Explaining the Sharp Decline in Birth Rates in Canada and the USA in 2020.

Birth rates in Canada and the USA declined sharply in March 2020 and deviated from historical trends. This decline was absent in similarly developed European countries. We argue that the selective decline was driven by incoming individuals, who would have travelled from abroad and given birth in Canada and the USA, had there been no travel restrictions during the COVID-19 pandemic. Furthermore, by leveraging data from periods before and during the COVID-19 travel restrictions, we quantified the extent of births by incoming individuals. In an interrupted time series analysis, the expected number of such births in Canada was 970 per month (95% CI: 710-1,200), which is 3.2% of all births in the country. The corresponding estimate for the USA was 6,700 per month (95% CI: 3,400-10,000), which is 2.2% of all births. A secondary difference-in-differences analysis gave similar estimates at 2.8% and 3.4% for Canada and the USA, respectively. Our study reveals the extent of births by recent international arrivals, which hitherto has been unknown and infeasible to study.

Electrochemical Methods for Water Purification, Ion Separations, and Energy Conversion.

Agricultural development, extensive industrialization, and rapid growth of the global population have inadvertently been accompanied by environmental pollution. Water pollution is exacerbated by the decreasing ability of traditional treatment methods to comply with tightening environmental standards. This review provides a comprehensive description of the principles and applications of electrochemical methods for water purification, ion separations, and energy conversion. Electrochemical methods have attractive features such as compact size, chemical selectivity, broad applicability, and reduced generation of secondary waste. Perhaps the greatest advantage of electrochemical methods, however, is that they remove contaminants directly from the water, while other technologies extract the water from the contaminants, which enables efficient removal of trace pollutants. The review begins with an overview of conventional electrochemical methods, which drive chemical or physical transformations via Faradaic reactions at electrodes, and proceeds to a detailed examination of the two primary mechanisms by which contaminants are separated in nondestructive electrochemical processes, namely electrokinetics and electrosorption. In these sections, special attention is given to emerging methods, such as shock electrodialysis and Faradaic electrosorption. Given the importance of generating clean, renewable energy, which may sometimes be combined with water purification, the review also discusses inverse methods of electrochemical energy conversion based on reverse electrosorption, electrowetting, and electrokinetic phenomena. The review concludes with a discussion of technology comparisons, remaining challenges, and potential innovations for the field such as process intensification and technoeconomic optimization.

Electrochemical removal of amphoteric ions.

Several harmful or valuable ionic species present in seawater, brackish water, and wastewater are amphoteric, weak acids or weak bases, and, thus, their properties depend on local water pH. Effective removal of these species can be challenging for conventional membrane technologies, necessitating chemical dosing of the feedwater to adjust pH. A prominent example is boron, which is considered toxic in high concentrations and often requires additional membrane passes to remove during seawater desalination. Capacitive deionization (CDI) is an emerging membraneless technique for water treatment and desalination, based on electrosorption of salt ions into charging microporous electrodes. CDI cells show strong internally generated pH variations during operation, and, thus, CDI can potentially remove pH-dependent species without chemical dosing. However, development of this technique is inhibited by the complexities inherent to the coupling of pH dynamics and ion properties in a charging CDI cell. Here, we present a theoretical framework predicting the electrosorption of pH-dependent species in flow-through electrode CDI cells. We demonstrate that such a model enables insight into factors affecting species electrosorption and conclude that important design rules for such systems are highly counterintuitive. For example, we show both theoretically and experimentally that for boron removal, the anode should be placed upstream and the cathode downstream, an electrode order that runs counter to the accepted wisdom in the CDI field. Overall, we show that to achieve target separations relying on coupled, complex phenomena, such as in the removal of amphoteric species, a theoretical CDI model is essential.

Recent Innovations in Footwear and the Role of Smart Footwear in Healthcare-A Survey.

