Fractal Electronics for Stimulating and Sensing Neural Networks: Enhanced Electrical, Optical, and Cell Interaction Properties.

Imagine a world in which damaged parts of the body - an arm, an eye, and ultimately a region of the brain - can be replaced by artificial implants capable of restoring or even enhancing human performance. The associated improvements in the quality of human life would revolutionize the medical world and produce sweeping changes across society. In this chapter, we discuss several approaches to the fabrication of fractal electronics designed to interface with neural networks. We consider two fundamental functions - stimulating electrical signals in the neural networks and sensing the location of the signals as they pass through the network. Using experiments and simulations, we discuss the favorable electrical performances that arise from adopting fractal rather than traditional Euclidean architectures. We also demonstrate how the fractal architecture induces favorable physical interactions with the cells they interact with, including the ability to direct the growth of neurons and glia to specific regions of the neural-electronic interface.

Fractal Resonance: Can Fractal Geometry Be Used to Optimize the Connectivity of Neurons to Artificial Implants?

In parallel to medical applications, exploring how neurons interact with the artificial interface of implants in the human body can be used to learn about their fundamental behavior. For both fundamental and applied research, it is important to determine the conditions that encourage neurons to maintain their natural behavior during these interactions. Whereas previous biocompatibility studies have focused on the material properties of the neuron-implant interface, here we discuss the concept of fractal resonance - the possibility that favorable connectivity properties might emerge by matching the fractal geometry of the implant surface to that of the neurons.To investigate fractal resonance, we first determine the degree to which neurons are fractal and the impact of this fractality on their functionality. By analyzing three-dimensional images of rat hippocampal neurons, we find that the way their dendrites fork and weave through space is important for generating their fractal-like behavior. By modeling variations in neuron connectivity along with the associated energetic and material costs, we highlight how the neurons' fractal dimension optimizes these constraints. To simulate neuron interactions with implant interfaces, we distort the neuron models away from their natural form by modifying the dendrites' fork and weaving patterns. We find that small deviations can induce large changes in fractal dimension, causing the balance between connectivity and cost to deteriorate rapidly. We propose that implant surfaces should be patterned to match the fractal dimension of the neurons, allowing them to maintain their natural functionality as they interact with the implant.

Using Fractal Iconography to Emulate Nature's Aesthetics.

This year's cover artists are members of a team of physicists and psy-chologists who create human-centered designs based on psychology experiments that investigate the positive impacts of viewing fractal patterns. These positive impacts include reduced physiological stress levels and enhanced cognitive skills. Here, the team explores the concept of 'fractal iconography' as an approach to employing computers to generate naturalistic art. Adopting this approach, three forms of fractal patterning ('fractal icons') are combined in a variety of ways to generate the rich complexity of nature's scenery. These composite fractals are remarkably effective at conveying nature's aesthetic power.

Monoclonal Antibodies Opsonize Burkholderia spp. and Reduce Intracellular Actin Tail Formation in a Macrophage Infection Assay.

Melioidosis is a neglected tropical disease caused by the bacterium Burkholderia pseudomallei. The bacterium is intrinsically resistant to various antibiotics, and melioidosis is therefore difficult to treat successfully without a relapse in infection. B. pseudomallei is an intracellular pathogen and therefore, to eradicate the infection, antimicrobials must be able to access bacteria in an intracellular niche. This study assessed the ability of a panel of monoclonal antibodies (MAbs) to opsonize Burkholderia species and determine the effect that each antibody has on bacterial virulence in vitro. Murine macrophage infection assays demonstrated that monoclonal antibodies against the capsule of B. pseudomallei are opsonizing. Furthermore, one of these monoclonal antibodies reduced bacterial actin tail formation in our in vitro assays, indicating that antibodies could reduce the intracellular spread of Burkholderia thailandensis. The data presented in this paper demonstrate that monoclonal antibodies are opsonizing and can decrease bacterial actin tail formation, thus decreasing their intracellular spread. These data have informed selection of an antibody for development of an antibody-antibiotic conjugate (AAC) for melioidosis. IMPORTANCE Melioidosis is difficult to treat successfully due to the causal bacterium being resistant to many classes of antibiotics, therefore limiting available therapeutic options. New and improved therapies are urgently required to treat this disease. Here, we have investigated the potential of monoclonal antibodies to target this intracellular pathogen. We have demonstrated that monoclonal antibodies can target the bacterium, increase uptake into macrophages, and reduce actin tail formation required by the bacterium for spread between cells. Through targeting the bacterium with antibodies, we hope to disarm the pathogen, reducing the spread of infection. Ultimately, we aim to use an opsonizing antibody to deliver antibiotics intracellularly by developing an antibody-antibiotic conjugate therapeutic for melioidosis.

