographic particle enhancement. Consequently, conditioned and unconditioned joints underwent MRI pre- and post-injection with 12 nm superparamagnetic iron oxide nanoparticles (SPIONs) to evaluate particle permeation in the context of matrix depletion and use of a clinical 1.5 Tesla MRI scanner. To gauge the potential pro-inflammatory effect of intra-articular nanoparticle delivery co-cultures of equine synovium and cartilage tissue were exposed to an escalating dose of SPIONs and IL-6, IL-10, IFN-γ and PGE2 were assessed in culture media. The chemotactic potential of growth media samples was subsequently assessed in transwell migration assays on isolated equine neutrophils. Results demonstrate an increase in MRI signal following conditioning of porcine joints which suggests that nanoparticle dependent compositional cartilage imaging is feasible. Tissue culture and neutrophil migration assays highlight a dose dependent inflammatory response following SPION exposure which at the imaging dose investigated was not different from controls. The preliminary safety and imaging data support the continued investigation of nanoparticle dependent compositional cartilage imaging. To our knowledge, this is the first report in using SPIONs as intra-articular MRI contrast agent for studying cartilage barrier function, which could potentially lead to a new diagnostic technique for early detection of cartilage disease.


Developmental profile of annexin IX and its possible role in programmed cell death of the Bombyx mori anterior silk gland.
During pupal metamorphosis, the anterior silk gland (ASG) of the silkworm, Bombyx mori, undergoes programmed cell death (PCD), which is triggered by 20-hydroxyecdysone (20E). Annexin IX (ANX IX) has been identified as a 20E-inducible gene in dying ASGs, and we show here that its expression is down-regulated in tissues destined to die but not in tissues that survive pupal metamorphosis. ANX IX expression was high in the ASGs during the feeding period, when the ecdysteroid titer was low, and decreased in response to the rising ecdysteroid titer that triggered pupal metamorphosis. Before gut purge, in vitro exposure of the ASGs to 20E levels corresponding to the ecdysteroid concentration present at the time of gut purge caused a decrease in ANX IX messenger RNA levels. Expression profiles of EcR and USP, and the 20E concentration-responses of these genes, indicate the importance of the relative abundance of EcR-A and EcR-B1 isoforms in ANX IX regulation. These results suggest an involvement of ANX IX in the determination of PCD timing by delaying or suppressing the response to the increase in hemolymph ecdysteroid concentration during the prepupal period.


Genetic diversity of group A rotavirus in swine in Canada.
Group A rotaviruses (RVA) in pigs have been poorly investigated in Canada. In a continued effort to fill this gap, ten finisher swine farms in Quebec, Canada, were sampled over a nine-month period. The presence of RVA was detected in healthy pigs on all farms investigated during the entire sampling period. The genotypes detected included G2, G5, G9 and G11; P[6], P[7], P[13], P[27] and P[34]; and I5 and I14. The predominant types were G2, P[13] and I5, which is different from previous global reports. Various fomites were consistently contaminated by RVA, suggesting that a resident viral flora remains in the farm environment and may play a role in the infection of incoming pigs. The results also suggest temporal or geographical specificities regarding strain distribution on pig farms.


Genotyping of CYP2C9 and VKORC1 polymorphisms predicts south Indian patients with deep vein thrombosis as fast metabolizers of warfarin/acenocoumarin.
Deep vein thrombosis (DVT) is a life-threatening disease. Warfarin and acenocoumarol are anticoagulants used to treat DVT and vary among individuals in terms of treatment response/toxicity. Single nucleotide polymorphisms (SNPs) in CYP2C9 and VKORC1 play a role in the pharmacokinetics and dynamics of warfarin and acenocoumarol and they determine the efficacy of treatment by controlling drug clearance in treated individuals. The aim of the current study was to genotype the critical SNPs of CYP2C9 and VKORC1 genes in a south Indian population in order to understand the metabolizer phenotype of patients with DVT. CYP2C9 (rs1799853, rs1057910, rs1057909, rs28371686) and VKORC1 (rs9923231) SNPs were genotyped in 124 cases of DVT. Genomic regions of these SNPs from genomic DNA were amplified with PCR and directly sequenced using Sanger sequencing except for the SNP rs1799853, which was detected using Sau96I restriction endonuclease-based digestion of variant alleles. Among south Indian patients with DVT, 6.5% (8/124) had the rs1799853 SNP of CYP2C9 and 11% (14/124) had the rs1057910 SNP while 16% (20/124) had the rs9923231 SNP of VKORC1 which were associated with the response to warfarin treatment. None of the patients tested positive for poor drug metabolizing genotypes of the CYP2C9 gene and only 1.6% of the south Indian population was sensitive to warfarin treatment. Genotyping results suggest that a relatively greater amount of the therapeutic drug is required to achieve/maintain the international normalized ratio (INR) in south Indian patients with DVT.


A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats.
The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study. In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250-3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments. DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count. Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males.


Associations of objectively measured physical activity and abdominal fat distribution.
Visceral adipose tissue (VAT) and physical activity are both independent predictors of Type 2 diabetes. Physical activity and overall obesity are inversely associated with each other. Yet the nature of the association between objectively measured dimensions of physical activity and abdominal fat distribution has not been well characterized. We aimed to do so in a middle-age to elderly population at high risk of diabetes. A cross-sectional analysis of 1134 participants of the ADDITION-PRO study. VAT and subcutaneous adipose tissue (SAT) were assessed one-dimensionally by ultrasonography and physical activity with combined accelerometry and HR monitoring. Linear regression of physical activity energy expenditure (PAEE) and time spent in different physical activity intensity levels on VAT and SAT was performed. Median body mass index (BMI) was 26.6 kg·m and PAEE was 28.1 kJ·kg·d, with 18.9 h·d spent sedentary, 4.5 h·d in light-intensity physical activity, and 0.4 h·d in moderate-intensity physical activity. PAEE was significantly negatively associated with VAT, and in women, PAEE was also significantly negatively associated with SAT. The difference in VAT was -1.1 mm (95% confidence interval [CI] = -1.8 to -0.3) per 10-kJ·kg·d increment, and the corresponding difference in SAT for women was -0.6 mm (95% CI = -1.2 to -0.04) in models adjusted for age, sex, and waist circumference. Exchanging 1 h of light physical activity with moderate physical activity was significantly associated with VAT (-4.5 mm, 95% CI = -7.6 to -1.5). Exchanging one sedentary hour with light physical activity was significantly associated with both VAT (-0.9 mm, 95% CI = -0.1 to -1.8) and SAT (-0.4 mm, 95% CI = -0.0 to -0.7). In this population with low physical activity levels, cross-sectional findings indicate that increasing overall physical activity and decreasing time spent sedentary is important to avoid the accumulation of metabolically deleterious VAT.


Exact feature extraction using finite rate of innovation principles with an application to image super-resolution.
The accurate registration of multiview images is of central importance in many advanced image processing applications. Image super-resolution, for example, is a typical application where the quality of the super-resolved image is degrading as registration errors increase. Popular registration methods are often based on features extracted from the acquired images. The accuracy of the registration is in this case directly related to the number of extracted features and to the precision at which the features are located: images are best registered when many features are found with a good precision. However, in low-resolution images, only a few features can be extracted and often with a poor precision. By taking a sampling perspective, we propose in this paper new methods for extracting features in low-resolution images in order to develop efficient registration techniques. We consider, in particular, the sampling theory of signals with finite rate of innovation and show that some features of interest for registration can be retrieved perfectly in this framework, thus allowing an exact registration. We also demonstrate through simulations that the sampling model which enables the use of finite rate of innovation principles is well suited for modeling the acquisition of images by a camera. Simulations of image registration and image super-resolution of artificially sampled images are first presented, analyzed and compared to traditional techniques. We finally present favorable experimental results of super-resolution of real images acquired by a digital camera available on the market.


