Anesthetic management of pediatric patients with rare diseases presents substantial perioperative challenges and risks. This study evaluated the clinical competency and specific educational needs of anesthesia practitioners in China regarding the perioperative management of this vulnerable patient population. A cross-sectional survey was conducted from May 2024 and March 2025, involving 2127 anesthesia practitioners across China. Data were collected via a validated anonymous questionnaire and analyzed through descriptive statistics and chi-square tests. Among the 2,127 participants, 93.5% were anesthesiologists and 6.5% were nurse anesthetists. Of these, 43.2% (919/2127) reported previous experience in administering anesthesia to children with rare diseases. Despite this exposure, self-assessed competency levels were notably insufficient. Only 9.0% (191/2127) of respondents reported comprehensive knowledge of pediatric rare diseases, and 15.0% (318/2127) expressed adequate confidence in perioperative management protocols. Objective assessment of specific knowledge domains revealed considerable deficiencies: 14.9% (317/2127) of respondents correctly identified contraindications in muscular dystrophy, 6.6% (141/2127) demonstrated adequate understanding of difficult airway indicators, and merely 3.9% (82/2127) accurately recognized depolarizing agent risks. Comparative analysis between self-rated high-familiarity and low-familiarity groups revealed that direct clinical exposure was significantly associated with practitioners' understanding of pediatric rare diseases. Regarding the development of future anesthesia support systems for pediatric rare diseases, practitioners identified two primary requirements: comprehensive diagnostic information (58.6%, 1246/2127) and detailed anesthesia contraindications (57.0%, 1212/2127). Additionally, 50.1% (1065/2127) of respondents emphasized the importance of real-time knowledge base updates to ensure access to current clinical guidelines and safety protocols. This study highlights substantial knowledge gaps and insufficient confidence among anesthesia practitioners in the perioperative management of children with rare diseases, underscoring an urgent need for enhanced training and robust support systems in this specialized area.
Rare diseases affect small, dispersed populations and are often studied through multisite designs where equity-relevant demographic data are essential for inclusive recruitment and accurate interpretation. This study examined how sociodemographic variables are collected and reported in rare disease research and evaluated their alignment with the PROGRESS-Plus framework, which outlines Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, social capital, and additional "Plus" factors such as age and disability status. A systematic review of peer-reviewed articles was conducted alongside an environmental scan of demographic instruments from governmental, health-system, academic, and rare disease organizations. Screening and extraction coded variables as reported, indirectly derivable, or not reported and compared them with established standards. Of 647 records identified, 37 met inclusion criteria. Reporting was dominated by age and sex, while most other equity-relevant variables including gender identity, sexual orientation, race/ethnicity, distinctions-based Indigenous identity, socioeconomic position, language, migration, disability/function, religion, occupation, and social capital, were inconsistently captured. Environmental scan instruments were more comprehensive, revealing a capture-to-reporting gap. Demographic reporting in rare disease research is heterogeneous and insufficient for equity-focused analyses. A concise, standards-aligned sociodemographic dataset is needed to improve transparency, comparability, and detection of inequities across rare disease populations.
Intrahepatic Cholestasis of Pregnancy (ICP) is the most common pregnancy-related liver disorder. ABCB4 heterozygous variants are implicated in ICP, but interpretation of rare variants remains challenging, leading to many variants of uncertain significance. This study compares predictions from multiple in silico tools on nine heterozygous missense variants identified in women with ICP. Using the Genomics England Research Environment, 253 women with ICP and whole-genome sequencing data were analysed. Variants with minor allele frequency < 0.05 were filtered, and nine rare missense variants were assessed using SIFT, PolyPhen, CADD, Vasor (ABCB4-specific), and AlphaMissense. Only 44% (4/9) of variants had consistent classification across all tools. Published functional studies often conflicted with predictions. For example, T175A showed no detectable effect in HepG2/HEK293 cells but was classified as likely pathogenic by Vasor and benign by AlphaMissense. Similarly, N510S impacted protein stability functionally and was deemed likely pathogenic by Vasor but benign by AlphaMissense. In silico tools show conflicting predictions for ABCB4 rare variants, highlighting the difficulty of classification without functional or segregation data as well as the heavy reliance on computational predictions.
