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In 2018, a panel of health economics and meningococcal disease experts convened to review methodologies, frameworks, and decision-making processes for economic evaluations of vaccines, with a focus on evaluation of vaccines targeting invasive meningococcal disease (IMD). The panel discussed vaccine evaluation methods across countries; IMD prevention benefits that are well quantified using current methods, not well quantified, or missing in current cost-effectiveness methodologies; and development of recommendations for future evaluation methods. Consensus was reached on a number of points and further consideration was deemed necessary for some topics. Experts agreed that the unpredictability of IMD complicates an accurate evaluation of meningococcal vaccine benefits and that vaccine cost-effectiveness evaluations should encompass indirect benefits, both for meningococcal vaccines and vaccines in general. In addition, the panel agreed that transparency in the vaccine decision-making process is beneficial and should be implemented when possible. Further discussion is required to ascertain: how enhancing consistency of frameworks for evaluating outcomes of vaccine introduction can be improved; reviews of existing tools used to capture quality of life; how indirect costs are considered within models; and whether and how the weighting of quality-adjusted life-years (QALY), application of QALY adjustment factors, or use of altered cost-effectiveness thresholds should be used in the economic evaluation of vaccines.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a group of functionally versatile proteins that play critical roles in the biogenesis, cellular localization and transport of RNA. Here, we outline a role for hnRNPs in gene regulatory circuits controlling sterol homeostasis. Specifically, we find that tissue-selective loss of the conserved hnRNP RALY enriches for metabolic pathways. Liver-specific deletion of RALY alters hepatic lipid content and serum cholesterol level. In vivo interrogation of chromatin architecture and genome-wide RALY-binding pattern reveal insights into its cooperative interactions and mode of action in regulating cholesterogenesis. Interestingly, we find that RALY binds the promoter region of the master metabolic regulator Srebp2 and show that it directly interacts with coactivator Nuclear Transcription Factor Y (NFY) to influence cholesterogenic gene expression. Our work offers insights into mechanisms orchestrating selective promoter activation in metabolic control and a model by which hnRNPs can impact health and disease states.

The impact of immunisation is best understood through a historical lens, since so many of the diseases which placed a burden on our population have been eliminated or controlled through immunisation. The United Kingdom (UK) National Health Service (NHS), which celebrated its 70 th birthday in 2018, is responsible for delivering the highly successful universal national immunisation programme. However, the first vaccines used in the UK were not part of a centrally coordinated programme until the 1960s. Resources that summarise the first 200 years of immunisation in the UK are not readily accessible. Here we provide a two part chronological insight into the history of the UK immunisation programme from primary sources. In Part I, we highlight the importance of wartime conditions, unprecedented vaccine development, and the polio outbreaks in the in driving developments in immunisation and discuss subsequent changes in the use of the original vaccines of the immunisation programme, namely, diphtheria, tetanus, pertussis, and polio. In Part 2, we discuss the formation of the Joint Committee on Vaccination and Immunisation and its role, working with public health agencies and advising the UK Governments on vaccine policy, to bring a comprehensive programme to defend the health of the population against serious infectious diseases, highlighting the importance of programme organisation and leadership., Competing Interests: Competing interests: SLa, SLo, NDM and MER declare that they have no conflicts of interest. DS reports personal fees from vaccine manufacturers, outside the submitted work. AJP reports grants from Okairos which ended in the past 36 months, and is Chair of the UK Department of Health’s Joint Committee on Vaccination and Immunisation and the EMA scientific advisory group on vaccines, and is a member of the WHO’s SAGE., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Explore how traumatic brain injury (TBI) is screened among spinal cord injury (SCI) patients across the continuum of care., Design: Retrospective chart review Setting: Emergency department, trauma, inpatient rehabilitation Participants: 325 patients with SCI from inpatient rehabilitation facility (IRF) between March 1, 2011 and December 31, 2014 were screened. 49 eligible subjects had traumatic SCI and received care in adjoining acute care (AC) hospital., Outcome Measures: Demographic characteristics and variables that capture diagnosis of TBI/SCI included documentation from ambulance, emergency department, AC, and IRF including ICD-9 codes, altered mental status, loss of consciousness (LOC), Glasgow Coma Score, Post Traumatic Amnesia (PTA), neuroimaging, and cognitive assessments., Results: Participants were male (81%), white (55%), privately insured (49%), and aged 39.3±18.0 years with 51% paraplegic and 49% tetraplegic. Mechanisms of injury were gunshot wound (31%), fall (29%), and motor vehicle accident (20%). TBI occurred in 65% of SCI individuals, however documentation of identification of TBI, LOC, and CT imaging results varied in H&P, discharge notes, and ICD-9 codes across the continuum. Cognitive assessments were performed on 16% of subjects., Conclusions: Documentation showed variability between AC and IRF and among disciplines. Imaging and GCS were more consistently documented than LOC and PTA. It is necessary to standardize screening processes between AC and IRF to identify dual diagnosis.