Use of programme theory to understand the differential effects of interventions across socio-economic groups in systematic reviews-a systematic methodology review.
Systematic review guidance recommends the use of programme theory to inform considerations of if and how healthcare interventions may work differently across socio-economic status (SES) groups. This study aimed to address the lack of detail on how reviewers operationalise this in practice. A methodological systematic review was undertaken to assess if, how and the extent to which systematic reviewers operationalise the guidance on the use of programme theory in considerations of socio-economic inequalities in health. Multiple databases were searched from January 2013 to May 2016. Studies were included if they were systematic reviews assessing the effectiveness of an intervention and included data on SES. Two reviewers independently screened all studies, undertook quality assessment and extracted data. A narrative approach to synthesis was adopted. A total of 37 systematic reviews were included, 10 of which were explicit in the use of terminology for 'programme theory'. Twenty-nine studies used programme theory to inform both their a priori assumptions and explain their review findings. Of these, 22 incorporated considerations of both what and how interventions do/do not work in SES groups to both predict and explain their review findings. Thirteen studies acknowledged 24 unique theoretical references to support their assumptions of what or how interventions may have different effects in SES groups. Most reviewers used supplementary evidence to support their considerations of differential effectiveness. The majority of authors outlined a programme theory in the "Introduction" and "Discussion" sections of the review to inform their assumptions or provide explanations of what or how interventions may result in differential effects within or across SES groups. About a third of reviews used programme theory to inform the review analysis and/or synthesis. Few authors used programme theory to inform their inclusion criteria, data extraction or quality assessment. Twenty-one studies tested their a priori programme theory. The use of programme theory to inform considerations of if, what and how interventions lead to differential effects on health in different SES groups in the systematic review process is not yet widely adopted, is used implicitly, is often fragmented and is not implemented in a systematic way.


Increasing Prevalence of Myopia in Europe and the Impact of Education.
To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E(3)) Consortium. The E(3) Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Variation in age-specific myopia prevalence for differing years of birth and educational level. There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively-whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia.


Ultrasound Evaluation of a Single Treatment With a Temperature Controlled Multi-Frequency Monopolar Radio Frequency Device for the Improvement of Localized Adiposity on the Abdomen and Flanks
BACKGROUND AND OBJECTIVES: Energy modalities used for fat reduction include cryotherapy, focused and unfocused ultrasound, radiofrequency, and laser. Two devices have been proven to reduce fat layer thickness using ultrasound as measurement after a single treatment. We hypothesized that a novel, high frequency monopolar radiofrequency device could increase the fat temperature enough to reduce its thickness as measured by ultrasound, without excessively increasing the temperature of the skin, leading to a safe, tolerable, and clinically relevant reduction of fat. STUDY DESIGN/MATERIALS AND METHODS: A high frequency monopolar radiofrequency platform was used to treat twelve patients on the abdomen or flanks (truSculpt® 3D, Cutera, Brisbane, CA). Each patient received one treatment session, consisting of 15-minute increments for four areas (60 minutes total). Each area (approximately 144 cm2) was treated with a gliding handpiece technique to a skin temperature of 44-45˚C, correlating to in vivo measurements of the subcutaneous layer of >45˚C. Patients were evaluated at eight- and twelve-weeks following treatment. Clinical efficacy was measured using 360˚ positioned clinical photography. Fat layer reduction was measured with ultrasound. Safety was assessed by the treating physician; patient comfort was assessed during treatment via a 10-point pain scale. RESULTS: All patients responded to treatment. Ultrasound measurements indicated mean fat layer reduction of 4.6 mm, which correlated with a 24% reduction in fat layer thickness at 12 weeks. A significant improvement was noted between the 8-week and the 12-week follow up. A high level of inter-patient consistency was achieved with most patients (10/12= 83%) having an average fat thickness reduction of >20%. No adverse events were observed, and pain scores during the treatment session ranged from 2 to 4 out of 10. CONCLUSION: High frequency monopolar radiofrequency device produced consistent and statistically significant fat thickness reduction from a single 60-minute treatment session, with minimal discomfort and no demonstrated side effects. Results are comparable to other hypo- and hyper-thermic fat treatment technologies. KEY WORDS: fat reduction, radiofrequency, monopolar RF, fat thickness reduction, body sculpting J Drugs Dermatol. 2020;19(1):28-34. doi:10.36849/JDD.2020.4568


Calorie intake and patient outcomes in severe acute kidney injury: findings from The Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study trial.
Current practice in the delivery of caloric intake (DCI) in patients with severe acute kidney injury (AKI) receiving renal replacement therapy (RRT) is unknown. We aimed to describe calorie administration in patients enrolled in the Randomized Evaluation of Normal vs. Augmented Level of Replacement Therapy (RENAL) study and to assess the association between DCI and clinical outcomes. We performed a secondary analysis in 1456 patients from the RENAL trial. We measured the dose and evolution of DCI during treatment and analyzed its association with major clinical outcomes using multivariable logistic regression, Cox proportional hazards models, and time adjusted models. Overall, mean DCI during treatment in ICU was low at only 10.9 ± 9 Kcal/kg/day for non-survivors and 11 ± 9 Kcal/kg/day for survivors. Among patients with a lower DCI (below the median) 334 of 729 (45.8%) had died at 90-days after randomization compared with 316 of 727 (43.3%) patients with a higher DCI (above the median) (P = 0.34). On multivariable logistic regression analysis, mean DCI carried an odds ratio of 0.95 (95% confidence interval (CI): 0.91-1.00; P = 0.06) per 100 Kcal increase for 90-day mortality. DCI was not associated with significant differences in renal replacement (RRT) free days, mechanical ventilation free days, ICU free days and hospital free days. These findings remained essentially unaltered after time adjusted analysis and Cox proportional hazards modeling. In the RENAL study, mean DCI was low. Within the limits of such low caloric intake, greater DCI was not associated with improved clinical outcomes. ClinicalTrials.gov number, NCT00221013.


Childhood sexual and physical abuse as risk factors for the development of bulimia nervosa: a community-based case control study.
There were two aims: First, to determine whether sexual or physical abuse in childhood or adolescence increases the risk of developing bulimia nervosa, and second, to see whether any increase in risk is specific to bulimia nervosa rather than being common to psychiatric disorders in general. A case control design with individual matching was used. There were two related case control comparisons based on community samples. One hundred and two young adult women with bulimia nervosa were compared with 204 control subjects without an eating disorder, and with 102 control subjects with other psychiatric disorders, all recruited from the same community source. An investigator-based interview was used to assess sexual and physical abuse. Sexual abuse involving physical contact was reported by 35% of the cases of bulimia nervosa. It was more common among this group than among the normal controls. Physical abuse was also reported by a minority of the cases of bulimia nervosa, and was more common among this group than among the normal controls. However, there were no significant differences between the cases of bulimia nervosa and the controls with general psychiatric disorder, except in the category of repeated severe sexual abuse: this was more common among the cases of bulimia nervosa although present only in small numbers within these two groups. The findings indicate that sexual and physical abuse are both risk factors for the development of bulimia nervosa. However, they are not present in the majority of cases. This indicates that other risk factors must operate in these cases. Sexual and physical abuse do not appear to be risk factors specific to bulimia nervosa; rather, they appear to be risk factors for psychiatric disorder in general in young adult women.