Smart shoes have ushered in a new era of personalised health monitoring and assistive technologies. Smart shoes leverage technologies such as Bluetooth for data collection and wireless transmission, and incorporate features such as GPS tracking, obstacle detection, and fitness tracking. As the 2010s unfolded, the smart shoe landscape diversified and advanced rapidly, driven by sensor technology enhancements and smartphones' ubiquity. Shoes have begun incorporating accelerometers, gyroscopes, and pressure sensors, significantly improving the accuracy of data collection and enabling functionalities such as gait analysis. The healthcare sector has recognised the potential of smart shoes, leading to innovations such as shoes designed to monitor diabetic foot ulcers, track rehabilitation progress, and detect falls among older people, thus expanding their application beyond fitness into medical monitoring. This article provides an overview of the current state of smart shoe technology, highlighting the integration of advanced sensors for health monitoring, energy harvesting, assistive features for the visually impaired, and deep learning for data analysis. This study discusses the potential of smart footwear in medical applications, particularly for patients with diabetes, and the ongoing research in this field. Current footwear challenges are also discussed, including complex construction, poor fit, comfort, and high cost.

Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19.

BACKGROUND: Coronavirus disease 2019 (Covid-19) may disproportionately affect people with cardiovascular disease. Concern has been aroused regarding a potential harmful effect of angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) in this clinical context. METHODS: Using an observational database from 169 hospitals in Asia, Europe, and North America, we evaluated the relationship of cardiovascular disease and drug therapy with in-hospital death among hospitalized patients with Covid-19 who were admitted between December 20, 2019, and March 15, 2020, and were recorded in the Surgical Outcomes Collaborative registry as having either died in the hospital or survived to discharge as of March 28, 2020. RESULTS: Of the 8910 patients with Covid-19 for whom discharge status was available at the time of the analysis, a total of 515 died in the hospital (5.8%) and 8395 survived to discharge. The factors we found to be independently associated with an increased risk of in-hospital death were an age greater than 65 years (mortality of 10.0%, vs. 4.9% among those ≤65 years of age; odds ratio, 1.93; 95% confidence interval [CI], 1.60 to 2.41), coronary artery disease (10.2%, vs. 5.2% among those without disease; odds ratio, 2.70; 95% CI, 2.08 to 3.51), heart failure (15.3%, vs. 5.6% among those without heart failure; odds ratio, 2.48; 95% CI, 1.62 to 3.79), cardiac arrhythmia (11.5%, vs. 5.6% among those without arrhythmia; odds ratio, 1.95; 95% CI, 1.33 to 2.86), chronic obstructive pulmonary disease (14.2%, vs. 5.6% among those without disease; odds ratio, 2.96; 95% CI, 2.00 to 4.40), and current smoking (9.4%, vs. 5.6% among former smokers or nonsmokers; odds ratio, 1.79; 95% CI, 1.29 to 2.47). No increased risk of in-hospital death was found to be associated with the use of ACE inhibitors (2.1% vs. 6.1%; odds ratio, 0.33; 95% CI, 0.20 to 0.54) or the use of ARBs (6.8% vs. 5.7%; odds ratio, 1.23; 95% CI, 0.87 to 1.74). CONCLUSIONS: Our study confirmed previous observations suggesting that underlying cardiovascular disease is associated with an increased risk of in-hospital death among patients hospitalized with Covid-19. Our results did not confirm previous concerns regarding a potential harmful association of ACE inhibitors or ARBs with in-hospital death in this clinical context. (Funded by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.).

A coherent feed-forward loop drives vascular regeneration in damaged aerial organs of plants growing in a normal developmental context.

Aerial organs of plants, being highly prone to local injuries, require tissue restoration to ensure their survival. However, knowledge of the underlying mechanism is sparse. In this study, we mimicked natural injuries in growing leaves and stems to study the reunion between mechanically disconnected tissues. We show that PLETHORA (PLT) and AINTEGUMENTA (ANT) genes, which encode stem cell-promoting factors, are activated and contribute to vascular regeneration in response to these injuries. PLT proteins bind to and activate the CUC2 promoter. PLT proteins and CUC2 regulate the transcription of the local auxin biosynthesis gene YUC4 in a coherent feed-forward loop, and this process is necessary to drive vascular regeneration. In the absence of this PLT-mediated regeneration response, leaf ground tissue cells can neither acquire the early vascular identity marker ATHB8, nor properly polarise auxin transporters to specify new venation paths. The PLT-CUC2 module is required for vascular regeneration, but is dispensable for midvein formation in leaves. We reveal the mechanisms of vascular regeneration in plants and distinguish between the wound-repair ability of the tissue and its formation during normal development.

