Teaching little kids big sentences: A randomized controlled trial showing that children with DLD respond to complex syntax intervention embedded within the context of preschool/kindergarten science instruction.

BACKGROUND: The language of the science curriculum is complex, even in the early grades. To communicate their scientific observations, children must produce complex syntax, particularly complement clauses (e.g., I think it will float; We noticed that it vibrates). Complex syntax is often challenging for children with developmental language disorder (DLD), and thus their learning and communication of science may be compromised. AIMS: We asked whether recast therapy delivered in the context of a science curriculum led to gains in complement clause use and scientific content knowledge. To understand the efficacy of recast therapy, we compared changes in science and language knowledge in children who received treatment for complement clauses embedded in a first-grade science curriculum to two active control conditions (vocabulary + science, phonological awareness + science). METHODS & PROCEDURES: This 2-year single-site three-arm parallel randomized controlled trial was conducted in Delaware, USA. Children with DLD, not yet in first grade and with low accuracy on complement clauses, were eligible. Thirty-three 4-7-year-old children participated in the summers of 2018 and 2019 (2020 was cancelled due to COVID-19). We assigned participants to arms using 1:1:1 pseudo-random allocation (avoiding placing siblings together). The intervention consisted of 39 small-group sessions of recast therapy, robust vocabulary instruction or phonological awareness intervention during eight science units over 4 weeks, followed by two science units (1 week) taught without language intervention. Pre-/post-measures were collected 3 weeks before and after camp by unmasked assessors. OUTCOMES & RESULTS: Primary outcome measures were accuracy on a 20-item probe of complement clause production and performance on ten 10-item unit tests (eight science + language, two science only). Complete data were available for 31 children (10 grammar, 21 active control); two others were lost to follow-up. Both groups made similar gains on science unit tests for science + language content (pre versus post, d = 2.9, p < 0.0001; group, p = 0.24). The grammar group performed significantly better at post-test than the active control group (d = 2.5, p = 0.049) on complement clause probes and marginally better on science-only unit tests (d = 2.5, p = 0.051). CONCLUSIONS & IMPLICATIONS: Children with DLD can benefit from language intervention embedded in curricular content and learn both language and science targets taught simultaneously. Tentative findings suggest that treatment for grammar targets may improve academic outcomes. WHAT THIS PAPER ADDS: What is already known on the subject We know that recast therapy focused on morphology is effective but very time consuming. Treatment for complex syntax in young children has preliminary efficacy data available. Prior research provides mixed evidence as to children's ability to learn language targets in conjunction with other information. What this study adds This study provides additional data supporting the efficacy of intensive complex syntax recast therapy for children ages 4-7 with Developmental Language Disorder. It also provides data that children can learn language targets and science curricular content simultaneously. What are the clinical implications of this work? As SLPs, we have to talk about something to deliver language therapy; we should consider talking about curricular content. Recast therapy focused on syntactic frames is effective with young children.

Hand gestures support word learning in patients with hippocampal amnesia.

Co-speech hand gesture facilitates learning and memory, yet the cognitive and neural mechanisms supporting this remain unclear. One possibility is that motor information in gesture may engage procedural memory representations. Alternatively, iconic information from gesture may contribute to declarative memory representations mediated by the hippocampus. To investigate these alternatives, we examined gesture's effects on word learning in patients with hippocampal damage and declarative memory impairment, with intact procedural memory, and in healthy and in brain-damaged comparison groups. Participants learned novel label-object pairings while producing gesture, observing gesture, or observing without gesture. After a delay, recall and object identification were assessed. Unsurprisingly, amnesic patients were unable to recall the labels at test. However, they correctly identified objects at above chance levels, but only if they produced a gesture at encoding. Comparison groups performed well above chance at both recall and object identification regardless of gesture. These findings suggest that gesture production may support word learning by engaging nondeclarative (procedural) memory.

ZFP191 is required by oligodendrocytes for CNS myelination.

The controlling factors that prompt mature oligodendrocytes to myelinate axons are largely undetermined. In this study, we used a forward genetics approach to identify a mutant mouse strain characterized by the absence of CNS myelin despite the presence of abundant numbers of late-stage, process-extending oligodendrocytes. Through linkage mapping and complementation testing, we identified the mutation as a single nucleotide insertion in the gene encoding zinc finger protein 191 (Zfp191), which is a widely expressed, nuclear-localized protein that belongs to a family whose members contain both DNA-binding zinc finger domains and protein-protein-interacting SCAN domains. Zfp191 mutants express an array of myelin-related genes at significantly reduced levels, and our in vitro and in vivo data indicate that mutant ZFP191 acts in a cell-autonomous fashion to disrupt oligodendrocyte function. Therefore, this study demonstrates that ZFP191 is required for the myelinating function of differentiated oligodendrocytes.

