LLukas22/scidocs huggingface dataset:
Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years.

OBJECTIVE
To evaluate cyclosporine 0.1% ophthalmic emulsion over a 1- to 3-year period in moderate to severe dry eye disease patients.


DESIGN
Nonrandomized, multicenter, open-label clinical trial extending 2 ophthalmic cyclosporine phase III clinical trials.


PARTICIPANTS
Four hundred twelve patients previously dosed for 6 to 12 months with cyclosporine 0.05% or 0.1% in prior phase III trials.


INTERVENTION
Patients instilled ophthalmic cyclosporine 0.1% twice daily into both eyes for up to 3 consecutive 12-month extension periods.


MAIN OUTCOME MEASURES
Corneal staining, Schirmer tests, and symptom severity assessments were conducted during the first 12-month extension, with a patient survey during the second 12-month extension. Biomicroscopy and visual acuity (VA) examinations, intraocular pressure (IOP) measurements, and adverse effects queries occurred at 6-month intervals.


RESULTS
Mean duration of treatment was 19.8 months. Improvements in objective and subjective measures of dry eye disease were modest, probably because of prior treatment with cyclosporine. Most survey respondents said their symptoms began to resolve in the first 3 months of cyclosporine treatment during the previous phase III clinical trials. At study exit, VA decreased in 12.6% (93/738) and increased in 5.4% (40/738) of eyes by > or =2 lines; severity of biomicroscopy findings increased in 3.4% (chemosis; 26/760), 7.2% (conjunctival hyperemia; 55/760), or 8.5% (tear film debris; 64/756) of eyes; and mean IOP increased 0.18 mmHg relative to baseline. The most common treatment-related adverse events were burning (10.9% of patients [45/412]), stinging (3.9% [16/412]), and conjunctival hyperemia (3.4% [14/412]). No serious treatment-related adverse events occurred. Most patients (95.2% [140/147]) said they would continue cyclosporine therapy; 97.9% (143/146) would recommend it to other dry eye patients.


CONCLUSIONS
Therapy of chronic dry eye disease with cyclosporine 0.1% ophthalmic emulsion for 1 to 3 years was safe, well tolerated, and not associated with systemic side effects. The results supplement the safety record of the commercially available cyclosporine 0.05% ophthalmic emulsion.
Education and reported onset of symptoms among individuals with Alzheimer disease.

OBJECTIVES
To examine whether reported age at onset of dementia symptoms among participants with Alzheimer disease (AD) is later for those with fewer years of education and, if so, to see if education is attributed to delayed detection of symptoms.


DESIGN
Case series.


SETTING
National Alzheimer's Coordinating Center Minimum Data Set (N=21 880 participants) and Washington University Alzheimer's Disease Research Center (N=1449 participants).


RESULTS
Reported age at onset of dementia symptoms is slightly younger in participants with more education. Participants with fewer years of education show greater clinical severity of Alzheimer disease at first assessment.


CONCLUSION
Symptoms of Alzheimer disease are recognized later among those with less education.
Eco-efficiency: Philosophy, Theory, and Tools

It is ironic that I am writing this column on the philosophy, theory, and tools of eco-efficiency, because I expressed my skepticism concerning the subject at the meeting that is the source of this special issue. The concept of eco-efficiency was first described by Schaltegger and Sturm (1989) and then widely publicized in 1992 in Changing Course (Schmidheiny 1992), a publication of the World Business Council for Sustainable Development (WBCSD). Since then it has been accepted
An Event-B formalization of KAOS goal refinement patterns

Goals play an important role in requirements engineering process, and consequently in systems development process. Whereas specifications allow us to answer the question ”WHAT the system does”, goals allow us to address the ”WHY, WHO, WHEN” questions [5]. Up to now, the main software development approaches using formal methods, such as Event-B, begins at the specification level. Our objective is to include requirements analysis within this process, and more precisely the KAOS method, which is a goal-oriented methodology for requirements engineering. The latter allows analysts to build requirements models and to derive requirements documents. Existing work that combine KAOS with formal methods generate a formal specification model from a KAOS requirements model. We aim at expressing KAOS goal models with a formal language (Event-B), hence staying at the same abstraction level. Thus we take advantage from the Event-B method: (i) it is possible to use the method during the whole development process and (ii) we can benefit from the industrial maturity of tools supporting the method. For that purpose, we propose a constructive approach in which Event-B models are built incrementally from KAOS goal models, driven by goal refinement patterns.
Heterogeneous landscapes and the role of refuge on the population dynamics of a specialist predator and its prey