Rational emotive education for reducing stress of undergraduate students of religious education program: An experimental study.

BACKGROUND: Rational emotive education (REE) program aims to improve the behavioral and mental health of students. This study objective was to evaluate the effect of an REE program on stress among undergraduate students of religious education program in Nigerian Universities. METHOD: One hundred and fifty (150) religious education undergraduates who had high level of stress participated in the study. Participants were assigned to 2 different groups. The treatment group had 75 participants and while control group also had 75 participants. Data collection was done using the Perceived Stress Scale (PSS-10) while data analysis was done using independent sample t test and paired t test statistics at .05 probability level. RESULTS: The REE program resulted in a significant decrease in level of stress among undergraduate students of religious education program in the treatment group compared with those students in the control group. Also, the effect of the REE program was maintained during the follow-up among undergraduate students of religious education program exposed to it. CONCLUSION: The REE program can be used to assist undergraduate students of religious education program to manage their stress.

Influence of parental education levels on eating habits of pupils in Nigerian primary schools.

This study investigated the eating habits of pupils in Nigerian primary schools based on the respective education levels of their parents.Data were obtained using the Child Eating Behavior Questionnaire (CEBQ). Participants included a total of 144 pupils who were purposively selected from 6 primary schools. Based on responses, a cross-sectional analytic study design was implemented to investigate how parental education levels (PELs) influenced the eating habits of their children. Data assessment was performed using a one-way between-group analysis of variance at the .05 probability level.PELs significantly affected the eating habits of participants, respectively. Specifically, low PEL was associated with more satiety responsiveness to food (F [2, 141] = 14.251, P < .001), higher responsiveness to food (F [2, 141] = 36.943, P = <.001) greater food enjoyment (F [2, 141] = 93.322, P < .001), greater drinking desires (F [2, 141] = 23.677, P < .001), and the tendency for emotional over-eating (F [2, 141] = 13.428, P < .001), while high PEL was associated with slower eating (F [2, 141] = 11.665, P < .001), fussier responses to food (F [2, 141] = 14.865, P < .001), and a higher tendency for emotional under-eating (F [2, 141] = 5.137, P < .01).This study examined PELs in relation to the respective eating habits of their children, who were attending Nigerian primary schools. Data showed that children with parents who had high, middle, and low education levels tended to exhibit progressively worse eating habits, in descending order.

Bullying experience of pupils in Nigerian primary schools.

