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High neonatal seizure burden is associated with worsened neurodevelopmental outcomes. We compared the efficacy of initial treatment with levetiracetam vs phenobarbital for maintaining low seizure burden in a retrospective cohort of 25 neonates monitored with video electroencephalography (EEG). Video EEG tracing were reviewed and paired with medication bolus times to determine seizure burden after treatment. Initial cumulative dose of phenobarbital was 20 mg/kg in all but 1 case; initial cumulative dose of levetiracetam ranged from 50 to 100 mg/kg. Eleven of 17 (65%) patients sustained seizure burden

The nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs.

For many patients with rotator cuff arthropathy, a reverse shoulder arthroplasty is a surgical option with good results in terms of pain and function. 5 , 6 , 17 Acromion fractures are a recognized postoperative complication, and increased tension on the deltoid is hypothesized as a possible contributing factor. 14 , 22 Fracture classification is as outlined: Type 1 are tip of the acromion fractures; type 2 are lateral acromion fractures; and type 3 are base of acromion fractures. 11 The prevalence of acromial fractures after reverse shoulder arthroplasty ranges between 0.8% to 10.2%, 11 but base of acromion fractures are relatively rare with incidence of approximately 1% in one review of 400 patients. 3 Most fractures of the acromial base occur within one year of surgery secondary to minor trauma. 3 While type 1 and 2 fractures may be managed nonoperatively or with a tension band technique, 4 , 7 , 18 the force of the deltoid on the acromion makes it challenging to manage an acromial base fracture nonoperatively. 9 , 19 Fracture location, however, may not affect long term outcomes. 20 Our patient sustained her type 3 acromial base fracture in a low energy twisting mechanism five years after index surgery, with underlying osteoporosis treated with bisphosphonate therapy considered to be a potentially contributing factor.

The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds have been described as antioxidant enzyme mimics, capable of eliminating ROS and/or reducing oxidative damage. In this study, we investigated the antioxidant activity of a water-soluble 1,10-phenantroline-octanediaoate Mn2+-complex on cells under oxidative stress, and assessed its capacity to attenuate alpha-synuclein (aSyn) toxicity and aggregation, a process associated with increased oxidative stress. This Mn2+-complex exhibited a significant antioxidant potential, reducing intracelular oxidation and increasing oxidative stress resistance in S. cerevisiae cells and in vivo, in G. mellonella, increasing the activity of the intracellular antioxidant enzymes superoxide dismutase and catalase. Strikingly, the Mn2+-complex reduced both aSyn oligomerization and aggregation in human cell cultures and, using NMR and DFT/molecular docking we confirmed its interaction with the C-terminal region of aSyn. In conclusion, the Mn2+-complex appears as an excellent lead for the design of new phenanthroline derivatives as alternative compounds for preventing oxidative damages and oxidative stress - related diseases.

Persistence of HIV through integration into host DNA in CD4(+) T cells presents a major barrier to virus eradication. Viral integration may be curtailed when CD8(+) T cells are triggered to kill infected CD4(+) T cells through recognition of histocompatibility leukocyte antigen (HLA) class I-bound peptides derived from incoming virions. However, this has been reported only in individuals with "beneficial'' HLA alleles that are associated with superior HIV control. Through interrogation of the pre-integration immunopeptidome, we obtain proof of early presentation of a virion-derived HLA-A*02:01-restricted epitope, FLGKIWPSH (FH9), located in Gag Spacer Peptide 2 (SP2). FH9-specific CD8(+) T cell responses are detectable in individuals with primary HIV infection and eliminate HIV-infected CD4(+) T cells prior to virus production in vitro. Our data show that non-beneficial HLA class I alleles can elicit an effective antiviral response through early presentation of HIV virion-derived epitopes and also demonstrate the importance of SP2 as an immune target.

