Search results for: Christopher Okechukwu Ndukwe

Authors: Hansraj Bookun, Rachel Xuan, Angela Tan, Kejia Wang, Animesh Singla, David Kim, Christopher Loupos, Jim Iliopoulos

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Introduction: Complex endovascular aortic aneursymal repairs with fenestrated and branched endografts require customised devices to exclude the pathology while reducing morbidity and mortality, which was historically associated with open repair of complex aneurysms. Such endovascular procedures have predominantly been performed in a large volume dedicated tertiary centres. We present here our nine year multidisciplinary experience with this technology in an Australian tertiary centre. Method: This was a cross-sectional, single-centre observational study of 670 patients who had undergone complex endovascular aortic aneurysmal repairs with conventional endografts, fenestrated endografts, and iliac-branched devices from January 2010 to July 2019. Descriptive statistics were used to characterise our sample with regards to demographic and perioperative variables. Homogeneity of the sample was tested using multivariant regression, which did not identify any statistically significant confounding variables. Results: 670 patients of mean age 74, were included (592 males) and the comorbid burden was as follows: ischemic heart disease (55%), diabetes (18%), hypertension (90%), stage four or greater kidney impairment (8%) and current or ex-smoking (78%). The main indications for surgery were elective aneurysms (86%), symptomatic aneurysms (5%), and rupture aneurysms (5%). 106 patients (16%) underwent fenestrated or branched endograft repairs. The mean length of stay was 7.6 days. 2 patients experienced reactionary bleeds, 11 patients had access wound complications (6 lymph fistulae, 5 haematoms), 11 patients had cardiac complications (5 arrhythmias, 3 acute myocadial infarctions, 3 exacerbation of congestive cardiac failure), 10 patients had respiratory complications, 8 patients had renal impairment, 4 patients had gastrointestinal complications, 2 patients suffered from paraplegia, 1 major stroke, 1 minor stroke, and 1 acute brain syndrome. There were 4 vascular occlusions requiring further arterial surgery, 4 type I endoleaks, 4 type II endoleaks, 3 episodes of thromboembolism, and 2 patients who required further arterial operations in the setting of patient vessels. There were 9 unplanned returns to the theatre. Discussion: Our numbers of 10 years suggest that we are not a dedicated high volume centre focusing on aortic repairs. However, we have achieved significantly low complication rates. This can be attributed to our multidisciplinary approach with the intraoperative involvement of skilled interventional radiologists and vascular surgeons as well as postoperative protocols with particular attention to spinal cord protection. Additionally, we have a ratified perioperative pathway that involves multidisciplinary team discussions of patient-related factors and lesion-centered characteristics, which allows for holistic, patient-centered care.

Keywords: aneurysm, aortic, endovascular, fenestrated

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Authors: Lalanthica Yogendran, Manassa Hany, Saira Pasha, Benjamin Chaucer, Simarpreet Kaur, Christopher Janusz

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Children and adolescent patients visit the Psychiatric Emergency Department (ED) for multiple reasons. Visiting the Psychiatric ED itself can be a traumatic experience that can affect an adolescents mental well-being, regardless of a history of mental illness. Despite this, limited research exists in this domain. Prospective studies have correlated adverse psychosocial determinants among adolescents to risk factors for poor well-being and unfavorable behavior outcomes. Studies have also shown that physiological stress is a contributor in the development of health problems and an increase in substance abuse in adolescents. This study aimed to retrospectively determine which psychosocial factors are associated with an increase in psychiatric ED visits. 600 charts of patients who had a psychiatric ED and inpatient admission visit from January 2014 through December 2014 were reviewed. Sociodemographics, diagnoses, ED visits and inpatient admissions were collected. Descriptive statistics, chi-square tests and independent t-test analyses were utilized to examine differences in the sample to determine which factors affected ED visits and admissions. The sample was 50% female, 35.2% self-identified black, and had a mean age of 13 years. The majority, 85%, went to public school and 17% were in special education. Attention Deficit Hyperactivity Disorder was the most common admitting diagnosis, found in 132(23%) responders. Most patients came from single parent household 305 (53%). The mean ages of patients that were sexually active, with legal issues, and reporting marijuana substance abuse were 15, 14.35, and 15 years respectively. Patients from two biological parent households had significantly fewer ED visits (1.2 vs. 1.7, p < 0.01) and admissions (0.09 vs. 0.26, p < 0.01). Among social factors, those who reported sexual, physical or emotional abuse had a significantly greater number of ED visits (2.1 vs. 1.5, p < 0.01) and admissions (0.61 vs. 0.14, p < 0.01) than those who did not. Patients that were sexually active or had legal issues or substance abuse with marijuana had a significantly greater number of admissions (0.43 vs. 0.17, p < 0.01), (0.54 vs. .18, p < 0.01) and (0.46 vs. 0.18, p < 0.01) respectively. This data supports the theory of the stability of a two parent home. Dual parenting plays a role in creating a safe space where a child can develop; this is shown by subsequent decreases in psychiatric ED visits and admissions. This may highlight the psychological protective role of a two parent household. Abuse can exacerbate existing psychiatric illness or initiate the onset of new disease. Substance abuse and legal issues result in early induction to the criminal system. Results show that this causes an increase in frequency of visits and severity of symptoms. Only marijuana, but not other illicit substances, correlated with higher incidence of psychiatric ED visits. This may speak to the psychotropic nature of tetrahydrocannabinols and their role in mental illness. This study demonstrates the array of psychosocial factors that lead to increased ED visits and admissions in children and adolescents.