Big data and RCT's in surgical oncology: Impact on improving hepatopancreatobiliary cancer surgical care on the global stage.

Randomized controlled clinical trials (RCTs) are at the heart of "evidence-based" medicine. Conducting well-designed RCTs for surgical procedures is often challenged by inadequate recruitment accrual, blinding, or standardization of the surgical procedure, as well as lack of funding and evolution of the treatment strategy during the many years over which such trials are conducted. In addition, most clinical trials are performed in academic high-volume centers with highly selected patients, which may not necessarily reflect a "real-world" practice setting. Large databases provide easy and inexpensive access to data on a large and diverse patient population at a variety of treatment centers. Furthermore, large database studies provide the opportunity to answer questions that would be impossible or very arduous to answer using RCTs, including questions regarding health policy efficacy, trends in surgical practice, access to health care, the impact of hospital volume, and adherence to practice guidelines, as well as research questions regarding rare disease, infrequent surgical outcomes, and specific subpopulations. Prospective data registries may also allow for quality benchmarking and auditing. There are several high-quality RCTs providing evidence to support current practices in hepatopancreatobiliary (HPB) oncology. Evidence from big data bridges the gap in several instances where RCTs are lacking. In this article, we review the evidence from RCTs and big data in HPB oncology identify the existing lacunae, and discuss the future directions of research in HPB oncology.

Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation.

BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).

Prospective evaluation of sleep disturbances in chronic pancreatitis and its impact on quality of life: a pilot study.

BACKGROUND: Patients with chronic pancreatitis (CP) have poor quality of life (QOL). Sleep disorders affect QOL when associated with chronic pain and opioid use. Hence patients with CP may have unrecognized sleep disturbances. AIMS: The aim of the study was to evaluate sleep disturbances in CP and its impact on QOL. METHODS: Established CP patients were prospectively enrolled after exclusion of patients with co-morbidities known to negatively affect sleep and QOL. Three questionnaires were used to identify sleep disturbances, PROMISv1SF8, Insomnia Severity Index, and Epworth Sleepiness Scale, and one for restless leg syndrome (RLS). PANQOLI and SF12 questionnaires were used to evaluate QOL. Two blinded sleep pulmonologists evaluated the responses. QOL assessments were then analyzed in patients with and without sleep disturbances. RESULTS: Of 89 patients, 48 met exclusion criteria, 41 were eligible, and 28 completed the study. Twenty patients (71%) had sleep disturbances with significantly worse scores across all 3 sleep questionnaires and also had lower scores on both PANQOLI (50 vs 76, p = 0.002) and SF-12 (physical component 29.3 vs 53.9, p < 0.001; mental component 36.4 vs 46.1, p = 0.03). Eleven patients (39%) had RLS and sleep disturbances. CONCLUSION: In patients with established CP there was a high prevalence of sleep disturbances and RLS with worse QOL representing a potential therapeutic target to improve QOL.

Non-vitamin K antagonist oral anticoagulants in patients with valvular heart disease.

The non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban have transformed the management of atrial fibrillation (AF), but are only approved by regulatory authorities for stroke prophylaxis in patients with so-called "non-valvular AF." This terminology has spawned confusion about which patients with valvular heart disease benefit from NOACs and which should be treated with vitamin K antagonists (VKAs) instead. Patients with valvular heart disease other than mechanical prosthetic valves or severe mitral stenosis (including those with bioprosthetic valves) were included in pivotal trials demonstrating the benefit of NOACs over VKAs, and consensus guidelines recommend NOACs over VKAs in these patients. Subsequent devoted randomized controlled trials in patients with AF and bioprosthetic valves, including transcatheter valves, have confirmed the safety of NOACs in this population. In patients with rheumatic mitral stenosis, observational studies indicate that NOACs may be safe and effective, but randomized controlled trials are ongoing. By contrast, a randomized controlled trial showed that dabigatran is harmful in patients with mechanical prosthetic mitral valves; however, these data may not extrapolate to patients with mechanical valve prostheses in other locations or to other NOACs, and randomized controlled trials are ongoing. In this review, we discuss these data in greater depth, and make recommendations for the use of NOACs in patients with valvular heart disease.

