Liver steatosis and increased ChREBP expression in mice carrying a liver specific SIRT1 null mutation under a normal feeding condition.
SIRT1, a homolog of yeast Sir2, is a type III NAD(+) dependent histone and protein deacetylase. Previous studies of mice carrying liver specific deletion of exon 4 of the Sirt1 gene revealed opposite responses of mutant mice to a high-fat diet in terms of fatty liver formation, which obscures the function of SRIT1 in liver development and lipid metabolism. To investigate this, we deleted exons 5 and 6 of Sirt1 in the liver by using a Cre-loxP approach. Western blot using an antibody to N-terminal SIRT1 does not detect a truncated protein in the liver of the mutant mice (Sirt1(flox5-6/flox5-6);Alb-Cre), suggesting a null mutation for SIRT1 is generated in the liver. Unlike the previously reported phenotypes, the Sirt1(flox5-6/flox5-6);Alb-Cre mice develop fatty liver under a normal feeding condition. The disease starts at two months of age and incidence increases as the animals become older, affecting 78% of them when they are over one year of age. We showed that the steatosis is accompanied by altered expression of a number of genes, including increased expression of ChREBP, which acts as one of the central determinants of lipid synthesis in the liver. This data uncovers an important role of SIRT1 in regulating lipid metabolism in the liver, and the SIRT1 mutant mice may serve as an animal model for studying human fatty liver disease and facilitate the development of effective therapeutic approach for the disease.


T cell recognition of an HLA-A2-restricted epitope derived from a cleaved signal sequence.
An alternative pathway for class I-restricted antigen presentation has been suggested on the basis of peptides bound to HLA-A2 molecules in cells lacking the transporter for antigen presentation (TAP). Most of these peptides were derived from signal sequences for translocation into the endoplasmic reticulum (ER). However, it is not known whether these peptides can be presented to T cells. The hydrophobic nature of an HLA-A2-restricted T cell epitope (M1 58-66) was exploited to test whether it could be presented to T cells when derived from a signal sequence. Replacing the signal sequence of the influenza virus hemagglutinin molecule H3 with an artificial sequence containing that HLA-A2-restricted T cell epitope resulted in efficient translocation of H3 molecules into the ER and transport to the cell surface. This signal sequence-derived epitope was presented to HLA-A2-restricted T cells. Involvement of cytosolic processing for this presentation is very unlikely, because (a) presentation occurred in cells lacking TAP; (b) expression of H3 molecules with the artificial signal sequence did not produce a detectable cytosolic form of H3; and (c) presentation of the same epitope expressed in cytosolic forms of antigen required TAP. Thus, a peptide derived from a signal sequence cleaved in the ER can provide an epitope for HLA-A2-restricted T cell recognition.


GLMdenoise: a fast, automated technique for denoising task-based fMRI data.
In task-based functional magnetic resonance imaging (fMRI), researchers seek to measure fMRI signals related to a given task or condition. In many circumstances, measuring this signal of interest is limited by noise. In this study, we present GLMdenoise, a technique that improves signal-to-noise ratio (SNR) by entering noise regressors into a general linear model (GLM) analysis of fMRI data. The noise regressors are derived by conducting an initial model fit to determine voxels unrelated to the experimental paradigm, performing principal components analysis (PCA) on the time-series of these voxels, and using cross-validation to select the optimal number of principal components to use as noise regressors. Due to the use of data resampling, GLMdenoise requires and is best suited for datasets involving multiple runs (where conditions repeat across runs). We show that GLMdenoise consistently improves cross-validation accuracy of GLM estimates on a variety of event-related experimental datasets and is accompanied by substantial gains in SNR. To promote practical application of methods, we provide MATLAB code implementing GLMdenoise. Furthermore, to help compare GLMdenoise to other denoising methods, we present the Denoise Benchmark (DNB), a public database and architecture for evaluating denoising methods. The DNB consists of the datasets described in this paper, a code framework that enables automatic evaluation of a denoising method, and implementations of several denoising methods, including GLMdenoise, the use of motion parameters as noise regressors, ICA-based denoising, and RETROICOR/RVHRCOR. Using the DNB, we find that GLMdenoise performs best out of all of the denoising methods we tested.


Enhanced urothelial ATP release and contraction following intravesical treatment with the cytotoxic drug, doxorubicin.
Intravesical administration of the cytotoxic drug doxorubicin is a common treatment for superficial carcinoma of the bladder, but it is associated with significant urological adverse effects. The aim of this study was to identify doxorubicin-induced changes in the local mechanisms involved in regulating bladder function. As a model of intravesical doxorubicin administration in patients, doxorubicin (1 mg/mL) was applied to the luminal surface of porcine bladders for 60 min. Following treatment, the release of urothelial/lamina propria mediators (acetylcholine (Ach), ATP and prostaglandin E2 (PGE2) and contractile responses of isolated tissue strips was investigated. Doxorubicin pretreatment did not affect contractile responses of detrusor muscle to carbachol, but did enhance neurogenic detrusor responses to electrical field stimulation (219 % at 5 Hz). Contractions of isolated strips of urothelium/lamina propria to carbachol were also enhanced (30 %) in tissues from doxorubicin pretreated bladders. Isolated strips of urothelium/lamina propria from control bladders demonstrated a basal release of all three mediators (Ach > ATP > PGE2), with increased release of ATP when tissues were stretched. In tissues from doxorubicin-pretreated bladders, the basal release of ATP was significantly enhanced (sevenfold), while the release of acetylcholine and PGE2 was not affected. The application of luminal doxorubicin, under conditions that mimic intravesical administration to patients, affects urothelial/lamina propria function (increased contractile activity and ATP release) and enhances efferent neurotransmission without affecting detrusor smooth muscle. These actions would enhance bladder contractile activity and sensory nerve activity and may explain the adverse urological effects observed in patients following intravesical doxorubicin treatment.


Pitch discrimination and melodic memory in children with autism spectrum disorders.
Pitch perception is enhanced among persons with autism. We extended this finding to memory for pitch and melody among school-aged children. The purpose of this study was to investigate pitch memory in musically untrained children with autism spectrum disorders, aged 7-13 years, and to compare it to that of age- and IQ-matched typically developing children. The children were required to discriminate isolated tones in two differing contexts as well to remember melodies after a period of 1 week. The tasks were designed to employ both short- and long-term memory for music. For the pitch discrimination task, the children first had to indicate whether two isolated tones were the same or different when the second was the same or had been altered to be 25, 35, or 45 cents sharp or flat. Second, the children discriminated the tones within the context of melody. They were asked whether two melodies were the same or different when the leading tone of the second melody was the same or had been altered to be 25, 35, or 45 cents sharp or flat. Long-term memory for melody was also investigated, as the children attempted to recall four different two-bar melodies after 1 week. The children with autism spectrum disorders demonstrated elevated pitch discrimination ability in the single-tone and melodic context as well as superior long-term memory for melody. Pitch memory correlated positively with scores on measures of nonverbal fluid reasoning ability. Superior short- and long-term pitch memory was found among children with autism spectrum disorders. The results indicate an aspect to cognitive functioning that may predict both enhanced nonverbal reasoning ability and atypical language development.


Molecular basis for specific recognition of both RNA and DNA by a zinc finger protein.
Transcription factor IIIA (TFIIIA) from Xenopus oocytes binds both the internal control region of the 5S ribosomal RNA genes and the 5S RNA transcript itself. The nucleic acid binding domain of TFIIIA contains nine tandemly repeated zinc finger motifs. A series of precisely truncated forms of this protein have been constructed and assayed for 5S RNA and DNA binding. Different sets of zinc fingers were found to be responsible for high affinity interactions with RNA and with DNA. These results explain how a single protein can exhibit equal affinities for these two very different nucleic acids.


Abdominal massage plus advice, compared with advice only, for neurogenic bowel dysfunction in MS: a RCT.
Between 50% and 80% of people with multiple sclerosis (PwMS) experience neurogenic bowel dysfunction (NBD) (i.e. constipation and faecal incontinence) that affects quality of life and can lead to hospitalisation. To determine the clinical effectiveness and cost-effectiveness of abdominal massage plus advice on bowel symptoms on PwMS compared with advice only. A process evaluation investigated the factors that affected the clinical effectiveness and possible implementation of the different treatments. A randomised controlled trial with process evaluation and health economic components. Outcome analysis was undertaken blind. The trial took place in 12 UK hospitals. PwMS who had 'bothersome' NBD. Following individualised training, abdominal massage was undertaken daily for 6 weeks (intervention group). Advice on good bowel management as per the Multiple Sclerosis Society advice booklet was provided to both groups. All participants received weekly telephone calls from the research nurse. The primary outcome was the difference between the intervention and control groups in change in the NBD score from baseline to week 24. Secondary outcomes were measured via a bowel diary, adherence diary, the Constipation Scoring System, patient resource questionnaire and the EuroQol-5 Dimensions, five-level version (EQ-5D-5L). A total of 191 participants were finalised, 189 of whom were randomised (two participants were finalised in error) (control group, n = 99; intervention group, n = 90) and an intention-to-treat analysis was performed. The mean age was 52 years (standard deviation 10.83 years), 81% (n = 154) were female and 11% (n = 21) were wheelchair dependent. Fifteen participants from the intervention group and five from the control group were lost to follow-up. The change in NBD score by week 24 demonstrated no significant difference between groups [mean difference total score -1.64, 95% confidence interval (CI) -3.32 to 0.04; p = 0.0558]; there was a significant difference between groups in the change in the frequency of stool evacuation per week (mean difference 0.62, 95% CI 0.03 to 1.21; p = 0.039) and in the number of times per week that participants felt that they emptied their bowels completely (mean difference 1.08, 95% CI 0.41 to 1.76; p = 0.002), in favour of the intervention group. Of participant interviewees, 75% reported benefits, for example less difficulty passing stool, more complete evacuations, less bloated, improved appetite, and 85% continued with the massage. A cost-utility analysis conducted from a NHS and patient cost perspective found in the imputed sample with bootstrapping a mean incremental outcome effect of the intervention relative to usual care of -0.002 quality-adjusted life-years (QALYs) (95% CI -0.029 to 0.027 QALYs). In the same imputed sample with bootstrapping, the mean incremental cost effect of the intervention relative to usual care was £56.50 (95% CI -£372.62 to £415.68). No adverse events were reported. Limitations include unequal randomisation, dropout and the possibility of ineffective massage technique. The increment in the primary outcome favoured the intervention group, but it was small and not statistically significant. The economic analysis identified that the intervention was dominated by the control group. Given the small improvement in the primary outcome, but not in terms of QALYs, a low-cost version of the intervention might be considered worthwhile by some patients. Research is required to establish possible mechanisms of action and modes of massage delivery. Current Controlled Trials ISRCTN85007023 and NCT03166007. This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 58. See the NIHR Journals Library website for further project information.


