Durability of Response to Abrocitinib in Patients with Moderate-to-Severe Atopic Dermatitis After Treatment Discontinuation in a Phase 2b Trial

ntroduction: Multiple clinical trials showed that 12 weeks of abrocitinib monotherapy was safe and effective for the treatment of moderateto-severe atopic dermatitis (AD). The reversibility of pharmacologic activity after abrocitinib discontinuation was not described. Methods: This post hoc analysis used data from a phase 2b study to evaluate maintenance of disease control during a 4-week drug-free follow-up period in patients with moderate-tosevere AD treated with once-daily abrocitinib (200 mg/100 mg) or placebo for 12 weeks. Proportions of patients who achieved and maintained 50% or 75% improvement in Eczema Area and Severity Index (EASI-50/EASI75), an Investigator’s Global Assessment (IGA) score of 0/1, or at least a 4-point improvement in the pruritus numeric rating scale (pruritus NRS4) were determined. Biomarkers of Janus kinase inhibition and AD disease were measured in blood samples. Results: Among week 12 responders to abrocitinib 200 mg, 77.4%, 42.3%, 21.1%, and 42.9% maintained their EASI-50, EASI-75, IGA, and pruritus NRS4 response at week 16; corresponding proportions of week 12 responders maintaining response to abrocitinib 100 mg were 51.9%, 35.0%, 33.3%, and 43.5%, respectively. Four weeks after abrocitinib discontinuation, all AD biomarkers reverted towar

Brute-Force Mapmaking with Compact Interferometers: A MITEoR Northern Sky Map from 128 MHz to 175 MHz

We present a new method for interferometric imaging that is ideal for the large fields of view and compact arrays common in 21 cm cosmology. We first demonstrate the method with the simulations for two very different low-frequency interferometers, the Murchison Widefield Array and the MIT Epoch of Reionization (MITEoR) experiment. We then apply the method to the MITEoR data set collected in 2013 July to obtain the first northern sky map from 128 to 175 MHz at ∼2° resolution and find an overall spectral index of −2.73 ± 0.11. The success of this imaging method bodes well for upcoming compact redundant low-frequency arrays such as Hydrogen Epoch of Reionization Array. Both the MITEoR interferometric data and the 150 MHz sky map are available at http://space.mit.edu/home/tegmark/omniscope.html.National Science Foundation (U.S.) (AST-0908848)National Science Foundation (U.S.) (AST-1105835)National Science Foundation (U.S.) (AST-1440343

May Measurement Month 2018: a pragmatic global screening campaign to raise awareness of blood pressure by the International Society of Hypertension

Aims Raised blood pressure (BP) is the biggest contributor to mortality and disease burden worldwide and fewer than half of those with hypertension are aware of it. May Measurement Month (MMM) is a global campaign set up in 2017, to raise awareness of high BP and as a pragmatic solution to a lack of formal screening worldwide. The 2018 campaign was expanded, aiming to include more participants and countries. Methods and results Eighty-nine countries participated in MMM 2018. Volunteers (≥18 years) were recruited through opportunistic sampling at a variety of screening sites. Each participant had three BP measurements and completed a questionnaire on demographic, lifestyle, and environmental factors. Hypertension was defined as a systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg, or taking antihypertensive medication. In total, 74.9% of screenees provided three BP readings. Multiple imputation using chained equations was used to impute missing readings. 1 504 963 individuals (mean age 45.3 years; 52.4% female) were screened. After multiple imputation, 502 079 (33.4%) individuals had hypertension, of whom 59.5% were aware of their diagnosis and 55.3% were taking antihypertensive medication. Of those on medication, 60.0% were controlled and of all hypertensives, 33.2% were controlled. We detected 224 285 individuals with untreated hypertension and 111 214 individuals with inadequately treated (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) hypertension. Conclusion May Measurement Month expanded significantly compared with 2017, including more participants in more countries. The campaign identified over 335 000 adults with untreated or inadequately treated hypertension. In the absence of systematic screening programmes, MMM was effective at raising awareness at least among these individuals at risk

The role of early college high school in P-16 success: a case study of students’ perceptions of Mission Early College High School effectiveness

textThe short existence of Early College High Schools has not allowed for considerable research to assess their operational effectiveness. Furthermore, the effectiveness perceptions and reactions of students enrolled at these schools have not been given ample opportunity to be studied – an integral component of any school’s operation. The purpose of the study is to focus on one specific ECHS while in its third year of existence to assess its operational effectiveness from the perspective of its students. The research methodology which was selected as appropriate for the study involves the use of qualitative research coupled with the case study method. In order to assess for reliable observations, currently enrolled students were interviewed to gain knowledge of their perception of the operational effectiveness at their early college high school. Additional qualitative data was utilized with an inductive analytic approach to provide for a detailed view of the school. Data was segmented into relevant parts to help identify emergent themes. The following themes emerged from the findings: attainable success; student roles and responsibilities; personalization; support to achieve higher-level work; highly qualified teachers; and engaging parents and community. The findings suggest that student perceptions reflect an effective school environment that enables them to meet the expectations of high school graduation and completion of up to two years of college credit. Moreover, the supplemental data collected provided evidence of effective school administration and instructional practices that foster the support and engagement of students to meet their needs as early college high school students. An objective study of an early college high school may assist its administrators to ascertain whether they are meeting the needs of their students. Future research concerning this topic may be able to utilize the results and conclusions of this study to further enrich the knowledge of effective early college high schools.Educational Administratio