Keywords: adolescent, child psychiatry, emergency department, substance abuse

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Authors: Ben Morrow, Patrick O'Hara, Natalie Ban, Tunai Marques, Molly Fraser, Christopher Bone

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Relative to commercial fisheries, recreational fisheries are often poorly understood and pose various challenges for monitoring frameworks. In British Columbia (BC), Canada, Pacific salmon are heavily targeted by recreational fishers while also being a key source of nutrient flow and crucial prey for a variety of marine and terrestrial fauna, including endangered Southern Resident killer whales (Orcinus orca). Although commercial fisheries were historically responsible for the majority of salmon retention, recreational fishing now comprises both greater effort and retention. The current monitoring scheme for recreational salmon fisheries involves aerial-roving creel surveys. However, this method has been identified as costly and having low predictive power as it is often limited to sampling fragments of fluid and temporally dynamic fisheries. This study used imagery from two shore-based autonomous cameras in a highly active recreational fishery around Sooke, BC, and evaluated their efficacy in supplementing existing aerial-roving surveys for monitoring a recreational salmon fishery. This study involved continuous monitoring and high temporal resolution (over one million images analyzed in a single fishing season), using a deep learning-based vessel detection algorithm and a custom image annotation tool to efficiently thin datasets. This allowed for the quantification of peak-season effort from a busy harbour, species-specific retention estimates, high levels of detected fishing events at a nearby popular fishing location, as well as the proportion of the fishery management area represented by cameras. Then, this study demonstrated how it could substantially enhance the temporal resolution of a fishery through diel activity pattern analyses, scaled monthly to visualize clusters of activity. This work also highlighted considerable off-season fishing detection, currently unaccounted for in the existing monitoring framework. These results demonstrate several distinct applications of autonomous cameras for providing enhanced detail currently unavailable in the current monitoring framework, each of which has important considerations for the managerial allocation of resources. Further, the approach and methodology can benefit other studies that apply shore-based camera monitoring, supplement aerial-roving creel surveys to improve fine-scale temporal understanding, inform the optimal timing of creel surveys, and improve the predictive power of recreational stock assessments to preserve important and endangered fish species.

Keywords: cameras, monitoring, recreational fishing, stock assessment

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Authors: Emma Worley, Mhairi De Sainte Croix, Savneet Lochab, Christopher Roberts, Mark Stroud, Mo Salehan, Kevin Jones