How, and where, a prey species survives predation by a specialist predator during low phases of population fluctuations or a cycle, and how the increase phase of prey population is initiated, are much-debated questions in population and theoretical ecology. The persistence of the prey species could be due mainly to habitats that act as refuges from predation and/or due to anti-predatory behaviour of individuals. We present models for the former conjecture in two (and three) habitat systems with a specialist predator and its favoured prey. The model is based on dispersal of prey between habitats with high reproductive output but high risk of predation, and less productive habitats with relatively low risk of predation. We illustrate the predictions of our model using parameters from one of the most intriguing vertebrate predator–prey systems, the multi-annual population cycles of boreal voles and their predators. We suggest that cyclic population dynamics could result from a sequence of extinction and re–colonization events. Field voles (Microtus agrestis), a key vole species in the system, can be hunted to extinction in their preferred meadow habitat, but persist in sub-optimal wet habitats where their main predator, the least weasel (Mustela nivalis nivalis) has a low hunting efficiency. Re–colonization of favourable habitats would occur after the predator population crashes. At the local scale, the model suggests that the periodicity and amplitude of population cycles can be strongly influenced by the relative availability of risky and safe habitats for the prey. Furthermore, factors like intra-guild predation may lead to reduced predation pressure on field voles in sub-optimal habitats, which would act as a refuge for voles during the low phase of their population cycles. Elasticity analysis suggested that our model is quite robust to changes in most parameters but sensitive to changes in the population dynamics of field voles in the optimal grassland habitat, and to the maximum predation rate of weasels.
Submucosal fibroids becoming endocavitary following uterine artery embolization: risk assessment by MRI.

OBJECTIVE
The purpose of our study was to assess the relationship between the endometrium and submucosal fibroids before and after uterine artery embolization (UAE).


MATERIALS AND METHODS
Contrast-enhanced pelvic 1.5-T MRI was performed in 49 women before and after UAE over a 2-year period. Dominant (largest diameter) fibroids in intramural, submucosal, subserosal, pedunculated subserosal, and endocavitary locations were assessed on pre- (baseline) and postembolization MRI. Size, locations of dominant fibroids relative to endometrium and serosa before and after embolization were compared. The ratio between the largest endometrial interface and the maximum dimension of the dominant submucosal fibroid (interface-dimension ratio) was determined on baseline MRI. The infarction rate for dominant fibroids was estimated after UAE.


RESULTS
One hundred forty dominant fibroids were identified on baseline MRI. Forty-nine (35%) were intramural, 39 (28%) were submucosal, 34 (24%) were subserosal, eight (6%) were pedunculated subserosal, and 10 (6%) were endocavitary in location on preembolization MRI. After UAE, of 39 dominant submucosal fibroids, 13 (33%) became endocavitary: complete (n = 4), partial (n = 9) on the basis of European Society of Gynaecological Endoscopy (ESGE) classification. The preembolization mean interface-dimension ratio and mean diameters for dominant fibroids that became endocavitary were significantly greater than for those that did not become endocavitary after embolization (0.65 vs 0.32, p < 0.005; 8 vs 5.4 cm, p < 0.05, respectively). All dominant submucosal fibroids showed 100% infarction after UAE.


