Search results for: Wilma Jack
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 78

Search results for: Wilma Jack

18 Predicting Success and Failure in Drug Development Using Text Analysis

Authors: Zhi Hao Chow, Cian Mulligan, Jack Walsh, Antonio Garzon Vico, Dimitar Krastev

Abstract:

Drug development is resource-intensive, time-consuming, and increasingly expensive with each developmental stage. The success rates of drug development are also relatively low, and the resources committed are wasted with each failed candidate. As such, a reliable method of predicting the success of drug development is in demand. The hypothesis was that some examples of failed drug candidates are pushed through developmental pipelines based on false confidence and may possess common linguistic features identifiable through sentiment analysis. Here, the concept of using text analysis to discover such features in research publications and investor reports as predictors of success was explored. R studios were used to perform text mining and lexicon-based sentiment analysis to identify affective phrases and determine their frequency in each document, then using SPSS to determine the relationship between our defined variables and the accuracy of predicting outcomes. A total of 161 publications were collected and categorised into 4 groups: (i) Cancer treatment, (ii) Neurodegenerative disease treatment, (iii) Vaccines, and (iv) Others (containing all other drugs that do not fit into the 3 categories). Text analysis was then performed on each document using 2 separate datasets (BING and AFINN) in R within the category of drugs to determine the frequency of positive or negative phrases in each document. A relative positivity and negativity value were then calculated by dividing the frequency of phrases with the word count of each document. Regression analysis was then performed with SPSS statistical software on each dataset (values from using BING or AFINN dataset during text analysis) using a random selection of 61 documents to construct a model. The remaining documents were then used to determine the predictive power of the models. Model constructed from BING predicts the outcome of drug performance in clinical trials with an overall percentage of 65.3%. AFINN model had a lower accuracy at predicting outcomes compared to the BING model at 62.5% but was not effective at predicting the failure of drugs in clinical trials. Overall, the study did not show significant efficacy of the model at predicting outcomes of drugs in development. Many improvements may need to be made to later iterations of the model to sufficiently increase the accuracy.

Keywords: data analysis, drug development, sentiment analysis, text-mining

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17 Prevalence of Adverse Events in Children and Adolescents on Antiretroviral Therapy: Examining the Pediatric Cohort in the Eastern Cape

Authors: Shannon Glaspy, Gerald Boon, Jack Lambert

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Studies on AE of highly active antiretroviral therapy (HAART) in children and adolescents are rare. The aim of this study is to observe the frequency of treatment limiting adverse drug reactions against years on ARVs and specific ARV regimen. Methods: A retrospective cohort study was conducted in East London, South Africa. All patient files in the pediatric (0 – 18 years) ARV cohort were examined, selecting only those patients started on HAART. ARV regimen changes explicitly due to AE, age on ARV treatment onset, age of AE onset, and gender were extrapolated. Eligible subjects were obtained from patient folders, anonymized and cross-referenced with data obtained from electronic records. A total of 1120 patients [592 male (52.9%) and 528 female (47.1%)] were charted by incidence and year. Additional information was extrapolated in cases where the patient experienced lipodystrophy and lipoatrophy to include the number of years on ARVs prior to the onset of the AE. Results: Of the 1120 HIV infected children of the hospital cohort, a total of 105 (9.37%) AE (53.3% male) observed were deemed eligible for the study due to completeness of medical history and agreement between electronic records and paper files. The AE cited were as follows: lipoatrophy 62 (5.53% of all subjects), lipodystrophy 27 (2.41%), neuropathy 9 (0.8%), anemia 2 (0.17%), Steven Johnsons Syndrome 1 (0.08%), elevated LFTs 1 (0.8%), breast hypertrophy (0.08%), gastritis 1 (0.08%) and rash 1 (0.08%). The most prevalence ARV regimens associated with the onset of the AE are: D4T/3TC/EFV 72 cases (64.86% of all AE), D4T/3TC/LOPr 24 cases (21.62%). Lipoatrophy and lipodystrophy combined represent 84.76% (89 cases) of all adverse events documented in this cohort. Within the 60 cases of lipoatrophy, the average number of years on ARVs associated with an AE is 3.54, with 14 cases experiencing an AE between 0-2 years of HAART. Within the 29 cases of lipodystrophy, the average number of years on ARVs associated with an AE is 3.89, with 4 cases experiencing an AE between 0-2 years on HAART. The regimen D4T/3TC/EFV is associated with 43 cases (71.66%) of lipoatrophy and 21 cases (72.41%) of lipodystrophy. D4T/3TC/LOPr is associated with 15 cases (25%) of lipoatrophy and 7 cases (24.14%) of lipodystrophy. The frequency of AE associated with ARV regimens could be misrepresented due to prevalence of different 1st line regimens which were not captured in this study, particularly with the systematic change of 1st line drugs from D4T to ABC in 2010. Conclusion: In this descriptive study we found a 9.37% prevalence of AE were significant enough to be treatment limiting among our cohort. Lipoatrophy accounted for 59.04% of all documented AE. Overall, D4T/3TC/EFV was associated with 64.86% of all AE, 71.66% of lipoatrophy cases and 72.41% of lipodystrophy cases.