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Awareness about the importance of teaching about diversity at medical school is growing. In the realm of diversity includes discussion around the LGBTQ+ community. At Bristol, diversity is taught in first or second year. However, echoing and expanding that teaching throughout the curriculum is needed. This feeds into the spiral curriculum but also highlights the relevance of the topic. It is well known that some people in the LGBTQ+ community struggle the access healthcare due to previous negative experiences. In 2019, 1 in 7 LGBTQ+ people avoided seeking medical care due to fears about discrimination. If people have fears about seeking medical help, then seeking help from Palliative care when they are at their most vulnerable situation can be even harder. To improve positive healthcare situations for people who identify as LGBTQ+ needs to start with talking. Along with some of our CTAs (clinical teaching assistants) we created a teaching session to explore the barriers faced by LGBTQ+ and incorporated communication stations into this. Our plan is to run this session as a three-hour session first discussing different topics: ethnical diversity, ‘coming out’, LGBTQ+ in the older generation, transgender. This will be followed by looking more closely at the barriers to accessing the hospice. The next part of the session will encompass two or three communication scenarios hopefully prompting further discussion and reflection on ways to improve our communication. The first scenario outline is a gay man/lesbian woman with lung cancer discussing options around the hospice. The second scenario is a transgender person with female genitalia who now has cervical cancer (as was not followed up on pap smears after the change of name). The third scenario is a HIV homosexual male patient who has been admitted with dementia. He has a partner but is not married. His next of kin is down as his parents but his parents do not know about his sexuality and HIV status. It allows discussion around confidentiality as well as broaching the meaning of ‘family’ in the LGBTQ+ community. We have chosen to pitch this teaching session to Bristol Year 4 students. They will be currently doing their 6-week Palliative care block, which fits in well. Each session will have four students attend. We have been lucky enough to have two CTAs (clinical teaching assistants) who identify as LGBTQ+ offer their experiences and help. They have been able to help us with the preparation and delivery of the session. Given anecdotal evidence and stories helps to highlight the importance and relevance of this session. The aim is to increase awareness of some factors that may contribute to people who identify as LGBTQ+ having a negative healthcare experience. By starting to talk about it allows awareness and only then will we be able to start to change and improve. Our aim, if the sessions run well, is to expand these sessions to different academy hospitals. Therefore, all Bristol 4th year students would have the opportunity to take part in the teaching session. We would like to expand our portfolio of case scenarios, to address so tricker topics such as a transgender person with dementia who reverts back to a different gender. We would also like to recruit a diverse range of actors, ideally people who identify as the patient in the scenario does. For example, a transgender person acts the transgender scenario. This would give authenticity and enhance the student’s learning experience.

Keywords: communication skills, healthcare barriers, LGBTQ+, palliative care

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Authors: Rishana Bilimoria, Selina Tang, Sajni Shah, Marianne Henien, Christopher Sproat

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Temporomandibular disorders (TMD) may affect up to a third of the general population, and there is evidence demonstrating the majority of Myofascial TMD cases improve after education and conservative measures. In 2015 our department implemented a modified care pathway for myofascial TMD patients in an attempt to improve the patient journey. This involved the use of an interactive group therapy approach to deliver education, reinforce conservative measures and promote self-management. Patient reported experience measures from the new group clinic revealed 71% patient satisfaction. This service is efficient in improving aspects of health status while reducing health-care costs and redistributing clinical time. Since its’ establishment, 52 hours of clinical time, resources and funding have been redirected effectively. This Quality Improvement Project was initiated because it was felt that this new service was being underutilised by our surgical teams. The ‘Plan-Do-Study-Act cycle’ (PDSA) framework was employed to analyse utilisation of the service: The ‘plan’ stage involved outlining our aims: to raise awareness amongst clinicians of the unified care pathway and to increase referral to this clinic. The ‘do’ stage involved collecting data from a sample of 96 patients over 4 month period to ascertain the proportion of Myofascial TMD patients who were correctly referred to the designated clinic. ‘Suitable’ patients who weren’t referred were identified. The ‘Study’ phase involved analysis of results, which revealed that 77% of suitable patients weren’t referred to the designated clinic. They were reviewed on other clinics, which are often overbooked, or managed by junior staff members. This correlated with our original prediction. Barriers to referral included: lack of awareness of the clinic, individual consultant treatment preferences and patient, reluctance to be referred to a ‘group’ clinic. The ‘Act’ stage involved presenting our findings to the team at a clinical governance meeting. This included demonstration of the clinical effectiveness of the care-pathway and explaining the referral route and criteria. In light of the evaluation results, it was decided to keep the group clinic and maximize utilisation. The second cycle of data collection following these changes revealed that of 66 Myofascial TMD patients over a 4 month period, only 9% of suitable patients were not seen via the designated pathway; therefore this QIP was successful in meeting the set objectives. Overall, employing the PDSA cycle in this QIP resulted in appropriate utilisation of the modified care pathway for patients with myofascial TMD in Guy’s Oral Surgery Department. In turn, this leads to high patient satisfaction with the service and effectively redirected 52 hours of clinical time. It permitted adoption of a collaborative working style with oral surgery colleagues to investigate problems, identify solutions, and collectively raise standards of clinical care to ensure we adopt a unified care pathway in secondary care management of Myofascial TMD patients.

