cssi/SciSciGPT-SciSciNet huggingface dataset:
Preterm birth and pre-eclampsia--bad news and good news

Our understanding and treatment of preterm labour and pre-eclampsia, the two major causes of perinatal mortality, morbidity, and long-range neurological disability, are improving. None the less, there is bad news as well as good news. The rate of preterm birth has not changed in the past 20 years despite efforts by obstetricians and their patients. Attempts to identify pregnancies at risk by demographic and epidemiological factors have been unsuccessful. After a huge financial investment, it is now established that ambulatory contraction monitoring increases the diagnosis of preterm labour but does not reduce preterm births. Many women have been treated with drugs in an attempt to inhibit uterine contractions. This strategy has also not reduced preterm births. Despite these pessimistic observations, there has been progress. A breakthrough is the recognition that not all preterm births are a result of the same cause, and that their pathophysiology is rarely just the early onset of term labour. Subclinical infection is present in the amniotic fluid, placenta, and membranes of many babies delivered after premature labour, but this is not the case for infants delivered early for medical indications. This raises hope that if these pregnancies could be recognised, treatment could perhaps ameliorate the infection, thus reducing preterm bii'ths. Current investigations search for this diagnosis by examining markers of vaginal infections as indicators of intrauterine infection. Studies suggest that cytokines and basement membrane components may also be useful markers. In a large observational study of 3000 low-risk women, one such marker identified 60% of babies delivered before 28 weeks' gestation. The same study assessed potential clinical markers and provided further evidence that preterm labour is multifactorial. Cervical length was an independent marker of preterm birth. As the length of the cervix, determined sonographically at 24 to 26 weeks' gestation, decreased, the risk of preterm birth increased. At the 10th centile for length, the risk increased seven fold. Finally, in another study, increased oestriol in saliva appeared to be a predictor of preterm birth occurring primarily after 32 weeks' gestation. Thus, perhaps at least three causes-subclinical infection, mechanical cervical factors, and hormonal effects--are involved in preterm births. Pre-eclampsia has met with similar successes and failures. It is now clear that aspirin will not prevent preeclampsia in a way that is clinically useful. Contrary to early studies and meta-analyses, several studies indicated that aspirin did not prevent pre-eclampsia in women at either low or high risk for the disorder. When the studies were viewed in total, however, there did seem to be a small effect. Thus, although aspirin did not seem to be the right choice, if our understanding of pre-eclampsia reaches a stage where a more appropriate treatment
Co-occurrence of ADHD and autism spectrum disorders: phenomenology and treatment

The Diagnostic and Statistical Manual of Mental Disorders (4th Edition) prohibits the co-diagnosis of attention-deficit/hyperactivity disorder (ADHD) and an autism spectrum disorder (ASD). However, recent studies indicate that co-occurrence of clinically significant ADHD and autistic symptoms is common, and that some genes may influence both disorders. Children with the combination of ADHD and motor coordination problems are particularly likely to have an ASD. These co-occurrences of symptoms are important since children with ASD in addition to ADHD symptoms may respond poorly to standard ADHD treatments or have increased side effects. Such children may benefit from additional classes of pharmacologic agents (i.e., alpha-agonists, selective serotonin reuptake inhibitors and neuroleptics). They may also benefit from social skills therapy, individual and family psychotherapy, behavioral therapy and other nonpharmacologic interventions.
Seasonal Patterns of Gastrointestinal Illness and Streamflow along the Ohio River

Waterborne gastrointestinal (GI) illnesses demonstrate seasonal increases associated with water quality and meteorological characteristics. However, few studies have been conducted on the association of hydrological parameters, such as streamflow, and seasonality of GI illnesses. Streamflow is correlated with biological contamination and can be used as proxy for drinking water contamination. We compare seasonal patterns of GI illnesses in the elderly (65 years and older) along the Ohio River for a 14-year period (1991–2004) to seasonal patterns of streamflow. Focusing on six counties in close proximity to the river, we compiled weekly time series of hospitalizations for GI illnesses and streamflow data. Seasonal patterns were explored using Poisson annual harmonic regression with and without adjustment for streamflow. GI illnesses demonstrated significant seasonal patterns with peak timing preceding peak timing of streamflow for all six counties. Seasonal patterns of illness remain consistent after adjusting for streamflow. This study found that the time of peak GI illness precedes the peak of streamflow, suggesting either an indirect relationship or a more direct path whereby pathogens enter water supplies prior to the peak in streamflow. Such findings call for interdisciplinary research to better understand associations among streamflow, pathogen loading, and rates of gastrointestinal illnesses.
Fast Hartley transforms for image processing

The fast Hartley transform (FHT) is used to transform two-dimensional image data. Because the Hartley transform is real-valued, it does not require complex operations. Both spectra and autocorrelations of two-dimensional ultrasound images of normal and abnormal livers were computed. >
Learning About Word Parts With Kidspiration

Knowing the meanings of common root words, prefixes, and suffixes may help students read and spell the longer words they begin to run into in the upper elementary grades. This article describes how students can use the Kidspiration computer program to quickly and easily create word webs that illustrate the meanings of common root words and affixes.
Long-term Follow-up of Patients With Chronic Hepatitis B Treated With Interferon Alfa