Genomic approaches to the genetics of alcoholism.
When studying complex diseases such as alcoholism that develop as a result of numerous genetic and environmental factors, researchers can use the sequence data that have become available both for the human and for animal genomes. For these analyses, investigators are being aided by efforts to identify and characterize functionally relevant DNA sequences in the entire genomic DNA sequence--a process called annotation. Various bioinformatics and annotation tools can help in this enterprise. These include four primary approaches: (1) precomputed, annotated public Web sites that provide a plethora of information; (2) in-house analyses from which users can choose the appropriate analyses for their purposes; (3) Web-based annotation systems that analyze a user's DNA sequence; and (4) private resources that provide access to annotated genomic sequences at cost. In addition to careful study of the DNA sequence for clues about function, expression studies of mRNA levels using gene chips provide information about the activity levels of thousands of genes that may vary in different tissues, different animals and people, or under different environmental conditions.


Maternal perchlorate levels in women with borderline thyroid function during pregnancy and the cognitive development of their offspring: data from the Controlled Antenatal Thyroid Study.
Thyroid dysfunction is associated with impaired cognitive development. Perchlorate decreases thyroidal iodine uptake, potentially reducing thyroid hormone production. It is unclear whether perchlorate exposure in early life affects neurodevelopment. Historical cohort analysis. From 2002 to 2006, 21,846 women at gestational age <16 weeks recruited from antenatal clinics in Cardiff, UK and Turin, Italy were enrolled in the Controlled Antenatal Thyroid Screening Study (CATS). We undertook a retrospective analysis of 487 mother-child pairs in mothers who were hypothyroid/hypothyroxinemic during pregnancy and analyzed whether first trimester maternal perchlorate levels in the highest 10% of the study population were associated with increased odds of offspring IQ being in the lowest 10% at 3 years of age. Maternal urinary perchlorate, offspring IQ. Urine perchlorate was detectable in all women (median 2.58 μg/L); iodine levels were low (median 72 μg/L). Maternal perchlorate levels in the highest 10% of the population increased the odds of offspring IQ being in the lowest 10% OR = 3.14 (95% CI 1.38, 7.13) P = .006 with a greater negative impact observed on verbal OR = 3.14 (95% CI 1.42, 6.90) P = .005 than performance IQ. Maternal levothyroxine therapy did not reduce the negative impact of perchlorate on offspring IQ. This is the first study using individual-level patient data to study maternal perchlorate exposure and offspring neurodevelopment and suggests that high-end maternal perchlorate levels in hypothyroid/hypothyroxinemic pregnant women have an adverse effect on offspring cognitive development, not affected by maternal levothyroxine therapy. These results require replication in additional studies, including in the euthyroid population.


Noninvasive functional imaging of cerebral blood volume with vascular-space-occupancy (VASO) MRI.
Functional MRI (fMRI) based on changes in cerebral blood volume (CBV) can probe directly vasodilatation and vasoconstriction during brain activation or physiologic challenges, and can provide important insights into the mechanism of blood oxygenation level-dependent (BOLD) signal changes. At present, the most widely used CBV fMRI technique in humans is called vascular-space-occupancy (VASO) MRI, and this article provides a technical review of this method. VASO MRI utilizes T1 differences between blood and tissue to distinguish between these two compartments within a voxel, and employs a blood-nulling inversion recovery sequence to yield an MR signal proportional to 1 - CBV. As such, vasodilatation will result in a VASO signal decrease and vasoconstriction will have the reverse effect. The VASO technique can be performed dynamically with a temporal resolution comparable with several other fMRI methods, such as BOLD or arterial spin labeling (ASL), and is particularly powerful when conducted in conjunction with these complementary techniques. The pulse sequence and imaging parameters of VASO can be optimized such that the signal change is predominantly of CBV origin, but careful considerations should be taken to minimize other contributions, such as those from the BOLD effect, cerebral blood flow (CBF) and cerebrospinal fluid (CSF). The sensitivity of the VASO technique is the primary disadvantage when compared with BOLD, but this technique is increasingly demonstrating its utility in neuroscientific and clinical applications.


Clonal growth of carp (Cyprinus carpio) T cells in vitro: long-term proliferation of Th2-like cells.
Carp kidney leukocytes co-cultured with a supporting cell layer resulted in proliferation of polyclonal CD4(+) αβT cells as described previously. These bulk-cultured T cells expressed transcripts for both T helper 1 cells (Th1) master regulator (T-bet) and T helper 2 cells (Th2) master regulator (GATA-3). To identify the Th subsets in bulk-cultured T cells, single cells were picked up from the bulk culture, proliferated, and characterized. The majority of the clones displayed characteristics consistent with CD4(+) αβT cell identity. These clones expressed both TCRα and TCRβ, but could not produce a TCRγδ heterodimer since they typically only expressed either TCRγ or TCRδ. These clones also expressed the TCR co-receptor genes CD4-1 or CD4-2, whereas they did not express CD8α or CD8β. In addition, GATA-3 was expressed whereas T-bet was not. Among these clones, one clone (KoThL5) continued to proliferate on the supporting cells and was successively transferred for more than 10 months and 90-100 passages. To characterize the KoThL5 cells by their cytokine production profile, they were stimulated with PHA and investigated by real-time RT-PCR. mRNA expression of Th2-related cytokine (IL-4/13B) was only enhanced in KoThL5 cells whereas both Th1-related cytokine (IFNγ) and Th2-related cytokines (IL-4/13A and IL-4/13B) were significantly enhanced in bulk-cultured T cells. Taken together, KoThL5 cells share some features with mammalian Th2 cells. This is the first study to describe in vitro cultures of teleost cell with Th2-like features. The KoThL5 cell line has considerable potential for addressing questions concerning the properties of teleost Th2 cells.


External memory BWT and LCP computation for sequence collections with applications.
Sequencing technologies produce larger and larger collections of biosequences that have to be stored in compressed indices supporting fast search operations. Many compressed indices are based on the Burrows-Wheeler Transform (BWT) and the longest common prefix (LCP) array. Because of the sheer size of the input it is important to build these data structures in external memory and time using in the best possible way the available RAM. We propose a space-efficient algorithm to compute the BWT and LCP array for a collection of sequences in the external or semi-external memory setting. Our algorithm splits the input collection into subcollections sufficiently small that it can compute their BWT in RAM using an optimal linear time algorithm. Next, it merges the partial BWTs in external or semi-external memory and in the process it also computes the LCP values. Our algorithm can be modified to output two additional arrays that, combined with the BWT and LCP array, provide simple, scan-based, external memory algorithms for three well known problems in bioinformatics: the computation of maximal repeats, the all pairs suffix-prefix overlaps, and the construction of succinct de Bruijn graphs. We prove that our algorithm performs O ( n maxlcp ) sequential I/Os, where n is the total length of the collection and maxlcp is the maximum LCP value. The experimental results show that our algorithm is only slightly slower than the state of the art for short sequences but it is up to 40 times faster for longer sequences or when the available RAM is at least equal to the size of the input.


Neural control of renin release.
1. Factors involved in the neural control of renin release have been reviewed. 2. Experimental evidence has been obtained that sympathetic stimulation releases renin from the kidney independently of local vasomotor changes. 3. The reflex control of renin release on postural change has been established. 4. The effect of diuretics on renin release has been studied and evidence of neural and non-neural mechanisms obtained. 5. The effect of suprarenal aortic stenosis has been studied; the findings suggest that renin release is in some way dependent on neural mechanisms. 6. The pathological significance of the neural control of renin release has been discussed.


