Researching mental health in minority ethnic communities: reflections on recruitment.
In this article we reflect on the recruitment of research participants to two related studies of experiences of mental health problems in Black and minority ethnic communities in the United Kingdom. A total of 65 people were recruited via three main strategies: the employment of bicultural recruiters, intensive information sharing about the studies, and work through local community groups. Three main issues seemed to affect recruitment: gatekeepers' attitudes, the (non)payment of participants, and reciprocal arrangements with local community groups. The type of strategy employed resulted in recruits with differing characteristics (although our sample was too small to draw generalizable conclusions). We conclude that to ensure that research participation is accessible to all, researchers must employ flexible recruitment methods that permit adaptation to specific needs arising out of health status, level of involvement with services, culture, and socioeconomic status. Systematic research into this part of the research process is needed.


Systematic Review and Meta-analysis: Gene Association Studies in Neonatal Sepsis.
Background Association studies of various gene variants in neonatal sepsis show conflicting results. Objective We performed a systematic review of candidate gene association studies in neonatal sepsis to provide pooled estimates of risk for selected gene variants. Methods We performed a search using MeSH terms "infection," "sepsis," "infant," "genetic variation," "polymorphism," and "genetic association studies." We included studies evaluating associations between neonatal sepsis and genetic variants (2000-2015). We excluded case reports/series, commentaries, narrative reviews, and nonhuman research. We assessed quality of studies using STREGA guidelines. Following estimation of odds ratios (ORs), data were pooled using random effects models. Results Twenty eight of 1,404 identified studies were included. Meta-analyses were performed for interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 as these gene variants were tested in multiple studies. TNF-α 308GG genotype demonstrated trends toward increased sepsis risk in the primary analysis of culture-proven sepsis (OR 1.18, 95% confidence interval [CI] 0.97-1.44). IL-10 1082GG genotype was associated with lower sepsis odds in very low-birth-weight (VLBW) infants (OR 0.51, 95% CI 0.29-0.91). Conclusion We uncovered an association between IL-10 1082 gene variation and sepsis in VLBW infants but did not identify associations between neonatal sepsis and TNF-α 308 or IL-6 gene variation. Larger cohort replication studies are required to validate these findings.


Fabrication of poly(ethylene glycol): gelatin methacrylate composite nanostructures with tunable stiffness and degradation for vascular tissue engineering.
Although synthetic polymers are desirable in tissue engineering applications for the reproducibility and tunability of their properties, synthetic small diameter vascular grafts lack the capability to endothelialize in vivo. Thus, synthetically fabricated biodegradable tissue scaffolds that reproduce important aspects of the extracellular environment are required to meet the urgent need for improved vascular grafting materials. In this study, we have successfully fabricated well-defined nanopatterned cell culture substrates made of a biodegradable composite hydrogel consisting of poly(ethylene glycol) dimethacrylate (PEGDMA) and gelatin methacrylate (GelMA) by using UV-assisted capillary force lithography. The elasticity and degradation rate of the composite PEG-GelMA nanostructures were tuned by varying the ratios of PEGDMA and GelMA. Human umbilical vein endothelial cells (HUVECs) cultured on nanopatterned PEG-GelMA substrates exhibited enhanced cell attachment compared with those cultured on unpatterned PEG-GelMA substrates. Additionally, HUVECs cultured on nanopatterned PEG-GelM substrates displayed well-aligned, elongated morphology similar to that of native vascular endothelial cells and demonstrated rapid and directionally persistent migration. The ability to alter both substrate stiffness and degradation rate and culture endothelial cells with increased elongation and alignment is a promising next step in recapitulating the properties of native human vascular tissue for tissue engineering applications.


Fatigue during breast cancer radiotherapy: an initial randomized study of cognitive-behavioral therapy plus hypnosis.
The study purpose was to test the effectiveness of a psychological intervention combining cognitive-behavioral therapy and hypnosis (CBTH) to treat radiotherapy-related fatigue. Women (n = 42) scheduled for breast cancer radiotherapy were randomly assigned to receive standard medical care (SMC) (n = 20) or a CBTH intervention (n = 22) in addition to SMC. Participants assigned to receive CBTH met individually with a clinical psychologist. CBTH participants received training in hypnosis and CBT. Participants assigned to the SMC control condition did not meet with a study psychologist. Fatigue was measured on a weekly basis by using the fatigue subscale of the Functional Assessment of Chronic Illness Therapy (FACIT) and daily using visual analogue scales. Multilevel modeling indicated that for weekly FACIT fatigue data, there was a significant effect of the CBTH intervention on the rate of change in fatigue (p < .05), such that on average, CBTH participants' fatigue did not increase over the course of treatment, whereas control group participants' fatigue increased linearly. Daily data corroborated the analyses of weekly data. The results suggest that CBTH is an effective means for controlling and potentially preventing fatigue in breast cancer radiotherapy patients.


Phosphatidylinositol synthase is required for lens structural integrity and photoreceptor cell survival in the zebrafish eye.
The zebrafish lens opaque (lop) mutant was previously isolated in a genetic screen and shown to lack rod and cone photoreceptors and exhibit lens opacity, or cataract, at 7 days post-fertilization (dpf). In this manuscript, we provide four different lines of evidence demonstrating that the lop phenotype results from a defect in the cdipt (phosphatidylinositol (PI) synthase; CDP-diacylglycerol-inositol 3-phosphatidyltransferase) gene. First, DNA sequence analysis revealed that the lop mutant contained a missense mutation in the lop open reading frame, which yields a nonconservative amino acid substitution (Ser-111-Cys) within the PI synthase catalytic domain. Second, morpholino-mediated knockdown of the cdipt-encoded PI synthase protein phenocopied the cdipt(lop/lop) mutant, with abnormal lens epithelial and secondary fiber cell morphologies and reduced numbers of photoreceptors. Third, microinjection of in vitro transcribed, wild-type cdipt mRNA into 1-4 cell stage cdipt(lop/lop) embryos significantly reduced the percentage of larvae displaying lens opacity at 7 dpf. Fourth, a cdipt retroviral-insertion allele, cdipt(hi559), exhibited similar lens and retinal abnormalities and failed to complement the cdipt(lop) mutant phenotype. To determine the initial cellular defects associated with the cdipt mutant, we examined homozygous cdipt(hi559/hi559) mutants prior to gross lens opacification at 6 dpf. The cdipt(hi559/hi559) mutants first exhibited photoreceptor layer disruption and photoreceptor cell death at 3 and 4 dpf, respectively, followed by lens dismorphogenesis by 5 dpf. RT-PCR revealed that the cdipt gene is maternally expressed and continues to be transcribed throughout development and into adulthood, in a wide variety of tissues. Using an anti-zebrafish PI synthase polyclonal antiserum, we localized the protein throughout the developing eye, including the photoreceptor layer and lens cortical secondary fiber cells. As expected, the polyclonal antiserum revealed that the PI synthase protein was reduced in amount in both the cdipt(lop/lop) and cdipt(hi559/hi559) mutants. Furthermore, we used a heterologous yeast phenotypic complementation assay to confirm that the wild-type zebrafish cdipt allele encodes functional PI synthase activity. Taken together, the cdipt-encoded PI synthase is required for survival of photoreceptor cells and lens epithelial and secondary cortical fiber cells. These zebrafish cdipt alleles represent excellent in vivo genetic tools to study the role of phosphatidylinositol and its phosphorylated derivatives in lens and photoreceptor development and maintenance.


Chronic left heart catheterization for microvascular blood flow determination in the rabbit: a minimally invasive technique using specially designed port devices.
This study describes a modified catheterization technique with subcutaneously implanted port catheters to be inserted in a retrograde manner across the aortic valve into the left heart ventricle through the right carotid artery to measure organ perfusion. The specially designed arterial port catheters were implanted in New Zealand rabbits (n = 11, 3.7 +/- 0.1 kg [mean +/- SEM]) under iv anesthesia (medetomidine/ketamine) and single-shot perioperative antibiotic therapy. Hemodynamics were registered continuously during the operation via an ear artery catheter. Implantation of ports was performed in all animals (11/11) without major complications (mean operation time: 70 +/- 3 min). We did not observe catheter-associated arrhythmia, fall in mean arterial pressure (MAP before and post OP: 70 +/- 2 and 68 +/- 2 Torr, respectively), or change in arterial oxygen saturation (SaO2 before and post OP: 89 +/- 3 and 95 +/- 2%, respectively). With a specifically modified microsurgical insertion technique, cerebral blood supply was effectively preserved as evidenced from postmortem histological examinations, cerebral blood flow determination with fluorescent microspheres, and measurement of S-100b protein serum concentrations, a specific marker of neuronal damage. The positioning of the catheter tip in the left ventricle was found to be correct in 10/11 animals. Repeated and atraumatic microsphere injections into the left ventricle have become feasible by transcutaneous puncture of subcutaneous port systems over several weeks under light sedation. Hence, this new approach (i) avoids the necessity of repeated intracardiac injections and port insertions via thoracotomy, thus reducing the perioperative stress for the animals, and (ii) allows for the first time minimally invasive repetitive and chronic measurements of regional organ blood flow under various experimental settings.


Enteroviruses, type 1 diabetes and hygiene: a complex relationship.
Type 1 diabetes (T1D) is an autoimmune disease in which the immune system mounts an attack on the host's insulin-producing beta cells. Because most cases of T1D cannot be attributed only to individual genetics, it is strongly inferred that there is a significant environmental contribution, such as infection, impacting disease development. The human enteroviruses (HEV) are common picornaviruses often implicated as triggers of human T1D, although precisely which of the numerous HEV may be involved in human T1D development is unknown. Experiments using non-obese diabetic (NOD) mice, commonly used to model T1D, show that induction of T1D by HEV infection in NOD mice is a multifactorial process involving both the virus and the host. Interestingly, results demonstrate that HEV infection of NOD mice can also induce long-term protection from T1D under certain conditions, suggesting that a similar mechanism may occur in humans. Based upon both experimental animal and observational human studies, we postulate that HEV have a dual role in T1D development and can either cause or prevent autoimmune disease. Whichever outcome occurs depends upon multiple variables in the host-virus equation, many of which can be deduced from results obtained from NOD mouse studies. We propose that the background to the sharply rising T1D incidences observed in the 20th century correlates with increased levels of hygiene in human societies. Viewing T1D in this perspective suggests that potential preventative options could be developed.