Chitin receptor CERK1 links salt stress and chitin-triggered innate immunity in Arabidopsis.
In nature, plants need to respond to multiple environmental stresses that require the involvement and fine-tuning of different stress signaling pathways. Cross-tolerance, in which plants pre-treated with chitin (a fungal microbe-associated molecular pattern) have improved salt tolerance, was observed in Arabidopsis, but is not well understood. Here, we show a unique link between chitin and salt signaling mediated by the chitin receptor CHITIN ELICITOR RECEPTOR KINASE 1 (CERK1). Transcriptome analysis revealed that salt stress-induced genes are highly correlated with chitin-induced genes, although this was not observed with other microbe-associated molecular patterns (MAMPs) or with other abiotic stresses. The cerk1 mutant was more susceptible to NaCl than was the wild type. cerk1 plants had an irregular increase of cytosolic calcium ([Ca2+ ]cyt ) after NaCl treatment. Bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation experiments indicated that CERK1 physically interacts with ANNEXIN 1 (ANN1), which was reported to form a calcium-permeable channel that contributes to the NaCl-induced [Ca2+ ]cyt signal. In turn, ann1 mutants showed elevated chitin-induced rapid responses. In short, molecular components previously shown to function in chitin or salt signaling physically interact and intimately link the downstream responses to fungal attack and salt stress.


Genome-Wide Evolutionary Analyses of G1P[8] Strains Isolated Before and After Rotavirus Vaccine Introduction.
Rotaviruses are the most important etiological agent of acute gastroenteritis in young children worldwide. Among the first countries to introduce rotavirus vaccines into their national immunization programs were Belgium (November 2006) and Australia (July 2007). Surveillance programs in Belgium (since 1999) and Australia (since 1989) offer the opportunity to perform a detailed comparison of rotavirus strains circulating pre- and postvaccine introduction. G1P[8] rotaviruses are the most prominent genotype in humans, and a total of 157 G1P[8] rotaviruses isolated between 1999 and 2011 were selected from Belgium and Australia and their complete genomes were sequenced. Phylogenetic analysis showed evidence of frequent reassortment among Belgian and Australian G1P[8] rotaviruses. Although many different phylogenetic subclusters were present before and after vaccine introduction, some unique clusters were only identified after vaccine introduction, which could be due to natural fluctuation or the first signs of vaccine-driven evolution. The times to the most recent common ancestors for the Belgian and Australian G1P[8] rotaviruses ranged from 1846 to 1955 depending on the gene segment, with VP7 and NSP4 resulting in the most recent estimates. We found no evidence that rotavirus population size was affected after vaccine introduction and only six amino acid sites in VP2, VP3, VP7, and NSP1 were identified to be under positive selective pressure. Continued surveillance of G1P[8] strains is needed to determine long-term effects of vaccine introductions, particularly now rotavirus vaccines are implemented in the national immunization programs of an increasing number of countries worldwide.


Sensory Differences and Mealtime Behavior in Children With Autism.
This study examined sensory differences and mealtime behaviors in children with autism spectrum disorder (ASD; n=34) and compared the results with those of similarly aged peers who were typically developing (TD; n=34). Results from parent-report and child-report questionnaires indicated that children with ASD scored significantly differently from TD peers on the measures of sensory differences and eating behaviors. Data also supported a correlation between sensory differences and eating difficulties in children with ASD. The results of this study will help caregivers and their children with ASD identify problem eating behaviors that may be associated with sensory differences. Sensory strategies and techniques offered by occupational therapy practitioners may contribute to greater success during mealtimes for children with ASD and their families, with increased comfort and less stress. The findings also support a need to further explore the influence of sensory differences on mealtime behaviors.


Screening for fetal and genetic abnormality: social and ethical issues.
In answer to questions raised by practitioners, an ethics of genetic screening is located in a tension between liberty and responsibility in three respects: (1) to nature and biological processes; (2) to the disposal of human life; and (3) to the relation of persons to society. Under (1), the obligation to pursue research, fundamental as well as applied, is affirmed, offering the benefit of economy with fetal life, but requiring discrimination between the beneficial, the trivial, and the bizarre. Under (2) the abortion question, when relevant to diagnosed abnormality, is discussed, not in the language of conflicting rights, but of the relation of duties to interests. Under (3) the familial and social dimensions of screening raise questions of the disclosure of information and the keeping or extending of confidences. Last comes the value placed on truth in two related areas of developing practice. In infertility treatment, the donors of gametes are required to remain anonymous. Gene tracing through families requires for its effectiveness some correspondence between assumed identity and genetic identity. This conflict of social policies should be resolved.


Maternal postpartum depression is a risk factor for infant emotional variability at 4 months.
Maternal postpartum depression (PPD) is a risk for disruption of mother-infant interaction. Infants of depressed mothers have been found to display less positive, more negative, and neutral affect. Other studies have found that infants of mothers with PPD inhibit both positive and negative affect. In a sample of 28 infants of mothers with PPD and 52 infants of nonclinical mothers, we examined the role of PPD diagnosis and symptoms for infants' emotional variability, measured as facial expressions, vocal protest, and gaze using microanalysis, during a mother-infant face-to-face interaction. PPD symptoms and diagnosis were associated with (a) infants displaying fewer high negative, but more neutral/interest facial affect events, and (b) fewer gaze off events. PPD diagnosis, but not symptoms, was associated with less infant vocal protest. Total duration of seconds of infant facial affective displays and gaze off was not related to PPD diagnosis or symptoms, suggesting that when infants of depressed mothers display high negative facial affect or gaze off, these expressions are more sustained, indicating lower infant ability to calm down and re-engage, interpreted as a disturbance in self-regulation. The findings highlight the importance of not only examining durations, but also frequencies, as the latter may inform infant emotional variability.


Non-High-Density Lipoproteins Cholesterol and Cardio-Metabolic Risk.
The concept of cardio metabolic risk and risk stratification for cardiovascular events are two distinct entities related with different stages of vascular development of the atherogenic process. In our analytical transversal study, we analyzed non-high-density lipoprotein cholesterol behavior and the correlations with traditional cardiovascular risk factors in a subpopulation with coronary pain and indication of angio coronarography. We tried to build a mathematical model in order to predict the non-HDLc, allowing additional cardiovascular risk reassesment. We included 214 patients hospitalized for symptoms and signs suggestive of coronary artery disease and thus indication of vascular invasive evaluation. The protocol of the vascular evaluation included: assessment of cardiovascular risk for fatal cardiovascular event within the next 10 years, the lipidic risk profile, coronarography and statistical analysis. We found a positive and highly statistically significant association between carotid artery intima-media thickness (c-IMT) and non-HDLc value (p <0.001). The mathematical model of linear regression showed the variability of non-HDLc depending on the following numeric variables: total cholesterol (TC), low density lipoproteins (LDL), triglycerides (TG), metabolic syndrome (MS); 97.5% of the non-HDLc variability was dependent on these variables. Non-HDLc is a useful prognostic factor in cardio-metabolic risk quantification. The interdependent relation between non-HDLc and cardio-metabolic risk factors justifies the inclusion of this parameter in cardio-metabolic risk prediction equation in subjects with metabolic syndrome.


Titanium for prosthodontic applications: a review of the literature.
Titanium has become a material of great interest in prosthodontics in recent years. A growing trend involves the use of titanium as an economical and biocompatible replacement for existing alloys for fixed and removable prostheses. However, long-term results of titanium casting, joining, and porcelain bonding have to be evaluated before this wonder metal can be used routinely in clinical dentistry. This article describes the development and properties of titanium and reviews the literature related to the use of titanium in prosthodontics, for the purpose of evaluating the present status and future trends in its use.


Three-Dimensional Evaluation of the Upper Airway Morphological Changes in Growing Patients with Skeletal Class III Malocclusion Treated by Protraction Headgear and Rapid Palatal Expansion: A Comparative Research.
The aim of this study was to evaluate the morphological changes of upper airway after protraction headgear and rapid maxillary expansion (PE) treatment in growing patients with Class III malocclusion and maxillary skeletal deficiency compared with untreated Class III patients by cone-beam computed tomography (CBCT). Thirty growing patients who have completed PE therapy were included in PE group. The control group (n = 30) was selected from the growing untreated patients with the same diagnosis. The CBCT scans of the pre-treatment (T1) and post-treatment (T2) of PE group and the control group were collected. Reconstruction and registration of the 3D models of T1 and T2 were completed. By comparing the data obtained from T1, T2 and control group, the morphological changes of the upper airway during the PE treatment were evaluated. Comparing with the data from T1 group, the subspinale (A) of maxilla and the upper incisor (UI) of the T2 group were moved in the anterior direction. The gnathion (Gn) of mandible was moved in the posterior-inferior direction. The displacement of the hyoid bone as well as the length and width of dental arch showed significant difference. The volume and mean cross-sectional area of nasopharynx, velopharynx and glossopharynx region showed significant difference. The largest anteroposterior/the largest lateral (AP/LR) ratios of the velopharynx and glossopharynx were increased, but the AP/LR ratio of the hypopharynx was decreased. In addition, the length and width of the maxillary dental arch, the displacement of the hyoid bone, the volume of nasopharynx and velopharynx, and the AP/LR ratio of the hypopharynx and velopharynx showed significant difference between the data from control and T2 group. The PE treatment of Class III malocclusion with maxillary skeletal hypoplasia leads to a significant increase in the volume of nasopharynx and velopharynx.