Randomized Controlled Trials, when feasible, give the strongest and most trustworthy empirical measures of causal effects. They are the gold standard in many clinical, social, and behavioral fields of study. However, the most important settings often involve the most sensitive data, therefore cause privacy concerns. In this paper, we outline a way to deploy an end-to-end privacy-preserving protocol for learning causal effects from Randomized Controlled Trials (RCTs). We are particularly focused on the difficult and important case where one party determines which treatment an individual receives, and another party measures outcomes on individuals, and these parties do not want to leak any of their information to each other, but still want to collectively learn a true causal effect in the world. Moreover, we show how such a protocol can be scaled to 500 million rows of data and more than a billion gates. We also offer an open source deployment of this protocol. We accomplish this by a three-stage solution, interconnecting and blending three privacy technologies--private set intersection, multiparty computation, and differential privacy--to address core points of privacy leakage, at the join, at the point of computation, and at the release, respectively. The first stage uses the Private-ID protocol[8] to create a private encrypted join of the users. The second stage utilizes the encrypted join to run multiple instances of a general purpose MPC over a sharded database to aggregate statistics about each experimental group while discarding individuals who took an action before they received treatment. The third stage adds distributed and calibrated Differential Privacy (DP) noise within the final MPC computations to the released aggregate statistical estimates of causal effects and their uncertainty measures, providing formal two-sided privacy guarantees. We also evaluate the performance of multiple open source general purpose MPC libraries for this task. We additionally demonstrate how we have used this to create a working ads effectiveness measurement product capable of measuring hundreds of millions of individuals per experiment.

Persistence of HIV through integration into host DNA in CD4

Background ‘Nudges' subtly alter the social and physical environment to enhance capacity for subconscious, self-interested behaviors, without actively restricting options. Nudges could offer a much-needed strategy to foster sustainable improvements in dietary behaviors and weight status. Aim To systematically review the effectiveness of nudge interventions designed to improve children's dietary behaviors within the family home (or another environment if judged transferable to the home). Methods English-language studies published January 1996–January 2015 were identified in MEDLINE, Embase, CINAHL, PsycINFO and PubMed, followed by dual screening and quality evaluation. Inclusion : controlled studies; nudge with in-home potential. Exclusion : medical health conditions. Results Of the 40 included studies, 33 (83%) showed improvement in dietary behaviors (e.g. more vegetables, smaller unhealthy portions) and were more effective in older children/adolescents. The quality of most studies was rated as weak (43%) or moderate (40%), with only six studies rated strong (15%), reflecting major issues with quality, effectiveness and generalizability. Nudges were typically assessed in isolation and examined immediate effects on behavior. Conclusion Despite substantial methodological limitations and inconsistencies, the literature indicates that nudges may improve children's immediate dietary behaviors. It is unclear whether these improvements could be sustained or affect body weight (PROSPERO, CRD42016036373).

Background Randomized controlled trials demonstrate that timely introduction of peanut to infants reduces the risk of peanut allergy. However, much debate remains regarding how to best achieve earlier peanut introduction at the population level. Our previous study in 2007-2011 (HealthNuts, n = 5300) indicated that few infants were consuming peanut in the first year. Australian infant feeding guidelines were updated in 2016 to recommend introducing peanut before 12 months for all infants. There were no data available on the subsequent effect on peanut introduction or peanut reactions. Objective We sought to assess the consequences of a nonscreening approach to allergenic food introduction in a population-based sample of infants in their first year of life. Methods EarlyNuts is a population-based, cross-sectional study of 12-month-old infants in Melbourne, Australia, recruited by using an identical sampling frame and methods to HealthNuts (72% response rate vs 73% response rate in HealthNuts). We report here on the first 860 participants recruited between November 2016 and October 2018. Results Most infants (88.6%; 95% CI, 86.1% to 90.7%) had introduced peanut by 12 months (median age, 6 months), an increase from 28.4% (95% CI, 27.2% to 29.7%) in the HealthNuts study. By 12 months, the majority of these (76.4%) had consumed peanut more than 4 times, and 28% were eating peanut more than once per week. Preliminary results on parent-reported reactions show that 4.0% of those consuming peanut by 12 months had possible IgE-mediated reactions. Conclusions There has been a striking shift toward earlier peanut introduction, with a 3-fold increase in peanut introduction by age 1 year in 2018 compared with 2007-2011.

Sarcoidosis is a multisystem inflammatory disease of unknown etiology. It is uncommon, with an incidence of approximately 16.5 per 100,000 men.1 It is characterized by noncaseating epithelioid granulomata that typically affect the chest, skin, eyes, and, much less commonly, the genital system (0.2% of cases). Sarcoidosis can affect any of the scrotal structures, although due to its rarity, investigation of solid masses of the testes are largely targeted towards excluding either a malignant or infective etiology.²We report a rare case of a 27-year-old male who presented with bilateral testicular and neck swellings. He underwent orchidectomy, and histopathology demonstrated sarcoidosis. He subsequently developed both pituitary and testicular sarcoidosis resulting in azoospermia. Through the administration of gonadotropins and surgical sperm retrieval we were able to retrieve sperm suitable for assisted reproductive technologies.This case illustrates the difficulties faced in managing the fertility of men who develop systemic sarcoidosis. It also highlights the diagnostic and therapeutic challenges faced by physicians when presented with a case of systemic sarcoidosis.