Keywords: ARV, adverse events, HAART, pediatric

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16 An Observational Study Assessing the Baseline Communication Behaviors among Healthcare Professionals in an Inpatient Setting in Singapore

Authors: Pin Yu Chen, Puay Chuan Lee, Yu Jen Loo, Ju Xia Zhang, Deborah Teo, Jack Wei Chieh Tan, Biauw Chi Ong

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Background: Synchronous communication, such as telephone calls, remains the standard communication method between nurses and other healthcare professionals in Singapore public hospitals despite advances in asynchronous technological platforms, such as instant messaging. Although miscommunication is one of the most common causes of lapses in patient care, there is a scarcity of research characterizing baseline inter-professional healthcare communications in a hospital setting due to logistic difficulties. Objective: This study aims to characterize the frequency and patterns of communication behaviours among healthcare professionals. Methods: The one-week observational study was conducted on Monday through Sunday at the nursing station of a cardiovascular medicine and cardiothoracic surgery inpatient ward at the National Heart Centre Singapore. Subjects were shadowed by two physicians for sixteen hours or consecutive morning and afternoon nursing shifts. Communications were logged and characterized by type, duration, caller, and recipient. Results: A total of 1,023 communication events involving the attempted use of the common telephones at the nursing station were logged over a period of one week, corresponding to a frequency of one event every 5.45 minutes (SD 6.98, range 0-56 minutes). Nurses initiated the highest proportion of outbound calls (38.7%) via the nursing station common phone. A total of 179 face-to-face communications (17.5%), 362 inbound calls (35.39%), 481 outbound calls (47.02%), and 1 emergency alert (0.10%) were captured. Average response time for task-oriented communications was 159 minutes (SD 387.6, range 86-231). Approximately 1 in 3 communications captured aimed to clarify patient-related information. The total duration of time spent on synchronous communication events over one week, calculated from total inbound and outbound calls, was estimated to be a total of 7 hours. Conclusion: The results of our study showed that there is a significant amount of time spent on inter-professional healthcare communications via synchronous channels. Integration of patient-related information and use of asynchronous communication channels may help to reduce the redundancy of communications and clarifications. Future studies should explore the use of asynchronous mobile platforms to address the inefficiencies observed in healthcare communications.

Keywords: healthcare communication, healthcare management, nursing, qualitative observational study

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15 Structural Health Assessment of a Masonry Bridge Using Wireless

Authors: Nalluri Lakshmi Ramu, C. Venkat Nihit, Narayana Kumar, Dillep

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Masonry bridges are the iconic heritage transportation infrastructure throughout the world. Continuous increase in traffic loads and speed have kept engineers in dilemma about their structural performance and capacity. Henceforth, research community has an urgent need to propose an effective methodology and validate on real-time bridges. The presented research aims to assess the structural health of an Eighty-year-old masonry railway bridge in India using wireless accelerometer sensors. The bridge consists of 44 spans with length of 24.2 m each and individual pier is 13 m tall laid on well foundation. To calculate the dynamic characteristic properties of the bridge, ambient vibrations were recorded from the moving traffic at various speeds and the same are compared with the developed three-dimensional numerical model using finite element-based software. The conclusions about the weaker or deteriorated piers are drawn from the comparison of frequencies obtained from the experimental tests conducted on alternative spans. Masonry is a heterogeneous anisotropic material made up of incoherent materials (such as bricks, stones, and blocks). It is most likely the earliest largely used construction material. Masonry bridges, which were typically constructed of brick and stone, are still a key feature of the world's highway and railway networks. There are 1,47,523 railway bridges across India and about 15% of these bridges are built by masonry, which are around 80 to 100 year old. The cultural significance of masonry bridges cannot be overstated. These bridges are considered to be complicated due to the presence of arches, spandrel walls, piers, foundations, and soils. Due to traffic loads and vibrations, wind, rain, frost attack, high/low temperature cycles, moisture, earthquakes, river overflows, floods, scour, and soil under their foundations may cause material deterioration, opening of joints and ring separation in arch barrels, cracks in piers, loss of brick-stones and mortar joints, distortion of the arch profile. Few NDT tests like Flat jack Tests are being employed to access the homogeneity, durability of masonry structure, however there are many drawbacks because of the test. A modern approach of structural health assessment of masonry structures by vibration analysis, frequencies and stiffness properties is being explored in this paper.

