Bovine tuberculosis (bTB) challenges intensive dairy production in Ethiopia and implementation of the test and slaughter control strategy is not economically acceptable in the country. Vaccination of cattle with Bacillus Calmette-Guerin (BCG) could be an important adjunct to control, which would require a diagnostic test to differentiate Mycobacterium bovis (M. bovis)-infected and BCG-vaccinated animals (DIVA role). This study describes evaluation of a DIVA skin test (DST) that is based on a cocktail (DSTc) or fusion (DSTf) of specific (ESAT-6, CFP-10 and Rv3615c) M. bovis proteins in Zebu-Holstein crossbred cattle in Ethiopia. The study animals used were 74 calves (35 BCG-vaccinated and 39 unvaccinated) aged less than three weeks at the start and 68 known bTB positive cows. Six weeks after vaccination, the 74 calves were tested with DSTc and the single intradermal cervical comparative tuberculin (SICCT) test. The cows were tested with DSTc and SICCT test. Reactions to DSTc were not observed in BCG-vaccinated and unvaccinated calves while SICCT test reactions were detected in vaccinated calves. DSTc reactions were detected in 95.6% of the cows and single intradermal tuberculin (SIT) positive reactions were found in 98.2% (95% confidence interval, CI, 92.1–100%). The sensitivity of DSTc was 95.6% (95% CI, 87.6–99.1%), and significantly (P<0.001) higher than the sensitivity (75%, 95% CI, 63.0-84.7%) of the SICCT test at 4mm cutoff. DSTf and DSTc reactions were correlated (r = 0.75; 95% CI =0.53–0.88). In conclusion, DSTc could differentiate M. bovis-infected from BCG-vaccinated cattle in Ethiopia. DST had higher sensitivity than the SICCT test. Hence, DSTc could be used as a diagnostic tool for bTB if BCG vaccination is implemented for the control of bTB in Ethiopia and other countries.

Mitral annular disjunction (MAD) is a structural abnormality of the mitral annulus, defined by a detachment of the atrial wall-mitral valvular junction from the left ventricular (LV) free wall. This structural abnormality in mitral annulus fibrosus is significantly associated with the presence of mitral valve prolapse (MVP) [1], but it can be also detected in normal cases as an anatomical variation of the mitral annulus fibrosus [2]. The main tools to detect MAD are echocardiography and cardiac magnetic resonance. Prevalence of MAD in the general population ranges from 7% [1] to 9% [2]. Several studies proved an association between MAD and arrhythmic events, independently of concomitant mitral valve abnormalities, suggesting the existence of a novel entity: MAD arrhythmic syndrome [3]. Herein we describe a case report of a middle age man with MAD who experienced ventricular arrhythmias and placement of an implantable cardioverter-defibrillator (ICD).

For 50 years, researchers have considered how time-dependent environmental effects can be included in cycle-dependent corrosion fatigue (CF) crack growth rate (CGR) models. Common assumptions are that cycle- and time-dependent contributions are separable, operate in parallel, are non-interacting and that total environmental CGR can be obtained by linear summation of cycle-dependent fatigue and time-dependent (SCC) CGRs. However, considered here are data and analyses that show that environmental CGRs may be greater than predicted by superposition models. A phenomenological model is developed to quantify the effect of crack-tip strain-rate due to fatigue stress-cycles on electrochemical activity at a crack tip and thereby synergistically increase crack growth rates by a cyclic-stress corrosion-cracking (C-SCC) mechanism.

