An Investigation to Validate the Grammar and Phonology Screening (GAPS) Test to Identify Children with Specific Language Impairment

The extraordinarily high incidence of grammatical language impairments in developmental disorders suggests that this uniquely human cognitive function is "fragile". Yet our understanding of the neurobiology of grammatical impairments is limited. Furthermore, there is no "gold-standard" to identify grammatical impairments and routine screening is not undertaken. An accurate screening test to identify grammatical abilities would serve the research, health and education communities, further our understanding of developmental disorders, and identify children who need remediation, many of whom are currently un-diagnosed. A potential realistic screening tool that could be widely administered is the Grammar and Phonology Screening (GAPS) test--a 10 minute test that can be administered by professionals and non-professionals alike. Here we provide a further step in evaluating the validity and accuracy (sensitivity and specificity) of the GAPS test in identifying children who have Specific Language Impairment (SLI)

Narrative skills in adolescents with a history of SLI in relation to non-verbal IQ scores

There is a debate about whether the language of children with primary language disorders and normal cognitive levels is qualitatively different from those with language impairments who have low or borderline non-verbal IQ (NVIQ). As children reach adolescence, this distinction may be even harder to ascertain, especially in naturalistic settings. Narrative may provide a useful, ecologically valid way in which to assess the language ability of adolescents with specific language impairment (SLI) who have intact or lowered NVIQ and to determine whether there is any discernable difference in every day language. Nineteen adolescents with a history of SLI completed two narrative tasks: a story telling condition and a conversational condition. Just under half the group (n = 8) had non-verbal IQs of 85. The remaining 11 had NVIQs in the normal range or above. Four areas of narrative (productivity, syntax, cohesion and performance) were assessed. There were no differences between the groups on standardized tests of language. However, the group with low NVIQ were poorer on most aspects of narrative, suggesting that cognitive level is important, even when language is the primary disorder. The groups showed similar patterns of differences between story telling and conversational narrative. It was concluded that adolescents with a history of SLI and poor cognitive levels have poorer narrative skills than those with normal range NVIQ even though these may not be detected by standardized assessment. Their difficulties present as qualitatively similar to those with normal range NVIQ and narratives appear impoverished rather than inaccurate

Maternal and neonatal bleeding complications in relation to peripartum management in hemophilia carriers:A systematic review

Currently, there is no consensus on the optimal management to prevent postpartum hemorrhage (PPH) in hemophilia carriers. We aimed to evaluate peripartum management strategies in relation to maternal and neonatal bleeding outcomes by performing an extensive database search up to August 2020. Seventeen case-reports/series and 11 cohort studies were identified of overall 'poor' quality describing 502 deliveries. The PPH incidence in the individual patient data was 63%; 44% for those women receiving prophylaxis to correct coagulation and 77% for those without (OR 0.23, CI 0.09-0.58) and in cohort data 20.3% (26.8% (11/41) vs. 19.4% (55/284) (OR: 1.53, 95% CI: 0.72-3.24), respectively. Peripartum management strategies mostly consisted of clotting factor concentrates, rarely of desmopressin or plasma. Tranexamic acid appears promising in preventing secondary PPH, but was not used consistently. Neonatal bleeding was described in 6 affected male neonates, mostly after instrumental delivery or emergency CS, but insufficient information was provided to reliably investigate neonatal outcome in relation to management. The high PPH risk seems apparent, at most mildly attenuated by prophylactic treatment. Prospective cohort studies are needed to determine the optimal perinatal management in hemophilia.Thrombosis and Hemostasi

Enzymatic Characterization of a Human Acyltransferase Activity

Non-histone protein acylation is increasingly recognized as an important posttranslational modification, but little is known as to the biochemical properties of protein serine acylating enzymes.We here report that we have identified a metal-stimulated serine octanoyltransferase activity in microsomes from human erythroleukemic (HEL) cells. The HEL acylating enzyme was linear with respect to time and protein, exhibited a neutral pH optimum (stimulated by cobalt and zinc), and inhibited by chelating reagents. Hydroxylamine treatment removed most, but not all, of the attached radioactivity. A salt extract of microsomal membranes contained the major portion of enzyme activity, indicating that this acyltransferase is not an integral membrane protein. Sucrose density fractionation showed that the acyltransferase activity is concentrated in the endoplasmic reticulum. In competition experiments, the acyltransferase was well inhibited by activated forms of fatty acids containing at least eight to fourteen carbons, but not by acetyl CoA. The zinc-stimulated HEL acyltransferase did not octanoylate proenkephalin, proopiomelanocortin, His-tagged proghrelin, or proghrelin lacking the amino-terminal His-tag stub of Gly-Ala-Met. The peptides des-acyl ghrelin and ACTH were also not acylated; however, des-acyl ghrelin containing the N-terminal tripeptide Gly-Ala-Met was acylated. Mutagenesis studies indicated a requirement for serine five residues from the amino terminus, reminiscent of myristoyl transferase, but not of ghrelin acylation. However, recombinant myristoyl transferase could not recapitulate the hydroxylamine sensitivity, zinc-stimulation, nor EDTA inhibition obtained with HEL acyltransferase, properties preserved in the HEL cell enzyme purified through four sequential chromatographic steps.In conclusion, our data demonstrate the presence of a zinc-stimulated acyltransferase activity concentrated in the endoplasmic reticulum in HEL cells which is likely to contribute to medium-chain protein lipidation