Childhood bullying leads to life-long scars and hinders adult development. Schoolchildren involved in bullying are at risk of developing behavioural difficulties, physical health problems and suicidal ideation. This research aimed to evaluate the bullying experience of pupils in Nigerian primary schools.The study is a cross-sectional analytic survey conducted from June to November 2019. A total of 1080 pupils in participated in the study. A self-report questionnaire containing 3 questions was used for collecting data. Analysis of the collected data was done using percentage and Chi-Squared at 0.05 probability level.Results indicate that 51.4% of the male pupils and 50.8% of females reported being victims of bullying. 51.8% of the males and 49.5% of females were found to be perpetrators of bullying. 39.6% of the males and 42.9% of the females were bystanders of bullying. 35.1% of the males and 34.1% of females have experienced any 2 of the categories while 11.2% of the males and 12.4% of the females have experienced all the categories of bullying. Results show a non-significant difference between male and female pupils on bullying victimization (χ = .036, P = .849), bullying perpetration (χ = .589, P = .443), and bullying bystander problem (χ = 1.194, P = .275).In conclusion, school bullying is an increasing problem among Nigerian schoolchildren. Initiatives must, therefore, be taken by the Nigerian government to further prevent and counter bullying problem in Nigerian primary schools. Interventions aimed at helping schools to develop effective policies to reduce bullying behaviour among pupils should be initiated.

Quality of life, support and smoking in advanced lung cancer patients: a qualitative study.

BACKGROUND: Lung cancer is the most common cancer and smoking is the principal cause. Due to poor survival rates, symptom palliation and promotion of health-related quality of life (HRQoL) are primary outcomes for lung cancer patients. Given the established relationship between smoking and lung cancer, patients who have smoked may feel stigmatised or guilty after diagnosis, and more pessimistic about their illness and likely outcomes. This may have adverse implications for HRQoL. OBJECTIVES: We explored HRQoL and support experiences among newly diagnosed patients with advanced lung cancer. DESIGN: Semistructured interviews were conducted with nine patients and analysed using interpretative phenomenological analysis. RESULTS: Patients described the physical, emotional and social impact of disease on HRQoL. Fear of compromising their immune system and adjusting to new relationship roles had a wide-ranging effect on patients' HRQoL. Patients acknowledged links between lung cancer and smoking but some continued to smoke. They were sensitive to the opinions of medical staff about smoking especially those who continued to smoke or recently quit. CONCLUSIONS: We conclude that staff should give clearer advice about the adverse implications of continued smoking. We discuss the potential value of diagnosis as a teachable moment for promoting smoking cessation among patients and family members.

Quality of reporting on patient and public involvement within surgical research: a systematic review.

BACKGROUND: Recruitment difficulties are a well-reported concern in surgical literature, which may be improved by patient and public involvement (PPI). PPI within research has been defined as being conducted "with" or "by" patients or members of the public rather than being "about" or "for" them. However, the extent to which PPI is used within surgical research is unknown. METHODS: Surgical literature was systematically reviewed using EMBASE, MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, and PubMed. Search terms related to (i) patients, (ii) involvement, (iii) perioperative care, and (iv) impact. Quality of PPI reporting was evaluated using the GRIPP (Guidance for Reporting Involvement of Patients and Public checklist and the guidelines developed by Wright and Foster. A patient representative advised on the purpose and analysis of this systematic review. RESULTS: Eight articles described PPI in surgical trials to improve the identification of research topics, study design, recruitment, retention, and data collection. Quality of PPI reporting was suboptimal, as none of the articles provided a clear account of how PPI was conceptualized. Training and support for patients, their involvement in dissemination, and a critique of the limitations of PPI were not reported. However, it was not clear whether this represents an underutilization of PPI or purely suboptimal reporting in surgery. CONCLUSIONS: There is a paucity of surgical research reporting upon PPI, and the quality of reporting is low. Further research to define appropriate standards for reporting on PPI activities may facilitate broadening the utilization and impact of PPI in surgical research.

Investigating hormonal adaptations to high altitude: five years of Defence Medical Services expeditions.

The military has a tradition of supporting and promoting scientific expeditions. The past five years have witnessed a series of Defence Medical Service (DMS) expeditions to mountainous areas of the world, which set out with the dual purpose of researching high altitude human physiology and promoting the uptake of adventurous pursuits within the military. Beginning with exercise Medical Sentinel to Aconcagua, Argentina, in 2007, members of the DMS have since conducted two expeditions to the Himalayas (expedition Imja Tse, 2009 and expedition Khumbu Ramble, 2011) before returning to South America, to the Cordillera Real mountain range in Bolivia, on expedition Bolivian Venture, in late May 2012. This article aims to provide a brief background to the rationale behind these expeditions, a brief description of our understanding of altitude sickness and a history of the adventures that members of the Defence Medical Services have been having contributing to that understanding.