Abstract BACKGROUND & AIMS: Therapy with interferon alfa (IFN-alpha) leads to remission of disease in one third of patients with chronic hepatitis B. The aim of this study was to better define the long-term prognosis of this outcome. METHODS: One hundred three patients with chronic hepatitis B who underwent IFN-alpha therapy in three clinical trials between 1984 and 1991 were followed up for serological status, biochemical evidence of liver disease, and liver complications or mortality through 1994. RESULTS: Among 103 patients, 31 (30%) responded to therapy with loss of hepatitis B e antigen and viral DNA from serum. Responders were more likely than nonresponders to be women, black, and to have more severe liver disease including cirrhosis (P CONCLUSIONS: The response to IFN-alpha therapy in chronic hepatitis B is usually a sustained improvement in disease markers and, when cirrhosis is considered, patient outcome. (Gastroenterology 1997 Nov;113(5):1660-7)
Extension of motion primitives and neighboring optimal control used in trajectory generation for RLVs

In recent years, the Department of Defense and NASA have imposed significant resources on developing advanced launch technologies. Reusable launch vehicle (RLV) program is one of such efforts to take the place of space shuttles for RLVs. Our previous research proposed a scheme of motion primitives (MPs) and neighboring optimal control (NOC) to deal with on-line failure recovery for an RLV during approach and landing (A&L). In this paper, more general system dynamics is employed and the extension of MPs and NOC used in the trajectory generation during both terminal area energy management (TAEM) and A&L is discussed.
Interactive model-based search for global optimization

Single-thread algorithms for global optimization differ in the way computational effort between exploitation and exploration is allocated. This allocation ultimately determines overall performance. For example, if too little emphasis is put on exploration, the globally optimal solution may not be identified. Increasing the allocation of computational effort to exploration increases the chances of identifying a globally optimal solution but it also slows down convergence. Thus, in a single-thread implementation of model-based search exploration and exploitation are substitutes. In this paper we propose a new algorithmic design for global optimization based upon multiple interacting threads. In this design, each thread implements a model-based search in which the allocation of exploration versus exploitation effort does not vary over time. Threads interact through a simple acceptance-rejection rule preventing duplication of search efforts. We show the proposed design provides a speedup effect which is increasing in the number of threads. Thus, in the proposed algorithmic design, exploration is a complement rather than a substitute to exploitation.
Estimating residential water demand in the absence of volumetric water pricing

Rapid population growth has significantly increased the magnitude of water shortages in California. Although water shortages already exist, some of the state's utility systems are still not providing their residents with financial incentives for water conservation. Instead of using water meters to charge households according to their actual water usage, they are charging a flat fee for unlimited water service. When flat fees are charged for unlimited water service, the per-unit cost for additional water is zero and the decision to consume more water is determined by other factors. This study estimates the factors that influence residential water demand in a city that is currently charging flat fees for unlimited water service. The results indicate that the number of home occupants and the square footage of grass landscaping significantly affect water usage and the relationships between these variables are quantified.
A Schur method for solving algebraic Riccati equations

In this paper a new algorithm for solving algebraic Riccati equations (both continuous-time and discrete-time versions) is presented. The method studied is a variant of the classical eigenvector approach and uses instead an appropriate set of Schur vectors thereby gaining substantial numerical advantages. Complete proofs of the Schur approach are given as well as considerable discussion of numerical issues. The method is apparently quite numerically stable and performs reliably on systems with dense matrices up to order 100 or so, storage being the main limiting factor. The description given below is a considerably abridged version of a complete report given in [0].
Ludwig's Angina in the Pediatric Population

As many as 1 in 3 of cases of Ludwig's angina occur in children and adolescents, and pediatricians are therefore ideally situated to detect these individuals at an early stage of their potentially life-threatening disease. The early identification and referral of children afflicted with Ludwig's angina to tertiary care centers allows for the rapid initiation of medical therapy and the consultation of those emergency services critical to providing such patients with optimal diagnostic and therapeutic interventions. This review provides an overview of the anatomical and pathophysiological considerations in Ludwig's angina and describes practical management principles to assist pediatricians in the diagnosis and treatment of this disease. Included in this review is an evidence-based algorithm for airway management.
Supported Excavations: Observational Method and Inverse Modeling

An inverse analysis procedure that uses construction monitoring data to update predictions of deformations for supported excavation systems is presented. The numerical procedure is used to optimize the finite element model of a 12.2-m-deep excavation through Chicago glacial clays by minimizing the errors between monitoring data and computed displacements. The field observations are obtained from inclinometer data that measured lateral movements of the soil behind the supporting walls on opposite sides of the excavation throughout construction. Five construction stages are defined for the inverse analysis. At every new construction stage, the inclinometer data relative to that stage are added to the observations already available to “recalibrate” the model of the excavation. The constitutive responses of the soils are represented by the hardening-soil (H-S) model. Of the six basic H-S input parameters, only one parameter per layer is optimized, while the other parameters are either kept constant or related...
Evidence that the first strand-transfer reaction of duck hepatitis B virus reverse transcription requires the polymerase and that strand transfer is not needed for the switch of the polymerase to the elongation mode of DNA synthesis