We report a case of fungal endophthalmitis caused by the rare fungus Fusicolla species in a 32-year-old female presenting with redness and pain in the right eye. The case illustrates the challenges in diagnosing infectious uveitis and highlights the importance of molecular diagnostics in identifying rare fungal pathogens. This is the first documented case of ocular involvement associated with this species.
Constrictive pericarditis is an uncommon but serious condition typically caused by idiopathic inflammation, prior cardiac surgery, or radiation. Malignancy is a rare etiology. A 62-year-old man with a history of tongue squamous cell carcinoma on long-term pembrolizumab presented with dyspnea, orthopnea, leg swelling, and ascites. Multimodal imaging revealed nodular pericardial thickening and constrictive physiology. Given lack of improvement on anti-inflammatory therapy and need to differentiate between metastatic disease versus immunotherapy-related inflammation, surgical pericardiectomy with biopsy was pursued. Histopathology confirmed poorly differentiated metastatic carcinoma invading the myocardium. Owing to poor prognosis, care was transitioned to hospice. Malignant pericardial involvement with constriction is a rare but important diagnostic consideration, particularly when atypical features or poor response to therapy are present. Immune checkpoint inhibitor-associated pericarditis can mimic malignant involvement, complicating noninvasive diagnosis. When advanced imaging cannot definitively distinguish between immune-mediated and malignant pericarditis, tissue diagnosis is necessary.
Fibrodysplasia ossificans progressiva (FOP) is a rare multisystem disorder with the triad of congenital hallux valgus, flare-ups and progressive heterotopic ossification. The flare-ups (episodes of painful soft-tissue swelling) start in early childhood, and progress to ossification with cumulative functional disability. We describe the cohort of FOP from a single tertiary center in Türkiye and highlight the phenotypic variabilities and diagnostic pitfalls. The subjects included 10 affected individuals (7 females and 3 males, aged 10 days to 20 years), whose diagnosis was confirmed with molecular tests, including full ACVR1 sequencing, targeted hotspot analysis, a gene panel for skeletal disorders, and whole-exome sequencing. Clinical and imaging data were retrospectively reviewed. The common pathogenic variant of FOP, c.617G > A, p.(Arg206His) of ACVR1, was found in 9 patients, while a rare variant, c.983G > A, p.(Gly328Glu) in one. All patients with the common variant exhibited the classical triad of FOP. Other morbidities included limited cervical mobility in 8, temporomandibular joint involvement in 4, scoliosis in 6, scalp nodules in 6, and brain anomalies in 2. Scalp nodules could be a transient finding with spontaneous regression and were an early manifestation in 2. One patient showed a distinctive brain malformation of FOP (pontine dysmorphism with fusion of the facial colliculi and dorsal bulging into the fourth ventricle). Four patients underwent biopsy prior to referral to our institution. One was coincidentally associated with Ewing sarcoma. The infant with the rare variant presented with limb reduction defects and brain malformation and had not yet developed flare-ups or heterotopic ossification. This single-center cohort from Türkiye confirms the key clinical features of FOP associated with both common and rare ACVR1 variants and expands the radiological findings with notable features such as pontine malformation. It also highlights scalp nodules as a potential early diagnostic clue, emphasizing the importance of early clinical recognition and timely molecular confirmation, while providing insights that may inform future therapeutic approaches. • Fibrodysplasia ossificans progressiva (FOP) is caused by activating variants in ACVR1, most commonly c.617GA, p.(Arg206His), and is characterized by congenital hallux valgus, flare-ups, and progressive heterotopic ossification • Early diagnosis is challenging, and misdiagnosis may lead to harmful invasive procedures such as biopsies. • This single-center cohort confirms the key features of FOP, expands the radiological spectrum (including pontine malformation), and identifies scalp nodules as an early diagnostic clue.