Keywords: masonry bridges, condition assessment, wireless sensors, numerical analysis modal frequencies

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14 The Coexistence of Creativity and Information in Convergence Journalism: Pakistan's Evolving Media Landscape

Authors: Misha Mirza

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In recent years, the definition of journalism in Pakistan has changed, so has the mindset of people and their approach towards a news story. For the audience, news has become more interesting than a drama or a film. This research thus provides an insight into Pakistan’s evolving media landscape. It tries not only to bring forth the outcomes of cross-platform cooperation among print and broadcast journalism but also gives an insight into the interactive data visualization techniques being used. The storytelling in journalism in Pakistan has evolved from depicting merely the truth to tweaking, fabricating and producing docu-dramas. It aims to look into how news is translated to a visual. Pakistan acquires a diverse cultural heritage and by engaging audience through media, this history translates into the storytelling platform today. The paper explains how journalists are thriving in a converging media environment and provides an analysis of the narratives in television talk shows today.’ Jack of all, master of none’ is being challenged by the journalists today. One has to be a quality information gatherer and an effective storyteller at the same time. Are journalists really looking more into what sells rather than what matters? Express Tribune is a very popular news platform among the youth. Not only is their newspaper more attractive than the competitors but also their style of narrative and interactive web stories lead to well-rounded news. Interviews are used as the basic methodology to get an insight into how data visualization is compassed. The quest for finding out the difference between visualization of information versus the visualization of knowledge has led the author to delve into the work of David McCandless in his book ‘Knowledge is beautiful’. Journalism in Pakistan has evolved from information to combining knowledge, infotainment and comedy. What is being criticized the most by the society most often becomes the breaking news. Circulation in today’s world is carried out in cultural and social networks. In recent times, we have come across many examples where people have gained overnight popularity by releasing songs with substandard lyrics or senseless videos perhaps because creativity has taken over information. This paper thus discusses the various platforms of convergence journalism from Pakistan’s perspective. The study concludes with proving how Pakistani pop culture Truck art is coexisting with all the platforms in convergent journalism. The changing media landscape thus challenges the basic rules of journalism. The slapstick humor and ‘jhatka’ in Pakistani talk shows has evolved from the Pakistani truck art poetry. Mobile journalism has taken over all the other mediums of journalism; however, the Pakistani culture coexists with the converging landscape.

Keywords: convergence journalism in Pakistan, data visualization, interactive narrative in Pakistani news, mobile journalism, Pakistan's truck art culture

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13 Analysis of Distance Travelled by Plastic Consumables Used in the First 24 Hours of an Intensive Care Admission: Impacts and Methods of Mitigation

Authors: Aidan N. Smallwood, Celestine R. Weegenaar, Jack N. Evans

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The intensive care unit (ICU) is a particularly resource heavy environment, in terms of staff, drugs and equipment required. Whilst many areas of the hospital are attempting to cut down on plastic use and minimise their impact on the environment, this has proven challenging within the confines of intensive care. Concurrently, as globalization has progressed over recent decades, there has been a tendency towards centralised manufacturing with international distribution networks for products, often covering large distances. In this study, we have modelled the standard consumption of plastic single-use items over the course of the first 24-hours of an average individual patient’s stay in a 12 bed ICU in the United Kingdom (UK). We have identified the country of manufacture and calculated the minimum possible distance travelled by each item from factory to patient. We have assumed direct transport via the shortest possible straight line from country of origin to the UK and have not accounted for transport within either country. Assuming an intubated patient with invasive haemodynamic monitoring and central venous access, there are a total of 52 distincts, largely plastic, disposable products which would reasonably be required in the first 24-hours after admission. Each product type has only been counted once to account for multiple items being shipped as one package. Travel distances from origin were summed to give the total distance combined for all 52 products. The minimum possible total distance travelled from country of origin to the UK for all types of product was 273,353 km, equivalent to 6.82 circumnavigations of the globe, or 71% of the way to the moon. The mean distance travelled was 5,256 km, approximately the distance from London to Mecca. With individual packaging for each item, the total weight of consumed products was 4.121 kg. The CO2 produced shipping these items by air freight would equate to 30.1 kg, however doing the same by sea would produce 0.2 kg CO2. Extrapolating these results to the 211,932 UK annual ICU admissions (2018-2019), even with the underestimates of distance and weight of our assumptions, air freight would account for 6586 tons CO2 emitted annually, approximately 130 times that of sea freight. Given the drive towards cost saving within the UK health service, and the decline of the local manufacturing industry, buying from intercontinental manufacturers is inevitable However, transporting all consumables by sea where feasible would be environmentally beneficial, as well as being less costly than air freight. At present, the NHS supply chain purchases from medical device companies, and there is no freely available information as to the transport mode used to deliver the product to the UK. This must be made available to purchasers in order to give a fuller picture of life cycle impact and allow for informed decision making in this regard.

Keywords: CO2, intensive care, plastic, transport

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12 Prediction of Outcome after Endovascular Thrombectomy for Anterior and Posterior Ischemic Stroke: ASPECTS on CT

Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen

Abstract:

Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.

Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

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11 Active Vibration Reduction for a Flexible Structure Bonded with Sensor/Actuator Pairs on Efficient Locations Using a Developed Methodology

Authors: Ali H. Daraji, Jack M. Hale, Ye Jianqiao

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With the extensive use of high specific strength structures to optimise the loading capacity and material cost in aerospace and most engineering applications, much effort has been expended to develop intelligent structures for active vibration reduction and structural health monitoring. These structures are highly flexible, inherently low internal damping and associated with large vibration and long decay time. The modification of such structures by adding lightweight piezoelectric sensors and actuators at efficient locations integrated with an optimal control scheme is considered an effective solution for structural vibration monitoring and controlling. The size and location of sensor and actuator are important research topics to investigate their effects on the level of vibration detection and reduction and the amount of energy provided by a controller. Several methodologies have been presented to determine the optimal location of a limited number of sensors and actuators for small-scale structures. However, these studies have tackled this problem directly, measuring the fitness function based on eigenvalues and eigenvectors achieved with numerous combinations of sensor/actuator pair locations and converging on an optimal set using heuristic optimisation techniques such as the genetic algorithms. This is computationally expensive for small- and large-scale structures subject to optimise a number of s/a pairs to suppress multiple vibration modes. This paper proposes an efficient method to determine optimal locations for a limited number of sensor/actuator pairs for active vibration reduction of a flexible structure based on finite element method and Hamilton’s principle. The current work takes the simplified approach of modelling a structure with sensors at all locations, subjecting it to an external force to excite the various modes of interest and noting the locations of sensors giving the largest average percentage sensors effectiveness measured by dividing all sensor output voltage over the maximum for each mode. The methodology was implemented for a cantilever plate under external force excitation to find the optimal distribution of six sensor/actuator pairs to suppress the first six modes of vibration. It is shown that the results of the optimal sensor locations give good agreement with published optimal locations, but with very much reduced computational effort and higher effectiveness. Furthermore, it is shown that collocated sensor/actuator pairs placed in these locations give very effective active vibration reduction using optimal linear quadratic control scheme.

Keywords: optimisation, plate, sensor effectiveness, vibration control

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10 Crosslinked Porous 3-Dimensional Cellulose Nanofibers/Gelatin Based Biocomposite Aerogels for Tissue Engineering Application

Authors: Ali Mirtaghavi, Andy Baldwin, Rajendarn Muthuraj, Jack Luo

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Recent advances in biomaterials have led to utilizing biopolymers to develop 3D scaffolds in tissue regeneration. One of the major challenges of designing biomaterials for 3D scaffolds is to mimic the building blocks similar to the extracellular matrix (ECM) of the native tissues. Biopolymer based aerogels obtained by freeze-drying have shown to provide structural similarities to the ECM owing to their 3D format and a highly porous structure with interconnected pores, similar to the ECM. Gelatin (GEL) is known to be a promising biomaterial with inherent regenerative characteristics owing to its chemical similarities to the ECM in native tissue, biocompatibility abundance, cost-effectiveness and accessible functional groups, which makes it facile for chemical modifications with other biomaterials to form biocomposites. Despite such advantages, gelatin offers poor mechanical properties, sensitive enzymatic degradation and high viscosity at room temperature which limits its application and encourages its use to develop biocomposites. Hydrophilic biomass-based cellulose nanofibrous (CNF) has been explored to use as suspension for biocomposite aerogels for the development of 3D porous structures with excellent mechanical properties, biocompatibility and slow enzymatic degradation. In this work, CNF biocomposite aerogels with various ratios of CNF:GEL) (90:10, 70:30 and 50:50) were prepared by freeze-drying technique, and their properties were investigated in terms of physicochemical, mechanical and biological characteristics. Epichlorohydrin (EPH) was used to investigate the effect of chemical crosslinking on the molecular interaction of CNF: GEL, and its effects on physicochemical, mechanical and biological properties of the biocomposite aerogels. Ultimately, chemical crosslinking helped to improve the mechanical resilience of the resulting aerogels. Amongst all the CNF-GEL composites, the crosslinked CNF: GEL (70:30) biocomposite was found to be favourable for cell attachment and viability. It possessed highly porous structure (porosity of ~93%) with pore sizes ranging from 16-110 µm, adequate mechanical properties (compression modulus of ~47 kPa) and optimal biocompatibility both in-vitro and in-vivo, as well as controlled enzymatic biodegradation, high water penetration, which could be considered a suitable option for wound healing application. In-vivo experiments showed improvement on inflammation and foreign giant body cell reaction for the crosslinked CNF: GEL (70:30) compared to the other samples. This could be due to the superior interaction of CNF with gelatin through chemical crosslinking, resulting in more optimal in-vivo improvement. In-vitro cell culture investigation on human dermal fibroblasts showed satisfactory 3D cell attachment over time. Overall, it has been observed that the developed CNF: GEL aerogel can be considered as a potential scaffold for soft tissue regeneration application.

