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Illustrated with over 800 colour images, this practical guide covers the unique morphology and disease spectrum in pediatric patients, ranging from normal physiologic changes to pathologic states. In addition, it covers newly described pediatric diseases, such as GATA-2 haploinsufficiency and reflects the latest WHO classification for hematolymphoid neoplasms. With the visual format of an atlas, the book provides a quick reference for trainees and physicians in hematopathology, as well as for hematologists and oncologists treating pediatric patients. An online version of the book with expandable figures can be accessed on Cambridge Core, via the code printed on the inside of the cover.
Children with genetic conditions may experience significant mental health difficulties such as anxiety and challenging behaviour. However, understanding of the feasibility and effectiveness of psychological interventions for emotional and behavioural problems in the context of genetic conditions is limited. Low-intensity psychological interventions have demonstrated promise in paediatric populations and may be able to address their mental health difficulties. A case series design was used to assess the feasibility of low-intensity interventions for emotional and behavioural difficulties in children and young people with genetic conditions recruited from a mental health drop-in centre at a tertiary hospital. Participants received seven weekly sessions with a trained practitioner. The intervention was based on existing modular treatments and evidence-based self-help materials. Feasibility and treatment satisfaction were assessed, as well as measures of symptoms of anxiety and challenging behaviour, treatment goals and quality of life, at baseline, during treatment and 6-month follow-up. Five participants received treatment for challenging behaviour, one for anxiety, and one for obsessive compulsive disorder. All participants completed treatment. Clinically significant change in the SDQ Total score was found in three participants. All participants demonstrated progress in goals and symptoms of emotional and behavioural difficulties over the course of treatment. Low-intensity psychological interventions for emotional and behavioural difficulties in children and young people with genetic conditions is feasible, acceptable and potentially beneficial. Further research is warranted to examine the effectiveness of the intervention and its use in clinical paediatric settings.
Key learning aims
(1) To gain a basic understanding of low-intensity psychological intervention in children and young people with genetic conditions.
(2) To enhance understanding of the practicalities and acceptability of delivering low-intensity psychological intervention to children and young people with genetic conditions and co-morbid emotional and behavioural difficulties.
(3) To learn about the potential clinical benefits of delivering low-intensity psychological intervention to children and young people with genetic conditions in the context of stepped care.
The Cambrian successions at the Chihuarruita Hill outcrop, Sonora, Mexico, have yielded two successive linguliform brachiopod assemblages that are transitional between Cambrian Stage 4 and the newly recognized global Wuliuan Stage. The lowermost assemblage includes Dictyonina sp., Paterina sp., Eothele sp., Hadrotreta rara? (Cooper), and Linnarssonia arellanoi? (Cooper), coming from the upper part of the Buelna Formation. The younger, recently named El Gavilán Formation contains a more diverse linguliform brachiopod assemblage, including Acrothele concava Cooper, Batenevotreta? mexicana n. sp., Dictyonina minutipuncta Cooper, Eothele sp., Eoobolus sp., Hadrotreta rara? (Cooper), Linnarssonia arellanoi? (Cooper), Micromitra sp., Paterina sp., and Prototreta sp. The El Gavilán Formation contains a diverse trilobite fauna suggesting Delamaran age in terms of the Laurentian regional stratigraphical scheme. The base of the global Wuliuan Stage and Miaolingian Series is defined by the first occurrence of Oryctocephalus indicus; in the absence of the index species, the base should be provisionally placed at the base of the El Gavilán Formation. The Wuliuan age of the brachiopod assemblage recovered from the El Gavilán Formation is supported by the occurrence of Acrothele in the Cambrian biostratigraphical succession of Himalaya, where the genus makes its first appearance in the Kaotaia prachina Zone. In addition, the co-occurrences of Acrothele and Eothele can be taken as an indication of the Wuliuan age of the fauna. A new biogeographic analysis confirms that the Eothele Fauna first appeared at the end of Cambrian Stage 4, as a result of increased faunal migration within the southern tropical latitudes directed from Australasian Gondwana to Laurentia.
OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.
A moderately diverse assemblage of brachiopods from the Latham Shale Lagerstätte (Cambrian Series 2, upper Stage 4) and the upper Cadiz Formation (Miaolingian, Wuliuan), California is described in detail for the first time. The fauna includes both linguliform and rhynchonelliform brachiopods—Hadrotreta primaea (Walcott, 1902), Paterina prospectensis (Walcott, 1884), Dictyonina pannula (White, 1874), and Mickwitzia occidens Walcott, 1908; and Nisusia fulleri Mount, 1981 and Wimanella highlandensis (Walcott, 1886), respectively—together with olenellid trilobites and hyolithids. The fauna differs from other Cambrian Konservat-Lagerstätten (notably Cambrian Series 2 Chengjiang and Guanshan Lagerstätten, eastern Yunnan) in that the brachiopod shell valves in many cases are still preserved with their original mineralization. Moreover, the excellently preserved shale-hosted valves even include cases with exquisite epithelial cell molds, otherwise only seen in acid-etched material from carbonate rocks. The pitted ornamentation in D. pannula closely resembles that described from Ordovician linguliforms. The unusual preservation of N. fulleri provides important clues for ancestral composition of the brachiopod shell. The two articulated rhynchonelliform species probably represent the oldest records of this group from the west Laurentia. The fauna could also represent the earliest onset of the transition from the Cambrian Evolutionary Fauna (CEF) to the Paleozoic Evolutionary Fauna (PEF).
Diverse and abundant fossil taxa have been described in the lower Cambrian Shipai Formation in the Three Gorges area of Hubei Province, South China, but the taxonomy and diversity of the co-occurring brachiopod fauna are still far from clear. Here we describe the brachiopod fauna recovered from the Shipai Formation in the Three Gorges area of South China, including representatives of the subphylum Linguliformea: linguloids (Lingulellotreta ergalievi, Eoobolus malongensis, and Neobolidae gen. indet. sp. indet.), and an acrotretoid (Linnarssonia sapushanensis); and representatives from the subphylum Rhynchonelliformea: the calcareous-shelled Kutorginates (Kutorgina sinensis, Kutorgina sp., and Nisusia liantuoensis). This brachiopod assemblage and the first occurrence of Linnarssonia sapushanensis shell beds permit correlation of the Shipai Formation in the Three Gorges area of Hubei Province with the Stage 4 Wulongqing Formation in the Wuding area of eastern Yunnan. This correlation is further strengthened by the first appearance datum (FAD) of the rhynchonelliform brachiopod Nisusia in the upper silty mudstone of both the Shipai and Wulongqing formations. The new well-preserved material, derived from siliciclastic rocks, also gives critical new insights into the fine shell structure of L. sapushanensis. Microstructural studies on micromorphic acrotretoids (like Linnarssonia) have previously been restricted to fossils that were acid-etched from limestones. This is the first study to carry out detailed comparative ultrastructural studies on acrotretoid shells preserved in siliciclastic rocks. This work reveals a hollow tube and solid column microstructure in the acrotretoid shells from the Shipai Formation, which is likely to be equivalent of traditional column and central canal observed in shells dissolved from limestones.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
Brachiopod shell accumulations are abundant and diverse in the lower Cambrian strata of Yunnan Province, South China, but most commonly they are composed of linguloid and acrotheloid brachiopods. Here, we describe the first record of shell beds with high-density accumulations of microscopic acrotretoid brachiopods (usually <2 mm in width) in the muddy deposits of the Wulongqing Formation (Guanshan Biota, Cambrian Stage 4) in the Wuding area of Yunnan Province. The acrotretoid shell beds from the Wulongqing Formation vary from thin mm-thick pavements to more well-developed beds, several centimeters thick. The occurrence of remarkably rich acrotretoid shell beds indicates that microscopic lingulates began to exert an important role in hardening and paving the soft-substrate seafloor during the early Cambrian evolution of Phanerozoic “mixgrounds.” The new Guanshan material is referred to a new species, Linnarssonia sapushanensis n. sp., which differs from other species of Linnarssonia mainly in having a well-developed internal pedicle tube, as well as a relatively longer dorsal median septum. The occurrence of Linnarssonia sapushanensis n. sp. in the Wulongqing Formation in eastern Yunnan extend the oldest record of the genus on the Yangtze Platform of South China back to at least Cambrian Stage 4.
