Short‐term physiological response to high‐frequency‐actuated pVAD support

Ventricular assist devices (VADs) are an established treatment option for heart failure (HF). However, the devices are often plagued by material‐related hemocompatibility issues. In contrast to continuous flow VADs with high shear stresses, pulsatile VADs (pVADs) offer the potential for an endothelial cell coating that promises to prevent many adverse events caused by an insufficient hemocompatibility. However, their size and weight often precludes their intracorporeal implantation. A reduction of the pump body size and weight of the pump could be achieved by an increase in the stroke frequency while maintaining a similar cardiac output. We present a new pVAD system consisting of a pump and an actuator specifically designed for actuation frequencies of up to 240 bpm. In vitro and in vivo results of the short‐term reaction of the cardiovascular system show no significant changes in left ventricular and aortic pressure between actuation frequencies from 60 to 240 bpm. The aortic pulsatility increases when the actuation frequency is raised while the heart rate remains unaffected in vivo. These results lead us to the conclusion that the cardiovascular system tolerates short‐term increases of the pVAD stroke frequencies.     

Magnesium Metabolism in 4‐Year‐Old to 8‐Year‐Old Children

Magnesium (Mg) is a key factor in bone health, but few studies have evaluated Mg intake or absorption and their relationship with bone mineral content (BMC) or bone mineral density (BMD) in children. We measured Mg intake, absorption, and urinary excretion in a group of children 4 to 8 years of age. Mg absorption was determined using a dual‐tracer stable isotope technique, with ²⁵Mg given intravenously and ²⁶Mg given orally. We found a small, but significantly greater Mg absorption efficiency (percentage absorption) in males than females (67% ± 12% versus 60% ± 8%, p = 0.02) but no difference in estimated net Mg retention (average of 37 mg/d in both males and females). Relating dietary Mg intake to estimated Mg retention showed that an intake of 133 mg/d, slightly above the current estimated average requirement (EAR) of 110 mg/d, led to a net average retention of 10 mg/d, the likely minimum growth‐related need for this age group. Covariate analysis showed that Mg intake and total Mg absorption, but not calcium intake or total absorption were significantly associated with both total body BMC and BMD. These results suggest that usual Mg intakes in small children in the United States meet dietary requirements in most but not all children. Within the usual range of children's diets in the United States, dietary Mg intake and absorption may be important, relatively unrecognized factors in bone health. © 2014 American Society for Bone and Mineral Research.     

State‐constrained optimal control applied to cell‐cycle‐specific cancer chemotherapy

In this paper, the optimal drug injection problem arising in cancer treatment by cell‐cycle‐specific chemotherapy is investigated. The optimal control problem is state constrained in which the stage cost reflects the concern of maximal drug injection, while the state constraint imposes a lower bound on the total number of cells in the bone marrow. It is shown that this problem can be approximately solved up to any desired precision by using an indexed family of state‐unconstrained optimal control problems. The state constraint is fulfilled for any member of the family. The existence of solutions is proved and the resulting approximation is characterized by appropriate two‐sided inequalities. Simulations are provided to show the efficiency and relevance of the proposed formulation. Copyright © 2007 John Wiley & Sons, Ltd.     

Exploring performance of,and attitudes to,Stop‐ and Mock‐Before‐You‐Block in preventing wrong‐side blocks

We conducted an online survey to assess the career experiences of wrong side blocks, the practice of Stop‐Before‐You‐Block, the recently described method of Mock‐Before‐You‐Block and attitudes to these. Respondents were 208 anaesthetists across nine hospitals (173 consultants or Staff and Associate Specialist doctors'), representing 3623 years of collective anaesthetic practice. There had been a total of 62 wrong side blocks (by 51 anaesthetists and one current trainee). Predisposing factors for this were commonly ascribed to distractions (35 (69%), for example due to rushing or teaching), patient positioning (9 (18%)) or miscommunication (6 (12%)). Two (4%) respondents felt they had performed Stop‐Before‐You‐Block too early; 62 (41%) of all respondents stated they performed Stop‐Before‐You‐Block as early as preparing the skin or on arrival of the patient in the anaesthetic room, and not any later. Twenty (10%) respondents admitted to not performing Stop‐Before‐You‐Block at all or only occasionally (including 5 (2%) who had performed a wrong side block). Mock‐Before‐You‐Block was easily understood (by 169 out of 197 (86%)) and 14 out of 61 (23%) respondents felt it would have prevented the wrong side error in their case. However, free‐text comments indicated that many anaesthetists were reluctant to use a method that interrupted their performance of the block. We conclude that considerable work is needed to achieve full compliance with Stop‐Before‐You‐Block at the correct time.     