Keywords: 3D scaffolds, aerogels, Biocomposites , tissue engineering

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9 Concussion: Clinical and Vocational Outcomes from Sport Related Mild Traumatic Brain Injury

Authors: Jack Nash, Chris Simpson, Holly Hurn, Ronel Terblanche, Alan Mistlin

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There is an increasing incidence of mild traumatic brain injury (mTBI) cases throughout sport and with this, a growing interest from governing bodies to ensure these are managed appropriately and player welfare is prioritised. The Berlin consensus statement on concussion in sport recommends a multidisciplinary approach when managing those patients who do not have full resolution of mTBI symptoms. There are as of yet no standardised guideline to follow in the treatment of complex cases mTBI in athletes. The aim of this project was to analyse the outcomes, both clinical and vocational, of all patients admitted to the mild Traumatic Brain Injury (mTBI) service at the UK’s Defence Military Rehabilitation Centre Headley Court between 1st June 2008 and 1st February 2017, as a result of a sport induced injury, and evaluate potential predictive indicators of outcome. Patients were identified from a database maintained by the mTBI service. Clinical and occupational outcomes were ascertained from medical and occupational employment records, recorded prospectively, at time of discharge from the mTBI service. Outcomes were graded based on the vocational independence scale (VIS) and clinical documentation at discharge. Predictive indicators including referral time, age at time of injury, previous mental health diagnosis and a financial claim in place at time of entry to service were assessed using logistic regression. 45 Patients were treated for sport-related mTBI during this time frame. Clinically 96% of patients had full resolution of their mTBI symptoms after input from the mTBI service. 51% of patients returned to work at their previous vocational level, 4% had ongoing mTBI symptoms, 22% had ongoing physical rehabilitation needs, 11% required mental health input and 11% required further vestibular rehabilitation. Neither age, time to referral, pre-existing mental health condition nor compensation seeking had a significant impact on either vocational or clinical outcome in this population. The vast majority of patients reviewed in the mTBI clinic had persistent symptoms which could not be managed in primary care. A consultant-led, multidisciplinary approach to the diagnosis and management of mTBI has resulted in excellent clinical outcomes in these complex cases. High levels of symptom resolution suggest that this referral and treatment pathway is successful and is a model which could be replicated in other organisations with consultant led input. Further understanding of both predictive and individual factors would allow clinicians to focus treatments on those who are most likely to develop long-term complications following mTBI. A consultant-led, multidisciplinary service ensures a large number of patients will have complete resolution of mTBI symptoms after sport-related mTBI. Further research is now required to ascertain the key predictive indicators of outcome following sport-related mTBI.

Keywords: brain injury, concussion, neurology, rehabilitation, sports injury

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8 Gathering Space after Disaster: Understanding the Communicative and Collective Dimensions of Resilience through Field Research across Time in Hurricane Impacted Regions of the United States

Authors: Jack L. Harris, Marya L. Doerfel, Hyunsook Youn, Minkyung Kim, Kautuki Sunil Jariwala

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Organizational resilience refers to the ability to sustain business or general work functioning despite wide-scale interruptions. We focus on organization and businesses as a pillar of their communities and how they attempt to sustain work when a natural disaster impacts their surrounding regions and economies. While it may be more common to think of resilience as a trait possessed by an organization, an emerging area of research recognizes that for organizations and businesses, resilience is a set of processes that are constituted through communication, social networks, and organizing. Indeed, five processes, robustness, rapidity, resourcefulness, redundancy, and external availability through social media have been identified as critical to organizational resilience. These organizing mechanisms involve multi-level coordination, where individuals intersect with groups, organizations, and communities. Because the nature of such interactions are often networks of people and organizations coordinating material resources, information, and support, they necessarily require some way to coordinate despite being displaced. Little is known, however, if physical and digital spaces can substitute one for the other. We thus are guided by the question, is digital space sufficient when disaster creates a scarcity of physical space? This study presents a cross-case comparison based on field research from four different regions of the United States that were impacted by Hurricanes Katrina (2005), Sandy (2012), Maria (2017), and Harvey (2017). These four cases are used to extend the science of resilience by examining multi-level processes enacted by individuals, communities, and organizations that together, contribute to the resilience of disaster-struck organizations, businesses, and their communities. Using field research about organizations and businesses impacted by the four hurricanes, we code data from interviews, participant observations, field notes, and document analysis drawn from New Orleans (post-Katrina), coastal New Jersey (post-Sandy), Houston Texas (post-Harvey), and the lower keys of Florida (post-Maria). This paper identifies an additional organizing mechanism, networked gathering spaces, where citizens and organizations, alike, coordinate and facilitate information sharing, material resource distribution, and social support. Findings show that digital space, alone, is not a sufficient substitute to effectively sustain organizational resilience during a disaster. Because the data are qualitative, we expand on this finding with specific ways in which organizations and the people who lead them worked around the problem of scarce space. We propose that gatherings after disaster are a sixth mechanism that contributes to organizational resilience.