Deletion of amino acids 79–88 in the duck hepatitis B virus reverse transcriptase had minimal effects on polymerase activities prior to the minus-strand DNA transfer reaction, yet it greatly diminished strand transfer and subsequent DNA synthesis. This mutation also reduced reverse transcription on exogenous RNA templates. The reaction on exogenous RNAs employed the phosphonoformic acid (PFA)-sensitive elongation mode of DNA synthesis rather than the PFA-resistant priming mode, despite the independence of DNA synthesis in this assay from the priming and minus-strand transfer reactions. These data provide experimental evidence that the polymerase is involved directly in the minus-strand transfer reaction and that the switch of the polymerase from the early PFA-resistant mode of DNA synthesis to the later PFA-sensitive elongation mode does not require the strand-transfer reaction.
Comparison of Aerially-Applied Gypchek Strains Against Gypsy Moth (Lepidoptera: Lymantriidae) in the Presence of an Entomophaga maimaiga Epizootic

The standard strain (LDP-226) of Gypchek®, a nucleopolyhedrovirus product registered by the USDA Forest Service against the gypsy moth, Lymantria dispar (L.), was compared against a strain, LdMNPV-203NL (NL = nonliquefying), that was developed for production in cell culture. Both strains were applied by air to U.S. government property in Prince Georges Co., MD, in early May 2003 at the rate of 1 x 1012 occlusion bodies per ha. The two goals of the study were (1) to compare the first and second wave effects of the two strains against gypsy moth populations; and (2) to delineate the combined effects of the applied virus and the expected epizootic of the gypsy moth specialist fungal entomopathogen Entomophaga maimaiga Humber, Shimazu, and Soper. Heavy rainfall in May and June preceded a massive epizootic of E. maimaiga, whose effects did not mask the first wave of viral mortality. When the effect of application sequence was considered, it was concluded that the two strains were equivalent in their first-wave impacts. High fungal-induced mid and late-season gypsy moth larval mortality suppressed the second wave of virus at all evaluation sites. There were no obvious differences in the second waves engendered by the two LdNPV strains in the greatly reduced late-instar larval population.
Operant Contingencies and the Origin of Cultures.

Writers from a variety of disciplines recognize that culture is composed of or depends on behavior, but is also somehow more than an unorganized collection of behavioral events. Biologist Bonner (1980) defined culture as “behavior transmitted from one individual to another by teaching and learning” (p. 17). Cultural anthropologist Harris (1964) stated, “human behavior constitutes the cultural field of inquiry” (p. 20). However, human responses “are definitely not cultural things,” (Harris, p. 22) but rather are the empirical events to which scientific operations must be applied to arrive at cultural classifications. Behavior analyst Baum (2000) stated, “culture consists of behavior andchrw(133) cultural change constitutes an evolutionary process” (p. 182).
Concurrent assessment of muscle activity (CAMA). A procedural approach to assess treatment goals.

The demonstration of efficacious and cost-effective treatments is a concern shared by all medical practitioners. The urgency in continuously addressing this concern should be perceived by all clinical physical therapists as the availability of the nation's health care dollar to rehabilitation personnel continues to dwindle. In 1982, only 19 cents of this dollar was allocated to all health care services outside the realms of physicians' services, nursing home care, and hospital costs.1 The advent of diagnostic related groups and prospective payment plans may shrink reimbursement monies for physical therapy services to patients with both acute and chronic conditions. Even before we might be confronted with this situation, we should recall that recognized leaders within the physical therapy community have urged its members to seek methods to quantify improvement objectively and to validate treatment procedures.2–4…
X-RAY CONVERSION PHYSICS EXPERIMENTS: LASER INTENSITY DISTRIBUTION, ENERGY TRANSPORT, HYDRODYNAMICS, AND OPACITY

To study the conversion of laser light into x-rays we have performed several experiments which isolate the significant physical issues. Three important areas have been experimentally examined: 1) the uniformity of focused laser beam, 2) thermal transport and hydrodynamics, and 3) the effects of material opacity. All of these experiments were performed with laser pulse widths of a few nanoseconds at laser light intensities of greater than 1014 W/cm2 on flat gold targets. The controlled study of the various aspects of this complicated process has led to a better understanding of the physical processes important to x-ray conversion.
Fairer Still the Woodlands: Mapping the Free Exercise Forest: Review of Kent Greenawalt, Religion and the Constitution

This Article is an appreciative review of a new masterwork on religious freedom by leading constitutional scholar, Kent Greenawalt. The book crisply summarizes the full range of founding principles of religious liberty in America – liberty of conscience, freedom of exercise, religious diversity and equality, separation of church and state, and disestablishment of religion – and calls for their proper balancing still today. It then lucidly analyzes the main American cases, statutes, and regulations that bear on the free exercise of religion. Greenawalt calls on courts to accommodate maximum expressions of religious conviction that are consistent with commitment to fairness and public welfare. He rebukes the Supreme Court’s reductionist reading of the Free Exercise Clause in Employment Division v. Smith (1990) to a guarantee of laws that are neutral and generally applicable. This new standard, still in place, fails to accommodate the need for religious accommodations and exemptions when general laws conflict with core claims of conscience and central commandments of the faith. While such accommodations of religion are now partly available through new federal and state statutes and free speech doctrines, Greenawalt urges a return to a more rigorous standard of free exercise review.
Global Experiential and Didactic Education Opportunities at US Colleges and Schools of Pharmacy