A novel approach to improving efficiency and cost saving in preoperative blood preparation.

BACKGROUND: Preoperative ordering of blood products has been an area of optimization due to considerable variability among physicians; overpreparation can lead to extra costs and underpreparation of blood can potentially compromise patient safety. STUDY DESIGN AND METHODS: We examined the potential cost savings of extending the storage interval of a presurgical type-and-screen sample from 7 to 14 days, thereby reducing the need for a new specimen on the day of surgery. RESULTS: Sensitivity analysis showed annual cost savings for our institution to be an estimated $38,770 ($22,420-$73,120). CONCLUSION: These results are even more robust when incorporating the additional potential savings from improved operating room efficiency.

A technique for continuous measurement of body movement from video.

The movements that we make with our body vary continuously along multiple dimensions. However, many of the tools and techniques presently used for coding and analyzing hand gestures and other body movements yield categorical outcome variables. Focusing on categorical variables as the primary quantitative outcomes may mislead researchers or distort conclusions. Moreover, categorical systems may fail to capture the richness present in movement. Variations in body movement may be informative in multiple dimensions. For example, a single hand gesture has a unique size, height of production, trajectory, speed, and handshape. Slight variations in any of these features may alter how both the speaker and the listener are affected by gesture. In this paper, we describe a new method for measuring and visualizing the physical trajectory of movement using video. This method is generally accessible, requiring only video data and freely available computer software. This method allows researchers to examine features of hand gestures, body movement, and other motion, including size, height, curvature, and speed. We offer a detailed account of how to implement this approach, and we also offer some guidelines for situations where this approach may be fruitful in revealing how the body expresses information. Finally, we provide data from a small study on how speakers alter their hand gestures in response to different characteristics of a stimulus to demonstrate the utility of analyzing continuous dimensions of motion. By creating shared methods, we hope to facilitate communication between researchers from varying methodological traditions.

Loss of Clcc1 results in ER stress, misfolded protein accumulation, and neurodegeneration.

Folding of transmembrane and secretory proteins occurs in the lumen of the endoplasmic reticulum (ER) before transportation to the cell surface and is monitored by the unfolded protein response (UPR) signaling pathway. The accumulation of unfolded proteins in the ER activates the UPR that restores ER homeostasis by regulating gene expression that leads to an increase in the protein-folding capacity of the ER and a decrease in the ER protein-folding load. However, prolonged UPR activity has been associated with cell death in multiple pathological conditions, including neurodegeneration. Here, we report a spontaneous recessive mouse mutation that causes progressive cerebellar granule cell death and peripheral motor axon degeneration. By positional cloning, we identify the mutation in this strain as a retrotransposon insertion in the Clcc1 gene, which encodes a putative chloride channel localized to the ER. Furthermore, we demonstrate that the C3H/HeSnJ inbred strain has late onset cerebellar degeneration due to this mutation. Interestingly, acute knockdown of Clcc1 expression in cultured cells increases sensitivity to ER stress. In agreement, GRP78, the major HSP70 family chaperone in the ER, is upregulated in Clcc1-deficient granule cells in vivo, and ubiquitinated proteins accumulate in these neurons before their degeneration. These data suggest that disruption of chloride homeostasis in the ER disrupts the protein-folding capacity of the ER, leading to eventual neuron death.

Kidney adysplasia and variable hydronephrosis, a new mutation affecting the odd-skipped related 1 gene in the mouse, causes variable defects in kidney development and hydronephrosis.

Many genes, including odd-skipped related 1 (Osr1), are involved in regulation of mammalian kidney development. We describe here a new recessive mutation (kidney adysplasia and variable hydronephrosis, kavh) in the mouse that leads to downregulation of Osr1 transcript, causing several kidney defects: agenesis, hypoplasia, and hydronephrosis with variable age of onset. The mutation is closely associated with a reciprocal translocation, T(12;17)4Rk, whose Chromosome 12 breakpoint is upstream from Osr1. The kavh/kavh mutant provides a model to study kidney development and test therapies for hydronephrosis.

A mouse Col4a4 mutation causing Alport glomerulosclerosis with abnormal collagen α3α4α5(IV) trimers.

