To the Editor,We have read with great interest the article entitled ‘Electrogram-only guided approach to His bundle pacing with minimal fluoroscopy: A single-center experience’ by Zanon et al1 in the latest issue of the journal. We would like to thank the authors for their study regarding the use of electrograms during implantation of the His lead with minimal or no fluoroscopy. Related radiation dose parameters such as fluoroscopy time and dose area product (DAP) were also presented. Radiation dose related to the fluoroscopy system is generally dependent on various autoregulated variables including the tube voltage, the tube current and the pulse duration. In addition, various programmable settings including the frame rate, collimation, and magnification are used to regulate the amount of radiation although the number of variables which can be programmed in the manufacturer specific system varies. Fluoroscopy time should not be an estimation factor for radiation dose because its correlation with other standard radiation measures is weak. Manufacturer specific calculations, either total time while pressing on the fluoroscopy pedal or only a sum of fluoroscopic pulses, make the radiation dose difficult to estimate. The air kerma area product, or DAP (Gy.cm2) is accepted as the most accurate measurement of radiation energy given for fluoroscopic purposes. Roughly, the effective dose (ED) (mSv) of fluoroscopic source of radiation can be calculated using a conversion factor of 0.20 from the DAP measurement. For instance, routine single/dual-chamber pacemaker/defibrillator implantation has an average ED of 4 mSv, compared to an average ED of nearly 20 mSv for a cardiac resynchronization therapy device implantation.2 The frame rate, collimation and magnification should be properly set to reduce the DAP/ED values.The frame rate seems as the most important programmable factor related to the radiation dose. Continuous fluoroscopy has generally the frame rate of ≥30 frames per second (fps), which is associated with increased radiation exposure. Therefore, the frame rate should be set as low as achievable. Decreasing the frame rate from 30 fps to 7.5 fps reduces the ED by 75%. Compensatory tube current increase generally occurs during pulsed fluoroscopy, which is associated with the same number of x-rays produced during continuous fluoroscopy. However, significantly decreased number of pulses cause significant reduction of radiation exposure in a linear way. The frame rates as low as ≤3 fps should be used during diagnostic and ablation procedures and device implantations in the electrophysiology laboratory although reduced temporal resolution.2,3 Furthermore, configuring the frame rate ≤1 fps using the ECG triggering or pacing artifact can be the best approach. Configuration of the pulsed fluoroscopy at the lowest frame rate needed has the greatest potential for ensuring radiation dose at the lowest level.Properly configured and applied collimation, reduction of radiation to an anatomical area that requires imaging, has an important role in reducing both the direct and the scattered radiation. Collimation, especially the asymmetric one, reduces visualization area and decreases the DAP/ED in a linear way. During the procedure, the use of collimation restricts the view on the cardiac contour. After viewing the whole anatomy, re-collimation should be performed.Another option for reducing the radiation dose is to set the largest field of view, or the smallest magnification, possible. In the smallest field of view mode, or the largest magnification mode, a smaller radiation area is projected in the image intensifier and, a larger image is produced on the screen. This process is related to a lower radiation output and a dimmer image. The fluoroscopy unit has an automatic system for controlling the brightness sensed. Therefore, the automatic system compensates for the lower brightness by increasing radiation exposure from the tube. With the use of magnification, the radiation dose increase in flat-panel detectors is lower compared to the image-intensifiers, however it is still remarkable.4In the light of all above-mentioned settings, the fluoroscopy time should not be used as an important variable measuring the radiation dose. Instead, the DAP/ED values should be reported.Keywords: dose area product/effective dose; fluoroscopy; programmable; radiation dose

Background: Transvenous permanent pacemaker related infection is a severe condition associated with significant morbidity and mortality. Leadless pacemakers may be more resistant to bacterial seeding during bloodstream infection because of its small surface area and encapsulation in the right ventricle. This study reports the incidence and outcomes of bacteraemia in patients implanted with a Micra leadless pacemaker. We present 18F-FDG PET/CT findings obtained in a sub-group of patients. Methods: We report a retrospective cohort study of 155 patients who underwent a Micra TPS implant procedure at the University Hospitals of Leuven between July 2015 and July 2019. We identified the patients who developed an episode of bacteraemia, proved by ≥2 positive blood cultures. Results: Of the 155 patients, 15 patients presented an episode of bacteraemia at a median of 226 days (range: 3-1129) days after the implant procedure. Gram positive species accounted for 73.3% (n=11) of the bacteraemia including Staphylococcus (n=5), Enterococcus (n=3) and Streptococcus (n=3). The source of infection was identified in 9 patients (60%) including endocarditis in 4 patients, urinary tract in 3 patients, and skin in 2 patients. 18F-FDG PET/CT imaging performed in 6 patients did not show sign of infection around the leadless pacemaker. Bacteraemia was resolved in all patients after adequate antibiotherapy. Four patients died early during follow up. For all other patients, there were no recurrence of bacteraemia during a median follow up of 263 days (range 15-1134). Conclusion: In our small cohort, no leadless pacemaker endocarditis was observed among patients with bacteraemia.