Objective. To assess the characteristics of global experiential and didactic education offerings in the pharmacy curricula.Methods. A 2-stage web-based review of US colleges and schools of pharmacy identified country locations of international advanced pharmacy practice experiences (APPE), globally focused didactic courses, and whether these offerings were interprofessional. Schools were contacted to confirm their offerings and were asked about student participation and demand.Results. Sixty-four percent of responding schools confirmed an international APPE offering in 67 different countries with an average graduating class participation of 6.1%. Forty-seven percent of responding schools confirmed a globally focused course offering with an average graduating class participation of 13.1%. Almost two thirds of international APPEs and a majority of courses were designated as interprofessional. Student demand did not outweigh supply for either.Conclusion. Colleges and schools of pharmacy in the United States ...
Interactions with Partners Are Key for Oceanic Nitrogen-Fixing Cyanobacteria: Ocean-dwelling cyanobacteria associate with a variety of other microorganisms, including those that are photosynthetic

Microorganisms shape biomes—in food webs of ecosystems, biogeochemical cycles, and disease—interacting with other microorganisms and with multicellular plants and animals. In oceans, for example, microorganisms are the most abundant life form, inhabiting an environment where viruses and microorganisms account for the bulk of the biomass. Thus, most living interactions in oceans likely involve single-celled microorganisms, be they Bacteria, Archaea, or Eukarya.
Galanin inhibition of enteric cholinergic neurotransmission: guanosine triphosphate-binding protein interactions with adenylate cyclase.

BACKGROUND: The ability of galanin, a unique 29 amino acid peptide, to affect cholinergic neurotransmission was examined in the guinea pig myenteric plexus. METHODS: The effects of galanin on tritiated acetylcholine ([3H]ACh) release were studied with cultured guinea pig myenteric plexus neurons. Functional correlations were made with longitudinal strips of ileal smooth muscle with attached myenteric plexus for examination of isometric contraction. RESULTS: Galanin abolished potassium-stimulated [3H]ACh release (170% +/- 18% of basal vs 109% +/- 16%). Galanin inhibited [3H]ACh release stimulated by forskolin or cholera toxin. [3H]ACh release stimulated by cholecystokin octapeptide, calcitonin gene-related peptide, substance P, or vasoactive intestinal peptide was also suppressed by galanin (10(-8) mol/L). Inhibitory effects were reversed by pertussis toxin preexposure, indicating involvement of guanosine triphosphate-binding proteins. Galanin inhibited contractility of longitudinal smooth muscle strips exposed to cholecystokinin-8 (EC50 7.0 X 10(-9) mol/L for cholecystokinin alone vs 1.3 X 10(-8) mol/L for cholecystokinin-8 plus galanin) and abolished contractile responses to calcitonin gene-related peptide. CONCLUSIONS: Galanin inhibits cholinergic neurotransmission in myenteric plexus neurons. Inhibitory effects involve guanosine triphosphate-binding protein mediation.
Structure Aware L1-graph for data clustering

In graph-oriented machine learning research, L1 graph is an efficient way to represent the connections of input data samples. Its construction algorithm is based on a numerical optimization motivated by Compressive Sensing theory. As a result, It is a nonparametric method which is highly demanded. However, the information of data such as geometry structure and density distribution are ignored. In this paper, we propose a Structure Aware (SA) L1 graph to improve the data clustering performance by capturing the manifold structure of input data. We use a local dictionary for each datum while calculating its sparse coefficients. SA-L1 graph not only preserves the locality of data but also captures the geometry structure of data. The experimental results show that our new algorithm has better clustering performance than L1 graph.
Painful Syndromes of the Foot: Diagnosis and Management

The human foot is subjected to a large number and variety of stresses. Consequently, virtually every person will at one time or another experience a painful disorder of the foot. The first line of treatment is normally footwear modification and relief from the inciting event or cause. When this is unsuccessful, various surgical procedures may often be of benefit.
Risk-Sensitive Planning with Probabilistic Decision Graphs

Probabilistic AI planning methods that minimize expected execution cost have a neutral attitude towards risk. We demonstrate how one can transform planning problems for risk-sensitive agents into equivalent ones for risk-neutral agents provided that exponential utility functions are used. The transformed planning problems can then be solved with these existing AI planning methods. To demonstrate our ideas, we use a probabilistic planning framework (“probabilistic decision graphs”) that can easily be mapped into Markov decision problems. It allows one to describe probabilistic effects of actions, actions with different costs (resource consumption), and goal states with different rewards. We show the use of probabilistic decision graphs for finding optimal plans for risk-sensitive agents in a stochastic blocks-world domain.
Expression of Heat Shock Protein 90 and the Effects of HSP90 Inhibitor (17-AAG) in Multiple Myeloma.

