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Background: Hirayama Disease (HD) is a rare disorder consisting of insidious onset of unilateral weakness and atrophy of the forearm and intrinsic hand muscles. Vein of Galen aneurysmal malformations (VGAMs) are rare congenital cerebral vascular malformations, consisting of high-flow arteriovenous shunting between a persistent median prosencephalic vein and arterial feeders. Methods: 14 years old boy known for VGAM presented with left-sided HD. His cervical MRI revealed enlarged epidural with anterior, left-ward displacement of the posterior dura and spinal cord. He underwent surgical treatment by laminotomies, along with tenting of an autologous duroplasty to the overlying laminae. Results: We decided to combine epidural venous plexus coagulation with posterior duraplasty and dural fixation using tenting suture which led to a favorable clinical outcome has not been previously proposed in the literature.
We hypothesize that in this context, an abnormal vasculature could also predispose to posterior epidural venous plexus engorgement, anterior dural displacement in cervical flexion, and microvascular changes in the anterior spinal arterial circulation, leading to the progressive anterior horn cell ischemia that lead to the clinical phenotype of HD. Conclusions: The association between HD and VGAM in this patient may provide clues with regard to the pathophysiology of HD.
Background: Poorly-defined cases (PDCs) of focal epilepsy are cases with no/subtle MRI abnormalities or have abnormalities extending beyond the lesion visible on MRI. Here, we evaluated the utility of Arterial Spin Labeling (ASL) MRI perfusion in PDCs of pediatric focal epilepsy. Methods: ASL MRI was obtained in 25 consecutive children presenting with poorly-defined focal epilepsy (20 MRI- positive, 5 MRI-negative). Qualitative visual inspection and quantitative analysis with asymmetry and Z-score maps were used to detect perfusion abnormalities. ASL results were compared to the hypothesized epileptogenic zone (EZ) derived from other clinical/imaging data and the resection zone in patients with Engel I/II outcome and >18 month follow-up. Results: Qualitative analysis revealed perfusion abnormalities in 17/25 total cases (68%), 17/20 MRI-positive cases (85%) and none of the MRI-negative cases. Quantitative analysis confirmed all cases with abnormalities on qualitative analysis, but found 1 additional true-positive and 4 false-positives. Concordance with the surgically-proven EZ was found in 10/11 cases qualitatively (sensitivity=91%, specificity=50%), and 11/11 cases quantitatively (sensitivity=100%, specificity=23%). Conclusions: ASL perfusion may support the hypothesized EZ, but has limited localization benefit in MRI-negative cases. Nevertheless, owing to its non-invasiveness and ease of acquisition, ASL could be a useful addition to the pre-surgical MRI evaluation of pediatric focal epilepsy.
Agoraphobic avoidance of everyday situations is a common feature in many mental health disorders. Avoidance can be due to a variety of fears, including concerns about negative social evaluation, panicking, and harm from others. The result is inactivity and isolation. Behavioural avoidance tasks (BATs) provide an objective assessment of avoidance and in situ anxiety but are challenging to administer and lack standardisation. Our aim was to draw on the principles of BATs to develop a self-report measure of agoraphobia symptoms.
The scale was developed with 194 patients with agoraphobia in the context of psychosis, 427 individuals in the general population with high levels of agoraphobia, and 1094 individuals with low levels of agoraphobia. Factor analysis, item response theory, and receiver operating characteristic analyses were used. Validity was assessed against a BAT, actigraphy data, and an existing agoraphobia measure. Test–retest reliability was assessed with 264 participants.
An eight-item questionnaire with avoidance and distress response scales was developed. The avoidance and distress scales each had an excellent model fit and reliably assessed agoraphobic symptoms across the severity spectrum. All items were highly discriminative (avoidance: a = 1.24–5.43; distress: a = 1.60–5.48), indicating that small increases in agoraphobic symptoms led to a high probability of item endorsement. The scale demonstrated good internal reliability, test–retest reliability, and validity.
The Oxford Agoraphobic Avoidance Scale has excellent psychometric properties. Clinical cut-offs and score ranges are provided. This precise assessment tool may help focus attention on the clinically important problem of agoraphobic avoidance.
Vitamin D deficiency is common among people with Intellectual and Developmental Disability (IDD) and is linked to worse health outcomes.
Our aims were to re-evaluate vitamin D testing and supplementation among inpatients with IDD, examine any correlates with physical health conditions including COVID-19 and make recommendations for the current regime of supplementation and testing within inpatient IDD services.