Genetic variants associated with deep vein thrombosis: the F11 locus.

BACKGROUND: Recent studies have found associations between deep vein thrombosis (DVT) and single nucleotide polymorphisms (SNPs) in a 4q35.2 locus that contains genes encoding factor XI (F11), a cytochrome P450 family member (CYP4V2), and prekallikrein (KLKB1). OBJECTIVE: We investigated which of the common SNPs in this locus are independently associated with DVT. METHODS: The study populations were the Leiden Thrombophilia Study (LETS) (443 DVT cases and 453 controls) and the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study) (2712 DVT cases and 4634 controls). We assessed the association between DVT and 103 SNPs in a 200 kb region using logistic regression. RESULTS: We found that two SNPs (rs2289252 and rs2036914 in F11) were independently associated with DVT. After adjusting for age, sex, and the other SNP, the odds ratios (risk vs. non-risk homozygotes) of these two SNPs were 1.49 for rs2289252 (95% CI, 1.25-1.76) and 1.33 for rs2036914 (95% CI, 1.11-1.59). We found that rs2289252 was also associated with FXI levels, as has been previously reported for rs2036914; these two SNPs remained associated with DVT with somewhat attenuated risk estimates after adjustment for FXI levels. CONCLUSION: Two SNPs, rs2289252 and rs2036914 in F11, appear to independently contribute to the risk of DVT, a contribution that is explained at least in part by an association with FXI levels.

Detailed genetic characterization of the interleukin-23 receptor in psoriasis.

Using a multi-tiered, case-control association design, scanning 25 215 gene-centric SNPs, we previously identified two psoriasis susceptibility genes: IL12B and IL23R. These results have recently been confirmed. To better characterize the IL23R psoriasis-association, we used a fine mapping strategy to identify 59 additional IL23R-linked SNPs, which were genotyped in our three independent, white North American sample sets (>2800 individuals in toto). A sliding window of haplotype association demonstrates colocalization of psoriasis susceptibility effects within the boundaries of IL23R across all sample sets, thereby decreasing the likelihood that neighboring genes, particularly IL12RB2, are driving the association at this region. Additional haplotype work identified two 5-SNP haplotypes with strong protective effects, consistent across our three sample sets (OR(common)=0.67; P(comb)=4.32E-07). Importantly, heterogeneity of effect was extremely low between sample sets for these haplotypes (P(Het)=0.961). Together, these protective haplotypes attain a frequency of 16% in controls, declining to 11% in cases. The characterization of association patterns within IL23R to specific predisposing/protective variants will play an important role in the elucidation of psoriasis etiology and other related phenotypes. Further, this work is essential to lay the foundation for the role of IL23R genetics in response to pharmaceutical therapy and dosage.

Dental abnormalities in children preparing for pediatric bone marrow transplantation.

The purpose of our study was to describe the types and frequencies of altered dental development in pediatric patients preparing for bone marrow transplantation (BMT). Retrospective review of the medical records and panoramic radiographs of all patients who underwent BMT at St Jude Children's Research Hospital between 1990 and 2000 for whom pre-BMT dental examination and panoramic radiography records were available. All patients were treated on institutional protocols. We recorded patient demographics and radiographic evidence of microdontia, hypodontia, taurodontia, root stunting, caries, enamel pearls, and pulpal calcifications. The 259 patients identified (150 male and 109 female) had a median age of 12.82 years (range, 3.18-25.93 years) at the time of BMT. In total, 203 were Caucasian, 38 were African-American, and 18 were of other races. In all, 150 (57.9%) had abnormal dentition. The most common dental abnormalities were caries (n=84), pulpal calcifications (n = 34), and dental extractions (n = 33). Developmental abnormalities occurred less frequently: taurodontia (n = 8), hypodontia (n = 10), microdontia (n = 11), and root stunting (n = 11). Dental abnormalities are prevalent in children undergoing BMT. Pre-transplant oral hygiene and dental examination should be standard care in order to minimize potential sites of infection.