Heat Shock Protein 90 (HSP90) is required for structural folding and maintenance of conformational integrity of various proteins, including several associated with cellular signaling. Recent studies utilizing 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of HSP90, demonstrated antitumor effect in solid tumors. In order to test whether HSP90 could be targeted in multiple myeloma (MM) patients, we first investigated expression of HSP90 by immunofluorescence and flow cytometric analysis in a myeloma cell line (U266) and primary myeloma cells. Following demonstration of HSP90 expression in myeloma cells, archival samples of 32 MM patients were analyzed by immunoperoxidase staining. Myeloma cells in all patients showed strong cytoplasmic expression of HSP90 in all samples and 55 % also demonstrated concurrent nuclear immunopositivity. Treatment of U266 and primary MM cells with 17AAG resulted in significantly increased apoptosis compared to untreated control cells. Analysis of anti-apoptotic BCL2 family proteins in MM cells incubated with 17-AAG revealed down-regulation of BCL-2, BCL-X L and MCL-1. Furthermore, while low concentration of bortezomib had no cell death, combination of 17AAG and bortezomib treatment revealed a synergistic apoptotic effect on the U266 cell line. These data suggest that targeted inhibition of HSP90 may prove to be a valid and innovative strategy for the development of future therapeutic options for MM patients.
Non‐random patterns of invasion and extinction reduce phylogenetic diversity in island bird assemblages

Anthropogenically driven changes in bird communities on oceanic islands exemplify the biotic upheaval experienced by island floras and faunas. While the influence of invasions and extinctions on species richness and beta-diversity of island bird assemblages have been explored, little is known about the impact of these invasions and extinctions on phylogenetic diversity. Here we quantify phylogenetic diversity of island bird assemblages resulting from extinctions alone, invasions alone, and the combination of extinctions and invasions in the historic time period (1500 CE to the current), and compare it to the expected phylogenetic diversity that would result if these processes involved randomly selected island bird species. We assessed phylogenetic diversity and structure at the scale of the island (n =152), the archipelago containing the islands (n=22), and the four oceans containing the archipelagos using three measures. We found that extinction, invasion, and the combination of invasion and extinction generally resulted in lower phylogenetic diversity than expected, regardless of the spatial scale examined. We conclude that extinction and invasion of birds on islands are non-random with respect to phylogeny and that these processes generally leave bird assemblages with lower phylogenetic diversity than we would expect under random invasion or extinction. This article is protected by copyright. All rights reserved.
Pi(4,5)P2 Clustering by the Ebola Virus Matrix Protein VP40

The Ebola virus protein VP40 is a peripheral protein that is trafficked to the lower leaflet of the plasma membrane. Upon membrane localization in its dimeric form, VP40 undergoes major structural rearrangements to form hexamers which further assemble into filaments and form the viral matrix that provides the major structure for the Ebola virus particles. VP40 hexamers and larger filaments have been shown to be stabilized by PI(4,5)P2 in the plasma membrane inner leaflet. Reduction in the plasma membrane levels of PI(4,5)P2 significantly reduce the formation of VP40 oligomers and virus-like particles. We computationally investigated the lipid-protein interactions in VP40 hexamers at the plasma membrane and quantified lipid-lipid self-clustering by calculating the fractional interaction matrix. We found that the VP40 hexamer significantly enhances the PI(4,5)P2 clustering. The radial pair distribution functions suggest a strong interaction between PI(4,5)P2 and the VP40 hexamer. The cationic side chains are found to mediate the PI(4,5)P2 clustering around the protein, with cholesterol filling the space between the interacting PI(4,5)P2 molecules. These computational studies support recent experimental data and provide new insights into the mechanisms by which VP40 assembles at the plasma membrane inner leaflet, alters membrane curvature, and forms new virus-like particles.
Impact of vaccine herd-protection effects in cost-effectiveness analyses of childhood vaccinations. A quantitative comparative analysis.