CONCLUSION
Submucosal fibroids with an interface-dimension ratio of greater than 0.55 are more likely to migrate into the endometrial cavity after UAE. The majority of these are expelled spontaneously without significant symptoms. Rarely, submucosal fibroids greater than 6 cm in size that become endocavitary may cause postprocedural complications requiring further intervention and medical treatment.
Theory and measurement of generalized problematic Internet use: A two-step approach

This study tested an updated cognitive-behavioral model of generalized problematic Internet use and reports results of a confirmatory analysis of the Generalized Problematic Internet Use Scale 2 (GPIUS2). Overall, the results indicated that a preference for online social interaction and use of the Internet for mood regulation, predict deficient self-regulation of Internet use (i.e., compulsive Internet use and a cognitive preoccupation with the Internet). In turn, deficient self-regulation was a significant predictor of the extent to which one’s Internet use led to negative outcomes. Results indicated the model fit the data well and variables in the model accounted for 27% of the variance in mood regulation scores, 65% of variance in participants’ deficient self-regulation scores, and 61% of variance in the negative outcome scores. 2010 Elsevier Ltd. All rights reserved.
A discontinuous Galerkin conservative level set scheme for interface capturing in multiphase flows

The accurate conservative level set (ACLS) method of Desjardins et al. [O. Desjardins, V. Moureau, H. Pitsch, An accurate conservative level set/ghost fluid method for simulating turbulent atomization, J. Comput. Phys. 227 (18) (2008) 8395–8416] is extended by using a discontinuous Galerkin (DG) discretization. DG allows for the scheme to have an arbitrarily high order of accuracy with the smallest possible computational stencil resulting in an accurate method with good parallel scaling. This work includes a DG implementation of the level set transport equation, which moves the level set with the flow field velocity, and a DG implementation of the reinitialization equation, which is used to maintain the shape of the level set profile to promote good mass conservation. A near second order converging interface curvature is obtained by following a height function methodology (common amongst volume of fluid schemes) in the context of the conservative level set. Various numerical experiments are conducted to test the properties of the method and show excellent results, even on coarse meshes. The tests include Zalesak’s disk, two-dimensional deformation of a circle, time evolution of a standing wave, and a study of the Kelvin–Helmholtz instability. Finally, this novel methodology is employed to simulate the break-up of a turbulent liquid jet. ! 2013 Elsevier Inc. All rights reserved.
Personal informatics in chronic illness management

Many 1 people 2 with 3 chronic illness suffer from debilitating symptoms or episodes that inhibit normal day-to-day function. Pervasive tools offer the possibility to help manage these conditions, particularly by helping people understand their conditions. But, it is unclear how to design these tools, as prior designs have focused on effortful tracking and many see those tools as a burden to use. We report here on an interview study with 12 individuals with chronic illnesses who collect personal data. We learn that these people are motivated through selfdiscovery and curiosity. We explore how these concepts may support the design of tools that engage curiosity and encourage self-discovery, rather than emphasize the behaviour change aspect of chronic illness management.
Summary of comprehensive systematic review: Rehabilitation in multiple sclerosis: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE
To systematically review the evidence regarding rehabilitation treatments in multiple sclerosis (MS).


METHODS
We systematically searched the literature (1970-2013) and classified articles using 2004 American Academy of Neurology criteria.


RESULTS
This systematic review highlights the paucity of well-designed studies, which are needed to evaluate the available MS rehabilitative therapies. Weekly home/outpatient physical therapy (8 weeks) probably is effective for improving balance, disability, and gait (MS type unspecified, participants able to walk ≥5 meters) but probably is ineffective for improving upper extremity dexterity (1 Class I). Inpatient exercises (3 weeks) followed by home exercises (15 weeks) possibly are effective for improving disability (relapsing-remitting MS [RRMS], primary progressive MS [PPMS], secondary progressive MS [SPMS], Expanded Disability Status Scale [EDSS] 3.0-6.5) (1 Class II). Six weeks' worth of comprehensive multidisciplinary outpatient rehabilitation possibly is effective for improving disability/function (PPMS, SPMS, EDSS 4.0-8.0) (1 Class II). Motor and sensory balance training or motor balance training (3 weeks) possibly is effective for improving static and dynamic balance, and motor balance training (3 weeks) possibly is effective for improving static balance (RRMS, SPMS, PPMS) (1 Class II). Breathing-enhanced upper extremity exercises (6 weeks) possibly are effective for improving timed gait and forced expiratory volume in 1 second (RRMS, SPMS, PPMS, mean EDSS 4.5); this change is of unclear clinical significance. This technique possibly is ineffective for improving disability (1 Class II). Inspiratory muscle training (10 weeks) possibly improves maximal inspiratory pressure (RRMS, SPMS, PPMS, EDSS 2-6.5) (1 Class II).
Epidemiologic features of the physical and sexual maltreatment of children in the Carolinas.

