Profound Limitations Research Articles

Limb Preservation Program and Peripheral Arterial Disease

Limb – derived from the old English ‘Lim’. A paired parts (Arm, Leg and Wing) of human that stick out/extends from the trunk of a body. Limb preservation refers to the crucial steps taken in order to save a damaged limb from amputation. Amputation of a limb may be needed when there is serious infection a wound that won’t heal or poor circulation that causes tissue to die. Patients with vascular disease are at high risk for foot and leg wounds that do not heal and may ultimately require amputation to save their lives. Severe cases of Peripheral Artery Disease (PAD) can cause irreversible tissue damage and increase the risk for amputation if not treated. The Limb Preservative Program focuses on saving limbs and also on the overall health and well being of the patient. Limb-Preservation Program (LPP) requires coordinated effort by clinicians, nurses, allied health professionals and administrators dedicated to the cause of saving and maintaining functional limbs. This is a significant consideration because over 1.5 million people live after the loss of a limb; this number is expected to increase due to the aging of the population and the worldwide exponential rise in diabetes mellitus. Peripheral Arterial Disease (PAD) is one the important cause of limb amputation. The prevalence of PAD continues to increase worldwide. It is important to identify patients with PAD because of the increased risk of myocardial infarction, stroke and cardiovascular death and impaired quality of life because of a profound limitation in exercise performance. Lower extremity PAD affects approximately 10% of population, with 30% to 40% of these patients presenting with claudication symptoms. Peripheral arterial disease is common, but the diagnosis frequently is overlooked because of subtle physical findings and lack of classic symptoms. Screening based on the ankle brachial index using doppler ultrasonography may be more useful than physical examination alone. Noninvasive modalities to locate lesions include duplex scanning, computed tomography angiogram, magnetic resonance angiography and invasive modalities peripheral angiogram is the gold standard. Major risk factors for peripheral arterial disease are cigarette smoking, diabetes mellitus, older age (Older than 40 years) hypertension, hyperlipidemia and hyperhomocystinemia. Intermittent claudication may be improved by risk-factor modification, exercise and pharmacologic therapy. Based on available evidence, a supervised exercise program is the most effective treatment. Effective drug therapies for peripheral arterial disease include aspirin (With or without dipyridamole) clopidogrel, cilostazol, and pentoxifylline. By contrast, Critical Limb Ischemia (CLI) is considered the most severe pattern of peripheral artery disease. It is defined by the presence of chronic ischemic rest pain, ulceration or gangrene attributable to the occlusion of peripheral arterial vessels. It is associated with a high risk of major amputation, cardiovascular events and death. The management of CLI should include an exercise program, guideline-based medical therapy to lower the cardiovascular risk. Most of the cases, revascularization is indicated to save limbs, an “Endovascular First” approach and lastly surgical approach if all measures were failed. The choice of the intervention is dependent on the anatomy of the stenotic or occlusive lesion, percutaneous interventions are appropriate when the lesion is focal and short but longer lesions must be treated with surgical revascularization to achieve acceptable long-term outcome. A LPP should include a patient support group as there is a significant mental component to loss of limb or living with a foot ulcer. A patient support group can be very important both preoperatively and postoperatively in helping patients deal with the clinical situation in maintaining functionality and mentaloutlook. Education can be incorporated into the program in the form of seminars for patients and referring physicians. Education is critical to achieve the goal of limb preservation through the reduction of amputation and enhancement of the patient’s quality of life. The LPP also provides a format for research that is increasingly important to the healthcare system. Chatt Maa Shi Hosp Med Coll J; Vol.22 (2); July 2023; Page 1-2

