Miracle-dz/UniFAR-FTUs huggingface dataset:
Early developmental trajectories associated with ASD in infants with tuberous sclerosis complex

Objective: We performed a longitudinal cohort study of infants with tuberous sclerosis complex (TSC), with the overarching goal of defining early clinical, behavioral, and biological markers of autism spectrum disorder (ASD) in this high-risk population. Methods: Infants with TSC and typically developing controls were recruited as early as 3 months of age and followed longitudinally until 36 months of age. Data gathered at each time point included detailed seizure history, developmental testing using the Mullen Scales of Early Learning, and social-communication assessments using the Autism Observation Scale for Infants. At 18 to 36 months, a diagnostic evaluation for ASD was performed using the Autism Diagnostic Observation Schedule. Results: Infants with TSC demonstrated delays confined to nonverbal abilities, particularly in the visual domain, which then generalized to more global delays by age 9 months. Twenty-two of 40 infants with TSC were diagnosed with ASD. Both 12-month cognitive ability and developmental trajectories over the second and third years of life differentiated the groups. By 12 months of age, the ASD group demonstrated significantly greater cognitive delays and a significant decline in nonverbal IQ from 12 to 36 months. Conclusions: This prospective study characterizes early developmental markers of ASD in infants with TSC. The early delay in visual reception and fine motor ability in the TSC group as a whole, coupled with the decline in nonverbal ability in infants diagnosed with ASD, suggests a domain-specific pathway to ASD that can inform more targeted interventions for these high-risk infants.
Urinary Sodium and Potassium Excretion and Dietary Sources of Sodium in Maputo, Mozambique

This study aimed to evaluate the urinary excretion of sodium and potassium, and to estimate the main food sources of sodium in Maputo dwellers. A cross-sectional evaluation of a sample of 100 hospital workers was conducted between October 2012 and May 2013. Sodium and potassium urinary excretion was assessed in a 24-h urine sample; creatinine excretion was used to exclude unlikely urine values. Food intake in the same period of urine collection was assessed using a 24-h dietary recall. The Food Processor Plus® was used to estimate sodium intake corresponding to naturally occurring sodium and sodium added to processed foods (non-discretionary sodium). Salt added during culinary preparations (discretionary sodium) was computed as the difference between urinary sodium excretion and non-discretionary sodium. The mean (standard deviation) urinary sodium excretion was 4220 (1830) mg/day, and 92% of the participants were above the World Health Organization (WHO) recommendations. Discretionary sodium contributed 60.1% of total dietary sodium intake, followed by sodium from processed foods (29.0%) and naturally occurring sodium (10.9%). The mean (standard deviation) urinary potassium excretion was 1909 (778) mg/day, and 96% of the participants were below the WHO potassium intake recommendation. The mean (standard deviation) sodium to potassium molar ratio was 4.2 (2.4). Interventions to decrease sodium and increase potassium intake are needed in Mozambique.
Linkage analysis of candidate endothelin pathway genes in nonsyndromic familial orofacial cleft

There is good evidence from linkage analysis and mouse model knockouts that the endothelin‐1 gene (EDN1) is a good candidate for non‐syndromic orofacial cleft (OFC) disease. EDN1 maps to the chromosomal region of the OFC1 locus in 6p23. Therefore we have examined three other candidate genes in the endothelin pathway (ECE1, EDNRA and EDNRB, which map to chromosomes 1, 4 and 13 respectively) in a linkage study of 9 families with OFC, where the disorder is not linked to chromosome 6p23. The total lod score for these 9 multiplex families never exceeded −2.00 and thus our data suggest that EDN1 and related genes are not involved in non‐syndromic familial OFC.
Nurses' perceptions of safety culture in long-term care settings.

