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Background: Immune-mediated necrotising myopathy is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase concentrations, and autoantibodies recognising 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or the signal recognition particle (SRP). No approved therapies exist for people with immune-mediated necrotising myopathy. Previous studies have suggested that complement activation might be pathogenic in immune-mediated necrotising myopathy; therefore, zilucoplan, a complement C5 (C5) inhibitor, could be a potential therapy. We aimed to evaluate the efficacy, safety, and tolerability of zilucoplan in adult participants with anti-HMGCR or anti-SRP autoantibody-positive immune-mediated necrotising myopathy. Methods: IMNM-01 was a phase 2, multicentre, randomised, double-blind, placebo-controlled study done at 15 hospital sites across the USA, the UK, France, and the Netherlands. Participants aged 18?74 years were eligible for inclusion if they had a clinically confirmed diagnosis of immune-mediated necrotising myopathy, positive serology for anti-HMGCR or anti-SRP autoantibodies, clinical evidence of weakness, serum total creatine kinase concentration of more than 1000 U/L at screening, and no change in glucocorticoids or other immunosuppressive therapies for 30 days before baseline or expected during the first 8 weeks of the study. Participants were randomly assigned (1:1) to receive daily subcutaneous zilucoplan (0?3 mg/kg) or placebo for 8 weeks by use of a computerised randomisation algorithm; with optional enrolment in the study open-label extension. Randomisation was stratified by autoantibody status. Participants and study staff were masked to treatment group assignment. Primary efficacy endpoint (in the intent-to-treat population, defined as all participants who were randomly assigned to a treatment group) was percent change from baseline to week 8 in creatine kinase concentrations. Safety analyses were performed on the safety population (participants who received at least one dose of study drug during the main study, irrespective of whether they continued to the extension period?study participants were analysed on the basis of the treatment received). This study is registered with ClinicalTrials.gov, NCT04025632. Findings: Between Nov 7, 2019, and Jan 7, 2021, we randomly assigned 27 participants (13 female and 14 male) to receive zilucoplan (n=12) or placebo (n=15). All 27 participants completed the 8-week main study. At week 8 there were no significant differences between treatment groups in median percent change of creatine kinase concentrations versus baseline (?15?1% [IQR ?31?1 to 3?2] in the zilucoplan group vs ?16?3% [?43?8 to 5?9] in the placebo group; p=0?46) and no clinically relevant improvement over time within the treatment group despite target engagement based on mode of action. There were no unexpected adverse safety or tolerability findings. Treatment-emergent adverse events were reported in nine (75%) of 12 participants in the zilucoplan group, and in 13 (87%) of 15 participants in the placebo group, and serious treatment-emergent adverse events were reported in zero participants in the zilucoplan group and three (20%) participants in the placebo group. The most frequent treatment-emergent adverse events were headache (four [33%] participants in the zilucoplan group and four [27%] participants in the placebo group) and nausea (three [25%] participants in the zilucoplan group and three [20%] participants in the placebo group). Interpretation: C5 inhibition does not appear to be an efficacious treatment modality for people with immune-mediated necrotising myopathy. Rather than being the primary driver for disease activity, complement activation might be secondary to muscle injury. Funding: Ra Pharmaceuticals (now part of UCB Pharma).

This research aims to study the benefits of using the renewable energy in the field of treatment of liquid radioactive waste which is contaminated with a mixture of radionuclides such as Cesium Cs-137, Uranium U-238, Radium Ra-226,etc. which their evaporation degree is too high (more than 600C0 ) . The sun energy as example for renewable energy is used in the process of evaporation of liquid radioactive waste which formed from the decontamination by washing metallic pipes and washing a contaminated soil to convert liquid radioactive waste to more stable and less size radioactive waste in a form of sediment which treated later using cement and then to disposal. The effect of evaporation using sun energy on the human and environment is studied in the laboratory using chemical and radioactive measurement devices. A very good results had been gotten because no level of a radioactive contamination had appeared on the filter which had used in the evaporation process. An electric heater also had used for evaporation process and the results were the same which refers that radioactive nuclides weren't evaporate because of using low temperature. Liquid radioactive waste had distillated, the distillated liquid was measured, and it was clear from any contamination and this shows that there is no diffusion of radionuclides during evaporation process, and in this process the Decontamination Factor (DF) is very high.