Impact of Functional Limitation on Quality of Life among Covid-19 Survivors

Background: It has been evident that after viral infections (e.g., SARS-1), patients often sustain functional limitations over a long period after discharge from the hospital. Persisting symptoms with subsequent progression to poor functional status have been reported in a substantial proportion of these patients. These patients are susceptible to developing reduced functional status that impact their ability to care for themselves and to perform usual activities of daily living in the months following hospital admission. Previous severe acute respiratory syndrome (SARS) outbreaks showed to affect the survivors lung function, exercise capacity, health-related quality of life (HrQoL), mental health, and lead to increased symptoms of fatigue and dyspnea from 6 months to 2 years after symptom onset. This study aims to assess those recovering from COVID-19 for symptoms of functional limitation and its impact on quality of life, thus identifying a group worthy of further study and early intervention. . Objective: To determine the impact of functional limitation on quality of life among COVID– 19 survivors Methods 87 patients exposed with covid-19 virus was followed up and assessed for functional limitation and quality of life. Participants were asked on a telephone to choose an appropriate option for each question in relation to current situation from the functional status scale and WHOQOL-BREF among COVID 19 survivors. Result: Karl Pearson correlation coefficient was used to determine the impact of functional limitation on quality of life among COVID19 survivors. Impact of functional limitation on four domains of quality of life was statistically significant at p<0.001. There was significantly strong negative correlation found between functional status scale and domain1 (r=-0.823) and functional status scale and domain 3 (r=-0.902) whereas there was significantly moderate negative correlation between functional status scale and domain 2 (r=0.584), functional status scale and domain 4 (r=-0.416). Conclusion: Present study concludes that there is a profound functional limitation after 6 months of post COVID. Hence the functional limitation and its associated symptoms need to be monitored and early intervention needs to be planned in post COVID19 patients.

‘Moving, moving, moving’: the social forces that perpetuate housing instability for women experiencing intimate partner violence

Housing scholars have demonstrated that intimate partner violence (IPV) is a key driver of housing instability. Contributing to existing housing literature that foregrounds the importance of material and psychological housing instability, our empirical research focuses on a novel programme providing supportive housing for women, the majority of whom are allocated housing to protect them from IPV. Our data includes in-depth interviews with the supportive housing tenants and practitioners, as well as administrative data. Our findings illuminate the close interrelation between material and psychological housing instability, and demonstrate how problems inherent in the private rental market interact with issues caused by perpetrators’ ongoing use of violence in ways that make it impossible for women to achieve either form of stability. The implication for housing scholars is to understand that although affordable housing is a protective measure, supportive housing models that rely on the private rental market, face profound limitations in achieving material and psychological housing stability for women who experience IPV.

Abstract 4204: Subcutaneous vs. orthotopic tumor models: A comparative assessment

Abstract The failure of murine tumor models to adequately simulate the native biological milieu and tissue architecture of human malignancies, has fomented much discourse surrounding the discord that exists between experimental outcomes and clinical settings. Orthotopic (OT) models, which are generated by the engraftment of tumor cells or fragments into recipient organs of the same histotype from which they were derived, has the advantage of recapitulating the appropriate vasculature, as well as cellular and stromal components as the site of origin. In the context of immunotherapy, there is increasing evidence that subcutaneous (SC) tumors bear a vastly different immunological profile compared to OT implants, a phenomenon dictated by tissue-specific recruitment of various immune subsets, and subsequently, impacts overall response. Therefore, establishing cancer models that better represent the natural tumor environment is imperative for addressing some of the foibles inherent to preclinical mouse models. To demonstrate the significance of the anatomical site of the tumor, we present a comparative assessment of the MC38 murine colon carcinoma model, in the context of SC and OT settings. In the SC model of MC38, administration of either 5mg/kg anti-mPD1, anti-mPDL1, or anti-mCTLA-4, failed to elicit any notable anti-tumor activity, as evidenced by 0% incidences of complete regressions (CR) and tumor free survivors (TFS) for all three therapeutic agents, and incidences of 11%, 5% and -22% increase in time to progression (ITP), respectively. However, mice bearing OT tumors, exhibited meaningful response to 5mg/kg anti-mPD1 and anti-mPDL1, both evoking incidences of 25% CR, 25% TFS and 108% ITP. Though the anti-mCTLA-4 treated cohort did not produce any CRs or TFS, there was, nonetheless, a 50% incidence of ITP. Taken together, the data clearly illustrates the distinct disparities in response between SC and OT tumors, with respect to immunomodulatory agents. Characterization of immune phenotype within both settings, and interrogation of additional mouse models are ongoing. The exigencies and profound limitations associated with bench to bedside translation have long encumbered the drug development process. Despite staggering financial investment in oncology research, effective treatments for a myriad of cancers remain elusive, and only 3.4% of cancer drug candidates are conferred with clinical approval. Employing modalities that adequately reproduce the molecular and structural frameworks of human tumors, is crucial to better elucidating the natural trajectory of cancer progression, thus facilitating more accurate evaluation of drug activity and therapeutic response in preclinical settings. OT models therefore represent a more disease-relevant preclinical approach compared to their subcutaneous counterparts, as they more reliably preserve the intrinsic infrastructure and complexities of patient tumors in situ. Citation Format: Kerry-Ann Bright, Sheri Barnes, Derrik Germain, Lauren Kucharczyk. Subcutaneous vs. orthotopic tumor models: A comparative assessment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4204.