Bioinformatics approaches to single-cell analysis in developmental biology.
Individual cells within the same population show various degrees of heterogeneity, which may be better handled with single-cell analysis to address biological and clinical questions. Single-cell analysis is especially important in developmental biology as subtle spatial and temporal differences in cells have significant associations with cell fate decisions during differentiation and with the description of a particular state of a cell exhibiting an aberrant phenotype. Biotechnological advances, especially in the area of microfluidics, have led to a robust, massively parallel and multi-dimensional capturing, sorting, and lysis of single-cells and amplification of related macromolecules, which have enabled the use of imaging and omics techniques on single cells. There have been improvements in computational single-cell image analysis in developmental biology regarding feature extraction, segmentation, image enhancement and machine learning, handling limitations of optical resolution to gain new perspectives from the raw microscopy images. Omics approaches, such as transcriptomics, genomics and epigenomics, targeting gene and small RNA expression, single nucleotide and structural variations and methylation and histone modifications, rely heavily on high-throughput sequencing technologies. Although there are well-established bioinformatics methods for analysis of sequence data, there are limited bioinformatics approaches which address experimental design, sample size considerations, amplification bias, normalization, differential expression, coverage, clustering and classification issues, specifically applied at the single-cell level. In this review, we summarize biological and technological advancements, discuss challenges faced in the aforementioned data acquisition and analysis issues and present future prospects for application of single-cell analyses to developmental biology.


A Dose Simulation X-Ray Software: An Innovating Tool to Reduce Chest Radiograph Exposure in Children.
Chest radiography is one of the most frequent x-ray examinations performed on children. Reducing the delivered dose is always a major task. The objective of our study was to determine the minimum dose to be delivered while maintaining the image quality of chest radiographs, using dose reduction simulation software. We included 60 children who had had a chest radiography in 5 groups established according to the diagnostic reference levels equitably represented by weight ranges. The software simulated for each radiograph 6 additional simulated photonic noise images corresponding to 100%, 80%, 64%, 50%, 40%, and 32% of the initial dose. The 360 radiographs were blindly scored by 2 radiologists, according to the 7 European quality criteria and a subjective criterion of interpretability, using a semiquantitative visual Lickert scale. There was no significant difference in scoring between the reference radiograph (100%) and simulated radiographs at 80% of the dose in children between 5 and 20 kg, 50% of the dose in children between 20 and 30 kg, and between simulated radiographs at 40% of the dose in children over 30 kg. Interobserver reproducibility was moderate to excellent. Chest radiography dose might be reduced by 20% in children between 5 and 20 kg, 50% in children between 20 and 30 kg, and 60% in children over 30 kg, without any difference in the image quality appreciation. Software that produced simulated x-ray with decreasing delivered dose is an innovating tool for an optimization process.


Medical savings accounts in Singapore: a critical inquiry.
With the United States currently experimenting with medical savings accounts (MSAs), it is appropriate to revisit the Singapore experience, where the practice has been in place for a decade and half. Singapore runs a modern, effective health system at a fraction of the cost of most systems operating in the developed West. Although MSAs contribute to the framework of a cultural rhetoric of personal responsibility for health care, this article argues that the heart of the Singapore system of health funding, with its financial discipline, is government control of inputs and outputs and strict rationing of health services according to wealth.


Thyroid tuberculosis: a case series and a review of the literature.
Objective. Tuberculosis of the thyroid gland is a very rare disease. The incidence of extrapulmonary tuberculosis has been showing a progressive increase in the recent years. We present three cases of primary thyroid tuberculosis. Methods. Two cases were diagnosed on the basis of fine-needle aspiration cytology (FNAC), as they presented with thyroid nodule. The third case was diagnosed on histopathology as the patient underwent total thyroidectomy for the left-side nodule which was a follicular lesion on FNAC. Tuberculosis was diagnosed on the other lobe. Results. All three patients were given antituberculous treatment for nine months, and their nodular lesions completely resolved after treatment. Conclusion. Although rare the, thyroid tuberculosis should be kept in mind in the differential diagnosis of thyroid masses, even in patient with no history and symptom of tuberculosis disease elsewhere.


Phonological awareness training and phonological therapy approaches for specific language impairment children with speech sound disorders: a comparative outcome study.
Children with specific language impairment (SLI) might present with speech sound disorder (SSD) and phonological awareness (PA) deficits which put them at risk of potential reading problems. This work aimed to organize an intervention program in Arabic for phonological training and to assess the effect of PA training versus the phonological therapy (PT) for children with SLI and SSD. The study was carried out on 60 children with comorbid SLI and SSD, aged 5-7 years. Children were equally divided into two groups; each group received language therapy combined with (PT or PA training). Measures of language development, phonological output, and PA were taken before therapy and at 4 month post-therapy for all children. The two therapy groups made nearly the same amount of progress in the development of language and phonological production, with no significant differences regarding language age and percent of consonants correct (PCC). The PA training group progressed more on the PA skills than children who received PT over the same time. PA training could facilitate the development of phonological skills by targeting the child's awareness of phonemes and improving the production of sound patterns.


Toxicokinetics of ibogaine and noribogaine in a patient with prolonged multiple cardiac arrhythmias after ingestion of internet purchased ibogaine.
Ibogaine is an agent that has been evaluated as an unapproved anti-addictive agent for the management of drug dependence. Sudden cardiac death has been described to occur secondary to its use. We describe the clinical effects and toxicokinetics of ibogaine and noribogaine in a single patient. For this purpose, we developed a LC-MS/MS-method to measure ibogaine and noribogaine plasma-concentrations. We used two compartments with first order absorption. The maximum concentration of ibogaine was 1.45 mg/L. Our patient developed markedly prolonged QTc interval of 647ms maximum, several multiple cardiac arrhythmias (i.e., atrial tachycardia and ventricular tachycardia and Torsades des Pointes). QTc-prolongation remained present until 12 days after ingestion, several days after ibogaine plasma-levels were low, implicating clinically relevant noribogaine concentrations long after ibogaine had been cleared from the plasma. The ratio k12/k21 for noribogaine was 21.5 and 4.28 for ibogaine, implicating a lower distribution of noribogaine from the peripheral compartment into the central compartment compared to ibogaine. We demonstrated a linear relationship between the concentration of the metabolite and long duration of action, rather than with parent ibogaine. Therefore, after (prolonged) ibogaine ingestion, clinicians should beware of long-term effects due to its metabolite.


An Observational Study of Honey Bee Colony Winter Losses and Their Association with Varroa destructor, Neonicotinoids and Other Risk Factors.
This article presents results of an analysis of honey bee losses over the winter of 2011-2012 in the Netherlands, from a sample of 86 colonies, located at 43 apiaries. The apiaries were selected using spatially stratified random sampling. Colony winter loss data were collected and related to various measures of colony strength recorded in summer, as well as data from laboratory analysis of sample material taken from two selected colonies in each of the 43 apiaries. The logistic regression model which best explained the risk of winter loss included, in order of statistical importance, the variables (1) Varroa destructor mite infestation rate in October 2011, (2) presence of the cyano-substituted neonicotinoids acetamiprid or thiacloprid in the first 2 weeks of August 2011 in at least one of the honey bee matrices honey, bees or bee bread (pollen), (3) presence of Brassica napus (oilseed rape) or Sinapis arvensis (wild mustard) pollen in bee bread in early August 2011, and (4) a measure of the unexplained winter losses for the postal code area where the colonies were located, obtained from a different dataset. We consider in the discussion that reduced opportunities for foraging in July and August because of bad weather may have added substantially to the adverse effects of acetamiprid and thiacloprid. A novel feature of this work is its use of postal code random effects from two other independent datasets collected in the annual national monitoring by questionnaires of winter losses of honey bees in the Netherlands. These were used to plan the sample selection and also in the model fitting of the data in this study. It should however be noted that the results of the present pilot study are based on limited data, which may consequently reveal strong factors but fail to demonstrate possible interaction effects.


Prevalence of metabolic syndrome among Filipino adults aged 20 years and over.
This study sought to determine the prevalence of metabolic syndrome, using data collected from 4,541 adults aged 20 years and over covered in the Fifth National Nutrition Survey conducted in 1998. The metabolic variables analyzed were: total cholesterol, LDL-c, HDL-c, triglycerides and fasting blood glucose. In addition, measurements of obesity such as body mass index (BMI), waist-to-hip ratio (WHR) and waist circumference (WC) as well as blood pressure were taken. Comparing the mean metabolic characteristics of the non-obese, total obese and the android obese, results showed significant differences in almost all the variables except for the HDL-c. By gender, non-significant differences were observed between males and females in the non-obese group in terms of the BMI and glucose levels and in the android group, in terms of total cholesterol. In all three groups, the biggest difference was observed in the mean triglycerides, where males had significantly higher mean than the females. Comparing adults with >125 mg/dl fasting blood sugar (FBS) there were higher rates of hypertension, high waist-to-hip ratio (WHR), high cholesterol, high triglycerides, high LDL-c, low HDL-c, among the overweight and obese than among those with normal BMI. In general, the proportion of subjects with co-morbid factors increased with higher levels of FBS, except for high cholesterol wherein no pattern was established. The highest prevalence of high FBS was found in both males (35.8%) and females (14.5%) with the following combined characteristics: high BMI, high WHR and high WC. Males with co-existing high BMI, high WHR, and high WC were observed to have the highest prevalence rate of hypertension (66.5%). Among females, the highest prevalence rate of hypertension (37.9%) was seen among those with high fasting blood sugar. The proportion of subjects with hypertension generally increased with age irrespective of the BMI status. One of the significant correlates of high FBS is waist-hip ratio. Males with WHR of equal or greater than 1 have almost six times the risk of having high FBS, while females with WHR of equal or greater than 0.85 have five times the risk of having high FBS compared to those with normal WHR. Among females with triglyceride levels of equal or greater than 200 mg/dL, the risk of having high FBS is five times compared to those with triglyceride levels below 200 mg/dL. Univariate analysis to see the effect of the type of obesity to dyslipidaemia and hypertension revealed that females with high waist circumference generally provided greater risk compared to those who were overweight and obese as well as those with android obesity. For males, high waist circumference had greater risk of developing high triglyceride and high LDL-c. Android obese males had greater risk to high FBS. The results showed that the prevalence rate of metabolic syndrome is 0.28%, based on the number of individuals with the following characteristics: high FBS, hypertensive, android obese, with body mass index (BMI) of > or =25.0 and high WC. Females had a higher rate than males - almost twice. Considering that metabolic syndrome, with its co-morbidity factors is prevalent among some Filipino adults aged 20 years and over, it is recommended that health programs geared towards minimizing the morbid risk factors be properly developed, promoted and fully implemented.