Keywords: communication, coordination, disaster management, information and communication technologies, interorganizational relationships, resilience, work

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7 Perception Differences in Children Learning to Golf with Traditional versus Modified (Scaled) Equipment

Authors: Lindsey D. Sams, Dean R. Gorman, Cathy D. Lirgg, Steve W. Dittmore, Jack C. Kern

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Golf is a lifetime sport that provides numerous physical and psychological benefits. The game has struggled with attrition and retention within minority groups and this has exposed the lack of a modified introduction to the game that is uniformly accessible and developmentally appropriate. Factors that have been related to sport participatory behaviors include perceived competence, enjoyment and intention. The purpose of this study was to examine self-reported perception differences in competence and enjoyment between learners using modified and traditional equipment as well as the potential effects these factors could have on intent for future participation. For this study, SNAG Golf was chosen to serve as the scaled equipment used by the modified equipment group. The participants in this study were 99 children (24 traditional equipment users/ 75 modified equipment users) located across the U.S. with ages ranging from 7 to 12 years (2nd-5th grade). Utilizing a convenience sampling method, data was obtained on a voluntary basis through surveys measuring children’s golf participation and self-perceptions concerning perceived competence, enjoyment and intention to continue participation. The scales used for perceived competence and enjoyment included Susan Harter’s Self-Perception Profile for Children (SPPC) along with the Physical Activity Enjoyment Scale (PACES). Analysis revealed no significant differences for enjoyment, perceived competence or intention between children learning with traditional golf equipment and modified golf equipment. This was true even though traditional equipment users reported significantly higher experience levels than that of modified users. Intention was regressed on the enjoyment and perceived competence variables. Congruent with current literature, enjoyment was a strong predictor of intention to continue participation, for both groups. Modified equipment users demonstrated significantly lower experience levels but reported similar levels of competence, enjoyment and intent to continue participation as reported by the more experienced, and potentially more skilled, traditional users. The ability to immediately generate these positive affects suggests the potential adoption of a more effective way to learn golf and a method that is conducive to participatory behaviors related to attrition and retention. These implications in turn, highlight an equipment candidate ideal for inception into physical education programs where new learners are introduced to various sports in safe and developmentally appropriate environments. A major goal of this study was to provide foundational research that instigates the further examination of golf’s introductory teaching methodologies, as there is a lack of its presence in current literature. Future research recommendations range from improvements in the current research design to expansive approaches related to the topic, such as progressive skill development, knowledge of the game’s tactical and strategic concepts, playing ability and teaching effectiveness when utilizing modified versus traditional equipment.

Keywords: adaptive sports, enjoyment, golf participation, modified equipment, perceived competence, SNAG golf

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6 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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5 Where do Pregnant Women Miss Out on Nutrition? Analysis of Survey Data from 22 Countries

Authors: Alexis D'Agostino, Celeste Sununtunasuk, Jack Fiedler

Abstract:

Background: Iron-folic acid (IFA) supplementation during antenatal care (ANC) has existed in many countries for decades. Despite this, low national coverage persists and women do not often consume appropriate amounts during pregnancy. USAID’s SPRING Project investigated pregnant women’s access to, and consumption of, IFA tablets through ANC. Cross-country analysis provided a global picture of the state of IFA-supplementation, while country-specific results noted key contextual issues, including geography, wealth, and ANC attendance. The analysis can help countries prioritize strategies for systematic performance improvements within one of the most common micronutrient supplementation programs aimed at reducing maternal anemia. Methodology: Using falter point analysis on Demographic and Health Survey (DHS) data collected from 162,958 women across 22 countries, SPRING identified four sequential falter points (ANC attendance, IFA receipt or purchase, IFA consumption, and number of tablets taken) where pregnant women fell out of the IFA distribution structure. SPRING analyzed data on IFA intake from DHS surveys with women of reproductive age. SPRING disaggregated these data by ANC participation during the most recent pregnancy, residency, and women’s socio-economic status. Results: Average sufficient IFA tablet use across all countries was only eight percent. Even in the best performing countries, only about one-third of pregnant women consumed 180 or more IFA tablets during their most recent pregnancy. ANC attendance was an important falter point for a quarter of women across all countries (with highest falter rates in Democratic Republic of the Congo, Nigeria, and Niger). Further analysis reveals patterns, with some countries having high ANC coverage but low IFA provision during ANC (DRC and Haiti), others having high ANC coverage and IFA provision but few women taking any tablets (Nigeria and Liberia), and countries that perform well in ANC, supplies, and initial consumption but where very few women consume the recommended 180 tablets (Malawi and Cambodia). Country-level analysis identifies further patterns of supplementation. In Indonesia, for example, only 62% of women in the poorest quintile took even one IFA tablet, while 86% of the wealthiest women did. This association between socioeconomic status and IFA intake held across nearly all countries where these data are available and was also visible in rural/urban comparisons. Analysis of ANC attendance data also suggests that higher numbers of ANC visits are associated with higher tablet intake. Conclusions: While it is difficult to disentangle which specific aspects of supply or demand cause the low rates of consumption, this tool allows policy-makers to identify major bottlenecks to scaling-up IFA supplementation during ANC. In turn, each falter point provides possible explanations of program performance and helps strategically identify areas for improved IFA supplementation. For example, improving the delivery of IFA supplementation in Ethiopia relies on increasing access to ANC, but also on identifying and addressing program gaps in IFA supply management and health workers’ practices in order to provide quality ANC services. While every country requires a customized approach to improving IFA supplementation, the multi-country analysis conducted by SPRING is a helpful first step in identifying country bottlenecks and prioritizing interventions.

