ENTERPRET: A Randomized Controlled Trial of Vedolizumab Dose Optimization in Patients With Ulcerative Colitis Who Have Early Nonresponse.

BACKGROUND & AIMS: Patients with ulcerative colitis (UC) may experience nonresponse to biologics, possibly as a result of low drug exposure. This trial assessed the efficacy of dose optimization in patients with UC who have early nonresponse to vedolizumab and high drug clearance. METHODS: ENTERPRET was a phase 4, open-label, randomized, controlled trial that included patients with moderate to severe UC who had high drug clearance at week 5 (serum concentration, <50 µg/mL) and nonresponse to standard vedolizumab treatment at week 6. At week 6, eligible patients were randomized 1:1 to receive standard dosing (300 mg every 8 weeks) or dose-optimized vedolizumab (600 mg at week 6, then 300 mg every 4 weeks; or 600 mg at week 6, then 600 mg every 4 weeks [based on week 5 serum concentration]). The primary end point was endoscopic improvement at week 30. RESULTS: Of 278 enrolled patients, 132 (47.5%) had a clinical response at week 6. From week 6, 108 patients received standard (n = 53) or dose-optimized vedolizumab (n = 55); among patients with nonresponse at week 6, 86.5% had high drug clearance. At week 30, 10 patients (18.9%) who received standard vedolizumab had endoscopic improvement vs 8 patients (14.5%) who received dose-optimized vedolizumab. Five patients (9.4%) who received standard vedolizumab had clinical remission at week 30 vs 5 patients (9.1%) who received dose-optimized vedolizumab; clinical response was observed in 17 (32.1%) and 17 patients (30.9%), respectively. Safety event rates were similar among treatment groups. CONCLUSIONS: In patients with early nonresponse and high drug clearance, vedolizumab dose optimization is probably not required. A proportion of patients benefited from continued treatment irrespective of the dose received. CLINICALTRIALS: gov: NCT03029143.

Vedolizumab, Adalimumab, and Methotrexate Combination Therapy in Crohn's Disease (EXPLORER).

BACKGROUND & AIMS: Although biologics have revolutionized the treatment of Crohn's disease (CD), an efficacy ceiling has been reached. Combining biologic therapies may improve remission rates. METHODS: EXPLORER, a phase 4, single-arm, open-label study, evaluated triple combination therapy with vedolizumab (300 mg on day 1, weeks 2 and 6, and then every 8 weeks), adalimumab (160 mg on day 2, 80 mg at week 2, then 40 mg every 2 weeks), and methotrexate (15 mg weekly) in biologic-naïve patients with newly diagnosed, moderate- to high-risk CD. Endoscopic remission at week 26 (primary end point; Simple Endoscopic Score for CD ≤2), clinical remission at weeks 10 and 26 (secondary end point; Crohn's Disease Activity Index <150), and incidences of adverse events and serious adverse events were evaluated. RESULTS: Among 55 enrolled patients, the mean CD duration was 0.4 years, the mean baseline Simple Endoscopic Score for CD was 12.6, and the mean baseline Crohn's Disease Activity Index was 265.5. At week 26, 19 patients (34.5%) were in endoscopic remission. At weeks 10 and 26, 34 (61.8%) and 30 patients (54.5%), respectively, were in clinical remission. Post hoc Bayesian analysis showed that the probabilities that triple combination therapy produced a higher endoscopic remission rate (33.5%; 95% credible interval, 22.4-45.7) than placebo (14%), vedolizumab monotherapy (27%), or adalimumab monotherapy (30%) were 99.9% or higher, 86.3%, and 71.4%, respectively. Six patients had serious adverse events. CONCLUSIONS: Combination therapy resulted in endoscopic and clinical remission at week 26 in 34.5% and 54.5% of patients, respectively, with no safety signal related to the treatment regimen. This supports further evaluation of combination therapy in CD. CLINICALTRIALS: gov number: NCT02764762.

A Color Tunable Quantum-Dot Light-Emitting Diode Device Driven by Variable Voltage.

A hole transporting layer (HTL) consisting of poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(4-sec-butylphenyl)diphenylamine)] doped with 4,4'-Bis(9H-carbazol-9-yl)biphenyl was designed for high-performance multicolor quantum-dot light-emitting diode (QLED) fabricated by an all-solution process technique. The band structure of the HTL is tailored via small molecule doping to create a cascade of highest occupied molecular orbital levels (HOMO) from the hole injection layer to the quantum-dot emissive layer (EML). This energy band tailoring significantly overcomes the energy barrier for hole injection and enables multicolor emission from a single device, which consists of mixture of red, green, and blue QDs as EML. The color tunability as a function of applied voltage is the most novel feature of our device. The color tunability was observed at a voltage of 2 V for red emission, 3 V for orange, 4 V for yellow and 6 V for greenish white and a high brightness of 15,000 cd m-2 was demonstrated for white emission, which is attributed to the efficient and balanced carriers' injection into the EML. The strategy of using tunable HOMO of the HTL in combination with color tunability of the EML as a function of applied voltage, pushes QLED a step closer to practical multicolor display applications.