Dental abnormalities after pediatric bone marrow transplantation.

Our purpose was to describe the types and frequencies of altered dental development in pediatric patients following bone marrow transplantation (BMT). A retrospective review of the medical records and panoramic radiographs of all patients who underwent BMT at St Jude Children's Research Hospital between 1990 and 2000, for whom pre-BMT and post-BMT dental examination and panoramic radiography records were available, is presented. All patients were treated on institutional protocols. We recorded patient demographics and radiographic evidence of microdontia, hypodontia, taurodontia, root stunting, caries, enamel pearls, dental restorations/extractions and pulpal calcification. The 99 patients identified (52 males, 47 females) had a median age of 13.5 years (range, 3.4-25.9 years) at the time of BMT. In all, 73 were Caucasian, 15 were African-American, and 11 were of other races. The frequency of radiographically evident root stunting in permanent teeth was significantly increased after BMT (P<0.001), but there was no significant change in the frequency of other dental abnormalities after BMT. Dental abnormalities are prevalent in survivors of childhood BMT, but only root stunting appeared to progress with BMT.

Human immune response to a plague vaccine comprising recombinant F1 and V antigens.

The human immune response to a new recombinant plague vaccine, comprising recombinant F1 (rF1) and rV antigens, has been assessed during a phase 1 safety and immunogenicity trial in healthy volunteers. All the subjects produced specific immunoglobulin G (IgG) in serum after the priming dose, which peaked in value after the booster dose (day 21), with the exception of one individual in the lowest dose level group, who responded to rF1 only. Three subjects, found to have an anti-rV titer at screening, were excluded from the overall analysis. Human antibody functionality has been assessed by quantification of antibody competing for binding to rV in vitro and also by the transfer of protective immunity in human serum into the naive mouse. Human and macaque IgG competed for binding to rV in vitro with a mouse monoclonal antibody, previously shown to protect mice against challenge with plague, suggesting that this protective B-cell epitope on rV is conserved between these three species. Total IgG to rV in individuals and the titer of IgG competing for binding to rV correlated significantly at days 21 (r = 0.72; P < 0.001) and 28 (r = 0.82; P < 0.001). Passive transfer of protective immunity into mice also correlated significantly with total IgG titer to rF1 plus rV at days 21 (r(2) = 98.6%; P < 0.001) and 28 (r(2) = 76.8%; P < 0.03). However, no significant vaccination-related change in activation of peripheral blood mononuclear cells was detected at any time. Potential serological immune correlates of protection have been investigated, but no trends specific to vaccination could be detected in cellular markers.

Investigation of fatigue crack growth in acrylic bone cement using the acoustic emission technique.

Failure of the bone cement mantle has been implicated in the loosening process of cemented hip stems. Current methods of investigating degradation of the cement mantle in vitro often require sectioning of the sample to confirm failure paths. The present research investigates acoustic emission as a passive experimental method for the assessment of bone cement failure. Damage in bone cement was monitored during four point bending fatigue tests through an analysis of the peak amplitude, duration, rise time (RT) and energy of the events emitted from the damage sections. A difference in AE trends was observed during failure for specimens aged and tested in (i) air and (ii) Ringer's solution at 37 degrees C. It was noted that the acoustic behaviour varied according to applied load level; events of higher duration and RT were emitted during fatigue at lower stresses. A good correlation was observed between crack location and source of acoustic emission, and the nature of the acoustic parameters that were most suited to bone cement failure characterisation was identified. The methodology employed in this study could potentially be used as a pre-clinical assessment tool for the integrity of cemented load bearing implants.

