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Human machine interaction (HMI) allows persons to control and interact with devices. Starting from elementary apparatus which acquires input biosignals to controlling various applications. Medical applications are amongst the very important applications of HMI. One of these medical applications is assisting fully/partially paralyzed patients to restore movements or freely move using exoskeletons or motorized wheelchairs. Helping patients with spinal cord injury or serious neurological diseases to restore their movements is a key role objective for most researchers in this field. In this paper, an EEG-based HMI system is proposed to assist patients with tetraplegia/quadriplegia to mentally control a motorized wheelchair so they can move freely and independently. EEG power spectrum (α, β, δ, θ, and γ) from the frontal lobe of brain is recorded, filtered and wirelessly sent to the wheelchair to control directions and engine status. Four different experiments were conducted using the proposed system in order to validate the performance. Two different GUIs scenarios (cross-shaped and horizontal bar) were used with the experiments. Results showed that the horizontal bar scenario considered more user friendly while the cross-shaped is the more suitable for navigation. The implemented system can be equipped with modules and sensors such as GPS, ultrasound and accelerometer that improve the system performance and reliability.

Medications are vital for patients and especially for those who are receiving treatment in hospitals. Providing medications for these people is essential to maintain their health. On the other hand, medication dispensing error is one of the most common challenges that face clinical pharmacists and medical staff. These errors frequently occurred due to poor medication systems and/or human factors (i.e. environmental conditions, fatigue or staff shortage). These factors may affect prescribing, transcribing, administration, dispensing and monitoring practices which can result in disability, severe harm and even death. Avoiding medication dispensing errors is the key motivation of this paper. Consequently, a biometric-based dispensing system has been designed and implemented. The system can be installed at hospital wards and used for delivering and monitoring inpatients doses. It consists of three parts; hardware, software and mechanical part. Three 4-phase stepper motors are used for controlling the mechanical part of this system. An optical fingerprint sensor is used which is compatible with the ESP32 low-power SoC for scanning patients’ fingerprints to recognize and store their data. The system directly updates its database whenever is used by the inpatients, so that nobody can get additional doses. This system is cost-effective, reliable and easy to use.

We analyzed samples obtained at baseline and 24 months in a mass azithromycin administration trial in Niger using quantitative polymerase chain reaction. In villages randomized to azithromycin, Shigella was the only pathogen reduced at 24 months (prevalence ratio, 0.36 [95% confidence interval: .17–.79]; difference in log quantity, −.42 [−.75 to −.10]).

Adenosine deaminase (ADA) deficiency causes ∼13% of cases of severe combined immune deficiency (SCID). Treatments include enzyme replacement therapy (ERT), hematopoietic cell transplant (HCT), and gene therapy (GT). We evaluated 131 patients with ADA-SCID diagnosed between 1982 and 2017 who were enrolled in the Primary Immune Deficiency Treatment Consortium SCID studies. Baseline clinical, immunologic, genetic characteristics, and treatment outcomes were analyzed. First definitive cellular therapy (FDCT) included 56 receiving HCT without preceding ERT (HCT); 31 HCT preceded by ERT (ERT-HCT); and 33 GT preceded by ERT (ERT-GT). Five-year event-free survival (EFS, alive, no need for further ERT or cellular therapy) was 49.5% (HCT), 73% (ERT-HCT), and 75.3% (ERT-GT; P < .01). Overall survival (OS) at 5 years after FDCT was 72.5% (HCT), 79.6% (ERT-HCT), and 100% (ERT-GT; P = .01). Five-year OS was superior for patients undergoing HCT at