Purpose: To present a unique case involving a 31-year-old male with Danon disease (diagnosed at 14) who received cardiac transplant and subsequent cardiac re-transplant., Research Design: Brief report/case study., Methods: Serial neuropsychological assessment across a 23-year span along with a review of school records and prior psychoeducational assessment., Results: A consistent pattern of higher level cognitive impairment from childhood through adulthood was found. This pattern is interpreted in light of the sparse literature regarding cognitive and adaptive functioning related to Danon disease., Conclusions: The noteworthy aspects of this case include the preservation of some academic abilities and an unexpected level of functional independence given cognitive concerns. This case study further explores the nature of the deficits related to Danon disease and highlights the benefits of neuropsychological evaluation to guide functional interventions and maximize level of independence across the life span.

Atherosclerosis is a complex and chronic disease characterized by lipid deposition in the vessel wall that leads to an inflammatory and proliferative cascade involving smooth muscle, endothelial, and immune cells. Despite substantial improvements in our understanding of mechanisms contributing to atherosclerosis and overall reduction in cardiovascular mortality, the absolute disease burden remains substantially high. The recent discovery of a new group of mediators known as long noncoding ribonucleic acids (lncRNAs) offers a unique opportunity for the development of novel diagnostic and therapeutic tools in atherothrombotic disease. A number of studies suggest that lncRNAs are important mediators in health and disease, and rapidly accumulating evidence implicates lncRNAs in regulatory circuits controlling atherosclerosis. In this review, the authors outline important contributions of lncRNAs to atherosclerosis and its associated risk factors, including hypercholesterolemia, diabetes, hypertension, and obesity., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Nuclear receptors regulate gene expression in response to environmental cues, but the molecular events governing the cell type specificity of nuclear receptors remain poorly understood. Here we outline a role for a long noncoding RNA (lncRNA) in modulating the cell type-specific actions of liver X receptors (LXRs), sterol-activated nuclear receptors that regulate the expression of genes involved in cholesterol homeostasis and that have been causally linked to the pathogenesis of atherosclerosis. We identify the lncRNA MeXis as an amplifier of LXR-dependent transcription of the gene Abca1, which is critical for regulation of cholesterol efflux. Mice lacking the MeXis gene show reduced Abca1 expression in a tissue-selective manner. Furthermore, loss of MeXis in mouse bone marrow cells alters chromosome architecture at the Abca1 locus, impairs cellular responses to cholesterol overload, and accelerates the development of atherosclerosis. Mechanistic studies reveal that MeXis interacts with and guides promoter binding of the transcriptional coactivator DDX17. The identification of MeXis as a lncRNA modulator of LXR-dependent gene expression expands understanding of the mechanisms underlying cell type-selective actions of nuclear receptors in physiology and disease.