Introduction：LAmbre occluder (Lifetech Scientific, Shenzhen, China), a new device for left atrial appendage (LAA) occlusion, is increasingly used, but the procedure for retrieval after dislodgement has rarely reported in human. Methods and Results：An 80-year-old male patient with permanent atrial fibrillation underwent the implantation of LAA occlusion device. The occluder dislodged to left atrium (LA) at the end of procedure. We failed to retrieve device in LA with a LASSO catheter and forceps with the 8.5F sheath. After it suddenly flowing into aortic arch, we successfully retrieved with a 14F flexible sheath and forceps. We also discussed reasons for the device dislodgment and reported experiences for device retrieval. Conclusion: Combination of the 14F flexible sheath and forceps could be used to retrieve the dislocation of LAA occlusion device.

Partial clonality is widespread across the tree of life, but most population genetics models are designed for exclusively clonal or sexual organisms. This gap hampers our understanding of the influence of clonality on evolutionary trajectories and the interpretation of population genetics data. We performed forward simulations of diploid populations at increasing rates of clonality (c), analysed their relationships with genotypic (clonal richness, R, and distribution of clonal sizes, Pareto β) and genetic (FIS and linkage disequilibrium) indices, and tested predictions of c from population genetics data through supervised machine learning. Two complementary behaviours emerged from the probability distributions of genotypic and genetic indices with increasing c. While the impact of c on R and Pareto β was easily described by simple mathematical equations, its effects on genetic indices were noticeable only at the highest levels (c>0.95). Consequently, genotypic indices allowed reliable estimates of c, while genetic descriptors led to poorer performances when c<0.95. These results provide clear baseline expectations for genotypic and genetic diversity and dynamics under partial clonality. Worryingly, however, the use of realistic sample sizes to acquire empirical data systematically led to gross underestimates (often of one to two orders of magnitude) of c, suggesting that many interpretations hitherto proposed in the literature, mostly based on genotypic richness, should be reappraised. We propose future avenues to derive realistic confidence intervals for c and show that, although still approximate, a supervised learning method would greatly improve the estimation of c from population genetics data.

This paper responds to one by Graham Martin and colleagues, who offered a critique of my previous publications on masks for the lay public in the Covid-19 pandemic. I address their charges that my co-authors and I had misapplied the precautionary principle; drawn conclusions that were not supported by empirical research; and failed to take account of potential harms. But before that, I remind Martin et al that the evidence on mask wearing goes beyond the contested trials and observational studies they place centre stage. I set out some key findings from basic science, epidemiology, mathematical modelling, case studies and natural experiments, and use this rich and diverse body of evidence as the backdrop for my rebuttal of their narrowly-framed objections. I challenge my critics’ apparent assumption that a particular kind of systematic review should be valorised over narrative and real-world evidence, since stories are crucial to both our scientific understanding and our moral imagination. I conclude by thanking my academic adversaries for the intellectual sparring match, but exhort them to remember our professional accountability to a society in crisis. It is time to lay straw men to rest and engage, scientifically and morally, with the dreadful tragedy that is unfolding across the world.

Objectives We aimed to investigate whether uncomplicated type A intramural hematoma (IMHA) patients with type 2 diabetes mellitus (DM) who underwent a “wait-and-watch strategy” and tight glycemic control had similar clinical outcomes as patients without DM who received the same treatment strategy. Methods Between January 2010 and December 2016, uncomplicated IMHA patients with and without diabetes mellitus were included and were propensity score matched to improve balance between the two groups. Cox proportional hazard models were constructed to identify the specific factors associated with aorta-related mortality. The Fine-Gray model for the competing risk analysis was used to estimate the aorta-related and non-aorta-related mortality in different groups during the follow-up period. Results 109 IMHA patients were included in this study, and 66 patients were included after matching. Patients without DM experienced significantly more aorta-related adverse events (51.6% vs 13.3%, P=0.001) and reinterventions than patients in the DM group (29.0% vs 6.7%, P=0.023). Cox regression analysis revealed that a higher matrix metalloproteinase-9 level (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.39-2.09, P<0.001) and larger maximum aortic diameter (HR, 1.41; 95% CI, 1.11-1.80, P=0.005) were associated with higher aorta-related mortality. The competing risk analysis revealed a significantly higher aorta-related mortality during the follow-up period in the no DM group than in the DM group (36.4%; 95% CI, 11.6%-82.3%, P=0.0294). Conclusions Uncomplicated IMHA patients with DM (receiving the “wait-and-watch strategy” and tight glycemic control) may have a lower aorta-related mortality, and rates of aorta-related adverse events and reinterventions than the no DM group.