The double burden of food insecurity and obesity among Latino youth: Understanding the role of generational status.
Obesity is linked to food insecurity and generational status; however, little is known about how both impact obesity risk among Latino youth. To investigate the joint effect of generational status and food insecurity on obesity prevalence among Latino youth. We pooled data from the 2011 to 2017 waves of the National Health Interview Survey to derive a sample Latino youth aged 12 to 17 (N = 7532). Four generational categories were constructed: first generation (foreign-born children); second generation (US-born child; foreign-born parent[s]); 2.5 generation (US-born child; one foreign-born parent and one US-born parent); third generation (US-born child; U.S.-born parent[s]). Food insecurity was defined by monthly instances of food scarcity over the past year. Obesity was measured using age- and sex-specific body mass index percentile cut-offs. Log-binomial multivariable regression models estimated the association between generational status and food insecurity categories on obesity. Obesity percentages among food-insecure households ranged from 12.8% in the first generation, 15.8% in the second, 24.3% in the 2.5, and 19.2% in the third. In fully adjusted models, 2.5 generation food secure youth had the highest prevalence of obesity (aPR: 1.53; 95% CI, 1.09-2.16) when compared with first generation food secure youth, followed by third generation food insecure youth (aPR: 1.49; 95% CI, 1.01-2.20). Food security status is associated with increased obesity prevalence among Latino youth across the generations. Given that obesity is a risk factor for top causes of mortality and morbidity, growing rates among this population is of public health and clinical importance.


Lung Ultrasound for Detection of Pulmonary Complications in Critically Ill Obstetric Patients in a Resource-Limited Setting.
Critically ill parturients have an increased risk of developing pulmonary complications. Lung ultrasound (LUS) could be effective in addressing the cause of respiratory distress in resource-limited settings with high maternal mortality. We aimed to determine the frequency, timing of appearance, and type of pulmonary complications in critically ill parturients in an obstetric unit in Sierra Leone. In this prospective observational study, LUS examinations were performed on admission, after 24 and 48 hours, and in case of respiratory deterioration. Primary endpoint was the proportion of parturients with one or more pulmonary complications, stratified for the presence of respiratory distress. Secondary endpoints included timing and types of complications, and their association with "poor outcome," defined as a composite of transfer for escalation of care or death. Of 166 patients enrolled, 35 patients (21% [95% CI: 15-28]) had one or more pulmonary complications, the majority diagnosed on admission. Acute respiratory distress syndrome (period prevalence 4%) and hydrostatic pulmonary edema (4%) were only observed in patients with respiratory distress. Pneumonia (2%), atelectasis (10%), and pleural effusion (7%) were present, irrespective of respiratory distress. When ultrasound excluded pulmonary complications, respiratory distress was related to anemia or metabolic acidosis. Pulmonary complications were associated with an increased risk of poor outcome (odds ratio: 5.0; 95% CI: 1.7-14.6; P = 0.003). In critically ill parturients in a resource-limited obstetric unit, LUS contributed to address the cause of respiratory distress by identifying or excluding pulmonary complications. These were associated with a poor outcome.


Dry-eye--is inflammation just the tip of the iceberg?
Dry eye syndrome (DES) has been described by The International Dry Eye WorkShop as ''multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear instability with potential damage to the ocular surface.'' Inflammation has been recognized as a primary contributor to the disease and was a tremendous step forward in the description and treatment of DES. Although most treatments of DES treat inflammation, the signs and symptoms of DES usually return shortly after discontinuing the use of the anti-inflammatory agent; We present a case of a 70-year-old patient who presents with significant dry eye symptoms for 2 years. She reports the need to wear sunglasses during all waking hours, both indoors and out, and had discontinued her hobby of gardening. She had ocular rosacea diagnosed at a previous ophthalmology practice and did not respond to any past treatments. The patient was treated with 25% platelet-rich plasma (PRP) and experienced significant improvement and a return to a normal quality of life that has continued for more than a year after discontinuing treatment; Our group is investigating the use of biologic therapeutics in the treatment of various forms of DES. We suggest that a clinically acceptable dosage of PRP provides the ocular surface with the components necessary to restore normal cellular tensegrity and provides a foundation to eliminate the recurrence of the inflammation associated with DES.


Angiotensin Regulation of Amygdala Response to Threat in High-Trait-Anxiety Individuals.
The antihypertensive drug losartan has been shown to improve memory in humans as well as learning and fear extinction in rodent models, highlighting its potential to have similar synergistic effects on exposure-based cognitive behavioral therapy for anxiety disorders. This study investigated the effect of losartan on neural correlates of processing threat versus safety stimuli in highly anxious individuals to identify potential pathways of how the drug might facilitate psychological treatment. Thirty healthy volunteers high in trait anxiety were randomly assigned to a single dose of losartan (50 mg) versus placebo before undergoing functional magnetic resonance imaging. We measured brain response to happy and fearful faces presented for 80 seconds to assess emotional processing and habituation over time. The placebo group showed similarly high left amygdala activation early on during presentation of fearful and happy faces, which decreased over time. In contrast, losartan reduced amygdala response to happy faces early on. In response to fearful faces, the drug prevented habituation, caused sustained amygdala activation, and led to increased activation in other brain areas associated with threat processing, such as the insula and putamen. Our findings suggest two distinct effects of losartan on emotional processing, including an improvement of early discrimination of stimuli as threatening versus safe, and facilitation of threat processing. Both processes are known to be relevant for successful exposure, highlighting two potential pathways by which losartan might exert facilitative effects on psychological treatment.


Gender differences and the trend in the acute myocardial infarction: a 10-year nationwide population-based analysis.
It is not clear whether gender is associated with different hospitalization cost and lengths for acute myocardial infarction (AMI). We identified patients hospitalized for primary diagnosis of AMI with (STEMI) or without (NSTEMI) ST elevation from 1999 to 2008 through a national database containing 1,000,000 subjects. As compared to that in 1999~2000, total (0.35‰ versus 0.06‰, P < 0.001) and male (0.59‰ versus 0.07‰, P < 0.001) STEMI hospitalization percentages were decreased in 2007~2008, but female STEMI hospitalization percentages were not different from 1999 to 2008. However, NSTEMI hospitalization percentages were similar over the 10-year period. The hospitalization age for AMI, STEMI, and NSTEMI was increased over the 10-year period by 14, 9, and 7 years in male, and by 18, 18, and 21 years in female. The female and male hospitalization cost and lengths were similar in the period. As compared to nonmedical center, the hospitalization cost for STEMI in medical center was higher in male patients, but not in female patients, and the hospitalization cost for NSTEMI was higher in both male and female gender. We found significant differences between male and female, medical center and non-medical center, or STEMI and NSTEMI on medical care over the 10-year period.


Melatonin-directed micellization: a case for tryptophan metabolites and their classical bioisosteres as templates for the self-assembly of bipyridinium-based supramolecular amphiphiles in water.
The bulk solution properties of amphiphilic formulations are derivative of their self-assembly into higher ordered supramolecular assemblies known as micelles and of their ordering at the air-water interface. Exerting control over the surface-active properties of amphiphiles and their propensity to aggregate in pure water is most often fine-tuned by covalent modification of their molecular structure. Nevertheless structural constraints which limit the performance of amphiphiles do emerge when trying to develop more sophisticated systems which undergo for example, shape-defined controlled assembly and/or respond to external stimuli. In this regard, the template-modulated assembly of the so-called "supramolecular amphiphiles" continues to make progress ordering molecules that otherwise have very little to no driving force to aggregate in a prescribed manner in aqueous solutions. Herein we describe the template-modulated micellization and ordering at the air-water interface of bipyridinium-based supramolecular amphiphiles triggered by host-guest interactions with high specificity for the neurotransmitter melatonin over its biosynthetic synthon l-tryptophan and the thermodynamic parameters governing the template-modulated micellization process. When bound to the bipyridinium units of micellized surfactant molecules, melatonin effectively serves as "molecular glue" capable of lowering the CMC by 52% as compared to untemplated solutions. Analysis of this system suggests that a hallmark of donor-acceptor template-modulated micellization in water is a strong positively correlated temperature dependence of the CMC and the absence of a U-shaped CMC-temperature curve. Our findings make a case for the incorporation of l-tryptophan-based metabolites and their classical synthetic pharmaceutical bioisosteres as potential targets/components of donor-acceptor CT-based supramolecular amphiphile systems/materials operating in water.


Regulating the active species of Ni(OH)2 using CeO2: 3D CeO2/Ni(OH)2/carbon foam as an efficient electrode for the oxygen evolution reaction.
Three dimensional (3D) N, O and S doped carbon foam (NOSCF) is prepared as a substrate for in situ vertically grown Ni(OH)2 nanosheets. As designed Ni(OH)2/NOSCF possesses strong electrostatic interactions with OH- ions due to many C[double bond, length as m-dash]O groups existing in NOSCF, which can facilitate the formation of crucial NiOOH intermediates during the OER process. CeO2 nanoparticles (NPs) of ∼3.3 nm in size are decorated on Ni(OH)2 nanosheets to design a highly efficient CeO2/Ni(OH)2/NOSCF electrocatalyst for the oxygen evolution reaction (OER). The CeO2 NP decorated Ni(OH)2/NOSCF not only exhibits a remarkably improved OER performance with an onset potential of 240 mV, outperforming most reported non-noble metal based OER electrocatalysts, but also possesses a small Tafel slope of 57 mV dec-1 and excellent stability under different overpotentials. The synergistic effect of producing more active species of NiIII/IV and accelerating the charge transfer for Ni(OH)2/NOSCF by the introduction of CeO2 NPs is also investigated. These results demonstrate the possibility of designing energy efficient OER catalysts with the assistance of earth abundant CeO2-based catalysts.