Opportunities for strengthening surveillance of meningococcal disease exist between and within countries in Latin America. In August of 2015, a workshop was convened in the city of São Paulo, Brazil, to address the following objectives: 1) to review meningococcal disease burden and vaccine use in Latin America; 2) to evaluate the effectiveness of current meningococcal surveillance practices in the region; 3) to identify challenges to meningococcal surveillance in the region; and 4) to outline steps for strengthening meningococcal surveillance and disease control in the region. Based on the workshop's discussions, recommendations for strengthening surveillance and controlling meningococcal disease in Latin America focus on improving: a) laboratory capabilities for diagnostic testing; b) communication regarding epidemiologic- and laboratory-based analyses; c) communication during outbreaks; d) monitoring of long-term disease outcomes; e) knowledge of vaccines against serogroup B disease; and f) criteria for defining and controlling meningococcal outbreaks. Overall, improving surveillance will help guide strategies for meningococcal disease prevention and control in Latin America., Competing Interests: Conflicts of interest. M.A.P. Sáfadi has received grants to support research projects and consultancy fees from vaccine manufacturers. M.T. Valenzuela has no conflicts or financial interests to declare. A.F. Carvalho has no conflicts or financial interests to declare. L.H. De Oliveira has no conflicts or financial interests to declare. D.M. Salisbury has provided paid consultancy services to vaccine manufacturers. J.K. Andrus has no conflicts or financial interests to declare.

Interest in addressing antimicrobial resistance (AMR) has grown recently but little effort has been made to consider how existing and new vaccines could impact on AMR. A 2017 Chatham House meeting considered the role of vaccines and how to demonstrate their value through their impact on AMR. Ways existing vaccines have reduced antibiotic prescribing and the prevalence of some resistant organisms were reviewed. Other new vaccines could have a similar impact. In gonorrhoea, where complete resistance has developed, vaccine may be the best option. Valuing the impact of vaccines on AMR was challenging: there were difficult methodological issues and a lack of data for modelling. A participant poll suggested priorities for accelerated vaccine development were tuberculosis, typhoid, influenza, RSV and gonorrhoea. More evidence is needed to convince policymakers but that vaccine development projects should be considered by funders on the same basis as those for new antibiotics or diagnostics., (Copyright © 2017. Published by Elsevier Ltd.)

Objective: To investigate trends of hospital-based health care utilization after admission to a level I trauma center after acute traumatic brain injury (TBI)., Design: Retrospective review., Setting: Large urban trauma hospital and a hospital council data registry consisting of 88 member institutions (>150 hospitals) covering 15,000 square miles., Participants: All patients (N=5291) admitted to a level I trauma center between January 1, 2006, and June 30, 2014, who experienced an acute TBI based on International Classification of Diseases, Ninth Revision coding., Interventions: Not applicable., Main Outcome Measures: Included the incidence and type of select hospital-based services received. Analyses were also categorized based on demographic and injury-related information., Results: Of the 5291 patients with newly acquired TBI who were admitted, 512 died, leaving 4779 patients for inclusion in the final analysis. Additional health care utilization from January 1, 2006, and June 30, 2014, was recorded for 3158 patients (66%), totaling 12,307 encounters, with a median of 3 encounters (interquartile range, 1-5) and a maximum of 102 encounters. Most nonadmission urgent or procedural visits (96%) and inpatient encounters (93%) occurred in the first year. Of all the additional encounters, 9769 visits were nonadmission urgent or procedural visits (79%) with a median charge of $1955. The most common type of encounter was elective (46%), followed by medical emergency (29%). Of the remaining 2538 inpatient encounters (21%), the mean length of stay was 6 days with a median charge of $28,450. Medical emergency (39%) and elective admissions (33%) again were the most common encounter type., Conclusions: This analysis encompasses health care utilization across the range of TBI severity and numerous hospital systems, allowing for a more comprehensive and objective identification of reasons for readmission. This represents an initial step to developing a preventive intervention to manage secondary complications postinjury., (Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