Rare bi-allelic variation is a major contributor to human disease risk, yet its effects are difficult to study at scale in population cohorts owing to the limited number of individuals with putatively deleterious bi-allelic genotypes and the challenges of accurately phasing low-frequency variants. Here, we present recessive, gene-based analyses of rare and low-frequency variants in up to 948,690 exome- or whole-genome-sequenced individuals across six biobanks with linked electronic health records. Through statistical phasing, we inferred putatively damaging compound-heterozygous genotypes, increasing the number of bi-allelic damaging genotypes by 19%. Restricting to predicted loss-of-function (pLoF) variants, we identified 5,563 genes harboring bi-allelic genotypes, a 19.8% increase in putative knockouts. We then considered all low-frequency variants (minor allele frequency [MAF] <5%) and performed gene-based recessive association testing using putatively damaging bi-allelic genotypes, identifying 58 significant associations (false discovery rate [FDR] ≤1% or prec≤7.5 × 10-7) after meta-analysis and Cauchy combination of nonsynonymous annotations. Comparing recessive and additive models, we found 17 instances where recessive effects were more pronounced, including several previously unreported associations, such as HBB with heart failure (prec = 2.6 × 10-14; padd = 0.98), LECT2 with height (prec = 3.7 × 10-14; padd = 4.1 × 10-10), and ENSG00000267561 with height (prec = 2.9 × 10-9; padd = 0.37). This study demonstrates the potential of federated approaches to study the effects of rare bi-allelic variation.
Adult intussusception is an uncommon clinical condition, representing a rare cause of intestinal obstruction. Unlike the pediatric form, most adult cases are secondary to an identifiable pathological lead point. Idiopathic intussusception, particularly involving the small bowel, is exceedingly rare and poses diagnostic and therapeutic challenges. We report the case of a 42-year-old woman with no prior abdominal surgery who presented with a three-day history of abdominal pain, vomiting, and cessation of stool and flatus. Physical examination revealed mild abdominal distension without peritoneal signs. Abdominal computed tomography demonstrated a jejuno-jejunal intussusception with the classic "target" configuration and no detectable underlying lesion. The patient underwent an exploratory laparotomy, which confirmed a jejuno-jejunal intussusception without any pathological lead point. Gentle manual reduction was performed, and no resection was required. The postoperative course was uneventful, and the patient was discharged on postoperative day three. Adult idiopathic intussusception is rare, accounting for a small minority of adult intussusception cases. CT imaging is the cornerstone of diagnosis, enabling visualization of characteristic features and assessment of complications. Surgical exploration remains the standard of care, with management tailored to intraoperative findings. Reduction without resection is justified when the bowel is viable, and no underlying pathology is evident. Idiopathic small bowel intussusception in adults is a diagnostic rarity that should be considered in cases of unexplained bowel obstruction. Early diagnosis and tailored surgical management can ensure favorable outcomes while avoiding unnecessary bowel resection.
Metaphyseal anadysplasia 1, which includes Spondyloepimetaphyseal dysplasia Missouri type, is a rare autosomal dominant skeletal dysplasia characterized by short stature, mild limb deformities, and transient metaphyseal irregularities that typically resolve with age. The condition is caused by heterozygous missense variants in the MMP13 gene, encoding matrix metalloproteinase 13, a key enzyme in endochondral ossification and extracellular matrix remodeling. Pathogenic variants in MMP13 are exceedingly rare, with only a few families reported. We report two siblings, aged 3 and 1 years, in Sweden, presenting with clinical and radiological features consistent with Metaphyseal anadysplasia 1. Their father, of Syrian origin, exhibited short stature and mild femoral bowing. Genetic analysis revealed a novel heterozygous missense variant c.217T>C, p.(Ser73Pro) in MMP13, inherited from the affected father, and located within the same MMP13 domain as previously reported patients. The family pedigree demonstrates multiple affected individuals with short stature and bowed femurs, consistent with autosomal dominant inheritance. Radiographic imaging of father confirmed persistent but mild skeletal abnormalities. This report expands the genotypic spectrum of Metaphyseal anadysplasia 1 and suggests a putative mutational hotspot in exon 2. It further emphasizes the importance of thorough clinical, radiological, and genetic evaluation in families with short stature and metaphyseal irregularities and a clinical long-term follow-up is proposed with regular radiographic monitoring.
