Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer's disease-related genes in mice.

Hypoxic-ischemic encephalopathy (HIE) in neonates causes mortality and neurologic morbidity, including poor cognition with a complex neuropathology. Injury to the cholinergic basal forebrain and its rich innervation of cerebral cortex may also drive cognitive pathology. It is uncertain whether genes associated with adult cognition-related neurodegeneration worsen outcomes after neonatal HIE. We hypothesized that neocortical damage caused by neonatal HI in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer's disease. We subjected non-transgenic (nTg) C57Bl6 mice and mice transgenically (Tg) expressing human mutant amyloid precursor protein (APP-Swedish variant) and mutant presenilin (PS1-ΔE9) to the Rice-Vannucci HI model on postnatal day 10 (P10). nTg and Tg mice with sham procedure were controls. Visual discrimination (VD) was tested for cognition. Cortical and hippocampal cholinergic axonal and IN pathology and Aß plaques, identified by immunohistochemistry for choline acetyltransferase (ChAT) and 6E10 antibody respectively, were counted at P210. Simple ChAT+ axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings in APP/PS1 Tg mice. In contrast, complex ChAT+ neuritic clusters (NC) occurred only in Tg mice; HI increased that burden. The abundance of ChAT+ clusters in specific regions correlated with decreased VD. The frequency of attritional ChAT+ INs in the entorhinal cortex (EC) was increased in Tg shams relative to their nTg counterparts, but HI obviated this difference. Cholinergic IN pathology in EC correlated with NC number. The Aß deposition in APP/PS1 Tg mice was not exacerbated by HI, nor did it correlate with other metrics. Adult APP/PS1 Tg mice have significant cortical cholinergic axon and EC ChAT+ IN pathologies; some pathology was exacerbated by neonatal HI and correlated with VD. Mechanisms of neonatal HI induced cognitive deficits and cortical neuropathology may be modulated by genetic risk, perhaps accounting for some of the variability in outcomes.

Characterising illness stages and recovery trajectories of eating disorders in young people via remote measurement technology (STORY): a multi-centre prospective cohort study protocol.

BACKGROUND: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse. METHODS: STORY follows 720 young people aged 16-25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Oura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months. DISCUSSION: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families.

Comparison of 4-week versus 8-week dietitian-led FODMAP diet group education sessions in tertiary care clinical practice for irritable bowel syndrome: A service evaluation.

BACKGROUND: The implementation of the fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet for irritable bowel syndrome (IBS) can be effectively delivered by dietitians in group settings. The initial FODMAP restriction phase is recommended to be followed for 4 weeks; however, limited efficacy data exist for 4-week FODMAP restriction in group education clinical practice. METHODS: We aimed to compare 4-week versus 8-week FODMAP group treatment pathways on clinical outcomes using a prospective service evaluation design of IBS patients attending FODMAP restriction (baseline) and reintroduction (follow-up) group sessions (between 2015 and 2019). Clinical outcomes included global symptom question (GSQ) measuring satisfactory relief, gastrointestinal symptom rating scale (GSRS), stool frequency (SF), stool consistency using Bristol stool form scale (BSFS), diet acceptability, patient satisfaction with group sessions and dietary adherence. Logistic regression was used to test for differences in treatment effects when clinical outcomes were compared between groups. RESULTS: Patients (n = 284) included were aged 18 to 86 years (mean ± SD [standard deviation], 44.6 ± 15.5), 80% female, and were split into 4-week (41%, 117/284) versus 8-week (59%, 167/284) pathways with no differences in baseline characteristics. Mean ± SD time gap between baseline and follow-up was 4.6 ± 0.9 weeks in the 4-week pathway and 9.6 ± 3.3 weeks in the 8-week pathway. When groups were compared at follow-up, no statistical differences were observed in any measures (GSQ, GSRS, SF, BSFS, dietary adherence, diet acceptability and patient satisfaction). CONCLUSION: A 4-week dietitian-led group FODMAP treatment pathway is as clinically effective and maintains patient acceptability when compared to 8-weeks and should be considered as part of routine clinical practice.

Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage.