A concussion knowledge survey was completed by 561 rehabilitation professionals across a wide range of disciplines in a nationwide rehabilitation hospital system. Item questions were structured to reflect key areas of concussion knowledge targeted in a prior consensus statement. The vast majority of staff provided responses consistent with the current concussion literature regarding concussion diagnosis and symptom presentation immediately after concussion. Greater variability was seen for items assessing beliefs about the typical recovery from concussion, best care practices, and long-term effects from concussion. Factors such as profession, years of experience, and work with concussion or traumatic brain injury were not consistently related to better performance on the survey. Prior concussion-focused education/training was related to better survey performance. This survey highlights the pressing need to educate frontline health providers regarding concussion recovery and best care practices.

Purpose/objective: To investigate the feasibility of brain-computer interface (BCI) with patients on an inpatient spinal cord injury (SCI) unit. Research Method/Design: This study included 25 participants aged 18-64 who sustained traumatic or nontraumatic SCI and did not have severe cognitive or psychiatric impairment. Participants completed a variety of screening measures related to cognition, psychological disposition, pain, and technology experience/interest. The Emotiv electroencephalography system was used in conjunction with a cube rotation and manipulation game presented on a laptop computer., Results: The majority of participants successfully completed the BCI game and reported enjoyment of the experience. Outside of a mild trend of lower performance among participants with a past or present head injury, there were no demographic variables, injury variables or screening measures significantly associated with BCI performance., Conclusions/implications: The BCI paradigm demonstrated feasibility and safety across participant age range, educational and vocational background, and level of injury. Despite the rapid integration of technology into rehabilitation health care settings, there are few evidence-based studies regarding the feasibility of technology with specific inpatient populations. Clinical implications and challenges of using this technology in a rehabilitation setting are discussed. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

The potential benefit of technology to enhance recovery after central nervous system injuries is an area of increasing interest and exploration. The primary emphasis to date has been motor recovery/augmentation and communication. This paper introduces two original studies to demonstrate how advanced technology may be integrated into subacute rehabilitation. The first study addresses the feasibility of brain computer interface with patients on an inpatient spinal cord injury unit. The second study explores the validity of two virtual environments with acquired brain injury as part of an intensive outpatient neurorehabilitation program. These preliminary studies support the feasibility of advanced technologies in the subacute stage of neurorehabilitation. These modalities were well tolerated by participants and could be incorporated into patients' inpatient and outpatient rehabilitation regimens without schedule disruptions. This paper expands the limited literature base regarding the use of advanced technologies in the early stages of recovery for neurorehabilitation populations and speaks favorably to the potential integration of brain computer interface and virtual reality technologies as part of a multidisciplinary treatment program.

Objective: In 2012, the highest numbers of West Nile Virus (WNV) cases were reported by the Center for Disease Control since 2003. This outbreak included over half of the identified patients being classified with one of the more debilitating neuroinvasive subtypes of WNV. Despite improvements in diagnosis and treatment options in symptom management, longitudinal research on WNV neurocognitive and functional outcomes is limited by sample size, retrospective review, and/or reliance on self-report measures for cognitive status and level of independence. This study describes the cases of 2 patients diagnosed with WNV as they complete rehabilitation across the continuum of care., Research Method: Review of two cases that experience different rehabilitation outcomes 4-18 months post diagnosis., Results: The cases presented here demonstrate the potentially differential courses of recovery and outcomes for physical (e.g., balance, ambulation, upper extremity function), cognitive (e.g., attention, executive functions, memory, language, visuospatial), and emotional functioning, as assessed via measures administered by the patient's physical therapists and neuropsychologists. These patients were evaluated as part of the standard clinical practice to monitor changes, track recovery, and provide recommendations across the continuum of care from admission to discharge from acute inpatient rehabilitation, during outpatient day neurorehabilitation, and while receiving outpatient neuropsychology services., Conclusions: These cases highlight the variability in rehabilitative course for individuals diagnosed with WNV. Consistent follow-up with patients is recommended to ensure management of remitting and chronic symptoms., ((c) 2015 APA, all rights reserved).)