Detecting Adaptation in Protein-Coding Genes Using a Bayesian Site-Heterogeneous Mutation-Selection Codon Substitution Model.
Codon substitution models have traditionally attempted to uncover signatures of adaptation within protein-coding genes by contrasting the rates of synonymous and non-synonymous substitutions. Another modeling approach, known as the mutation-selection framework, attempts to explicitly account for selective patterns at the amino acid level, with some approaches allowing for heterogeneity in these patterns across codon sites. Under such a model, substitutions at a given position occur at the neutral or nearly neutral rate when they are synonymous, or when they correspond to replacements between amino acids of similar fitness; substitutions from high to low (low to high) fitness amino acids have comparatively low (high) rates. Here, we study the use of such a mutation-selection framework as a null model for the detection of adaptation. Following previous works in this direction, we include a deviation parameter that has the effect of capturing the surplus, or deficit, in non-synonymous rates, relative to what would be expected under a mutation-selection modeling framework that includes a Dirichlet process approach to account for across-codon-site variation in amino acid fitness profiles. We use simulations, along with a few real data sets, to study the behavior of the approach, and find it to have good power with a low false-positive rate. Altogether, we emphasize the potential of recent mutation-selection models in the detection of adaptation, calling for further model refinements as well as large-scale applications.


Verbal working memory dysfunction in schizophrenia: an FMRI investigation.
Impaired processing of working memory information is one of the cognitive deficits seen in patients with schizophrenia. This study aims at corroborating the differences in the brain activities involved in the process of working memory between patients with schizophrenia and the controls. Twelve patients with schizophrenia and 11 controls participated in the study. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the performance of a two-back verbal working memory paradigm using the Korean alphabet as mnemonic content. Group analysis revealed that inferior fontal, middle frontal, and superior temporal region showed decreased cortical activities in the patient group compared to those of the controls. This study showed a decreased activation in inferior fontal (BA 47), middle frontal (BA 6), and superior temporal (BA 22/38) neural networks from the patient group and confirmed the earlier findings on the impaired working memory of schizophrenic patients in the fMRI investigation.


The spatial structure in liquid water.
Liquid state structure has traditionally been characterized with the radial distribution functions between atoms. Although these functions are routinely available from x-ray diffraction and neutron scattering experiments or from computer simulations, they cannot be interpreted unambiguously to provide the spatial order in a molecular liquid. A direct approach to determining the spatial structure in the liquid state is demonstrated here. Three-dimensional maps representing the local atomic densities are presented for several water models. These spatial maps provide a picture of the short-range order in liquid water which reveals specific details of its local structure that are important in the understanding of its properties.


Evaluation of contextual influences on the medication administration practice of paediatric nurses.
This paper is a report of a study conducted to explore the impact of preidentified contextual themes (related to work environment and socialization) on nursing medication practice. Medication administration is a complex aspect of paediatric nursing and an important component of day-to-day nursing practice. Many attempts are being made to improve patient safety, but many errors remain. Identifying and understanding factors that influence medication administration errors are of utmost importance. A cross-sectional survey was conducted with a sample of 278 paediatric nurses from the emergency department, intensive care unit and medical and surgical wards of an Australian tertiary paediatric hospital in 2004. The response rate was 67%. Contextual influences were important in determining how closely medication policy was followed. Completed questionnaires were returned by 185 nurses (67%). Younger nurses aged <34 years thought that their medication administration practice could be influenced by the person with whom they checked the drugs (P = 0.001), and that there were daily circumstances when it was acceptable not to adhere strictly to medication policy (P < 0.001), including choosing between following policy and acting in the best interests of the child (P = 0.002). Senior nurses agreed that senior staff dictate acceptable levels of medication policy adherence through role modelling (P = 0.01). Less experienced nurses reported greater confidence with computer literacy (P < 0.001). Organizations need to employ multidisciplinary education programmes to promote universal understanding of, and adherence to, medication policies. Skill mix should be closely monitored to ensure adequate support for new and junior staff.


Lung Parenchymal Signal Intensity in MRI: A Technical Review with Educational Aspirations Regarding Reversible Versus Irreversible Transverse Relaxation Effects in Common Pulse Sequences.
Lung parenchyma is challenging to image with proton MRI. The large air space results in ~l/5th as many signal-generating protons compared to other organs. Air/tissue magnetic susceptibility differences lead to strong magnetic field gradients throughout the lungs and to broad frequency distributions, much broader than within other organs. Such distributions have been the subject of experimental and theoretical analyses which may reveal aspects of lung microarchitecture useful for diagnosis. Their most immediate relevance to current imaging practice is to cause rapid signal decays, commonly discussed in terms of short T2* values of 1 ms or lower at typical imaging field strengths. Herein we provide a brief review of previous studies describing and interpreting proton lung spectra. We then link these broad frequency distributions to rapid signal decays, though not necessarily the exponential decays generally used to define T2* values. We examine how these decays influence observed signal intensities and spatial mapping features associated with the most prominent torso imaging sequences, including spoiled gradient and spin echo sequences. Effects of imperfect refocusing pulses on the multiple echo signal decays in single shot fast spin echo (SSFSE) sequences and effects of broad frequency distributions on balanced steady state free precession (bSSFP) sequence signal intensities are also provided. The theoretical analyses are based on the concept of explicitly separating the effects of reversible and irreversible transverse relaxation processes, thus providing a somewhat novel and more general framework from which to estimate lung signal intensity behavior in modern imaging practice.


Multidimensional metrics of niche space for use with diverse analytical techniques.
Multidimensional data are integral to many community-ecological studies and come in various forms, such as stable isotopes, compound specific analyses (e.g., amino acids and fatty acids), and both biodiversity and life history traits. Scientists employing such data often lack standardized metrics to evaluate communities in niche space where more than 2 dimensions are involved. To alleviate this problem, we developed a graphing and analytical approach for use with more than two variables, based on previously established stable isotope bi-plot metrics. We introduce here our community metrics as R scripts. By extending the original metrics to multiple dimensions, we created n-dimensional plots and metrics to characterize any set of quantitative measurements of a community. We demonstrate the utility of these metrics using stable isotope data; however, the approaches are applicable to many types of data. The resulting metrics provide more and better information compared to traditional analytic frameworks. The approach can be applied in many branches of community ecology, and it offers accessible metrics to quantitatively analyze the structure of communities across ecosystems and through time.


Near-infrared silver cluster optically signaling oligonucleotide hybridization and assembling two DNA hosts.
Silver clusters with ~10 atoms form within DNA strands, and the conjugates are chemical sensors. The DNA host hybridizes with short oligonucleotides, and the cluster moieties optically respond to these analytes. Our studies focus on how the cluster adducts perturb the structure of their DNA hosts. Our sensor is comprised of an oligonucleotide with two components: a 5'-cluster domain that complexes silver clusters and a 3'-recognition site that hybridizes with a target oligonucleotide. The single-stranded sensor encapsulates an ~11 silver atom cluster with violet absorption at 400 nm and with minimal emission. The recognition site hybridizes with complementary oligonucleotides, and the violet cluster converts to an emissive near-infrared cluster with absorption at 730 nm. Our key finding is that the near-infrared cluster coordinates two of its hybridized hosts. The resulting tertiary structure was investigated using intermolecular and intramolecular variants of the same dimer. The intermolecular dimer assembles in concentrated (~5 μM) DNA solutions. Strand stoichiometries and orientations were chromatographically determined using thymine-modified complements that increase the overall conjugate size. The intramolecular dimer develops within a DNA scaffold that is founded on three linked duplexes. The high local cluster concentrations and relative strand arrangements again favor the antiparallel dimer for the near-infrared cluster. When the two monomeric DNA/violet cluster conjugates transform to one dimeric DNA/near-infrared conjugate, the DNA strands accumulate silver. We propose that these correlated changes in DNA structure and silver stoichiometry underlie the violet to near-infrared cluster transformation.


Maintenance N-acetyl cysteine treatment for bipolar disorder: a double-blind randomized placebo controlled trial.
N-acetyl cysteine (NAC) is a glutathione precursor that has been shown to have antidepressant efficacy in a placebo-controlled trial. The current study aimed to investigate the maintenance effects of NAC following eight weeks of open-label treatment for bipolar disorder. The efficacy of a double blind randomized placebo controlled trial of 2 g/day NAC as adjunct maintenance treatment for bipolar disorder was examined. Participants (n = 149) had a Montgomery Asberg Depression Rating Score of ≥12 at trial entry and, after eight weeks of open-label NAC treatment, were randomized to adjunctive NAC or placebo, in addition to treatment as usual. Participants (primarily outpatients) were recruited through public and private services and through newspaper advertisements. Time to intervention for a mood episode was the primary endpoint of the study, and changes in mood symptoms, functionality and quality of life measures were secondary outcomes. There was a substantial decrease in symptoms during the eight-week open-label NAC treatment phase. During the subsequent double-blind phase, there was minimal further change in outcome measures with scores remaining low. Consequently, from this low plateau, between-group differences did not emerge on recurrence, clinical functioning or quality of life measures. There were no significant between-group differences in recurrence or symptomatic outcomes during the maintenance phase of the trial; however, these findings may be confounded by limitations. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12607000074493).