Studying illicit substance exposure among urban adolescents using forensic science

There are critical challenges to measuring substance use exposure, particularly among adolescents, with major limitations to the most common methods of assessment – self-report and biomarker (urine, saliva) analysis. This study examines the use of wipe sampling as a measure of adolescent illicit substance exposure. Among low-income families, this study compared forensically analyzed wipe samples from 51 adolescents’ homes and cell phones with self-reported substance use to identify overlaps and discrepancies. There were major gaps between adolescents reporting any substance use in the past year and adolescents whose homes and/or cell phones tested positive for illicit substances via wipe sample analysis. This study builds upon previous adolescent substance use and exposure research, highlighting the profound limitations of self-reported use, and introducing wipe sampling as an effective measure of toxicant exposure. Wipe samples also provide a means to examine environmental contexts in new novel ways.

Research Highlights.

Research Highlights.

A Hybrid Deep CNN-SVM Approach for Brain Tumor Classification

Background: Feature extraction process is noteworthy in order to categorize brain tumors. Handcrafted feature extraction process consists of profound limitations. Similarly, without appropriate classifier, the promising improved results can’t be obtained. Objective: This paper proposes a hybrid model for classifying brain tumors more accurately and rapidly is a preferable choice for aggravating tasks. The main objective of this research is to classify brain tumors through Deep Convolutional Neural Network (DCNN) and Support Vector Machine (SVM)-based hybrid model. Methods: The MRI images are firstly preprocessed to improve the feature extraction process through the following steps: resize, effective noise reduction, and contrast enhancement. Noise reduction is done by anisotropic diffusion filter, and contrast enhancement is done by adaptive histogram equalization. Secondly, the implementation of augmentation enhances the data number and data variety. Thirdly, custom deep CNN is constructed for meaningful deep feature extraction. Finally, the superior machine learning classifier SVM is integrated for classification tasks. After that, this proposed hybrid model is compared with transfer learning models: AlexNet, GoogLeNet, and VGG16. Results: The proposed method uses the ‘Figshare’ dataset and obtains 96.0% accuracy, 98.0% specificity, and 95.71% sensitivity, higher than other transfer learning models. Also, the proposed model takes less time than others. Conclusion: The effectiveness of the proposed deep CNN-SVM model divulges by the performance, which manifests that it extracts features automatically without overfitting problems and improves the classification performance for hybrid structure, and is less time-consuming. Keywords: Adaptive histogram equalization, Anisotropic diffusion filter, Deep CNN, E-health, Machine learning, SVM, Transfer learning.

Disasters in the Anthropocene: a storm in a teacup?

Dramatic alterations to the natural environment due to human activity have produced a permanent rupture in the Earth system; the relative stable epoch of the Holocene has given way to a volatile Anthropocene. Acceptance of these claims means that we now live in this altered physical reality, inviting us to rethink how we conceptualise disasters. Yet, disaster scholars have been hesitant to apply the Anthropocene label and to acknowledge the profound changes that it can bring to the study of disasters. This paper queries whether this label is a necessary adage or unnecessary baggage for disaster studies by examining the possibilities and the challenges associated with engaging with the Anthropocene. An analysis of the concepts, causes, and consequences of disasters reveals how the Anthropocene provides, as the very least, a theoretical heuristic for challenging linear temporal assumptions, the epistemological status of uncertainty, and the location of agency in disaster studies.