Knockdown of PCBER1, a gene of neolignan biosynthesis, resulted in increased poplar growth.
Poplar trees displayed an increased plant height due to the transgenic knockdown of PCBER1, a gene of lignan biosynthesis. The wood composition was slightly altered in both overexpression and knockdown lines. The gene PHENYLCOUMARAN BENZYLIC ETHER REDUCTASE1 (PCBER1) is well known as an important gene in the synthesis of lignans, a group of diverse phenylpropanoid derivatives. They are widely distributed in the plant kingdom and may have a role in both plant defense and growth regulation. To analyze its role in biomass formation and wood composition in poplar, both overexpression and knockdown approaches have been performed. Transgenic lines were analyzed on genetic and phenotypic levels, and partly in regard to their biomass composition. While the PCBER1 overexpression approach remained unremarkable concerning the plant height, biomass composition of obtained transgenic lines was modified. They had a significantly increased amount of ethanol extractives. The PCBER1 knockdown resulted in significantly deviating plants; after 17 months of greenhouse cultivation, transgenic plants were up to 38% higher compared to non-transgenic wild type. Most examined transgenic lines did not reveal a significantly enhanced stem diameter after three vegetation periods in the greenhouse. Significant changes were not obtained with regard to the three major wood components, lignin, cellulose and hemicelluloses. As a slight but not significant reduction in ethanol extractives was detected, the hypothesis arises that the lignan content could be influenced. Lignans become important in the pharmaceutical industry and clinical studies concerning cancer and other diseases, thus further investigations on lignan formation in poplar and its connection to biomass formation seem promising.


Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting.
Recently, reports have suggested that chronic cannabis abuse can result in cyclical vomiting, or cannabinoid hyperemesis syndrome. With the increasing prevalence of cannabis use in the United States, this syndrome may be encountered in the emergency department. The authors describe a case of a 30-year-old man who presented to the emergency department with diffuse abdominal pain, nausea, and intractable vomiting. He reported symptomatic relief with prolonged hot showers. Results of a urine drug screen were positive for cannabis, and the patient admitted to chronic cannabis use for years. Results of the drug screen, combined with the patient's symptomatic relief with hot showers, led to the diagnosis of cannabinoid hyperemesis syndrome. The patient was admitted to the hospital and underwent pharmaceutical treatment. However, hot showers continued to be the mainstay of the patient's symptomatic relief. Four days after presentation, the patient's symptoms resolved and he was discharged from the hospital.


Hidden bias in the DUD-E dataset leads to misleading performance of deep learning in structure-based virtual screening.
Recently much effort has been invested in using convolutional neural network (CNN) models trained on 3D structural images of protein-ligand complexes to distinguish binding from non-binding ligands for virtual screening. However, the dearth of reliable protein-ligand x-ray structures and binding affinity data has required the use of constructed datasets for the training and evaluation of CNN molecular recognition models. Here, we outline various sources of bias in one such widely-used dataset, the Directory of Useful Decoys: Enhanced (DUD-E). We have constructed and performed tests to investigate whether CNN models developed using DUD-E are properly learning the underlying physics of molecular recognition, as intended, or are instead learning biases inherent in the dataset itself. We find that superior enrichment efficiency in CNN models can be attributed to the analogue and decoy bias hidden in the DUD-E dataset rather than successful generalization of the pattern of protein-ligand interactions. Comparing additional deep learning models trained on PDBbind datasets, we found that their enrichment performances using DUD-E are not superior to the performance of the docking program AutoDock Vina. Together, these results suggest that biases that could be present in constructed datasets should be thoroughly evaluated before applying them to machine learning based methodology development.


Prospective associations between prenatal adversities and borderline personality disorder at 11-12 years.
The aetiological pathways to borderline personality disorder (BPD) remain only partly elucidated. Retrospective research indicates that prenatal adversity may be an important early risk factor in the development of BPD. This requires corroboration with prospective longitudinal studies. A community sample of 6050 mothers and their children (born between April 1991 and December 1992) were assessed. Maternal anxiety and depression and maternal alcohol and tobacco consumption were assessed during pregnancy (18 and 32 weeks gestation). Postnatal risks, including maladaptive parenting (suboptimal parenting and parent conflict), family adversity, maternal anxiety and depression and maternal alcohol and tobacco consumption, were assessed during early childhood. Internalizing and externalizing symptoms were assessed in late childhood. Trained psychologists interviewed children in late childhood to ascertain the presence of BPD (at least five probable/definite symptoms). In unadjusted analyses, all prenatal risk factors (i.e., maternal alcohol and tobacco consumption and maternal anxiety and depression) were significantly associated with BPD. Following adjustment for sex, birthweight and postnatal exposure to anxiety and depression respectively, maladaptive parenting, family adversity and child's internalizing and externalizing symptoms, prenatal anxiety at 18 weeks gestation [odds ratio (OR) 1.57, 95% confidence interval (CI) 1.18-2.09] and depression at 18 weeks (OR 1.59, 95% CI 1.08-2.32) and 32 weeks (OR 1.57, 95% CI 1.14-2.18) gestation remained significantly associated with BPD. This study provides prospective evidence of associations between prenatal adversities and BPD at 11-12 years. Prenatal anxiety and depression were independently associated with BPD, suggesting that they may exert direct effects on BPD during the prenatal period. This highlights the importance of programmes to reduce maternal stress during pregnancy.


Influence of irregular gaps between primary mirror segments on telescope image quality.
We study the effect of gaps between the segments on image quality of the extremely large ground-based telescope. We show that if the width of the gap changes arbitrarily from one intersegment boundary to another, the regular diffraction pattern is distorted and speckles appear. Two mechanisms producing irregularity in the gaps' distribution are considered: a random shift of the segment's center and an error in the segment's shape. The analytical approach allows an estimation of ensemble averaged characteristics of the point-spread function, such as a halo and high-order diffraction peaks. We deliver simple formulas for the quantitative estimation of the position and the intensity of the halo as well as the intensity of the diffraction peaks.


Association of the mu-opioid receptor gene with smoking cessation.
We investigated the association of the OPRM1 genotype with long-term smoking cessation and change in body mass index (BMI) following a smoking cessation attempt among smokers who attempted to quit using the nicotine replacement therapy (NRT) patch or placebo in a randomized controlled trial, and were followed-up over an 8-year period following their initial cessation attempt. We also investigated possible sex differences in these relationships, given evidence for sex differences in smoking cessation and central opioid mechanisms, as well as some evidence for sex differences in response to NRT. Our results indicate that OPRM1 genotype may moderate the effect of transdermal nicotine patch compared to placebo during active treatment, with a benefit of active NRT treatment evident in the OPRM1 AA genotype group only and those carrying one or more copies of the G allele demonstrating no benefit of active NRT versus placebo patch. Our results also indicate a sex difference in change in BMI at 8-year follow-up following a smoking cessation attempt, with ex-smokers demonstrating an increase in BMI, and this increase being greater in female subjects than in male subjects. We did not observe any association of OPRM1 genotype with change in BMI, although there was a trend for genotype to influence the observed sex difference in change in BMI over time. Future studies should attempt to replicate these findings, and investigate the relationship between both short- and long-term weight gain and smoking cessation and investigate possible mechanisms that may underlie these processes. Future studies should also investigate the role of OPRM1 genotype and smoking cessation on other appetitive and reward behaviours such as alcohol consumption.


[Scientific evidence in medicine: the only alternative?].
The present article aims to reflect on the current situation of medical sciences by incorporating a critical discussion of knowledge atomization, which can be a consequence of the pragmatism of scientific evidence. The article proposes to integrate the contributions of quantitative and qualitative methodologies in health sciences, paying attention to qualitative and quantitative designs that take into account the complexity of human beings and their axiological, social, and cultural referents.The authors defend and argue for the need for health research to contemplate five useful dimensions for decision-making, approaching the object of the study and without eliminating the subject and his/her polyhedral and complex circumstances. Medicine must unavoidably consider technological and technical knowledge, but this training must not elude the necessary relational and communicative competences. Scientific and medical updating implies a constant close association between technical rigor and improved links among the individuals involved (health professionals and the public), with a careful and respectful attitude. Community activity and the gradual establishment of complicities are put forward as the basis for an integrative health model, with biopsychosocial roots, both at a theoretical and a practical level.


Chems4EU: chemsex use and its impacts across four European countries in HIV-positive men who have sex with men attending HIV services.
Chemsex in a European context is the use of any of the following drugs to facilitate sex: crystal methamphetamine, mephedrone and gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) and, to a lesser extent, cocaine and ketamine. This study describes the prevalence of self-reported recreational drug use and chemsex in HIV-positive men who have sex with men (MSM) accessing HIV services in four countries. It also examines the problematic impacts and harms of chemsex and access to chemsex-related services. This is a cross-sectional multi-centre questionnaire study of HIV-positive MSM accessing nine HIV services in the UK, Spain, Greece and Italy. In all, 1589 HIV-positive MSM attending HIV services in four countries completed the questionnaire. The median age of participants was 38 years (interquartile range: 32-46 years) and 1525 (96.0%) were taking antiretroviral therapy (ART). In the previous 12 months, 709 (44.6%) had used recreational drugs, 382 (24.0%) reported chemsex and 104 (6.5%) reported injection of chemsex-associated drugs ('slamsex'). Of the 382 engaging in chemsex, 155 (40.6%) reported unwanted side effects as a result of chemsex and 81 (21.2%) as a result of withdrawal from chemsex. The reported negative impacts from chemsex were on work (25.1%, 96), friends/family (24.3%, 93) and relationships (28.3%, 108). Fifty-seven (14.9%) accessed chemsex-related services in the past year, 38 of whom (67%) felt the service met their needs. A quarter of participants self-reported chemsex in the past 12 months. There were high rates of harms from chemsex across all countries, including negative impacts on work, friends/family and relationships. Although a minority of those engaging in chemsex accessed support, most found this useful.


Observations on parasitism in deep-sea hydrothermal vent and seep limpets.
Parasite burdens of shallow-water molluscs have been well documented, but little is known about parasite burdens of molluscs from deep-sea chemosynthetic environments (e.g. hydrothermal vents and seeps). Chemosynthetic habitats are characterized by high concentrations of reduced sulfur and, in the case of vents, high heavy metal concentrations. These compounds are noxious and even stress-inducing in some environments, but are part of the natural chemical milieu of vents and seeps. To examine parasite types and infection intensities in limpets from vents and seeps we documented parasite burdens in 4 limpet species from 4 hydrothermal vent fields (3 on the East Pacific Rise, 1 on the Mid-Atlantic Ridge) and 1 seep site (Florida Escarpment). Approximately 50 % of all limpets examined were infected with 1 or more types of parasites. Limpet parasites were predominantly rickettsia-like inclusions in the digestive and gill epithelia. Limpets collected from the vent field on the Mid-Atlantic Ridge were free of parasites. We detected no histopathological effects that we could attribute to parasites.