Regulation of type 3 deiodinase in rodent liver and adipose tissue during fasting.
Fasting induces profound changes in the hypothalamus-pituitary-thyroid axis and peripheral thyroid hormone (TH) metabolism, ultimately leading to lower serum thyroid hormone (TH) concentrations. In the present study, we aimed to investigate the regulation of type 3 deiodinase (D3) during fasting in two metabolic tissues: liver and white adipose tissue (WAT). To this end, we studied the effect of modulation of the mammalian target of rapamycin (mTOR) and hypoxia inducible factor 1α (HIF1α) on D3 expression in primary rat hepatocytes and in 3T3-L1 adipocytes. In addition, we studied the role of the constitutive androstane receptor (CAR) on liver TH metabolism using primary hepatocytes and CAR-/- mice. Twenty-four-hour fasting increased liver Dio3 expression in mice. Inhibition of mTOR using mTOR inhibitors markedly induced Dio3 mRNA expression in primary hepatocytes; this increase was accompanied by a small increase in D3 activity. Stimulation of these cells with a CAR agonist induced both Dio3 mRNA expression and activity. Fasting increased hepatic D3 expression in WT but not in CAR-/- mice. In WAT, Dio3 mRNA expression increased five-fold after 48-h fasting. Treatment of 3T3-L1 adipocytes with mTOR inhibitors induced Dio3 mRNA expression, whereas stimulation of these cells with cobalt chloride, a compound that mimics hypoxia and stabilizes HIF1α, did not induce Dio3 mRNA expression. In conclusion, our results indicate an important role of mTOR in the upregulation of D3 in WAT and liver during fasting. Furthermore, CAR plays a role in the fasting induced D3 increase in the liver.


Kv1.1 channels regulate early postnatal neurogenesis in mouse hippocampus via the TrkB signaling pathway.
In the postnatal brain, neurogenesis occurs only within a few regions, such as the hippocampal sub-granular zone (SGZ). Postnatal neurogenesis is tightly regulated by factors that balance stem cell renewal with differentiation, and it gives rise to neurons that participate in learning and memory formation. The Kv1.1 channel, a voltage-gated potassium channel, was previously shown to suppress postnatal neurogenesis in the SGZ in a cell-autonomous manner. In this study, we have clarified the physiological and molecular mechanisms underlying Kv1.1-dependent postnatal neurogenesis. First, we discovered that the membrane potential of neural progenitor cells is highly dynamic during development. We further established a multinomial logistic regression model for cell-type classification based on the biophysical characteristics and corresponding cell markers. We found that the loss of Kv1.1 channel activity causes significant depolarization of type 2b neural progenitor cells. This depolarization is associated with increased tropomyosin receptor kinase B (TrkB) signaling and proliferation of neural progenitor cells; suppressing TrkB signaling reduces the extent of postnatal neurogenesis. Thus, our study defines the role of the Kv1.1 potassium channel in regulating the proliferation of postnatal neural progenitor cells in mouse hippocampus.


Multiclass semisupervised learning based upon kernel spectral clustering.
This paper proposes a multiclass semisupervised learning algorithm by using kernel spectral clustering (KSC) as a core model. A regularized KSC is formulated to estimate the class memberships of data points in a semisupervised setting using the one-versus-all strategy while both labeled and unlabeled data points are present in the learning process. The propagation of the labels to a large amount of unlabeled data points is achieved by adding the regularization terms to the cost function of the KSC formulation. In other words, imposing the regularization term enforces certain desired memberships. The model is then obtained by solving a linear system in the dual. Furthermore, the optimal embedding dimension is designed for semisupervised clustering. This plays a key role when one deals with a large number of clusters.


Hydrazone switches and things in between.
This feature article surveys the various ways by which a structurally simple hydrazone can be used in accessing different functional materials, mainly photo/chemically activated switches, fluorophores and sensors. The modularity of this functional group enabled us to develop new switching mechanisms, pathways, cascades and loops, while addressing challenges in the field, such as waste accumulation, how to control cross-talk between different types of switches, developing photochromic compounds with benign activation wavelengths, among others. All of these advances are expected to play, in one permutation or another, an important role in the coming decades in the field of molecular switches and machines.


Biobank research: time for discussion and debate.
The establishment of biobanks is gaining prominence globally. The open and evolving nature of biobanks has profound ethical, legal and social implications for individual and group autonomy, informed consent, privacy, confidentiality, secondary use of samples and data over time, return of results, data sharing, benefit sharing with communities, and premature or unplanned closure. Complexities also emerge because of increasing international collaborations, and differing national positions. Public consultation and involvement are very necessary to the success of biobanks. Implementing national laws in an internationally consistent manner is problematic.


Long-term peritoneal dialysis before transplantation and intra-abdominal infection after simultaneous pancreas-kidney transplantations.
To investigate whether long-term peritoneal dialysis before transplantation entails a higher risk than hemodialysis for intra-abdominal infection after bladder-drained simultaneous pancreas-kidney transplantations. Large single-center case-control study. A large university hospital (referral center). In all, 189 bladder-drained simultaneous pancreas-kidney transplantations were done from January 1, 1986, to December 31, 1994: before transplantations were performed, 32 recipients (17%) were undergoing peritoneal dialysis, 71 recipients (38%) were undergoing hemodialysis, and 86 recipients (46) were not undergoing dialysis. The intra-abdominal infection rate after transplantation and the rate of graft loss due to infection. Intra-abdominal infections developed in 33 recipients (18%) after transplantation. Graft and patient survival rates were significantly lower for recipients with vs without an infection (P < .001 for both). Both the dialysis mode and dialysis dependence did not affect the infection rate: of the 33 recipients with an infection, 7 (21%) were undergoing peritoneal dialysis, 15 (46%) were undergoing hemodialysis, and 11 (33%) were not undergoing dialysis before transplantation (P = .3). The rate of graft loss due to infection was not significantly different for recipients who were undergoing peritoneal dialysis vs hemodialysis (P = .1). However, it was higher for recipients who were undergoing dialysis (peritoneal dialysis and hemodialysis) vs those patients who were not undergoing dialysis (P = .04). Candidates for simultaneous pancreas-kidney transplantation should undergo the transplantation preemptively (ie, before they become dependent on dialysis) because the rate of graft loss due to infection was higher for recipients who were undergoing dialysis (irrespective of the dialysis mode). If dialysis cannot be avoided, the choice of peritoneal dialysis vs hemodialysis can be individualized, since these dialysis modes do not have significantly different rates of infection or of graft loss due to infection.


Slit-lamp Pars Plana Needle Hyaloidotomy-Zonulotomy-Iridotomy for the Treatment of Spontaneous Malignant Glaucoma.
An 88-year-old woman with a history of recent complicated pacemaker insertion presented with acute-onset malignant glaucoma recalcitrant to conservative medical therapy. Surgical intervention was discussed; however, given her complex cardiac history and recent postoperative state, the risk of anesthesia-related systemic adverse events was deemed unacceptably high. As such, a slit-lamp procedure was recommended to break the attack of malignant glaucoma. Here within, we report a novel technique of breaking an attack of malignant glaucoma by needling the anterior hyaloid face at the slit lamp. With this technique, a 25-G needle was entered through the pars plana and was advanced through the anterior hyaloid face, zonules, and peripheral iridotomy to create a unicameral eye and successfully break the malignant closure attack.