Attention-deficit/hyperactivity disorder (ADHD) is associated with a higher risk of burn injury than in the normal population. Nevertheless, the influence of methylphenidate (MPH) on the risk of burn injury remains unclear. This retrospective cohort study analysed the effect of MPH on the risk of burn injury in children with ADHD.
Data were from Taiwan's National Health Insurance Research Database (NHIRD). The sample comprised individuals younger than 18 years with a diagnosis of ADHD (n = 90 634) in Taiwan's NHIRD between January 1996 and December 2013. We examined the cumulative effect of MPH on burn injury risk using Cox proportional hazards models. We conducted a sensitivity analysis for immortal time bias using a time-dependent Cox model and within-patient comparisons using the self-controlled case series model.
Children with ADHD taking MPH had a reduced risk of burn injury, with a cumulative duration of treatment dose-related effect, compared with those not taking MPH. Compared with children with ADHD not taking MPH, the adjusted hazard ratio for burn injury was 0.70 in children taking MPH for <90 days (95% confidence interval (CI) 0.64–0.77) and 0.43 in children taking MPH for ≥90 days (95% CI 0.40–0.47), with a 50.8% preventable fraction. The negative association of MPH was replicated in age-stratified analysis using time-dependent Cox regression and self-controlled case series models.
This study showed that MPH treatment was associated with a lower risk of burn injury in a cumulative duration of treatment dose-related effect manner.
Little is known about methylphenidate (MPH) use and mortality outcomes.
To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis.
This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4–17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan.
The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67–0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01–1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70–0.98).
MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.
Successful management of focal spasticity requires access to botulinum toxin type A (BoNT-A) injections, physiotherapy, occupational therapy, and orthoses/bracing. To assess the quality of focal spasticity care across Canada, we sent a survey consisting of 22 questions to physiatrists involved in the management of outpatient spasticity. Thirty-four physiatrists from all 10 provinces responded to the survey. Wait time for BoNT-A treatment averaged 12.7 weeks from time of referral across Canada. More than 75% of patients faced barriers to obtaining physical therapy and orthoses. Access to best quality care for spasticity patients across Canada varies widely.
The genitourinary (GU) system includes the kidneys, ureters, bladder, urethra, penis, scrotum, and female genitalia. Of the 27.7 million patients per year presenting to emergency departments (ED) for traumatic injury, about 10% of these traumas primarily involve the GU system, and another 10–15% of patients with abdominal trauma will have GU injuries as well.1 GU trauma patients are predominantly young (80% less than the age of 45 years) and male (85% of all patients).2 Delays or missed diagnosis of GU trauma can result in increased morbidity and mortality due to preventable complications with long term consequences.3
A simple and facile stereolithography 3D printing technique was utilized to fabricate piezoelectric photopolymer-based polyvinylidene fluoride (PVDF) blends. Different process variables, such as solvent (N,N-dimethylformamide, DMF) to PVDF ratio and PVDF solution to photopolymer resin (PR) ratio, were engineered to enhance the dispersion of the PVDF into the PR so as to achieve the maximum piezoelectric coupling coefficient. Our results demonstrate that a ratio of 1:10 (PVDF:DMF) and 2 wt%-PVDF/PR was optimal for the best dissolution of the PVDF, 3D printability, and piezoelectric properties. Under these conditions, the blend generated ±0.121 nA under 80 N dynamic loading excitation. We believe that the findings of this work would promote many further studies on the mass production of flexible piezoelectric polymer blends with higher quality finished surface and design flexibility.