تنقسم البلاغة العربية إلی ثلاثة علوم: علم المعاني والبیان والبدیع. یقوم علم المعاني بإيراد الأسالیب المصممة وفقاً لاقتضاء الحال لدی المطلقي، ویعرف بعلم البیان إيراد المعنی الواحد بطرق مختلفة في وضوح الدلالة على ذلك المعنى وعلم البدیع یبحث عن كیفیة تزیین الكلام. لقد تحدث العلماء الكبار في هذا الصدد وقدموا بعض الآراء منهم صفي الدین الحلي. تقوم هذه الدراسة إلی استكشاف وجهات النظر لصفي الدين الحلي الذي یعد عالماً في علم البلاغة عبر المنهج الوصفي - التحليلي لأبيات دیوانه. لذلك بدایةً نقدم كل موضوع من المواضيع البلاغیة التي ذكرها هذا العالم الكبير في أبياته التعلیمیة ثمّ نقارن آراء العلماء الآخرين في هذه المواضيع. عادةً نشاهد الأراء المتشابهة ولكن یبدو أن رؤیة صفي الدین الحلي في بعض الموضوعات لاسیَّما المیزات التي تختص بالمتكلم أوسع من رؤیة بقیة البلاغیین.

Rapid on-site evaluation (ROSE) performed during endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA) has shown significant value. However, ROSE may not be available for some pulmonary centers. Performing ROSE can be challenging and stressful due to time constrains for preparing, staining and reviewing the cytology slides between passes.A retrospective cytology report review of EBUS-FNA procedures performed between October 2014 and May 2019 revealed 516 cases that were included in the study. The number of passes for each procedure was documented. The adequacy rates were assessed at 4 different study points; ≤3 passes, ≤5 passes, at odd passes only, and the even passes only. The study groups results were compared to the overall ROSE and the final cytology adequacy.The overall ROSE interpretation was adequate in 370 (71.7%) and inadequate in 146 (28.3%). After reviewing the Papanicolaou stained slides and cell blocks, the final cytology results were adequate in 473 (91.7%) and inadequate in 43 (8.3%) of the cases. The number of passes per procedure ranged from 1 to 17. Our results showed that ROSE evaluation of the first 5 passes during the EBUS-FNA procedure could achieve the similar adequacy rate compared to the overall ROSE evaluation of all the passes.To achieve the most benefits of ROSE and to reduce the procedure time for EBUS-FNA, we recommend performing ROSE for ≤5 passes depending on the adequacy, and save all additional passes for cell blocks preparation if more than 5 passes are attempted.

It is unknown if patients with neuromuscular diseases prefer in-person or virtual telemedicine visits. We studied patient opinions and preference on virtual versus in-person visits, and the factors influencing such preferences.Telephone surveys, consisting of 11 questions, of patients from 10 neuromuscular centers were completed.Five hundred and twenty surveys were completed. Twenty-six percent of respondents preferred virtual visits, while 50% preferred in-person visits. Sixty-four percent reported physical interaction as "very important." For receiving a new diagnosis, 55% preferred in-person vs 35% reporting no preference. Forty percent were concerned about a lack of physical examination vs 20% who were concerned about evaluating vital signs. Eighty four percent reported virtual visits were sufficiently private. Sixty eight percent did not consider expenses a factor in their preference. Although 92% were comfortable with virtual communication technology, 55% preferred video communications, and 19% preferred phone calls. Visit preference was not significantly associated with gender, diagnosis, disease severity, or symptom management. Patients who were concerned about a lack of physical exam or assessment of vitals had significantly higher odds of selecting in-person visits than no preference.Although neither technology, privacy, nor finance burdened patients in our study, more patients preferred in-person visits than virtual visits and 40% were concerned about a lack of physical examination. Interactions that occur with in-person encounters had high importance for patients, reflecting differences in the perception of the patient-physician relationship between virtual and in-person visits.