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve in humans. Spike protein mutations increase transmission and potentially evade antibodies raised against the original sequence used in current vaccines. Our evaluation of serum neutralizing activity in both persons soon after SARS-CoV-2 infection (in April 2020 or earlier) or vaccination without prior infection confirmed that common spike mutations can reduce antibody antiviral activity. However, when the persons with prior infection were subsequently vaccinated, their antibodies attained an apparent biologic ceiling of neutralizing potency against all tested variants, equivalent to the original spike sequence. These findings indicate that additional antigenic exposure further improves antibody efficacy against variants. IMPORTANCE As SARS-CoV-2 evolves to become better suited for circulating in humans, mutations have occurred in the spike protein it uses for attaching to cells it infects. Protective antibodies from prior infection or vaccination target the spike protein to interfere with its function. These mutations can reduce the efficacy of antibodies generated against the original spike sequence, raising concerns for reinfections and vaccine failures, because current vaccines contain the original sequence. In this study, we tested antibodies from people infected early in the pandemic (before spike variants started circulating) or people who were vaccinated without prior infection. We confirmed that some mutations reduce the ability of antibodies to neutralize the spike protein, whether the antibodies were from past infection or vaccination. Upon retesting the previously infected persons after vaccination, their antibodies gained the same ability to neutralize mutated spike as the original spike, suggesting that the combination of infection and vaccination drove the production of enhanced antibodies to reach a maximal level of potency. Whether this can be accomplished by vaccination alone remains to be determined, but the results suggest that booster vaccinations may help improve efficacy against spike variants through improving not only antibody quantity, but also quality.

Monogenic disorders of the blood system have the potential to be treated by autologous stem cell transplantation of ex vivo genetically modified hematopoietic stem and progenitor cells (HSPCs). The sgRNA/Cas9 system allows for precise modification of the genome at single nucleotide resolution. However, the system is reliant on endogenous cellular DNA repair mechanisms to mend a Cas9-induced double stranded break (DSB), either by the non-homologous end joining (NHEJ) pathway or by the cell-cycle regulated homology-directed repair (HDR) pathway. Here, we describe a panel of ectopically expressed DNA repair factors and Cas9 variants assessed for their ability to promote gene correction by HDR or inhibit gene disruption by NHEJ at the HBB locus. Although transient global overexpression of DNA repair factors did not improve the frequency of gene correction in primary HSPCs, localization of factors to the DSB by fusion to the Cas9 protein did alter repair outcomes toward microhomology-mediated end joining (MMEJ) repair, an HDR event. This strategy may be useful when predictable gene editing outcomes are imperative for therapeutic success.

Coronary artery bypass grafting (CABG) is the standard treatment modality in revascularization of the myocardium. However, the graft failure remains the major complication following CABG procedure. Involvement of mitochondrial damage-associated molecular patterns (mt-DAMPs) in the pathogenesis of vein-graft failure is largely unknown. Here, we investigated the expression of major protein-mt-DAMPs, cytochrome-C (Cyt-C), heat shock protein-60 (Hsp-60), mitochondrial transcription factor A (mtTFA), in the occluded graft and associated tissues, including distal left anterior descending (LAD), LAD adjacent to anastomosis, and left internal mammary artery (LIMA) in the microswine CABG model. The protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) was significantly decreased in the graft and LIMA, whereas the protein expression of hypoxia inducible factor-1 alpha (HIF-1α) and Cyt-C was decreased and that of mtTFA and Hsp60 was increased in all tissues compared to controls. There was no significant difference in the protein expression of citrate synthase, complex-1, and mitochondrial pyruvate dehydrogenase in the graft and associated tissues compared to control. Hypoxia in cultured smooth muscle cells (SMCs) significantly upregulated all mitochondrial biomarkers and mt-DAMPs compared to normoxia. The increased reactive oxygen species (ROS) content and compromised membrane integrity in the hypoxic SMCs correlated well with increased mt-DAMPs in the graft and associated tissues, suggesting a possible role of mt-DAMPs in the pathogenesis of graft failure. These findings suggest that the pathological signals elicited by mt-DAMPs could reveal targets for better therapeutic approaches and diagnostic strategies in the management of CABG graft failure.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human β-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic βAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types.

The aim of this work is to study the effect of aggregate type on the physico-mechanical properties and microstructure of bio-mortar (BM). Three different aggregates such as sand, dolomite and basal...