Biological responses of Lumbriculus variegatus exposed to fluoranthene-spiked sediment.

Lumbriculus variegatus was used as a bioassay organism to examine the impact of the sediment-associated polycyclic aromatic hydrocarbon (PAH) fluoranthene on behavior, reproduction, and toxicokinetics. The number of worms increased between the beginning and end of the experiment at 59 microg x g(-1) fluoranthene, but at the next higher treatment (108 microg x g(-1)) the number of worms found was lower and not different from the control. Worms exposed to 95 microg x g(-1) also exhibited increased reproduction when fed a yeast-cerophyl-trout chow mixture. On a total biomass basis, only the 95 microg x g(-1) exposure with food exhibited a statistically significant increase over the nonfed control. Evaluation of reproduction at the two highest treatments was compromised by a brief aeration failure 2 days before the end of the experiment. The behavioral responses were followed as changes in biological burial rate (sediment reworking rate) of a 137Cs-labeled marker layer. The biological burial rate increased toward a plateau as the concentration increased from the control (3.9 microg x g(-1) dry weight total PAH) to 355 microg x g(-1) dry weight fluoranthene in sediment. The aeration failure had minimal impact on the determination of reworking rate because all the data for the rate determination were collected prior to the aeration failure. Uptake and elimination rates declined with increasing treatment concentration across the range of fluoranthene concentrations, 59-355 microg x g(-1) dry weight sediment. The disconnect between the increasing biological burial rates and the decreasing toxicokinetics rates with increasing exposure concentration demonstrates that the toxicokinetic processes are dominated by uptake and elimination to interstitial water. The bioaccumulation factor (concentration in the organisms on a wet weight basis divided by the concentration in sediment on a dry weight basis) ranged from 0.92 to 1.88 on day 10 and declined to a range of 0.52 to 0.99 on day 28 with the lowest value at the highest dose.

Primary uncemented total hip arthroplasty in patients <40 years old: 10- to 14-year results using first-generation proximally porous-coated implants.

Eighty-two consecutive primary first-generation uncemented total hip arthroplasties (72 patients) performed in patients <40 years old were reviewed with minimum follow-up of 10 years. Of 82 hips, 24 (29.3%) have been revised to date. The estimated survival free of aseptic revision or radiographic failure was 81.3% at 10 years for the acetabular components. The estimated survival free of aseptic revision or radiographic failure was 84.9% at 10 years for the femoral component. In this exclusively young patient cohort, there was a high failure rate of the acetabular component and the femoral component. The data in this report can serve as a baseline for comparison of newer implants and operative methods.

Radiographic assessment of cemented humeral components in shoulder arthroplasty.

Forty-three shoulder arthroplasties performed with the use of cemented Neer II humeral components and followed radiographically for a mean of 6.6 years (range, 2-20 years) were analyzed. A humeral component was considered radiographically "at risk" for clinical loosening when a radiolucent line 2 mm or greater in width was present in 3 or more zones or tilt or subsidence was identified on sequential radiographs by 2 or 3 of the 3 independent observers. None of the components was considered to have tilted or subsided. Radiolucent lines of any size were present in 16 shoulders and were wider than 2 mm in 9 shoulders. They were limited to 1 zone in 8 shoulders and to 2 zones in 7 shoulders. Only 1 component (2%) with a 2-mm radiolucent line in 3 zones was judged to be "at risk." The incidence, extent, and thickness of humeral radiolucent lines were significantly higher in total arthroplasties than in hemiarthroplasties (P <.05). Clinically important changes around cemented Neer II humeral components are uncommon. Humeral radiolucent lines develop more frequently in the presence of a glenoid component. Data from this study can be used as one benchmark to compare with alternate methods of humeral component fixation.