The study population comprised inpatients who were in any of the Northgate Hospital IDD inpatient services in Northumberland, UK. The wards sampled were the Medium Secure Unit, Low Secure Unit, Hospital Based Rehabilitation Wards and Specialist Autism Inpatient Service. Records of all inpatients between January 2019 and July 2020 were examined for 25-hydroxyvitamin D [25(OH)D] level, ward area, supplementation status, test seasonality, medication, and health status.
We performed a correlation to see whether there was an association between vitamin D level and length of time on treatment. In addition, comparison of the replete and inadequate group for age, ethnicity, seasonality, ward location and psychotropic medication was undertaken.
Data on physical health risk factors, obesity and COVID-19 infection were also collected. The physical comorbidities were described in order to evaluate whether any emerging patterns relating to COVID-19 infection were emerging.
There were 67 inpatients in Northgate IDD services on 1 January 2019, with 11 further patients admitted up to the end of the sampling period on 31 July 2020. Nineteen patients were discharged during that period, so the sample comprised 78 patients.
Ages were comparable across three of the ward areas, except for an older group of patients in the hospital-based rehabilitation setting. Mean 25(OH)D level for supplemented (800IU/day) patients was 75nmol/l (SD 20) compared to 40nmol/l (SD 19) in the non-supplemented group (p < 0.001).
Thirty-eight percent of those who were inpatients during the first wave of the COVID-19 pandemic developed symptoms, but the small sample size could not establish vitamin D levels as a predictor of outcome.
Our findings show that clinicians continue to offer vitamin D supplementation for inpatients, at a dose of 800IU (20μg) per day.
The mean vitamin D levels we observed were higher for those on supplements compared to our 2013 baseline data, whereas patients not on supplementation now had levels akin to those found previously. Vitamin D (800IU/day) supplementation is effective but adequacy of the nationally recommended dose of 400IU/day is unclear. Links to COVID-19 merit further research.
To audit the current practice of pharmacological management of Borderline Personality Disorder with NICE Clinical guideline [CG78]: Borderline personality disorder:
23 patient records were analysed in the last 18months with a diagnosis of EUPD to compare current practice against NICE clinical guidance. (2009)
1) Use a single drug.
2) Use the minimum effective dose.
3) Agree with the person the target symptoms, monitoring arrangements and anticipated duration of treatment. Antipsychotic drugs should not be used for medium, long term treatment.
4) Drug treatment should not be used specifically for borderline personality disorder or for the individual symptoms or behaviour associated. (Repeated self-harm, marked emotional instability, risk taking behaviour and transient psychotic symptoms).
5) Short-term use of sedative medication may be considered cautiously as part of the overall treatment plan in a crisis. The duration of treatment should be no longer than 1 week.
6) When considering drug treatment, provide the person with written material about the drug. This should include evidence for the drug's effectiveness in the treatment of borderline personality disorder and for any comorbid condition, and potential harm.
7) Review the effectiveness and tolerability of previous and current treatments.
8) Discontinue ineffective treatments.
Borderline Personality Disorder is common in psychiatric settings with a reported prevalence of 20%.
As per NICE Guidance (CG 78), no medications have been found effective for the longer term treatment of personality difficulties.
This audit was carried out to review if patients were offered psychiatric reviews to discuss the medications they are using, the effectiveness of these, and any potential side effects.
Good practice compliance of 90-100% was noted where >90% compliance was seen in areas where the effectiveness and tolerability of current and previous medication was reviewed by the clinicians under Structured Clinical Management. Also was noted that antipsychotics were not used for medium to long term in patients with Borderline Personality Disorder in the cohort.
The following areas were non-compliant with the NICE recommendations where a compliance <79% has been achieved.
When prescribing, use a single drug (avoid polypharmacy), agree target symptoms, monitoring and duration, provide written information, discuss evidence for effectiveness in treatment of borderline personality disorder.
Partial compliance was achieved (80-89%) with use of sedatives for less than 1 week and discontinuation of ineffective treatment.
To re-evaluate vitamin D testing and supplementation among in-patients with intellectual and developmental disability (IDD) and examine any correlates with physical health conditions, including COVID-19. Records of all in-patients between January 2019 and July 2020 (n = 78) were examined for 25-hydroxyvitamin D (25(OH)D) level, ward area, supplementation status, test seasonality, medication and health status.
The mean 25(OH)D level for supplemented (800 IU/day) patients was 75 nmol/L (s.d. = 20), compared with 40 nmol/L (s.d. = 19) in the non-supplemented group (P < 0.001). Thirty-eight percent of those who were in-patients during the first wave of the COVID-19 pandemic developed symptoms, but the small sample size could not establish vitamin D levels as a predictor of outcome.