Keywords: myofascial, quality Improvement, PDSA, TMD

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Authors: Iorwase Derek Kaka’an, Peter Smolianov, Steven Dion, Christopher Schoen, Jaclyn Norberg, Charles Gabriel Iortimah

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This study examines the current state of football in Nigeria to identify the country's practices, which could be useful internationally, and to determine areas for improvement. Over 200 sources of literature on sport delivery systems in successful sports nations were analyzed to construct a globally applicable model of elite football integrated with mass participation, comprising of the following three levels: macro (socio-economic, cultural, legislative, and organizational), meso (infrastructures, personnel, and services enabling sports programs) and micro level (operations, processes, and methodologies for the development of individual athletes). The model has received scholarly validation and has shown to be a framework for program analysis that is not culturally bound. It has recently been utilized for further understanding such sports systems as US rugby, tennis, soccer, swimming, and volleyball, as well as Dutch and Russian swimming. A questionnaire was developed using the above-mentioned model. Survey questions were validated by 12 experts including academicians, executives from sports governing bodies, football coaches, and administrators. To identify best practices and determine areas for improvement of football in Nigeria, 116 coaches completed the questionnaire. Useful exemplars and possible improvements were further identified through semi-structured discussions with 10 Nigerian football administrators and experts. Finally, a content analysis of the Nigeria Football Federation's website and organizational documentation was conducted. This paper focuses on the micro level of Nigerian football delivery, particularly talent search and development as well as advanced athlete preparation and support. Results suggested that Nigeria could share such progressive practices as the provision of football programs in all schools and full-time coaches paid by governments based on the level of coach education. Nigerian football administrators and coaches could provide better football services affordable for all, where success in mass and elite sports is guided by science focused on athletes' needs. Better implemented could be international best practices such as lifelong guidelines for health and excellence of everyone and integration of fitness tests into player development and ranking as done in best Dutch, English, French, Russian, Spanish, and other European clubs; integration of educational and competitive events for elite and developing athletes as well as fans as done at the 2018 World Cup Russia; and academies with multi-stage athlete nurturing as done by Ajax in Africa as well as Barcelona FC and other top clubs expanding across the world. The methodical integration of these practices into the balanced development of mass and elite football will help contribute to international sports success as well as national health, education, crime control, and social harmony in Nigeria.

Keywords: football, high performance, mass participation, Nigeria, sport development

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Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

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Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

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Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

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Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

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Authors: Daniel Rowe, Christopher R. Vogel, Richard H. J. Willden

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The University of Oxford’s recirculating water flume is a combined wave and current test tank with a 1 m depth, 1.1 m width, and 10 m long working section, and is capable of flow speeds up to 1 ms−1 . This study documents the hydrodynamic characteristics of the facility in preparation for experimental testing of horizontal axis tidal stream turbine models. The turbine to be tested has a rotor diameter of 0.6 m and is a modified version of one of two model-scale turbines tested in previous experimental campaigns. An Acoustic Doppler Velocimeter (ADV) was used to measure the flow at high temporal resolution at various locations throughout the flume, enabling the spatial uniformity and turbulence flow parameters to be investigated. The mean velocity profiles exhibited high levels of spatial uniformity at the design speed of the flume, 0.6 ms−1 , with variations in the three-dimensional velocity components on the order of ±1% at the 95% confidence level, along with a modest streamwise acceleration through the measurement domain, a target 5 m working section of the flume. A high degree of uniformity was also apparent for the turbulence intensity, with values ranging between 1-2% across the intended swept area of the turbine rotor. The integral scales of turbulence exhibited a far higher degree of variation throughout the water column, particularly in the streamwise and vertical scales. This behaviour is believed to be due to the high signal noise content leading to decorrelation in the sampling records. To achieve more realistic levels of vertical velocity shear in the flume, a simple procedure to practically generate target vertical shear profiles in open-channel flows is described. Here, the authors arranged a series of non-uniformly spaced parallel bars placed across the width of the flume and normal to the onset flow. By adjusting the resistance grading across the height of the working section, the downstream profiles could be modified accordingly, characterised by changes in the velocity profile power law exponent, 1/n. Considering the significant temporal variation in a tidal channel, the choice of the exponent denominator, n = 6 and n = 9, effectively provides an achievable range around the much-cited value of n = 7 observed at many tidal sites. The resulting flow profiles, which we intend to use in future turbine tests, have been characterised in detail. The results indicate non-uniform vertical shear across the survey area and reveal substantial corner flows, arising from the differential shear between the target vertical and cross-stream shear profiles throughout the measurement domain. In vertically sheared flow, the rotor-equivalent turbulence intensity ranges between 3.0-3.8% throughout the measurement domain for both bar arrangements, while the streamwise integral length scale grows from a characteristic dimension on the order of the bar width, similar to the flow downstream of a turbulence-generating grid. The experimental tests are well-defined and repeatable and serve as a reference for other researchers who wish to undertake similar investigations.