Keywords: iron and folic acid, supplementation, antenatal care, micronutrient

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4 Feasibility of Implementing Digital Healthcare Technologies to Prevent Disease: A Mixed-Methods Evaluation of a Digital Intervention Piloted in the National Health Service

Authors: Rosie Cooper, Tracey Chantler, Ellen Pringle, Sadie Bell, Emily Edmundson, Heidi Nielsen, Sheila Roberts, Michael Edelstein, Sandra Mounier Jack

Abstract:

Introduction: In line with the National Health Service’s (NHS) long-term plan, the NHS is looking to implement more digital health interventions. This study explores a case study in this area: a digital intervention used by NHS Trusts in London to consent adolescents for Human Papilloma Virus (HPV) immunisation. Methods: The electronic consent intervention was implemented in 14 secondary schools in inner city, London. These schools were statistically matched with 14 schools from the same area that were consenting using paper forms. Schools were matched on deprivation and English as an additional language. Consent form return rates and HPV vaccine uptake were compared quantitatively between intervention and matched schools. Data from observations of immunisation sessions and school feedback forms were analysed thematically. Individual and group interviews were undertaken with implementers parents and adolescents and a focus group with adolescents were undertaken and analysed thematically. Results: Twenty-eight schools (14 e-consent schools and 14 paper consent schools) comprising 3219 girls (1733 in paper consent schools and 1486 in e-consent schools) were included in the study. The proportion of pupils eligible for free school meals, with English as an additional language and students' ethnicity profile, was similar between the e-consent and paper consent schools. Return of consent forms was not increased by the implementation of the e-consent intervention. There was no difference in the proportion of pupils that were vaccinated at the scheduled vaccination session between the paper (n=14) and e-consent (n=14) schools (80.6% vs. 81.3%, p=0.93). The transition to using the system was not straightforward, whilst schools and staff understood the potential benefits, they found it difficult to adapt to new ways of working which removed some level or control from schools. Part of the reason for lower consent form return in e-consent schools was that some parents found the intervention difficult to use due to limited access to the internet, finding it hard to open the weblink, language barriers, and in some cases, the system closed a few days prior to sessions. Adolescents also highlighted the potential for e-consent interventions to by-pass their information needs. Discussion: We would advise caution against dismissing the e-consent intervention because it did not achieve its goal of increasing the return of consent forms. Given the problems embedding a news service, it was encouraging that HPV vaccine uptake remained stable. Introducing change requires stakeholders to understand, buy in, and work together with others. Schools and staff understood the potential benefits of using e-consent but found the new ways of working removed some level of control from schools, which they found hard to adapt to, possibly suggesting implementing digital technology will require an embedding process. Conclusion: The future direction of the NHS will require implementation of digital technology. Obtaining electronic consent from parents could help streamline school-based adolescent immunisation programmes. Findings from this study suggest that when implementing new digital technologies, it is important to allow for a period of embedding to enable them to become incorporated in everyday practice.

Keywords: consent, digital, immunisation, prevention

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3 Arab and Arab-American Writers as Mediators between Arab and American Cultures in Response to Contemporary Media Representation of Arabs

Authors: Mansoor Mohammed Abdu Al-Gabali

Abstract:

