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•This is the largest summary to date of the management of people with hemophilia A on emicizumab prophylaxis undergoing surgery.•Major and minor surgeries were performed safely in people receiving emicizumab, regardless of factor VIII inhibitor status.

Objective: This study assessed the efficacy of olanzapine in delaying or preventing conversion to psychosis and reducing symptoms in people with prodromal symptoms of schizophrenia. Method: This randomized trial occurred at four North American clinics in the Prevention Through Risk Identification, Management, and Education project. Outpatients received olanzapine (5-15 mg/day, N=31) or placebo (N=29) during a 1-year double-blind treatment period and no treatment during a 1-year follow-up period. Efficacy measures included the conversion-to-psychosis rate and Scale of Prodromal Symptoms scores. Results: During the treatment year, 16.1% of olanzapine patients and 37.9% of placebo patients experienced a conversion to psychosis, a nearly significant difference. The hazard of conversion among placebo patients was about 2.5 times that among olanzapine-treated patients, which also approached significance. In the follow-up year, the conversion rate did not differ significantly between groups. During treatment, the mean score for prodromal positive symptoms improved more in the olanzapine group than in the placebo group, and the mixed-model repeated-measures least-squares mean score showed significantly greater improvement between weeks 8 and 28 with olanzapine. The olanzapine patients gained significantly more weight (mean=8.79 kg, SD=9.05, versus mean= 0.30 kg, SD=4.24). Conclusions: A significant treatment difference in the conversion-to-psychosis rate was not demonstrated. However, these results may be influenced by low power. The nearly significant differences suggest that olanzapine might reduce the conversion rate and delay onset of psychosis. Olanzapine was efficacious for positive prodromal symptoms but induced weight gain. Further treatment research in this phase of illness is warranted.

Patients included in clinical trials do not necessarily reflect the real-world population.

Omalizumab improves clinical outcomes in patients with asthma. Several studies have shown lung function improvements with omalizumab; however, this has not been examined exclusively in adolescents.

Omalizumab is approved to treat chronic spontaneous urticaria (CSU) and can improve quality of life (QoL). Although studies show omalizumab improves one aspect of QoL, sleep, time to no sleep interference and association with urticaria activity has not been fully explored.

The anti-IgE antibody omalizumab is effective for patients with moderate-to-severe allergic asthma, but the impact of baseline patient characteristics on long-term response to omalizumab has not been well studied.

Omalizumab is approved for the treatment of chronic spontaneous urticaria (CSU); however, the impact of baseline angioedema status and IgE level on the response to omalizumab is not fully explored.

Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown.

There are sex-related disparities in asthma. Before puberty, males have increased prevalence and severity of asthma compared with females, and this pattern reverses after the onset of puberty. Omalizumab, an IgE antibody, is an effective treatment for allergic asthma, but sex-specific responses have not been studied in detail.

Chronic spontaneous urticaria (CSU) is a debilitating skin disorder associated with decreased quality of life and psychological comorbidities. Omalizumab is currently the only biologic approved for the treatment of CSU, however data is lacking describing the pattern of response to omalizumab, including the time to a clinically meaningful response.

Background Postural stability is of great importance because imbalances and muscle weakness are significant risk factors for falls experienced by the elderly. Hip arthrosis, which causes pain and gait disorders that affect balance control, is common in the ageing population.Aim The aim of this study was to assess postural stability in patients with unilateral hip arthrosis before total hip arthroplasty.Methods The study population consisted of 52 patients with hip arthrosis (study group) and 47 subjects with no history of clinical symptoms of hip pain. The groups did not differ statistically in terms of age and BMI. Static balance was assessed by conducting a quantitative analysis of balance reaction parameters in a quiet standing position with the eyes open and closed.Results Analysis of the collected data revealed numerous statistically significant differences between patients with unilateral hip arthrosis before total hip arthoplasty and the asymptomatic group for parameters tested with eyes closed (p<0.05). We observed higher values of total length of centre of pressure (COP), sway path (SP), length of COP path in the medial-lateral plane (SPML), maximal amplitude between the 2 most distant points in the medial-lateral plane (MaxML), mean COP velocity (MV), and mean COP velocity in medial-lateral (MVML) in the study group.