Keywords: acoustic doppler Velocimeter, experimental hydrodynamics, open-channel flow, shear profiles, tidal stream turbines

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Authors: Chunyang Miao, Bingxin Li, Shanglong Ning, Christopher J. B. Ford

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While it is challenging to fabricate electronic devices close to atomic dimensions in conventional top-down lithography, molecular electronics is promising to help maintain the exponential increase in component densities via using molecular building blocks to fabricate electronic components from the bottom up. It offers smaller, faster, and more energy-efficient electronic and photonic systems. A self-assembled monolayer (SAM) of molecules is a layer of molecules that self-assembles on a substrate. They are mechanically flexible, optically transparent, low-cost, and easy to fabricate. A large-area multi-layer structure has been designed and investigated by the team, where a SAM of designed molecules is sandwiched between graphene and gold electrodes. Each molecule can act as a quantum dot, with all molecules conducting in parallel. When a source-drain bias is applied, significant current flows only if a molecular orbital (HOMO or LUMO) lies within the source-drain energy window. If electrons tunnel sequentially on and off the molecule, the charge on the molecule is well-defined and the finite charging energy causes Coulomb blockade of transport until the molecular orbital comes within the energy window. This produces ‘Coulomb diamonds’ in the conductance vs source-drain and gate voltages. For different tunnel barriers at either end of the molecule, it is harder for electrons to tunnel out of the dot than in (or vice versa), resulting in the accumulation of two or more charges and a ‘Coulomb staircase’ in the current vs voltage. This nanostructure exhibits highly reproducible Coulomb-staircase patterns, together with additional oscillations, which are believed to be attributed to molecular vibrations. Molecules are more isolated than semiconductor dots, and so have a discrete phonon spectrum. When tunnelling into or out of a molecule, one or more vibronic states can be excited in the molecule, providing additional transport channels and resulting in additional peaks in the conductance. For useful molecular electronic devices, achieving the optimum orbital alignment of molecules to the Fermi energy in the leads is essential. To explore it, a drop of ionic liquid is employed on top of the graphene to establish an electric field at the graphene, which screens poorly, gating the molecules underneath. Results for various molecules with different alignments of Fermi energy to HOMO have shown highly reproducible Coulomb-diamond patterns, which agree reasonably with DFT calculations. In summary, this large-area SAM molecular junction is a promising candidate for future electronic circuits. (1) The small size (1-10nm) of the molecules and good flexibility of the SAM lead to the scalable assembly of ultra-high densities of functional molecules, with advantages in cost, efficiency, and power dissipation. (2) The contacting technique using graphene enables mass fabrication. (3) Its well-observed Coulomb blockade behaviour, narrow molecular resonances, and well-resolved vibronic states offer good tuneability for various functionalities, such as switches, thermoelectric generators, and memristors, etc.

Keywords: molecular electronics, Coulomb blokade, electron-phonon coupling, self-assembled monolayer

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Authors: Rachael Andrews, Viktoria McMillan, Shuaib Nasser, Christopher M. Roberts