More is different with a vengeance.

In his 1972 landmark paper "More is Different," Philip W. Anderson established "complexity" as a fundamentally important subject of inquiry. He highlighted the profound limitations of reductionist approaches in understanding nature's complexity, and he set in motion new lines of investigation that have, among other things, led to systems biology.

Mitochondrial surface coating with artificial lipid membrane improves the transfer efficacy

Extracellular mitochondria are present and act as non-cell-autonomous signals to support energetic homeostasis. While mitochondria allograft is a promising approach in rescuing neurons, glia, and vascular cells in CNS injury and disease, there are profound limitations in cellular uptake of mitochondria together with the efficacy. Here, we modified mitochondria by coating them with cationic DOTAP mixed with DOPE via a modified inverted emulsion method to improve mitochondrial transfer and efficacy. We initially optimized the method using control microbeads and liposomes followed by using mitochondria isolated from intact cerebral cortex of male adult C57BL/6J mice. After the coating process, FACS analysis indicated that approximately 86% of mitochondria were covered by DOTAP/DOPE membrane. Moreover, the artificial membrane-coated mitochondria (AM-mito) shifted the zeta-potential toward positive surface charge, confirming successful coating of isolated mitochondria. Mitochondrial proteins (TOM40, ATP5a, ACADM, HSP60, COX IV) and membrane potentials were well maintained in AM-mito. Importantly, the coating improved mitochondrial internalization and neuroprotection in cultured neurons. Furthermore, intravenous infusion of AM-mito immediately after focal cerebral ischemia-reperfusion amplified cerebroprotection in vivo. Collectively, these findings indicate that mitochondrial surface coating with artificial lipid membrane is feasible and may improve the therapeutic efficacy of mitochondria allograft.

Improving template-based CT data evaluation by integrating CMM reference data into a CAD model-based high fidelity triangle mesh

ABSTRACT Industrial X-ray computed tomography is a relatively recent technology in the field of 3D coordinate metrology. The available technical solutions represent capable systems, which are continuously adapted for different applications. Nonetheless, some profound limitations and technical challenges remain (e.g. effects of the polychromatic X-ray spectrum and a strong correlation between image quality and measurement duration), which require continuous efforts in order to improve the accuracy of such systems in the context of dimensional metrology. Therefore, this contribution demonstrates the integration of CMM measurement data into a CAD model in order to generate full reference measurements, which can be used to evaluate the measurement accuracy of CT systems. Currently, much effort is being made in order to improve simulations of CT systems with the goal to realistically recreate real CT measurements. In order to validate the simulation model by comparison against physical CT measurements, the geometry of the measurement object has to be known as accurately as possible. The presented approach shows how to generate geometries from CMM reference data which are suited to be used as an input for CT simulation tools. Detailed technical descriptions of the algorithms are given and demonstrated based on real measurements.