Systematic reviews of nutritional interventions indicate limited efficacy in reducing childhood obesity, but their blanket conclusions could obscure promising components. This narrative review sought more detail on effective components within nutrition-related interventions involving children aged 2 to 11 years. In May 2016, the World Health Organization (WHO) searched the Cochrane Library and PubMed for relevant reviews. From 36 reviews, we screened 182 nutrition-related randomized trials for inclusion. We then reviewed those that reported at least 1 statistically significant (P

This chapter aims to address corporative social responsibility (CSR) as a key element of co-creative culture in developing sustainability in practice of regional innovation. This point is drawn from a lesson learned from a case study of a renewable energy project, which is called Winds of Change (WoC) in Denmark. In this chapter, the authors firstly regard creativity as a pathway to develop sustainability from a socio-cultural approach that also provides a basis of understanding that in the practice of developing sustainability, it requires a co-creative culture. Therefore, they use a systems view and examine co-creative behaviors in the case of WoC through the interplays between three dimensions including domain, field, and individuals (or organizations). Using this case, the authors conclude that a better sustainable world requires a better practice of CSR among organizations based on which the different actors should contribute to their cooperative efforts in a co-creation process of developing sustainability.

Has the precipitous rise in inequality in the United States since the 1970s been a primarily American phenomenon, or is it simply the most extreme example of a larger international trend? The authors in this syllabus have emphasized the uniqueness of American inequality - in part to draw attention to the importance of national policy, in part as a rhetorical appeal that inequality is not a necessary fact of modern life, and in part to argue against explanations that attribute rising inequality to skills-based technological change (SBTC) or “globalization.” According to Hacker and Pierson, the rise of inequality “has been substantially more meteoric in the United States than in other rich nations... The hyperconcentration of income in the United States... sets the United States apart from other rich nations, calling into serious doubt the usual explanation for America’s winner-take-all economy, SBTC.”1Therefore, American politics is to blame for rising inequality, not transnational economic or political trends. Increases in inequality in other nations, especially the Anglo-Saxon countries, they attribute to economic competition with, and interconnection to the U.S. Also, “these [English-speaking] nations have also generally emulated U.S. public policymore than other nations have.” But what is distinctly American about the policies that they refer to?

Only a few homes in the US have demonstrated net zero energy performance over a full year. Of the successful net zero energy projects for detached single-family homes, most have been newly constructed, rather than retrofits. A cost-effective retrofit strategy for single-family homes could expand net zero options to a broader segment of the housing stock, a segment with a relatively high energy consumption per household. Also, most net zero energy projects are limited to the structures on the property, and are focused on energy, rather than greenhouse gas (GHG), primarily carbon dioxide (CO2) emissions. Expanding the scope to incorporate not only energy from structures, but also a household's CO2 emissions from structures and vehicles would enable the evaluation of strategies to reduce all Scope 1 and 2 emissions. These are the emissions that a household has direct control over, namely the direct combustion or emission of CO2 and the emissions caused by the household's use of electricity.One family...

As teachers look for ways to improve practice and enhance student engagement, referral to the literature leads to a dichotomy between specific activity and heavy academic research on metadata and learning analytics. This paper is intended to tread the pathway between the two so that teachers can, using the findings, introduce video for flipped classes, or online teaching. Taking 5 iterations of an action research approach the authors present the techniques and principles for making an interactive video and clear examples of lesson design. The research was conducted at a Danish higher education institution in technical subjects, but the methods are applicable to most teaching situations. The outcomes are, that paying attention to the process of recording existing lecture content leads to interactive video. This new content can be embedded in a structured lesson design and can greatly improve educational outcomes and student engagement. The researchers’ goal was to create and sustain smart, rich and active learning environments in both online and in classroom environments, and utilize existing content across both platforms.