Amyotrophic lateral sclerosis (ALS) is a fatal disease that causes degeneration of motor neurons (MNs) and paralysis. ALS can be caused by mutations in the gene that encodes copper/zinc superoxide dismutase (SOD1). SOD1 is known mostly as a cytosolic antioxidant protein, but SOD1 is also in the nucleus of non-transgenic (tg) and human SOD1 (hSOD1) tg mouse MNs. SOD1's nuclear presence in different cell types and subnuclear compartmentations are unknown, as are the nuclear functions of SOD1. We examined hSOD1 nuclear localization and DNA damage in tg mice expressing mutated and wildtype variants of hSOD1 (hSOD1-G93A and hSOD1-wildtype). We also studied ALS patient-derived induced pluripotent stem (iPS) cells to determine the nuclear presence of SOD1 in undifferentiated and differentiated MNs. In hSOD1-G93A and hSOD1-wildtype tg mice, choline acetyltransferase (ChAT)-positive MNs had nuclear hSOD1, but while hSOD1-wildtype mouse MNs also had nuclear ChAT, hSOD1-G93A mouse MNs showed symptom-related loss of nuclear ChAT. The interneurons had preserved parvalbumin nuclear positivity in hSOD1-G93A mice. hSOD1-G93A was seen less commonly in spinal cord astrocytes and, notably, oligodendrocytes, but as the disease emerged, the oligodendrocytes had increased mutant hSOD1 nuclear presence. Brain and spinal cord subcellular fractionation identified mutant hSOD1 in soluble nuclear extracts of the brain and spinal cord, but mutant hSOD1 was concentrated in the chromatin nuclear extract only in the spinal cord. Nuclear extracts from mutant hSOD1 tg mouse spinal cords had altered protein nitration, footprinting peroxynitrite presence, and the intact nuclear extracts had strongly increased superoxide production as well as the active NADPH oxidase marker, p47phox. The comet assay showed that MNs from hSOD1-G93A mice progressively (6-14 weeks of age) accumulated DNA single-strand breaks. Ablation of the NCF1 gene, encoding p47phox, and pharmacological inhibition of NADPH oxidase with systemic treatment of apocynin (10 mg/kg, ip) extended the mean lifespan of hSOD1-G93A mice by about 25% and mitigated genomic DNA damage progression. In human postmortem CNS, SOD1 was found in the nucleus of neurons and glia; nuclear SOD1 was increased in degenerating neurons in ALS cases and formed inclusions. Human iPS cells had nuclear SOD1 during directed differentiation to MNs, but mutant SOD1-expressing cells failed to establish wildtype MN nuclear SOD1 levels. We conclude that SOD1 has a prominent nuclear presence in the central nervous system, perhaps adopting aberrant contexts to participate in ALS pathobiology.

The quality of teaching behaviors in learning environments of DHH students.

Classrooms are complex learning environments, with instruction, climate, and teacher-student interactions playing important roles in students' academic progress. To investigate the learning environments of deaf and hard-of-hearing (DHH) students, we developed a new observational tool called the Quality of the Learning Environment-DHH rating scale (QLE-DHH) and rated 98 teachers of DHH students being educated in a range of classroom environments. The present study sought to (1) determine if the items on the QLE-DHH are good indicators of theoretically meaningful dimensions of classroom quality; (2) determine to what extent these dimensions predicted language and reading outcomes of DHH students; and (3) examine how teachers of DHH students were rated on the indicators of classroom quality. The findings suggested that the QLE-DHH has excellent structural validity. Ratings predicted student reading outcomes. Finally, the QLE-DHH was able to capture teachers' strengths and skills in need of improvement. The QLE-DHH appears to hold promise for use in both research and teacher preparation programs.

Group education on the low FODMAP diet improves gastrointestinal symptoms but neither anxiety or depression in irritable bowel syndrome.