Clinical Trial Design in Ulcerative Colitis: Interpreting Evolving Endpoints Based on Post Hoc Analyses of the Vedolizumab Phase 3 Trials GEMINI 1 and VISIBLE 1.

Background: The 12-point total Mayo score including a Physician's Global Assessment (PGA) of disease activity has been used to assess outcomes in clinical trials for ulcerative colitis (UC). In 2016, the US Food and Drug Administration (FDA) issued guidance advising the removal of the PGA in future trials. We examined how endpoints in UC trials have evolved and conducted a post hoc analysis of the GEMINI 1 and VISIBLE 1 trials to understand how the use of a 9-point modified Mayo score, excluding PGA, compares with the total Mayo score. Methods: Endpoint definitions of clinical remission in phase 3 trials were extracted from published literature and ClinicalTrials.gov. The difference (%Δ) between the proportions of patients in GEMINI 1 and VISIBLE 1 achieving clinical remission with vedolizumab versus placebo at week 52 was measured according to 4 endpoint definitions. Results: Trials completed up to the end of 2019 used the total Mayo score to assess clinical remission. Most trials that were completed or estimated to be completed by June 2020 or later used modified Mayo scores. Post hoc analysis revealed decreasing endpoint stringency was associated with increasing %Δ values. The modified Mayo score definition most like the definition recommended by the FDA produced %Δ values like those reported using the total Mayo score in GEMINI 1 and VISIBLE 1. Conclusions: Endpoint definitions for UC clinical trials have evolved following FDA guidance. The efficacy of vedolizumab, measured using modified Mayo scoring, was comparable to values reported using the total Mayo score.

Quantum dots for light emitting diodes.

In this article we discuss the development and key advantages of quantum dot based light emitting diode (QD-LED) and other applications based on their color purity, stability, and solution processibility. Analysis of quantum dot based LEDs and the main challenges faced in this field, such as the QD luminescence quenching, QD charging in thin films, and external quantum efficiency are discussed in detail. The description about how different optical down-conversion and structures enabled researchers to overcome these challenges and to commercialize the products. The recent developments about how to overcome these difficulties have also been discussed in this article.

Enhanced electrical efficiency of quantum dot based LEDs with TiO2 as the electron transport layer fabricated under the optimized annealing-time conditions.

We report Quantum dot based light emitting diodes (QD-LEDs) fabricated under the optimized annealing conditions of TiO2 films used as the electron transport layer (ETL) in the device. Films of different thicknesses were fabricated by varying annealing conditions leading to the improved electrical properties in QD-LEDs. Under the optimized annealing conditions both the turn-on voltage and voltage-drop across the device were minimized as a result of the increased electrical conductivity of ETL. Due to the minimum turn-on voltage and voltage-drop across the device the overall electrical performance of QD-LED device in our case has been improved by 81.5 percent.

Retroreflection and diffraction of a Bose-Einstein condensate by evanescent standing wave potential.

The characteristic of the angular distributions of accelerated Bose-Einstein condensate (BEC) atoms incidence on the surface is designed using the mathematical modeling method. Here, we proposed the idea to study retroreflection and diffraction of a BEC from an evanescent standing wave potential (ESWP). The ESWP is formed by multiple reflections of the laser beam from the surface of the prism under the influence of gravity. After BEC's reflection and diffraction, the so-called BEC's density rainbow patterns develop due to the interference which depends on the surface structure which we model with the periodic decaying evanescent field. The interaction of accelerated bosonic atoms with a surface can help to demonstrate surface structures or to determine surface roughness, or to build future high spatial resolution and high sensitivity magnetic-field sensors in two-dimensional systems.

A Novel Phototransistor Device with Dual Active Layers Composited of CsPbBr3 and ZnO Quantum Dots.

Taking advantage of a large light absorption coefficient, long charge carrier diffusion length and low-cost solution processing, all-inorganic halides perovskite CsPbBr3 quantum dots (QDs) are combined with a ZnO QD film to construct a high-performance photodetector. In this work, a novel photodetector device based on transistor structure with dual active layers composed of CsPbBr3 and ZnO film is proposed. In this structure, CsPbBr3 film functions as the light-absorbing layer and ZnO film acts as the conducting layer. Owing to the high electron mobility and hole-blocking nature of the ZnO QDs film, the photo-induced electron-hole pairs can be separated efficiently. As a result, the device exhibits high performance with response of 43.5 A/W, high detection up to 5.02 × 1011 Jones and on/off ratio of 5.6 × 104 under 365 nm light illumination. Compared with the ZnO-only phototransistor (the photodetector with the structure of transistor) the performance of the CsPbBr3 phototransistor showed significant improvement, which is superior to the majority of photodetectors prepared by perovskite. This work demonstrates that the ZnO QDs film can be applied in the photodetector device as a functional conducting layer, and we believe that the hybrid CsPbBr3/ZnO phototransistor would promote the development of low-cost and high-performance photodetectors.

