Pulling the \u27Trigger\u27 on the Hatch-Waxman Act\u27s 180-Day Exclusivity Using Inter Partes Review, 14 J. Marshall Rev. Intell. Prop. L. 453 (2015)

The America Invents Act has put in place quick and efficient mechanisms for challenging granted patents in an Article I adversarial setting. And the Hatch-Waxman Act has been the roadmap for generic drug approval-related patent infringement action in Article III courts. An interesting, heretofore unaddressed question lurks at an intersection of the two pieces of enterprising legislation: What impact should a final decision canceling patent claims under the AIA setting have on the forfeiture of 180-day exclusivity under the Hatch-Waxman Act? The 180-day exclusivity is an important piece in the Hatch-Waxman game of chess. This comment presents both the case for and against pulling the forfeiture trigger on the 180-day exclusivity via the new AIA setting. Going further, the comment highlights pragmatic and policy justifications for pulling the trigger, thereby proposing grounds for a conformant legislative action

Trial Evaluation Protocol Research Learning Communities (The RLC programme)

The Research Learning Communities programme aims to improve Literacy and Mathematics outcomes of Children in Need (CIN) and Looked After Children (LAC), by supporting Subject Leads, Designated Teachers and year 5 and 6 teachers in primary schools to further develop and implement research-informed teaching strategies. The RLC programme will be developed and delivered by the School of Education in Durham University, between October 2021 and May 2022. Although the programme was previously delivered to schools and was evaluated, it is the first time that it will be focusing on supporting teachers to develop evidence-based teaching strategies specifically for CIN/LAC. To do so, trained facilitators will develop and deliver a series of six workshops, preceded by an introductory session, and closed by a final ‘moving forward’ session, with Subject Leads and Designated Teachers across 240 primary schools in 6 local authorities (LAs). To evaluate the RLC programme, this study will conduct an impact evaluation, an implementation and process evaluation, and a cost analysis using a mixed methods approach. In summary: • The impact evaluation will involve a randomised control trial (RCT) of year 6 pupils’ CIN/LAC KS2 scores in Literacy and Mathematics, supplied by the National Pupil Database (NPD); and an assessment of teachers’ knowledge of academic/action research, attitudes towards the use of research, use of academic/action research in practice, and implementation of improved teaching practices for CIN/LAC, assessed through a pre- and post- teacher questionnaire. • The implementation and process evaluation (IPE) will also draw on the pre- and post- teacher questionnaires, and, in addition, include a series of case studies, (consisting of interviews with school leaders and teachers in intervention and control schools) and observations of RLC workshops. • The cost analysis will collect data on delivery team costs for the implementation of the programme, teacher cover costs to attend RLC workshops and sessions, programme costs (such as costs incurred by virtual schools to recruit schools into the programme), as well as costs for facilities, equipment, and materials, among others. This data will be gathered by the delivery team and through teachers in the teacher questionnaire. Note: Since recruitment for the programme is still ongoing at the time of writing, this trial protocol has been developed based on an estimated number of schools and local authorities provided by the WWCSC. We have also estimated the number of teachers and CIN/LAC per school based on publicly available data. An updated protocol will be published after school recruitment has been finalised

CD4+CD25+ T cells protect against experimentally induced asthma and alter pulmonary dendritic cell phenotype and function

The role of natural CD4+CD25+ regulatory T (T reg) cells in the control of allergic asthma remains poorly understood. We explore the impact of T reg cell depletion on the allergic response in mice susceptible (A/J) or comparatively resistant (C3H) to the development of allergen-induced airway hyperresponsiveness (AHR). In C3H mice, anti-CD25–mediated T reg cell depletion before house dust mite treatment increased several features of the allergic diathesis (AHR, eosinophilia, and IgE), which was concomitant with elevated T helper type 2 (Th2) cytokine production. In similarly T reg cell–depleted A/J mice, we observed a moderate increase in airway eosinophilia but no effects on AHR, IgE levels, or Th2 cytokine synthesis. As our experiments suggested that T reg cell depletion in C3H mice before sensitization was sufficient to enhance the allergic phenotype, we characterized dendritic cells (DCs) in T reg cell–depleted C3H mice. T reg cell–depleted mice had increased numbers of pulmonary myeloid DCs with elevated expression of major histocompatibility complex class II, CD80, and CD86. Moreover, DCs from T reg cell–depleted mice demonstrated an increased capacity to stimulate T cell proliferation and Th2 cytokine production, which was concomitant with reduced IL-12 expression. These data suggest that resistance to allergen-driven AHR is mediated in part by CD4+CD25+ T reg cell suppression of DC activation and that the absence of this regulatory pathway contributes to susceptibility

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Underwater document recognition

In this thesis, we propose an Image Quality Assessment and Comparison metrics for Image denoising algorithms. It is well known that image denoising plays a significant role in various Image related applications. Motivated by this, we attempt to develop Image quality assessment and comparison metrics specifically targeting image denoising algorithms. We have prepared a dataset containing images of text documents with appropriate noise specifically to meet the needs of this project. Images are denoised using different algorithms and then fed into an OCR engine to obtain text, we then compare it with text obtained using ground truth images which do not have any added noise to assess denoised image quality obtained using different algorithms