Background Inclusion of vaccine herd-protection effects in cost-effectiveness analyses (CEAs) can impact the CEAs-conclusions. However, empirical epidemiologic data on the size of herd-protection effects from original studies are limited. Methods We performed a quantitative comparative analysis of the impact of herd-protection effects in CEAs for four childhood vaccinations (pneumococcal, meningococcal, rotavirus and influenza). We considered CEAs reporting incremental-cost-effectiveness-ratios (ICERs) (per quality-adjusted-life-years [QALY] gained; per life-years [LY] gained or per disability-adjusted-life-years [DALY] avoided), both with and without herd protection, while keeping all other model parameters stable. We calculated the size of the ICER-differences without vs with-herd-protection and estimated how often inclusion of herd-protection led to crossing of the cost-effectiveness threshold (of an assumed societal-willingness-to-pay) of $50,000 for more-developed countries or X3GDP/capita (WHO-threshold) for less-developed countries. Results We identified 35 CEA studies (20 pneumococcal, 4 meningococcal, 8 rotavirus and 3 influenza vaccines) with 99 ICER-analyses (55 per-QALY, 27 per-LY and 17 per-DALY). The median ICER-absolute differences per QALY, LY and DALY (without minus with herd-protection) were $15,620 (IQR: $877 to $48,376); $54,871 (IQR: $787 to $115,026) and $49 (IQR: $15 to $1,636) respectively. When the target-vaccination strategy was not cost-saving without herd-protection, inclusion of herd-protection always resulted in more favorable results. In CEAs that had ICERs above the cost-effectiveness threshold without herd-protection, inclusion of herd-protection led to crossing of that threshold in 45% of the cases. This impacted only CEAs for more developed countries, as all but one CEAs for less developed countries had ICERs below the WHO-cost-effectiveness threshold even without herd-protection. In several analyses, recommendation for the adoption of the target vaccination strategy depended on the inclusion of the herd protection effect. Conclusions Inclusion of herd-protection effects in CEAs had a substantial impact in the estimated ICERs and made target-vaccination strategies more attractive options in almost half of the cases where ICERs were above the societal-willingness to pay threshold without herd-protection. More empirical epidemiologic data are needed to determine the size of herd-protection effects across diverse settings and also the size of negative vaccine effects, e.g. from serotype substitution.
TREATMENT OF ANTERIOR SHOULDER SUBLUXATION USING THE MULLIGAN CONCEPT AND REFLEX NEUROMUSCULAR STABILIZATION: A CASE REPORT.

Background and purpose Shoulder instability, a common issue among athletes who engage in contact sports, may lead to recurrent subluxations, or partial dislocations of the shoulder. Young athletic patients generally respond poorly to the nonsurgical treatments for shoulder instability that are commonly utilized. The purpose of this case report is to describe the effects of the treatment guided by the Mulligan Concept (MC) coupled with reflex neuromuscular stabilization (RNS) also known as reactive neuromuscular training (RNT), on an adolescent football player with glenohumeral joint (GHJ) instability who sustained a traumatic anterior subluxation. Case description The MC shoulder Mobilization with Movement (MWM) and RNS were applied in the treatment of an anterior shoulder subluxation injury sustained by a competitive adolescent football player. The Numeric Pain Rating Scale (NPRS), the Disability in the Physically Active (DPA) scale, the Patient specific Functional Scale (PSFS) and the Shoulder Pain and Disability Index (SPADI), were administered in order to identify patient-reported outcomes. Outcomes The shoulder MWM and RNS provided immediate relief of all of the patient's pain and increased ROM after the first treatment. The use of the coupled treatments resulted in a resolution of pain, an increase in range of motion (ROM) and improvement in perceived stability. A minimal clinically important difference (MCID) was reported on the NPRS and minimal detectable changes (MDC) were reported on the NRS and PSFS, after the first treatment. Equally important, MCIDs were reported on the DPA scale and SPADI scale over the course of treatment. Discussion In this case report, the MC shoulder MWM, coupled with RNS, was an effective treatment for this patient and provided a short time to resolution (6 treatments; 19 days) compared to other descriptions of recovery in the literature. Clinicians treating patients who display anterior shoulder instability can consider this as a viable treatment option. Even though current literature indicates that surgery is an optimal treatment for reducing recurrent subluxations, in young athletes who participate in contact sports, the effects of surgery are substantial. Therefore, the consideration of the presented option for non-operative treatment is important. Level of evidence 4-Case Report.
Buridan on the Metaphysics of the Soul

Normore's chapter focuses on the metaphysical issues stemming from Buridan's conception of the union of body and soul, also considered in the broader context of the union of substantial form and matter in general. Normore's argument traces in particular the rather strange metaphysical and mereological ramifications of Buridan's “homogeneity-thesis” of material substances (the thesis that all material substances by themselves, without their accidental dispositions, must be homogeneous: every quantitative part of a material substance is of the same kind as is the whole), as presented in Buridan's difficult discussion in Book II, q. 7.
Validation of a Self-Monitoring Tool for Use in Exercise Therapy.

Abstract Background Aerobic exercise at a subsymptom heart rate has been recommended as therapy for postconcussion syndrome. Assessing adherence with an accurate heart rate-monitoring instrument is difficult, limiting the proliferation of large-scale randomized controlled trials. Objective To evaluate the validity of the Fitbit Charge HR compared with electrocardiogram (EKG) to monitor heart rate during a treadmill-based exercise protocol. Design A methods comparison study. Setting Sports medicine research center within a tertiary care institution. Participants A convenience sample of 22 healthy participants (12 female) aged 18-26 years (mean age: 22 ± 2 years). Methods Fitbit Charge HR heart rate measurements were compared with EKG data concurrently collected while participants completed the Buffalo Concussion Treadmill Test. Main Outcome Measures Agreement between Fitbit Charge HR and EKG was assessed by intraclass correlation coefficients (ICC 3,1 ), Bland-Altman limits of agreement, and percent error. Results We observed a strong single-measure absolute agreement between Fitbit Charge HR and EKG (intraclass correlation coefficient=0.83; 95% confidence interval 0.67-0.90). Fitbit Charge HR underestimated heart rate compared with EKG (mean difference=−6.04 bpm; standard deviation=10.40 bpm; Bland-Altman 95% limits of agreement=−26.42 to 14.35 bpm). A total of 69.9% of Fitbit heart rate measurements were within 10% error compared with EKG, and 91.5% of all heart rate measurements were within 20% error. Conclusions Although the mean bias in measuring heart rate was relatively small, the limits of agreement between the Fitbit Charge HR and EKG were broad. Thus, the Fitbit Charge HR would not be a suitable option for monitoring heart rate within a narrow range. For the purposes of postconcussion exercise therapy, the relatively inexpensive cost, easy implementation, and low maintenance make Fitbit Charge HR a viable option for assessing adherence to an exercise program when expensive clinical equipment is unavailable. Level of Evidence II
Ion Velocity Distributions in Dipolarization Events: Beams in the Vicinity of the Plasma Sheet Boundary