Purpose:The aim of the study was to analyze the results of the hip joint torques within the patients with osteoarthritis (OA). A total of 119 women were divided into 3 groups performing 3 dimensional strength tests. For the measurements a new apparatus was invented and used. Specially designed position was safety and comfortable during testing OA and elderly women.Results:Significant differences (p≤0.05) in strength tests were found both between body side and muscle groups in most of the performed tests. The biggest unilateral deficit in OA group was found in muscles most important for gait and weight bearing − 0.55 for both flexors and extensors. Surprisingly no lateral difference was found for the hip joint adductors. Analysis of the correlation coefficient between the hip joint muscles proved that complex movements needed well-developed coordination between the muscle groups. The most important agonist muscle coordination occurs between hip extensors and abductors − 0.68 to 0.80.Conclusion:Unilateral hip OA affecting older women is directly responsible for significantly lower muscle strength when compared with both control groups. Lost of balance and coordination needed for dynamic actions like gait is caused by strength asymmetry of crucial hip muscles as well as near zero correlation between important agonist muscles.

For patients with asthma, the dose/frequency of omalizumab is determined by bodyweight and pretreatment IgE levels. Since patients who fall outside the dosing table are treated with omalizumab, we assessed patient-reported outcomes (Asthma Control Test [ACT], Global Evaluation of Treatment Effectiveness [GETE], Work Productivity and Activity Impairment [WPAI-Asthma]) stratified by where they fell on the omalizumab dosing table.

Chronic spontaneous urticaria (CSU/CIU) is a debilitating skin disorder. The EAACI/GA2LEN/EDF/WAO guidelines recommend omalizumab as second-line treatment (after H1-antihistamines) for 6 months before switching to cyclosporin-A. However, in clinical practice the decision to discontinue omalizumab is often made before the recommended 6 months, and, although characteristics including lower IgE levels and higher BMI may be associated with poor response, these same patients may benefit from longer treatment/up-dosing.

Spatial chromatin organization is crucial for transcriptional regulation and might be particularly important in neurons since they dramatically change their transcriptome in response to external stimuli. We show that stimulation of neurons causes condensation of large chromatin domains. This phenomenon can be observed in vitroin cultured rat hippocampal neurons as well as in vivoin the amygdala and hippocampal neurons. Activity-induced chromatin condensation is an active, rapid, energy-dependent, and reversible process. It involves calcium-dependent pathways but is independent of active transcription. It is accompanied by the redistribution of posttranslational histone modifications and rearrangements in the spatial organization of chromosome territories. Moreover, it leads to the reorganization of nuclear speckles and active domains located in their proximity. Finally, we find that the histone deacetylase HDAC1 is the key regulator of this process. Our results suggest that HDAC1-dependent chromatin reorganization constitutes an important level of transcriptional regulation in neurons.

Escobar: National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dunn:Genentech, Inc.: Consultancy; Nationwide Children's Hospital: Current Employment; World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Spire: Honoraria; ATHN: Research Funding; Takeda: Research Funding; BioMarin: Research Funding; uniQure: Consultancy. Quon:Octapharma: Honoraria; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Shire/Takeda: Speakers Bureau; Orthopaedic Institute for Children: Current Employment. Trzaskoma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Lee:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ko:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Carpenter:Novo Nordisk: Honoraria; Genentech, Inc.: Honoraria; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Shire: Research Funding; Hemostasis & Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Kedrion: Honoraria.

The severity of asthma (SOA) score is based on a validated disease-specific questionnaire that addresses frequency of asthma symptoms, use of systemic corticosteroids, use of other asthma medications, and history of hospitalization/intubation for asthma. SOA does not require measurements of pulmonary function. This study compared the ability of SOA to predict clinical outcomes in the EXCELS (Epidemiological Study of Xolair [omalizumab]: Evaluating Clinical Effectiveness and Long-term Safety in Patients with Moderate to Severe Asthma) patient population vs three other asthma assessment tools. EXCELS is a large, ongoing, observational study of patients with moderate to severe persistent asthma and reactivity to perennial aeroallergens.