Development of Adenovirus Containing Liposomes Produced by Extrusion vs. Homogenization: A Comparison for Scale-Up Purposes

Adenovirus (Ad) is a widely studied viral vector for cancer therapy as it can be engineered to cause selective lysis of cancer cells. However, Ad delivery is limited in treating cancers that do not have coxsackievirus and adenovirus receptors (CAR). To overcome this challenge, Ad-encapsulated liposomes were developed that enhance the delivery of Ads and increase therapeutic efficacy. Cationic empty liposomes were manufactured first, to which an anionic Ad were added, which resulted in encapsulated Ad liposomes through charge interaction. Optimization of the liposome formula was carried out with series of formulation variables experiments using an extrusion process, which is ideal for laboratory-scale small batches. Later, the optimized formulation was manufactured with a homogenization technique—A high shear rotor-stator blending, that is ideal for large-scale manufacturing and is in compliance with Good Manufacturing Practices (GMP). Comparative in vitro transduction, physicochemical characterization, long-term storage stability at different temperature conditions, and in vivo animal studies were performed. Ad encapsulated liposomes transduced CAR deficient cells 100-fold more efficiently than the unencapsulated Ad (p ≤ 0.0001) in vitro, and 4-fold higher in tumors injected in nude mice in vivo. Both extrusion and homogenization performed similarly–with equivalent in vitro and in vivo transduction efficiencies, physicochemical characterization, and long-term storage stability. Thus, two Ad encapsulated liposomes preparation methods used herein, i.e., extrusion vs. homogenization were equivalent in terms of enhanced Ad performance and long-term storage stability; this will, hopefully, facilitate translation to the clinic

A Study on Liaison between Boey Score and Perforated Peptic Ulcer in View of Postoperative Morbidity and Mortality

Introduction Several factors associated with poor outcome in perforated peptic ulcer have been identified: delay in diagnosis, coexistent medical illness, shock on admission, leukocytosis, and old age. Such factors increase morbidity and mortality in perforated peptic ulcer disease. Careful resuscitation and perioperative optimization play a significant role in reducing morbidity and mortality associated with perforated peptic ulcer disease. Methods A prospective study of 60 cases who were operated for perforated peptic ulcer was done at Sheth L.G. Municipal General Hospital affiliated with AMCMET Medical College & Research Centre, Ahmedabad. Categorization of these patients was done according to Boey score and their outcome was accessed. Objective The aim of this study was to appraise and analyze Boey score in operated cases of perforated ulcer disease. Results The morbidity and mortality rate in this study were 31.67% and 11.67%, respectively. The morbidity rate increased gradually with increase in Boey score: 8.69, 36.84, 50, and 62.5% for 0, 1, 2, and 3 score, respectively (p < 0.01). The mortality rate was increased progressively with increasing Boey score: 0, 5.26, 30, and 37.5% for 0, 1, 2, and 3 score, respectively, and this relationship was statistically significant (p-value < 0.01). The mean duration of hospital stay was 9.43 ± 4.10 days and p-value was less than 0.001. The area under curve in receiver-operating characteristic curve analysis was 0.854 and 0.751 for mortality and morbidity, respectively. Conclusion Boey score is simple, clinically relevant and can precisely predict postoperative morbidity and mortality and the length of hospital stay

Demographic and histopathologic profile of pediatric brain tumors: A hospital-based study

Background: Very few hospital-based or population-based studies are published in the context to the epidemiologic profile of pediatric brain tumors (PBTs) in India and Indian subcontinent. Aim: To study the demographic and histopathologic profile of PBTs according to World Health Organization 2007 classification in a single tertiary health care center in India. Materials and Methods: Data regarding age, gender, topography, and histopathology of 76 pediatric patients (0–19 years) with brain tumors operated over a period of 24 months (January-2012 to December-2013) was collected retrospectively and analyzed using EpiInfo 7. Chi-square test and test of proportions (Z-test) were used wherever necessary. Results: PBTs were more common in males (55.3%) as compared to females (44.7%) with male to female ratio of 1.23:1. Mean age was 10.69 years. Frequency of tumors was higher in childhood age group (65.8%) when compared to adolescent age group (34.2%). The most common anatomical site was cerebellum (39.5%), followed by hemispheres (22.4%). Supratentorial tumors (52.6%) were predominant than infratentorial tumors (47.4%). Astrocytomas (40.8%) and embryonal tumors (29.0%) were the most common histological types almost contributing more than 2/3rd of all tumors. Craniopharyngiomas (11.8%) and ependymomas (6.6%) were the third and fourth most common tumors, respectively. Conclusion: Astrocytomas and medulloblastomas are the most common tumors among children and adolescents in our region, which needs special attention from the neurosurgical department of our institute. Demographic and histopathologic profile of cohort in the present study do not differ substantially from that found in other hospital-based and population-based studies except for slight higher frequency of craniopharyngiomas