The US, as well as many countries, are being beseeched by more natural and man-made events; both small (e.g., shootings) and geographically vast (e.g., floods). Due to a myriad of issues, traditional first responders i.e., EMS, fire department, and police cannot be expected to be the only trained lifesavers on the scene. In the US (as in many countries), it is imperative to begin the discussion to better understand the role of the “injured” and “immediate” responders and how they interact with the “first” responders.
To open a discussion amongst disaster experts about the merits of training and subsequent promotion of a curriculum for “immediate” responders.
After recent evaluations of events, it is postulated that there are three categories of responders: the injured, the immediate, and the first (EMS, fire department, police). The premise upon which disaster risk reduction and building community resilience are achieved begin with strengthening, empowering, and equipping local populations with the appropriate tools. This would involve education, skills, and training. With the average general public trained, and if they are one of the first two categories, then the community would not only be better able to assist themselves, but also be able to integrate into the recovery process much more quickly and fully. By doing this, they will be empowered to take care of themselves, neighbors, and community, which in turn increases local resilience.
Hurricane Harvey made landfall in southeast Texas in August 2017, causing unprecedented flooding throughout the Texas coastal region. Residents of affected regions were forced to evacuate to nearby unaffected areas, including Dallas, TX, where a large shelter operation was opened for 23 days to care for those evacuees. Retrospective evaluation of pharmaceutical prescribing patterns for the evacuees who self-presented to the Megashelter Medical Clinic (MMC) established in the shelter contributes to developing evidence-based planning strategies for healthcare delivery in the post-disaster setting.
To describe the pharmacy needs of a displaced population following a large-scale evacuation after a hurricane
De-identified prescription records written and filled at a shelter pharmacy were reviewed, looking at both cost and category of medications dispensed over time.
Approximately 41% of evacuees with a total of 2,654 visits utilized the MMC clinic, resulting in 1,590 prescriptions filled with an associated cost of $78,039. The most commonly prescribed drug categories were cardiovascular (21.2%), neuropsychotropic (15.6%), infectious disease (12.5%), and endocrine (9.6%). While the most commonly dispensed were antihypertensives, diabetes treatment-related prescriptions, antibacterials, antidepressants, and NSAIDs, the costliest individual prescriptions were antiretrovirals and antipsychotics.
Prescribing patterns for the MMC differed from normal prescribing patterns of a general population. Of the prescriptions dispensed at the MMC, pharmaceutical prescription patterns suggest the immediate needs of evacuees differ from later needs. There is a greater need for chronic disease management in the early phase of shelter operations, and an increasing need for neuropsychotropic and infectious disease prescriptions over time. Understanding overall patterns of drug utilization over the duration of the shelter provides valuable insight on post-disaster medical resource utilization in evacuee populations.
In 2013, a multinational collaboration met to improve the global and nation-specific preparedness and response in managing casualties from nuclear and radiological disasters. From this meeting, a survey was developed and distributed in both Japanese and English. The results published four years later illustrate a lack of understanding about radiation and risks to the health care provider.
To dispel myths and increase understanding regarding trauma treatment and healthcare risks for healthcare providers during a radiologic event.
IRB approved survey and literature review
A total of 418 surveys were analyzed. Although 44% of participants acknowledged that they had taken at least one radiological training course, the majority of the respondents were still not comfortable with radiological emergencies.
Despite the plethora of both online and in-person radiological training availability, healthcare providers are not comfortable with the topic. Based on information from the survey, it is important to dispel myths and educate healthcare providers so that they have reasonable expectations regarding risks and to ensure that they are comfortable coming to work. By doing this, there will be an adequate healthcare presence to help take care of patients who are not only in need of immediate trauma and radiologic exposure care but also with non-affected patients coming for emergent and scheduled health care needs.
After Hurricane Harvey and the flooding that ensued, 3,829 displaced persons were transported from their homes and sheltered in the Dallas Convention Center. This large general population sheltering operation was medically supported by the onsite Mega-Shelter Medical Clinic (MMC). In an altered standard of care environment, a number of multi-disciplinary medical services were provided including emergent management, acute pediatric and adult care, psychiatric/behavioral services, onsite pharmaceutical, and durable medical equipment distribution, epidemiologic surveillance, and select laboratory services.