Mesomelic dysplasia Savarirayan-type or ID4-related (MDST) is an ultra-rare skeletal dysplasia caused by chromosome 6p22.3 microdeletions. To date, only four cases have been reported. Here, we report a fifth case, a 9 year-old female with severe mesomelic lower limb shortening and characteristic radiographic findings, highly resembling those identified in previous MDST patients. No deletion was identified by array. However, whole genome sequencing (WGS) revealed a de novo inversion at 6p22.3. As hypothesized for deletions detected in this disorder we predict that the structural variant disrupts several topologically associated domains (TADs) in the region and is likely to place ID4 in closer proximity to more telomerically located limb enhancers, which could result in enhancer adoption and potentially lead to ID4 limb misexpression. Thus, this case broadens the genetic spectrum in MDST and provides further support to the role of ID4 dysregulation as the main underlying molecular mechanism of this ultra-rare skeletal disorder.
Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors composed of cells exhibiting an epithelioid morphology. These cells typically arrange around small blood vessels (perivascular spaces) and display dual differentiation characteristics of smooth muscle cells and melanocytes. Diagnosis is challenging due to the absence of specific symptoms or tumor markers. This case features a young male patient with a large hepatic PEComa, whose imaging findings resemble those of hepatocellular carcinoma. We have detailed the entire process from diagnosis to treatment to aid in differential diagnosis and surgical planning. A 31-year-old male patient with no prior medical history underwent a routine health examination 20 days prior to presentation. Although the patient was asymptomatic, ultrasound revealed an incidental hepatic lesion measuring 58 × 50 × 45 mm (maximum diameter 58 mm, or 5.8 cm). The screening center suspected a hemangioma. Subsequently, he presented to our hospital. Comprehensive imaging studies, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), revealed a 58 mm-diameter space-occupying lesion in segments V and VIII of the right hepatic lobe. Imaging findings initially raised suspicion for hepatocellular carcinoma. To minimize surgical trauma and preserve liver function, our team discussed surgical approaches and ultimately decided on a laparoscopic partial hepatectomy. During the procedure, we obtained a specimen for pathological examination. The final histopathological analysis confirmed the diagnosis of a PEComa with undetermined malignant potential. The patient recovered smoothly postoperatively and was successfully discharged. PEComa has an insidious onset and is rare. Early diagnosis is often challenging, and imaging studies typically show no highly specific findings. Clinical diagnosis frequently relies on biopsy. In terms of treatment, radical resection (R0 resection, i.e., negative margins) represents the definitive therapeutic approach.
Accurate detection of KRAS codon mutations is essential for precision oncology in colorectal cancer (CRC), yet conventional liquid biopsy methods often lack sufficient sensitivity for rare ctDNA variants, particularly in early diseases. We developed a three-dimensional (3D) plasmonic KRAS microarray integrating blocked recombinase polymerase amplification with plasmon-enhanced fluorescence. Quencher-modified blocking probes suppress wild-type DNA while selectively enabling mutant signal amplification. A single primer-probe set per codon allows comprehensive detection of all substitutions within KRAS codons 12/13, 61, and 146. The platform achieved detection down to 1 fM by direct hybridization and 100 zM after blocked amplification, exceeding conventional PCR and next-generation sequencing sensitivity. Codon-level specificity was validated in CRC cell lines, with distinct signals for each mutation. Clinical analysis of 58 patients showed 100% concordance between tissue, plasma, and urine in mutation-positive malignant cases when sufficient input was available, indicating accurate reflection of tumor profiles. In benign tumors, detection was rare despite tissue mutations, likely due to limited ctDNA release.This plasmonic microarray enables ultra-sensitive, specific, and non-invasive detection, supporting early diagnosis, minimal residual disease monitoring, and longitudinal CRC management.