Not Praying to An Idol: Kant and Kierkegaard on Prayer

Not Praying to An Idol:Kant and Kierkegaard on Prayer Dennis Sansom (bio) According to Nelly Viallanex, one of Soren Kierkegaard's motives in writing about prayer is to keep people from praying to an idol. "Prayer is supposed to establish a relationship with the true God and not with an idol that would usurp the name."1 I would also say this is true of Immanuel Kant's writings about prayer. Both seem to be aware of what we might call the "philosophical problem" of prayer: 1. God is infinite, eternal, limitless, perfect, and uncorruptible, hence sui generis. 2. We are historically finite and limited both by what our cognitive abilities enable us to know, unaware of our myriad biases. 3. Because of number one, we cannot know the being of God. 4. Because of number two, we are not cognitively or psychologically equipped to pray to God. 5. If we maintain that we pray to God, we contradict numbers three and four. 6. Therefore, to pray actually to God, we must affirm the truths of numbers one and two while overcoming the restrictions of numbers three and four. Kant argues that we cannot do number six, whereas Kierkegaard believes we can. The difference between them is not necessarily that they have different views of God but that they differ on what happens in prayer. I want to explain the reasons Kant and Kierkegaard differ on prayer and why Kierkegaard's account of how we can communicate with God in prayer, even in our profound limitations, does not suffer the confines Kant puts on prayer and that it may satisfactorily respond to the philosophical problem of prayer. To clarify why Kant and Kierkegaard explain prayer the way they do, I position their accounts within their overall systems, within the core claims that drive their thinking, for their estimations of prayer derive from basic convictions underlying their philosophical thinking. KANT ON REASON AND PRAYER Kant pursued a number of philosophical topics—for example, the relationship between theoretical and practical knowledge, the possibility of synthetic [End Page 90] a priori knowledge, conceiving how the noumenal might be known in the phenomena—but one of the most important might be found in the tension between the stretching and retreating actions of reason.2 Even though amazingly complex in its development, Kant's explanation of pure reason follows a simple process. We first experience objects through intuitions about their place within the world (that is, how they fit spatially and temporally), then we conceptually understand those experiences according to a priori categories such as quantity, quality, relations, and modality, and finally, we attempt to bring unity to our experiences by formulating comprehensive ideas through the synthesizing work of reason.3 However, this great accomplishment of reason reflects a strain within its operations—it both stretches towards metaphysical claims about the whole of experiences that might inform us, for example, about the soul, the world, and even God, but, driven by its own operating restriction that all concepts must be based on experiences, it retreats from articulating such conclusions. Reason tries to unify what we understand about the world into a concept, resulting in it being driven by what Kant calls the "ascending line,"4 in which we keep trying to incorporate into more comprehensive concepts what we must assume conditions our knowledge of the world. In fact, this pursuit is a "requirement of reason,"5 which compels us "to hypostatize this idea of the sum-total of all reality"6 and even to consider there may be archetypical "ideals" (recalling Plato's ideals) that provide reason. Reason "with a standard, which enables it to estimate, by comparison, the degree of incompleteness in the objects presented to it."7 Thus, we cannot completely abandon the prospects of metaphysics.8 Yet, because all purely rational ideas must emerge from how we experience objects spatially and temporally, and because we do not experience such things as the soul or archetypical ideals, we must resist conferring ontological reality to these metaphysical claims. We cannot presume that the hoped-for imaginative, archetypical ideals would "furnish rules or standards for explanation or examination."9 In fact, in comparison to...

A Systematic Review investigating the Effectiveness of Exercise training in Glycogen Storage Diseases.

Glycogen storage diseases (GSDs) are rare inborn errors of carbohydrate metabolism typically with skeletal muscle and liver involvement. In those with skeletal muscle involvement, the majority display symptoms of exercise intolerance which can cause profound exercise limitation and impair everyday living and quality of life (QoL). There are no curative treatments for GSDs, thus therapeutic options, such as exercise training, are aimed at improving QoL by alleviating signs and symptoms. In order to investigate the effectiveness of exercise training in adults with GSDs, we systematically reviewed the literature. In this review we conducted searches within SCOPUS and MEDLINE to identify potential papers for inclusion. These papers were independently assessed for inclusion and quality by two authors. We identified 23 studies which included aerobic training, strength training or respiratory muscle training in patients with McArdles (n = 41) and Pompe disease (n = 139). In McArdle disease, aerobic exercise training improved aerobic capacity (VO2 peak) by 14-111% with further benefits to functional capacity and well-being. Meanwhile, strength training increased muscle peak power by 100-151% and reduced disease severity. In Pompe disease, a combination of aerobic and strength training improved VO2 peak by 9-10%, muscle peak power by 64%, functional capacity and well-being. Furthermore, respiratory muscle training (RMT) improved respiratory muscular strength [maximum inspiratory pressure (MIP) increased by up to 65% and maximum expiratory pressure (MEP) by up to 70%], with additional benefits shown in aerobic capacity, functional capacity and well-being. This adds to the growing body of evidence which suggests that supervised exercise training is safe and effective in improving aerobic capacity and muscle function in adults with McArdle or Pompe disease. However, the literature base is limited in quality and quantity with a dearth of literature regarding exercise training in other GSD subtypes.