Vaccines have made a major contribution to global health in recent decades but they could do much more. In November 2011, a Royal Society discussion meeting, 'New vaccines for global health', was held in London to discuss the past contribution of vaccines to global health and to consider what more could be expected in the future. Papers presented at the meeting reviewed recent successes in the deployment of vaccines against major infections of childhood and the challenges faced in developing vaccines against some of the world's remaining major infectious diseases such as human immunodeficiency virus (HIV), malaria and tuberculosis. The important contribution that development of more effective veterinary vaccines could make to global health was also addressed. Some of the social and financial challenges to the development and deployment of new vaccines were reviewed. The latter issues were also discussed at a subsequent satellite meeting, 'Accelerating vaccine development', held at the Kavli Royal Society International Centre. Delegates at this meeting considered challenges to the more rapid development and deployment of both human and veterinary vaccines and how these might be addressed. Papers based on presentations at the discussion meeting and a summary of the main conclusions of the satellite meeting are included in this issue of Philosophical Transactions of the Royal Society B.

The vaccine landscape has changed considerably over the last decade with many new vaccines and technological developments, unprecedented progress in reaching out to children and the development of new financing mechanisms. At the same time, there are more demands and additional expectations of national policy makers, donors and other interested parties for increased protection through immunization. The Global Immunization Vision and Strategy (GIVS), which broadens the previous scope of immunization efforts, sets a number of goals to be met by countries. The WHO has recently reviewed and adjusted both its policy making structure and processes for vaccines and immunization to include an enlarged consultation process to generate evidence-based recommendations, thereby ensuring the transparency of the decision making process and improving communications. This article describes the process of development of immunization policy recommendations at the global level and some of their impacts. It focuses on the roles and modes of operating of the Strategic Advisory Group of Experts on immunization, which is the overarching advisory group involved with the issuance of policy recommendations, monitoring and facilitating the achievement of the GIVS goals. The article also describes the process leading to the publication of WHO vaccine position papers, which provide WHO recommendations on vaccine use. WHO vaccine-related recommendations have become a necessary step in the pathway to the introduction and use of vaccines, especially in developing countries and, consequently, have a clear and significant impact.

The introduction of a vaccine against human papillomavirus (HPV), a sexually transmitted virus that is the causal factor of at least 95% of invasive cervical cancer, could significantly reduce the number of cases of cervical cancer occurring in the UK each year. To ensure that individuals are protected before onset of sexual activity, it is likely that the vaccine will be offered to children around 10 years of age. It is important that parents' attitudes to HPV vaccination are taken into account, particularly as the subject relates to sexual health issues. In order to gauge parents' initial responses to the addition of HPV vaccine to the immunisation programme and identify the issues needing further research, in-depth interviews were held with parents of girls and boys aged 8-10 years. Our results show that most parents have not heard of HPV and were not aware of the role of HPV in cervical cancer. There were concerns about offering a vaccine that protects against a sexually transmitted infection to children and that the vaccine should be offered at an older age in conjunction with a sex education program. In order to avoid rejection of this vaccine, work needs to take place now to raise awareness of HPV as a cause of cervical cancer prior to any introduction of the vaccination program.

The U.K. immunization program is managed through a tightly connected process that links the ways policy is developed, submitted to independent expert review and recommendation, adopted into strategy, and implemented into practice. There is one advisory body for immunization. Its recommendations, once accepted by government, are centrally funded, and vaccines are provided at no cost to recipients. Although the present system has worked well, changes in health care management at the peripheral level mean that the immunization program will need to adapt to retain the health gains achieved. Rates of vaccine-preventable disease are at historically low levels, although challenges related to costs and effectiveness remain.