Using combined MHD/test particle simulations, we further explore characteristic ion velocity distributions in relation to magnetotail reconnection and dipolarization events, focusing on distributions at and near the plasma sheet boundary layer (PSBL). Simulated distributions right at the boundary are characterized by a single earthward beam, as discussed earlier (Birn et al., 2015). However, farther inside, the distributions consist of multiple beams parallel and anti-parallel to the magnetic field, remarkably similar to recent Magnetospheric Multi-Scale (MMS) observations. The simulations provide insight into the mechanisms: the lowest earthward beam results from direct acceleration at an earthward propagating dipolarization front (DF), with a return beam at somewhat higher energy. A higher-energy earthward beam results from dual acceleration, first near the reconnection site and then at the DF, again with a corresponding return beam resulting from mirroring closer to Earth. Multiple acceleration at the X-line or the propagating DF with intermediate bounces may produce even higher-energy beams. Particles contributing to the lower-energy beams are found to originate from the PSBL with thermal source energies, increasing with increasing beam energy. In contrast, the highest-energy beams consist mostly of particles that have entered the acceleration region via cross-tail drift with source energies in the supra-thermal range.
Effect of Multimodal Analgesia on Opioid Use After Open Ventral Hernia Repair.

There is limited data on enhanced recovery after surgery (ERAS) protocols after ventral hernia repair (VHR). This study reports the impact of multimodal analgesia on opioid use after open VHR. Retrospective review of open VHR treated during the initial 6 months after ERAS implementation. Protocol focused on opioid sparing using intraoperative ketamine and/or lidocaine infusion, selective epidural anesthesia, and postoperative ketamine infusion, ketorolac, and acetaminophen. Four groups were analyzed: 1—ERAS protocol with epidural analgesia, 2—historical controls with epidural analgesia prior to ERAS, 3—ERAS protocol without epidural, and 4—historical controls without epidural analgesia, prior to ERAS. Continuous variables were analyzed using ANOVA or Kruskal-Wallis tests, and subgroup analysis using Student’s t test or Mann-Whitney U test. Discrete variables were analyzed using Pearson’s chi-square test or Fisher’s exact test. Patients differed in hernia width, but were similar in comorbidity and operative technique. There was no difference in length of stay or readmission. Use of ERAS nearly eliminated patient-controlled analgesia use (group 1, 2.7%; group 2, 68.4%; group 3, 0%; group 4, 65.7%; p < 0.001). ERAS significantly reduced narcotic requirements on postoperative days 0, 1, and 2 (p < 0.001). To account for the bias of selective epidural analgesia, groups 1 and 2 (epidural) and groups 3 and 4 (no epidural) were compared separately. Opioid requirement and PCA use remained significantly lower in patients in the ERAS pathway. Implementation of multimodal analgesia in the perioperative and postoperative setting significantly reduced opioid use after VHR.
Clinical outcomes and differential effects of PI3K pathway mutation in obese versus non-obese patients with cervical cancer.

// Perry Grigsby 1, 2, 3 , Adnan Elhammali 4 , Fiona Ruiz 1 , Stephanie Markovina 1, 2 , Michael D. McLellan 5 , Christopher A. Miller 5 , Anupama Chundury 1 , Ngoc-Anh L. Ta 6 , Ramachandran Rashmi 1 , John D. Pfeifer 7, 8 , Robert S. Fulton 5 , Todd DeWees 1 and Julie K. Schwarz 1, 2, 9 1 Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO, USA 2 Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA 3 Division of Nuclear Medicine, Mallinckrodt Institute, Washington University School of Medicine, St. Louis, MO, USA 4 Department of Radiation Oncology, MD Anderson Cancer Center, University of Texas Health Science Center, Houston, TX, USA 5 McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA 6 Saint Louis University School of Medicine, St. Louis, MO, USA 7 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA 8 Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA 9 Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA Correspondence to: Julie K. Schwarz, email: jschwarz@wustl.edu Keywords: obesity; cervical cancer; PI3K; PTEN; mutation Received: September 07, 2017 Accepted: December 13, 2017 Published: December 23, 2017 ABSTRACT The purpose of this study was to evaluate the effect of obesity and obesity-associated factors on the outcomes of patients with cervical cancer. Outcomes were evaluated in 591 patients with FIGO Ib to IV cervical cancer treated uniformly with definitive radiation. Patients were stratified into 3 groups based upon pretreatment Body Mass Index (BMI): A ≤ 18.5; B 18.6 – 34.9; and C ≥ 35. The 5-year freedom from failure rates were 58, 59, and 73% for BMI groups A, B, and C (p = 0.01). Overall survival rates were 50, 59, and 68%, respectively (p = 0.02). High expression of phosphorylated AKT (pAKT) was associated with poor outcomes only in non-obese patients. Obese patients with PI3K pathway mutant tumors had a trend toward favorable outcomes, while a similar effect was not observed in non-obese patients. Compared to similar tumors from non-obese hosts, PIK3CA and PTEN mutant tumors from obese patients failed to express high levels of phosphorylated AKT and its downstream targets. These results show that patients with obesity at the time of diagnosis of cervical cancer exhibit improved outcomes after radiation. PI3K/AKT pathway mutations are common in obese patients, but are not associated with activation of AKT signaling.
Impacts of booming concrete production on water resources worldwide