Changes in the estimated time course of the motoneuron afterhyperpolarization induced by tendon vibration.
Group Ia afferents are activated vigorously with high-frequency tendon vibration and provide excitatory input to the agonist muscle and inhibitory input to the antagonist muscle group via inhibitory interneurons. The purpose of this experiment was to determine whether the afterhyperpolarization (AHP) time course in humans is altered in response to tendon vibration. The AHP time course is estimated using the interval death rate (IDR) analysis, a transform of the motor unit action potential train. Single motor units from tibialis anterior (TA) were recorded as subjects held low force dorsiflexor contractions for 600 s with and without vibration. The vibratory stimulus was superimposed on the low force contraction either to the tendon of the TA or the antagonist Achilles tendon. During TA tendon vibration, the time course of the AHP, as expressed by its time constant (τ), decreased from 35.5 ms in the previbration control condition to 31.3 ms during the vibration (P = 0.003) and returned to 36.3 ms after the vibration was removed (P = 0.002). The AHP τ during vibration of the antagonist Achilles tendon (38.6 ms) was greater than the previbration control condition (33.6 ms; P = 0.001). It is speculated that the reduction in AHP time constant with TA vibration may have resulted alone or in combination with a modulation of motoneuron gain, an alteration of persistent inward currents and/or the restructuring of synaptic noise. A decrease in firing probability, possibly reflecting Ia reciprocal inhibition, may have been responsible for the larger AHP time constant.


T cells become licensed in the lung to enter the central nervous system.
The blood–brain barrier (BBB) and the environment of the central nervous system (CNS) guard the nervous tissue from peripheral immune cells. In the autoimmune disease multiple sclerosis, myelin-reactive T-cell blasts are thought to transgress the BBB and create a pro-inflammatory environment in the CNS, thereby making possible a second autoimmune attack that starts from the leptomeningeal vessels and progresses into the parenchyma. Using a Lewis rat model of experimental autoimmune encephalomyelitis, we show here that contrary to the expectations of this concept, T-cell blasts do not efficiently enter the CNS and are not required to prepare the BBB for immune-cell recruitment. Instead, intravenously transferred T-cell blasts gain the capacity to enter the CNS after residing transiently within the lung tissues. Inside the lung tissues, they move along and within the airways to bronchus-associated lymphoid tissues and lung-draining mediastinal lymph nodes before they enter the blood circulation from where they reach the CNS. Effector T cells transferred directly into the airways showed a similar migratory pattern and retained their full pathogenicity. On their way the T cells fundamentally reprogrammed their gene-expression profile, characterized by downregulation of their activation program and upregulation of cellular locomotion molecules together with chemokine and adhesion receptors. The adhesion receptors include ninjurin 1, which participates in T-cell intravascular crawling on cerebral blood vessels. We detected that the lung constitutes a niche not only for activated T cells but also for resting myelin-reactive memory T cells. After local stimulation in the lung, these cells strongly proliferate and, after assuming migratory properties, enter the CNS and induce paralytic disease. The lung could therefore contribute to the activation of potentially autoaggressive T cells and their transition to a migratory mode as a prerequisite to entering their target tissues and inducing autoimmune disease.


The risk of second primary cancer after nasopharyngeal cancer: a systematic review.
Second primary cancers (SPCs) after nasopharyngeal cancer (NPC) are rare, but have an impact on the follow-up of this patient population. The aim of this study is to systematically review the literature to determine the prevalence and most typical sites of SPCs after NPC. We searched the databases of PubMed, Web of Science, and Scopus for articles on SPCs after NPC. The Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines were followed. This review includes data on 89 168 patients with NPC from 21 articles. The mean occurrence for SPCs was 6.6% and varied from 4.9% in endemic areas to 8.7% in non-endemic areas. The most frequent locations of SPCs were oral cavity, pharynx, nose and paranasal sinuses, esophagus and lung. There is an increased risk for a SPC after NPC management, especially in non-endemic areas. However, their mean rate is lower than after other head and neck carcinomas.


Insomnia and endothelial function - the HUNT 3 fitness study.
Insomnia is associated with increased risk of coronary heart disease (CHD), but the underlying mechanisms are not understood. To our knowledge, no previous studies have examined insomnia in relation to endothelial function, an indicator of preclinical atherosclerosis. Our aim was to assess the association of insomnia with endothelial function in a large population based study of healthy individuals. A total of 4 739 participants free from known cardiovascular or pulmonary diseases, cancer, and sarcoidosis, and who were not using antihypertensive medication were included in the study. They reported how often they had experienced difficulties falling asleep at night, repeated awakenings during the night, early awakenings without being able to go back to sleep, and daytime sleepiness. Endothelial function was measured by flow mediated dilation (FMD) derived from the brachial artery. We found no consistent association between the insomnia symptoms and endothelial function in multiadjusted models, but individual insomnia symptoms may be related to endothelial function. Among women who reported early awakenings, endothelial function may be lower than in women without this symptom (p = 0.03). This study provided no evidence that endothelial function, an early indicator of atherosclerosis, is an important linking factor between insomnia and CHD. Further studies are needed to explore the complex interrelation between sleep and cardiovascular pathology.


The dangers of hazards.
Concerns about the quality and reproducibility of scientific papers have emphasised the uncertainty of observations in the biological sciences. Focussing on this problem in the types of science that often underlie regulations affecting population exposures has clear implications for regulatory studies. Recent comments on the IARC process of hazard identification in the field of carcinogenesis have identified problems in dealing with public information content and regulatory value of the Monograph system. What is the value of a system that does not clearly identify its methodology for defining a hazard and which does not provide realistic estimates of risk?


Polymyxin B induces lysis of marine pseudoalteromonads.
Polymyxin B (PMB) is a cationic antibiotic that interacts with the envelopes of gram-negative bacterial cells. The therapeutic use of PMB was abandoned for a long time due to its undesirable side effects; however, the spread of resistance to currently used antibiotics has forced the reevaluation of PMB for clinical use. Previous studies have used enteric bacteria to examine the mode of PMB action, resulting in a somewhat limited understanding of this process. This study examined the effects of PMB on marine pseudoalteromonads and demonstrates that the frequently accepted view that "what is true for Escherichia coli is true for all bacteria" does not hold true. We show here that in contrast to the growth inhibition observed for enteric bacteria, PMB induces lysis of pseudoalteromonads, which is not prevented by high concentrations of divalent cations. Furthermore, we demonstrate that a high membrane voltage is required for the interaction of PMB with the cytoplasmic membranes of pseudoalteromonads, further elucidating the mechanisms by which PMB interacts with the cell envelopes of those gram-negative bacteria.


Improvement in Recovery of Hemodynamic Responses by Extended Kalman Filter With Non-Linear State-Space Model and Short Separation Measurement.
The purpose of this study is to describe the noise reduction in the hemodynamic responses, obtained by functional near-infrared spectroscopy (fNIRS), using the proposed extended Kalman filter (EKF) with a non-linear state-space model, aided by the short separation (SS) measurement. The authors used the simulated data by adding the synthetic hemodynamic response function (HRF) to the multi-distance four-channel fNIRS signals obtained during the resting state. EKF was used to estimate the non-linear state-space model designed based on the Balloon model. The SS channel was used as a regressor that is sensitive only to superficial noises. The whole segments were grouped by the existence of motion artifacts (MAs) to investigate the improvement by EKF compared to the linear Kalman filter (LKF) and adaptive filter (AF) in extracting neural-evoked hemodynamic. Kalman-based approaches were better than AF in reducing noises. Using EKF, the averages of the decreased errors and increased correlation between the recovered and true HRF were 34% in oxy-hemoglobin and 62% in deoxy-hemoglobin concentrations in segments having MAs, compared with LKF. In the MA-free condition, EKF is more robust to the poor quality of signals in noise reduction than LKF. The proposed non-linear Kalman approach is better in noise reduction than AF and LKF especially in noisy deoxy-hemoglobin concentrations, and less affected by the conditions of measurements and contaminations by MAs. The proposed method can be used for reducing superficial noises and MAs from fNIRS signals as an upgraded alternative to existing AFs.


Impact of Implementing Antenatal Syphilis Point-of-Care Testing on Maternal Mortality in KwaZulu-Natal, South Africa: An Interrupted Time Series Analysis.
Syphilis infection has been associated with an increased risk of HIV infection during pregnancy which poses greater risk for maternal mortality, and antenatal syphilis point-of-care (POC) testing has been introduced to improve maternal and child health outcomes. There is limited evidence on the impact of syphilis POC testing on maternal outcomes in high HIV prevalent settings. We used syphilis POC testing as a model to evaluate the impact of POC diagnostics on the improvement of maternal mortality in KwaZulu-Natal, South Africa. We extracted 132 monthly data points on the number of maternal deaths in facilities and number of live births in facilities for 12 tertiary healthcare facilities in KwaZulu-Natal (KZN), South Africa from 2004 to 2014 from District Health Information System (DHIS) health facility archived. We employed segmented Poisson regression analysis of interrupted time series to assess the impact of the exposure on maternal mortality ratio (MMR) before and after the implementation of antenatal syphilis POC testing. We processed and analyzed data using Stata Statistical Software: Release 13. (Stata, Corp LP, College Station, TX, USA). The provincial average annual maternal mortality ratio (MMR) was estimated at 176.09 ± 43.92 ranging from a minimum of 68.48 to maximum of 225.49 per 100,000 live births. The data comprised 36 temporal points before the introduction of syphilis POC test exposure and 84 after the introduction in primary health care clinics in KZN. The average annual MMR for KZN from 2004 to 2014 was estimated at 176.09 ± 43.92. A decrease in MMR level was observed during 2008 after syphilis POC test implementation, followed by a rise during 2009. Analysis of the MMR trend estimates a significant 1.5% increase in MMR trends during the period before implementation and 1.3% increase after implementation of syphilis POC testing (p < 0.001). Although our finding suggests a brief reduction in the MMR trend after the implementation of antenatal syphilis POC testing, a continued increase in syphilis rates is seen in KwaZulu-Natal, South Africa. The study used one of the most powerful quasi-experimental research methods, segmented Poisson regression analysis of interrupted time series to model the impact of syphilis POC on maternal outcome. The study finding requires confirmation by use of more rigorous primary study design.