BACKGROUND: The low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet is an effective dietitian-led treatment for irritable bowel syndrome (IBS). An increasing demand of IBS patient referrals has warranted group FODMAP education led by specialist dietitians. Psychological co-morbidities are common in IBS, although how the low FODMAP diet influences psychological outcomes is not understood. The present study aimed to evaluate symptom related outcomes of the diet following group education and assess its effect on psychological profiles. METHODS: An observational, prospective study was conducted in 55 IBS patients who attended FODMAP Restriction and FODMAP Reintroduction group sessions. Data were collected at baseline and follow-up after FODMAP Restriction and analysed using descriptive and McNemar's tests. Primary outcome was evaluated by IBS Symptom Severity Score (IBS-SSS). Secondary psychological outcomes included anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and risk of eating disorder questionnaire (SCOFF). RESULTS: After FODMAP Restriction, 27 of 55 (54%) patients reported clinically relevant symptom improvement, as defined by a reduction in the IBS-SSS ≥50 points, whereas no differences were recorded in the proportion of patients identified with clinical anxiety (p = 1.000) or clinical depression (p = 0.375). Positively, no increased risk of an eating disorder was observed. CONCLUSIONS: The present study provides data supporting the efficacy of the low FODMAP diet in IBS patients who attended dietitian led group education settings in tertiary care. Clinically significant improvements in gastrointestinal symptoms were observed, although with no impact on clinical levels of anxiety, depression or the risk of an eating disorder.

Targeting the mitochondrial permeability transition pore for neuroprotection in a piglet model of neonatal hypoxic-ischemic encephalopathy.

Neonatal hypoxic-ischemic encephalopathy (HIE) causes significant morbidity despite treatment with therapeutic hypothermia. Mitochondrial dysfunction may drive the mechanisms underlying neuronal cell death, thereby making mitochondria prime targets for neuroprotection. The mitochondrial permeability transition pore (mPTP) is one such target within mitochondria. In adult animal models, mPTP inhibition is neuroprotective. However, evidence for mPTP inhibition in neonatal models of neurologic disease is less certain. We tested the therapeutic efficacy of the mPTP small molecule inhibitor GNX-4728 and examined the developmental presence of brain mPTP proteins for drug targeting in a neonatal piglet model of hypoxic-ischemic brain injury. Male neonatal piglets were randomized to hypoxia-ischemia (HI) or sham procedure with GNX-4728 (15 mg/kg, IV) or vehicle (saline/cyclodextrin/DMSO, IV). GNX-4728 was administered as a single dose within 5 min after resuscitation from bradycardic arrest. Normal, ischemic, and injured neurons were counted in putamen and somatosensory cortex using hematoxylin and eosin staining. In separate neonatal and juvenile pigs, western blots of putamen mitochondrial-enriched fractions were used to evaluate mitochondrial integrity and the presence of mPTP proteins. We found that a single dose of GNX-4728 did not protect putamen and cortical neurons from cell death after HI. However, loss of mitochondrial matrix integrity occurred within 6h after HI, and while mPTP components are present in the neonatal brain their levels were significantly different compared to that of a mature juvenile brain. Thus, the neonatal brain mPTP may not be a good target for current neurotherapeutic drugs that are developed based on adult mitochondria.

Multi-Parametric Evaluation of Cerebral Hemodynamics in Neonatal Piglets Using Non-Contrast-Enhanced Magnetic Resonance Imaging Methods.