Concrete is the most-used construction material worldwide. Previous studies on the environmental impacts of concrete production have mainly focused on the materials involved and energy consumption, as well as CO2 emissions; little is known, however, about its water consumption as well as the effective measures to reduce such consumption. We quantify water use of global concrete production in 2012 and project the value to 2050. The results show that concrete production was responsible for 9% of global industrial water withdrawals in 2012 (this is approximately 1.7% of total global water withdrawal). In 2050, 75% of the water demand for concrete production will likely occur in regions that are expected to experience water stress. Among possible ways of mitigating water demand are choosing the appropriate selection of electricity fuel mixes and improved processing of raw materials; however, these strategies may conflict with greenhouse gas emissions reduction goals. This work develops a baseline estimate for water consumption and withdrawal for concrete production and identifies locations for targeted mitigation. Little is known about the water impacts of concrete production. This study quantifies this impact globally for 2012 and projects it to 2050. It also evaluates in which regions the impacts will be more severe, based on the availability of renewable water resources.
SPECIFICITY OF THE IMMUNE RESPONSE AS A FUNCTION OF THE CARRIER

Some 50 years ago Landsteiner showed the feasibility of the carrier method for eliciting hapten-specific antibodies in suitable hosts. Since then numerous investigators have successfully applied this methodology to obtain antibodies against a vast number of different haptens (Landsteiner, 1945). In every instance, until recently, the haptens were conjugated to the carrier by covalent bonds, and with but one exception the haptens were small molecules. Goebel and Avery (1931) reported that a pneumococcal capsular polysaccharide, which is not immunogenic in rabbits when injected in chemically pure form, became immunogenic once it was conjugated chemically to a carrier protein. Plescia et al. (1964) first showed that a carrier need not be conjugated chemically to a hapten, that a carrier need only form a stable complex with the hapten. Methylated bovine serum albumin (MBSA), complexed electrostatically with denatured DNA or type III pneumococcal capsular polysaccharide, proved to be an effective carrier. Rabbits, immunized with these complexes, produced DNA and polysaccharide-specific antibodies.
The Evolution of Ultraviolet Vision in Vertebrates

Molecular evolutionary analyses reveal that the vertebrate ancestor used ultraviolet (UV) vision. Many nonavian species have inherited UV vision from this ancestor, whereas many other species have acquired violet (or blue) vision by replacing some amino acids at ∼10 critical sites in the ancestral UV pigment. In the avian lineage, the ancestor acquired violet vision, but some of its descendants have restored UV vision by a single amino acid change. A survey of UV vision in different species reveals that the usefulness of having UV vision depends strongly not only on animals’ ecological backgrounds and behavioral characteristics, but also on the physiology of the eye.
Strategic Decisions in Conservation: Using Species Distribution Modeling to Match Ecological Requirements to Available Habitat

Identifying a species’ geographic range is the first step in understanding whether the range is changing or being disturbed, fragmented, or modified by some other process. A species’ range is constrained in part by specific environmental limiting factors that collectively define the environmental space of the species or its habitat needs. Other factors, such as dispersal and interspecific competition, further constrain a species’ geographic distribution. However, environmental space creates a primary restriction on a species’ current geographic distribution that is easily measured and analyzed. Understanding environmental conditions, how those conditions interact across geographic space, and how the spatial distribution of those conditions may change through time can be informative for making conservation decisions. This chapter addresses the following questions: (1) What environmental conditions make up suitable habitat for endemic species of the Colorado Plateau? (2) Where do those conditions currently exist on the landscape? (3) Will those conditions persist in the future?
Time in the Classical and Medieval Worldviews

Over the course of their evolution, humans have developed an awareness of time so they could put in order the past, the present, and the future. Historically, the awareness of time was by no means universal or uniform. Ancient cultures all employed different models and techniques for measuring the duration and passage of time. In this chapter, we will briefly chart the intellectual history of time, exploring the early ideas that laid the groundwork upon which our contemporary concepts of time are based.