The spike (S) glycoprotein of SARS-Cov-2 facilitates viral entry into target cells via the cell surface receptor angiotensin-converting enzyme 2 (ACE2). Third generation HIV-1 lentiviral vectors can be pseudotyped to replace the native CD4 tropic envelope protein of the virus and thereby either limit or expand the target cell population. We generated a modified S glycoprotein of SARS-Cov-2 to pseudotype lentiviral vectors which efficiently transduced ACE2-expressing cells with high specificity and contain minimal off-target transduction of ACE-2 negative cells. By utilizing optimized codons, modifying the S cytoplasmic tail domain, and including a mutant form of the spike protein (D614G), we generated an expression plasmid encoding the optimized protein that produces S pseudotyped lentiviral vectors at an infectious titer (TU/mL) 1000-fold higher than the unmodified S protein. S pseudotyped replication-defective lentiviral vectors eliminate the need for biosafety-level-3 laboratories required when developing therapeutics against SARS-CoV-2 with live infectious virus. Furthermore, S pseudotyped vectors with high activity and specificity may be used as tools to understand the development of immunity against SARS-CoV-2, to develop assays of neutralizing antibodies and other agents that block viral binding, and to allow in vivo imaging studies of ACE-2 expressing cells. Funding: This work was supported by a UCLA David Geffen School of Medicine (DGSOM) and Broad Stem Cell Research Center (BSCRC) COVID 19 Research Award. Dr. Lili Yang (UCLA) and Dr. Pin Wang (USC) provided the ACE2 expressing 293T cell line (ACE-293T). Dr. Jocelyn Kim (UCLA) provided the VeroE6 cell lines. The Flow Cytometry Core of the UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the Virology Core of the UCLA Center for AIDS Research (CFAR) (5P30 AI028697) were used to support studies.

Monitoring the heart activities for old people or people with medical history (Arrhythmia or CHD) is targeted by most new medical technologies. This paper demonstrated an in-patient real-time monitoring system for heart rate estimation. A ratio of beats per minute (BPM) is continuously recorded, streamed and archived to the cloud via WeMos WiFi development board. This cost effective system is simply based on two sub-systems: BPM data acquisition through pulse sensor and WeMos-based communication systems. The streamed BPM data are saved instantaneously in Google drive as spreadsheets which can only be accessed by authorized persons wherever the internet service is available. Thus, the person in charge can remotely observe the patient’s status and do analytics for the archived data. A pilot study with eight subjects was carried out to validate the developed BPM tele-monitoring system. Encouraging results have been achieved.

β-globin lentiviral vectors (β-LV) have faced challenges in clinical translation for gene therapy of sickle cell disease (SCD) due to low titer and sub-optimal gene transfer to hematopoietic stem and progenitor cells (HSPCs). To overcome the challenge of preserving efficacious expression while increasing vector performance, we used published genomic and epigenomic data available through ENCODE to redefine enhancer element boundaries of the β-globin locus control region (LCR) to construct novel ENCODE core sequences. These novel LCR elements were used to design a β-LV of reduced proviral length, termed CoreGA-AS3-FB, produced at higher titers and possessing superior gene transfer to HSPCs when compared to the full-length parental β-LV at equal MOI. At low vector copy number, vectors containing the ENCODE core sequences were capable of reversing the sickle phenotype in a mouse model of SCD. These studies provide a β-LV that will be beneficial for gene therapy of SCD by significantly reducing the cost of vector production and extending the vector supply.