BACKGROUND: Disruption of brain oxygen delivery and consumption after hypoxic-ischemic injury contributes to neonatal mortality and neurological impairment. Measuring cerebral hemodynamic parameters, including cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ), is clinically important. PURPOSE: Phase-contrast (PC), velocity-selective arterial spin labeling (VSASL), and T2 -relaxation-under-phase-contrast (TRUPC) are magnetic resonance imaging (MRI) techniques that have shown promising results in assessing cerebral hemodynamics in humans. We aimed to test their feasibility in quantifying CBF, OEF, and CMRO2 in piglets. STUDY TYPE: Prospective. ANIMAL MODEL: Ten neonatal piglets subacutely recovered from global hypoxia-ischemia (N = 2), excitotoxic brain injury (N = 6), or sham procedure (N = 2). FIELD STRENGTH/SEQUENCE: VSASL, TRUPC, and PC MRI acquired at 3.0 T. ASSESSMENT: Regional CBF was measured by VSASL. Global CBF was quantified by both PC and VSASL. TRUPC assessed OEF at the superior sagittal sinus (SSS) and internal cerebral veins (ICVs). CMRO2 was calculated from global CBF and SSS-derived OEF. End-tidal carbon dioxide (EtCO2 ) levels of the piglets were also measured. Brain damage was assessed in tissue sections postmortem by counting damaged neurons. STATISTICAL TESTS: Spearman correlations were performed to evaluate associations among CBF (by PC or VSASL), OEF, CMRO2 , EtCO2 , and the pathological neuron counts. Paired t-test was used to compare OEF at SSS with OEF at ICV. RESULTS: Global CBF was 32.1 ± 14.9 mL/100 g/minute and 30.9 ± 8.3 mL/100 g/minute for PC and VSASL, respectively, showing a significant correlation (r = 0.82, P < 0.05). OEF was 54.9 ± 8.8% at SSS and 46.1 ± 5.6% at ICV, showing a significant difference (P < 0.05). Global CMRO2 was 79.1 ± 26.2 µmol/100 g/minute and 77.2 ± 12.2 µmol/100 g/minute using PC and VSASL-derived CBF, respectively. EtCO2 correlated positively with PC-based CBF (r = 0.81, P < 0.05) but negatively with OEF at SSS (r = -0.84, P < 0.05). Relative CBF of subcortical brain regions and OEF at ICV did not significantly correlate, respectively, with the ratios of degenerating-to-total neurons (P = 0.30, P = 0.10). DATA CONCLUSION: Non-contrast MRI can quantify cerebral hemodynamic parameters in normal and brain-injured neonatal piglets. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

Neurologic effects of short-term treatment with a soluble epoxide hydrolase inhibitor after cardiac arrest in pediatric swine.

BACKGROUND: Cardiac arrest (CA) is the most common cause of acute neurologic insult in children. Many survivors have significant neurocognitive deficits at 1 year of recovery. Epoxyeicosatrienoic acids (EETs) are multifunctional endogenous lipid signaling molecules that are involved in brain pathobiology and may be therapeutically relevant. However, EETs are rapidly metabolized to less active dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH), limiting their bioavailability. We hypothesized that sEH inhibition would improve outcomes after CA in an infant swine model. Male piglets (3-4 kg, 2 weeks old) underwent hypoxic-asphyxic CA. After resuscitation, they were randomized to intravenous treatment with an sEH inhibitor (TPPU, 1 mg/kg; n = 8) or vehicle (10% poly(ethylene glycol); n = 9) administered at 30 min and 24 h after return of spontaneous circulation. Two sham-operated groups received either TPPU (n = 9) or vehicle (n = 8). Neurons were counted in hematoxylin- and eosin-stained sections from putamen and motor cortex in 4-day survivors. RESULTS: Piglets in the CA + vehicle groups had fewer neurons than sham animals in both putamen and motor cortex. However, the number of neurons after CA did not differ between vehicle- and TPPU-treated groups in either anatomic area. Further, 20% of putamen neurons in the Sham + TPPU group had abnormal morphology, with cell body attrition and nuclear condensation. TPPU treatment also did not reduce neurologic deficits. CONCLUSION: Treatment with an sEH inhibitor at 30 min and 24 h after resuscitation from asphyxic CA does not protect neurons or improve acute neurologic outcomes in piglets.

Mean Diffusivity in Striatum Correlates With Acute Neuronal Death but Not Lesser Neuronal Injury in a Pilot Study of Neonatal Piglets With Encephalopathy.