Pattern formation mechanisms of self-organizing reaction-diffusion systems.

Embryonic development is a largely self-organizing process, in which the adult body plan arises from a ball of cells with initially nearly equal potency. The reaction-diffusion theory first proposed by Alan Turing states that the initial symmetry in embryos can be broken by the interplay between two diffusible molecules, whose interactions lead to the formation of patterns. The reaction-diffusion theory provides a valuable framework for self-organized pattern formation, but it has been difficult to relate simple two-component models to real biological systems with multiple interacting molecular species. Recent studies have addressed this shortcoming and extended the reaction-diffusion theory to realistic multi-component networks. These efforts have challenged the generality of previous central tenets derived from the analysis of simplified systems and guide the way to a new understanding of self-organizing processes. Here, we discuss the challenges in modeling multi-component reaction-diffusion systems and how these have recently been addressed. We present a synthesis of new pattern formation mechanisms derived from these analyses, and we highlight the significance of reaction-diffusion principles for developmental and synthetic pattern formation.

Risk/Benefit Tradeoff of Antithrombotic Therapy in Patients With Atrial Fibrillation Early and Late After an Acute Coronary Syndrome or Percutaneous Coronary Intervention: Insights From AUGUSTUS.

BACKGROUND: In AUGUSTUS (Open-Label, 2×2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs Vitamin K Antagonist and Aspirin vs Aspirin Placebo in Patients With Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention), patients with atrial fibrillation and a recent acute coronary syndrome and those undergoing percutaneous coronary intervention had less bleeding with apixaban than vitamin K antagonist (VKA) and with placebo than aspirin. However, the number of ischemic events was numerically higher with placebo. The aim of this analysis is to assess the tradeoff of risk (bleeding) and benefit (ischemic events) over time with apixaban versus VKA and aspirin versus placebo. METHODS: In AUGUSTUS, 4614 patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention on a P2Y12 inhibitor were randomized to blinded aspirin or placebo and to open-label apixaban or VKA for 6 months. In a post hoc analysis, we compared the risk of 3 composite bleeding outcomes and 3 composite ischemic outcomes from randomization through 30 days and from 30 days to 6 months with apixaban and VKA and with aspirin and placebo. RESULTS: Compared with VKA, apixaban had either a lower or a similar risk of bleeding and ischemic outcomes from randomization to 30 days and from 30 days to 6 months. From randomization to 30 days, aspirin caused more severe bleeding (absolute risk difference, 0.97% [95% CI, 0.23-1.70]) and fewer severe ischemic events (absolute risk difference, -0.91% [95% CI, -1.74 to -0.08]) than placebo. From 30 days to 6 months, the risk of severe bleeding was higher with aspirin than placebo (absolute risk difference, 1.25% [95% CI, 0.23-2.27]), whereas the risk of severe ischemic events was similar (absolute risk difference, -0.17% [95% CI, -1.33 to 0.98]). CONCLUSIONS: In patients with atrial fibrillation and recent acute coronary syndrome or percutaneous coronary intervention receiving a P2Y12 inhibitor, apixaban is preferred over VKA. Use of aspirin immediately and for up to 30 days results in an equal tradeoff between an increase in severe bleeding and a reduction in severe ischemic events. After 30 days, aspirin continues to increase bleeding without significantly reducing ischemic events. These results inform shared, patient-centric decision making on the ideal duration of the use of aspirin after an acute coronary syndrome or percutaneous coronary intervention in patients with atrial fibrillation receiving oral anticoagulation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02415400.

RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis.