Background and ObjectivesThe goal of this work was to determine whether locally acting ACE-083 is safe and well tolerated and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.MethodsThis phase 2 study enrolled adults with CMT1 or CMTX (N = 63). Part 1 was open label and evaluated the safety and tolerability of different dose levels of ACE-083 for use in part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally into the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-m walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests.ResultsIn part 1 (n = 18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious adverse events, TEAEs of grade 3 or greater, or death reported. In part 2 (n = 45 enrolled, n = 44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (least-squares mean difference 13.5%;p= 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate to mild injection-site reactions were the most common TEAEs.DiscussionDespite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo.Trial Registration InformationClinical Trials Registration:NCT03124459.Classification of EvidenceThis study provides Class II evidence that intramuscular ACE-083 is safe and well tolerated and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX.

DMD pathogenic variants for Duchenne and Becker muscular dystrophy are detectable with high sensitivity by standard clinical exome analyses of genomic DNA. However, up to 7% of DMD mutations are deep intronic and analysis of muscle-derived RNA is an important diagnostic step for patients who have negative genomic testing but abnormal dystrophin expression in muscle. In this study, muscle biopsies were evaluated from 19 patients with clinical features of a dystrophinopathy, but negative clinical DMD mutation analysis. Reverse transcription-polymerase chain reactionor high-throughput RNA sequencingmethods identified 19 mutations with one of three pathogenic pseudoexon types: deep intronic point mutations, deletions or insertions, and translocations. In association with point mutations creating intronic splice acceptor sites, we observed the first examples of DMD pseudo 3'-terminal exon mutations causing high efficiency transcription termination within introns. This connection between splicing and premature transcription termination is reminiscent of U1 snRNP-mediating telescripting in sustaining RNA polymerase II elongation across large genes, such as DMD. We propose a novel classification of three distinct types of mutations identifiable by muscle RNA analysis, each of which differ in potential treatment approaches. Recognition and appropriate characterization may lead to therapies directed toward full-length dystrophin expression for some patients.

IntroductionThe COVID 19 pandemic was highlighted by a rise in hospital admissions secondary to respiratory decompensation. This was accompanied by an increase in ICU admissions, endotracheal intubation and mechanical ventilation. As a consequence, tracheostomies became essential in preventing complications of prolonged intubation and to facilitate weaning from sedation and mechanical ventilation. With the lack of international consensus on tracheostomy technique and optimal timing, we present our experience with 377 percutaneous tracheostomies performed on critically ill COVID 19 patients.ObjectiveTo report the outcomes of critically ill patients with COVID-19 who underwent percutaneous tracheostomy during a period of 24 months.MethodsA retrospective single-center electronic chart review was performed on all ICU patients who underwent percutaneous tracheostomy after respiratory failure secondary to COVID-19 between March 2020 to March 2022.ResultsA total of 377 percutaneous tracheostomies were performed. The mean duration between intubation and percutaneous tracheostomy was 17.4 days (3-61). The study included 222 males (59%) and 155 females (41%).The mean age of patients was 56.2 years (17-94), with a mean BMI was 31.3 (14-68).The commonest comorbidities among patients were diabetes mellitus (50%) and hypertension (48%).Complications were encountered in 85 cases (23%), with the commonest overall complication being minor bleeding.203 patients (54%) were weaned from sedation. The mean duration between tracheostomy and weaning from sedation was 7.5 days (1 – 47 days). 156 patients (41%) were weaned from MV. The mean duration between tracheostomy and weaning from MV was 12.9 days (1 – 58 days). There was a total of 236 (63%) deaths reported during the period of this study.No deaths were attributable to the surgical procedure.ConclusionPercutaneous tracheostomy can be safely performed in patients with COVID-19. With lack of conclusive objective data regarding the optimal timing for tracheostomy, we recommend that tracheostomy be performed as soon as possible after the 7thday endotracheal intubation.