Metabolic stress induces a Wnt-dependent cancer stem cell-like state transition.
Reciprocal interactions between cancer cells and the tumor microenvironment drive multiple clinically significant behaviors including dormancy, invasion, and metastasis as well as therapy resistance. These microenvironment-dependent phenotypes share typical characteristics with cancer stem cells (CSC). However, it is poorly understood how metabolic stress in the confined tumor microenvironment contributes to the emergence and maintenance of CSC-like phenotypes. Here, we demonstrate that chronic metabolic stress (CMS) in a long-term nutrient deprivation induces a Wnt-dependent phenoconversion of non-stem cancer cells toward stem-like state and this is reflected in the transcriptome analysis. Addition of Wnt3a as well as transfection of dominant-negative Tcf4 establishes an obligatory role for the Wnt pathway in the acquisition of CSC-like characteristics in response to metabolic stress. Furthermore, systematic characterization for multiple single cell-derived clones and negative enrichment of CD44+/ESA+ stem-like cancer cells, all of which recapitulate stem-like cancer characteristics, suggest stochastic adaptation rather than selection of pre-existing subclones. Finally, CMS in the tumor microenvironment can drive a CSC-like phenoconversion of non-stem cancer cells through stochastic state transition dependent on the Wnt pathway. These findings contribute to an understanding of the metabolic stress-driven dynamic transition of non-stem cancer cells to a stem-like state in the tumor metabolic microenvironment.


Comparative analysis of dietary guidelines in the Spanish-Speaking Caribbean.
Dietary guidelines are important education and policy tools to address local nutrition concerns. The current paper presents a comparative analysis of nutrition messages from three Spanish-speaking Caribbean countries (Cuba, Puerto Rico and Dominican Republic) to explore how these dietary guidelines address common public health nutrition concerns, contextualized in different changing food environments and food culture similarities. Qualitative, comparative analysis of current dietary guideline documents and key recommendations. Key recommendations were categorized into sixteen themes (two diet-based, ten food-based and four 'other'). Only the Cuban dietary guidelines included diet-based key recommendations. Of the ten food-based key recommendations, only four themes overlapped across the three dietary guidelines (the encouragement of fruits and vegetables, addressing protein sources and fat). Other overlaps were found between dietary guideline pairs, except between Cuba and Puerto Rico. Further analysis revealed differences in levels of specificity and acknowledgement of local dietary patterns and issues, as well as the need to revise the guidelines to account for current scientific advances. The present study underscored the importance of context in the framing of dietary advice and the influence of national socio-economic and political situations on nutrition policy and education efforts. The results contribute to inform efforts to improve nutrition communication in the region and among migrant communities.


Plant-based vaccines for animal health.
Plant-based vaccines are recombinant protein subunit vaccines. Ideally, the choice of plant species used to produce the selected antigen should allow for oral delivery in the form of an edible vaccine. These vaccines are well suited to combat diseases where there is a clear antigen candidate, and where the costs of production or delivery for any current vaccine are prohibitive. Several academic and industrial research groups are currently investigating the use of plant-based vaccines in both humans and animals. To date, the most advanced human vaccine projects have successfully completed phase I clinical trials, and animal vaccine projects have given promising data in early phase trials targeting specific animal species. In this article the advantages offered by plant-based vaccines will be presented, progress on the most advanced vaccine candidates will be summarised, and the path ahead will be outlined. Although the focus of this paper is on the application of plant-based vaccines in the field of animal health, principally their use in domestic livestock, examples of the use of plant-based vaccines in the field of human health will also be discussed.


Food addiction symptomology, impulsivity, mood, and body mass index in people with type two diabetes.
This research explored how food addiction (FA) and impulsivity (non-planning, motor, and attentional) relate to body mass index (BMI) in a sample of people with type 2 diabetes (t2d). Participants with t2d (N = 334, Mage = 41.0, SDage = 9.5, 66% female, MBMI = 37.6 kg/m(2), SDBMI = 8.0 kg/m(2)) completed an online survey including the Depression Anxiety Stress Scale (DASS-21), the Barratt Impulsiveness Scale (BIS-II), and the Yale Food Addiction Scale (YFAS). Results demonstrated that over 70% of the sample with t2d met the YFAS criteria for FA. Results also demonstrated that participants classified as FA had significantly higher BMI, t (332) = 12.11, p < .001. The food addict classification group also had a significantly higher percentage of obese participants, χ(2) (2) = 87.1, p < .001, phi = .511. Utilising a cross-sectional design to predict BMI, significant forward stepwise multiple regression demonstrated that FA (β = .386) and impulsivity (non-planning) (β = .286) were significant predictors. In combination FA and impulsivity (non-planning) significantly explained 38% of BMI variance; however depression, anxiety, and stress did not significantly improve the model. These results suggest FA and impulsivity (non-planning) are more salient cross-sectional predictors of BMI, in people with t2d, than indices of depression, anxiety, stress and impulsivity (motor and attentional). These results, implicating FA in the development of obesity, have important ramifications for potential future treatment methods of t2d where FA symptomology could be routinely screened, and if present, treated via addiction models rather than purely attempting to treat the potential consequences of FA.


Cyclin partners determine Pho85 protein kinase substrate specificity in vitro and in vivo: control of glycogen biosynthesis by Pcl8 and Pcl10.
In Saccharomyces cerevisiae, PHO85 encodes a cyclin-dependent protein kinase (Cdk) with multiple roles in cell cycle and metabolic controls. In association with the cyclin Pho80, Pho85 controls acid phosphatase gene expression through phosphorylation of the transcription factor Pho4. Pho85 has also been implicated as a kinase that phosphorylates and negatively regulates glycogen synthase (Gsy2), and deletion of PHO85 causes glycogen overaccumulation. We report that the Pcl8/Pcl10 subgroup of cyclins directs Pho85 to phosphorylate glycogen synthase both in vivo and in vitro. Disruption of PCL8 and PCL10 caused hyperaccumulation of glycogen, activation of glycogen synthase, and a reduction in glycogen synthase kinase activity in vivo. However, unlike pho85 mutants, pcl8 pcl10 cells had normal morphologies, grew on glycerol, and showed proper regulation of acid phosphatase gene expression. In vitro, Pho80-Pho85 complexes effectively phosphorylated Pho4 but had much lower activity toward Gsy2. In contrast, Pcl10-Pho85 complexes phosphorylated Gsy2 at Ser-654 and Thr-667, two physiologically relevant sites, but only poorly phosphorylated Pho4. Thus, both the in vitro and in vivo substrate specificity of Pho85 is determined by the cyclin partner. Mutation of PHO85 suppressed the glycogen storage deficiency of snf1 or glc7-1 mutants in which glycogen synthase is locked in an inactive state. Deletion of PCL8 and PCL10 corrected the deficit in glycogen synthase activity in both the snf1 and glc7-1 mutants, but glycogen synthesis was restored only in the glc7-1 mutant strain. This genetic result suggests an additional role for Pho85 in the negative regulation of glycogen accumulation that is independent of Pcl8 and Pcl10.


Genome-wide conserved non-coding microsatellite (CNMS) marker-based integrative genetical genomics for quantitative dissection of seed weight in chickpea.
Phylogenetic footprinting identified 666 genome-wide paralogous and orthologous CNMS (conserved non-coding microsatellite) markers from 5'-untranslated and regulatory regions (URRs) of 603 protein-coding chickpea genes. The (CT)n and (GA)n CNMS carrying CTRMCAMV35S and GAGA8BKN3 regulatory elements, respectively, are abundant in the chickpea genome. The mapped genic CNMS markers with robust amplification efficiencies (94.7%) detected higher intraspecific polymorphic potential (37.6%) among genotypes, implying their immense utility in chickpea breeding and genetic analyses. Seventeen differentially expressed CNMS marker-associated genes showing strong preferential and seed tissue/developmental stage-specific expression in contrasting genotypes were selected to narrow down the gene targets underlying seed weight quantitative trait loci (QTLs)/eQTLs (expression QTLs) through integrative genetical genomics. The integration of transcript profiling with seed weight QTL/eQTL mapping, molecular haplotyping, and association analyses identified potential molecular tags (GAGA8BKN3 and RAV1AAT regulatory elements and alleles/haplotypes) in the LOB-domain-containing protein- and KANADI protein-encoding transcription factor genes controlling the cis-regulated expression for seed weight in the chickpea. This emphasizes the potential of CNMS marker-based integrative genetical genomics for the quantitative genetic dissection of complex seed weight in chickpea.