Vitamin D (800 IU/day) supplementation is effective but the adequacy of the nationally recommended dose of 400 IU/day is unclear. Links to COVID-19 merit further research.
ABSTRACT IMPACT: My work is on the development of a novel tumor immunotherapy to treat various types of cancer OBJECTIVES/GOALS: As iNKT cells can have direct and indirect killing effects on tumor cells, we propose a novel strategy for activating iNKT cells, via a PLGA nanoparticle delivery platform, to promote anti-tumor immune responses. METHODS/STUDY POPULATION: Poly-lactic-co-glycolic acid (PLGA) nanoparticles can be reproducibly loaded with an iNKT cell glycolipid agonist, alpha-galactosylceramide (αGalCer), and a tumor associated antigen, ovalbumin (OVA). We then test our nanoP prophylactically and therapeutically against a murine model of melanoma, B16F10-OVA. RESULTS/ANTICIPATED RESULTS: These dual-loaded PLGA nanoparticles rapidly activate iNKT cells in vivo to produce IFNgamma. Furthermore, in an in vivo model of melanoma, using B16F10-OVA cells, both prophylactic and therapeutic administration of nanoparticles containing αGalCer and OVA led to decreased tumor cell growth and increased survival. We also show our nanoparticle therapy has synergistic potential with clinically used immune checkpoint blockade (ICB) therapies, anti-PD-1 and anti-CTLA-4, indicated by the significance increase in survival and lower tumor growth rate of ICB +nanoP treated mice compared to either ICB or nanoP alone. DISCUSSION/SIGNIFICANCE OF FINDINGS: This novel delivery system provides a platform with tremendous potential to harness iNKT cells for cancer immunotherapy purposes against many cancer types.
ABSTRACT IMPACT: Our research focuses on determining rural-urban disparities in chronic obstructive pulmonary disease (COPD) management to improve COPD health outcomes in rural areas. OBJECTIVES/GOALS: Several methods exist to distinguish rural from urban areas, but it is not clear which method relates most directly to rural-urban health care disparities. To address this, we compared different measures of rurality to measures of chronic obstructive pulmonary disease (COPD) processes of care among a national sample of veterans. METHODS/STUDY POPULATION: Retrospective analysis of patients with COPD (2016-2019 by ICD-10 codes) using national Veterans Affairs (VA) data. We assessed rurality by: 1) patient’s residential address, 2) assigned primary care clinic address, and 3) drive time from the patient’s residence to closest primary care clinic. Rurality designations of the residential address and primary care clinic address into urban, rural, and highly rural areas are based on the Rural Urban Commuting Area (RUCA) codes. The dependent variables were binary outcomes of: 1) documentation of a pulmonary clinic encounter and 2) evidence of spirometry to confirm the diagnosis of COPD. RESULTS/ANTICIPATED RESULTS: Of 6,765,951 veterans, 1,157,002 (17%) had COPD (Table 1). Although approximately 40% of patients with COPD reside in addresses that are rural and highly rural, a large majority are assigned to primary care clinics in urban areas (82.8%) and reside within 30 minutes to the closest primary care clinic (76.7%) (Table 2). Compared to defining rurality based on patient’s residential address or drive time to closest primary care, defining rurality based on the assigned primary care clinic address was associated with a larger disparity in rates of pulmonary encounter. In contrast, the drive time from the patient’s residence to the closest primary care was the strongest predictor of receipt of spirometry (Figure 1 and Table 3). DISCUSSION/SIGNIFICANCE OF FINDINGS: Estimates of the severity of rural-urban disparities varied based on the definition of rurality used. For two process measures, definitions of rurality based on where the patient received primary care generated more evidence of disparities than definitions based solely on the patient’s residential address.
The authors distinguish knowledge and belief attributions, emphasizing the role of the former in mental-state attribution. This does not, however, warrant diminishing interest in the latter. Knowledge attributions may not entail mental-state attributions or metarepresentations. Even if they do, the proposed features are insufficient to distinguish them from belief attributions, demanding that we first understand each underlying representation.
Although we, as archaeologists, recognize the value in teaching nonprofessionals about our discipline and the knowledge it generates about the human condition, there are few of these specialists compared to the number of archaeologists practicing today. In this introductory article to the special section titled “Touching the Past to Learn the Past,” we suggest that, because of our unique training as anthropologists and archaeologists, each of us has the potential to contribute to public archaeology education. By remembering our archaeological theory, such as social memory, we can use the artifacts we engage with on a daily basis to bridge the disconnect between what the public hopes to gain from our interactions and what we want to teach them. In this article, we outline our perspective and present an overview of the other three articles in this section that apply this approach in their educational endeavors.