To describe how onsite medical care in the adapted environment of a large population shelter can provide comparable services and limit the direct impact on the local medical community.
A retrospective chart review of medical records was generated for all clinical encounters at the MMC. Data were sorted by daily census, disease surveillance, medical decision making, treatment, and transport destinations.
40.7% of registered evacuees utilized the MMC accounting for a total of 2,654 clinic visits by 1,560 unique patients representing all age groups. During the sustained MMC operations, 8% of patients required emergency transport and 500 additional patient transports were arranged for clinic appointments. No deaths occurred and no iatrogenic morbidity was reported.
Medical care was provided for a large number of evacuees which mitigated the potential impact on the local medical infrastructure. The provision of medical services in a large population shelter may necessitate adaptation to the standard of care. However, despite the nontraditional clinical setting, care delivery was not compromised.
Ultrasound applications are widespread, and their utility in resource-limited environments are numerous. In disasters, the use of ultrasound can help reallocate resources by guiding decisions on management and transportation priorities. These interventions can occur on-scene, at triage collection points, during transport, and at the receiving medical facility. Literature related to this specific topic is limited. However, literature regarding prehospital use of ultrasound, ultrasound in combat situations, and some articles specific to disaster medicine allude to the potential growth of ultrasound utilization in disaster response.
To evaluate the utility of point-of-care ultrasound in a disaster response based on studies involving ultrasonography in resource-limited environments.
A narrative review of MEDLINE, MEDLINE InProcess, EPub, and Embase found 20 articles for inclusion.
Experiences from past disasters, prehospital care, and combat experiences have demonstrated the value of ultrasound both as a diagnostic and interventional modality.
Current literature supports the use of ultrasound in disaster response as a real-time, portable, safe, reliable, repeatable, easy-to-use, and accurate tool. While both false positives and false negatives were reported in prehospital studies, these values correlate to accepted false positive and negative rates of standard in-hospital point-of-care ultrasound exams. Studies involving austere environments demonstrate the ability to apply ultrasound in extreme conditions and to obtain high-quality images with only modest training and real-time remote guidance. The potential for point-of-care ultrasound in triage and management of mass casualty incidents is there. However, as these studies are heterogeneous and observational in nature, further research is needed as to how to integrate ultrasound into the response and recovery phases.
The Dallas Convention Center received over 3800 evacuees because of the unprecedented flooding caused by Hurricane Harvey. A multidisciplinary medical clinic was established onsite to address evacuee needs for medical evaluations, emergency care, chronic disease management, pharmaceuticals, durable medical equipment, and local health services integration. To operate efficiently, the Dallas Mega-Shelter Emergency Operations Center (EOC) worked with the Mega-Shelter Medical Clinic (MMC) under a fluid incident command (IC) structure that was National Incident Management System (NIMS) compliant. Iterations of MMC IC demonstrated maturations in organizational structure while supporting MMC operations that varied from rigid NIMS doctrine.
To explore the use of a fluid IC structure at a large evacuation medical shelter after Hurricane Harvey.
We observed evolutions of IC organizational charts and operational impacts.
Modifications through just-in-time iterations of the IC organizational chart were posted and reviewed with MMC IC and EOC sector chiefs. Changes in the organizational chart were noted to improve identification of logistical needs, supply delivery, coordinate with other agencies, and to make decisions for resource typing and personnel utilization. Adaptations also improved communication, which led to timely situational awareness and reporting accuracy.
MMC medical services were improved by allowing modifications and adaptations to NIMS compliant MMC IC organizational roles and duty assignments. The fluidity of IC structure with ability for just-in-time modifications directly impacted the provision of disaster medical services. Unique situational awareness, coordination of care pathways within the local innate health infrastructure, compliance with health service regulations, and personnel resource typing all contributed to and benefitted from these IC modifications. MMC and EOC IC collaboration facilitated effective communication and maintained an appropriate span of control and efficient activity reporting.