Refractive error and monocular viewing strengthen the hollow-face illusion.
We measured the strength of the hollow-face illusion--the 'flipping distance' at which perception changes between convex and concave--as a function of a lens-induced 3 dioptre refractive error and monocular/binocular viewing. Refractive error and closing one eye both strengthened the illusion to approximately the same extent. The illusion was weakest viewed binocularly without refractive error and strongest viewed monocularly with it. This suggests binocular cues disambiguate the illusion at greater distances than monocular cues, but that both are disrupted by refractive error. We argue that refractive error leaves the ambiguous low-spatial-frequency shading information critical to the illusion largely unaffected while disrupting other, potentially disambiguating, depth/distance cues.


Visual and refractive outcomes and complications in femtosecond laser-assisted versus conventional phacoemulsification cataract surgery: findings from a randomised, controlled clinical trial.
To compare visual and refractive outcomes, changes in intraocular pressure (IOP), and complications of femtosecond laser-assisted cataract surgery (FLACS) to conventional phacoemulsification surgery (CPS) in paired eyes from the same patients. This is a secondary analysis of an intraindividual, randomised, controlled clinical trial including 110 paired eyes from 55 patients that were randomised into either FLACS or CPS groups. Outcomes were recorded at baseline and postoperatively during a 3-month follow-up period. Uncorrected distance visual acuity and corrected distance visual acuity were similar between FLACS and CPS over the follow-up period (p>0.05). The mean absolute refractive error was not significantly different between the two groups at postoperative month 1 (POM1) (0.3±0.2 D in FLACS vs 0.4±0.3 D in CPS, p=0.18) and month 3 (POM3) (0.3±0.3 D in FLACS vs 0.3±0.3 D in CPS, p=0.71). IOP was statistically higher in the FLACS group on postoperative day 1 (20.6±5.7 mm Hg for FLACS and 18.0±4.9 mm Hg for CPS, p=0.01). However, it was similar between the two groups subsequently (p>0.05). Intraoperatively, one case of posterior capsular block syndrome was observed in the FLACS group. Postoperatively, one case of newly developed glaucoma was observed in the FLACS group and one case of retinal tears in the CPS group. The 3-month postoperative refractive and visual outcomes were comparable between FLACS and CPS in paired eyes from the same patients. Complication rate was low in the study population.


Few-Example Object Detection with Model Communication.
In this paper, we study object detection using a large pool of unlabeled images and only a few labeled images per category, named "few-example object detection". The key challenge consists in generating trustworthy training samples as many as possible from the pool. Using few training examples as seeds, our method iterates between model training and high-confidence sample selection. In training, easy samples are generated first and, then the poorly initialized model undergoes improvement. As the model becomes more discriminative, challenging but reliable samples are selected. After that, another round of model improvement takes place. To further improve the precision and recall of the generated training samples, we embed multiple detection models in our framework, which has proven to outperform the single model baseline and the model ensemble method. Experiments on PASCAL VOC'07, MS COCO'14, and ILSVRC'13 indicate that by using as few as three or four samples selected for each category, our method produces very competitive results when compared to the state-of-the-art weakly-supervised approaches using a large number of image-level labels.


Left Ventricular Structure and Function in Elite Swimmers and Runners.
Sport-specific differences in the left ventricle (LV) of land-based athletes have been observed; however, comparisons to water-based athletes are sparse. The purpose of this study was to examine differences in LV structure and function in elite swimmers and runners. Sixteen elite swimmers [23 (2) years, 81% male, 69% white] and 16 age, sex, and race matched elite runners participated in the study. All athletes underwent resting echocardiography and indices of LV dimension, global LV systolic and diastolic function, and LV mechanics were determined. All results are presented as swimmers vs. runners. Early diastolic function was lower in swimmers including peak early transmitral filling velocity [76 (13) vs. 87 (11) cm ⋅ s-1, p = 0.02], mean mitral annular peak early velocity [16 (2) vs. 18 (2) cm ⋅ s-1, p = 0.01], and the ratio of peak early to late transmitral filling velocity [2.68 (0.59) vs. 3.29 (0.72), p = 0.005]. The diastolic mechanics index of time to peak untwisting rate also occurred later in diastole in swimmers [12 (10)% diastole vs. 5 (4)% diastole, p = 0.01]. Cardiac output was larger in swimmers [5.8 (1.5) vs. 4.7 (1.2) L ⋅ min-1, p = 0.04], which was attributed to their higher heart rates [56 (6) vs. 49 (6) bpm, p < 0.001] given stroke volumes were similar between groups. All other indices of LV systolic function and dimensions were similar between groups. Our findings suggest enhanced early diastolic function in elite runners relative to swimmers, which may be attributed to faster LV untwisting.


Volume Flow Measurements in Arteriovenous Dialysis Access in Patients with and without Steal Syndrome.
Introduction. Dialysis associated steal syndrome (DASS) constitutes a serious risk for patients undergoing vascular access operations. We aim to assess the measured volume flow using ultrasound in patients with clinically suspected steal syndrome and determine differences in flow among types of arteriovenous (AV) access. Methods. Patients with permanent hemodialysis access with and without ischemic steal underwent duplex ultrasound (US) exams for the assessment of volume flow and quantitative evidence of hemodynamic steal. Volume flow was measured in the proximal feeding artery. Results. 118 patients underwent US of which 82 (69.5%) had clinical evidence of steal. Women were more likely to develop steal compared to men (chi-squared test P < 0.04). Mean volume flow in patients with steal was 1542 mL/min compared to 1087 mL/min (P < 0.002) in patients without evidence of steal. A significant difference in flow volumes in patients with and without steal was only seen in patients with a brachial-cephalic upper arm AV fistula (AVF) (P < 0.002). When comparing different types of access with steal, brachial-cephalic upper arm AVFs had higher volume flows than the upper extremity AV graft (AVG) group (P = 0.04). Conclusion. In patients with DASS, women were more likely to develop steal syndrome. Significantly higher volume flows were seen with brachial-cephalic upper arm AVF in patients with steal compared to those without. A physiologic basis of this US finding may be present, which warrants further study into the dynamics of flow and its relationship to the underlying peripheral arterial pathology in the development of ischemic steal.


The transmission dynamics of canine American cutaneous leishmaniasis in Huánuco, Peru.
The epidemiology of canine American cutaneous leishmaniasis (ACL) due to Leishmania (Viannia) spp. was investigated in Huánuco, Peru to 1) describe the natural course of canine L. (Viannia) infections and 2) assess the role of domestic dogs as ACL reservoir hosts. Over a three-year period 1,022 dogs were surveyed, with cumulative village L. (Viannia) prevalence being 26% (range = 0-100%). The incidence of L. (Viannia) was estimated to be 0.285 dogs/year (95% confidence interval [CI] = 0.160-0.410) using cross-sectional data and 0.291 dogs/year (95% CI = 0.195-0.387) using data from 108 dogs that were surveyed prospectively. The recovery rate was estimated to be 0.456 dogs/year (95% CI = 0.050-0.862) and 0.520 dogs/year (95% CI = 0.302-0.738), respectively. Using those findings, the basic reproduction number was estimated to be R0 approximately to 1.9; if dogs were the principal ACL reservoirs, the mean yearly effort (i.e., coverage or elimination) of a dog control intervention (e.g., collaring, culling, or vaccination) to ensure the elimination of L. (Viannia) spp. transmission would be as low as 47%.


Comparison of refractive outcomes after photorefractive keratectomy with different optical zones using Mel 90 excimer laser.
A larger optical zone for photorefractive keratectomy may improve optical quality and stability. However, there is need for limiting ablation diameter in that a larger ablation diameter requires greater ablation depth, and minimizing ablation depth may reduce adverse effects on postoperative wound healing, haze and keratoectasia. In this study, we compared the changes in clinical outcomes and the degree of regression between a 6.0 mm optical zone and 6.5 mm optical zone following PRK. The records of 95 eyes that had undergone PRK with a 6.0 OZ (n = 40) and a 6.5 OZ (n = 55) were retrospectively reviewed. We compared data including the spherical equivalent of manifest refraction (SE of MR), simulated K (Sim K), thinnest corneal thickness, change in thinnest corneal thickness (the initial value divided by corrected diopter [ΔTCT/CD]), Q value, corneal higher order aberrations (HOAs) and spherical aberration (SA) pre-operation, at 3 and 6 months postoperative and at the last follow-up visit (Mean; 20.71 ± 10.52, 17.47 ± 6.57 months in the 6.0 and 6.5 OZ group, respectively). There were no significant differences in the SE of MR, Sim K and UDVA between the 6.0 OZ group and the 6.5 OZ group over 1 year of follow-up after PRK, and the 6.0 OZ group required less ΔTCT/CD than the 6.5 OZ group. The 6.5 OZ group showed better results in terms of post-operative HOAs of RMS, SA and Q value. When comparing that pattern of change in Sim K, there was no significant difference between the 6.0 OZ group and the 6.5 OZ group. The clinical refractive outcomes and regression after PRK using Mel 90 excimer laser with a 6.0 OZ were comparable to those with a 6.5 OZ.