In recent years, the use of bioprosthetic valve (BPV) has increased significantly with both surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) due to reasons such as the advantage of not using anticoagulants. Nevertheless major disadvantage of all BPV is the risk of early structural valve deterioration, leading to valve dysfunction, and requires reoperation, which significantly increases the risk of mortality or major morbidity especially after SAVR. There are a limited number of TAV-in-TAV case reports due to TAVI BPV degeneration. In our knowledge this is the second report of TAV-in-TAV implantation wherein a previously implanted transfemoral 25-mm nonmetallic Direct Flow SVD valve treated with ViV TAVI via Edwards Sapien XT.

Background Fractional flow reserve (FFR) is a well-established method for the evaluation of coronary artery stenosis before PCI. However, whether FFR assessment should be routinely used before CABG remains unclear. Our aim was to compare the outcomes of using FFR with that of conventional CAG (coronary angiography) in guiding CABG. Method This systematic review and meta-analysis was performed according to the PRISMA guidelines. Six studies were included, of which four were double-arm (two prospectively randomised) and two single-arm, reporting data on 1931 patients. A meta-analysis was done for double-arm studies, comparing rates of overall death, MACCE, target vessel revascularisation, spontaneous MI and graft patency. The data of all six studies were entered in a pooled analysis for the endpoints of overall death, spontaneous MI and target vessel revascularisation. Results Meta-analysis demonstrated significantly lower death rates in the FFR-guided than the CAG-guided group (p=0.03) and no significant differences in the rates of MACCE, target vessel revascularisation, spontaneous MI and graft patency. In pooled analysis, FFR-guided group was linked with lower rates of overall death and spontaneous MI. Graft occlusion rate was significantly lower after FFR in one retrospective study, however, this difference was lost in meta-analysis (p=0.24). Conclusion In this meta-analysis, FFR-guided CABG was associated with lower overall death rate and was, at least, non-inferior in the endpoints of MACCE, target vessel revascularisation, spontaneous MI and graft patency than CAG-guided CABG. Further randomized trials are needed to define the role of FFR in guiding CABG surgery.

The nascent wave of disruptive competition in the current business environment brought about by the fourth industrial revolution (Fashion 4.0 or Apparel 4.0) is enormous. Therefore, it is paramount important to apparel industry to be flexible enough to respond quickly to the unstable customers’ demand through continuous improvement of their process efficiency and productivity. This study aims at achieving an optimal trouser assembly line balancing using simulation-based optimization via design of experiment. The empirical study is conducted at Southern Range Nyanza Limited (NYTIL) garment facility and a complex trouser assembly line with 72 operations is considered. The discrete event simulation of the trouser assembly line is developed using Arena simulation software. The local optimal solution is obtained from simulation experimentation and is adopted for the optimization process. The OptQuest tool is utilized to solve a single objective function (throughput) optimization problem. The results show that average throughput increases from the existing design (490 pieces per day) to local optimal design (638) and global optimal design (762). Consequently, the line efficiency increases from 61.2% to 79.7% to 95.2% respectively. The high increase in line efficiency and average throughput confirms the suitability assembly line balancing using simulation-based optimization via design of experiment.

During the COVID-19 pandemic, ER visits have drastically decreased for non-COVID conditions such as appendicitis, heart attack and stroke. Patients may be avoiding seeking medical attention for fear of catching the deadly condition or as an unintended consequence of stay-at-home orders. This delay in seeking care can lead to increased morbidity and mortality, which has not been figured in the assessment of the extent of damage caused by this pandemic. This case illustrates an example of “collateral damage” caused by COVID-19 pandemic. What would have been a standard STEMI treated with timely and successful stenting of a dominant right coronary artery occlusion, became a much more dangerous post-infarction VSD; all because of a 2-day delay in seeking medical attention by an unsuspecting patient.

