Since the Asian economic crisis in 1997-98, the Singapore government has embraced neoliberal globalization to a degree not matched elsewhere in East or Southeast Asia. Yet the consolidation and ...expansion of Singapore's state companies are also integral to this strategy. These companies are increasingly the objects of critical attention from elements of international capital that are seeking to make inroads into various sectors of the Singapore economy. This includes pressures to reform governance systems from which state companies derive competitive advantages. This article examines the nature and political strength of these challenges, the responses to them by the Singapore government, and the implications of this for the future of the authoritarian regime. The article also analyzes the changing geopolitical context within which such disputes are being played out. Security concerns by the U.S. government in particular, it is argued, are mediating conflict over state companies and presenting new opportunities for the authoritarian regime to consolidate.
The Supplemental Security Income Program (SSI) provides financial support to low-income households with children and youth with severe disabilities. The program included children when it began in the ...early 1970s. The numbers of children receiving SSI benefits increased substantially in the early 1990s, in part through an expansion of the listings of mental health conditions with which children could become eligible. Over the past 20 years, larger numbers of children have received SSI benefits for mental disorders, and these increases have led to questions from the press and Congress regarding these numbers. Do they indicate more of an increase in mental disorders among SSI children than in the general population? The National Academy of Medicine (NAM; formerly the Institute of Medicine) convened a study panel to examine what is known about mental disorders among the child SSI population and how that compares with evidence about mental disorders in children in general. The NAM report provides detailed information about how SSI works, about the changing numbers of children receiving SSI for mental disorders, and some comparisons with other evidence about rising rates of mental disorders in the general population and especially among children living in poverty. The report indicates that increasing numbers of children with mental disorders in SSI mirror similar increases in the population in general. This article summarizes key evidence from the NAM report and suggests the implications for pediatricians.
Objectives
Cerebral palsy (CP) is the most common childhood motor disability, yet its link to single‐gene disorders is under‐characterized. To explore the genetic landscape of CP, we conducted whole ...exome sequencing (WES) in a cohort of patients with CP.
Methods
We performed comprehensive phenotyping and WES on a prospective cohort of individuals with cryptogenic CP (who meet criteria for CP; have no risk factors), non‐cryptogenic CP (who meet criteria for CP; have at least one risk factor), and CP masqueraders (who could be diagnosed with CP, but have regression/progressive symptoms). We characterized motor phenotypes, ascertained medical comorbidities, and classified brain MRIs. We analyzed WES data using an institutional pipeline.
Results
We included 50 probands in this analysis (20 females, 30 males). Twenty‐four had cryptogenic CP, 20 had non‐cryptogenic CP, five had CP masquerader classification, and one had unknown classification. Hypotonic‐ataxic subtype showed a difference in prevalence across the classification groups (p = 0.01). Twenty‐six percent of participants (13/50) had a pathogenic/likely pathogenic variant in 13 unique genes (ECHS1, SATB2, ZMYM2, ADAT3, COL4A1, THOC2, SLC16A2, SPAST, POLR2A, GNAO1, PDHX, ACADM, ATL1), including one patient with two genetic disorders (ACADM, PDHX) and two patients with a SPAST‐related disorder. The CP masquerader category had the highest diagnostic yield (n = 3/5, 60%), followed by the cryptogenic CP category (n = 7/24, 29%). Fifteen percent of patients with non‐cryptogenic CP (n = 3/20) had a Mendelian disorder on WES.
Interpretation
WES demonstrated a significant prevalence of Mendelian disorders in individuals clinically diagnosed with CP, including in individuals with known CP risk factors.
Insulin-like growth factors (IGFs) are bound in the circulation to specific binding proteins (BP). The predominant BP is a GH-dependent glycosylated protein of 42-49 kDa on sodium dodecyl ...sulfate-polyacrylamide gel electrophoresis (BP-3), whereas nonglycosylated GH-independent IGFBPs of 32 kDa and less are minor constituents. Primary cultures of rat osteoblastic cells constitutively produce IGFBP species of 32 kDa, while GH induces the accumulation of BP-3. To examine whether BP-3 could regulate the biological activity of IGF-I on osteoblasts, we compared the effects of recombinant native human IGF-I (hIGF-I) on primary cultures of osteoblasts in the presence and absence of GH. hIGF-I stimulated cell replication and alpha 1(I) collagen gene expression in a dose-dependent manner, and these effects were potentiated by the presence of GH, which increased the accumulation of BP-3. To further examine this correlation, we compared the effects of two IGF-I peptides on the osteoblastic cell line PyMS, which constitutively produces BP-3, to those in RCT-3 cells, which do not secrete this IGFBP. Using hIGF-I and Gln3,Ala4,Tyr15,Leu16IGF-I (QAYLIGF-I), a mutated IGF-I with reduced affinity to IGFBPs, we found that at equimolar concentrations hIGF-I produced higher stimulation than QAYLIGF-I on 3Hthymidine incorporation, cell replication, and collagen gene expression in PyMS cells. In contrast, both IGF-I peptides had similar potency in RCT-3 cells. Hence, these data show that the accumulation of BP-3 correlates with enhanced hIGF-I activity on osteoblastic cells, suggesting that BPs may act locally to augment the effects of IGF-I in bone.