Sentence Repetition in Deaf Children with Specific Language Impairment in British Sign Language

Children with specific language impairment (SLI) perform poorly on sentence repetition tasks across different spoken languages, but until now, this methodology has not been investigated in children who have SLI in a signed language. Users of a natural sign language encode different sentence meanings through their choice of signs and by altering the sequence and inflections of these signs. Grammatical information is expressed through movement and configurational changes of the hands and face. The visual modality thus influences how grammatical morphology and syntax are instantiated. How would language impairment impact on the acquisition of these types of linguistic devices in child signers? We investigated sentence repetition skills in a group of 11 deaf children who display SLI in British Sign Language (BSL) and 11 deaf controls with no language impairment who were matched for age and years of BSL exposure. The SLI group was significantly less accurate on an overall accuracy score, and they repeated lexical items, overall sentence meaning, sign order, facial expressions, and verb morphological structures significantly less accurately than controls. This pattern of language deficits is consistent with the characterization of SLI in spoken languages even though expression is in a different modality. We conclude that explanations of SLI, and of poor sentence repetition by children with this disorder, must be able to account for both the spoken and signed modalities

Macroscopic brain architecture changes and white matter pathology in acromegaly: a clinicoradiological study

Although long-term exposure of the brain to increased GH/IGF-1 likely influences cerebral functions, no in vivo studies have been directed towards changes of the brain structure in acromegaly. Here, we used high resolution magnetic resonance images to compare volumes of gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) of forty-four patients with acromegaly to an age and gender matched, healthy control group (n = 44). In addition, white matter lesions (WMLs) were quantified and graded. Patients exhibited larger GM (+3.7% compared with controls, P = 0.018) and WM volumes (+5.1%, P = 0.035) at the expense of CSF. Differences of WML counts between patients and controls were subtle, however, showing more patients in the 21–40 lesions category (P = 0.044). In conclusion, this MRI study provides first evidence that acromegalic patients exhibit disturbances of the macroscopic brain tissue architecture. Furthermore, acromegalic patients may have an increased risk of neurovascular pathology, likely due to secondary metabolic and vascular comorbidities

A meta-analysis of CAG (cytarabine, aclarubicin, G-CSF) regimen for the treatment of 1029 patients with acute myeloid leukemia and myelodysplastic syndrome

The regimen of cytarabine, aclarubicin and G-CSF (CAG) has been widely used in China and Japan for treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We searched literature on CAG between 1995 and 2010 and performed a meta-analysis to determine its overall efficacy using a random-effects or fixed-effects model. Thirty five trials with a total of 1029 AML (n = 814) and MDS (n = 215) patients were included for analysis. The CR rate of AML (57.9%) was significantly higher than that of MDS (45.7%) (p < 0.01). No difference in CR was noted between the new (56.7%) and relapsed/refractory AML (60.1%) (p > 0.05). The CR rate was also significantly higher in patients with favorable (64.5%) and intermediate (69.6%) karyotypes than those with unfavorable one (29.5%) (p < 0.05). Remarkably, the CR rate of CAG was significantly higher than those of non-CAG regimens (odds ratio 2.43). CAG regimen was well tolerated, with cardiotoxicity in 2.3% and early death in 5.2% of the cases. In conclusion, CAG regimen was an effective and safe regimen for the treatment of AML, and may be more effective than non-CAG regimens. Randomized controlled trials are strongly recommended to evaluate its efficacy and safety in comparison with the current standard treatment

Interprofessional Consensus Regarding Design Requirements for Liquid-Based Perinatal Life Support (PLS) Technology

Liquid-based perinatal life support (PLS) technology will probably be applied in a first-in-human study within the next decade. Research and development of PLS technology should not only address technical issues, but also consider socio-ethical and legal aspects, its application area, and the corresponding design implications. This paper represents the consensus opinion of a group of healthcare professionals, designers, ethicists, researchers and patient representatives, who have expertise in tertiary obstetric and neonatal care, bio-ethics, experimental perinatal animal models for physiologic research, biomedical modeling, monitoring, and design. The aim of this paper is to provide a framework for research and development of PLS technology. These requirements are considering the possible respective user perspectives, with the aim to co-create a PLS system that facilitates physiological growth and development for extremely preterm born infants