The cycle industry, M & U Cycles Ltd is a sister concern of Meghna group was established in 1982 in Gazipur, Dhaka. At Present 600 nos. or above worker works in this M & U Cycles industry. In The Last year from this M & U Cycles industry total 1, 30,000 Pcs bicycle assembled/produced and exported to different countries.The Product of Bicycle which exports from Bangladesh has great opportunities to earn foreign exchanges i.e. foreign currency can be used to develop this country. Now a Days, as per we know the total annual turnover of M & U Cycles Ltd only from export 30 million USD per year .Thats why this is great opportunities by exporting bicycle from Bangladesh.While my study for preparing this internship report it seems to me that particular sector (Bicycles) is very much facing the financial problem. The loan interest rate is too high for the sector to accomplish export processing, and also that sector is very much depended on import of raw materials. It seems to me that M & U Cycles Ltd, is always try to get their sustainable growth in the competitive market. In very recent time the government of Bangladesh has taken some significant decision to face the situation of economic recession. The governments takes a package of Tk 25000-30000 crore in order to priorities protection of the export oriented industries, agricultural growth, employment generation and social security to offset the negative effects of the global economic crisis. They also recommended creation of an export stabilization fund, retention and skill development for returning migrant workers, infrastructure development and simplification and streamliner of rules and procedures to help entrepreneur. According to IMF gradation, Bangladesh ranked as the 48th largest economy in the world in 2008. The economy has grown at the rate of 6.7%. The Bicycles industry sector must be played a very significant role there. In spite of economical recession of the world as well as in the country, M & U Cycles Ltd is one of the participators of earning foreign currency in Bangladesh. In the package are also measures like adoption of effective steps to provide necessary scope and facilities to workers and employees to perform social responsibility by management to fulfill compliance with standards set by the foreign buyers, reducing import dependence through ensuring supply of quality local raw materials in production of Bicycle exports.

Introduction/Aims. Primary lateral sclerosis (PLS) is exceedingly rare and has been an enigmatic disease. Recent progress has drastically changed this perception, with early biomarkers being investigated and potential medications for PLS emerging at the preclinical stage. The aim of this paper is to describe a study of PLS natural history and discuss the limitations and proposed solutions to the study of a rare and slowly progressive disease. Methods. The PLS Natural History Study is a 30-site, 24-month, prospective study that is supported by multiple funding sources. The study aims to enroll 50 early PLS (disease duration ≤4 years) and 50 definite PLS (disease duration 4 to 15 years) participants using modified PLS Diagnostic Criteria. Smartphone-based assessments including semi-quantitative and quantitative measures and patient-reported outcomes are utilized. In-person quantitative measures are also completed during site visits. The change in the PLS Functional Rating Scale score is the primary outcome. The study utilizes the NeuroBANK® patient-centric data capture and management platform. The biostatistical analysis plan has been developed. Results. In one year, 28 participants have been recruited. Enrollment has been much slower than anticipated due to the COVID-19 pandemic, the rarity of PLS, and potential study competition for internal resources from ALS clinical trials. Discussion. We discuss the need for more innovative methods to enroll and study individuals with such rare diseases and propose a number of mechanisms by which more efficient enrollment could be facilitated.

the article suggests a method for constructing classifier of external environmental impacts on functioning of information systems. Defined parameters of external influences on the system, presented using the fuzzy machine sets, and fuzzy rules are developed classifier.