The 1782 Gaming Bill and Lottery Regulation Acts (1782 and 1787): Gambling and the Law in Later Georgian Britain

AbstractThis article brings forward new evidence regarding the circumstances surrounding the origins and authorship of the Gaming Bill of 1782, which was designed to suppress the roulette‐type game of ‘Even and Odd’. Hitherto, this Bill has presented something of a puzzle, not only in terms of why it was proposed, but its strange fate; it was never signed into law. The Gaming Bill is viewed alongside a parallel series of parliamentary measures from the 1780s aimed at regulating more tightly the official lottery and derivatives thereof, including, most controversially, lottery insurance, one aspect of which was betting on the outcomes of the lottery draw. By placing these initiatives within a single analytical frame, much can be learnt about the role of parliament and the law in regulating gambling in this period, but also the profound limits of the law in this sphere.

Effects of Acute Physical Therapy Services on Individuals with Acute Decompensated Heart Failure

<h3>Research Objectives</h3> 1) To describe the characteristics of patients admitted with acute decompensated heart failure (ADHF) that are referred to Acute Physical Therapy Services (APTS), 2) To determine if there were significant differences in initial and discharge measurements using four functional outcome measures (five minute walk test [5mWT], modified 30 second chair rise test [30CRT], six-minute walk test [6MWT], and timed up and go test [TUG], 3) To determine if patients' discharge performance could be predicted from initial performance. <h3>Design</h3> Prospective, pre and post, cohort study. <h3>Setting</h3> Academic hospital. <h3>Participants</h3> All subjects (N=102) were admitted patients with admitting diagnosis of acute decompensated heart failure and were refereed to APTS. <h3>Interventions</h3> The intervention was APTS (therapeutic exercises, transfer training, gait training, balance retraining, and patient education). Each subject received as needed intervention in each session due to limited activity tolerance, lasting between 30 to 60 minutes or as tolerated. <h3>Main Outcome Measures</h3> 6MWT to measure aerobic capacity; 5mWT to measure gait speed; TUG to assess falls, 30CRT to measure leg strength, and GROC to measure perceived progress at discharge. <h3>Results</h3> At initial evaluation, all FOM showed marked functional limitations (mean 5mWT=.723 meter/seconds; mean 30CRT=7.8 repetitions; mean 6MWT=525 feet; mean TUG=22.21 seconds). At discharge evaluation, all FOM showed significant improvement at p≤ .0005 (mean 5mWT=.795 meter/seconds; mean 30CRT=9.35 repetitions; mean 6MWT=635.65 feet; mean TUG=20.694 seconds). Significant mean differences (p≤ .001) were found in 30CRT (1.68 repetitions), in 6MWT (110.45 feet), and in TUG (-2.16 seconds), when compared the initial and discharge measurements. All initial scores were able to significantly predict discharge measurements at p≤ .005. <h3>Conclusions</h3> This study found profound functional limitations in those admitted with ADHF. During hospitalization, those subjects who received APTS made significant improvements in all four FOM. In addition, FOM at discharge can be predicted using initial admission scores. Lastly, the findings of this study add support to the effectiveness of APTS in maximizing medical management for patients admitted with ADHF. <h3>Author(s) Disclosures</h3> All authors have no conflict of interest to disclose.

Childhood Vaccinations and Type 1 Diabetes.