PURPOSE To describe perceptions of workplace safety culture among nurses employed in long-term care (LTC) settings. DESIGN A cross-sectional survey. Respondents were licensed nurses (N=550) with membership in gerontological nursing professional organizations in the United States (n=296), Canada (n=251), and other (n=3). METHODS An anonymous, self-administered, mail-in questionnaire, which included the Hospital Survey on Patient Safety Culture as well as questions about individual and institutional characteristics. The survey included key aspects of safety culture, such as work setting, supervisor support, communication about errors, and frequency of events reported. FINDINGS Nurse-managers reported significantly more positive safety culture perceptions compared with licensed staff nurses. Additionally, licensed nurses employed in government-run facilities had significantly less positive safety culture perceptions compared with those working in nonprofit organizations. CONCLUSIONS Interventions designed to improve safety culture in LTC settings should be focused on the concerns of licensed staff nurses and the improvement of communication between these nurses and their managers. CLINICAL RELEVANCE Enhancing safety culture in long-term care settings may facilitate improvements in resident safety. Assessment of workplace safety culture is the first step in identifying barriers that nurses face to provide safe resident care.
Malondialdehyde and Measures of Antioxidant Activity in Subjects from the Belfast Elderly Longitudinal Free‐Living Aging Study

Abstract: Glutathione and glutathione peroxidase activity are important components in the complex body defense against oxidative damage. In this study, we have measured malondialdehyde (MDA) as a marker of oxidative stress, the antioxidant glutathione (GSH), and activity of the antioxidant enzyme (GSHPx), in a cohort of free‐living elderly subjects from the Belfast Elderly Longitudinal Free‐living Aging STudy (BELFAST), hypothesizing that free‐living Senieur‐approximated nonagenarians might demonstrate enhanced antioxidant defense mechanisms. The main finding in the BELFAST octo/nonagenarians was that plasma antioxidant glutathione increased in nonagenarian compared with septo/octogenarian subjects (P= .015), whereas conversely antioxidant glutathione peroxidase activity fell in the nonagenarian group (P < .0001). In the same subject group, malondialdehyde, a measure of lipid peroxidation, showed no change across the age groups (P= .73). These results might overall represent a situation in which elderly survivors in the BELFAST study have evolved a sort of free radical/antioxidant equilibrium as a mechanism of successful aging.
A pilot clinical trial of a recombinant ricin vaccine in normal humans

Ricin, a highly potent toxin produced by castor beans, is classified by the Centers for Disease Control and Prevention as a level B biothreat because it is easily produced, readily available, and highly stable. There have been >750 cases of documented ricin intoxication in humans. There is no approved vaccine for ricin. Ricin contains a lectin-binding B chain and a ribotoxic A chain (RTA). In addition to its ribotoxic site, we have identified a separate site on RTA that is responsible for inducing vascular leak syndrome (VLS) in humans. We have generated a recombinant RTA with two amino acid substitutions that disrupt its ribotoxic site (Y80A) and its VLS-inducing site (V76M). This mutant recombinant RTA (named RiVax) was expressed and produced in Escherichia coli and purified. When RiVax was injected i.m. into mice it protected them against a ricin challenge of 10 LD50s. Preclinical studies in both mice and rabbits demonstrated that RiVax was safe. Based on these results, we have now conducted a pilot clinical trial in humans under an investigational new drug application submitted to the Food and Drug Administration. In this study, three groups of five normal volunteers were injected three times at monthly intervals with 10, 33, or 100 μg of RiVax. The vaccine was safe and elicited ricin-neutralizing Abs in one of five individuals in the low-dose group, four of five in the intermediate-dose group, and five of five in the high-dose group. These results justify further development of the vaccine.
Hormonal Contraceptives and Cerebral Venous Thrombosis Risk: A Systematic Review and Meta-Analysis

Objectives: Use of oral contraceptive pills (OCP) increases the risk of cerebral venous sinus thrombosis (CVST). Whether this risk varies by type, duration, and other forms of hormonal contraceptives is largely unknown. This systematic review and meta-analysis update the current state of knowledge. Methods: We performed a search to identify all published studies on the association between hormonal contraceptive use and risk of CVST in women aged 15–50 years. Results: Of 861 studies reviewed, 11 were included. The pooled odds of developing CVST in women aged 15–50 years taking OCPs was 7.59 times higher compared to women not taking OCPs (OR = 7.59, 95% CI 3.82–15.09). Data are insufficient to make conclusions about duration of use and other forms of hormonal contraceptives. Conclusion: Oral contraceptive pills use increases the risk of developing CVST in women of reproductive age. Future studies are required to determine if duration and type of hormonal contraceptives modify this risk.
Autonomy and behavior control.