A spontaneous mutation termed bilateral wasting kidneys (bwk) was identified in a colony of NONcNZO recombinant inbred mice. These mice exhibit a rapid increase of urinary albumin at an early age associated with glomerulosclerosis, interstitial nephritis, and tubular atrophy. The mutation was mapped to a location on chromosome 1 containing the Col4a3 and Col4a4 genes, for which mutations in the human orthologs cause the hereditary nephritis Alport syndrome. DNA sequencing identified a G-to-A mutation in the conserved GT splice donor of Col4a4 intron 30, resulting in skipping of exon 30 but maintaining the mRNA reading frame. Protein analyses showed that mutant collagen α3α4α5(IV) trimers were secreted and incorporated into the glomerular basement membrane (GBM), but levels were low, and GBM lesions typical of Alport syndrome were observed. Moving the mutation into the more renal damage-prone DBA/2J and 129S1/SvImJ backgrounds revealed differences in albuminuria and its rate of increase, suggesting an interaction between the Col4a4 mutation and modifier genes. This novel mouse model of Alport syndrome is the only one shown to accumulate abnormal collagen α3α4α5(IV) in the GBM, as also found in a subset of Alport patients. These mice will be valuable for testing potential therapies, for understanding abnormal collagen IV structure and assembly, and for gaining better insights into the mechanisms leading to Alport syndrome, and to the variability in the age of onset and associated phenotypes.

How Prior Knowledge, Gesture Instruction, and Interference After Instruction Interact to Influence Learning of Mathematical Equivalence.

Although children learn more when teachers gesture, it is not clear how gesture supports learning. Here, we sought to investigate the nature of the memory processes that underlie the observed benefits of gesture on lasting learning. We hypothesized that instruction with gesture might create memory representations that are particularly resistant to interference. We investigated this possibility in a classroom study with 402 second- and third-grade children. Participants received classroom-level instruction in mathematical equivalence using videos with or without accompanying gesture. After instruction, children solved problems that were either visually similar to the problems that were taught, and consistent with an operational interpretation of the equal sign (interference), or visually distinct from equivalence problems and without an equal sign (control) in order to assess the role of gesture in resisting interference after learning. Gesture facilitated learning, but the effects of gesture and interference varied depending on type of problem being solved and the strategies that children used to solve problems prior to instruction. Some children benefitted from gesture, while others did not. These findings have implications for understanding the mechanisms underlying the beneficial effect of gesture on mathematical learning, revealing that gesture does not work via a general mechanism like enhancing attention or engagement that would apply to children with all forms of prior knowledge.

Consolidation and transfer of learning after observing hand gesture.

Children who observe gesture while learning mathematics perform better than children who do not, when tested immediately after training. How does observing gesture influence learning over time? Children (n = 184, ages = 7-10) were instructed with a videotaped lesson on mathematical equivalence and tested immediately after training and 24 hr later. The lesson either included speech and gesture or only speech. Children who saw gesture performed better overall and performance improved after 24 hr. Children who only heard speech did not improve after the delay. The gesture group also showed stronger transfer to different problem types. These findings suggest that gesture enhances learning of abstract concepts and affects how learning is consolidated over time.

Emoji as gesture in digital communication: Emoji improve comprehension of indirect speech.

As reliance on digital communication grows, so does the importance of communicating effectively with text. Yet when communicating with text, benefits from other channels, such as hand gesture, are diminished. Hand gestures support comprehension and disambiguate characteristics of the spoken message by providing information in a visual channel supporting speech. Can emoji (pictures used to supplement text communication) perform similar functions? Here, we ask whether emoji improve comprehension of indirect speech. Indirect speech is ambiguous, and appropriate comprehension depends on the receiver decoding context cues, such as hand gesture. We adapted gesture conditions from prior research (Kelly et al., 1999, Experiment 2) to a digital, text-based format, using emoji rather than gestures. Participants interpreted 12 hypothetical text-message exchanges that ended with indirect speech, communicated via text only, text+emoji, or emoji only, in a between-subjects design. Like that previously seen for hand gesture, emoji improved comprehension. Participants were more likely to correctly interpret indirect speech in the emoji-only condition compared with the text+emoji and the text-only conditions, and more likely in the text+emoji condition compared to the text-only condition. Thus, emoji are not mere decoration, but rather are integrated with text to communicate and disambiguate complex messages. Similar to gesture in face-to-face communication, emoji improve comprehension during text-based communication.

Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration.