CONTEXT
Child maltreatment remains a significant public health and social problem in the United States. Incidence data rely on substantiated reports of maltreatment known to official social service agencies.


OBJECTIVE
The objective of this study was to describe the epidemiologic features of child physical and sexual abuse, on the basis of maternal self-reports.


DESIGN, SETTING, AND PARTICIPANTS
Computer-assisted, anonymous, cross-sectional, telephone surveys (N = 1435) were conducted with mothers of children 0 to 17 years of age in North and South Carolina. Mothers were asked about potentially abusive behaviors used by either themselves or their husbands or partners in the context of other disciplinary practices. They were also asked about their knowledge of any sexual victimization their children might have experienced.


MAIN OUTCOME MEASURES
The incidence of physical and sexual maltreatment determined through maternal reports.


RESULTS
Use of harsh physical discipline, equivalent to physical abuse, occurred with an incidence of 4.3%. Shaking of very young children as a means of discipline occurred among 2.6% of children <2 years of age. Mothers reported more frequent physical discipline of their children, including shaking, for themselves than for fathers or father figures. Nearly 11 of 1000 children were reported by their mothers as having been sexually victimized within the past year. The incidence of physical abuse determined with maternal self-reports was 40 times greater than that of official child physical abuse reports, and the sexual abuse incidence was 15 times greater. For every 1 child who sustains a serious injury as a result of shaking, an estimated 150 children may be shaken and go undetected. There was no statistically significant difference in the overall rates of physical or sexual maltreatment between the 2 states.


CONCLUSIONS
Official statistics underestimate the burden of child maltreatment. Supplemental data obtained with alternative strategies can assist policymakers and planners in addressing needs and services within communities and states. These data support the need for continued interventions to prevent maltreatment.
Sea Anemone Toxin (ATX II) Modulation of Heart and Skeletal Muscle Sodium Channel α-Subunits Expressed in tsA201 Cells

We have expressed recombinant α-subunits of hH1 (human heart subtype 1), rSkM1 (rat skeletal muscle subtype 1) and hSkM1 (human skeletal muscle) sodium channels in human embryonic kidney cell line, namely the tsA201 cells and compared the effects of ATX II on these sodium channel subtypes. ATX II slows the inactivation phase of hH1 with little or no effect on activation. At intermediate concentrations of ATX II the time course of inactivation is biexponential due to the mixture of free (fast component, τfast h ) and toxin-bound (slow component, τslow h ) channels. The relative amplitude of τslow h allows an estimate of the IC50 values ∼11 nm. The slowing of inactivation in the presence of ATX II is consistent with destabilization of the inactivated state by toxin binding. Further evidence for this conclusion is: (i) The voltage-dependence of the current decay time constants (τ h ) is lost or possibly reversed (time constants plateau or increase at more positive voltages in contrast to these of untreated channels). (ii) The single channel mean open times are increased by a factor of two in the presence of ATX II. (iii) The recovery from inactivation is faster in the presence of ATX II. Similar effects of ATX II on rSkM1 channel behavior occur, but only at higher concentrations of toxin (IC50= 51 nm). The slowing of inactivation on hSkM1 is comparable to the one seen with rSkM1. A residual or window current appears in the presence of ATX II that is similar to that observed in channels containing mutations associated with some of the familial periodic paralyses.
Variational Attention for Sequence-to-Sequence Models

The variational encoder-decoder (VED) encodes source information as a set of random variables using a neural network, which in turn is decoded into target data using another neural network. In natural language processing, sequence-to-sequence (Seq2Seq) models typically serve as encoderdecoder networks. When combined with a traditional (deterministic) attention mechanism, the variational latent space may be bypassed by the attention model, and thus becomes ineffective. In this paper, we propose a variational attention mechanism for VED, where the attention vector is also modeled as Gaussian distributed random variables. Results on two experiments show that, without loss of quality, our proposed method alleviates the bypassing phenomenon as it increases the diversity of generated sentences.1
Cell-to-cell pathway dominates xylem-epidermis hydraulic connection in Tradescantia fluminensis (Vell. Conc.) leaves