Background: Measles is a highly contagious virus that reemerged in 2019 with the highest number of reported cases in the United States since 1992. Beginning in March 2019, The Johns Hopkins Hospital (JHH) responded to an influx of patients with concern for measles as a result of outbreaks in Maryland and the surrounding states. We report the JHH Department of Infection Control and Hospital Epidemiology (HEIC) response to this measles outbreak using a multidisciplinary measles incident command system (ICS). Methods: The JHH HEIC and the Johns Hopkins Office of Emergency Management established the HEIC Clinical Incident Command Center and coordinated a multipronged response to the measles outbreak with partners from occupational health services, microbiology, the adult and pediatric emergency departments, marketing and communication and local and state public health departments. The multidisciplinary structure rapidly developed, approved, and disseminated tools to improve the ability of frontline providers to quickly identify, isolate, and determine testing needs for patients suspected to have measles infection and reduce the risk of secondary transmission. The tools included a triage algorithm, visitor signage, staff and patient vaccination guidance and clinics, and standard operating procedures for measles evaluation and testing. The triage algorithms were developed for phone or in-person and assessed measles exposure history, immune status, and symptoms, and provided guidance regarding isolation and the need for testing. The algorithms were distributed to frontline providers in clinics and emergency rooms across the Johns Hopkins Health System. The incident command team also distributed resources to community providers to reduce patient influx to JHH and staged an outdoor measles evaluation and testing site in the event of a case influx that would exceed emergency department resources. Results: From March 2019 through June 2019, 37 patients presented with symptoms or concern for measles. Using the ICS tools and algorithms, JHH rapidly identified, isolated, and tested 11 patients with high suspicion for measles, 4 of whom were confirmed positive. Of the other 26 patients not tested, none developed measles infection. Exposures were minimized, and there were no secondary measles transmissions among patients. Conclusions: Using the ICS and development of tools and resources to prevent measles transmission, including a patient triage algorithm, the JHH team successfully identified, isolated, and evaluated patients with high suspicion for measles while minimizing exposures and secondary transmission. These strategies may be useful to other institutions and locales in the event of an emerging or reemerging infectious disease outbreak.
Disclosures: Aaron Milstone reports consulting for Becton Dickinson.
In “New World Order, Old World Ways: Hemingway’s Colonialism and Postcolonialism,” Marc K. Dudley looks specifically to how well Hemingway studies of the past twenty years has engaged the tenents of postcolonial theory, which critiques the political oppressions of imperialism, both political and cultural. As he argues, criticism has mostly focused on Hemingway’s ethics, arguing in the main that between his first African safari in 1933–1934 and his final one twenty years later he grew in his awareness of the Third World political scene, which allowed him to tentatively overcome his ethnocentrism. That space, many critics argue, can be measured in the differences between Green Hills of Africa (1935) and the posthumously published True at First Light (1999) and the full manuscript from which it was culled, Under Kilimanjaro (2005). In addition to Africa, Dudley explores Hemingway’s political awareness of Cuba, from its late-nineteenth-century fight for independence from Spain to the revolutions of both 1933 and 1939. Texts examined include To Have and Have Not (1937) and the oft-ignored story “Nobody Ever Dies” (1939).
Most human beings grow up speaking more than one language; a lot of us also acquire an additional language or languages other than our mother tongue. This Element in the Second Language Acquisition series investigates the human capacity to learn additional languages later in life and introduces the seminal processes involved in this acquisition. The authors discuss how to analyze learner data and what the findings tell us about language learning; critically assessing a leading theory of how adults learn a second language: Generative SLA. This theory describes both universal innate knowledge and individual experiences as crucial for language acquisition. This Element makes the relevant connections between first and second language acquisition and explores whether they are fundamentally similar processes. Slabakova et al. provide fascinating pedagogical questions that encourage students and teachers to reflect upon the experiences of second language learners.
This chapter is a reflection or insider’s view provided by a former President of the Federal Reserve Bank of New York and long-standing member of the BIS Board of Directors, William Dudley. Based on his first-hand experience, and in reference to the crucial decade following the global financial crisis of 2007–9, his contribution reflects on the usefulness of the BIS as the global cooperative organisation of central banks. The BIS continues to play a crucial role as a forum for information exchange and discussions among central bankers and for informal networking. In addition, through its research, meetings and policy work it enables international consensus-building with a view to promoting global financial stability. The contribution also identifies some areas in which the BIS can and should further improve, in particular in terms of its transparency, diversity and inclusiveness. The efficient coordination of work and the ongoing cooperation between the BIS and the other key stakeholders in the international financial system, in particular the IMF and the World Bank, also figures high on the agenda.