Measurement of apolipoprotein E and amyloid β clearance rates in the mouse brain using bolus stable isotope labeling.
Abnormal proteostasis due to alterations in protein turnover has been postulated to play a central role in several neurodegenerative diseases. Therefore, the development of techniques to quantify protein turnover in the brain is critical for understanding the pathogenic mechanisms of these diseases. We have developed a bolus stable isotope-labeling kinetics (SILK) technique coupled with multiple reaction monitoring mass spectrometry to measure the clearance of proteins in the mouse brain. Cohorts of mice were pulse labeled with 13C6-leucine and the brains were isolated after pre-determined time points. The extent of label incorporation was measured over time using mass spectrometry to measure the ratio of labeled to unlabeled apolipoprotein E (apoE) and amyloid β (Aβ). The fractional clearance rate (FCR) was then calculated by analyzing the time course of disappearance for the labeled protein species. To validate the technique, apoE clearance was measured in mice that overexpress the low-density lipoprotein receptor (LDLR). The FCR in these mice was 2.7-fold faster than wild-type mice. To demonstrate the potential of this technique for understanding the pathogenesis of neurodegenerative disease, we applied our SILK technique to determine the effect of ATP binding cassette A1 (ABCA1) on both apoE and Aβ clearance. ABCA1 had previously been shown to regulate both the amount of apoE in the brain, along with the extent of Aβ deposition, and represents a potential molecular target for lowering brain amyloid levels in Alzheimer's disease patients. The FCR of apoE was increased by 1.9- and 1.5-fold in mice that either lacked or overexpressed ABCA1, respectively. However, ABCA1 had no effect on the FCR of Aβ, suggesting that ABCA1 does not regulate Aβ metabolism in the brain. Our SILK strategy represents a straightforward, cost-effective, and efficient method to measure the clearance of proteins in the mouse brain. We expect that this technique will be applicable to the study of protein dynamics in the pathogenesis of several neurodegenerative diseases, and could aid in the evaluation of novel therapeutic agents.


The association of reduced folate carrier 80G>A polymorphism to outcome in childhood acute lymphoblastic leukemia interacts with chromosome 21 copy number.
The reduced folate carrier (RFC) is involved in the transport of methotrexate (MTX) across the cell membrane. The RFC gene (SLC19A1) is located on chromosome 21, and we hypothesized that the RFC80 G>A polymorphism would affect outcome and toxicity in childhood leukemia and that this could interact with chromosome 21 copy number in the leukemic clone. A total of 500 children with acute lymphoblastic leukemia treated according to the common Nordic treatment protocols were included, and we found that the RFC AA variant was associated with a 50% better chance of staying in remission compared with GG or GA variants (P = .046). Increased copy numbers of chromosome 21 appear to improve outcome also in children with GA or GG variant. In a subset of 182 children receiving 608 high-dose MTX courses, we observed higher degree of bone marrow toxicity in patients with the RFC AA variant compared with GA/GG variants (platelet 73 vs 99/105 x 10(9)/L, P = .004, hemoglobin 5.6 vs 5.9/6.0 mmol/L, P = .004) and a higher degree of liver toxicity in patients with RFC GG variant (alanine aminotransferase 167 vs 127/124 U/L, P = .05). In conclusion, the RFC 80G>A polymorphism interacts with chromosome 21 copy numbers and affects both efficacy and toxicity of MTX.


Effect of garlic intake on inflammatory mediators: a systematic review and meta-analysis of randomised controlled trials.
Garlic is a species in the onion genus, Allium. Data have shown that garlic has anti-inflammatory activity; however, the findings are inconclusive and inconsistent. We aimed to evaluate the impact of garlic intake on inflammatory mediators through systematic review and meta-analysis of existing data. Electronic databases were completely investigated using databases of ISI Web of Science, Medline, Scopus, Cochrane Library and EMBASE until October 2019. A random effects model and the generic reverse variance procedure were used for quantitative data production. Sensitivity analyses and prespecified subgroup were done to evaluate potential heterogeneity. Random effect meta-regression was conducted to investigate the effects of possible confounders on the assessed effect size. Ten trials with one observational study, including 530 participants, met the eligibility criteria. The findings showed reduction in the tumour necrosis factor alpha (TNF-α) (-0.31 pg/mL, 95% CI -1.07 to 0.46) and C reactive protein (CRP) levels (-0.20 mg/L, 95% CI -1.4 to 1.05) following supplementation with garlic, although it had no marked impact on the interleukin 6 (IL-6) level (0.37 pg/mL, 95% CI -0.58 to 1.33). In the subgroup analysis, we found that garlic supplementation significantly decreased TNF-α, highly sensitive CRP and IL-6 levels in subgroups of >8, >6 and ≥4 weeks of intervention duration, respectively, and dose of garlic consumption between 2 and 2.4 g/day. These findings suggested that current evidence may support garlic as an adjunct to pharmacological management of metabolic diseases. CRD42018108816.


Ratio of Range of Motion of the Ankle and Surrounding Joints After Total Ankle Replacement: A Radiographic Cohort Study.
This study attempted to identify where motion occurs after total ankle replacement, the difference in range-of-motion contributions between fixed-bearing and mobile-bearing total ankle replacements, and the contribution of abnormal peritalar motion. We hypothesized that sagittal plane radiographic assessment would demonstrate that actual ankle motion through the prosthesis is less than the total arc of ankle motion that may be observed clinically secondary to contributions from adjacent joints. Patients underwent routine standardized weight-bearing maximum dorsiflexion and plantar flexion sagittal radiographs. Sagittal plane ankle and foot measurements were performed on each dorsiflexion and plantar flexion radiograph to determine the total arc of ankle motion, actual ankle motion through the prosthesis, motion through the subtalar and talonavicular joints, and midfoot motion. Motion radiographs were routinely made at 1 year postoperatively and at the time of the most recent follow-up. A minimum follow-up of 2 years was required of all patients. There were 197 patients who met the inclusion criteria (75 INBONE, 52 Salto Talaris, and 70 STAR prostheses). The mean time to the latest radiographs (and standard deviation) was 42.9 ± 18.8 months. The mean actual ankle motion through the prosthesis was 25.9° ± 12.2°, which was significantly less (p < 0.001) than the mean total motion arc of 37.6° ± 12.0°. The motion of the ankle accounted for 68% of total range of motion, and motion of the peritalar joints accounted for 32%. There was no significant difference (p > 0.05) among the 3 prostheses or when comparing fixed and mobile-bearing designs for both ranges of motion. This study demonstrates that actual ankle motion after total ankle replacement is approximately 12° less than the total arc of motion that might be observed clinically because of increased midfoot and subtalar motion. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Detection of methicillin-resistant Staphylococcus aureus using double duplex real-time PCR and dye Syto 9.
A screening method for methicillin-resistant Staphylococcus aureus (MRSA) using real-time polymerase chain reaction (PCR) and dye Syto 9 was developed and evaluated. The assay was based on the two duplex reactions run simultaneously. The detection reaction amplified staphylococcal cassette chromosome mec (SCCmec) right extremity sequences and S. aureus-specific 442-bp DNA (Sa442). The control reaction amplified S. aureus-specific nuclease gene nuc and a marker of methicillin resistance, mecA. The method was evaluated by analyzing 214 clinical S. aureus isolates yielding 98.7 % sensitivity, 100 % specificity, 100 % positive predictive value and 96.6 % negative predictive value for detection of MRSA. The detection limit was determined to be 15-80 genome copies per real-time PCR. It was able to discriminate between MRSA, methicillin resistant coagulase negative staphylococci and methicillin susceptible S. aureus (MSSA) isolates containing only small fragments of the right extremity of the SCCmec (MSSA revertants).


Women convicted of promoting prostitution of a minor are different from women convicted of traditional sexual offenses: a brief research report.
Some jurisdictions have legally decreed that certain nonsexual offenses (e.g., promoting prostitution of a minor, arson, burglary) can be considered sexual offenses. Offenders convicted of these crimes can be subjected to sexual offender-specific social control policies such as registration, as well as be included in sexual offender research such as recidivism studies. No studies, however, have systematically examined differences and similarities between this new class of sexual offenders and more traditional sexual offenders. The current study used a sample of 94 women convicted of sexual offenses to investigate whether women convicted of promoting prostitution of a minor differed on demographic and criminogenic features from those convicted of more traditional sexual offenses. Results show that women convicted of promoting prostitution offenses have criminal histories more consistent with general criminality and exhibit more general antisocial features than women convicted of traditional sexual offenses. These results support the notion that the inclusion of legally defined sexual offenders with traditional ones obscures important differences in criminogenic features among these women.


Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior.
The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA's effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.


Return to Work Among Young Adult Survivors of Allogeneic Hematopoietic Cell Transplantation in the United States.
Young adult (YA) survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk for late psychosocial challenges, including the inability to return to work post-HCT. Work-related outcomes in this population remain understudied, however. We conducted this study to assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YAs and to analyze the patient-, disease-, and HCT-related factors associated with their work status at 1 year post-HCT. Using Center for International Blood and Marrow Transplant Research data, we evaluated the post-HCT work status (full-time, part-time work, unemployed, or medical disability) of 1365 YA HCT survivors who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at 4 time points: 6 months, 1 year, 2 years, and 3 years post-HCT. Percentages of post-HCT work status categories at the 1-year time point were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression. From 6 months to 3 years post-HCT, the percentage of survivors working full-time increased from 18.3% to 50.7% and the percentage working part-time increased from 6.9% to 10.5%. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1 year post-HCT. Female sex (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.40 to 0.77), HCT Comorbidity Index score ≥3 (OR, 0.57; 95% CI, 0.39 to 0.82), pre-HCT unemployment (OR, 0.37; 95% CI, 0.24 to 0.56), medical disability (OR, 0.44; 95% CI, 0.28 to 0.70), development of grade III-IV acute graft-versus-host disease (OR, 0.52; 95% CI, 0.34 to 0.80), and relapse within 1 year post-HCT (OR, 0.34; 95% CI, 0.21 to 0.56) were associated with a lower likelihood of employment at 1 year post-HCT. Compared with myeloablative conditioning (MAC) with total body irradiation (TBI), MAC without TBI (OR, 1.71; 95% CI, 1.16 to 2.53) was associated with a greater likelihood of employment at 1 year post-HCT. Graduate school-level education (OR, 2.47; 95% CI, 1.49 to 4.10) was also associated with a greater likelihood of employment at 1 year post-HCT. Although the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective interventions to support return to work in this population.