Purpose Heart Transplantation (HTX) is an established therapy for endstage Heart Failure with excellent long term results. However, shortage of donor organs leads to increased use of extended criteria organs and rising numbers of high risk recipients on the high-urgency list and on mechanical circulatory support (MCS). Donor organ machine perfusion (MP) allows continuous warm perfusion of the beating heart, thus reducing time of ischemia as well as allowing for standardized evaluation. AIM: analyze outcome of HTX using donor heart MP. Methods In a retrospective single-center study, data from a prospectively collected database were analyzed. From July 2018 to September 2020, eleven hearts were retrieved and perfused using the Organ Care System (OCS), 9 hearts were transplanted. Criteria to use the OCS were 1) estimated ischemic time > 4 hours for any reason, 2) inotropes > 0.25 µg/kg/min, 3) LV-EF Results All patients survived the procedure and the 30-day interval [time since HTX 8-799 d]. No MP related complications were noted. One patient died after 233 days due to sepsis. 4 patients were on temporary ECLS support in the early postoperative period (6-12d) due to initial right ventricular dysfunction. Graft ejection fraction beyond 14 days was ≥ 50% in all cases. Endomyocardial biopsies showed no rejection or mild rejection 1R in two cases (21d and 3 months surveillance biopsy). Two donor hearts were rejected after OCS perfusion 1) because of previously unknown coronary artery disease (angiography on OCS) and 2) due to underestimated aortic valve insufficiency and severe septum hypertrophy. Conclusion Ex vivo normothermic MP during organ procurement is a safe and promising technique to expand the donor pool. Reduction of cold ischemic time while providing additional donor heart assessment and reconditioning options may increase the number of acceptable donor hearts and improve results. Future clinical trials will bring further evidence, clear guidelines regarding application of MP have to be developed.

Purpose Ex vivo lung perfusion (EVLP) offers a unique potential in evaluation, optimization and transplantation of lungs that would otherwise potentially be rejected. Between 2016 and 2020 208 lung transplants (LuTx) were performed and 22 donor lungs were evaluated by EVLP of which 16 were transplanted. Aim of the study was to compare mid-term results in LuTx recipients with or without the use of EVLP. Methods In a retrospective single-center analysis data from a prospectively collected database were analysed. The EVLP group (n=16) consisted of donor lungs classified as marginal and were evaluated by EVLP and afterwards transplanted. The non EVLP group (n=16) consisted of conventional LuTx recipients matched for age and pulmonary disease. Both groups were compared for the endpoints survival, primary graft dysfunction, rejection episodes and chronic allograft dysfunction. Results Recipient age was 55 ± 6 years in EVLP group and 57 ± 5 years non EVLP group (n.s.). Female gender was present in 36% EVLP patients and 50% non EVLP (n.s.). The rate PGD grade 1 at 72 h post-LTx was 14% in both groups (each2/16). In non EVLP group 1recipient was PGD 2 (7%). PGD3 was present only in the EVLP group 14% (2/16) vs. 0% in control. At last visit, post-LuTx, forced expiratory volume in 1 s (FEV1%) as percentage of predicted best was similar in the EVLP and non-EVLP group (77% vs. 78%). Chronic lung allograft dysfunction was diagnosed in one non EVLP patient and one EVLP patient during follow up post-LuTx. In the EVLP group 2 patients had rejection episodes subjected to treatment and 6 patients in the non EVLP group (n.s.). Survival at 1 year was 81% for the EVLP group and 94% in non EVLP group (n.s.). Conclusion Recipients transplanted with extended criteria donor lungs, thoroughly evaluated by EVLP show similar mid term outcomes as conventionally transplanted lungs from standard donors. EVLP shall increase the number of acceptable donor lungs. Future clinical trials will bring further evidence; clear guidelines regarding application of machine perfusion have to be developed.

Breast cancer is one of the leading reason of death among women. Nevertheless, medications for this fatal disease are still away of ambitions. Patients (thought to have breast cancer) should go through several advanced medical diagnostic procedures like mammography, biopsy analysis, ultrasound imaging, etc. Mammography is one of the medical imaging techniques used for detecting breast cancer. However, its resulted images may not be clear enough or helpful for physician to diagnose each case correctly. This fact has pushed researchers towards developing effective ways to enhance images throughout using various enhancement algorithms. In this paper, a comparison amongst these applied algorithms was done to evaluate the optimum enhancement technique. A morphology enhancement, which is resulted from combining top-hat operation and bottom-hat operation, was used as a proposed enhancement algorithm. The proposed enhancement algorithm was compared to three other well-known enhancement algorithms, specifically histogram equalization, logarithmic transform, and gamma correction with different gamma values. Twenty-five mammographic images were taken from the mammography image analysis society (MIAS) database samples. The minimum entropy difference value (EDV) was used as metric to evaluate the best enhancement algorithm. Results has approved that the proposed enhancement algorithm gave the best-enhanced images in comparison to the aforementioned algorithms.