Hospital/clinical ethics committees' notion: an overview.
Hospital ethics committees (HECs) help clinicians deal with the ethical challenges which have been raised during clinical practice. A comprehensive literature review was conducted to provide a historical background of the development of HECs internationally and describe their functions and practical challenges of their day to day work. This is the first part of a comprehensive literature review conducted between February 2014 and August 2016 by searching through scientific databases. The keyword ethics committee, combined with hospital, clinic, and institution, was used without a time limitation. All original and discussion articles, as well as other scientific documents were included. Of all the articles and theses found using these keywords, only 56 were consistent with the objectives of the study. Based on the review goals, the findings were divided into three main categories; the inception of HECs in the world, the function of HECs, and the challenges of HECs. According to the results, the Americas Region and European Region countries have been the most prominent considering the establishment of HECs. However, the majority of the Eastern Mediterranean Region and South-East Asia Region countries are only beginning to establish these committees in their hospitals. The results highlight the status and functions of HECs in different countries and may be used as a guide by health policymakers and managers who are at the inception of establishing these committees in their hospitals.


Large-scale validation of a quantum mechanics based scoring function: predicting the binding affinity and the binding mode of a diverse set of protein-ligand complexes.
Computational methods to calculate binding affinity in protein-ligand interaction are of immense interest because of obvious practical applications in structure-based drug design. Scoring functions attempt to calculate the variation in binding affinity of ligands-inhibitors bound to protein targets at various levels of theory. In this study we use semiempirical quantum mechanics to design a scoring function that can calculate the electrostatic interactions and solvation free energy expected during complexation. This physically based approach has the ability to capture binding affinity trends in a diverse range of protein-ligand complexes. We also show the predictive power of this scoring function within protein targets and its ability to score ligand poses docked to a protein target. We also demonstrate the ability of this scoring function to discriminate between native and decoy poses and highlight the crucial role played by electrostatic interactions in molecular recognition. Finally we compare the performance of our scoring function with other available scoring functions in the literature.


Comparative analysis of health system performance in Montreal and New York: the importance of context for interpreting indicators.
Although eliminating financial barriers to care is a necessary condition for improving access to health services, it is not sufficient. Given the contrasting health systems with regard to financing and organization of health insurance in the United States and Canada, there is a long history of comparing these countries. We extend the empirical studies on the Canadian and US health systems by comparing access to ambulatory care as measured by hospitalization rates for ambulatory care sensitive conditions (ACSC) in Montreal and New York City. We find that, in New York, ACSC rates were more than twice as high (12.6 per 1000 population) as in Montreal (4.8 per 1000 population). After controlling for age, sex, and number of diagnoses, significant differences in ACSC rates are present in both cities, but are more pronounced in New York. Our findings are consistent with the hypothesis that universal, first-dollar health insurance coverage has contributed to lower ACSC rates in Montreal than New York. However, Montreal's surprisingly low ACSC rate calls for further research.


A Novel Multisensory Stimulation and Data Capture System (MADCAP) for Investigating Sensory Trajectories in Infancy.
Sensory processing differences, including responses to auditory, visual, and tactile stimuli, are ideal targets for early detection of neurodevelopmental risks, such as autism spectrum disorder. However, most existing studies focus on the audiovisual paradigm and ignore the sense of touch. In this paper, we present a multisensory delivery system that can deliver audio, visual, and tactile stimuli in a controlled manner and capture peripheral physiological, eye gaze, and electroencephalographic response data. The novelty of the system is the ability to provide affective touch. In particular, we have developed a tactile stimulation device that delivers tactile stimuli to infants with precisely controlled brush stroking speed and force on the skin. A usability study of 10 3-20 month-old infants was conducted to investigate the tolerability and feasibility of the system. Results have shown that the system is well tolerated by infants and all the data were collected robustly. This paper paves the way for future studies charting the sensory response trajectories in infancy.


Challenges for Ex Situ Conservation of Wild Bananas: Seeds Collected in Papua New Guinea Have Variable Levels of Desiccation Tolerance.
Ex situ seed conservation of banana crop wild relatives (Musa spp. L.), is constrained by critical knowledge gaps in their storage and germination behaviour. Additionally, challenges in collecting seeds from wild populations impact the quality of seed collections. It is, therefore, crucial to evaluate the viability of seeds from such collecting missions in order to improve the value of future seed collections. We evaluate the seed viability of 37 accessions of seven Musa species, collected from wild populations in Papua New Guinea, during two collecting missions. Seeds from one mission had already been stored in conventional storage (dried for four months at 15% relative humidity, 20 °C and stored for two months at 15% relative humdity, -20 °C), so a post-storage test was carried out. Seeds from the second mission were assessed freshly extracted and following desiccation. We used embryo rescue techniques to overcome the barrier of germinating in vivo Musa seeds. Seeds from the first mission had low viability (19 ± 27% mean and standard deviation) after storage for two months at 15% relative humidity and -20 °C. Musa balbisiana Colla seeds had significantly higher post-storage germination than other species (p < 0.01). Desiccation reduced germination of the seeds from the second collecting mission, from 84 ± 22% (at 16.7 ± 2.4% moisture content) to 36 ± 30% (at 2.4 ± 0.8% moisture content). There was considerable variation between and (to a lesser extent) within accessions, a proportion of individual seeds of all but one species (Musa ingens N.W.Simmonds) survived desiccation and sub-zero temperature storage. We identified that seeds from the basal end of the infructescence were less likely to be viable after storage (p < 0.001); and made morphological observations that identify seeds and infructescences with higher viability in relation to their developmental maturity. We highlight the need for research into seed eco-physiology of crop wild relatives in order to improve future collecting missions.


Edge principal components and squash clustering: using the special structure of phylogenetic placement data for sample comparison.
Principal components analysis (PCA) and hierarchical clustering are two of the most heavily used techniques for analyzing the differences between nucleic acid sequence samples taken from a given environment. They have led to many insights regarding the structure of microbial communities. We have developed two new complementary methods that leverage how this microbial community data sits on a phylogenetic tree. Edge principal components analysis enables the detection of important differences between samples that contain closely related taxa. Each principal component axis is a collection of signed weights on the edges of the phylogenetic tree, and these weights are easily visualized by a suitable thickening and coloring of the edges. Squash clustering outputs a (rooted) clustering tree in which each internal node corresponds to an appropriate "average" of the original samples at the leaves below the node. Moreover, the length of an edge is a suitably defined distance between the averaged samples associated with the two incident nodes, rather than the less interpretable average of distances produced by UPGMA, the most widely used hierarchical clustering method in this context. We present these methods and illustrate their use with data from the human microbiome.


Infectivity and pathogenicity of the oomycete Aphanomyces invadans in Atlantic menhaden Brevoortia tyrannus.
Atlantic menhaden Brevoortia tyrannus develop characteristic skin ulcers in response to infection by the oomycete Aphanomyces invadans. To investigate pathogenicity, we conducted a dose response study. Juvenile menhaden were inoculated subcutaneously with 0, 1, 5, 10, 100, and 500 secondary zoospores per fish and monitored for 37 d post-injection (p.i.). Survival rates declined with increasing zoospore dose, with significantly different survivorship curves for the different doses. Moribund and dead fish exhibited characteristic ulcerous lesions at the injection site starting at 13 d p.i. None of the sham-injected control fish (0 zoospore treatment) died. The LD50 (lethal dose killing 50% of exposed menhaden) for inoculated fish was estimated at 9.7 zoospores; however, some fish receiving an estimated single zoospore developed infections that resulted in death. Menhaden were also challenged by aqueous exposure and confirmed that A. invadans was highly pathogenic by this more environmentally realistic route. Fish that were acclimated to culture conditions for 30 d, and presumably free of skin damage, then aqueously exposed to 100 zoospores ml(-1), exhibited 14% lesion prevalence with 11% mortality. Net-handled fish that were similarly infected had a significantly higher lesion prevalence (64%) and mortality (64%). Control fish developed no lesions and did not die. Scanning electron microscopy of fish skin indicated that zoospores adhered to intact epidermis, germinated and penetrated the epithelium with a germ tube. Our results indicate that A. invadans is a primary pathogen of menhaden and is able to cause disease at very low zoospore concentrations.