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Background and objective: The National Review of Asthma Deaths (NRAD) found that asthma management and care was inadequate in 26% of cases reviewed. Major shortfalls identified were adherence to national guidelines and standards and, particularly, the organisation of care, including supervision and monitoring in primary care, with 70% of cases reviewed having at least one avoidable factor in this area. 5.4 million people in the UK are diagnosed with and actively treated for asthma, and approximately 60,000 are admitted to hospital with acute exacerbations each year. The majority of people with asthma receive management and treatment solely in primary care. This has therefore created concern that many people within the UK are receiving sub-optimal asthma care resulting in unnecessary morbidity and risk of adverse outcome. NRAD concluded that a national asthma audit programme should be established to measure and improve processes, organisation, and outcomes of asthma care. Objective: To develop a primary care dataset enabling extraction of information from GP practices in Wales and providing robust data by which results and lessons could be drawn and drive service development and improvement. Methods: A multidisciplinary group of experts, including general practitioners, primary care organisation representatives, and asthma patients was formed and used as a source of governance and guidance. A review of asthma literature, guidance, and standards took place and was used to identify areas of asthma care which, if improved, would lead to better patient outcomes. Modified Delphi methodology was used to gain consensus from the expert group on which of the areas identified were to be prioritised, and an asthma patient and carer focus group held to seek views and feedback on areas of asthma care that were important to them. Areas of asthma care identified by both groups were mapped to asthma guidelines and standards to inform and develop primary and secondary care datasets covering both adult and pediatric care. Dataset development consisted of expert review and a targeted consultation process in order to seek broad stakeholder views and feedback. Results: Areas of asthma care identified as requiring prioritisation by the National Asthma Audit were: (i) Prescribing, (ii) Asthma diagnosis (iii) Asthma Reviews (iv) Personalised Asthma Action Plans (PAAPs) (v) Primary care follow-up after discharge from hospital (vi) Methodologies and primary care queries were developed to cover each of the areas of poor and variable asthma care identified and the queries designed to extract information directly from electronic patients’ records. Conclusion: This paper describes the methodological approach followed to develop primary care datasets for a National Asthma Audit. It sets out the principles behind the establishment of a National Asthma Audit programme in response to a national asthma mortality review and describes the development activities undertaken. Key process elements included: (i) mapping identified areas of poor and variable asthma care to national guidelines and standards, (ii) early engagement of experts, including clinicians and patients in the process, and (iii) targeted consultation of the queries to provide further insight into measures that were collectable, reproducible and relevant.

Keywords: asthma, primary care, general practice, dataset development

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Authors: Judy M. Obliosca, Olivia Vest, Sandra Poulos, Kelsi Smith, Tammy Ferguson, Abigail Powers Lott, Alicia K. Smith, Yang Xu, Christopher K. Tison

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Post-Traumatic Stress Disorder (PTSD) is a mental health problem that people may develop after experiencing traumatic events such as combat, natural disasters, and major emotional challenges. Tragically, the number of military personnel with PTSD correlates directly with the number of veterans who attempt suicide, with the highest rate in the Army. Research has shown epigenetic risks in those who are prone to several psychiatric dysfunctions, particularly PTSD. Once initiated in response to trauma, epigenetic alterations in particular, the DNA methylation in the form of 5-methylcytosine (5mC) alters chromatin structure and represses gene expression. Current methods to detect DNA methylation, such as bisulfite-based genomic sequencing techniques, are laborious and have massive analysis workflow while still having high error rates. A faster and simpler detection method of high sensitivity and precision would be useful in a clinical setting to confirm potential PTSD etiologies, prevent other psychiatric disorders, and improve military health. A nano-enhanced Surface Plasmon Resonance imaging (SPRi)-based assay that simultaneously detects site-specific 5mC base (termed as PTSD base) in methylated genes related to PTSD is being developed. The arrays on a sensing chip were first constructed for parallel detection of PTSD bases using synthetic and genomic DNA (gDNA) samples. For the gDNA sample extracted from the whole blood of a PTSD patient, the sample was first digested using specific restriction enzymes, and fragments were denatured to obtain single-stranded methylated target genes (ssDNA). The resulting mixture of ssDNA was then injected into the assay platform, where targets were captured by specific DNA aptamer probes previously immobilized on the surface of a sensing chip. The PTSD bases in targets were detected by anti-5-methylcytosine antibody (anti-5mC), and the resulting signals were then enhanced by the universal nanoenhancer. Preliminary results showed successful detection of a PTSD base in a gDNA sample. Brighter spot images and higher delta values (control-subtracted reflectivity signal) relative to those of the control were observed. We also implemented the in-house surface activation system for detection and developed SPRi disposable chips. Multiplexed PTSD base detection of target methylated genes in blood DNA from PTSD patients of severity conditions (asymptomatic and severe) was conducted. This diagnostic capability being developed is a platform technology, and upon successful implementation for PTSD, it could be reconfigured for the study of a wide variety of neurological disorders such as traumatic brain injury, Alzheimer’s disease, schizophrenia, and Huntington's disease and can be extended to the analyses of other sample matrices such as urine and saliva.