BACKGROUND: Diffusion MRI is routinely used to evaluate brain injury in neonatal encephalopathy. Although abnormal mean diffusivity (MD) is often attributed to cytotoxic edema, the specific contribution from neuronal pathology is unclear. PURPOSE: To determine whether MD from high-resolution diffusion tensor imaging (DTI) can detect variable degrees of neuronal degeneration and pathology in piglets with brain injury induced by excitotoxicity or global hypoxia-ischemia (HI) with or without overt infarction. STUDY TYPE: Prospective. ANIMAL MODEL: Excitotoxic brain injury was induced in six neonatal piglets by intrastriatal stereotaxic injection of the glutamate receptor agonist quinolinic acid (QA). Three piglets underwent global HI or a sham procedure. Piglets recovered for 20-96 hours before undergoing MRI (n = 9). FIELD STRENGTH/SEQUENCE: 3.0T MRI with DTI, T1 - and T2 -weighted imaging. ASSESSMENT: MD, fractional anisotropy (FA), and qualitative T2 injury were assessed in the putamen and caudate. The cell bodies of normal neurons, degenerating neurons (excitotoxic necrosis, ischemic necrosis, or necrosis-apoptosis cell death continuum), and injured neurons with equivocal degeneration were counted by histopathology. STATISTICAL TESTS: Spearman correlations were used to compare MD and FA to normal, degenerating, and injured neurons. T2 injury and neuron counts were evaluated by descriptive analysis. RESULTS: The QA insult generated titratable levels of neuronal pathology. In QA, HI, and sham piglets, lower MD correlated with higher ratios of degenerating-to-total neurons (P < 0.05), lower ratios of normal-to-total neurons (P < 0.05), and greater numbers of degenerating neurons (P < 0.05). MD did not correlate with abnormal neurons exhibiting nascent injury (P > 0.99). Neuron counts were not related to FA (P > 0.30) or to qualitative injury from T2 -weighted MRI. DATA CONCLUSION: MD is more accurate than FA for detecting neuronal degeneration and loss during acute recovery from neonatal excitotoxic and HI brain injury. MD does not reliably detect nonfulminant, nascent, and potentially reversible neuronal injury. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2 J. Magn. Reson. Imaging 2020;52:1216-1226.

The Relation Between Dialect Density and the Codevelopment of Writing and Reading in African American Children.

The purpose of this longitudinal study was to examine the influence of spoken dialect density on writing and on the codevelopment of reading and writing in African American English-speaking (AAE) children from first through fifth grades. The sample included 869 students, ranging in age from 5.8 to 12.5 years. Results indicated that dialect density had a negative influence concurrently and longitudinally on reading and writing in AAE-speaking children. High dialect users tended to have weak reading and writing skills and heavier dialect density slowed growth in reading and writing. However, this effect was moderated by the effects of reading and writing on each other. Reading had a facilitative effect on writing even in the presence of heavy dialect use.

Language and Reading Progress of Young Deaf and Hard-of-Hearing Children.

We examined the language and reading progress of 336 young DHH children in kindergarten, first and second grades. Trained assessors tested children's language, reading, and spoken and fingerspelled phonological awareness in the fall and spring of the school year. Children were divided into groups based on their auditory access and classroom communication: a spoken-only group (n = 101), a sign-only group (n = 131), and a bimodal group (n = 104). Overall, children showed delays in language and reading compared to norms established for hearing children. For language, vocabulary standard scores were higher than for English syntax. Although delayed in language, children made expected gains based on hearing norms from kindergarten to second grade. Reading scores declined from kindergarten to second grade. Spoken-only and bimodal children had similar word reading and reading comprehension abilities and higher scores than sign-only children. Spoken-only children had better spoken phonological awareness and nonword reading skills than the other two groups. The sign-only and bimodal groups made similar and significant gains in ASL syntax and fingerspelling phonological awareness.

Facilitating the adherence journey of children, adolescents, and adults on long-term growth hormone therapy.

Growth hormone deficiency in children and adolescents is treated with recombinant growth hormone injections, with the aim of helping patients reach a final height that falls within their genetically predicted adult height. While this treatment is very successful, overcoming issues of patient adherence is a challenge at each stage of the treatment journey, from early childhood to adulthood. An advisory board of senior endocrine nurses convened to discuss what strategies and tools work well in achieving adherence, and the best practices they identified-including the key strategies of choice, information, teamwork, and support-were presented at the 2016 meeting of The Endocrine Society. The advisers agreed that key steps to improve adherence include: patient/carer-centric endocrine nursing services, good-quality education and support, patient autonomy (where possible), broader treatment choice (in terms of device and self-injection), optimal follow-up from childhood to adulthood, and sharing of best practices.

Hypoxia-Ischemia and Hypothermia Independently and Interactively Affect Neuronal Pathology in Neonatal Piglets with Short-Term Recovery.

