Complete callosal agenesis, pontocerebellar hypoplasia, and axonal neuropathy due to AMPD2 loss.

Objective: To determine the molecular basis of a severe neurologic disorder in a large consanguineous family with complete agenesis of the corpus callosum (ACC), pontocerebellar hypoplasia (PCH), and peripheral axonal neuropathy.

Methods: Assessment included clinical evaluation, neuroimaging, and nerve conduction studies (NCSs). Linkage analysis used genotypes from 7 family members, and the exome of 3 affected siblings was sequenced.

Familial cortical dysplasia caused by mutation in the mammalian target of rapamycin regulator NPRL3.

We describe first cousin sibling pairs with focal epilepsy, one of each pair having focal cortical dysplasia (FCD) IIa. Linkage analysis and whole-exome sequencing identified a heterozygous germline frameshift mutation in the gene encoding nitrogen permease regulator-like 3 (NPRL3). NPRL3 is a component of GAP Activity Towards Rags 1, a negative regulator of the mammalian target of rapamycin complex 1 signaling pathway.

Singapore's regional health systems-a data-driven perspective on frequent admitters and cross utilization of healthcare services in three systems.

Introduction: With population health management being a priority in the Singapore, this paper aims to provide a data-driven perspective of the population health management initiatives to aid program planning and serves as a baseline for evaluation of future implemented programs.

Methods: A database with information on patient demographics, health services utilization, cost, diagnoses and chronic disease information from 2008 to 2013 for three regional health systems in Singapore was used for analysis. Patients with three or more inpatient admissions were considered as "Frequent Admitters.

ARID1B-mediated disorders: Mutations and possible mechanisms.

Mutations in the gene encoding AT-rich interactive domain-containing protein 1B (ARID1B) were recently associated with multiple syndromes characterized by developmental delay and intellectual disability, in addition to nonsyndromic intellectual disability. While the majority of ARID1B mutations identified to date are predicted to result in haploinsufficiency, the underlying pathogenic mechanisms have yet to be fully understood. ARID1B is a DNA-binding subunit of the Brahma-associated factor chromatin remodelling complexes, which play a key role in the regulation of gene activity.

Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with α-synuclein pathology.

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a ∼45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.

Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features.

Age-related degenerative and malignant diseases represent major challenges for health care systems. Elucidation of the molecular mechanisms underlying carcinogenesis and age-associated pathologies is thus of growing biomedical relevance. We identified biallelic germline mutations in SPRTN (also called C1orf124 or DVC1) in three patients from two unrelated families.

Expanding the phenotypic spectrum of ARID1B-mediated disorders and identification of altered cell-cycle dynamics due to ARID1B haploinsufficiency.

Background: Mutations in genes encoding components of the Brahma-associated factor (BAF) chromatin remodeling complex have recently been shown to contribute to multiple syndromes characterised by developmental delay and intellectual disability. ARID1B mutations have been identified as the predominant cause of Coffin-Siris syndrome and have also been shown to be a frequent cause of nonsyndromic intellectual disability. Here, we investigate the molecular basis of a patient with an overlapping but distinctive phenotype of intellectual disability, plantar fat pads and facial dysmorphism.

The successful, rapid transition to a new model of graduate medical education in Singapore.

Graduate medical education (GME) in Singapore recently underwent major reform (2009-2012), leading to accreditation of residency programs by the Accreditation Council for Graduate Medical Education-International (ACGME-I) within two years of the initial commitment to change. The main aims of the reforms were to implement best practices in GME, to provide better support structures for program administration, and to bring all specialty training under one administrative umbrella. The authors outline the historic development of GME in Singapore, the complexities of the model in place immediately prior to ACGME-I accreditation, and the difficulties addressed by the proposed changes, leading to a description of implementation efforts at the National University Hospital of Singapore, a university-affiliated academic medical center.

Intelligent analysis of acute bed overflow in a tertiary hospital in Singapore.

Hospital beds are a scarce resource and always in need. The beds are often organized by clinical specialties for better patient care. When the Accident & Emergency Department (A&E) admits a patient, there may not be an available bed that matches the requested specialty.

Cost-effectiveness analysis of hospital infection control response to an epidemic respiratory virus threat.

The outbreak of influenza A pandemic (H1N1) 2009 prompted many countries in Asia, previously strongly affected by severe acute respiratory syndrome (SARS), to respond with stringent measures, particularly in preventing outbreaks in hospitals. We studied actual direct costs and cost-effectiveness of different response measures from a hospital perspective in tertiary hospitals in Singapore by simulating outbreaks of SARS, pandemic (H1N1) 2009, and 1918 Spanish influenza. Protection measures targeting only infected patients yielded lowest incremental cost/death averted of 23,000 (US dollars) for pandemic (H1N1) 2009.