Specific monoclonal antibodies against embryonic chicken adipose tissue cell membranes and their application against developing adipocytes

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to [email protected], referencing the URI of the item.Includes bibliographical references (leaves 31-37).Issued also on microfiche from Lange Micrographics.Use of anti-adipocyte monoclonal antibodies (MAb) for reduction of fat mass in chickens was investigated in two experiments. Reduction of adipose tissue mass was obtained only in Experiment II. In Experiment I, 132 fertilized broiler chicken eggs were injected with 23 []g control mouse IgG or MAb against chicken adipocyte plasma membranes. Control IgG or MAb was injected into the allantoic age was observed when a mixture of three MAb at 0, 0.05, 0.1, 0.2, or 0.4 mg was injected at circulation at 14 or 17 d of embryogenesis. Sixty-six uninjected fertilized eggs were a negative control. Hatched chicks were randomly placed in replicate brooder pens and fed ad libitum. Body weight and feed intake were periodically measured. Approximately half of the chicks were killed at 2 weeks of age and heart, liver, bursa, and spleen weights were collected. At 2 and 6 weeks of age whole body, femoral, pectoral, and abdominal adipose weights were collected. In Experiment II, a dose-related reduction of relative abdominal depot mass at 6 weeks of 15 d of embryogenesis. Hatch rate was significantly reduced at the 0.4 mg dose. Subsequently, 180 eggs at 15 d of embryogenesis were an uninjected control or were injected with 0.2 mg of either a control mouse IgG or MAb against chicken adipocyte plasma membranes. At 2 weeks of age, femoral and pectoral adipose tissues, major organs, and total body weights were not affected by MAb injection. Abdominal fat pad mass as a percentage of body weight was reduced (P [] 0.05) > 28% by 6 weeks of age. Neither femoral nor pectoral adipose proportions of body weight were significantly affected. Growth rate, feed intake, and total body weight at 6 weeks of age were not significantly affected. Anti-adipocyte MAb injections at 15 d of embryogenesis significantly reduced (P < 0.05) relative abdominal adipose tissue mass by 6 weeks of age, while total body weight and feed intake were not affected. A dose-dependent reduction of adipose tissue mass was observed later in life after the embryo was exposed to monoclonal antibodies against adipocyte cell membranes

Interpreting the Relationship Among Itch, Sleep, and Work Productivity in Patients with Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of JADE MONO-2

BACKGROUNDAbrocitinib, an oral, once-daily Janus kinase 1-selective inhibitor, improved itch severity, sleep, and work productivity versus placebo in patients with moderate-to-severe atopic dermatitis. OBJECTIVEThe aim of this study was to investigate relationships among itch, sleep, and work productivity in the phase III JADE MONO-2 clinical trial. METHODSA repeated-measures longitudinal model was used to examine relationships between itch (using the Peak Pruritus Numerical Rating Scale [PP-NRS] or Nighttime Itch Scale [NTIS]) and sleep disturbance/loss (using the Patient-Oriented Eczema Measure sleep item and SCORing AD Sleep Loss Visual Analog Scale) and, separately, between itch and work productivity (using the Work Productivity and Activity Impairment-Atopic Dermatitis Version 2.0 questionnaire). Mediation modelling was used to investigate the effect of treatment (abrocitinib vs placebo) on work impairment via improvements in itch and sleep. RESULTSThe relationships between itch/sleep and itch/work productivity were approximately linear. PP-NRS scores of 0, 4-6, and 10 were associated with 0 days, 3-4 days, and 7 days per week of disturbed sleep, respectively. PP-NRS or NTIS scores of 0-1, 4-5, and 10 were associated with 0-10%, 20-30%, and >50% overall work impairment, respectively. Seventy-five percent of the effect of abrocitinib on reducing work impairment was indirectly mediated by improvement in itch, followed by sleep. CONCLUSIONThese results quantitatively demonstrate that reducing itch severity is associated with improvements in sleep and work productivity. Empirical evidence for the mechanism of action of abrocitinib showed that itch severity is improved, which reduces sleep loss/sleep disruption and, in turn, improves work productivity. CLINICAL TRIAL REGISTRATIONNCT03575871

Autonomously Responsive Membranes for Chemical Warfare Protection

Stimuli-responsive materials offer new opportunities to resolve long-standing material challenges and are rapidly gaining pivotal roles in diverse applications. For example, smart protective garments that rapidly transport water vapor and autonomously block chemical threats are expected to enable an effective new paradigm of adaptive personal protection. However, the incorporation of these seemingly incompatible properties into a single responsive system remains elusive. Herein, a bistable membrane that can rapidly, selectively, and reversibly transition from a highly breathable state in a safe environment to a chemically protective state when exposed to organophosphate threats such as sarin is demonstrated. Dynamic response to chemical stimuli is achieved through the physical collapse of an ultrathin copolymer layer on the membrane surface, which efficiently gates transport through membrane pores composed of single-walled carbon nanotubes (SWNTs). The adoption of nanometer-wide SWNTs for ultrafast moisture conduction enables a simultaneous boost in size-sieving selectivity and water-vapor permeability by decreasing nanotube diameter, thereby overcoming the breathability/protection trade-off that limits conventional membrane materials. Adaptive multifunctional membranes based on this platform greatly extend the active use of a protective garment and present exciting opportunities in many other areas including separation processes, sensing, and smart delivery