Deep reinforcement learning (DRL) algorithms are rapidly making inroads into fluid mechanics, following the remarkable achievements of these techniques in a wide range of science and engineering applications. In this paper, a deep reinforcement learning (DRL) agent has been employed to train an artificial neural network (ANN) using computational fluid dynamics (CFD) data to perform active flow control (AFC) around a 2-D circular cylinder. Flow control strategies are investigated at a diameter-based Reynolds number Re_D = 100 using advantage actor-critic (A2C) algorithm by means of two symmetric plasma actuators located on the surface of the cylinder near the separation point. The DRL agent interacts with the computational fluid dynamics (CFD) environment through manipulating the non-dimensional burst frequency (f+) of the two plasma actuators, and the time-averaged surface pressure is used as a feedback observation to the deep neural networks (DNNs). The results show that a regular actuation using a constant non-dimensional burst frequency gives a maximum drag reduction of 21.8 %, while the DRL agent is able to learn a control strategy that achieves a drag reduction of 22.6%. By analyzing the flow-field, it is shown that the drag reduction is accompanied with a strong flow reattachment and a significant reduction in the mean velocity magnitude and velocity fluctuations at the wake region. These outcomes prove the great capabilities of the deep reinforcement learning (DRL) paradigm in performing active flow control (AFC), and pave the way toward developing robust flow control strategies for real-life applications.

37-year-old man presented to the emergency department with a three-hour history of severe, generalized abdominal pain. Computed tomography of abdomen revealed two distal ileoileal intussusceptions with high suspicion of 3 cm mass within the intussusception around the ileocecal region. Laparoscopic right hemicolectomy with extracorporeal ileocolic anastomosis which showed Meckel

Management of nutritional needs is of paramount importance in cancer patients and nasogastric feeding is the most common method. Nasal cavity being a richly innervated region, is also a hallway for the exposure of the same to external environment. Any trauma or pressure to these nerve endings result in unilateral headache mimicking Sluder’s neuralgia. Nasogastric tube may irritate the nasal mucosa and exert pressure on the nasal turbinates. We believe that the persistent headache in patients with NG tube is distinctly significant that it interferes with the physical comfort of patient. It also influences the sleep patterns, thereby causing repercussions in the emotional well-being. Head and neck oncologists being the primary clinicians, it is imperative to consider the Sluder’s neuralgia in patients with nasogastric tube feeding. This mandates a prospective study to describe the clinical features and the treatment of ‘NGT neuralgia’.

We report a patient with cardiogenic shock (CS) in the course of acute right ventricular myocardial infarction (MI). Our case highlights the use of continuous veno-venous hemofiltration as a novel treatment option for acute kidney injury in the setting of CS and the use of rotational_atherectomy in patients with MI.

Promoting the application potential of graphenes in biomolecule adsorption and detection is of great significance in the field of nanobiotechnology. In this paper, the density functional theory calculation was used to study the adsorption and sensing of L-cysteine on graphene-based compounds, single-vacancy and double-vacancy graphenes (XSV and XDV) doped with 3p-bolck elements (Al, Si, P, and S). Along with the dopant changing from Al to S, XSV exhibits decreasing exothermical chemisorption to endothermical chemi-sorption, while XDV exhibits decreasing exothermical chemisorption to endothermical physisorption. L-cysteine adsorption on XDV is weaker than corresponding adsorption on XSV. Valence electron number, and atomic ionization potential, modulated by the 3p-block dopant, and X-C interaction, modulated by the vacancy type, contribute to adsorption mechanism of L-cysteine on XGs. The study could facilitate applications of Al, Si, P and S doped graphenes in biosensing technology, biomolecule immobilization, bioseparation and other fields.

Abstract Generally, investigations on nanomedicine involve conventional imaging techniques for obtaining static images on nanoparticle internalization at a single time point where various phases can be overlooked. In contrast, 3D live-cell imaging can be used for obtaining cellular retention of drugs at various phases, and cells can be followed for days. This article demonstrates the application of time-lapse microscopy in the investigation of Poly-L-lysine coated ZnO nanoparticle dynamics. In this work, a laser scanning confocal microscope has been employed to quantify the dynamics of internalization particles and reactive oxygen species generation (ROS) using volumetric imaging. Firstly, we show that simultaneous spatial mapping of nanoparticle uptake in MCF-7 cells and ROS in a single cell can be used to identify the interdependence between the accumulation of particles and ROS generation. Secondly, monitoring of ROS formation and cytotoxicity using the same imaging platform offers an advantage over monitoring these parameters using various instruments. Finally, the ability of the fluorescent particles in inducing a significant reduction in cell viability suggests its potential to be used as a therapeutic agent. The proposed framework opens up a new avenue of research for investigating mechanistic aspects of ZnO particle adsorption in vitro through long term imaging. Keywords: Fluorescent ZnO particle, Time-lapse microscopy, 3D Live-cell imaging, laser scanning confocal microscope, Reactive oxygen species