Phakomatoses, also known as neurocutaneous syndromes are rare disorders characterized by multisystem involvement with variable neurological manifestations in children, including intracranial vascular malformations. Cavernous malformations may present with acute haemorrhage and stroke-like symptoms. Diagnostic difficulty arises when radiologic findings suggest a benign lesion, yet histopathology reveals discordant malignant pathology. An 8-year-old female presented with sudden-onset left hemiparesis and recurrent seizures. Physical examination revealed multiple cutaneous naevi, raising suspicion of a syndromic association. Brain magnetic resonance imaging demonstrated a well-circumscribed right parietal intra-axial lesion with a "popcorn" appearance and hypointense susceptibility blooming, highly suggestive of a cavernous malformation. Cranial computed tomography scan subsequently showed an associated large intracerebral haematoma. The patient underwent right parietal craniotomy with haematoma evacuation and excision of the lesion. The immediate postoperative course was initially satisfactory with neurological improvement. Histopathological examination of the excised specimen, however, revealed a malignant neoplasm, establishing a significant radiologic-histologic discordance which fundamentally altered the diagnostic interpretation. The patient had a relapse of symptoms two months after surgery, with repeat neuroimaging showing multicentric tumour recurrence, necessitating referral for adjuvant neuro-oncologic management. This case illustrates a rare diagnostic pitfall and challenge in paediatric neurosurgery, where a malignant intracranial tumour mimicked a cavernous malformation in the context of cutaneous stigmata. The report emphasizes the limitations of neuroimaging alone and underscores the importance of careful clinicoradiologic correlation, histopathological confirmation, and multidisciplinary evaluation when managing presumed vascular lesions in children, particularly in resource-limited settings.
BACKGROUND Kennedy disease, also known as spinal and bulbar muscular atrophy (SBMA), is a rare and incurable X-linked neuromuscular disorder mainly affecting men aged 30 to 60 years. Polymyositis can present similarly, but can be excluded by measuring muscle enzymes, performing muscle imaging, and electromyography. This report describes the case of a 52-year-old man with a 10-year history of progressive limb weakness due to Kennedy disease, established by genetic testing. CASE REPORT A 52-year-old man presented with a 10-year history of gradually progressive proximal limb weakness and persistently elevated creatine kinase levels ranging from 808-2300 U/L (normal 39-308 U/L). One year prior to this admission, the limb weakness had worsened, but initial electromyography, neuroimaging, and muscle biopsy showed no specific abnormalities. Despite a trial of immunosuppressive therapy due to suspected polymyositis, there was no clinical improvement. Neurological examination later revealed gynecomastia, proximal muscle atrophy, and bilateral tongue atrophy with tremor. Electromyography showed chronic neurogenic changes and reduced sensory nerve action potentials. Repeat expansion analysis identified a hemizygous pathogenic CAG repeat expansion in exon 1 of the androgen receptor gene using a short-read next-generation sequencing-based repeat detection algorithm (ExpansionHunter), with an estimated repeat number of 51 (range 50-53). At 6-month follow-up, the patient demonstrated mild progression of motor symptoms but remained functionally stable. CONCLUSIONS This report presents a rare case of Kennedy disease, initially diagnosed as polymyositis, and highlights the importance of follow-up with genetic testing when neurological and electromyography investigations are not typical for polymyositis. Early identification of Kennedy disease helps avoid unnecessary immunosuppressive treatments.