BACKGROUND: Hydroxychloroquine or chloroquine, often in combination with a second-generation macrolide, are being widely used for treatment of COVID-19, despite no conclusive evidence of their benefit. Although generally safe when used for approved indications such as autoimmune disease or malaria, the safety and benefit of these treatment regimens are poorly evaluated in COVID-19. METHODS: We did a multinational registry analysis of the use of hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19. The registry comprised data from 671 hospitals in six continents. We included patients hospitalised between Dec 20, 2019, and April 14, 2020, with a positive laboratory finding for SARS-CoV-2. Patients who received one of the treatments of interest within 48 h of diagnosis were included in one of four treatment groups (chloroquine alone, chloroquine with a macrolide, hydroxychloroquine alone, or hydroxychloroquine with a macrolide), and patients who received none of these treatments formed the control group. Patients for whom one of the treatments of interest was initiated more than 48 h after diagnosis or while they were on mechanical ventilation, as well as patients who received remdesivir, were excluded. The main outcomes of interest were in-hospital mortality and the occurrence of de-novo ventricular arrhythmias (non-sustained or sustained ventricular tachycardia or ventricular fibrillation). FINDINGS: 96 032 patients (mean age 53·8 years, 46·3% women) with COVID-19 were hospitalised during the study period and met the inclusion criteria. Of these, 14 888 patients were in the treatment groups (1868 received chloroquine, 3783 received chloroquine with a macrolide, 3016 received hydroxychloroquine, and 6221 received hydroxychloroquine with a macrolide) and 81 144 patients were in the control group. 10 698 (11·1%) patients died in hospital. After controlling for multiple confounding factors (age, sex, race or ethnicity, body-mass index, underlying cardiovascular disease and its risk factors, diabetes, underlying lung disease, smoking, immunosuppressed condition, and baseline disease severity), when compared with mortality in the control group (9·3%), hydroxychloroquine (18·0%; hazard ratio 1·335, 95% CI 1·223-1·457), hydroxychloroquine with a macrolide (23·8%; 1·447, 1·368-1·531), chloroquine (16·4%; 1·365, 1·218-1·531), and chloroquine with a macrolide (22·2%; 1·368, 1·273-1·469) were each independently associated with an increased risk of in-hospital mortality. Compared with the control group (0·3%), hydroxychloroquine (6·1%; 2·369, 1·935-2·900), hydroxychloroquine with a macrolide (8·1%; 5·106, 4·106-5·983), chloroquine (4·3%; 3·561, 2·760-4·596), and chloroquine with a macrolide (6·5%; 4·011, 3·344-4·812) were independently associated with an increased risk of de-novo ventricular arrhythmia during hospitalisation. INTERPRETATION: We were unable to confirm a benefit of hydroxychloroquine or chloroquine, when used alone or with a macrolide, on in-hospital outcomes for COVID-19. Each of these drug regimens was associated with decreased in-hospital survival and an increased frequency of ventricular arrhythmias when used for treatment of COVID-19. FUNDING: William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women's Hospital.

Transcatheter aortic valve replacement associated infective endocarditis case series: broadening the criteria for diagnosis is the need of the hour.

BACKGROUND: Transcatheter valve replacement (TAVR) is an important therapeutic intervention for patients with aortic valve stenosis. As TAVR has become available to a broader population, there has been an increase in the number of less common, yet potentially catastrophic, complications. TAVR related infective endocarditis (TAVR-IE) is a rare, but potentially fatal, complication. CASE SERIES: We present here two patients that we encountered for TAVR associated infective endocarditis. Our first patient presented 5 weeks after his TAVR. His initial presentation was consistent with signs of sepsis. The patient then developed Mobitz type I block during hospital course. His TEE was negative for features of infective endocarditis. Due to high suspicion, patient was taken for surgical exploration and was found to have multiple foci of vegetation adhered to the stent frame. Our second patient presented with new onset pulmonary edema, worsening heart failure and systemic inflammatory response. A TEE was done for persistent MSSA bacteremia which showed stable prosthetic valve function with no signs of infective endocarditis. Patient was discharged with a prolonged course of intravenous antibiotics. Patient was re-admitted for worsening sepsis and blood cultures were positive for MSSA. Patient was taken for surgical exploration of his prosthetic aortic valve which showed purulent aortic root abscess. CONCLUSION: Through these cases, we aim to raise awareness on TAVR-IE. Due to the atypical clinical presentation, the modified Duke criteria may not be sufficient to diagnose TAVR-IE. Transesophageal echocardiogram in TAVR-IE may be negative or indeterminate. Prosthetic valve shadow may obscure smaller vegetations and/or smaller abscesses. A negative transesophageal echocardiogram should not rule out TAVR-IE and further diagnostic imaging modalities should be considered. PET/CT after administration of 18F-FDG (fluorodeoxyglucose) is a useful diagnostic tool in the diagnosis of infective endocarditis where TEE has been negative or inconclusive. Multi-modal imaging, in addition to the modified Duke criteria, can facilitate early diagnosis and improved mortality outcomes.