Metaphyseal‐Loading Anterolaterally‐Flared Femoral Stem in Cementless Total Hip Arthroplasty: Five‐ to Eleven‐Year Follow‐Up Evaluation

Using a nonlinear three‐dimensional finite element analysis simulating loading conditions, we designed a new type of proximal‐fitting, anterolaterally‐flared, arc‐deposit hydroxyapatite‐coated anatomical femoral stem (FMS‐anatomic stem; Japan Medical Materials, Osaka, Japan) for cementless total hip arthroplasty (THA) for Japanese patients with dysplastic hip osteoarthritis. The aim of the present study was to analyze the clinical and radiographic outcomes of the new stem. We reviewed 143 consecutive patients (164 hips; 13 men, 14 hips; 130 women, 150 hips; age at surgery, 56.6 ± 7.6 years, mean ± SD, range, 30–74) who underwent cementless THA using the FMS‐anatomic stem at a single institution, with a follow‐up period of 7.6 ± 1.6 years (range, 5.3–11.0). Harris Hip score improved from 46.1 ± 12.6 before surgery to 90.0 ± 8.9 points post‐THA. The 7.6‐year survival rate of the stem was 99.0% after revision for aseptic loosening. Radiographs at follow‐up confirmed the stability of the femoral stems within the femoral canal in all cases, with sufficient bone ingrowth. None of the patients had subsidence of the stem exceeding 2.0 mm within the femoral canal or changes in varus or valgus position of more than 2.0°. The FMS‐anatomic stem provided excellent results in patients with dysplastic hip osteoarthritis. Our analysis confirmed reduced radiolucency around the stem in Gruen zones, minimal subsidence, appropriate stress shielding, and promising medium‐term stability within the femoral canal in our patients.     

Heterogeneity in the Antibody Response to Foot‐and‐Mouth Disease Primo‐vaccinated Calves

Foot‐and‐mouth disease (FMD) vaccines are routinely used as effective control tools in large regions worldwide and to limit outbreaks during epidemics. Vaccine‐induced protection in cattle has been largely correlated with the FMD virus (FMDV)‐specific antibodies. Genetic control of cattle immune adaptive responses has been demonstrated only for peptide antigens derived from FMDV structural proteins. Here, we quantify the heterogeneity in the antibody response of cattle primo‐vaccinated against FMD and study its association with the genetic background in Holstein and Jersey sires. A total of 377 FMDV‐seronegative calves (122 and 255 calves from 16 and 15 Holstein and Jersey sires, respectively) were included in the study. Samples were taken the day prior to primo‐vaccination and 45 days post‐vaccination (dpv). Animals received commercial tetravalent FMD single emulsion oil vaccines formulated with inactivated FMDV. Total FMDV‐specific antibody responses were studied against three viral strains included in the vaccine, and antibody titres were determined by liquid‐phase blocking ELISA. Three linear hierarchical mixed regression models, one for each strain, were formulated to assess the heterogeneity in the immune responses to vaccination. The dependent variables were the antibody titres induced against each FMDV strain at 45 dpv, whereas sire's ‘breed’ was included as a fixed effect, ‘sire’ was included as a random effect, and ‘farm’ was considered as a hierarchical factor to account for lack of independence of within herd measurements. A significant association was found between anti‐FMDV antibody responses and sire's breed, with lower immune responses found in the Jersey sires’ offspring compared with those from Holstein sires. No significant intrabreed variation was detected. In addition, farm management practices were similar in this study, and results of the serological assays were shown to be repeatable. It therefore seems plausible that differences in the immune response may be expected in the event of a mass vaccination campaigns.     

MPC‐based tracking for real‐time systems subject to time‐varying polytopic constraints

This paper presents a real‐time MPC‐based tracking strategy for linear systems subject to time‐varying constraints. The framework is quite general because the time‐varying constraints can apply both to the state and to the input. To handle the problem, a polytopic invariant set computed off‐line is homogeneously dilated or contracted on‐line to fit the polytopic time‐varying constraints. The invariant set is used as an admissible terminal constraint set so that it guarantees stability and convergence in the tracking task. The on‐line cost of the homothetic invariant set computation is low enough to cope with systems subject to stringent real‐time constraints. Copyright © 2015 John Wiley & Sons, Ltd.     