The role of uterine fibroids (leiomyomata) in infertility has been the subject of debate for many years. Its importance as a topic of research has further increased as women delay childbirth into their 30s and 40s, when the incidence of fibroids is significantly increased. This article reviews the evidence for mechanisms by which fibroids may decrease fertility and the diagnostic and therapeutic options available to clinicians faced with a couple with fertility problems where fibroids are present. The majority of studies have looked at the location of fibroids within the uterus (submucosal, intramural and subserosal) to help determine their impact on fertility and spontaneous abortion rates. These studies have underlined the importance of location and distortion of the uterine cavity for fertility, although meta-analysis has highlighted a number of study design issues with suboptimal localization of fibroid position being a common problem in interpreting the exact role of intramural fibroids. Apart from p...

In recent years, more and more biological sensors are being connected wirelessly. This makes them much more versatile and allows a greater degree of mobility to the wearer. However, there are downsides to the move to wireless. In wireless body area sensor network (WBASNs), power consumption and storage limitations are major obstacles that need to be addressed. Increasing capacity often means increasing weight and cost, especially when batteries are concerned. Therefore, it is important to minimize the power and storage requirements as much as possible. One approach to this is through aggregation. By having sensors report their data to a cluster head (CH), their information can be combined and volume of transmitted data reduced. Less data means more information can be stored before that data needs to be offloaded. In addition less data means fewer packets need to be sent increasing the life of the sensor. Polynomial regression can be used to create a formula that approximates this information. This paper assesses the effectiveness of this type of regression as applied to biological data of patients. This is done first by measuring the degree of compression (compression ratio). Then we evaluate the accuracy of the polynomial (correlation coefficient) for different types of patients' data. Lastly it compares these results to existing models in order to assess its effectiveness as an aggregation technique.

Numerous solutions have been proposed to improve the efficiency of wireless sensor networks (WSNs). Data aggregation, which reduces the data redundancy so as to mitigate energy consumption, is one of desirable solutions. One common feature of geographically close-by data known as spatial correlation, has been utilized for eliminating redundant information. To reduce redundancy and enhance eventual performance, we explore the possibility of combining sensing data with similar characteristics without considering spatial information.We define this relationship of data as characteristic correlation and propose an automatic procedure to discover characteristic correlation between sensor nodes (SNs) with limited overheads. Furthermore, we introduce a novel characteristic correlation based data aggregation approach that allows any SN to compress unlimited number of packets into virtual packets up to a constant number. With experimental and simulation results, our proposed approach is illustrated as an effective data aggregation method in term of data accuracy.

Recent advances in Wireless Body Area Sensor Network (WBASN) technology has become a leading approach for several promising applications in the medical field. WBASN is the network is built with different kinds of physiological sensors which measures different vital parameters on the human body for the purpose of monitoring the patients. Prediction and modeling are very two important issues which are required to address while building a WBASN. To enhance the long-term critical health monitoring, a robust predictive approach should be incorporated in every WBASN system and it leads to saving computation time and increasing the energy.In this paper, we describe the use of polynomial regression for predicting and modeling biological functions. We also describe how effective different orders of polynomials can be. There are four functions that we use for this purpose: blood pressure, scalp EEG signals, the walking gait of people with neurodegenerative disorders, and lastly motor movement signals. We have also used two different degrees of polynomial functions to determine the predictive value.

Background Attention and inhibition are core executive-function deficits in FRagile X syndrome (FXS). This pilot study evaluated the feasibility, reproducibility, and clinical relevance of the KiTAP, a computer-based pictorial measure of attention and inhibition with an enchanted-castle theme, in an FXS cohort. Methods The 8-subtest KiTAP battery (as many subtests as each could perform) was given to 36 subjects with FXS, of variable age and cognitive/behavioral functioning, and 29 were retested, with an interval of 2 to 4 weeks between sessions. Subjects were rated by parents on the Aberrant Behavior Checklist-Community Edition (ABC-C) and Behavior Assessment System for Children, Second Edition (BASC-2). Feasibility, ceiling and basal effects, and data range and distribution analyses were used to eliminate outliers and invalid data points. Reproducibility of scores was analyzed using intraclass correlation coefficients (ICCs) and validity/clinical relevance was assessed by correlating KiTAP scores with ABC-C and BASC-2 scores. Results Most of the participants with FXS were able to complete the Alertness, Distractibility, Flexibility, and Go/NoGo subtests.About 50 to 60% completed the Visual Scanning and Vigilance subtests, and 20 to 25% completed the Sustained Attention and Divided Attention subtests. A panel of seven scores from four subtests were identified as feasible for most subjects, lacked excessive ceiling, basal, or learning effects, exhibited an acceptable range and distribution of scores, had good reproducibility (ICC > 0.7), and correlated with behavioral ratings for hyperactivity or attention (P < 0.01). Only minor differences in performance on the KiTAP were seen between mental age-matched cohorts of subjects with FXS and non-FXS intellectual disability. Conclusions The KiTAP can be administered to cohorts with FXS over a wide range of function with valid reproducible scores. With additional validation, it could represent a useful outcome measure for assessment of attention/executive-function abilities in clinical trials targeted to these core deficits in FXS.

Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet full criteria for ASD. Recent major advances have been made in the understanding of the neurobiology and functions of FMRP, the FMR1 (fragile X mental retardation 1) gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to the dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to the dysregulated translational pathway. These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model at multiple stages of development. Clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess cognitive change that might be associated with treatment. Genes known to be causes of ASD interact with the translational pathway defective in FXS, and it has been hypothesized that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction between FXS and ASD. Therefore, targeted treatments developed for FXS may also target subgroups of ASD, and clinical trials in FXS may serve as a model for the development of clinical trial strategies for ASD and other cognitive disorders.

Ecological and phylogenetic influences on maxillary dentition in snakes. The maxillary dentition of snakes was used as a system with which to investigate the relative importance of the interacting forces of ecological selective pressures and phylogenetic constraints in determining morphology. The maxillary morphology of three groups of snakes having different diets, with each group comprising two distinct lineages—boids and colubroids— was examined. Our results suggest that dietary selective pressures may be more significant than phylogenetic history in shaping maxillary morphology.

Chemical and modal analyses have been made for a series of ten homogeneous specimens of meta-sediments, with identical metamorphic histories, from the aureôle of the Ardara pluton. Results showed that total amount of garnet was determined by the quanity of “free ferrous oxide” (assuming that the reaction: FeO + Fe2O3→ Fe3O4, has gone to completion) in the rock. Size distribution curves showed that each specimen contained crystals with a preferred radius and throughout the series a quantitative relation between the preferred radius and the frequency distribution about this value was observed.Measurement of the number of crystals per unit volume showed that this gave trends with functions of the chemical composition of the rock. A discussion of the mechanism of garnet formation in terms of chemical laws of nucleation and growth is given.

In an attempt to obtain information about garnet nucleation a series of eleven apparently homogeneous metamorphic rocks, from a small area near Mallaig, Inverness, Scotland, have been analysed to determine bulk chemical and modal compositions, garnet grain size and number of garnet crystals occurring in unit volume of rock (N). No correlation of N with any function of chemical and modal compositions could be found, and it is therefore concluded that, if the influence of trace components can be neglected, externally imposed factors (for example, time-temperature variation) or internal physical factors (for example, the surface area of the rock just prior to garnet formation) must exert a controlling influence on garnet nucleation. It was found, however, that in each specimen, there was a preferred crystal radius and the relative frequency of occurrence about this preferred value was constant for all samples studied. Preliminary comparison with other systems, investigated by the authors, suggested that the nature of this relationship may provide evidence of the conditions under which these rocks recrystallized.

A study of the composition and crystal size distribution of garnet from four metamorphic aureoles in the west of Ireland has been carried out in an attempt to derive information about the external factors controlling garnet formation. Garnet compositions varied between And 10 Gro 90 and And 30 Gro 70 . The distribution curves all fit the same equation (Galwey & Jones 1963). Possible explanations of variations in the distribution functions for different aureoles are considered and it is concluded that these were controlled by rate of heating of the host-rock during metamorphism.

To develop a statistically derived but clinically usable antenatal risk scoring system.Data from 20,985 pregnancies were statistically analyzed to identify significant risk factors. Logistic regression analysis was then used to produce a final scoring system, which was subsequently tested for validity on a separate population of 3120 pregnancies.Twenty-seven significant antenatal variables were included in the final scoring system. Application of the system in early pregnancy resulted in a predictive accuracy of 0.73; at the onset of labor, predictive accuracy was 0.91. At the time of labor, 87% of poor outcomes were accurately identified by allocation of only 16% of the women to the high-risk group.It was possible to develop a risk scoring system with a predictive accuracy higher than any previously reported statistically derived score. Summation of the logistic coefficients provides a score that by comparison with a chosen threshold identifies a high-risk pregnancy. In this way, despite the complexity of statistical analysis, all clinicians can quickly apply this scoring system.