The objective of the study was to investigate the chronic effect of low frequency whole body vibration (WBV) on isometric and eccentric strength of knee extensors with different force exertion capacity. It was hypothesized that (1) four-week WBV intervention with the low frequency domain would enhance muscle strength and (2) the improvement would be more pronounced in the weaker muscle. To test our hypothesis twenty patients with acute stroke were recruited. Ten patients were randomly assigned to vibration and the remaining ten patients served for control.The patients in the vibration group received WBV with 20 Hz frequency three times per week standing on a vibration platform in half squat position meanwhile flexing and extending the joints and placing the weight from one leg to the other. Knee extensor strength was determined under isometric and eccentric contraction before and after WBV intervention. Myoelectrical activity (EMG) of the vastus lateralis muscle was also measured.Significant improvement was revealed in the vibration group only. The maximum isometric torque and EMG activity increased significantly for both paretic and non-paretic leg, but the improvement was threefold greater in the vibration group. No significant alteration was found in rate of torque development. Maximum eccentric torque and EMG increased significantly for the paretic leg only. Mechanical work enhanced significantly in the paretic side only.The results of our study indicate that the selection of the effective vibration frequency depends upon the physical condition of neuromuscular system. Low vibration frequency intervention can increase the strength in weak muscles due to neuromuscular impairment and restricted physical activity.

Background:Emicizumab is indicated for prophylaxis in persons with hemophilia A (PwHA) of all ages, with/without factor (F)VIII inhibitors (exact label may vary by country). For older persons receiving emicizumab, however, their care may be complicated by comorbidities. Prevalence and early onset of cardiovascular (CV) risk factors, including hypertension, are common among PwHA (Humphries, et al. Adv Med Sci 2018; Sood, et al. Blood Adv 2018). Human immunodeficiency virus (HIV), which is likely to be more common in older PwHA, is associated with increased risk of heart disease (Shah, et al. Circulation 2018), and co-infection of HIV with hepatitis C virus (HCV) increases the risk of end-stage liver disease and worsens HCV progression (Papadopoulos, et al. Ann Gastroenterol 2018). Data regarding emicizumab in older PwHA with comorbidities (CV risk factors or concomitant HIV and/or HCV infection) are limited. This post hoc analysis of PwHA in four Phase III studies evaluated efficacy and safety of emicizumab in PwHA aged ≥50 years with CV risk factors or HIV and/or HCV infection.

AbstractOur aim in this paper is threefold. First, we will set out a few broad observations on the use Apollodorus makes of the word 'Ελλάς in the surviving books and epitomes of the Bibliotheke, noting that his usage is restricted and that this restriction has larger implications for the overall structure of the work (I). Second, we will show that in one case (1. 47) the word has been widely misunderstood in the available translations and that the example provides a glimpse at Apollodorus' sources (II). Third, we will argue that in another case (1. 74) there has been an error in textual transmission and the word does not, in fact, occur at all (III).

ABSTRACTObjectives:To better understand the effects of drotrecogin alfa (activated) (DrotAA) in severe sepsis patients, and the natural progression of severe sepsis, by creating a database of severe sepsis patients using the appropriate statistical analysis methods to integrate data from various trials.Patients and methods:Patient-level data from five severe sepsis trials, conducted by the same sponsor (Eli Lilly and Company, Indianapolis, IN, USA), were combined in an integrated database. Patients from various studies were included and received either DrotAA at 24 μg/kg/h for 96 hours ( n= 3228) or placebo ( n= 1231), in addition to standard supportive care. The following adjustments to the analyses were made to allow for the combined, and thus non-randomized, nature of the data: (1) differences in observed outcomes between studies were investigated to assess the extent of study-to-study variation before combining study-level data across trials for statistical analysis; (2) random study effects were included in models for patient-level data to capture potential extraneous study-to-study variation; and (3) propensity scores were computed and included as covariates in models for patient-level data to adjust for the non-randomized nature of the data.Results:Baseline characteristics were similar across the studies, supporting the combination of study-level data across trials. Comparing aggregate event rates between the two treatment arms yielded a relative risk for mortality (DrotAA versus placebo) of 0.79 (95% confidence interval [CI] 0.71–0.88), p< 0.0001. For patient-level analyses, after adjustment for 13 independent variables and random study effects, the odds ratio for mortality in the DrotAA versus placebo patients was 0.71 (95% CI 0.59–0.86), p= 0.0003. With adjustment for 13 independent variables and propensity score, the odds ratio was 0.79 (95% CI 0.67–0.93), p= 0.006. Limitations of this integrated database include the modest total number of the trials in the database and the fact that only one component trial in the database contributed data from both placebo and DrotAA-treated patients.Summary:A robust severe sepsis database was developed which will be suitable for future studies on the progression of severe sepsis and the mechanism of action of DrotAA. Initial analysis of data from INDEPTH provides additional evidence that treatment of severe sepsis patients with DrotAA is associated with a sustained survival advantage throughout 28‐day follow-up.