The role of social media for patients and consumer health. Contribution of the IMIA Consumer Health Informatics Working Group.
: To provide an overview on social media for consumers and patients in areas of health behaviours and outcomes. A directed review of recent literature. : We discuss the limitations and challenges of social media, ranging from social network sites (SNSs), computer games, mobile applications, to online videos. An overview of current users of social media (Generation Y), and potential users (such as low socioeconomic status and the chronically ill populations) is also presented. Future directions in social media research are also discussed. : We encourage the health informatics community to consider the socioeconomic class, age, culture, and literacy level of their populations, and select an appropriate medium and platform when designing social networked interventions for health. Little is known about the impact of second-hand experiences faciliated by social media, nor the quality and safety of social networks on health. Methodologies and theories from human computer interaction, human factors engineering and psychology may help guide the challenges in designing and evaluating social networked interventions for health. Further, by analysing how people search and navigate social media for health purposes, infodemiology and infoveillance are promising areas of research that should provide valuable insights on present and emergening health behaviours on a population scale.


The effectiveness of peroneal nerve stimulation combined with neuromuscular electrical stimulation in the management of knee osteoarthritis: A randomized controlled single-blind study.
This study aimed to compare the effectiveness of neuromuscular electrical stimulation (NMES) combined with peroneal nerve stimulation (PNS) on muscle strength around the knee, proprioception, pain, functional status, and quality of life in patients with knee osteoarthritis (OA). The prospective, randomized, single-blinded, controlled trial included 63 patients with clinical and radiological diagnoses of knee OA between December 2019 and March 2020. The patients were divided into two groups: Group 1 (NMES+PNS, n=31) and Group 2 (NMES, n=32). The patients were followed up at two and six weeks. Main outcome measures were the Visual Analog Scale, Western Ontario and McMaster Universities Arthritis Index, Nottingham Health Profile, and 100-m walking test, quadriceps muscle strength, hamstring muscle strength (HMS), and joint position sense were evaluated using a computer-controlled isokinetic dynamometer at 60°/sec, 90°/sec, and 120°/sec angular velocities. The proprioception was evaluated at 30° and 60° flexion angles using the same device. Two patients from Group 1 and two patients from Group 2 were excluded from the study after they failed to show up for the six-week control. As a result, the study was completed with 59 patients (30 females, 29 males; 55.9±6.1 years; range, 40 to 65 years). There was a significant difference between the two groups in the 100-m walking test parameter at the six-week control in favor of Group 1 (p<0.05). There was a significant difference in favor of Group 1 in the parameters of proprioception (30° and 60°) and HMS (60° and 90°) in both the two-week evaluation and six-week controls (p<0.05). The HMS 120° parameter showed a significant difference in favor of Group 1 at the six-week control (p<0.05). In patients with knee OA, we believe that PNS combined with NMES may be more effective than NMES treatment alone in terms of proprioception, HMS, and functional status.


Driving factors and mode transformation regarding health technology assessment (HTA) in China: Problems and recommendations.
As the reform of Chinese medical and health undertakings has advanced (since 2015), the admission, pricing and payment policies regarding the new health technologies of China have undergone significant changes, and health technology assessment (HTA) has gradually become one of the current reform and research hotspots in China. Based on the perspective of HTA driving factors and the development mode, this paper proposes a two-stage mode of HTA development in China, namely, the mode driven by the management of new heath technology admission and another one driven by new health technology pricing and medical insurance payment. In addition, the paper also proposes the challenges that HTA faces in China under the current mode, including the development system, process standard, data mechanism, and policy application. Besides, recommendations are provided for the further development of HTA construction in China, including strengthening the development system of regional HTA centers, formulating HTA process guidance, building a database, improving evaluation quality and intensifying policy integration.


Targeted misexpression of Hox-4.6 in the avian limb bud causes apparent homeotic transformations.
In the limb bud the 5' members of the Hox-4 gene cluster are expressed in a nested set of overlapping domains which are progressively restricted in the posterior and distal directions. These domains arise early in limb bud development and come to approximate the primordia of the major structural elements of the limb along the anterior/posterior axis (Fig. 1). This pattern, and the fact that surgical manipulations which lead to mirror image duplications along the anterior/posterior axis give rise to mirror image duplications of the domains of expression of these genes, have led to the proposal that these transcription factors specify positional identity along the anterior/posterior axis. Here we test this hypothesis directly using replication-competent retroviral vectors to expand the domain of expression of the Hox-4.6 gene anteriorly during limb development in vivo. We report that alteration of the domain of expression of the Hox-4.6 gene in the developing limb leads to reproducible pattern alterations consistent with a posterior homeotic transformation.


Economic development and wage inequality: A complex system analysis.
Adapting methods from complex system analysis, this paper analyzes the features of the complex relationship between wage inequality and the development and industrialization of a country. Development is understood as a combination of a monetary index, GDP per capita, and a recently introduced measure of a country's economic complexity: Fitness. Initially the paper looks at wage inequality on a global scale, over the time period 1990-2008. Our empirical results show that globally the movement of wage inequality along with the ongoing industrialization of countries has followed a longitudinally persistent pattern comparable to the one theorized by Kuznets in the fifties: countries with an average level of development suffer the highest levels of wage inequality. Next, the study narrows its focus on wage inequality within the United States. By using data on wages and employment in the approximately 3100 US counties over the time interval 1990-2014, it generalizes the Fitness-Complexity metric for geographic units and industrial sectors, and then investigates wage inequality between NAICS industries. The empirical time and scale dependencies are consistent with a relation between wage inequality and development driven by institutional factors comparing countries, and by change in the structural compositions of sectors in a homogeneous institutional environment, such as the counties of the United States.


Morph-specific metabolic rate and the timing of reproductive senescence in a color polymorphic dragon.
Polymorphism has fascinated biologists for over a century because morphs persist within populations through evolutionary time in spite of showing disparate behavioral and physiological phenotypes; any one morph should go to fixation with the slightest fitness advantage over the others. Surely there must be trade-offs that balance selection on them. The polychromatic morphs of the Australian painted dragon lizard, Ctenophorus pictus, are one such system. The male color morphs of painted dragons have different physiological and behavioral traits including reproductive tactics, hormone levels, and the rate of body condition loss through the reproductive season. Due to their differences in physiology and reproductive tactics, we tested the hypotheses that male morphs would differ in resting metabolic rates (RMRs) and that the morphs' RMR would decline at different rates through the mating season. We found that bib-morphs (yellow gular patch) differ in RMR with bibbed (more aggressive) males having consistently higher RMR than non-bibbed males. Furthermore, we show that male dragons experience a decline in RMR as they age from reproductively active to inactive. We also found that the RMR of bibbed males has higher repeatability than non-bibbed males. Our results reinforce previous hypotheses about the morph-specific costs of bearing a gular patch in painted dragons.


Analysis of radiocarbon, stable isotopes and DNA in teeth to facilitate identification of unknown decedents.
The characterization of unidentified bodies or suspected human remains is a frequent and important task for forensic investigators. However, any identification method requires clues to the person's identity to allow for comparisons with missing persons. If such clues are lacking, information about the year of birth, sex and geographic origin of the victim, is particularly helpful to aid in the identification casework and limit the search for possible matches. We present here results of stable isotope analysis of (13)C and (18)O, and bomb-pulse (14)C analyses that can help in the casework. The (14)C analysis of enamel provided information of the year of birth with an average absolute error of 1.8±1.3 years. We also found that analysis of enamel and root from the same tooth can be used to determine if the (14)C values match the rising or falling part of the bomb-curve. Enamel laydown times can be used to estimate the date of birth of individuals, but here we show that this detour is unnecessary when using a large set of crude (14)C data of tooth enamel as a reference. The levels of (13)C in tooth enamel were higher in North America than in teeth from Europe and Asia, and Mexican teeth showed even higher levels than those from USA. DNA analysis was performed on 28 teeth, and provided individual-specific profiles in most cases and sex determination in all cases. In conclusion, these analyses can dramatically limit the number of possible matches and hence facilitate person identification work.