Keywords: epigenetic assay, DNA methylation, PTSD, whole blood, multiplexing

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Authors: Nicki Mohammadi, Emma Reford, Natalia Romano Spica, Laura Tabacof, Jenna Tosto-Mancuso, David Putrino, Christopher P. Kellner

Abstract:

Introductory Statement: The onset of the COVID-19 pandemic demanded an unprecedented need for the rapid development, dispersal, and application of infection testing. However, despite the impressive mobilization of resources, individuals were incredibly limited in their access to tests, particularly during the initial months of the pandemic (March-April 2020) in New York City (NYC). Access to COVID-19 testing is crucial in understanding patients’ illness experiences and integral to the development of COVID-19 standard-of-care protocols, especially in the context of overall access to healthcare resources. Succinct Description of basic methodologies: 18 Patients in a COVID-19 Remote Patient Monitoring Program (Precision Recovery within the Mount Sinai Health System) were interviewed regarding their experience with COVID-19 during the first wave (March-May 2020) of the COVID-19 pandemic in New York City. Patients were asked about their experiences navigating COVID-19 diagnoses, the health care system, and their recovery process. Transcribed interviews were analyzed for thematic codes, using grounded theory to guide the identification of emergent themes and codebook development through an iterative process. Data coding was performed using NVivo12. References for the domain “testing” were then extracted and analyzed for themes and statistical patterns. Clear Indication of Major Findings of the study: 100% of participants (18/18) referenced COVID-19 testing in their interviews, with a total of 79 references across the 18 transcripts (average: 4.4 references/interview; 2.7% interview coverage). 89% of participants (16/18) discussed the difficulty of access to testing, including denial of testing without high severity of symptoms, geographical distance to the testing site, and lack of testing resources at healthcare centers. Participants shared varying perspectives on how the lack of certainty regarding their COVID-19 status affected their course of recovery. One participant shared that because she never tested positive she was shielded from her anxiety and fear, given the death toll in NYC. Another group of participants shared that not having a concrete status to share with family, friends and professionals affected how seriously onlookers took their symptoms. Furthermore, the absence of a positive test barred some individuals from access to treatment programs and employment support. Concluding Statement: Lack of access to COVID-19 testing in the first wave of the pandemic in NYC was a prominent element of patients’ illness experience, particularly during their recovery phase. While for some the lack of concrete results was protective, most emphasized the invalidating effect this had on the perception of illness for both self and others. COVID-19 testing is now widely accessible; however, those who are unable to demonstrate a positive test result but who are still presumed to have had COVID-19 in the first wave must continue to adapt to and live with the effects of this gap in knowledge and care on their recovery. Future efforts are required to ensure that patients do not face barriers to care due to the lack of testing and are reassured regarding their access to healthcare. Affiliations- 1Department of Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY 2Abilities Research Center, Department of Rehabilitation and Human Performance, Icahn School of Medicine at Mount Sinai, New York, NY

Keywords: accessibility, COVID-19, recovery, testing

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Authors: Margaret Boone Rappaport, Christopher J. Corbally

Abstract:

The ancient ape ancestral population from which living great ape and human species evolved had demographic features affecting their evolution. The population was large, had great genetic variability, and natural selection was effective at honing adaptations. The emerging populations of chimpanzees and humans were affected more by founder effects and genetic drift because they were smaller. Natural selection did not disappear, but it was not as strong. Consequences of the 'population crash' and the human effective population size are introduced briefly. The history of the ancient apes is written in the genomes of living humans and great apes. The expansion of the brain began before the human line emerged. Coalescence times for some genes are very old – up to several million years, long before Homo sapiens. The mismatch between gene trees and species trees highlights the anthropoid speciation processes, and gives the human genome history a fuzzy, probabilistic quality. However, it suggests traits that might form a foundation for capacities emerging later. A theoretical model is presented in which the genomes of early ape populations provide the substructure for the emergence of religious capacity later on the human line. The model does not search for religion, but its foundations. It suggests a course by which an evolutionary line that began with prosimians eventually produced a human species with biologically based religious capacity. The model of the sequential emergence of religious capacity relies on cognitive science, neuroscience, paleoneurology, primate field studies, cognitive archaeology, genomics, and population genetics. And, it emphasizes five trait types: (1) Documented, positive selection of sensory capabilities on the human line may have favored survival, but also eventually enriched human religious experience. (2) The bonobo model suggests a possible down-regulation of aggression and increase in tolerance while feeding, as well as paedomorphism – but, in a human species that remains cognitively sharp (unlike the bonobo). The two species emerged from the same ancient ape population, so it is logical to search for shared traits. (3) An up-regulation of emotional sensitivity and compassion seems to have occurred on the human line. This finds support in modern genetic studies. (4) The authors’ published model of morality's emergence in Homo erectus encompasses a cognitively based, decision-making capacity that was hypothetically overtaken, in part, by religious capacity. Together, they produced a strong, variable, biocultural capability to support human sociability. (5) The full flowering of human religious capacity came with the parietal expansion and smaller face (klinorhynchy) found only in Homo sapiens. Details from paleoneurology suggest the stage was set for human theologies. Larger parietal lobes allowed humans to imagine inner spaces, processes, and beings, and, with the frontal lobe, led to the first theologies composed of structured and integrated theories of the relationships between humans and the supernatural. The model leads to the evolution of a small population of African hominins that was ready to emerge with religious capacity when the species Homo sapiens evolved two hundred thousand years ago. By 50-60,000 years ago, when human ancestors left Africa, they were fully enabled.