COVID-19, the disease resulting from infection by a novel coronavirus: SARS-Cov2 that has rapidly spread since November 2019 leading to a global pandemic. SARS-Cov2 has infected over 2.8 million people and caused over 180,000 deaths worldwide. Although most cases are mild, a subset of patients develop a severe and atypical presentation of Acute Respiratory Distress Syndrome (ARDS) that is characterised by a cytokine release storm (CRS). Paradoxically, treatment with anti-inflammatory agents and immune regulators has been associated with worsening of ARDS. We hypothesize that the intrinsic circadian clock of the lung and the immune system may regulate individual components of CRS and thus chronotherapy may be used to effectively manage ARDS in COVID-19 patients.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder that causes the progressive loss of motoneurons, and unfortunately, there is no effective treatment to stop the disease. Multiple pathological mechanisms are interconnected in the neuropathology of this disorder, including abnormal aggregation of proteins, neuroinflammation and dysregulation of the ubiquitin proteasome system. Such complex mechanisms, together with the lack of reliable animal models of the disease, have hampered drug discovery in the last decades. Protein kinases, key pharmacological targets in several diseases, have been linked to ALS, as they play a central role in numerous of these pathological mechanisms. Therefore, several inhibitors are currently in their way to achieve a clinical proof of concept in ALS patients. In this review we recapitulate the protein kinase inhibitors currently in development for this disease together with their molecular targets and their involvement in the pathobiology of ALS.

I moved out of our shared bedroom of nearly 10 years on 3/22/2020. It was not a difficult decision as we have two young children and wondered what would happen if both of us became ill at the same time. As a Maternal-Fetal medicine physician in New York City, I was acutely aware of the coming COVID-19 crisis, and its potential ramifications on the health of my family, friends, patients and community. I am trained to function well in emergencies, and in this case, it was a quick and seemingly logical next-step to sleep separately.This decision also comes along with an already in place full-scale decontamination effort that begins as soon as I enter our home. This involves minimizing what jewelry, clothing, food and bags go back and forth between the hospital and my home, 3-shoe changes, stripping off my clothing and placing everything into the wash, and then running to the shower. None of these choices were rooted in years of medical science, given the novelty of the virus, and paucity of data on the SARS-CoV-2 (COVID-19). I used early data regarding transmission as well as anecdotal reports from friends in Asia who seemed to suggest that it was highly contagious and highly transmissible. Thus, when I recently learned that there is a science and a history surrounding how pathogens have shaped human psychological adaptations. As we are forced to confront the longstanding evolutionary pressure of pathogen avoidance regarding what to eat, and touch and who to be intimate with, it no longer feels theoretical.1Looking back at what I’ve gained and what I’m missing over this last month, I am acutely aware of how much less we are touching as a family and in my medical practice, and I miss it. As I say goodnight to my family and retreat to our windowless den, I am both thankful for a place to sleep that is near enough to be able to peek at their beautiful sleeping faces, while sad that I feel less at ease hugging or kissing them. While every health care worker on the front-line of this crisis has drawn different boundaries (some more or less extreme), my decision to sleep in a separate room, create a decontamination routine, and be less physically affectionate with my children was the only way I could feel in control in an uncontrollable situation.Medical professionals know that touch, rooted in the amygdala of the brain, cannot be separated from the expression of empathy and solidarity that it provides.2 In medicine, touch has long been hypothesized to have an impact on health and development over our lifespan. Dr. Cascio and her team at the Vanderbilt Kennedy Center for Human Development describe social touch as “a powerful force in human development, shaping social reward, attachment, cognitive, communication, and emotional regulation from infancy and throughout life.3” Many of the babies of the mothers I care for will begin their lives in the Neonatal Intensive Care Unit where the science surrounding touch as part of healthcare is widely accepted and engrained in the culture. Skin-to-skin and kangaroo care, the act of carrying your child in a pouch-like device, have been shown to improve breastfeeding, bonding, and neurocognitive development4,5 In fact, the World Health Organization currently has an ongoing international trial looking at the benefits of survival on low-birthweight infants of kangaroo care initiated immediately after birth on survival of low birth weight infants.6 Later in life, touch, relationship quality and intimacy continue to drive good health and have been associated with improved cognitive function in the Rotterdam Study7,8and improved cardiovascular outcomes in the National Social Life Health and Aging Project.8 Their findings suggest physical touch may have positive health implications for older adults.Prior to the pandemic, physicians were already sounding alarms about the loss of medical touch in modern medicine. In a 2011 TED talk with over 1.7 million views, renowned author and physician Abraham Verghese discussed the power of physician touch and the physical exam as he tried to revive the culture of bedside medicine.9 With this pandemic all of that has changed. We are all exceedingly careful to prevent transmission and yet try to provide care and solace in new ways. At the bedside, a gloved hand continues to provide care and comfort. I am happily finding ways to connect with patients through smiling eyes behind a mask, and jokes or phrases that now replace touch. I find myself more commonly expressing words of empathy in telemedicine visits to fill in for the gaps that touch might have provided before. I ask many, many questions to understand symptoms if I cannot see the patient in person. Due to the surrounding events, I am undertaking the fulfilling process of learning a new skill in medicine, to express my emotions on a screen and affect patients’ lives in ways similar to that of an in-person visit.As we raise our family in this time of pandemic, I am thankful that my husband is doing “double-duty” in the realm of hugging and kissing, and has always been a physically affectionate father to our children. I try to tell them how much I love them with greater frequency and despite the concerted effort there are days it’s almost impossible to share our apartment without being physically close. The psychological impact this crisis will have on them is yet to be determined. I hope time will find them healthy, more resilient and grateful at the end of this journey.But tonight, as they sleep soundly in their beds for another night, I am still saddened that I’m not doing the usual kissing and hugging as I tuck them into bed, and it feels like a true loss, among the many others. I am not sleeping as soundly these days for a multitude of reasons including the guest bed, the strangeness of being alone after so many years, and the exponential rise in screen time for work and media consumption. I am truly hopeful we will return to a time when we can more freely touch and care for the people we love and the patients we value so much. In the simplest of internet searches, touch has so many definitions. Touch can mean to be in close contact, but it can also mean to affect.10 COVID-19 has affected us in innumerable ways, and as healthcare workers navigate a post-COVID landscape, I’m hopeful we can continue to innovate and find safe ways to incorporate medical touch into a practice that will be forever changed.Acknowledgements : I would like to acknowledge our patients for their immense flexibility in this changing landscape, the support of my division and department, and my family. I’d like to thank Dr. Gwendolyn Quinn and my husband David Lee, for their significant editorial assistance.