The contemporary model of vertebral column joint dysfunction and impact of high-velocity, low-amplitude controlled vertebral thrusts on neuromuscular function.

PURPOSE: There is growing evidence that vertebral column function and dysfunction play a vital role in neuromuscular control. This invited review summarises the evidence about how vertebral column dysfunction, known as a central segmental motor control (CSMC) problem, alters neuromuscular function and how spinal adjustments (high-velocity, low-amplitude or HVLA thrusts directed at a CSMC problem) and spinal manipulation (HVLA thrusts directed at segments of the vertebral column that may not have clinical indicators of a CSMC problem) alters neuromuscular function. METHODS: The current review elucidates the peripheral mechanisms by which CSMC problems, the spinal adjustment or spinal manipulation alter the afferent input from the paravertebral tissues. It summarises the contemporary model that provides a biologically plausible explanation for CSMC problems, the manipulable spinal lesion. This review also summarises the contemporary, biologically plausible understanding about how spinal adjustments enable more efficient production of muscular force. The evidence showing how spinal dysfunction, spinal manipulation and spinal adjustments alter central multimodal integration and motor control centres will be covered in a second invited review. RESULTS: Many studies have shown spinal adjustments increase voluntary force and prevent fatigue, which mainly occurs due to altered supraspinal excitability and multimodal integration. The literature suggests physical injury, pain, inflammation, and acute or chronic physiological or psychological stress can alter the vertebral column's central neural motor control, leading to a CSMC problem. The many gaps in the literature have been identified, along with suggestions for future studies. CONCLUSION: Spinal adjustments of CSMC problems impact motor control in a variety of ways. These include increasing muscle force and preventing fatigue. These changes in neuromuscular function most likely occur due to changes in supraspinal excitability. The current contemporary model of the CSMC problem, and our understanding of the mechanisms of spinal adjustments, provide a biologically plausible explanation for how the vertebral column's central neural motor control can dysfunction, can lead to a self-perpetuating central segmental motor control problem, and how HVLA spinal adjustments can improve neuromuscular function.

Phase I and registry study of autologous bone marrow concentrate evaluated in PDE5 inhibitor refractory erectile dysfunction.

BACKGROUND: Bone marrow mononuclear cells have been successfully utilized for numerous regenerative purposes. In the current study, patients suffering from erectile dysfunction (ED) unresponsive to phosphodiesterase 5 inhibitors were administered autologous bone marrow concentrate delivered intracavernously utilizing a point of care FDA cleared medical device. METHODS: A total of 40 patients were treated in the primary trial and 100 in the clinical registry, with the longest follow up of 12 months. RESULTS: Minimal treatment associated adverse effects where observed related to short term bruising at the site of harvest or injection. No long-term adverse events were noted related to the intervention. Mean improvements in IIEF-5 score were 2 in the Caverstem 1.0 low dose group, 3 in the high dose Caverstem 1.0 group and 9 in the Caverstem 2.0 group. Furthermore, improvements peaked by 3 months and maintained at 6 months follow-up. CONCLUSION: These data support the safety and efficacy of point of care, minimally to non-manipulated, non-expanded bone marrow concentrate for the treatment of ED. Trial registration Funded by Creative Medical Health, Inc.; Clinicaltrials.gov number: NCT03699943; https://clinicaltrials.gov/ct2/show/NCT03699943?term=caverstem&rank=1; initially registered December 12, 2015.

CNN and LSTM-Based Emotion Charting Using Physiological Signals.