nology raises important issues for our understanding of human nature and our moral views about how people ought to influence one another. On the theoretical level we find claims that an adequate explanatory scheme for understanding human behavior can dispense with notions of free will, dignity, and autonomy. On the practical level we are faced with claims of effectiveness, efficiency, and moral legitimacy for methods of influencing people such as operant conditioning, psychotropic drugs, electrical stimulation of the brain, and psychosurgery. The theoretical and practical issues are, of course, linked. Our views as to what it is permissible to do to people reflect our views about the existence and desirability of various conditions. If autonomy is neither desirable nor possible then the question whether different methods affect autonomy in different ways will hardly be an interesting one. If, on the other hand, autonomy is both possible and desirable, then the possibility that various techniques of controlling behavior affect autonomy in distinctive ways, and to different degrees, may play a crucial role in our normative debates about such matters.
Toward Integration of Biological and Physiological Functions at Multiple Levels

An aim of systems physiology today can be stated as to establish logical and quantitative bridges between phenomenological attributes of physiological entities such as cells and organs and physical attributes of biological entities, i.e., biological molecules, allowing us to describe and better understand physiological functions in terms of underlying biological functions. This article illustrates possible schema that can be used for promoting systems physiology by integrating quantitative knowledge of biological and physiological functions at multiple levels of time and space with the use of information technology infrastructure. Emphasis will be made for systematic, modular, hierarchical, and standardized descriptions of mathematical models of the functions and advantages for the use of them.
Have Exchange Rates Become More Closely Tied? Evidence from a New Multivariate GARCH Model

We analyze the time-dependence of exchange rate correlations using a new multivariate GARCH model. This model consists of two parts. First, we transform the exchange rate changes into their principal components and specify univariate GARCH models for all components. Second, we use the inverse of the principal components construction to transform the condi- tional component moments back into those of the exchange rate changes themselves. The model is easy to estimate, as it requires only univariate GARCH estimations. Nevertheless, it outperforms the popular constant conditional correlations and factor GARCH models. We find that the ma- jor U.S. dollar exchange rates have become more loosely instead of closely tied since the eighties.
Enhanced SOA formation from mixed anthropogenic and biogenic emissions during the CARES campaign

Abstract. The CARES campaign was conducted during June, 2010 in the vicinity of Sacramento, California to study aerosol formation and aging in a region where anthropogenic and biogenic emissions regularly mix. Here, we describe measurements from an Aerodyne High Resolution Aerosol Mass Spectrometer (AMS), an Ionicon Proton Transfer Reaction Mass Spectrometer (PTR-MS), and trace gas detectors (CO, NO, NO x ) deployed on the G-1 research aircraft to investigate ambient gas- and particle-phase chemical composition. AMS measurements showed that the particle phase is dominated by organic aerosol (OA) (85% on average) with smaller concentrations of sulfate (5%), nitrate (6%) and ammonium (3%) observed. PTR-MS data showed that isoprene dominated the biogenic volatile organic compound concentrations (BVOCs), with monoterpene concentrations generally below the detection limit. Using two different metrics, median OA concentrations and the slope of plots of OA vs. CO concentrations (i.e., ΔOA/ΔCO), we contrast organic aerosol evolution on flight days with different prevailing meteorological conditions to elucidate the role of anthropogenic and biogenic emissions on OA formation. Airmasses influenced predominantly by biogenic emissions had median OA concentrations of 2.2 μg m −3 and near zero ΔOA/ΔCO. Those influenced predominantly by anthropogenic emissions had median OA concentrations of 4.7 μg m −3 and ΔOA/ΔCO ratios of 35–44 μg m −3 ppmv. But, when biogenic and anthropogenic emissions mixed, OA levels were enhanced, with median OA concentrations of 11.4 μg m −3 and ΔOA/ΔCO ratios of 77–157 μg m −3 ppmv. Taken together, our observations show that production of OA was enhanced when anthropogenic emissions from Sacramento mixed with isoprene-rich air from the foothills. After considering several anthropogenic/biogenic interaction mechanisms, we conclude that NO x concentrations play a strong role in enhancing SOA formation from isoprene, though the chemical mechanism for the enhancement remains unclear. If these observations are found to be robust in other seasons and in areas outside of Sacramento, regional and global aerosol modules will need to incorporate more complex representations of NO x -dependent SOA mechanisms and yields into their algorithms. Ultimately, accurately predicting OA mass concentrations and their effect on radiation balance will require a mechanistically-based treatment of the interactions of biogenic and anthropogenic emissions.
FACTORS INFLUENCING THE SURVIVAL OF SPIROCHETES IN THE FROZEN STATE