A patient who has fully recovered from COVID-19 can help patients currently fighting infection by donating plasma. Because it is an infection killer, the plasma now contains antibodies against COVID-19. These antibodies provided the immune system with one way to fight the virus when it was sick, so plasma can be used to fight diseases. Therefore, this paper monitoring recovering patients based on the clustering of data and classifying them using fuzzy hierarchical clustering to reach the plasma as soon as possible.

In urban-traffic scenarios, massive mobile terminals can provide more comprehensive and accurate environmental sensing data with various built-in sensors. Humans can also collect environmental information as task executors. Therefore, facing different sensing requirements from environmental monitoring, intelligent transportation, urban management, and other fields, if we make good use of the sensing abilities of mobile terminals and humans, we can provide more supporting data for them. This paper proposes a multitasking-oriented participant-recruitment algorithm for vehicular crowd sensing based on the Combine-S algorithm that could merge-common sensing requirements in the time and space dimensions to solve the problem of overlapping requirements among multiple tasks. Combine-S could also be integrated with a greedy recruitment algorithm to improve the sensing effect and reduce sensing costs. We used the OMNet++ simulators that are used for simulating urban transportation and IoTKeywords-Genetic Algorithm, NSL-KDD, Intrusion Detection system, Fast Learning Network.

Importance Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life. Objective To evaluate the clinical effects of zilucoplan, a subcutaneously (SC) self-administered macrocyclic peptide inhibitor of complement component 5, in a broad population of patients with moderate to severe gMG. Design, Setting, and Participants This randomized, double-blind, placebo-controlled phase 2 clinical trial at 25 study sites across North America recruited participants between December 2017 and August 2018. Fifty-seven patients were screened, of whom 12 did not meet inclusion criteria and 1 was lost to follow-up after randomization but before receiving study drug, resulting in a total of 44 acetylcholine receptor autoantibody (AChR-Ab)–positive patients with gMG with baseline Quantitative Myasthenia Gravis (QMG) scores of at least 12, regardless of treatment history. Interventions Patients were randomized 1:1:1 to a daily SC self-injection of placebo, 0.1-mg/kg zilucoplan, or 0.3-mg/kg zilucoplan for 12 weeks. Main Outcomes and Measures The primary and key secondary end points were the change from baseline to week 12 in QMG and MG Activities of Daily Living scores, respectively. Significance testing was prespecified at a 1-sided α of .10. Safety and tolerability were also assessed. Results The study of 44 patients was well balanced across the 3 treatment arms with respect to key demographic and disease-specific variables. The mean age of patients across all 3 treatment groups ranged from 45.5 to 54.6 years and most patients were white (average proportions across 3 treatment groups: 78.6%-86.7%). Clinically meaningful and statistically significant improvements in primary and key secondary efficacy end points were observed. Zilucoplan at a dose of 0.3 mg/kg SC daily resulted in a mean reduction from baseline of 6.0 points in the QMG score (placebo-corrected change, –2.8;P = .05) and 3.4 points in the MG Activities of Daily Living score (placebo-corrected change, –2.3;P = .04). Clinically meaningful and statistically significant improvements were also observed in other secondary end points, the MG Composite and MG Quality-of-Life scores. Outcomes for the 0.1-mg/kg SC daily dose were also statistically significant but slower in onset and less pronounced than with the 0.3-mg/kg dose. Rescue therapy (intravenous immunoglobulin or plasma exchange) was required in 3 of 15, 1 of 15, and 0 of 14 participants in the placebo, 0.1-mg/kg zilucoplan, and 0.3-mg/kg zilucoplan arms, respectively. Zilucoplan was observed to have a favorable safety and tolerability profile. Conclusions and Relevance Zilucoplan yielded rapid, meaningful, and sustained improvements over 12 weeks in a broad population of patients with moderate to severe AChR-Ab–positive gMG. Near-complete complement inhibition appeared superior to submaximal inhibition. The observed safety and tolerability profile of zilucoplan was favorable. Trial Registration ClinicalTrials.gov Identifier:NCT03315130.