Unprotected Sex with Injecting Drug Users among Iranian Female Sex Workers: Unhide HIV Risk Study.
Purpose. To assess the prevalence and associated factors of unprotected sex with injecting drug users (IDUs) among a sample of female sex workers (FSWs) in Iran. Methods. This cross-sectional study included 144 FSWs who were interviewed as a part of Unhide HIV Risk Study, a national behavioral survey focusing on various high-risk populations, including IDUs, FSWs, and Men who have Sex with Men (MSMs) in 2009. The survey was conducted in eight provinces in Iran using respondent-driven sampling. Participants' sociodemographic status, HIV knowledge, and HIV attitude were analyzed via logistic regression to determine the predictors of unprotected sex with IDU(s) during the past month. Results. Nineteen percent of FSWs reported at least one occasion of unprotected sex with IDU(s) in the month preceding the study. Higher educational level (OR = -0.653, 95%CI = -1.192 to -0.115), perceived HIV risk (OR = -1.047, 95%CI = -2.076 to -0.019), and perceived family intimacy during childhood (OR = -1.104, 95%CI = -1.957 to -0.251) were all independently associated with lower odds of having unprotected sex with IDU(s) in the month preceding the study. Age, marital status, living condition, HIV knowledge, and perceived behavioral control did not affect the odds of FSWs having sex with IDUs. Conclusion. Perceived HIV risk, which is a modifiable factor, seems to be a promising target for harm reduction interventions amongst Iranian female sex workers. Data presented here may aid in reducing or eliminating the role of sex workers as a bridge for HIV transmission from IDUs to the general population in Iran.


Insect pests of pigeonpea and their management.
Pigeonpea (Cajanus cajan) is an important crop in semi-arid tropical and subtropical farming systems, providing high quality vegetable protein, animal feed, and firewood. Insect pests feeding on flowers, pods, and seeds are the most important biotic constraint affecting pigeonpea yields. This review summarizes the biology and ecology of the three most important groups of pests: flower- and pod-feeding Lepidoptera, pod-sucking Hemiptera, and seed-feeding Diptera and Hymenoptera. Recent research investigating the complex interactions among pigeonpea, its key pests, and their natural enemies is also reviewed. These relationships have implications on the pest status of individual species and on possible control strategies. Pigeonpea pest management research has focused until recently on the identification and development of resistant cultivars and on chemical control. Future research must focus on environmentally sound pest management strategies that are compatible with the needs and limitations of pigeonpea farmers. Several priority areas for research are suggested.


Association between infant breastfeeding and early childhood caries in the United States.
Despite limited epidemiologic evidence, concern has been raised that breastfeeding and its duration may increase the risk of early childhood caries. The objective of this study was to assess the potential association of breastfeeding and other factors with the risk for early childhood caries among young children in the United States. Data about oral health, infant feeding, and other child and family characteristics among children 2 to 5 years of age (N = 1576) were extracted from the 1999-2002 National Health and Nutrition Examination Survey. The association of breastfeeding and its duration, as well as other factors that previous research has found associated with early childhood caries, was examined in bivariate analyses and by multivariable logistic and Poisson regression analyses. After adjusting for potential confounders significant in bivariate analyses, breastfeeding and its duration were not associated with the risk for early childhood caries. Independent associations with increased risk for early childhood caries were older child age, poverty, being Mexican American, a dental visit within the last year, and maternal prenatal smoking. Poverty and being Mexican American also were independently associated with severe early childhood caries, whereas characteristics that were independently associated with greater decayed and filled surfaces on primary teeth surfaces were poverty, a dental visit within the last year, 5 years of age, and maternal smoking. These data provide no evidence to suggest that breastfeeding or its duration are independent risk factors for early childhood caries, severe early childhood caries, or decayed and filled surfaces on primary teeth. In contrast, they identify poverty, Mexican American ethnic status, and maternal smoking as independent risk factors for early childhood caries, which highlights the need to target poor and Mexican American children and those whose mothers smoke for early preventive dental visits.


Viscoelastic properties of chondrocytes from normal and osteoarthritic human cartilage.
The deformation behavior and mechanical properties of articular chondrocytes are believed to play an important role in their response to mechanical loading of the extracellular matrix. This study utilized the micropipette aspiration test to measure the viscoelastic properties of chondrocytes isolated from macroscopically normal or end-stage osteoarthritic cartilage. A three-parameter standard linear solid was used to model the viscoelastic behavior of the cells. Significant differences were found between the mechanical properties of chondrocytes isolated from normal and osteoarthritic cartilage. Specifically, osteoarthritic chondrocytes exhibited a significantly higher equilibrium modulus (0.33 +/- 0.23 compared with 0.24 +/- 0.11 kPa), instantaneous modulus (0.63 +/- 0.51 compared with 0.41 +/- 0.17 kPa), and apparent viscosity (5.8 +/- 6.5 compared with 3.0 +/- 1.8 kPa-s) compared with chondrocytes isolated from macroscopically normal, nonosteoarthritic cartilage. The elastic moduli and relaxation time constant determined experimentally in this study were used to estimate the apparent biphasic properties of the chondrocyte on the basis of the equation for the gel relaxation time of a biphasic material. The differences in viscoelastic properties may reflect alterations in the structure and composition of the chondrocyte cytoskeleton that have previously been associated with osteoarthritic cartilage. Coupled with earlier theoretical models of cell-matrix interactions in articular cartilage, the increased elastic and viscous properties suggest that the mechanical environment of the chondrocyte may be altered in osteoarthritic cartilage.


Imagery in cognitive behavioral supervision.
This article describes the role of imagery in supervision which is a part of the work of both the supervisee and the supervisor. Imagination bears outstanding importance in psychotherapy and supervision. The relevant texts for this narrative review were identified through the Web of Science and PubMed databases, within the period 1990-2019. The search terms included: Supervision, Cognitive behavioural therapy, Imagination, Imagery, Imagery rescripting, Therapeutic relationship, Supervisory relationship. The report also includes information from the books referred to by the articles. The supervisory experiences of the authors were also incorporated. The theoretical part is supplemented with case vignettes of strategies using imagination in CBT supervision. Working with imagery can be used in transformative experiential learning. It can help to better map the situation with the patient, including its emotional components and basic psychological needs, to realise how the therapeutic relationship is set up, as well as to rework own therapist attitudes, schemas and emotional - behavioural responses, and plan future steps in the therapy. Many therapy steps could be learned during imagery exercises. Imagery also helps to understand and regulate the supervisory relationship. It is useful to integrate imagery to the supervision. Using imagery can help to understand the patient, the therapeutic relationship better, and to plan optimal therapeutic strategies, as well as reflect/self-reflect and train difficult skills which promote professional and personal growth.


Effectiveness of Knee Injury and Anterior Cruciate Ligament Tear Prevention Programs: A Meta-Analysis.
Individuals frequently involved in jumping, pivoting or cutting are at increased risk of knee injury, including anterior cruciate ligament (ACL) tears. We sought to use meta-analytic techniques to establish whether neuromuscular and proprioceptive training is efficacious in preventing knee and ACL injury and to identify factors related to greater efficacy of such programs. We performed a systematic literature search of studies published in English between 1996 and 2014. Intervention efficacy was ascertained from incidence rate ratios (IRRs) weighted by their precision (1/variance) using a random effects model. Separate analyses were performed for knee and ACL injury. We examined whether year of publication, study quality, or specific components of the intervention were associated with efficacy of the intervention in a meta-regression analysis. Twenty-four studies met the inclusion criteria and were used in the meta-analysis. The mean study sample was 1,093 subjects. Twenty studies reported data on knee injury in general terms and 16 on ACL injury. Maximum Jadad score was 3 (on a 0-5 scale). The summary incidence rate ratio was estimated at 0.731 (95% CI: 0.614, 0.871) for knee injury and 0.493 (95% CI: 0.285, 0.854) for ACL injury, indicating a protective effect of intervention. Meta-regression analysis did not identify specific intervention components associated with greater efficacy but established that later year of publication was associated with more conservative estimates of intervention efficacy. The current meta-analysis provides evidence that neuromuscular and proprioceptive training reduces knee injury in general and ACL injury in particular. Later publication date was associated with higher quality studies and more conservative efficacy estimates. As study quality was generally low, these data suggest that higher quality studies should be implemented to confirm the preventive efficacy of such programs.


Associations between television viewing and consumption of commonly advertised foods among New Zealand children and young adolescents.
To explore how time spent watching television (TV) is associated with the dietary behaviours of New Zealand children and young adolescents. Secondary data analysis of a nationally representative, cross-sectional survey. In homes or schools of New Zealand school students. In total, 3275 children aged 5 to 14 years. The odds of being overweight or obese increased with duration of TV viewing for children and adolescents when controlling for age, sex, ethnicity, socio-economic status and physical activity. Children and adolescents who watched the most TV were significantly more likely to be higher consumers of foods most commonly advertised on TV: soft drinks and fruit drinks, some sweets and snacks, and some fast foods. Both children and adolescents watching two or more hours of TV a day were more than twice as likely to drink soft drinks five times a week or more (P = 0.03 and P = 0.04, respectively), eat hamburgers at least once a week (both P = 0.02), and eat French fries at least once a week (both P < 0.01). These findings suggest that longer duration of TV watching (thus, more frequent exposure to advertising) influences the frequency of consumption of soft drinks, some sweets and snacks, and some fast foods among children and young adolescents. Efforts to curtail the amount of time children spend watching TV may result in better dietary habits and weight control for children and adolescents. Future studies examining the impact of advertising on children's diets through interventions and international comparisons of legislation would provide more definitive evidence of the role of advertising in child and adolescent obesity.