Recent studies have demonstrated the great advantages of marine reserves in solving bycatch problems by maintaining the persistence of endangered species without sacrificing the fisheries yields of target species. However, transient phenomena rather than equilibrium states of population dynamics still require further research. Here, with a simple and general model, the transient dynamics of strong stock fish species are investigated under the condition of weak stock persistence. A surprising and counter-intuitive finding is that fisheries yields can strongly fluctuate even if population density both inside and outside marine reserve only slightly varies, leading to transient inconsistency between the population densities and fisheries yields. This finding suggests that population density dynamics cannot be used to predict the transient phenomena of fisheries yields (or vice versa) in fisheries management. These results will deepen our understanding of the transient phenomenon in marine ecology.

We report a case of COVID-19 with only atypical CT findings; tree-in-bud appearance and centri-lobular nodules. Some COVID-19 cases show only atypical CT findings. Physicians should make comprehensive judgements.

This work aims to investigate the anisotropic fracture and energy dissipation characteristics of marbles cored along an angle of 0°, 30°, 60° and 90° with respect to interbed planes, subjected to multi-level cyclic loading conditions. Rock fatigue deformation, strength, lifetime and dissipated energy first decreases and then increases with increasing interbed orientation, they get to the minimum for sample having 30° interbed orientation. Rock stiffness degradation is significant with the increase of cyclic level and the stiffness evolution is affected by interbed structure. The incremental rate of dissipated energy becomes faster with increase of cyclic loading level and it presents an abrupt increasing trend at the last cyclic loading level. A damage evolution model was first established based on the dissipated energy to describe the two-phase damage accumulation characteristics. It suggests that the proposed model fits well to the testing data and favorably represents the non-linear characteristics of damage accumulation.

African swine fever (ASF) is emerging in Vietnam and poses a continuing severe threat to the swine industry. A histopathological study of clinical samples collected during the August to September 2019 outbreak of ASF was performed to determine the characteristic lesions. We analyzed samples from eight ASFV-infected farms. Histopathological results revealed the characteristic lesions of the acute to the subacute clinical form of ASF. Immunohistochemical results showed ASFV viral antigen distribution in mononuclear cells/macrophage in various organs, hepatocytes, and renal tubular epithelium. Molecular analysis of partial capsid protein 72 gene revealed that ASFV strain from the eight separate outbreaks belonged to genotype II.

Repurposing of existing antiviral drugs, immunological modulators, and supportive therapies represents a promising path toward rapidly developing new control strategies to mitigate the devastating public health consequences of the COVID-19 pandemic. A comprehensive text-mining and manual curation approach was used to comb and summarize the most pertinent information from existing clinical trials. Drugs with previous efficacy against related betacoronaviruses like SARS and MERS were also systematically evaluated as potentially promising candidates for drug repositioning.