Whole-exome sequencing (WES) represents a significant breakthrough in clinical genetics, and identifies a genetic etiology in up to 30% of cases of intellectual disability (ID). Using WES, we ...identified seven unrelated patients with a similar clinical phenotype of severe intellectual disability or neurodevelopmental delay who were all heterozygous for de novo truncating variants in the AT-hook DNA-binding motif-containing protein 1 (AHDC1). The patients were all minimally verbal or nonverbal and had variable neurological problems including spastic quadriplegia, ataxia, nystagmus, seizures, autism, and self-injurious behaviors. Additional common clinical features include dysmorphic facial features and feeding difficulties associated with failure to thrive and short stature. The AHDC1 gene has only one coding exon, and the protein contains conserved regions including AT-hook motifs and a PDZ binding domain. We postulate that all seven variants detected in these patients result in a truncated protein missing critical functional domains, disrupting interactions with other proteins important for brain development. Our study demonstrates that truncating variants in AHDC1 are associated with ID and are primarily associated with a neurodevelopmental phenotype.
Under ongoing climate change and increasing anthropogenic activity, which continuously challenge ecosystem resilience, an in-depth understanding of ecological processes is urgently needed. Lakes, as ...providers of numerous ecosystem services, face multiple stressors that threaten their functioning. Harmful cyanobacterial blooms are a persistent problem resulting from nutrient pollution and climate-change induced stressors, like poor transparency, increased water temperature and enhanced stratification. Consistency in data collection and analysis methods is necessary to achieve fully comparable datasets and for statistical validity, avoiding issues linked to disparate data sources. The European Multi Lake Survey (EMLS) in summer 2015 was an initiative among scientists from 27 countries to collect and analyse lake physical, chemical and biological variables in a fully standardized manner. This database includes in-situ lake variables along with nutrient, pigment and cyanotoxin data of 369 lakes in Europe, which were centrally analysed in dedicated laboratories. Publishing the EMLS methods and dataset might inspire similar initiatives to study across large geographic areas that will contribute to better understanding lake responses in a changing environment.
While biomedical risks contribute to poor pregnancy and neonatal outcomes in African American (AA) populations, behavioral and psychosocial risks (BPSR) may also play a part. Among low income AA ...women with psychosocial risks, this report addresses the impacts on pregnancy and neonatal outcomes of an integrated education and counseling intervention to reduce BPSR, as well as the contributions of other psychosocial and biomedical risks. Subjects were low income AA women ≥18 years living in the Washington, DC, metropolitan area and seeking prenatal care. Subjects (n = 1,044) were screened for active smoking, environmental tobacco smoke exposure (ETSE), depression, or intimate partner violence (IPV) and then randomized to intervention (IG) or usual care (UCG) groups. Data were collected prenatally, at delivery, and postpartum by maternal report and medical record abstraction. Multiple imputation methodology was used to estimate missing variables. Rates of pregnancy outcomes (miscarriage, live birth, perinatal death), preterm labor, Caesarean section, sexually transmitted infection (STI) during pregnancy, preterm birth (<37 weeks), low birth weight (<2,500 g), very low birth weight (<1,500 g), small for gestational age, neonatal intensive care unit (NICU) admission, and >2 days of hospitalization were compared between IG and UCG. Logistic regression models were created to predict outcomes based on biomedical risk factors and the four psychosocial risks (smoking, ETSE, depression, and IPV) targeted by the intervention. Rates of adverse pregnancy and neonatal outcomes were high and did not differ significantly between IG and UCG. In adjusted analysis, STI during the current pregnancy was associated with IPV (OR = 1.41, 95% CI 1.04–1.91). Outcomes such as preterm labor, caesarian section in pregnancy and preterm birth, low birth weight, small for gestational age, NICU admissions and >2 day hospitalization of the infants were associated with biomedical risk factors including preexisting hypertension and diabetes, previous preterm birth (PTB), and late initiation of prenatal care, but they were not significantly associated with active smoking, ETSE, depression, or IPV. Neither the intervention to reduce BPSR nor the psychosocial factors significantly contributed to the pregnancy and neonatal outcomes. This study confirms that biomedical factors significantly contribute to adverse outcomes in low income AA women. Biomedical factors outweighed psychosocial factors in contributing to adverse pregnancy and neonatal outcomes in this high-risk population. Early identification and management of hypertension, diabetes and previous PTB in low income AA women may reduce health disparities in birth outcomes.
Level of evidence
I.
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