This paper addresses the growing interest among non-Arab individuals in understanding the realities of Arab peoples and their cultures. The global media, particularly after the September 11 attacks, has contributed to negative and misrepresentative portrayals of Arabs. The paper aims to critically analyze various representations of identity, culture, and politics in the works of three contemporary Arab and Arab-American women writers. By exploring the perspectives and attitudes of these writers, the paper aims to challenge and rectify the misrepresentation created by the media and foster mutual understanding between Arab and American societies. Research Aim: The aim of this research is to examine the writings of Arab and Arab-American women in order to highlight the strengths and awareness of Arab cultures. It seeks to show how these writers create spaces for responding to the misrepresentation perpetuated by the media. The research contributes to bridging the gaps between Arab and American societies and fostering better mutual understanding. Methodology: This paper adopts a multidisciplinary approach, drawing on theoretical concepts from cultural studies. It also utilizes an inductive historical methodology to trace the works under study. The combination of these approaches allows for a comprehensive analysis of the representations of Arab peoples and cultures. Findings: The paper argues that the writings of Arab and Arab-American women demonstrate a multiplicity of perspectives and attitudes toward contemporary issues. It highlights the richness and diversity of their writing, as well as the connections they make between different periods of history and various sites of representation. The paper concludes that these writings transcend personal stories to incorporate broader national and global dialogues, emphasizing the commonalities shared by humanity and the socially contextualized issues that deserve respect. Theoretical Importance: This research holds theoretical importance in the field of cultural studies. It builds upon the works of scholars such as Jack Shaeen and Evelyn Alsultany, that have documented and critiqued the negative media representations of Arabs. By examining the writings of Arab and Arab-American women, this paper contributes to the theoretical understanding of cultural responses to media misrepresentation and the creation of spaces for mutual understanding. Data Collection and Analysis Procedures: The data collection for this research involved a thorough examination and analysis of the selected works by Elmaz Abinader, Diana Abu-Jaber, and Rajaa Al-Sanea. These works were scrutinized to identify the unique ways in which they tackled contemporary issues prevalent in Arab and Arab-American societies. Through close textual analysis and the application of cultural theories, the researchers were able to discern the underlying themes and messages conveyed in the writings. Question Addressed: The primary question addressed in this research is, "How do the writings of Arab and Arab-American women respond to the misrepresentation of Arab cultures in the media?" By exploring this question, the paper aims to shed light on the strengths and awareness of Arab cultures and to promote a more comprehensive understanding between Arabs and non-Arabs. Conclusion: This research concludes that the writings of Arab and Arab-American women serve as mediators between Arab and American cultures in response to the misrepresentation created by the media. These writings go beyond personal narratives, addressing broader social and cultural issues and seeking to highlight the commonalities shared by all human beings. The paper emphasizes the need for mutual respect and understanding in order to bridge the gaps between Arab and American societies and rectify the negative images that have been perpetuated in the media.

Keywords: Arabs, films, media, negotiation

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2 Modeling Competition Between Subpopulations with Variable DNA Content in Resource-Limited Microenvironments

Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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1 Assessing Diagnostic and Evaluation Tools for Use in Urban Immunisation Programming: A Critical Narrative Review and Proposed Framework

Authors: Tim Crocker-Buque, Sandra Mounier-Jack, Natasha Howard

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Background: Due to both the increasing scale and speed of urbanisation, urban areas in low and middle-income countries (LMICs) host increasingly large populations of under-immunized children, with the additional associated risks of rapid disease transmission in high-density living environments. Multiple interdependent factors are associated with these coverage disparities in urban areas and most evidence comes from relatively few countries, e.g., predominantly India, Kenya, Nigeria, and some from Pakistan, Iran, and Brazil. This study aimed to identify, describe, and assess the main tools used to measure or improve coverage of immunisation services in poor urban areas. Methods: Authors used a qualitative review design, including academic and non-academic literature, to identify tools used to improve coverage of public health interventions in urban areas. Authors selected and extracted sources that provided good examples of specific tools, or categories of tools, used in a context relevant to urban immunization. Diagnostic (e.g., for data collection, analysis, and insight generation) and programme tools (e.g., for investigating or improving ongoing programmes) and interventions (e.g., multi-component or stand-alone with evidence) were selected for inclusion to provide a range of type and availability of relevant tools. These were then prioritised using a decision-analysis framework and a tool selection guide for programme managers developed. Results: Authors reviewed tools used in urban immunisation contexts and tools designed for (i) non-immunization and/or non-health interventions in urban areas, and (ii) immunisation in rural contexts that had relevance for urban areas (e.g., Reaching every District/Child/ Zone). Many approaches combined several tools and methods, which authors categorised as diagnostic, programme, and intervention. The most common diagnostic tools were cross-sectional surveys, key informant interviews, focus group discussions, secondary analysis of routine data, and geographical mapping of outcomes, resources, and services. Programme tools involved multiple stages of data collection, analysis, insight generation, and intervention planning and included guidance documents from WHO (World Health Organisation), UNICEF (United Nations Children's Fund), USAID (United States Agency for International Development), and governments, and articles reporting on diagnostics, interventions, and/or evaluations to improve urban immunisation. Interventions involved service improvement, education, reminder/recall, incentives, outreach, mass-media, or were multi-component. The main gaps in existing tools were an assessment of macro/policy-level factors, exploration of effective immunization communication channels, and measuring in/out-migration. The proposed framework uses a problem tree approach to suggest tools to address five common challenges (i.e. identifying populations, understanding communities, issues with service access and use, improving services, improving coverage) based on context and available data. Conclusion: This study identified many tools relevant to evaluating urban LMIC immunisation programmes, including significant crossover between tools. This was encouraging in terms of supporting the identification of common areas, but problematic as data volumes, instructions, and activities could overwhelm managers and tools are not always suitably applied to suitable contexts. Further research is needed on how best to combine tools and methods to suit local contexts. Authors’ initial framework can be tested and developed further.

Keywords: health equity, immunisation, low and middle-income countries, poverty, urban health

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