Therapeutic hypothermia is the standard of clinical care for moderate neonatal hypoxic-ischemic encephalopathy. We investigated the independent and interactive effects of hypoxia-ischemia (HI) and temperature on neuronal survival and injury in basal ganglia and cerebral cortex in neonatal piglets. Male piglets were randomized to receive HI injury or sham procedure followed by 29 h of normothermia, sustained hypothermia induced at 2 h, or hypothermia with rewarming during fentanyl-nitrous oxide anesthesia. Viable and injured neurons and apoptotic profiles were counted in the anterior putamen, posterior putamen, and motor cortex at 29 h after HI injury or sham procedure. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) identified genomic DNA fragmentation to confirm cell death. Though hypothermia after HI preserved viable neurons in the anterior and posterior putamen, hypothermia prevented neuronal injury in only the anterior putamen. Hypothermia initiated 2 h after injury did not protect against apoptotic cell death in either the putamen or motor cortex, and rewarming from hypothermia was associated with increased apoptosis in the motor cortex. In non-HI shams, sustained hypothermia during anesthesia was associated with neuronal injury and corresponding viable neuron loss in the anterior putamen and motor cortex. TUNEL confirmed increased neurodegeneration in the putamen of hypothermic shams. Anesthetized, normothermic shams did not show abnormal neuronal cytopathology in the putamen or motor cortex, thereby demonstrating minimal contribution of the anesthetic regimen to neuronal injury during normothermia. We conclude that the efficacy of hypothermic protection after HI is region specific and that hypothermia during anesthesia in the absence of HI may be associated with neuronal injury in the developing brain. Studies examining the potential interactions between hypothermia and anesthesia, as well as with longer durations of hypothermia, are needed.

2D Molecular Superconductor to Insulator Transition in the ß''-(BEDT-TTF)2[(H2O)(NH4)2M(C2O4)3]·18-crown-6 Series (M = Rh, Cr, Ru, Ir).

The series of salts ß''-(BEDT-TTF)2[(H2O)(NH4)2M(C2O4)3]·18-crown-6 show ambient-pressure superconductivity when M = Cr, Rh. Evidence indicates that the previously reported Cr and Rh salts show a bulk Berezinski-Kosterlitz-Thouless superconducting transition. The isostructural ruthenium and iridium salts are reported here. The Ir salt represents the first radical-cation salt to contain a 5d tris(oxalato)metalate anion. The Ru and Ir salts do not show superconductivity but instead undergo a broad chemically induced metal to insulator transition at 155 K for ruthenium and at 100 K for iridium. The c axes of the Ru and Ir salts are much shorter than those of the Rh and Cr salts. Thus, the more stable metallic state of the Cr and Rh salts is associated with the more strongly 2D electronic systems. The different low-temperature behavior of the Ru and Ir salts, which exhibit a smaller interlayer spacing, could originate from a structural change in the anionic layer which thus can be easily transmitted to the donor layers and generate a localized state. However, another possibility is that it originates from Berezinski-Kosterlitz-Thouless effects.

Individual Differences in Addition Strategy Choice: A Psychometric Evaluation.

The Strategy Choice Model (SCM) is a highly influential theory of human problem-solving. One strength of this theory is the allowance for both item and person variance to contribute to problem-solving outcomes, but this central tenet of the model has not been empirically tested. Explanatory Item Response Theory (EIRT) provides an ideal approach to testing this core feature of SCM, as it allows for simultaneous estimation of both item and person effects on problem-solving outcomes. We used EIRT to test and confirm this central tenet of the SCM for adolescents' (n = 376) solving of addition problems. The approach also allowed us to identify the strategy choices of adolescents who still struggle with basic arithmetic. The synthesis of SCM theory and EIRT modeling has implications for more fully investigating the sources of individual differences in students' problem solving, and for identifying problem-solving patterns associated with poor academic achievement.

Modality and Interrelations Among Language, Reading, Spoken Phonological Awareness, and Fingerspelling.