Titration experiments made with relapsing fever spirochetes before and after freezing showed the following: 1. With each freezing and thawing there is a slight but regular decrease in virulence, which decrease bears no relation to the duration of storage at – 78°C. Ordinarily infectivity is destroyed by more than 4 refreezings. 2. There was not always close correlation between motility and infectivity. 3. Cooling spirochetes from 0°C. to –78°C. over a 2 to 6 hour period damages them only slightly more than does rapid cooling, but warming from – 78°C. to 0°C. over a 2 to 6 hour period kills most of the organisms. Rapid thawing, as in a water bath, damages the spirochetes less than thawing more slowly, as at room temperature. 4. At storage temperatures of –12°C. and –20°C. there is a gradual decrease in virulence over a period of days or weeks, and by the 6th week the infectivity of the material is markedly reduced.
Hippocampal encoding of non‐spatial trace conditioning

Trace eyeblink classical conditioning is a non‐spatial learning paradigm that requires an intact hippocampus. This task is hippocampus‐dependent because the auditory tone conditioned stimulus (CS) is temporally separated from the corneal airpuff unconditioned stimulus (US) by a 500‐ms trace interval. Our laboratory has performed a series of neurophysiological experiments that have examined the activity of pyramidal cells in the CA1 area of the hippocampus during trace eyeblink conditioning. We have found that the non‐spatial stimuli involved in this paradigm are encoded in the hippocampus in a logical order that is necessary for their association and the subsequent expression of behavioral learning. Although there were many profiles of single neurons responding to the CS‐US trial during training, the majority of the neurons showed an increase in activity to the airpuff‐US. Prior to learning, it appears that hippocampal cells and ensembles of cells were preferentially attending to the stimulus with immediate behavioral importance, the US. Hippocampal cells then began to respond to the associated neutral stimulus, the CS. Shortly thereafter, animals began to show increases in the behavioral expression of CRs. In some experiments, hippocampal neurons from aged animals exhibited impairments in the encoding of CS and US information. These aged animals were not able to associate these stimuli and acquire trace eyeblink CRs. Our findings along with the findings of other spatial learning studies, suggest that the hippocampus is involved in encoding information about discontiguous sets of stimuli, either spatial or nonspatial, especially early in the learning process. Hippocampus 1999;9:385–396. © 1999 Wiley‐Liss, Inc.
Self-Efficacy, Collective Efficacy and the Psychological Well-Being of Groups in Transition

This study sought to determine the differential influence of self- and collective efficacy beliefs on the psychological well-being of individuals within a community in transition. A cross-sectional survey design was used to collect data from 1050 Setswana speaking participants from urban (n = 451) and rural (n = 599) areas in the North-West Province of South-Africa. The Community Collective Efficacy Scale (CCES) and the Generalized Self-Efficacy Scale (GSE), as well as the Affectometer 2 (AFM) and Satisfaction with Life Scale (SWLS) were administered. Descriptive statistics, as well as correlational and regression analyses were conducted to determine the association between self-efficacy and collective efficacy, and the different measures of psychological well-being. Results indicated that participants from the urban context reported higher levels of both self-efficacy and collective efficacy, as well as higher levels of psychological well-being than their rural counterparts. A strong and significant relationship was found between self-efficacy and collective efficacy, and between efficacy beliefs and psychological well-being. Efficacy beliefs are important factors in the prediction of psychological well-being. Raising either self-efficacy or collective efficacy should lead to higher psychological well-being and better adjustment during the process or urbanisation.
Pigmented Purpuric Dermatosis: Clinicopathologic Characterization in a Pediatric Series