Chloroquine resistant malaria in neonates.

OBJECTIVE: To analyze the clinical presentation, treatment given, and outcome of patients suffering from congenital and acquired malaria in neonatal period. DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Paediatrics Ward-2, QAMC/BVH, Bahawalpur for 02 years from October 2001 to October 2003. PATIENTS AND METHODS: The study included 45 cases of neonatal malaria. Thirty cases of malaria, admitted during first ten days of life, diagnosed as congenital malaria, were kept in group A, while 15 cases admitted in the ward from the age of 11 to 28 days, labeled as acquired malaria, were named group B. The clinical features at the time of presentation were noted in each group from the charts having positive malarial parasite (M.P.) on thick and thin slides. The diagnosed cases were treated with the standard dose of chloroquine sulphate. Those patients who improved clinically as well as revealed no parasite on follow-up were labeled as chloroquine sensitive. On the other hand, patients showing poor clinical response with persistence of the parasites in the blood or initially disappearing but later again having a clinical disease with positive M.P. on follow-up, were labeled as chloroquine resistant. They were treated with quinine sulphate. Outcome was compared in both the groups regarding the pattern of chloroquine resistance and death/ survival. Data was collected on which Fischer's exact test of significance was performed to know the level of significance. P-value of < 0.05 was taken as statistically significant. RESULTS: Low birth weight, severe hemolytic anemia with history of fever in the mother were main features in group A while in group B fever, anaemia and history of blood transfusion were marked features. In group A 76.66% were caused by Plasmodium (P.) falciparum. While in group B 60% were caused by Plasmodium vivax. In group A 26.66% were chloroquine resistant while 33.65% were chloroquine resistant in group B. The mortality was 16.66% in group A and 13.33% in group B. CONCLUSION: Intrauterine growth retardation, hemolytic jaundice and history of fever in the mother in the last trimester of pregnancy in the congenital while fever, history of blood transfusion in the neonates in acquired malaria but pallor in both the groups, were important clinical features. Pattern of chloroquine resistance and mortality in both the groups was not statistically different.

Flexible photovoltaic cells based on a graphene-CdSe quantum dot nanocomposite.

We have fabricated the flexible photoelectrode by loading graphene sheets modified with CdSe QDs. A power conversion efficiency of ∼0.6% and an incident photon to current conversion efficiency of 17% have been achieved for this flexible photovoltaic cell based on a graphene-CdSe nanocomposite.

Safety, immunogenicity and dose ranging of a new Vi-CRM197 conjugate vaccine against typhoid fever: randomized clinical testing in healthy adults.

BACKGROUND: Typhoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute for Global Health developed a conjugate vaccine (Vi-CRM197) for infant vaccination concomitantly with EPI vaccines, either starting at 6 weeks with DTP or at 9 months with measles vaccine. We report the results from a Phase 1 and a Phase 2 dose ranging trial with Vi-CRM197 in European adults. METHODOLOGY: Following randomized blinded comparison of single vaccination with either Vi-CRM197 or licensed polysaccharide vaccines (both containing 25·0 µg of Vi antigen), a randomised observer blinded dose ranging trial was performed in the same center to compare three concentrations of Vi-CRM197 (1·25 µg, 5·0 µg and 12·5 µg of Vi antigen) with the polysaccharide vaccine. PRINCIPAL FINDINGS: All vaccines were well tolerated. Compared to the polysaccharide vaccine, Vi-CRM197 induced a higher incidence of mild to moderate short lasting local pain. All Vi-CRM197 formulations induced higher Vi antibody levels compared to licensed control, with clear dose response relationship. CONCLUSIONS: Vi-CRM197 did not elicit safety concerns, was highly immunogenic and is therefore suitable for further clinical testing in endemic populations of South Asia. TRIAL REGISTRATION: ClinicalTrials.gov NCT01123941 NCT01193907.

Effect of different growing media on the growth and development of Dahlia (Dahlia pinnata) under the agro-climatic condition of Dera Ismail Khan.

An experiment was conducted to investigate the effect of different growing media on the growth and development of Dahlia (Dahlia pinnata). Seven different growing media including sand, silt, leaf mold, sand + silt, sand + leaf mold, silt + leaf mold and sand + silt + leaf mold, were used to check the growth and development of dahlia in pots. The over all best performance was recorded in media sand + silt + leaf mold for almost all the parameters; plant height (42.08 cm), stem thickness (1.93 cm), number of branches per plant (3.6), minimum days to flowering (91.66), number of flowers per plant (10.6), number of petals per flower (13), diameter of flower (8.8 cm) and vase life of flower (5 days). The media leaf mold alone also performed significantly well for all the parameters including the maximum 42.55 leaves per plant. Sand, when used alone as a growing medium showed the least response and provided unsatisfactory results for all the parameters.