Semi‐xenotransplantation: the regenerative medicine‐based approach to immunosuppression‐free transplantation and to meet the organ demand

Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine‐based approach termed “semi‐xenotransplantation” (SX) seeks to overcome these obstacles by combining the availability and reproducibility of animal organs with the biocompatibility and functionality of human allografts. Compared to conventional xenotransplantation wherein the whole organ is animal‐derived, SX grafts are cleansed of their antigenic cellular compartment to produce whole‐organ extracellular matrix scaffolds that retain their innate structure and vascular channels. These scaffolds are then repopulated with recipient or donor human stem cells to generate biocompatible semi‐xenografts with the structure and function of native human organs. While numerous hurdles must be still overcome in order for SX to become a viable treatment option for end‐stage organ failure, the immense potential of SX for meeting the urgent needs for a new source of organs and immunosuppression‐free transplantation justifies the interest that the transplant community is committing to the field.     

Applying a cognitive‐emotional model to nonsuicidal self‐injury

The recently proposed cognitive‐emotional model of nonsuicidal self‐injury (NSSI) draws on emotion regulation models and social cognitive theory to understand the onset, maintenance, and cessation of NSSI. We tested the prediction of the model that the relationship between emotional reactivity and NSSI is moderated by specific cognitions about self‐injury (i.e., self‐efficacy to resist NSSI, NSSI outcome expectancies), emotion regulation, and rumination. A sample of 647 university students aged 17–25 years (M = 19.92, SD = 1.78) completed self‐report measures of the constructs of interest. As expected, we found that emotional reactivity was positively related to NSSI, particularly for people who had weak self‐efficacy to resist NSSI. However, emotional reactivity was negatively related to NSSI for people who were more likely to use expressive suppression to regulate emotion. Implications for the theoretical understanding of NSSI are discussed.     

Recent progress in immune‐based interventions to prevent HIV‐1 transmission to children

Globally, 150,000 new paediatric human immunodeficiency virus type 1 (HIV‐1) infections occurred in 2015. There remain complex challenges to the global elimination of paediatric HIV‐1 infection. Thus, for the global community to achieve elimination of new paediatric HIV‐1 infections, innovative approaches need to be explored. Immune‐based approaches to prevention of mother‐to‐child transmission (MTCT) may help fill some of the remaining gaps and provide new opportunities to achieve an AIDS‐free generation. Immune‐based interventions to prevent MTCT of HIV‐1 may include paediatric HIV vaccines and passive immunization approaches. Recent discoveries providing evidence of robust immune responses to HIV in infants open new and exciting prospects for paediatric HIV vaccines. Moreover, successful vaccination of infants has a different set of requirements than vaccination of adults and may be easier to achieve. Proof‐of‐concept has been established over the last two decades that passively administered HIV‐1 Env‐specific monoclonal antibody (mAbs) can prevent chimeric simian human immunodeficiency virus (SHIV) transmission to newborn nonhuman primates. There has been tremendous progress in isolating and characterizing broadly neutralizing antibodies to HIV, and clinical testing of these antibodies for treatment and prevention in both infants and adults is a major effort in the field. Immune‐based interventions need to be actively explored as they can provide critically important tools to address persistent challenges in MTCT prevention. It is a pivotal time for the field with active discussions on the best strategy to further reduce HIV infection of infants and accomplish the World Health Organization Fast‐Track 2030 goals to eliminate new paediatric HIV infections.     

miR‐21 expression is related to particle‐induced osteolysis pathogenesis

Previous studies have found that microRNA‐21 (miR‐21) is an important functional factor during osteoclast differentiation. Abnormal osteoclastogenesis induced by wear particles is the main cause of aseptic loosening in joint replacements. The aim of the present study is to investigate the possible role of miR‐21 in the pathogenesis of particle‐induced osteolysis (PIO). miR‐21 expression was examined in a PIO mouse model using real‐time (RT‐PCR). Osteoclastogenesis was determined by a tartrate resistant acid phosphatase (TRAP) quantification method. A toluidine blue staining assay was used to examine calvarial osteolysis. The results demonstrated that miR‐21 was significantly upregulated in the PIO animal model. Knocking out miR‐21 in the particle‐stimulated tissue could ameliorate osteolysis symptoms. Additionally, through our analysis of PDCD4 and AP‐1 expression, we suggest that the feedback loop of AP‐1, miR‐21, and PDCD4 might have an important influence on the development of PIO and that miR‐21 is a potential target for implant loosening therapies. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1837–1842, 2012