Pigmentary purpuras (PPs) are a group of chronic disorders of unknown origin seldom described in children. With this study we sought to better characterize PP eruptions, including clinical evolution and management. A retrospective chart review from 2003 to 2013 querying characteristics of children with a biopsy‐proven diagnosis of PP in the Centre Hospitalier Universitaire Ste‐Justine dermatology clinic (Montreal, Quebec, Canada) was performed. Follow‐up was obtained through telephone interviews. Descriptive statistical analysis was used. Of the 17 subjects, 8 were male and the mean age of onset was 9 years. PP was asymptomatic in 11 patients, pruritic in 3, and of cosmetic concern in 3. Schamberg's disease was the most frequent subtype in 12 cases. Resolution of PP was found in 13 cases with a median duration of less than 1 year (range 6 months–9 years). Five patients experienced spontaneous clearing without treatment, and improvement was observed in 75% of cases treated with topical corticosteroids and 100% with narrowband ultraviolet B (nbUVB). No associated disease, significant drug exposure, or contact allergens were found. Those findings support that PPs in children are idiopathic, chronic eruptions that can benefit from watchful waiting, although topical corticosteroids or nbUVB are may be useful if the patient or family desires faster resolution. This study was limited by its small size, its retrospective nature, and selection and recall bias.
Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice.

Peroxisome proliferator-activated receptor alpha (PPAR alpha)-null mice were used to investigate the nature of the relationship between the normal circadian rhythm of hepatic PPAR alpha expression and the expression of the lipogenic and cholesterogenic sterol regulatory element-binding protein (SREBP)-regulated genes, acetyl-CoA carboxylase, fatty acid synthase (FAS), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoAR). The expression of FAS and HMG-CoAR varied rhythmically over the diurnal cycle in the normal mice, with patterns that were the opposite of that of PPAR alpha. The diurnal variation of lipogenic and cholesterogenic gene expression was attenuated or abolished in the PPAR alpha-null mice. This resulted in decreased expression compared with normal mice, but only during the dark phase of the cycle, when food intake was high. The diurnal variation in hepatic fatty acid and cholesterol synthesis was also abolished in the PPAR alpha-null animals and the variations in the concentration of plasma triacylglycerol, nonesterified fatty acids, and cholesterol were all attenuated. The failure of HMG-CoAR expression to increase during the feeding period in the PPAR alpha-null mice was associated with a decrease in hepatic nonesterified cholesterol content and an increase in cholesteryl ester compared with normal mice. There was no defect in the downregulation of hepatic HMG-CoAR mRNA in response to dietary cholesterol in the PPAR alpha-null mice. Under these conditions, hepatic PPAR gamma expression increased in both the control and PPAR alpha-deficient mice. The results suggest that PPAR alpha-deficiency disturbs the normal circadian regulation of certain SREBP-sensitive genes in the liver, but does not affect their response to dietary cholesterol. -- Patel, D. D. , B. L. Knight, D. Wiggins, S. M. Humphreys, and G. F. Gibbons. Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice. J. Lipid Res. 2001. 42: 328--337.
The Polyanalgesic Consensus Conference (PACC): Recommendations for Trialing of Intrathecal Drug Delivery Infusion Therapy

Intrathecal (IT) drug infusion is an appropriate and necessary tool in the algorithm to treat refractory cancer and noncancer pain. The decision‐making steps/methodology for selecting appropriate patients for implanted targeted drug delivery systems is controversial and complicated. Therefore, a consensus on best practices for determining appropriate use of IT drug infusion may involve testing/trialing this therapy before implantation.