Bronchopulmonary dysplasia (BPD) was first described by Northway et al in 1967. This article describes the evolution of our understanding of the pathophysiology of BPD and the approaches to treatments of this illness developed over the past fifty years. These interventions had their roots in the understanding of the principles of the surface tension present at air- liquid interfaces, which were developed over 150 years before BPD’s initial description. Improving outcomes in neonatal care have led to greater survival of preterm and very preterm infants, and to an evolution of the pathogenesis and pathology of BPD, from an illness caused primarily by barotrauma and oxygen toxicity to one of interruption of lung development. While the incidence of BPD has remained about the same in recent decades, this is because survival of infants born at lower gestational ages is increasing. Understanding of molecular, genetic and physiologic mechanisms has led to newer treatments that have mitigated some of the harmful effects of prolonged mechanical ventilation. Recognition of BPD as a chronic multi-system disease has resulted in further improvements in care after discharge from neonatal intensive care. Since many of the origins of chronic obstructive lung disease in adults are based in childhood respiratory illnesses, improving outcomes of BPD in infancy and childhood will undoubtedly lead to improved respiratory outcomes in the adults that these children will become.

Rationale, aims and objectives: Clinical incident reports are the primary means by which UK hospitals are alerted to avoidable harm in healthcare. However, data demonstrating the patterns in real-world reporting by healthcare workers have never been published in the UK. Though this journal has previously published survey data describing the discrepancies between respondents’ own behaviour compared to the incidence of perceived avoidable harm, we set out to collect data on actual reporting patterns between healthcare workers. Given the concerns raised by Robert Francis following the Mid-Staffordshire Inquiry, we specifically wished to examine the rate of reporting of doctors compared to other healthcare workers. Methods: We selected for incidents causing at least ‘moderate’ levels of harm, theorising that such levels of harm are most likely to be noticed by doctors. Data from 2011 to 2019 from the clinical governance departments of 2 NHS hospitals was requested and all available data subsequently charted. Results: This is the first study examining NHS incident reporting patterns in the medical profession. We demonstrated a stark level of underreporting of clinical incidents causing harm ranging from ‘moderate’ to death by doctors. This was particularly dramatic at the non-consultant grade level. In 1 hospital, only 2 deaths were reported by non-consultant grade doctors in 6 years. Notably 1 hospital had not stored any incident reporting data until 2017. Conclusion: The reporting behaviour of doctors has not significantly changed despite the Francis Reports. This could be improved by creating incentives for doctors to engage with patient safety initiatives and disclosure of error, as well as the use of automated systems.

Atrial fibrillation (AF) remains a growing problem in the United States and worldwide, imposing a high individual and health system burden, including increased resource consumption due to repeated hospitalizations, stroke, dementia, heart failure, and death. This comprehensive review summarizes the most recent data on sex-related differences in risks associated with AF. Women with AF have increased risk of stroke and death compared to men, and possible reasons for this disparity are explored. Women also continue to have worse symptoms and quality of life, and poorer outcomes with stroke prevention, as well as with rate and rhythm control management strategies. Many current rhythm control treatment strategies for AF, including cardioversion and ablation, are used less frequently in women as compared to men, whereas women are more likely to be treated with rate control strategies or anti-arrhythmic drugs. Sex differences should be considered in treating women with AF to improve outcomes and women and men should be offered the same interventions for AF. We need to improve the evidence base to understand if variation in utilization of rate and rhythm control management between men and women represents health inequities or appropriate clinical judgement.