Soy isoflavones, estrogen therapy, and breast cancer risk: analysis and commentary.
There has been considerable investigation of the potential for soyfoods to reduce risk of cancer, and in particular cancer of the breast. Most interest in this relationship is because soyfoods are essentially a unique dietary source of isoflavones, compounds which bind to estrogen receptors and exhibit weak estrogen-like effects under certain experimental conditions. In recent years the relationship between soyfoods and breast cancer has become controversial because of concerns--based mostly on in vitro and rodent data--that isoflavones may stimulate the growth of existing estrogen-sensitive breast tumors. This controversy carries considerable public health significance because of the increasing popularity of soyfoods and the commercial availability of isoflavone supplements. In this analysis and commentary we attempt to outline current concerns regarding the estrogen-like effects of isoflavones in the breast focusing primarily on the clinical trial data and place these concerns in the context of recent evidence regarding estrogen therapy use in postmenopausal women. Overall, there is little clinical evidence to suggest that isoflavones will increase breast cancer risk in healthy women or worsen the prognosis of breast cancer patients. Although relatively limited research has been conducted, and the clinical trials often involved small numbers of subjects, there is no evidence that isoflavone intake increases breast tissue density in pre- or postmenopausal women or increases breast cell proliferation in postmenopausal women with or without a history of breast cancer. The epidemiologic data are generally consistent with the clinical data, showing no indication of increased risk. Furthermore, these clinical and epidemiologic data are consistent with what appears to be a low overall breast cancer risk associated with pharmacologic unopposed estrogen exposure in postmenopausal women. While more research is required to definitively allay concerns, the existing data should provide some degree of assurance that isoflavone exposure at levels consistent with historical Asian soyfood intake does not result in adverse stimulatory effects on breast tissue.


Position paper: timely interventions in severe acute pancreatitis are crucial for survival.
Severe acute pancreatitis has high mortality, but multiple and timely interventions can improve survival. Early in the course of the disease aggressive fluid resuscitation is needed for the prevention and treatment of shock. In conjunction with leaking capillaries this results in increased tissue edema, which may lead to intra-abdominal hypertension and abdominal compartment syndrome. Invasive hemodynamic monitoring is essential for optimizing fluid therapy while monitoring of intra-abdominal pressure is necessary for identification patients at risk of developing abdominal compartment syndrome. Abdominal compartment syndrome develops usually within the first days after hospitalization. Conservative treatment modalities are useful in prevention but also in the treatment of abdominal compartment syndrome. If conservative management fails surgical decompression of abdomen may be needed. Multiple organ dysfunction syndrome and increased intra-abdominal pressure predispose patients with severe pancreatitis to secondary infections. Extrapancreatic infections predominate during the first week of the disease, whereas infection of pancreatic necrosis usually develops later. Early enteral nutrition reduces the risk of infections whereas advantage of prophylactic antibiotics is lacking evidence. Surgery for infected pancreatic necrosis is associated with high mortality when performed within the first two weeks of the disease. Therefore surgery should be postponed as late as possible, preferably later than four weeks after disease onset.


The effect of variation in interpretation of the La Trobe radiographic foot atlas on the prevalence of foot osteoarthritis in older women: the Chingford general population cohort.
The prevalence of foot osteoarthritis (OA) is much less understood than hip, knee and hand OA. The foot is anatomically complex and different researchers have investigated different joints with lack of methodological standardisation across studies. The La Trobe Foot Atlas (LFA) is the first to address these issues in providing quantitative assessment of radiographic foot OA, but has not been tested externally. The aim of this study was to evaluate three different interpretive approaches to using the LFA for grading OA when scoring is difficult due to indistinct views of interosseous space and joint contour. Foot radiographs of all remaining participants (n = 218) assessed in the Chingford Women Study 23 year visit (mean (SD) for age: 75.5 years (5.1)) were scored using the LFA defined protocol (Technique 1). Two revised scoring strategies were applied to the radiographs in addition to the standard LFA analyses. Technique 2 categorised joints that were difficult to grade as 'missing'. Technique 3 included joints that were difficult to grade as an over estimated score. Radiographic OA prevalence was defined for the foot both collectively and separately for individual joints. When radiographs were scored using the LFA (Technique 1), radiographic foot OA was present in 89.9%. For Technique 2 the presence of radiographic foot OA was 83.5% and for Technique 3 it was 97.2%. At the individual joint level, using Technique 1, the presence of radiographic foot OA was higher with a wider range (18.3-74.3%) than Technique 2 (17.9-46.3%) and lower with a wider range (18.3-74.3%) than Technique 3 (39.9-79.4%). The three different ways of interpreting the LFA scoring system when grading of individual joints is technically difficult and result in very different estimates of foot OA prevalence at both the individual joint and global foot level. Agreement on the best strategy is required to improve comparability between studies.


Biomechanical analysis of hindfoot fixation using an intramedullary rod.
To measure the stiffness of the hindfoot when fixed with an intramedullary rod placed in a retrograde manner, two biomechanical experiments were carried out on five matched pairs of cadaveric below knee specimens. Experiment 1: In the right leg of each pair, an intramedullary rod was placed in a retrograde fashion through the calcaneus, talus, and into the tibial intramedullary canal. Biomechanical testing was done to determine hindfoot stiffness, with and without distal and proximal transverse interlocking screws. The uninstrumented left leg of each pair was tested as a control. Experiment 2: A series of similar biomechanical experiments were done on the same specimens to determine the effect on hindfoot stiffness of an intramedullary rod with one distal screw as compared with a method of tibiotalocalcaneal fixation using three cross-cannulated screws. The results show that an intramedullary rod placed in a retrograde manner stiffens the hindfoot and the placement of interlocking screws enhances that effect (Experiment 1). The intramedullary rod with one distal screw inserted provides more stiffness to the hindfoot than does three cross-cannulated screws (Experiment 2).


Self-motion leads to mandatory cue fusion across sensory modalities.
When perceiving properties of the world, we effortlessly combine multiple sensory cues into optimal estimates. Estimates derived from the individual cues are generally retained once the multisensory estimate is produced and discarded only if the cues stem from the same sensory modality (i.e., mandatory fusion). Does multisensory integration differ in that respect when the object of perception is one's own body, rather than an external variable? We quantified how humans combine visual and vestibular information for perceiving own-body rotations and specifically tested whether such idiothetic cues are subjected to mandatory fusion. Participants made extensive size comparisons between successive whole body rotations using only visual, only vestibular, and both senses together. Probabilistic descriptions of the subjects' perceptual estimates were compared with a Bayes-optimal integration model. Similarity between model predictions and experimental data echoed a statistically optimal mechanism of multisensory integration. Most importantly, size discrimination data for rotations composed of both stimuli was best accounted for by a model in which only the bimodal estimator is accessible for perceptual judgments as opposed to an independent or additive use of all three estimators (visual, vestibular, and bimodal). Indeed, subjects' thresholds for detecting two multisensory rotations as different from one another were, in pertinent cases, larger than those measured using either single-cue estimate alone. Rotations different in terms of the individual visual and vestibular inputs but quasi-identical in terms of the integrated bimodal estimate became perceptual metamers. This reveals an exceptional case of mandatory fusion of cues stemming from two different sensory modalities.


Cyclical population dynamics of automatic versus controlled processing: An evolutionary pendulum.
Psychologists, neuroscientists, and economists often conceptualize decisions as arising from processes that lie along a continuum from automatic (i.e., "hardwired" or overlearned, but relatively inflexible) to controlled (less efficient and effortful, but more flexible). Control is central to human cognition, and plays a key role in our ability to modify the world to suit our needs. Given its advantages, reliance on controlled processing may seem predestined to increase within the population over time. Here, we examine whether this is so by introducing an evolutionary game theoretic model of agents that vary in their use of automatic versus controlled processes, and in which cognitive processing modifies the environment in which the agents interact. We find that, under a wide range of parameters and model assumptions, cycles emerge in which the prevalence of each type of processing in the population oscillates between 2 extremes. Rather than inexorably increasing, the emergence of control often creates conditions that lead to its own demise by allowing automaticity to also flourish, thereby undermining the progress made by the initial emergence of controlled processing. We speculate that this observation may have relevance for understanding similar cycles across human history, and may lend insight into some of the circumstances and challenges currently faced by our species. (PsycINFO Database Record


Visual and tactile learning of ground structures in desert ants.
Place defining landmarks that have been studied intensively in insect navigation are large, voluminous objects visible to the insect from quite some distance. Here, we show that in desert ants, Cataglyphis fortis, local variations in ground properties can also serve as landmarks. The ants were trained to forage within a linear channel, in which the floor adjacent to the nest entrance was altered in optical and tactile properties. When ants were later tested within a test channel that ran parallel to the training channel, they recognized this landmark and centred their search on the part of the ground structure during training that was closest to the nest entrance. Hence, physical properties of the ground can be learnt and used as cues defining, for example, the position of the nest. In a second series of experiments the ants were presented with ground structures that differed in their visual and tactile properties from the training structure. We show that the absence of either the correct tactile properties or the correct optical properties of the ground structure make the ants reject the previously accepted structure. Hence small ground structures are recognized by the ants as familiar landmarks only if both visual and tactile information coincides with what the ants have experienced during training.


Isolation and partial characterisation of a putative monoterpene synthase from Melaleuca alternifolia.
Melaleuca alternifolia (Cheel) is an Australia native tree harvested for its monoterpene-rich, essential oil. Monoterpene synthases (E.C. 188.8.131.52) were partially purified from the flush growth of the commercially important, high terpinen-4-ol chemotype of M. alternifolia. The purified fractions produced an acyclic monoterpene, linalool that is not present in the essential oil. To further characterise the monoterpene synthase, a cDNA library was constructed and 500 expressed sequence tags (ESTs) were sequenced to isolate putative terpene synthases. A single clone with similarity to the TspB gene sub-family of angiosperm monoterpene and isoprene synthases was isolated but was truncated at the 5' end. This single clone was used to design a probe for a cDNA library and was applied to isolate a full-length clone. This gene encoded a polypeptide 583 amino acids in length (67 kDa) including a putative transit peptide. Heterologous expression of the gene in Escherichia coli and subsequent assay of the recombinant enzyme did not result in the production of terpinen-4-ol, the major constituent of tea tree oil, or of its precursor sabinene hydrate. Significant quantities of linalool were observed in these assays, and in the assays of monoterpene synthase activity of a native enzyme in vitro, but the racemic nature of the linalool means that it may have a non-enzymatic origin.