Misfolded proteins are associated with several pathological conditions including neurodegeneration. Although some of these abnormally folded proteins result from mutations in genes encoding disease-associated proteins (for example, repeat-expansion diseases), more general mechanisms that lead to misfolded proteins in neurons remain largely unknown. Here we demonstrate that low levels of mischarged transfer RNAs (tRNAs) can lead to an intracellular accumulation of misfolded proteins in neurons. These accumulations are accompanied by upregulation of cytoplasmic protein chaperones and by induction of the unfolded protein response. We report that the mouse sticky mutation, which causes cerebellar Purkinje cell loss and ataxia, is a missense mutation in the editing domain of the alanyl-tRNA synthetase gene that compromises the proofreading activity of this enzyme during aminoacylation of tRNAs. These findings demonstrate that disruption of translational fidelity in terminally differentiated neurons leads to the accumulation of misfolded proteins and cell death, and provide a novel mechanism underlying neurodegeneration.

A pre-registered, multi-lab non-replication of the action-sentence compatibility effect (ACE).

The Action-sentence Compatibility Effect (ACE) is a well-known demonstration of the role of motor activity in the comprehension of language. Participants are asked to make sensibility judgments on sentences by producing movements toward the body or away from the body. The ACE is the finding that movements are faster when the direction of the movement (e.g., toward) matches the direction of the action in the to-be-judged sentence (e.g., Art gave you the pen describes action toward you). We report on a pre-registered, multi-lab replication of one version of the ACE. The results show that none of the 18 labs involved in the study observed a reliable ACE, and that the meta-analytic estimate of the size of the ACE was essentially zero.

Heat shock factor-1 modulates p53 activity in the transcriptional response to DNA damage.

Here we define an important role for heat shock factor 1 (HSF1) in the cellular response to genotoxic agents. We demonstrate for the first time that HSF1 can complex with nuclear p53 and that both proteins are co-operatively recruited to p53-responsive genes such as p21. Analysis of natural and synthetic cis elements demonstrates that HSF1 can enhance p53-mediated transcription, whilst depletion of HSF1 reduces the expression of p53-responsive transcripts. We find that HSF1 is required for optimal p21 expression and p53-mediated cell-cycle arrest in response to genotoxins while loss of HSF1 attenuates apoptosis in response to these agents. To explain these novel properties of HSF1 we show that HSF1 can complex with DNA damage kinases ATR and Chk1 to effect p53 phosphorylation in response to DNA damage. Our data reveal HSF1 as a key transcriptional regulator in response to genotoxic compounds widely used in the clinical setting, and suggest that HSF1 will contribute to the efficacy of these agents.

Acute Hemolytic Transfusion Reaction Due to Pooled Platelets: A Rare but Serious Adverse Event.

A female patient aged 65 years with blood group A with relapsed lymphoma had thrombocytopenia; leukocyte-reduced group O prestorage pooled platelet concentrates (PPLTs) were transfused without adverse events. She was discharged home, but 1.5 hours later she returned with fever and dark urine. Hypotension and tachycardia developed; she was admitted to the intensive care unit. Post-transfusion blood and urine samples were obtained. Serial dilutions from 5 donor testing tubes and a simulated PLT pool were performed and read at immediate spin and IgG. Testing confirmed an acute hemolytic transfusion reaction (AHTR): elevated lactate dehydrogenase (996 U/L; normal range 135 U/L-225 U/L) and undetectable haptoglobin (<10 mg/dL; normal range 30 mg/dL-200 mg/dL) levels. Urinalysis showed dark amber urine but no significant quantity of red blood cells. At 37ºC the simulated pool and donor number 5 had high-titer anti-A. As a precaution, the donor was permanently deferred. Research has shown that PLT-associated AHTR has occurred with apheresis platelets but is very rare with whole blood-derived PLTs.

Parenting and Home Environment in Childhood and Adolescence and Alcohol Use Disorder in Adulthood.

PURPOSE: Parenting is a modifiable factor affecting the development of alcohol use disorder (AUD); however, the persistence of this effect into adulthood remains poorly understood. This study aimed to explore the longitudinal relationship between positive parenting and AUD in adulthood. METHODS: Data were gathered from the Christchurch Health and Development Study (CHDS), a birth cohort of 1,265 children born in Christchurch (New Zealand) in mid-1977. Positive parenting was quantified to age 16, and included the extent to which cohort members self-reported: high scores on measures of maternal and paternal care; low scores on a measure of maternal and paternal overprotection; high scores on a measure of parental attachment; low scores on a measure of parental intimate partner violence; and occasional or no use of physical punishment. Outcome measures were AUD incidence and symptoms at ages 15-35, with potential confounding factors and time-dynamic covariates included. RESULTS: There was a significant association between positive parenting and AUD outcomes, with higher levels of positive parenting associated with a lower incidence of AUD and AUD symptoms. Controlling for confounding factors reduced the association between positive parenting and AUD outcomes, but they remained statistically significant. Adjustment for mental health, life stress, and employment reduced the magnitude of the association between positive parenting and alcohol outcomes to statistical nonsignificance. CONCLUSIONS: Parenting factors in childhood and adolescence are linked to AUD outcomes in adulthood, as well as mental health, substance use, and life stress. Investment in positive parenting in adolescence may reduce AUD and associated harms in adulthood.