i. Rationale, Aims and Objectives: Despite guideline recommendations against their use, clinicians prescribe benzodiazepines for various symptoms to patients with posttraumatic stress disorder (PTSD). Clinicians’ reasons in making these decisions are not fully understood. This qualitative study sought to characterize factors identified by prescribing clinicians in clinical decision making in PTSD regarding the use of benzodiazepines. ii. Methods: The descriptive study involved semi-structured interviews with 26 prescribing clinicians across thirteen VA medical centers. Our overall aim in the study was to explore clinicians’ benzodiazepine practices in veterans with a PTSD diagnosis. We audio-recorded, transcribed, and analyzed the interviews using grounded theory methodology. iii. Results: Facilitators and barriers that contribute to benzodiazepine prescribing to veterans with PTSD included organizational, provider, and patient aspects. Most providers interviewed indicated that they inherited patients already on these medications initiated by other clinicians. These providers, as well as others interviewed, voiced concerns that tapering benzodiazepines may cause more harm than the risks of maintenance, particularly in older patients. Clinicians who noted consistent treatment practices among their hospital colleagues found it easier to decrease both new and maintenance benzodiazepine prescribing. iv. Conclusions: Patients with PTSD at increased risk of harms, such as older patients, are still receiving benzodiazepines suggesting that innovative solutions are now needed to decrease use. Specific protocols for inherited patient caseloads, increased dissemination of effective psychotherapies for symptoms such as insomnia and anxiety and the use of direct to consumer educational materials should help to foster needed culture change and increased evidence-based PTSD practice.

Background: To assess the efficacy and prognosis of computed tomography (CT)-guided 125I radioactive seeds implantation brachytherapy (RSI-BT) for recurrent nasopharyngeal carcinoma (NPC) after external beam radiotherapy (EBRT). Methods: Thirty-one patients with recurrent NPC (forty-one lesions) after EBRT from February 2003 to January 2019 were enrolled in this retrospective study. The work-follow of CT-guidance RSI-BT was: indication selection, patient set-up and immobilization on CT couch, CT-simulation, preoperative planning, prescription doses (PD) definition of 110-160Gy, seed implantation, postoperative dosimetric evaluation and postoperative follow-up. Median radioactivity of RSI was 0.43 (range 0.22-0.79, average 0.61) mCi. Median actuarial number of 125I seeds was 24 (range 3-83, average 37). Median value of post-operative D90 was 118.5 (range 62.4-246, average 136.2) Gy. Local control (LC) and overall survival (OS) were investigated for their relationship with the prognosis. The adverse events were evaluated by the Radiation Therapy Oncology Group (RTOG) classification criteria. Results: Median follow-up was 41.9 (range 2.1-60.2, average 44.1) months. Median LC was 35.8 (range 2.1-60.2, average 34.9) months. LC at 1-, 3- and 5-year was 71.3%, 41.9% and 27.9%, respectively. Median OS was 22.6 (range 2.1~60.2, average 27.1) months. OS at 1-, 3- and 5-years was 57.7%, 23.8% and 11.9%, respectively. Univariate analysis suggested that sex (P=0.037) and frequency of previous EBRT (P=0.001) were prognostic factors influencing LC. Moreover, univariate analysis also suggested that frequency of previous EBRT (P=0.012) was prognostic factors influencing OS. Prevalence of side effects (≥grade 3) was 6.5%. Conclusion: 125I RSI-BT was a safe and feasible salvage treatment for recurrent NPC after EBRT. Key words: recurrent nasopharyngeal carcinoma; External beam radiotherapy; 125I seed implantation brachytherapy; overall survival; local control; side effects.

Background: Bedqauiline (BDQ) is a relatively new agent for multidrug (MDR) and extremely drug resistant (XDR) TB. It is important to look for cardiac safety and the bizarre adverse reactions after initiation of the drugs from the real world studies. Methods: An observational study was conducted on the institutionalized MDR and XDR patients under the conditional access program of BDQ in India. Daily ECG, adverse events and change in laboratory values for first two weeks were recorded with mortality and serious adverse events till first three months of initiation of BDQ containing regimen. Results: Among the total of 49 patients, nausea (n=33) was the most reported side effect. Though a mean rise of QTcF (12%) was noted after 14 days, individually, both prolongations (QTcF >440 ms) and shortening (from baseline values) of QTcF were noted in 95.92% (n=47) and 89.8% (n=44) patients. Three distinct QT patterns noted in ECG were, a) initial rise then fall (n=8), b) initial fall then rise (n=9) and c) rise followed by further rise (32). There was no serious adverse event leading to drug withdrawal or mortality in the first three months. Conclusions: Prolongation of QTcF occurs in alarming numbers during first two weeks of BDQ therapy as well as shortened QT. However, BDQ was otherwise tolerated well by the real world MDR & XDR-TB patients in short term. Intensive ECG and clinical monitoring is recommended to detect possible serious implications of such ECG changes in the long term.