Phenomenological study exploring ethics in prehospital research from the paramedic's perspective: experiences from the Paramedic-2 trial in a UK ambulance service.
We set out to investigate paramedics' views of ethics and research, drawing on experiences from Paramedic-2, a randomised controlled trial comparing epinephrine and placebo in out-of-hospital cardiac arrest (OHCA). An interpretative phenomenological approach was adopted. A purposive sample of paramedics (n=6) from North East Ambulance Service NHS Foundation Trust were invited to a semi-structured, in-depth interview. Three superordinate themes emerged: (1) morality, (2) emotion and (3) equipoise. Some viewed Paramedic-2 as an opportunity to improve OHCA outcomes for the many, viewing participation as a moral obligation; others viewed the study as unethical, equating participation with immoral behaviour. Morality was a motivator to drive individual action. Positive and negative emotions were exhibited by the paramedics involved reflecting the wider view each paramedic held about trial participation. Those morally driven to participate in Paramedic-2 discussed their pride in being associated with the trial, while those who found participation unethical, discussed feelings of guilt and regret. Individual experience and perceptions of epinephrine guided each paramedic's willingness to accept or reject equipoise. Some questioned the role of epinephrine in OHCA; others believed withholding epinephrine was synonymous to denying patient care. A paucity of evidence exists to support any beneficial role of epinephrine in OHCA. Despite this, some paramedics were reluctant to participate in Paramedic-2 and relied on their personal perceptions and experiences of epinephrine to guide their decision regarding participation. Failure to acknowledge the importance of individual perspectives may jeopardise the success of future out-of-hospital trials.


Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study.
An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded type IV collagen (C4M), and citrullinated and MMP-degraded vimentin (VICM), were higher in the serum of cancer patients than in healthy controls. However, it is not known if these biomarkers could predict an increased risk of cancer. The aim of this study was to investigate whether C1M, C4M, and VICM were elevated prior to diagnosis of solid cancers in a large prospective study. Between 1999 and 2001, 5,855 postmenopausal Danish women ages 48 to 89 years enrolled in the Prospective Epidemiologic Risk Factor study. Baseline demographics and serum were collected at the time of registration. Follow up cancer diagnoses were obtained from the Danish Cancer Registry in 2014. Serum C1M, C4M, and VICM levels were measured by competitive ELISAs. A total of 881 women were diagnosed with solid cancers after baseline. C1M, C4M, and VICM levels were significantly elevated in women diagnosed less than 1 year after baseline. C1M and VICM, but not C4M, were independent predictors of increased risk of cancer. C1M, C4M, and VICM are elevated prior to cancer diagnosis. C1M and VICM are both independent predictors of increased cancer risk. C1M and VICM are predictors for increased risk of cancer. Cancer Epidemiol Biomarkers Prev; 25(9); 1348-55. ©2016 AACR.


Helical metallohost-guest complexes via site-selective transmetalation of homotrinuclear complexes.
We have designed a new type of bis(N2O2) chelate ligand that affords a C-shaped O6 site on the metalation of the N2O2 sites. UV-vis and 1H NMR titration clearly showed that the complexation between H4L and zinc(II) acetate affords 1:3 complex [LZn3]2+ via a highly cooperative process. Although the O6-recognition site of the dinuclear metallohost [LZn2] is filled with the additional Zn2+, the O6 site can bind a guest ion with concomitant release of the initially bound Zn2+. The novel recognition process "guest exchange" took place quantitatively when rare earth metals were used as a guest. In the case of alkaline earth metals, selectivity of Ca2+ > Sr2+ > Ba2+ >> Mg2+ was observed. On the other hand, the transmetalation did not take place at all when alkali metals were used for the guest. Accordingly, the trinuclear complex [LZn3]2+ is excellent in discriminating charge of the guest ions. The metallohost-guest complexes thus obtained have a helical structure, and the radius d and winding angle theta of the helix depend on the size of the guest. The La3+ complex has the smallest theta (288 degrees), and the Sc3+ complex has the largest theta (345 degrees). Because the radius and winding angles of helices are tunable by changing the guest ion, the helical metallohost-guest complexes are regarded as a molecular spring or coil. Consequently, site-specific metal exchange of trinuclear complex [LZn3]2+ described here will be utilized for highly selective ion recognition, site-selective synthesis of (3d)2(4f) trimetallic complexes, and construction of "tunable" metallohelicenes.


Impact of the 2017 Blood Pressure Guidelines by the American Academy of Pediatrics in overweight/obese youth.
The aim of this study was to compare the impact of the European Society of Hypertension Guidelines 2016 (ESHG2016) and the American Academy of Pediatrics Guidelines 2017 (AAPG2017) on the screening of hypertension and classification of abnormal left ventricular geometry (ALVG) in overweight/obese youth. This study included 6137 overweight/obese youth; 437 had echocardiographic assessment. Hypertension was defined using either ESHG2016 or AAPG2017. ALVG was defined using 95th percentile for age and sex of left ventricular mass index (LVMi) and/or relative wall thickness (RWT) more than 0.38 (juvenile cut-offs) according to ESHG2016 or LVMi more than 51 g/h and/or RWT more than 0.42 (adult cut-offs) according to AAPG2017. Prevalence of youth at a high risk of hypertension was 13% higher using AAPG2017 than ESHG2016. The increase was larger in overweight youth at least 13 years of age (+43%). Using the juvenile cut-offs for ALVG, youth at a high risk of hypertension by ESHG2016 had an odds ratio [95% confidence interval (95% CI)] of 3.03 (1.31-7.05) for left ventricular concentric remodelling (LVcr) and 2.53 (1.43-4.47) for concentric left ventricular hypertrophy (cLVH) as compared with youth with normal LVG. Similarly, in youth at a high risk of hypertension by AAPG2017, the odds ratio for LVcr was 3.28 (1.45-7.41, P < 0.001) and 3.02 (95% CI: 1.73-5.27, P < 0.001) for cLVH. Using the adult cut-offs, no significant difference in ALVG was found with both guidelines. The prevalence of overweight/obese youth at a high risk of hypertension increased by 13% comparing AAPG2017 vs. ESHG2016. The juvenile cut-offs for ALVG were more effective than the adult criteria in intercepting individuals with a potentially higher cardiovascular risk.


Overview of the transcriptome profiles identified in hagfish, shark, and bichir: current issues arising from some nonmodel vertebrate taxa.
Because of their crucial phylogenetic positions, hagfishes, sharks, and bichirs are recognized as key taxa in our understanding of vertebrate evolution. The expression patterns of the regulatory genes involved in developmental patterning have been analyzed in the context of evolutionary developmental studies. However, in a survey of public sequence databases, we found that the large-scale sequence data for these taxa are still limited. To address this deficit, we used conventional Sanger DNA sequencing and a next-generation sequencing technology based on 454 GS FLX sequencing to obtain expressed sequence tags (ESTs) of the Japanese inshore hagfish (Eptatretus burgeri; 161,482 ESTs), cloudy catshark (Scyliorhinus torazame; 165,819 ESTs), and gray bichir (Polypterus senegalus; 34,336 ESTs). We deposited the ESTs in a newly constructed database, designated the "Vertebrate TimeCapsule." The ESTs include sequences from genes that can be effectively used in evolutionary developmental studies; for instance, several encode cartilaginous extracellular matrix proteins, which are central to an understanding of the ways in which evolutionary processes affected the skeletal elements, whereas others encode regulatory genes involved in craniofacial development and early embryogenesis. Here, we discuss how hagfishes, sharks, and bichirs contribute to our understanding of vertebrate evolution, we review the current status of the publicly available sequence data for these three taxa, and we introduce our EST projects and newly developed database.


Legal, ethical, and conceptual bottlenecks to the development of useful genomic tests.
This article discusses advances in genomic research in the context of the debate surrounding gene patent rights and the limited rights of patient-participants in translational research. In addition, the author explores statutory and regulatory hurdles to advances in disease diagnosis, such the Bayh-Dole Act, Medicare Legislation, and the Health Insurance Portability and Accountability Act. The author questions the effectiveness of increasingly commercialized academic research and the limited success of the private sector in genomic research. The author concludes that future genomic research will require significantly increased patient participation, which may necessitate a reshaping of the pharmaceutical approach to medicine and the limited stake that patients have in the breakthroughs developed through their participation in the process.


Variable responses of human microbiomes to dietary supplementation with resistant starch.
The fermentation of dietary fiber to various organic acids is a beneficial function provided by the microbiota in the human large intestine. In particular, butyric acid contributes to host health by facilitating maintenance of epithelial integrity, regulating inflammation, and influencing gene expression in colonocytes. We sought to increase the concentration of butyrate in 20 healthy young adults through dietary supplementation with resistant starch (unmodified potato starch-resistant starch (RS) type 2). Fecal samples were collected from individuals to characterize butyrate concentration via liquid chromatography and composition of the microbiota via surveys of 16S rRNA-encoding gene sequences from the Illumina MiSeq platform. Random Forest and LEfSe analyses were used to associate responses in butyrate production to features of the microbiota. RS supplementation increased fecal butyrate concentrations in this cohort from 8 to 12 mmol/kg wet feces, but responses varied widely between individuals. Individuals could be categorized into three groups based upon butyrate concentrations before and during RS: enhanced, high, and low (n = 11, 3, and 6, respectively). Fecal butyrate increased by 67 % in the enhanced group (from 9 to 15 mmol/kg), while it remained ≥11 mmol/kg in the high group and ≤8 mmol/kg in the low group. Microbiota analyses revealed that the relative abundance of RS-degrading organisms-Bifidobacterium adolescentis or Ruminococcus bromii-increased from ~2 to 9 % in the enhanced and high groups, but remained at ~1.5 % in the low group. The lack of increase in RS-degrading bacteria in the low group may explain why there was no increase in fecal butyrate in response to RS. The microbiota of individuals in the high group were characterized by an elevated abundance of the butyrogenic microbe Eubacterium rectale (~6 % in high vs. 3 % in enhanced and low groups) throughout the study. We document the heterogeneous responses in butyrate concentrations upon RS supplementation and identify characteristic of the microbiota that appear to underlie this variation. This study complements and extends other studies that call for personalized approaches to manage beneficial functions provided by gut microbiomes.


Imagery vividness before and during the PCI-HAP: a partial replication.
This study sought to replicate an earlier study wherein imagery vividness before and during a phenomenological hypnotic assessment procedure was assessed, while also measuring trance (hypnoidal) state effects and several other variables. Correlational and regression analyses for that study suggested that imagery vividness during hypnotism was predicted by combined imagery vividness before hypnotism and trance (altered) state effects during hypnotism. The present study procured a larger sample employing a similar design and a similar subject pool. With the current study, although trance state effects and imagery vividness before hypnotism still significantly predicted hypnotic imagoic suggestibility (imagery during hypnotism), the variance accounted for was appreciably less. The meaning of these results as a function of the methodology used is discussed.