Introduction: Heart Failure (HF) is categorized according to the AHA/ACC 2013 HF Guidelines based on Left Ventricular Ejection Fraction (LVEF); HF with Reduced Ejection Fraction (HFrEF, EF≤40%), and HF with preserved EF (HFpEF, EF ≥ 50%). There is a group of “borderline” patients with EF 41%-49%, termed Heart Failure with Mid-Range Ejection Fraction (HFmrEF). Given this category is not well understood, we sought to evaluate clinical characteristics and management patterns for patients with HFmrEF. Methods: A systematic review was performed using Ovid MEDLINE, EMBASE, Cochrane CENTRAL and LILACS (1946 – 03/2018). Search terms included HF, mid-range, borderline LVEF with several ranges (40-50 or 40-45 or 45-50). Variables characterizing clinical features and medications were extracted for each HF group and adjusted odds ratios (ORs) were pooled. Results: Of 1,131 abstracts identified, 24 met inclusion criteria (total patients 480,188). Patients with HFmrEF compared to those with HFrEF were more likely to be female (OR 1.42), have hypertension [HTN] (OR 1.34) and diabetes (OR 1.11), higher SBP (OR 1.17), better NYHA-FC (FC I OR 1.73, FC II 1.33), less likely to have coronary artery disease [CAD] (OR 0.74) and more likely to be treated with ACEI, ARB, BB, Digoxin, MRA and statins (Figure 1-2). HFmrEF patients when compared to those with HFpEF were less likely to be female (OR 0.54) or have HTN (OR 0.68), and more likely to have CAD (OR 1.25), and to be treated with HF medications and statins. Conclusions: Patients with HFmrEF have higher SBP and better NYHA-FC (I and II) compared to HFrEF patients and are less likely to be female and more likely to have CAD compared to HFpEF patients. Further research is needed to help guide management in this unique but clinically important population. Figure 1A. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFrEF vs HFmrEF patients Figure 1B. Forest plot of adjusted ORs comparing baseline clinical characteristics of HFmrEF vs HFpEF patients Figure 2A. Forest plot of adjusted ORs comparing medications used in HFrEF vs HFmrEF patients Figure 2B. Forest plot of adjusted ORs comparing medications used in HFmrEF vs HFpEF patients

Composite materials have been widely used in many applications but understanding their failure behavior is always challenging. For years, numerical investigation has been the effective alternative, even though the underlying theories related to composite materials are complicated. This study aims to investigate the improved strength of hybridization by comparing the failure behavior of glass-epoxy composite laminate and hybrid glass-graphite-epoxy laminate under transverse sinusoidal load. The composite and hybrid composite laminates with various aspect ratios were modelled using ANSYS. The plates were simply supported and transverse sinusoidal load were applied until failure occurs. Initially, numerical validation was performed and the simulated results are found to be close to the 3D elasticity analytical results. In general, most simulated parameters produced error less than 2% and thus proving the reliability of the finite element models and implementation. The first ply failure (FPF) and last ply failure (LPF) curves were plotted to compare the failure trend of glass-epoxy composite laminate and its hybrid laminate. The results showed no significant difference in the FPF trend but hybridization could withstand up to 80% more normalized load in terms of the LPF. In conclusion, the present study has shed new knowledge about the failure behavior of hybrid laminate and thus, this knowledge could be applied in designing hybrid composite laminates.

El trasplante de organos ha experimentado un enorme desarrollo en las ultimas decadas, lo que ha permitido mejorar en gran medida el pronostico de los pacientes con distintos tipos de insuficiencia visceral terminal. Sin embargo, han aparecido complicaciones relacionadas de forma directa o indirecta con el trasplante, mas concretamente con los tratamientos que implica. Este articulo esta dedicado a las complicaciones osteoarticulares de los trasplantes de organos, prestando especial atencion a los mecanismos fisiopatologicos y a las modalidades terapeuticas adecuadas a estas delicadas situaciones.