Type 1 diabetes (T1D) is the most common paediatric endocrine disease, and its frequency has been found to increase worldwide. Similar to all conditions associated with poorly regulated glucose metabolism, T1D carries an increased risk of infection. Consequently, careful compliance by T1D children with schedules officially approved for child immunization is strongly recommended. However, because patients with T1D show persistent and profound limitations in immune function, vaccines may evoke a less efficient immune response, with corresponding lower protection. Moreover, T1D is an autoimmune condition that develops in genetically susceptible individuals and some data regarding T1D triggering factors appear to indicate that infections, mainly those due to viruses, play a major role. Accordingly, the use of viral live attenuated vaccines is being debated. In this narrative review, we discussed the most effective and safe use of vaccines in patients at risk of or with overt T1D. Literature analysis showed that several problems related to the use of vaccines in children with T1D have not been completely resolved. There are few studies regarding the immunogenicity and efficacy of vaccines in T1D children, and the need for different immunization schedules has not been precisely established. Fortunately, the previous presumed relationship between vaccine administration and T1D appears to have been debunked, though some doubts regarding rotavirus vaccines remain. Further studies are needed to completely resolve the problems related to vaccine administration in T1D patients. In the meantime, the use of vaccines remains extensively recommended in children with this disease.

New Class of Derma-Pharmaceutical used to Alleviate Pain, Neuropathy and Increase Wound Healing

Many people in the general population battle intense chronic pain daily and it disrupts their quality of life. Current OTC therapies provide mixed results and have profound limitations. However, the Hydroglide Body and Facial Lotion is a patent-pending product that delivers consistently positive outcomes. It’s a dual-fighting agent for dermatological issues and is useful for general body aches as well as for debilitating and excruciating pain.

The Need for a Human Pangenome Reference Sequence.

The reference human genome sequence is inarguably the most important and widely used resource in the fields of human genetics and genomics. It has transformed the conduct of biomedical sciences and brought invaluable benefits to the understanding and improvement of human health. However, the commonly used reference sequence has profound limitations, because across much of its span, it represents the sequence of just one human haplotype. This single, monoploid reference structure presents a critical barrier to representing the broad genomic diversity in the human population. In this review, we discuss the modernization of the reference human genome sequence to a more complete reference of human genomic diversity, known as a human pangenome.

Public transport availability and healthcare use for Australian adults aged 18–60 years, with and without disabilities

IntroductionPublic transport (PT) availability may be more important for people with disabilities (PWD), as typically they have greater healthcare needs and mobility barriers compared with people without disabilities. This paper investigates how PT availability is associated with healthcare use for people aged 18–60 years, with and without disabilities in Australia. MethodWe used unique Australian healthcare use administrative data linked to the 2016 Census, where individuals report whether they have a disability (severe or profound core activity limitation). These data were merged with detailed information on local area PT availability for Australia's 21 largest cities. We estimated regression models to examine the association between PT availability and different types of healthcare use, while controlling for individual characteristics and larger area attributes. ResultsPT availability was positively associated with visits to general practitioners (GP), with a higher magnitude observed for people with disabilities (PWD). While people without disabilities had on average 0.1 more GP visits per year when PT availability was high compared with low, PWD on average visited their GP 0.5 more times per year if they lived in areas with high as opposed to low PT availability. Nervous system prescriptions (which includes antidepressants) were 0.27 per year fewer for PWD living in areas with high compared with low PT availability. Conversely, nervous system scripts were 0.06 higher for people without disability with high compared with low PT availability. ConclusionWe conclude that PT availability is likely to be a key factor of healthcare use. Increasing PT availability may help overcome some barriers to healthcare use for PWD. Our findings are also consistent with PT increasing access to preventive care, which may reduce the severity or better management of illnesses. PT can play an important role in improving health and decreasing health inequalities between those with and without disabilities.

Evaluating the WHO’s framing and crisis management strategy during the early stage of COVID-19 outbreak

The outbreak of COVID-19 has posed an unprecedented threat to the functioning of our society and led to a substantial loss of lives. In this paper, we systematically analyzed the World Health Organization (WHO)’s policy framing and management of the pandemic. The performance of the WHO can be evaluated in two aspects: the timeliness of their risk assessment, such as the announcements of a Public Health Emergency of International Concern (PHEIC) and pandemic, and the communication interfaces between the WHO and other stakeholders. Our study reveals that, while the WHO has made timely decisions in risk assessments, there were profound limitations in the current communication interfaces and feedback loops between the WHO, member states and other stakeholders. We recommend redesigning the current alert system so that the level of warning and the accompanying policy recommendations could more accurately reflect the threat and escalating nature of a pandemic outbreak.