The Challenge of Rich Vocabulary Instruction for Children With Developmental Language Disorder.

Purpose The aims of the study were to explore responses of children with developmental language disorder (DLD) to rich vocabulary instruction and to identify potential factors that contribute to outcomes. Method Children with DLD participated in a language intervention embedded within a science camp. Using parent and clinician reports, standardized tests, probes, notes, and video, we derived descriptions of seven of the campers who received a vocabulary intervention that incorporated principles of rich instruction. We present them here as a case series. Results Five cases responded to the intervention with modest gains in Tier 2 science vocabulary and science knowledge. One case demonstrated no response, and another was unable to complete the intervention. The latter two cases presented with triple risks: DLD, executive function deficits, and stressors associated with poverty. In comparison, the best responder also lived in poverty and had DLD, but he had intact executive function, strengths in extant vocabulary, stronger knowledge of science, better engagement in the science and language intervention activities, and was older. Other factors that seemed to contribute to outcomes included the complexity of the word forms and dosage. Conclusions Translating research on rich instruction to clinical practice is challenging. This case series motivated hypotheses about the nature of the challenge and what to do about it, the primary one being that the modest success of rich vocabulary instruction for children with DLD is not a limitation of the approach itself but rather a reflection of the difficulty of delivering the intervention while tailoring the targets, approach, and dosage to the needs of individual children with DLD. Supplemental Material https://doi.org/10.23641/asha.13667699.

SARS-CoV-2 Testing of 11,884 Healthcare Workers at an Acute NHS Hospital Trust in England: A Retrospective Analysis.

Healthcare workers (HCWs) are known to be at increased risk of infection with SARS-CoV-2, although whether these risks are equal across all roles is uncertain. Here we report a retrospective analysis of a large real-world dataset obtained from 10 March to 6 July 2020 in an NHS Foundation Trust in England with 17,126 employees. 3,338 HCWs underwent symptomatic PCR testing (14.4% positive, 2.8% of all staff) and 11,103 HCWs underwent serological testing for SARS-CoV-2 IgG (8.4% positive, 5.5% of all staff). Seropositivity was lower than other hospital settings in England but higher than community estimates. Increased test positivity rates were observed in HCWs from BAME backgrounds and residents in areas of higher social deprivation. A multiple logistic regression model adjusting for ethnicity and social deprivation confirmed statistically significant increases in the odds of testing positive in certain occupational groups, most notably domestic services staff, nurses, and health-care assistants. PCR testing of symptomatic HCWs appeared to underestimate overall infection levels, probably due to asymptomatic seroconversion. Clinical outcomes were reassuring, with only a small minority of HCWs with COVID-19 requiring hospitalization (2.3%) or ICU management (0.7%) and with no deaths. Despite a relatively low level of HCW infection compared to other UK cohorts, there were nevertheless important differences in test positivity rates between occupational groups, robust to adjustment for demographic factors such as ethnic background and social deprivation. Quantitative and qualitative studies are needed to better understand the factors contributing to this risk. Robust informatics solutions for HCW exposure data are essential to inform occupational monitoring.

Ozone impacts of natural gas development in the Haynesville Shale.

The Haynesville Shale is a subsurface rock formation located beneath the Northeast Texas/Northwest Louisiana border near Shreveport. This formation is estimated to contain very large recoverable reserves of natural gas, and during the two years since the drilling of the first highly productive wells in 2008, has been the focus of intensive leasing and exploration activity. The development of natural gas resources within the Haynesville Shale is likely to be economically important but may also generate significant emissions of ozone precursors. Using well production data from state regulatory agencies and a review of the available literature, projections of future year Haynesville Shale natural gas production were derived for 2009-2020 for three scenarios corresponding to limited, moderate, and aggressive development. These production estimates were then used to develop an emission inventory for each of the three scenarios. Photochemical modeling of the year 2012 showed increases in 2012 8-h ozone design values of up to 5 ppb within Northeast Texas and Northwest Louisiana resulting from development in the Haynesville Shale. Ozone increases due to Haynesville Shale emissions can affect regions outside Northeast Texas and Northwest Louisiana due to ozone transport. This study evaluates only near-term ozone impacts, but the emission inventory projections indicate that Haynesville emissions may be expected to increase through 2020.