Cornelia de Lange syndrome is a rare congenital disorder marked by considerable clinical variability, including intellectual disability, growth retardation, distinctive facial features, limb abnormalities, and multisystem involvement. The condition is primarily linked to mutations in genes encoding components of the cohesin complex that are essential for chromosomal stability and gene regulation. We report a case of a mild type of Cornelia de Lange syndrome caused by a de novo mutation in an Iranian family. We investigated a 19-year-old Iranian male individual presenting with developmental delay, borderline intellectual disability, dysmorphic facial features, and multisystem involvement. Whole-exome sequencing was performed to identify causative variants. A de novo heterozygous variant affecting the start codon of NIPBL (NM_133433.4:c.2T>A; NP_597677.2:p.Met1Lys) was identified. This variant was absent from population databases and predicted to disrupt normal translation initiation. Sanger sequencing and co-segregation analysis confirmed the genetic findings. In silico tools and population databases were utilized to assess variant pathogenicity. Clinically, the patient exhibited classical Cornelia de Lange syndrome features with relatively mild intellectual impairment compared with typical loss-of-function cases, consistent with the hypothesis of potential use of alternative start sites. This case shows a known NIPBL start-loss variant's correlation with a relatively mild clinical presentation and offers more genotype-phenotype evidence for it. This finding suggests a possible role for downstream translation initiation as a modifier of disease severity, although further functional validation is required. Comprehensive genetic analysis remains essential for accurate diagnosis, prognosis, and counseling in patients with Cornelia de Lange syndrome.
Ambulatory anesthesia has grown rapidly, encompassing more complex procedures and higher-risk patients. Analysis of closed claims reveals that while major complications and mortality remain rare, moderate injuries such as dental trauma, nerve damage, and communication-related issues are frequent and remained largely stable in frequency over the past decade. Patient comorbidities-including obesity, obstructive sleep apnea, and diabetes-significantly increase perioperative risks. Improving patient safety in this setting depends on careful risk assessment, multimodal analgesia, opioid-sparing techniques, and transitional care strategies. Future efforts must prioritize evidence-based protocols, national standards, and innovative monitoring to ensure safe, high-quality outcomes.
Central nervous system (CNS) metastases from Wilms tumor (WT) are exceedingly rare. Intracerebral hemorrhage secondary to metastatic WT is even less common, and the management of such cases is further complicated when patients are receiving a direct oral anticoagulant (DOAC) like Rivaroxaban, for which pediatric reversal guidelines are lacking. We report on the case of a 5-year-old boy with relapsed stage IV Wilms tumor who presented with rapidly progressive neurological deterioration caused by brain metastases with extensive intraparenchymal and intraventricular hemorrhage while receiving Rivaroxaban due to prior thrombosis. An emergent craniotomy and tumor resection was safely performed after emergent reversal of anticoagulation with Rivaroxaban using Andexanet alfa, administered in this pediatric patient with off-label consent in the setting of a life-threatening intracranial hemorrhage requiring emergent neurosurgical intervention. No excessive intraoperative bleeding was noted. Treatment for relapsed WT according to the SIOP-UMBRELLA-Protocol was initiated. Three weeks after Andexanet alfa treatment, a thrombotic event in the left iliac veins occurred, requiring anticoagulation with unfractionated heparin. This case highlights the therapeutic challenges of managing intracranial hemorrhage in a pediatric patient requiring emergent neurosurgical debulking in the setting of Rivaroxaban anticoagulation. To our knowledge, this is the second case reporting on Rivaroxaban reversal through Andexanet alfa in children. Early multidisciplinary intervention, meticulous neurosurgical management and continuation of oncologic therapy can lead to favorable outcomes even in such complex presentations.