Modulation of the osteoclast Ca2+ receptor by extracellular protons: possible linkage between Ca2+ sensing and extracellular acidification.
We report a sensitivity of the osteoclast cell surface Ca2+ receptor to extracellular protons. Freshly isolated rat osteoclasts were exposed to the known agonists of the Ca2+ receptor, Ca2+ and Ni2+, in extracellular solutions set at different pH values. Decreasing the extracellular pH from 7.8 to 4.0 units markedly potentiated the cytosolic Ca2+ signals elicited in response to Ca2+ receptor activation by either Ni2+ (50 microM, 500 microM or 5 mM) or Ca2+ (5 mM). Each response consisted of a rapid and usually transient elevation of cytosolic [Ca2+]. Maximal cytosolic [Ca2+] responses were obtained at pH values of 6.6 (for 5 mM-[Ni2+]) and 4.0 units (for 5 mM-[Ca2+]). Finally, the effects of extracellular pH persisted in Ca(2+)-free, EGTA-containing solutions, suggesting a modulation of intracellular Ca2+ release.


Pre-hospital ECG in patients undergoing primary percutaneous interventions within an integrated system of care: reperfusion times and long-term survival benefits.
Treatment delay is a powerful predictor of survival in STEMI patients undergoing primary PCI. We investigated the effectiveness of pre-hospital triage with direct referral to PCI, alongside more conventional referral strategies. From January 2003 to December 2007, 1,619 STEMI patients were referred for primary PCI at our cathlab through two main triage groups: i.e., 1) following pre-hospital triage (n=524), 2) via more conventional triages (n=1,095) represented by the S. Orsola-Malpighi hospital emergency department triage (hub hospital) and local hospital triage. Pre-hospital diagnosis was associated with a 76 minute reduction in pain-to-balloon time (143 [107-216] vs. 219 [149-343], p=0.001) allowing mechanical revascularisation within 90 minutes from the first medical contact in the vast majority of the patients (>80%). Clinically, pre-hospital triage showed no significant reductions in terms of adjusted long-term mortality (HR 0.81, 95% CI 0.61-1.08; p=0.16) in the overall population. However, significant adjusted survival benefits were observed in high-risk groups (i.e., cardiogenic shock, TIMI risk score >30, diabetes mellitus). This study shows that pre-hospital diagnosis allows for significant reductions in primary PCI treatment delays and suggests the hypothesis that this referral strategy might provide long-term survival benefits especially in high-risk patients.


Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease.
Approximately 25% of subjects with common variable immunodeficiency (CVID) develop autoimmune disease. We analyzed T cell subsets, specifically regulatory T cells along with B cell subsets to determine whether there were changes in regulatory T cells which would correlate with the autoimmune disease clinical phenotype in CVID subjects. We hypothesized that regulatory T cell (CD4+CD25hiCD127lo) suppressive function would be impaired in CVID subjects with autoimmune disease. Using purified, sorted Treg from CVID subjects (n=14) and from healthy controls (HC, n=5) in standard suppression assays, we found the suppressive function of Treg from CVID subjects with autoimmune disease (CVID w/ AI, n=8) to be significantly attenuated compared to CVID subjects with no autoimmune disease (CVID w/o AI, n=6) and to HC (n=5). A number of proteins associated with Treg function were decreased in expression as detected through immunofluorescent antibody via flow cytometry (mean fluorescence intensity (MFI) of FoxP3, Granzyme A, XCL1, pSTAT5, and GITR in Treg was significantly lower (by up to 3 fold) in CVID w/ AI compared to CVID w/o AI and HC. Furthermore, a statistically significant correlation was found between intracellular MFI of FoxP3, Granzyme A, and pSTAT5 in Treg and the degree of Treg dysfunction. These results suggest that attenuation of Treg function is associated with autoimmune disease in CVID subjects and may contribute to autoimmune pathogenesis.


Refining Prognosis for Intracerebral Hemorrhage by Early Reassessment.
Prognostic assessments, which are crucial for decision-making in critical illnesses, have shown unsatisfactory reliability. We compared the accuracy of a widely used prognostic score against a model derived from clinical data obtained 5 days after admission for patients with intracerebral hemorrhage (ICH), a condition for which prognostication has proven notoriously challenging and prone to bias. Patients enrolled in a prospective observational cohort study of spontaneous ICH underwent hourly Glasgow Coma Scale (GCS) assessment. Outcome was measured at 3 months using the modified Rankin Scale (mRS). We analyzed the change in correlation between GCS and 3-month mRS scores from admission through day 5, and compared the performance of a parsimonious set of day 5 clinical variables against the ICH score. Data was collected on 254 subjects. The ICH score and day 5 GCS score were both correlated with 3-month mRS score (p < 0.001), but the correlation was stronger with day 5 GCS score (p < 0.05 by Fisher z-transformation). Premorbid mRS score, intraventricular hemorrhage and day 5 GCS score were independent predictors of outcome (all p < 0.05 in ordinal regression model). While ICH score correctly classified good (mRS 0-3) vs. poor (mRS 4-6) outcome in 73% of cases, the day 5 model correctly classified 83% of cases. A simple reassessment after 5 days of care significantly improves the accuracy of prognosticating outcome in patients with ICH. These data confirm the feasibility and potential utility of early reassessments in refining prognosis for patients who survive early stabilization of a severe neurologic injury.


Corrective jitter motion shows similar individual frequencies for the arm and the finger.
A characteristic of visuomotor tracking of non-regular oscillating stimuli are high-frequency jittery corrective motions, oscillating around the tracked stimuli. However, the properties of these corrective jitter responses are not well understood. For example, does the jitter response show an idiosyncratic signature? What is the relationship between stimuli properties and jitter properties? Is the jitter response similar across effectors with different inertial properties? To answer these questions, we measured participants' jitter frequencies in two tracking tasks in the arm and the finger. Thirty participants tracked the same set of eleven non-regular oscillating stimuli, vertically moving on a screen, once with forward-backward arm movements (holding a tablet stylus) and once with upward-downward index finger movements (with a motion tracker attached). Participants' jitter frequencies and tracking errors varied systematically as a function of stimuli frequency and amplitude. Additionally, there were clear individual differences in average jitter frequencies between participants, ranging from 0.7 to 1.15 Hz, similar to values reported previously. A comparison of individual jitter frequencies in the two tasks showed a strong correlation between participants' jitter frequencies in the finger and the arm, despite the very different inertial properties of the two effectors. This result suggests that the corrective jitter response stems from common neural processes.


Microbial exposure during early life has persistent effects on natural killer T cell function.
Exposure to microbes during early childhood is associated with protection from immune-mediated diseases such as inflammatory bowel disease (IBD) and asthma. Here, we show that in germ-free (GF) mice, invariant natural killer T (iNKT) cells accumulate in the colonic lamina propria and lung, resulting in increased morbidity in models of IBD and allergic asthma as compared with that of specific pathogen-free mice. This was associated with increased intestinal and pulmonary expression of the chemokine ligand CXCL16, which was associated with increased mucosal iNKT cells. Colonization of neonatal-but not adult-GF mice with a conventional microbiota protected the animals from mucosal iNKT accumulation and related pathology. These results indicate that age-sensitive contact with commensal microbes is critical for establishing mucosal iNKT cell tolerance to later environmental exposures.