In patients with Down's syndrome, late onset seizures may have a relationship with the clinical onset of dementia.
to explore the profile of patients in Memory Clinic (MC) in Barnet Learning Disability Service.
Retrospective study of case notes of 41 patients with Learning Disability (LD) who were registered in MC from 2004 to 2007.
Among the patients with different level of LD attending MC the gender distribution was as follows 27 (65.9%) were women and 14 (34.1%) were men. Most of the patients 25 (60.9%) were middle aged (35-49 years old). Patients with Down's syndrome consisted of 31(75.6%). 17 (41.5%) patients were diagnosed with dementia. 24(58.5%) showed borderline results. All patients with diagnosis of dementia had Down's syndrome whereas among those without definitive diagnose of dementia predominated people with mild to moderate LD.
Neuropsychological testing included Dementia Questionnaire for Mentally Retarded Persons (DMR), Psychiatric Assessment Schedule for Adults with Developmental Disabilities (PAS-AD).
12 (26.3%) had epilepsy. The seizure started during childhood and at middle age. Those with childhood epilepsy had the better seizure control. In individuals with late onset epilepsy the beginning of the seizures preceded cognitive decline.
The analysis of patients registered in MC showed the prevalence of middle aged persons with Down's syndrome. The dementia was established in 41.5% of patients with Down's syndrome.
A bimodal distribution for seizure onset in childhood and middle age was described. Late onset of epilepsy was associated with clinical onset of dementia.
The prevalence rate of dementia in older adults with intellectual disability (ID) is comparable with that of the general population and is significantly higher in people with Down Syndrome (DS). It is recommended that diagnosis should be made following history, physical and mental state examination, cognitive assessment, blood tests and, ideally, neuroimaging. However, experience suggests that dementia may be underdiagnosed in this patient group thereby restricting access to appropriate management.
We aimed to elucidate the barriers to a timely diagnosis of dementia in the ID population attending a specialised ID memory clinic in London, UK.
We conducted a service review of the Clinic, retrospectively reviewing the records of all patients seen in 2011 to assess attendance and diagnosis rate, co-morbid physical and mental illness and the completion of neuroimaging and blood tests.
32 patients were seen at least once during 2011 in the memory clinic, of whom 11 (34%) received a diagnosis of dementia. 22 (69%) of those seen had DS and 18 (56%) were male. 12 (38%) patients have thyroid dysfunction and 8 (25%) have epilepsy. 23 patients had completed a DLD in the past year and 14 (44%) had completed more than one DLD. 12 (38%) patients had a previous brain scan and 27 (84%) patients had had blood tests in the previous year.
Comorbid physical illnesses, consistent attendance at appointments, access to psychological assessment and willingness to undergo neuroimaging and phlebotomy are significant barriers to diagnosis of dementia in patients with ID.
Executive functions (EF) drive health and educational outcomes and therefore are increasingly common treatment targets. Most treatment trials rely on questionnaires to capture meaningful change because ecologically valid, pediatric performance-based EF tasks are lacking. The Executive Function Challenge Task (EFCT) is a standardized, treatment-sensitive, objective measure which assesses flexibility and planning in the context of provocative social interactions, making it a “hot” EF task.
We investigate the structure, reliability, and validity of the EFCT in youth with autism (Autism Spectrum Disorder; n = 129), or attention deficit hyperactivity disorder with flexibility problems (n = 93), and typically developing (TD; n = 52) youth.
The EFCT can be coded reliably, has a two-factor structure (flexibility and planning), and adequate internal consistency and consistency across forms. Unlike a traditional performance-based EF task (verbal fluency), it shows significant correlations with parent-reported EF, indicating ecological validity. EFCT performance distinguishes youth with known EF problems from TD youth and is not significantly related to visual pattern recognition, or social communication/understanding in autistic children.
The EFCT demonstrates adequate reliability and validity and may provide developmentally appropriate, treatment-sensitive, and ecologically valid assessment of “hot” EF in youth. It can be administered in controlled settings by masked administrators.
The Office of Information and Regulatory Affairs (OIRA) in the Executive Office of the President coordinates the federal government’s regulatory agenda, reviews executive branch agencies’ draft regulations, and oversees government-wide information quality, peer review, privacy, and statistical policies. Remarkably, its regulatory oversight functions, and the benefit-cost framework underlying them, have not changed significantly through six very different presidential administrations. This article examines the evolution of executive regulatory oversight and analysis from the 1970s to today, exploring the reasons for its durability and whether the current imposition of a regulatory budget challenges the bipartisan nature of regulatory practice.