Novel trends in affective computing are based on reliable sources of physiological signals such as Electroencephalogram (EEG), Electrocardiogram (ECG), and Galvanic Skin Response (GSR). The use of these signals provides challenges of performance improvement within a broader set of emotion classes in a less constrained real-world environment. To overcome these challenges, we propose a computational framework of 2D Convolutional Neural Network (CNN) architecture for the arrangement of 14 channels of EEG, and a combination of Long Short-Term Memory (LSTM) and 1D-CNN architecture for ECG and GSR. Our approach is subject-independent and incorporates two publicly available datasets of DREAMER and AMIGOS with low-cost, wearable sensors to extract physiological signals suitable for real-world environments. The results outperform state-of-the-art approaches for classification into four classes, namely High Valence-High Arousal, High Valence-Low Arousal, Low Valence-High Arousal, and Low Valence-Low Arousal. Emotion elicitation average accuracy of 98.73% is achieved with ECG right-channel modality, 76.65% with EEG modality, and 63.67% with GSR modality for AMIGOS. The overall highest accuracy of 99.0% for the AMIGOS dataset and 90.8% for the DREAMER dataset is achieved with multi-modal fusion. A strong correlation between spectral- and hidden-layer feature analysis with classification performance suggests the efficacy of the proposed method for significant feature extraction and higher emotion elicitation performance to a broader context for less constrained environments.

Eye and Voice-Controlled Human Machine Interface System for Wheelchairs Using Image Gradient Approach.

Rehabilitative mobility aids are being used extensively for physically impaired people. Efforts are being made to develop human machine interfaces (HMIs), manipulating the biosignals to better control the electromechanical mobility aids, especially the wheelchairs. Creating precise control commands such as move forward, left, right, backward and stop, via biosignals, in an appropriate HMI is the actual challenge, as the people with a high level of disability (quadriplegia and paralysis, etc.) are unable to drive conventional wheelchairs. Therefore, a novel system driven by optical signals addressing the needs of such a physically impaired population is introduced in this paper. The present system is divided into two parts: the first part comprises of detection of eyeball movements together with the processing of the optical signal, and the second part encompasses the mechanical assembly module, i.e., control of the wheelchair through motor driving circuitry. A web camera is used to capture real-time images. The processor used is Raspberry-Pi with Linux operating system. In order to make the system more congenial and reliable, the voice-controlled mode is incorporated in the wheelchair. To appraise the system's performance, a basic wheelchair skill test (WST) is carried out. Basic skills like movement on plain and rough surfaces in forward, reverse direction and turning capability were analyzed for easier comparison with other existing wheelchair setups on the bases of controlling mechanisms, compatibility, design models, and usability in diverse conditions. System successfully operates with average response time of 3 s for eye and 3.4 s for voice control mode.

Indole-2-Carboxamides Are Active against Mycobacterium abscessus in a Mouse Model of Acute Infection.

Nontuberculous mycobacteria (NTM) pathogens particularly infect patients with structural lung disorders. We previously reported novel indole-2-carboxamides (ICs) that are active against a wide panel of NTM pathogens. This study discloses in vivo data for two lead molecules (compounds 5 and 25) that were advanced for efficacy studies in Mycobacterium abscessus-infected mouse models. Oral administration of the lead molecules showed a statistically significant reduction in the bacterial loads in lung and spleen of M. abscessus-infected mice.

Hospital participation in clinical trials for patients with acute myocardial infarction: Results from the National Cardiovascular Data Registry.

BACKGROUND: Little is known about the proportion of hospitals in the United States that offer clinical trial enrollment opportunities and how patient outcomes differ between hospitals that do and do not participate in clinical trials. METHODS: In the nationwide Chest Pain-MI registry, we described the proportion of hospitals that enrolled patients with acute myocardial infarction (MI) in clinical trials from 2009 to 2014. Hospital-level adherence to every eligible MI performance measure was compared between hospitals that did and did not enroll patients in clinical trials. Using linked Medicare data, we also compared 1-year major adverse cardiovascular events (MACE: death, MI, heart failure, or stroke) among patients ≥65 years old treated at trial versus nontrial hospitals. RESULTS: Among 766 hospitals, 430 (56.1%) enrolled ≥1 MI patient in a clinical trial during the study period, but the proportion of hospitals enrolling patients in clinical trials declined from 36.8% in 2009 to 26.6% in 2014. Complete adherence to performance measures was delivered to a greater proportion of patients at trial hospitals than nontrial hospitals (72.6% vs 64.9%, P < .001; adjusted OR 1.07, 95% CI 1.03-1.12). One-year MACE rates were also lower for trial hospitals (adjusted HR 0.96, 95% CI 0.93-0.99). CONCLUSIONS: Hospitals are becoming less likely to engage in clinical trials for patients with MI. Patients admitted to hospitals that participated in clinical trials more often received guideline-adherent care and had better long-term outcomes.