International audience; Polyethylene-based polymers as biomedical materials can contribute to a wide range of biomechanical applications. Therefore, it is important to identify, analyse, and predict with precision their mechanical behaviour. Polyethylene materials are semi-crystalline systems consisting of both amorphous and crystalline phases interacting in a rather complex manner. When the amorphous phase is in the rubbery state, the mechanical behaviour is strongly dependent on the crystal fraction, therefore leading to essentially thermoplastic or elastomeric responses. In this study, the finite deformation stress-strain response of polyethylene materials is modelled by considering these semi-crystalline polymers as two-phase heterogeneous media in order to provide insight into the role of crystalline and amorphous phases on the macro-behaviour and on the material deformation resistances, i.e. intermolecular and network resistances. A hyperelastic-viscoplastic model is developed in contemplation of representing the overall mechanical response of polyethylene materials under large deformation. An evolutionary optimization procedure based on a genetic algorithm is developed to identify the model parameters at different strain rates. The identification results show good agreement with experimental data, demonstrating the usefulness of the proposed approach: the constitutive model, with only one set of identified parameters, allows reproducing the stress-strain behaviour of polyethylene materials exhibiting a wide range of crystallinities, the crystal content becoming the only variable of the model.

Etude descriptive semantique et syntaxique de la suffixation du nom en « n » en arabe. Dans le cadre de la theorie des barrieres, la fonction des differents types de « tanwīn » peut etre ramenee a celle de « lieur par defaut » d'un element (+N) en liaison avec la marque de son statut referentiel ou prediquant

Of 39 consecutive cadaver donors tested, DR antigens could not be detected in 17. Following 3 h incubation of the B lymphocytes at 37 degrees C, eight of the donors with no detectable DR antigens had two DR antigens and nine had one DR antigen. In addition, there were nine cases in which a potential cadaver donor had one antigen before incubation and two DR antigens following incubation. The simple technique of pre-incubating B lymphocytes before testing has helped considerably in prospectively typing cadaver donors for HLA-DR.

The Waring problem deals with the decomposition of integers into sums of kth powers. Consider

1. Introduction. Recently two Japanese authors (1) gave a beautifully simple proof of Selberg's fundamental lemma in the theory of distribution of primes. The proof is based on a curious twist in the Möbius inversion formula. The object of this note is to show that their proof may be extended to a proof of the result for algebraic fields corresponding to Selberg's lemma. Shapiro (2) has already derived this result using Selberg's methods and deduced as a consequence the prime ideal theorem.

• Eight children with acute leukemia in relapse were hypokalemic during their hospital course. All had accompanying hypophosphatemia, and three had mild metabolic alkalosis. Potassium chloride supplementation in each case resulted in resolution of the electrolyte and acid-base disturbances. These findings were not present in patients with conditions newly diagnosed or those in remission. The pathogenesis of the electrolyte and acid-base disturbances was not evident and was not related to antibiotic or cytotoxic drug therapy, but may have been related to the patients' poor nutritional status. Seven of the eight patients died within six months of the hypokalemic episode. Hypokalemia may be a common accompaniment of terminal leukemia. ( Am J Dis Child 130:937-940, 1976)

Prospective kidney transplant recipients, who have broadly reactive cytotoxic antibodies, are currently at a considerable disadvantage in competing for shared kidneys since they tend not to be considered as candidates because of the likelihood of kidney wastage subsequent to positive crossmatch tests. Alternative to extensive shipping, storage and crossmatch testing by the harvesting center, is the prediction of crossmatch outcome on the basis of donor HLA type and recipient sera characteristics. A prediction method was developed that yields approximately 85% correct predictions. The method was validated by predicting crossmatch outcome of 67 consecutive cadaveric donors tested against 87 recipients and is suggested as useful for guiding kidney sharing programs.

A case of hemolytic uremic syndrome (HUS) in a 3 year old boy, who presented with diffuse rectal bleeding is discussed. On barium enema, there was evidence of acute colitis with submucosal hemorrhage. The probable relationship of these findings to the pathogenetic intravascular coagulopathy and the prodromal stage of HUS is discussed.