Better understanding of the mechanisms underlying early reading skills can lead to improved interventions. Hence, the purpose of this study was to examine multivariate associations among reading, language, spoken phonological awareness, and fingerspelling abilities for three groups of deaf and hard-of-hearing (DHH) beginning readers: those who were acquiring only spoken English (n = 101), those who were visual learners and acquiring sign (n = 131), and those who were acquiring both (n = 104). Children were enrolled in kindergarten, first, or second grade. Within-group and between-group confirmatory factor analysis showed that there were both similarities and differences in the abilities that underlie reading in these three groups. For all groups, reading abilities related to both language and the ability to manipulate the sublexical features of words. However, the groups differed on whether these constructs were based on visual or spoken language. Our results suggest that there are alternative means to learning to read. Whereas all DHH children learning to read rely on the same fundamental abilities of language and phonological processing, the modality, levels, and relations among these abilities differ.

Delayed injury of hippocampal interneurons after neonatal hypoxia-ischemia and therapeutic hypothermia in a murine model.

Delayed hippocampal injury and memory impairments follow neonatal hypoxia-ischemia (HI) despite the use of therapeutic hypothermia (TH). Death of hippocampal pyramidal cells occurs acutely after HI, but characterization of delayed cell death and injury of interneurons (INs) is unknown. We hypothesize that injury of INs after HI is: (i) asynchronous to that of pyramidal cells, (ii) independent of injury severity, and (iii) unresponsive to TH. HI was induced in C57BL6 mice at p10 with unilateral right carotid ligation and 45 min of hypoxia (FiO2 = 0.08). Mice were randomized to normothermia (36 °C, NT) or TH (31 °C) for 4 hr after HI and anesthesia-exposed shams were use as controls. Brains were studied at 24 hr (p11) or 8 days (p18) after HI. Vglut1, GAD65/67, PSD95, parvalbumin (PV) and calbindin-1 (Calb1) were measured. Cell death was assessed using cresyl violet staining and TUNEL assay. Hippocampal atrophy and astroglyosis at p18 were used to assess injury severity and to correlate with number of PV + INs. VGlut1 level decreased by 30% at 24 hr after HI, while GAD65/67 level decreased by ∼50% in forebrain 8 days after HI, a decrease localized in CA1 and CA3. PSD95 levels decreased in forebrain by 65% at 24 hr after HI and remained low 8 days after HI. PV + INs increased in numbers (per mm2 ) and branching between p11 and p18 in sham mice but not in NT and TH mice, resulting in 21-52% fewer PV + INs in injured mice at p18. Calb1 protein and mRNA were also reduced in HI injured mice at p18. At p18, somatodendritic attrition of INs was evident in all injured mice without evidence of cell death. Neither hippocampal atrophy nor astroglyosis correlated with the number of PV + INs at p18. Thus, HI exposure has long lasting effects in the hippocampus impairing the development of the GABAergic system with only partial protection by TH independent of the degree of hippocampal injury. © 2018 Wiley Periodicals, Inc.

New enrollment under the affordable care act: leading the way for community health centers in Southern California.

BACKGROUND: The Affordable Care Act (ACA) has improved healthcare access in the community health centers that have played a critical role in enrolling low income and minority patients. This study examined the ACA enrollment for one of the largest federally qualified community health centers in the country. METHODS: An exploratory sequential mixed method study was used as the main qualitative and quantitative approach for this study. Key stakeholders (n = 6) were interviewed as part of the qualitative component, and information about barriers and best practices were acquired. As part of the quantitative analysis, we examined cross-sectional data among 59,272 AltaMed enrollees in 2013-2015. We analyzed data on age, gender, language, ethnicity, and enrollment periods. The interviews were conducted first and followed by the data analysis. RESULTS: AltaMed was the top enroller of patients in ACA insurance plans in California (2013-14 and 2014-15) through the state exchange and Medicaid expansion. Using key stakeholder interviews, 5 main barriers were identified and 5 innovative solutions that allowed AltaMed to enroll people into the state exchange and Medicaid expansion. Barriers to enrollment included training, new workflows, and enrollment of Young Invincibles, and these enrollment barriers were overcome with community health workers. CONCLUSION: Enrollment barriers were overcome through AltaMed's community-based approach and long term community partnerships.