Feralisation targets different genomic loci to domestication in the chicken.
Feralisation occurs when a domestic population recolonizes the wild, escaping its previous restricted environment, and has been considered as the reverse of domestication. We have previously shown that Kauai Island's feral chickens are a highly variable and admixed population. Here we map selective sweeps in feral Kauai chickens using whole-genome sequencing. The detected sweeps were mostly unique to feralisation and distinct to those selected for during domestication. To ascribe potential phenotypic functions to these genes we utilize a laboratory-controlled equivalent to the Kauai population-an advanced intercross between Red Junglefowl and domestic layer birds that has been used previously for both QTL and expression QTL studies. Certain sweep genes exhibit significant correlations with comb mass, maternal brooding behaviour and fecundity. Our analyses indicate that adaptations to feral and domestic environments involve different genomic regions and feral chickens show some evidence of adaptation at genes associated with sexual selection and reproduction.


X-ray absorption spectroscopy of GeO2 glass to 64 GPa.
The structural behavior of GeO2 glass has been investigated up to 64 GPa using results from x-ray absorption spectroscopy in a diamond anvil cell combined with previously reported density measurements. The difference between the nearest Ge-O distances of glassy and rutile-type GeO2 disappears at the Ge-O distance maximum at 20 GPa, indicating completion of the tetrahedral-octahedral transition in GeO2 glass. The mean-square displacement σ(2) of the Ge-O distance in the first Ge-O shell increases progressively to a maximum at 10 GPa, followed by a substantial reduction at higher pressures. The octahedral glass is, as expected, less dense and has a higher compressibility than the corresponding crystalline phase, but the differences in Ge-O distance and density between the glass and the crystals are gradually eliminated over the 20-40 GPa pressure range. Above 40 GPa, GeO2 forms a dense octahedral glass with a compressibility similar to that of the corresponding crystalline phase (α-PbO2 type). The EXAFS and XANES spectra show evidence for subtle changes in the dense glass continuing to occur at these high pressures. The Ge-O bond distance shows little change between 45-64 GPa, and this may reflect a balance between bond shortening and a gradual coordination number increase with compression. The density of the glass is similar to that of the α-PbO2-type phase, but the Ge-O distance is longer and is close to that in the higher-coordination pyrite-type phase which is stable above ∼60 GPa. The density data provide evidence for a possible discontinuity and change in compressibility at 40-45 GPa, but there are no major changes in the corresponding EXAFS spectra. A pyrite-type local structural model for the glass can provide a reasonable fitting to the XAFS spectra at 64 GPa.


Interactions of peripheral proteins with model membranes as viewed by molecular dynamics simulations.
Many cellular signalling and related events are triggered by the association of peripheral proteins with anionic lipids in the cell membrane (e.g. phosphatidylinositol phosphates or PIPs). This association frequently occurs via lipid-binding modules, e.g. pleckstrin homology (PH), C2 and four-point-one, ezrin, radixin, moesin (FERM) domains, present in peripheral and cytosolic proteins. Multiscale simulation approaches that combine coarse-grained and atomistic MD simulations may now be applied with confidence to investigate the molecular mechanisms of the association of peripheral proteins with model bilayers. Comparisons with experimental data indicate that such simulations can predict specific peripheral protein-lipid interactions. We discuss the application of multiscale MD simulation and related approaches to investigate the association of peripheral proteins which contain PH, C2 or FERM-binding modules with lipid bilayers of differing phospholipid composition, including bilayers containing multiple PIP molecules.


Acceptability and potential effectiveness of commercial portion control tools amongst people with obesity.
Exposure to large portion sizes is a risk factor for obesity. Specifically designed tableware may modulate how much is eaten and help with portion control. We examined the experience of using a guided crockery set (CS) and a calibrated serving spoon set (SS) by individuals trying to manage their weight. Twenty-nine obese adults who had completed 7-12 weeks of a community weight-loss programme were invited to use both tools for 2 weeks each, in a crossover design, with minimal health professional contact. A paper-based questionnaire was used to collect data on acceptance, perceived changes in portion size, frequency, and type of meal when the tool was used. Scores describing acceptance, ease of use and perceived effectiveness were derived from five-point Likert scales from which binary indicators (high/low) were analysed using logistic regression. Mean acceptance, ease of use and perceived effectiveness were moderate to high (3·7-4·4 points). Tool type did not have an impact on indicators of acceptance, ease of use and perceived effectiveness (P>0·32 for all comparisons); 55 % of participants used the CS on most days v. 21 % for the SS. The CS was used for all meals, whereas the SS was mostly used for evening meals. Self-selected portion sizes increased for vegetables and decreased for chips and potatoes with both tools. Participants rated both tools as equally acceptable, easy to use and with similar perceived effectiveness. Formal trials to evaluate the impact of such tools on weight control are warranted.


Adsorption behaviors of methylene blue on sunflower stem pith.
Adsorption behaviors of methylene blue (MB) from aqueous solution using sunflower stem pith (SSP) as adsorbent were investigated. The effects of adsorption conditions such as adsorption time, initial concentration of MB and dosage of SSP on the detoxification of MB were examined. The equilibrium adsorption data were analyzed using three well-known isotherms: Langmuir, Freundlich and Temkin. The results indicated that the Langmuir isotherm fitted well to the data as compared with another isotherm model. The maximum adsorption capacity calculated by the Langmuir isotherm model was 277 mg/g at 338 K. Kinetic analyses were conducted using pseudo first order, pseudo second order and the Elovich model. The regression results showed that the MB adsorption was described by the pseudo second order model. Different thermodynamic parameters such as Gibb's free energy (ΔGo), standard enthalpy change (ΔHo) and standard entropy change (ΔSo) were also evaluated. The results showed that the detoxification of MB using SSP as adsorbent was feasible, non-spontaneous and exothermic under experimental conditions.


Spreading and sustaining best practices for home care of older adults: a grounded theory study.
Improving health care quality requires effective and timely spread of innovations that support evidence-based practices. However, there is limited rigorous research on the process of spread, factors influencing spread, and models of spread. It is particularly important to study spread within the home care sector given the aging of the population, expansion of home care services internationally, the high proportion of older adult users of home care services, and the vulnerability of this group who are frail and live with multiple chronic conditions. The purpose of this study was to understand how best practices related to older adults are spread within home care organizations. Four home care organizations in Ontario, Canada that had implemented best practices related to older adults (falls prevention, pain management, management of venous leg ulcers) participated. Using a qualitative grounded theory design, interviews were conducted with frontline providers, managers, and directors at baseline (n = 44) and 1 year later (n = 40). Open, axial, and selective coding and constant comparison analysis were used. A model of the process of spread of best practices within home care organizations was developed. The phases of spread included (1) committing to change, (2) implementing on a small scale, (3) adapting locally, (4) spreading internally to multiple users and sites, and (5) disseminating externally. Factors that facilitated progression through these phases were (1) leading with passion and commitment, (2) sustaining strategies, and (3) seeing the benefits. Project leads, champions, managers, and steering committees played vital roles in leading the spread process. Strategies such as educating/coaching and evaluating and feedback were key to sustaining the change. Spread occurred within the home care context of high staff and manager turnover and time and resource constraints. Spread of best practices is optimized through the application of the phases of spread, allocation of resources to support spread, and implementing strategies for ongoing sustainability that address potential barriers. Further research will help to understand how best practices are spread externally to other organizations.