Keywords: genetic drift, genomics, parietal expansion, religious capacity

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Authors: Tom S. Owens, Tom A. Calverley, Benjamin S. Stacey, Christopher J. Marley, George Rose, Lewis Fall, Gareth L. Jones, Priscilla Williams, John P. R. Williams, Martin Steggall, Damian M. Bailey

Abstract:

Introduction and aims: Sports-related concussion (SRC) represents a significant and growing public health concern in rugby union, yet remains one of the least understood injuries facing the health community today. Alongside increasing SRC incidence rates, there is concern that prior recurrent concussion may contribute to long-term neurologic sequelae in later-life. This may be due to an accelerated decline in cerebral perfusion, a major risk factor for neurocognitive decline and neurodegeneration, though the underlying mechanisms remain to be established. The present study hypothesised that recurrent concussion in current professional rugby union players would result in elevated systemic oxidative-nitrosative stress, reflected by a free radical-mediated reduction in nitric oxide (NO) bioavailability and impaired cerebrovascular and cognitive function. Methodology: A longitudinal study design was adopted across the 2017-2018 rugby union season. Ethical approval was obtained from the University of South Wales Ethics Committee. Data collection is ongoing, and therefore the current report documents result from the pre-season and first half of the in-season data collection. Participants were initially divided into two subgroups; 23 professional rugby union players (aged 26 ± 5 years) and 22 non-concussed controls (27 ± 8 years). Pre-season measurements were performed for cerebrovascular function (Doppler ultrasound of middle cerebral artery velocity (MCAv) in response to hypocapnia/normocapnia/hypercapnia), cephalic venous concentrations of the ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), NO (ozone-based chemiluminescence) and cognition (neuropsychometric tests). Notational analysis was performed to assess contact in the rugby group throughout each competitive game. Results: 1001 tackles and 62 injuries, including three concussions were observed across the first half of the season. However, no associations were apparent between number of tackles and any injury type (P > 0.05). The rugby group expressed greater oxidative stress as indicated by increased A•- (P < 0.05 vs. control) and a subsequent decrease in NO bioavailability (P < 0.05 vs. control). The rugby group performed worse in the Ray Auditory Verbal Learning Test B (RAVLT-B, learning, and memory) and the Grooved Pegboard test using both the dominant and non-dominant hands (visuomotor coordination, P < 0.05 vs. control). There were no between-group differences in cerebral perfusion at baseline (MCAv: 54 ± 13 vs. 59 ± 12, P > 0.05). Likewise, no between-group differences in CVRCO2Hypo (2.58 ± 1.01 vs. 2.58 ± 0.75, P > 0.05) or CVRCO2Hyper (2.69 ± 1.07 vs. 3.35 ± 1.28, P > 0.05) were observed. Conclusion: The present study identified that the rugby union players are characterized by impaired cognitive function subsequent to elevated systemic-oxidative-nitrosative stress. However, this appears to be independent of any functional impairment in cerebrovascular function. Given the potential long-term trajectory towards accelerated cognitive decline in populations exposed to SRC, prophylaxis to increase NO bioavailability warrants consideration.

Keywords: cognition, concussion, mild traumatic brain injury, rugby

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