A steady supply of water is indispensable for leaves to fulfil their photosynthetic function. Understanding water movement in leaves, especially factors that regulate the movement of water flux from xylem to epidermis, requires that the nature of the transport pathway be elucidated. To determine the hydraulic linkage between xylem and epidermis, epidermal cell turgor pressure (P t) in leaves of Tradescantia fluminensis was monitored using a cell pressure probe in response to a 0.2 MPa step change in xylem pressure applied at the leaf petiole. Halftime of P t changes $$ {\left( {T^{x}_{{1/2}} } \right)} $$ were 10–30 times greater than that of water exchange across an individual cell membrane $$ {\left( {T^{m}_{{1/2}} } \right)}, $$ suggesting that cell-to-cell water transport constitutes a significant part of the leaf hydraulic path from xylem to epidermis. Furthermore, perfusion of H2O2 resulted in increases of both $$ T^{m}_{{1/2}} $$ and $$ T^{x}_{{1/2}} $$ by a factor of 2.5, indicating that aquaporins may play a role in the xylem to epidermis hydraulic link. The halftime for water exchange $$ {\left( {T^{m}_{{1/2}} } \right)} $$ did not differ significantly between cells located at the leaf base (2.5 s), middle (2.6 s) and tip (2.5 s), indicating that epidermal cell hydraulic properties are similar along the length of the leaf. Following the pressure application to the xylem (0.2 MPa), P t changed by 0.12, 0.06 and 0.04 MPa for epidermal cells at the base, middle and the tip of the leaf, respectively. This suggests that pressure dissipation between xylem and epidermis is significant, and that the pressure drop along the vein may be due to its structural similarities to a porous pipe, an idea which was further supported by measurements of xylem hydraulic resistance using a perfusion technique.
Magnesium sulphate at 30 to 34 weeks’ gestational age: neuroprotection trial (MAGENTA) - study protocol

BACKGROUND
Magnesium sulphate is currently recommended for neuroprotection of preterm infants for women at risk of preterm birth at less than 30 weeks' gestation, based on high quality evidence of benefit. However there remains uncertainty as to whether these benefits apply at higher gestational ages.The aim of this randomised controlled trial is to assess whether giving magnesium sulphate compared with placebo to women immediately prior to preterm birth between 30 and 34 weeks' gestation reduces the risk of death or cerebral palsy in their children at two years' corrected age.


METHODS/DESIGN



DESIGN
Randomised, multicentre, placebo controlled trial.


INCLUSION CRITERIA
Women, giving informed consent, at risk of preterm birth between 30 to 34 weeks' gestation, where birth is planned or definitely expected within 24 hours, with a singleton or twin pregnancy and no contraindications to the use of magnesium sulphate.Trial entry & randomisation: Eligible women will be randomly allocated to receive either magnesium sulphate or placebo.Treatment groups: Women in the magnesium sulphate group will be administered 50 ml of a 100 ml infusion bag containing 8 g magnesium sulphate heptahydrate [16 mmol magnesium ions]. Women in the placebo group will be administered 50 ml of a 100 ml infusion bag containing isotonic sodium chloride solution (0.9%). Both treatments will be administered through a dedicated IV infusion line over 30 minutes.Primary study outcome: Death or cerebral palsy measured in children at two years' corrected age.


SAMPLE SIZE
1676 children are required to detect a decrease in the combined outcome of death or cerebral palsy, from 9.6% with placebo to 5.4% with magnesium sulphate (two-sided alpha 0.05, 80% power, 5% loss to follow up, design effect 1.2).


DISCUSSION
Given the magnitude of the protective effect in the systematic review, the ongoing uncertainty about benefits at later gestational ages, the serious health and cost consequences of cerebral palsy for the child, family and society, a trial of magnesium sulphate for women at risk of preterm birth between 30 to 34 weeks' gestation is both important and relevant for clinical practice globally.


TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry - ACTRN12611000491965.