Focuses on the attempt by Longus to create at the beginning of his third book an echo of the famous Mytilenean debate between Diodotus and Cleon in Thucydides' history. Connections between Longus and Thucydides in the novel's second and third books; Claim that Longus uses a Thucydidean tag to describe Daphnis' escape from the rough justice of the Methymnaeans; Implications of Longus' dismissal of history as a relevant force in the lives of his hero and heroine.

We present aspects of a general approach for the analysis of second-harmonic response at a metal/electrolyte interface. Analysis is based on a combination of principles from classical system identification and pattern recognition with a previously derived explicit and general representation of modulated second-harmonic response on the molecular level. This study emphasizes the adaptation of our approach and associated representation for the formulation of feature variables whose purpose is to extract features associated with observed trends in modulated second-harmonic signals. Our development introduces the concept of representing the multidimensional processes responsible for second-harmonic generation by means of a one-dimensional stationary stochastic process. This approach allows us to extract trends in experimental data correlated with molecular level charge displacements and resonant effects. The paper concludes with a series of analyses that illustrate the applicability of our approach and suggest possible pathways for its extension.

Powders and thin coatings of ceria and titania were synthesized from aqueous and solvent-based precursors. Thin coatings were deposited on polished 304 stainless steel coupons by dipping them in the appropriate sol-gel oxide precursors. The coatings were subsequently densified and crystallized at several hundreds of degrees. It was possible to obtain dense titania coatings by applying thin coatings of cerium dioxide prior to titania on stainless steel substrates. Underlayer ceria coatings proved to be pivotal in obtaining dense titania coatings and preserving the integrity of the stainless steel while going through the high temperature treatments. The effect of processing parameters such as the atmosphere of heat-treatment, and temperature on the microstructure and crystal structure of the films and powders of ceria and titania was investigated. X-ray diffraction was used to identify the crystal structure of films and powders upon heat-treatment. Electrochemical measurements in NaCl, and analytical techniques such as SEM and EDX were used to evaluate the corrosion performance and pitting morphology of coated samples. A composite coating of ceria and titania was able to prevent crevice corrosion and increase the pitting resistance of the 304 stainless steel relative to the uncoated substrate.

Optical second harmonic generation is used to investigate the characteristics of a Langmuir film of hematoporphyrin IX dimethyl ester on water. Interfacial molecular orientation is determined by the construction of a system response function based on general and consistent assumptions concerning the distribution of second‐order non‐linear hyperpolarizabilities and the second harmonic intensity variation for compressed and expanded versions of the film. Two dominant average hyperpolarizability axes are observed for the individual molecules making up the film. Further, it is found that the molecules tend to align towards the vertical as the film is compressed from the maximum mean molecular area of 130 Å to the minimum mean molecular area of 70 Å2. The molecular tilt angle varies from 44° under maximum compression to 71° under full expansion. These results show good quantitative agreement with previous investigations of Langmuir films of similar molecules.© 1997 by John Wiley & Sons, Ltd.

We present a general approach for establishing correlations between the optical second-harmonic (SH) response generated from a metal/electrolyte interface and the interface structure. Our approach entails the construction of a response function for optical second-harmonic generation (SHG) from the metal surface in the presence of an electrolyte and an applied electrochemical field. The response function approach, a powerful and general method, is developed here for the first time for SHG data. Here, the response function describes the nonlinear optical response of a mesoscopic region of the surface to an applied static mesoscopic electric field and is a characterization of how the electrostatic nature of the surface responds to changes in the concentration and composition of the electrolyte. We construct the response function from experimental measurements of the SH response and from models representing known interface structure. A significant aspect of our approach is that it combines, through the modification of the response function, existing models of metal-interface structure with models for mechanisms of SHG response. Our approach provides, therefore, a framework for correlating existing and emerging models of the double layer with optical experimental measurements. Case study analyses of prototype interface systems are presented here, demonstrating applications of our approach.