Diagnosis and treatment of vertebral column metastases.
The vertebral column is recognized as the most common site for bony metastases in patients with systemic malignancy. Patients with metastatic spinal tumors may present with pain, neurologic deficit, or both. Some tumors are asymptomatic and are detected during screening examinations. Treatment options include medical therapy, surgery, and radiation. However, diversity of patient condition, tumor pathology, and anatomical extent of disease complicate broad generalizations for treatment. Historically, surgery was considered the most appropriate initial therapy in patients with spinal metastasis with the goal of eradication of gross disease. However, such an aggressive approach has not been practical for many patients. Now, operative intervention is often palliative, with pain control and maintenance of function and stability the major goals. Surgery is reserved for neurologic compromise, radiation failure, spinal instability, or uncertain diagnosis. Recent literature has revealed that surgical outcomes have improved with advances in surgical technique, including refinement of anterior, lateral, posterolateral, and various approaches to the anterior spine, where most metastatic disease is located. We review these surgical approaches for which a team of surgeons often is needed, including neurosurgeons and orthopedic, general, vascular, and thoracic surgeons. Overall, a multimodality approach is useful in caring for these patients. It is important that clinicians are aware of the various therapeutic options and their indications. The optimal treatment of individual patients with spinal metastases should include consideration of their neurologic status, anatomical extent of disease, general health, age, and qualilty of life.


Assessment of genetic diversity and population structure of Xanthomonas oryzae pv. oryzae with a repetitive DNA element.
A repetitive DNA element cloned from Xanthomonas oryzae pv. oryzae was used to assess the population structure and genetic diversity of 98 strains of X. oryzae pv. oryzae collected between 1972 and 1988 from the Philippine Islands. Genomic DNA from X. oryzae pv. oryzae was digested with EcoRI and analyzed for restriction fragment length polymorphisms (RFLPs) with repetitive DNA element as a probe. Twenty-seven RFLP types were identified; there was no overlap of RFLP types among the six races from the Philippines. Most variability (20 RFLP types) was found in strains of races 1, 2, and 3, which were isolated from tropical lowland areas. Four RFLP types (all race 5) were found among strains isolated from cultivars grown in the temperate highlands. The genetic diversity of the total population of X. oryzae pv. oryzae was 0.93, of which 42% was due to genetic differentiation between races. The genetic diversities of strains collected in 1972 to 1976, 1977 to 1981, and 1982 to 1986, were 0.89, 0.90, and 0.92, respectively, suggesting a consistently high level of variability in the pathogen population over the past 15 years. Cluster analysis based on RFLP banding patterns showed five groupings at 85% similarity. The majority of strains from a given race were contained within one cluster, except for race 3 strains, which were distributed in three of the five clusters.


Innovative strategy with potential to increase hemodialysis efficiency and safety.
Uremic toxins are mainly represented by blood urine nitrogen (BUN) and creatinine (Crea) whose removal is critically important in hemodialysis (HD) for kidney disease. Patients undergoing HD have a complex illness, resulting from: inadequate removal of organic waste, dialysis-induced oxidative stress and membrane-induced inflammation. Here we report innovative breakthroughs for efficient and safe HD by using a plasmon-induced dialysate comprising Au nanoparticles (NPs)-treated (AuNT) water that is distinguishable from conventional deionized (DI) water. The diffusion coefficient of K3Fe(CN)6 in saline solution can be significantly increased from 2.76, to 4.62 × 10(-6) cm s(-1), by using AuNT water prepared under illumination by green light-emitting diodes (LED). In vitro HD experiments suggest that the treatment times for the removals of 70% BUN and Crea are reduced by 47 and 59%, respectively, using AuNT water instead of DI water in dialysate, while additionally suppressing NO release from lipopolysaccharide (LPS)-induced inflammatory cells.


Emergent leadership among tenants with psychiatric disabilities living in supported housing.
The overall aim of this study was to explore the experiences of people with psychiatric disabilities living as tenants in independent, supported apartments for the first time. Supported housing provides an alternative to structured, custodial housing models, such as foster homes, or board-and-care homes, for clients in public mental health systems. This article reports findings on how leadership emerged among tenants after making the transition from custodial to supported housing. Semi-structured interviews were conducted with tenants (n = 24) and included questions on their housing history, current living situation, relationships with staff, participation, and understanding or experience of leadership. Interviews were transcribed verbatim, codes generated, and a thematic analysis conducted using a constructivist approach. The findings revealed an understanding and appreciation of leadership among tenants, who identified six pathways to leadership in their housing as a response to unmet tenant needs. Most tenant leaders emerged outside of formal authority or power structures. Supported housing provides a unique social setting and empowering community where the potential of persons with psychiatric disabilities to assume leadership may be realized and further developed. Mental health professionals working in community housing networks are well placed to harness these face-to-face tenant communities, and their natural leaders, as an additional tool in promoting tenant recovery, mutual help, neighbourhood integration, and the broader exercise of citizenship.


Which Clinical and Patient Factors Influence the National Economic Burden of Hospital Readmissions After Total Joint Arthroplasty?
The Affordable Care Act of 2010 advanced the economic model of bundled payments for total joint arthroplasty (TJA), in which hospitals will be financially responsible for readmissions, typically at 90 days after surgery. However, little is known about the financial burden of readmissions and what patient, clinical, and hospital factors drive readmission costs. (1) What is the incidence, payer mix, and demographics of THA and TKA readmissions in the United States? (2) What patient, clinical, and hospital factors are associated with the cost of 30- and 90-day readmissions after primary THA and TKA? (3) Are there any differences in the economic burden of THA and TKA readmissions between payers? (4) What types of THA and TKA readmissions are most costly to the US hospital system? The recently developed Nationwide Readmissions Database from the Healthcare Cost and Utilization Project (2006 hospitals from 21 states) was used to identify 719,394 primary TJAs and 62,493 90-day readmissions in the first 9 months of 2013 based on International Classification of Diseases, 9th Revision, Clinical Modification codes. We classified the reasons for readmissions as either procedure- or medical-related. Cost-to-charge ratios supplied with the Nationwide Readmissions Database were used to compute the individual per-patient cost of 90-day readmissions as a continuous variable in separate general linear models for THA and TKA. Payer, patient, clinical, and hospital factors were treated as covariates. We estimated the national burden of readmissions by payer and by the reason for readmission. The national rates of 30- and 90-day readmissions after THA were 4% (95% confidence interval [CI], 4.2%-4.5%) and 8% (95% CI, 7.5%-8.1%), respectively. The national rates of 30- and 90-day readmissions after primary TKA were 4% (95% CI, 3.8%-4.0%) and 7% (95% CI, 6.8%-7.2%), respectively. The five most important variables responsible for the cost of 90-day THA readmissions (in rank order, based on the Type III F-statistic, p < 0.001) were length of stay (LOS), all patient-refined diagnosis-related group (APR DRG) severity, type of readmission (that is, medical- versus procedure-related), hospital ownership, and age. Likewise, the five most important variables responsible for the cost of 90-day TKA readmissions were LOS, APR DRG severity, gender, hospital procedure volume, and hospital ownership. After adjusting for covariates, mean 90-day readmission costs reimbursed by private insurance were, on average, USD 1324 and USD 1372 greater than Medicare (p < 0.001) for THA and TKA, respectively. In the 90 days after TJA, two-thirds of the total annual readmission costs were covered by Medicare. In 90 days after THA, more readmissions were still associated with procedure-related complications, including infections, dislocations, and periprosthetic fractures, which in aggregate account for 59% (95% CI, 59.1%-59.6%) of the total readmission costs to the US healthcare system. For TKA, 49% of the total readmission cost (95% CI, 48.8%-49.6%) in 90 days for the United States was associated with procedure issues, most notably including infections. Hospital readmissions up to 90 days after TJA represent a massive economic burden on the US healthcare system. Approximately half of the total annual economic burden for readmissions in the United States is medical and unrelated to the joint replacement procedure and half is related to procedural complications. This national study underscores LOS during readmission as a primary cost driver, suggesting that hospitals and doctors further optimize, to the extent possible, the clinical pathways for the hospitalization of readmitted patients. Because patients readmitted as a result of infection, dislocation, and periprosthetic fractures are the most costly types of readmissions, efforts to reduce the LOS for these types of readmissions will have the greatest impact on their economic burden. Additional clinical research is needed to determine the extent to which, if any, the LOS during readmissions can be reduced without sacrificing quality or access of care.


Genetic parameters and direct, maternal and heterosis effects on litter size in a diallel cross among three commercial varieties of Iberian pig.
The Iberian pig is one of the pig breeds that has the highest meat quality. Traditionally, producers have bred one of the available varieties, exclusively, and have not used crosses between them, which has contrasted sharply with other populations of commercial pigs for which crossbreeding has been a standard procedure. The objective of this study was to perform an experiment under full diallel design among three contemporary commercial varieties of Iberian pig and estimate the additive genetic variation and the crossbreeding effects (direct, maternal and heterosis) for prolificacy. The data set comprised 18 193 records for total number born and number born alive from 3800 sows of three varieties of the Iberian breed (Retinto, Torbiscal and Entrepelado) and their reciprocal crosses (Retinto × Torbiscal, Torbiscal × Retinto, Retinto × Entrepelado, Entrepelado × Retinto, Torbiscal × Entrepelado and Entrepelado × Torbiscal), and a pedigree of 4609 individuals. The analysis was based on a multiple population repeatability model, and we developed a model comparison test that indicated the presence of direct line, maternal and heterosis effects. The results indicated the superiorities of the direct line effect of the Retinto and the maternal effect of the Entrepelado populations. All of the potential crosses produced significant heterosis, and additive genetic variation was higher in the Entrepelado than it was in the other two populations. The recommended cross for the highest yield in prolificacy is a Retinto father and an Entrepelado mother to generate a hybrid commercial sow.