Pediatric sepsis is a leading cause of global morbidity and mortality, yet high-resolution, granular subnational assessments remain scarce. Chile and Mexico are the only countries in Latin America that possess robust vital registration systems and open access databases with marginal levels of missing cases. This offers a unique opportunity to quantify the subnational burden of pediatric sepsis, identify healthcare system constrictions, and guide targeted public health interventions. This retrospective longitudinal study analyzed official hospital discharge and non-fetal death records of pediatrics (< 10 years old) from Chile and Mexico between 2014 and 2024. Age-standardized incidence (ASIR) and mortality (ASMR) rates, standardized ratios, and the mortality-to-incidence ratio (MIR), were calculated to assess mortality relative to subnational hospital output. A novel dynamic risk stratification matrix was developed to classify ICD-10 sepsis-related causes into four risk/severity quadrants based on year-specific ASIR and MIR indicators. A total of 656,234 discharges and 2,035 deaths in Chile, and 964,452 discharges and 77,252 deaths in Mexico were analyzed. Subnational trends were highly heterogeneous. Chile exhibited a predominantly low pediatric MIR (median < 1%) with isolated hotspots with significant structural deviations to the North. High-severity sepsis causes in Chile were relatively rare. Conversely, Mexico displayed an alarmingly high MIR (median 7.2%), with systemic persistency in States such as Chiapas and Nuevo León. Strikingly, high-severity causes in Mexico (e.g., unspecified septicaemia, bacterial meningitis) were highly frequent, accounting for 88-97% of pediatric sepsis deaths. Furthermore, systemic instances of code-specific MIR > 1.0 in Mexico suggest significant health system fragmentation and decoupling of hospital discharge from vital statistic registries. Pediatric sepsis in Latin America encompasses distinct realities, ranging from localized critical care gaps to high-lethality persistency. One-size-fits-all national policies may be inadequate. These findings advocate for precision public health, urging the deployment of decentralized, data-driven interventions and specialized resource allocation based on high-risk subnational hotspot identification.
Many neurodevelopmental disorders are associated with significantly impaired communication that impacts the individuals and their families' daily activities. The objective of this study is to evaluate the effectiveness of multiple scoring algorithms for the Observer-Reported Communication Ability (ORCA) measure in assessing communication abilities in individuals living with Angelman syndrome and other neurodevelopmental disorders with severe language impairments. This secondary data analysis used caregiver-reported data from the ORCA validation study (n = 249) and the Angelman Syndrome Natural History Study (n = 165). Performance of the scoring algorithms was evaluated based on item response theory information functions, the percentage of scores at the floor and ceiling, and the Pearson correlation of scores between the ORCA measure and the Communication and Symbolic Behaviors Scale (CSBS). The ORCA measure's scoring algorithms, which include both emerging and mastery levels of communication behaviors ("Emerging & Mastery"), captured lower levels of ability with greater precision than the algorithm that only assesses mastery levels of behaviors. For overall communication ability in the validation study, the Emerging & Mastery algorithm had floor and ceiling effects of 0.4% each, while the Mastery algorithm had effects of 1.2% and 0.0%, respectively. Both ORCA scoring algorithms for overall communication had strong correlations with the CSBS (r = 0.85 and 0.83, respectively). Similar results were found when scoring ability at the expressive, receptive, and pragmatic (social) communication levels. Selection of the appropriate ORCA scoring algorithm for use in research studies should be based on the communication concept of interest for the intervention being evaluated and the characteristics of the neurodevelopmental disorder population being assessed. This study reinforces the need for robust assessment tools that can adapt to the unique challenges of rare disease populations.
The Desperation Threshold Model (DTM) seeks to explain conflicting findings about the risk propensity of people living in poverty, predicting risk aversion when they can still meet their basic needs, and risk taking when they cannot. The DTM makes assumptions: that people have a conception of basic needs, that their ability to meet these motivates their decisions, and that they modulate risky decisions depending on their ability to do so. The realism of these assumptions has not yet been investigated. To start filling this gap, we investigated experiences of poverty through the lens of the DTM, using two complementary approaches: a pre-registered online survey with British participants (n = 300) and semi-structured qualitative interviews with very low-income individuals in France (n = 14). Our results imply that basic needs have both a context-general component and context-specific elaborations. Furthermore, participants often relied on social and institutional resources when experiencing financial adversity, indicating that measuring only personal income or wealth might not accurately capture the resources available to people. With respect to the DTM's main predictions, most individuals close to-but still above-the desperation threshold exhibited caution and took a safety-first approach, consistent with risk-averse behavior. Risky or antisocial behaviors (e.g., cheating, stealing) emerged only in rare instances of severe financial hardship and complete lack of external support. These results suggest that the DTM's main assumptions are empirically grounded but that they need to be qualified in specific ways. They also suggest that abstract models like the DTM can capture something about the experience of people living in conditions of poverty.