We present an analysis of second-harmonic (SH) response from metal surfaces that is based on a model representation whose associated parameters are defined in terms of nonlinear polarizabilities originating from charge displacement occurring on a molecular level. Our analysis suggests that the general functional dependence of SH response at a metal/electrolyte interface on the time-independent (dc) electric field is typically different from that implied by previous models. The analysis shows that our model representation is sufficiently general for extracting features from second-harmonic generation (SHG) data in order to analyze such data by methods based on system identification and pattern recognition. Our model, which is based on a classical representation of the nonlinear response of bound (or constrained) charge, is found to be consistent with trends observed in experimental measurements of second-harmonic response as a function of surface charge density. The results of this analysis suggest that SH data are relatively rich in terms of features that can be correlated with local surface structure and that the data should be interpreted by means of a more general model representation than has been previously proposed.

Various training devices have been developed to facilitate 'plyometric' training, one such device being the 'pendulum swing'. To assess the effectiveness of the pendulum swing, the results of a 3 week training programme using a combination of pendulum swing and weight-training exercises were compared to those of a weight-training programme. Subjects were assigned to one of two groups (n = 9) for weight-training only or for combined pendulum and weight-training. Both groups performed the same number of exercise repetitions. Measurements of isometric knee and hip extension-flexion, 1-RM squat weight, maximum jump height and power for a counter-movement jump were taken pre-training, 2 days after the end of the programme and 2 weeks after the end of the programme.The data were analysed using two-way MANOVA and MANCOVA techniques. Both methods showed significant (P<0.05) increases in knee and hip extension strength. Hip and knee flexion strength increased only for the weight-trained group. Counter-movement jump height increased for both groups (weight-trained, P<0.05; combined, P<0.01). Maximum power increased only for the combined group (P<0.05). When the pre-training scores were used as a covariate, the weight-trained group showed a greater increase in hip flexion and extension strength and knee flexion strength than the combined training group (P<0.05). The combined group showed the greatest increase in knee extensor strength.It is concluded that the pendulum system induces a training effect which could be used to supplement weight-training for improving vertical jump performance.

The aim of this study was to compare the effects of conventional weight-training (control) with an experimental programme. The training programme consisted of 12 sessions, 3 a week for 4 weeks. The experimental group (n= 12) performed sets of forearm flexion with a barbell until a 20% decline in maximal force was noted. The controls (n=ll) trained according to established weight-training principles. Isometric tests were performed on both the right and left forearm flexors and during forearm flexion with a barbell: the tests were continued for a 3-week post-experimental period. The subjects were matched on all tests at the start of the experiment.Larger reductions in muscle torque within the training sessions were noted among the experimental subjects -19.8 ± 2.0, 16.9 ± 1.9 and 18.0 ± 1.8% for right, left and combined elbow flexion respectively, compared to 11.8 ± 2.7, 14.9 ± 4.1 and 13.4 ± 3.1% for the controls. The volume of training (number of lifts) was 30.4% higher for the experimental subjects. Muscle strength increased in both groups (P<0.05). The controls improved by 12.7 ± 6.9, 24.9 ± 22.1, 18.3 ± 12.3 and 30.3 ± 11.1% for right, left, combined isometric strength and the barbell test respectively. These did not differ significantly from the corresponding results for the experimental group - 7.6 + 8.8, 17.0 ± 12.4, 11.8 ± 9.3 and 29.1 + 10.6% (P> 0.05). Neither the decrease in force during a single training session nor the volume of training were related to the training effect expressed as an increase in muscle force (P>0.05). The effectiveness of the conventional programme in producing similar improvements in muscle strength to the experimental programme suggests that a high volume of training is unnecessary for strength gains.

Omalizumab has demonstrated efficacy in clinical trials of patients with asthma, but real-world data are needed.

Data examining associations between asthma exacerbations, triggers, and asthma-related quality of life (QOL) in children with severe/difficult-to-treat asthma are unavailable.

Angioedema, present in some patients with chronic idiopathic/spontaneous urticaria (CIU/CSU), may have a negative effect on patient quality of life.