Objectives: In this study, we designed a new technique for open septal reduction using a polydioxanone (PDS) plate and compared it with closed reduction. Design, Setting, Participants: This study included nineteen consecutive patients with nasoseptal fracture: ten receiving open reduction with a PDS plate (PDS group) and nine undergoing closed reduction (CR group). Open septal reduction was performed after closed reduction for nasal bone fracture. A mucoperichondrial flap was unilaterally elevated, and the deviated septal cartilage was reduced. The PDS plate was inserted horizontally above the vomerine suture. Surgical outcome was analyzed with three-dimensional volumetry and with a quality-of-life scale for nasal obstruction (NOSE scale). Results: Complications included one case of septal perforation in the CR group and one case of PDS exposure and septal hematoma in the PDS group. In the 3D volumetric analysis of the PDS group, the median value of the nasal cavity change significantly differed between 1.14 mL (interquartile range; 0.46 to 2.4) at the preoperative CT scan and 0.33 mL (interquartile range; -0.22 to 1.29) at the postoperative CT scan (**p = 0.0039). The NOSE scale revealed significant improvement in nasal obstruction postsurgically (median value, 42.5 to 7.5; *p = 0.0139) in the PDS group. Conclusion: PDS plates potentially present a new concept of open septal reduction in terms of septal reinforcement compared with the subtractive approach of open septal reduction.

The global pandemic outbreak, SARS-COV-2, which causes COVID-19, has coerced numerous pharmaceutical companies to sprint for the vaccine and therapeutic biologics development. Most of the therapeutic biologics are common human IgG antibodies, which were identified by next-generation sequencing with the B cells from the convalescent patients in less than one-month post-infection. While the global public health emergency calls for medications urgently, it saves lives to expedite the clinical trials of biologics as much as possible, hence the biologics development strategies are unprecedentedly challenged. Since the advent of therapeutic biologics, transfection, and selection strategy has been continuously improving for developing more robust cell lines with greater productivity and efficiency. Next-generation sequencing (NGS) has also been implemented into cell bank testing for acceleration. These recent advances enable us to rethink and reshape the chemistry, manufacturing and controls (CMC) strategy against the pandemic outbreaks, to start supplying cGMP materials for the life-saving clinical trials as soon as possible. We elucidated an accelerated CMC workflow for biologics against pandemics, including using cGMP-compliant pool materials for Phase I clinical trials, selecting the final clone with similar product quality as Phase I materials for late-stage development and commercial production and matching product quality among different manufacturing stages.

In modeling cell culture growth using unstructured model, two types of equations are normally used: logistic and Monod. However, these two equations are known for their limitations to model death phase of cell culture growth and to account for dead cells accumulation data. In this paper, we present a modeling framework whereby both Logistic and Monod equations can be used in a single set of equations system to overcome these limitations. First, it can be shown that the increase of total cell population that consists of viable and dead cells follows a logistic growth pattern with its own intrinsic growth rate and total carrying capacity. Furthermore, a hybrid Logistic-Monod equation with first-order decay kinetics can be used to model viable cell growth data with decline phase effectively. With this paradigm, a pseudo-rate equation can be written to account for dead cells accumulation data using population balancing with a simple understanding that dead cell population is simply the difference between total and viable cells. These equations can be adjoined with substrate consumption and product generation rate equations to depict complete batch growth data that covers exponential growth and death phases. This modeling framework has been fitted successfully to fit batch growth data of two cell lines from published literature with complete depictions of dead cell accumulation and cell viability profiles. The implication of this modeling framework for chemostat culture performance analysis is further investigated.