Models of occupational therapy service provision in the school system.
Occupational therapy is a related service when provided within the public schools, which means that services must enhance or support educational goals. Three service provision models have been described for school therapists: direct service, monitoring, and consultation. Direct service addresses individualized needs that require specialized intervention strategies which can safely be performed only by the occupational therapist. Monitoring, which is sometimes referred to as integrated programming, uses therapeutic expertise within functional tasks to maximize opportunities for practice and generalization. Consultation addresses problems by enabling others to work more effectively on the educational goals they have set for the students. Evidence is accumulating to demonstrate that each model is effective when chosen and applied appropriately. This paper reviews each model, provides examples of studies that have been conducted, and suggests directions for future research.


Demequina activiva sp. nov., isolated from a tidal flat.
A Gram-stain-positive, facultatively anaerobic, non-spore-forming, non-flagellated and rod-shaped or ovoid bacterial strain, designated BS-12M(T), was isolated from a tidal flat sediment on the South Sea, South Korea. Strain BS-12M(T) grew optimally at 35 °C, at pH 7.0-8.0 and in the presence of 2.0% (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain BS-12M(T) fell within the cluster comprising the type strains of species of the genus Demequina, joining the type strain of Demequina aestuarii with which it shared the highest sequence similarity (98.6%). It exhibited 16S rRNA gene sequence similarity of 96.1-97.9% to the type strains of other species of the genus Demequina. The peptidoglycan type of strain BS-12M(T) was A4β based on L-Orn -L-Ser -D-Glu. Strain BS-12M(T) contained demethylmenaquinone-9(H4) as the major menaquinone and anteiso-C15:0 and C16:0 as the major fatty acids. The major polar lipids of strain BS-12M(T) were phosphatidylinositol and phosphatidylinositolmannoside. The DNA G+C content of strain BS-12M(T) was 70.7 mol% and its DNA-DNA relatedness values with the type strains of five phylogenetically related species of the genus Demequina were 15-34%. Differential phenotypic properties, together with phylogenetic and genetic distinctiveness, revealed that strain BS-12M(T) is separate from other species of the genus Demequina. On the basis of the data presented, strain BS-12M(T) is considered to represent a novel species of the genus Demequina, for which the name Demequina activiva sp. nov. is proposed. The type strain is BS-12M(T) ( =KCTC 29674(T) = NBRC 110675T).


Heavy metal mutagenicity: insights from bioinorganic model chemistry.
The mutagenicity of metal species may be the result of a direct interaction with the target molecule DNA. Possible scenarios leading to nucleobase mispairing are discussed, and selected examples are presented. They include changes in nucleobase selectivity as a consequence of alterations in acid-base properties of nucleobase atoms and groups involved in complementary H bond formation, guanine deprotonation, and stabilization of rare nucleobase tautomers by metal ions. Oxidative nucleobase damage brought about by metal species will not be considered.


Pediatric endurance and limb strengthening (PEDALS) for children with cerebral palsy using stationary cycling: a randomized controlled trial.
Effective interventions to improve and maintain strength (force-generating capacity) and endurance are needed for children with cerebral palsy (CP). This study was performed to examine the effects of a stationary cycling intervention on muscle strength, locomotor endurance, preferred walking speed, and gross motor function in children with spastic diplegic CP. This was a phase I randomized controlled trial with single blinding. The interventions were performed in community-based outpatient physical therapy clinics. Outcome assessments were performed in university laboratories. Sixty-two ambulatory children aged 7 to 18 years with spastic diplegic CP and Gross Motor Function Classification System levels I to III participated in this study. Participants were randomly assigned to cycling or control (no-intervention) groups. Thirty intervention sessions occurred over 12 weeks. Primary outcomes were peak knee extensor and flexor moments, the 600-Yard Walk-Run Test, the Thirty-Second Walk Test, and the Gross Motor Function Measure sections D and E (GMFM-66). Significant baseline-postintervention improvements were found for the 600-Yard Walk-Run Test, the GMFM-66, peak knee extensor moments at 120 degrees /s, and peak knee flexor moments at 30 degrees /s for the cycling group. Improved peak knee flexor moments at 120 degrees/s were found for the control group only, although not all participants could complete this speed of testing. Significant differences between the cycling and control groups based on change scores were not found for any outcomes. Limitations Heterogeneity of the patient population and intrasubject variability were limitations of the study. Significant improvements in locomotor endurance, gross motor function, and some measures of strength were found for the cycling group but not the control group, providing preliminary support for this intervention. As statistical differences were not found in baseline-postintervention change scores between the 2 groups; the results did not demonstrate that stationary cycling was more effective than no intervention. The results of this phase I study provide guidance for future research.


Experiences of being parents of young adults living with recessive limb-girdle muscular dystrophy from a salutogenic perspective.
Recessive limb-girdle muscular dystrophies (LGMD2) involve progressive muscle weakness. Parental support is important for young adults living with LGMD2, but no study has been identified focusing on the parents' experiences. The salutogenic perspective concentrates on how daily life is comprehended, managed and found meaningful, i.e. the person's sense of coherence. The aim of this study was to describe, from a salutogenic perspective, experiences of being parents of young adults living with LGMD2. Nineteen participants were included. Data were collected by semi-structured interviews and the self-administrated 13-item sense of coherence questionnaire. Interview data were analysed with content analysis and related to self-rated sense of coherence. The result shows experiences of being influenced, not only by thoughts and emotions connected to the disease but also by caregiving duties and the young adults' well-being. Simultaneously, difficulty in fully grasping the disease was expressed and uncertainty about progression created worries about future management. Trying their best to support their young adults to experience well-being and to live fulfilled lives, the importance of having a social network, support from concerned professionals and eventually access to personal assistance was emphasized. The need to have meaningful pursuits of one's own was also described. The median sense of coherence score was 68 (range 53-86). Those who scored high (≥68) described satisfaction with social network, external support provided, work and leisure activities to a greater extent than those who scored low (<68). The result shows that the young adults' disease has a major impact on the parents' lives. Assessment of how the parents comprehend, manage and find meaning in everyday life may highlight support needed to promote their health.


Once-weekly prophylaxis with glycoPEGylated recombinant factor VIII (N8-GP) in severe haemophilia A: Safety and efficacy results from pathfinder 2 (randomized phase III trial).
Turoctocog alfa pegol (N8-GP) is a site-specific, 40 kDa glycoPEGylated recombinant factor VIII (FVIII) product with an extended half-life. The comprehensive main phase of the pivotal pathfinder 2 trial showed N8-GP dosed every 4 days (Q4D) provided favourable safety and efficacy for preventing bleeds in 175 patients with haemophilia A. We investigated the safety and efficacy of N8-GP prophylaxis when administered weekly (Q7D) for 24 weeks to patients with low bleeding rates in the pathfinder 2 extension trial. Patients (≥12 years) with ≤2 bleeds during the preceding 6 months of the pathfinder 2 main phase were eligible for randomization to receive N8-GP 50 IU/kg Q4D or 75 IU/kg Q7D. Safety and efficacy endpoints were incidence of FVIII inhibitors and annualized bleeding rate (ABR), respectively. Fifty-five of 143 (38.5%) patients on prophylaxis who continued into the extension phase were randomized to receive 50 IU/kg Q4D (n = 17) or 75 IU/kg Q7D (n = 38). Nine patients in the Q7D cohort reverted to 50 IU/kg Q4D. No inhibitors were detected. In both cohorts, >50% of patients experienced no bleeds. Median ABR for overall, joint, spontaneous, traumatic and muscle was 0.00 for both cohorts. Overall estimated success rate for treating bleeding episodes was 87.5%; 94.7% of bleeds were controlled with ≤2 injections. Weekly N8-GP was well tolerated and efficacious and may benefit selected "low bleeder" patients with haemophilia A.


A Bayesian committee machine.
The Bayesian committee machine (BCM) is a novel approach to combining estimators that were trained on different data sets. Although the BCM can be applied to the combination of any kind of estimators, the main foci are gaussian process regression and related systems such as regularization networks and smoothing splines for which the degrees of freedom increase with the number of training data. Somewhat surprisingly, we find that the performance of the BCM improves if several test points are queried at the same time and is optimal if the number of test points is at least as large as the degrees of freedom of the estimator. The BCM also provides a new solution for on-line learning with potential applications to data mining. We apply the BCM to systems with fixed basis functions and discuss its relationship to gaussian process regression. Finally, we show how the ideas behind the BCM can be applied in a non-Bayesian setting to extend the input-dependent combination of estimators.


Sleep Pattern and Predictors of Sleep Disturbance Among Family Caregivers of Terminal Ill Patients With Cancer in Taiwan: A Longitudinal Study.
Sleep disturbance commonly has a negative impact on the well-being of family caregivers (FCs) of terminally ill patients with cancer. The effect of sleep disturbance on FCs has not been explored through long-term follow-up studies in Taiwan. The purposes of this study were to (1) identify the trajectory of sleep quality of FCs of terminally ill patients with cancer in Taiwan and (2) examine the determinants of sleep disturbance through a longitudinal follow-up until patient death. A prospective, longitudinal study was conducted among 95 FCs of terminally ill patients with cancer. The FCs' sleep quality was measured subjectively by using the Pittsburgh Sleep Quality Index and objectively by wearing a wrist actigraphy for 48 hours each month during the 6-month follow-up assessments. The trajectory and determinants of sleep quality were identified using a generalized estimation equation approach. The FCs' sleep quality significantly decreased as the patient's death approached. Family caregivers who were women or older, had a relative with a longer survival period after diagnosis, reported higher levels of depression and fatigue, and provided lower levels of assistance to their relatives experienced more sleep disturbance. The sleep quality of Taiwanese FCs significantly deteriorated as the death of the terminally ill patients with cancer approached. Early detection of the FCs' sleep disturbance, increasing their self-awareness of sleep problems, and providing nonpharmacological interventions and psychosocial support may be helpful for FCs to improve their quantity and quality of sleep.