Distinct contributions of attention and working memory to visual statistical learning and ensemble processing

The brain exploits redundancies in the environment to efficiently represent the complexity of the visual world. One example of this is ensemble processing, which provides a statistical summary of elements within a set (e.g., mean size). Another is statistical learning, which involves the encoding of stable spatial or temporal relationships between objects. It has been suggested that ensemble processing over arrays of oriented lines disrupts statistical learning of structure within the arrays (Zhao, Ngo, McKendrick, & Turk-Browne, 2011). Here we asked whether ensemble processing and statistical learning are mutually incompatible, or whether this disruption might occur because ensemble processing encourages participants to process the stimulus arrays in a way that impedes statistical learning. In Experiment 1, we replicated Zhao and colleagues' finding that ensemble processing disrupts statistical learning. In Experiments 2 and 3, we found that statistical learning was unimpaired by ensemble processing when task demands necessitated (a) focal attention to individual items within the stimulus arrays and (b) the retention of individual items in working memory. Together, these results are consistent with an account suggesting that ensemble processing and statistical learning can operate over the same stimuli given appropriate stimulus processing demands during exposure to regularities

Healthcare utilization and spending by children with cancer on Medicaid

BackgroundChildren with cancer are a unique patient population with high resource, complex healthcare needs. Understanding their healthcare utilization could highlight areas for care optimization.ProcedureWe performed a retrospective, cross‐sectional analysis of the 2014 Truven Marketscan Medicaid Database to explore clinical attributes, utilization, and spending among children with cancer who were Medicaid enrollees. Eligible patients included children (ages 0–18 years) with cancer (Clinical Risk Group 8). Healthcare utilization and spending (per member per month, PMPM) were assessed overall and across specific healthcare services.ResultsChildren with cancer (n = 5,405) represent less than 1% of the 1,516,457 children with medical complexity in the dataset. Children with cancer had high services use: laboratory/radiographic testing (93.0%), outpatient specialty care (83.4%), outpatient therapy/treatment (53.4%), emergency department (43.7%), hospitalization (31.5%), home healthcare (9.5%). PMPM spending for children with cancer was $3,706 overall and$2,323 for hospital care.ConclusionChildren with cancer have high healthcare resource use and spending. Differences in geographic distribution of services for children with cancer and the trajectory of spending over the course of therapy are areas for future investigation aimed at lowering costs of care without compromising on health outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138316/1/pbc26569_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138316/2/pbc26569.pd

Visual attentional load influences plasticity in the human motor cortex

Neural plasticity plays a critical role in learning, memory, and recovery from injury to the nervous system. Although much is known about the physical and physiological determinants of plasticity, little is known about the influence of cognitive factors. In this study, we investigated whether selective attention plays a role in modifying changes in neural excitability reflecting long-term potentiation (LTP)like plasticity. We induced LTP-like effects in the hand area of the human motor cortex using transcranial magnetic stimulation (TMS). During the induction of plasticity, participants engaged in a visual detection task with either low or high attentional demands. Changes in neural excitability were assessed by measuring motor-evoked potentials in a small hand muscle before and after the TMS procedures. In separate experiments plasticity was induced either by paired associative stimulation (PAS) or intermittent theta-burst stimulation (iTBS). Because these procedures induce different forms of LTP-like effects, they allowed us to investigate the generality of any attentional influence on plasticity. In both experiments reliable changes in motor cortex excitability were evident under low-load conditions, but this effect was eliminated under high-attentional load. In a third experiment we investigated whether the attentional task was associated with ongoing changes in the excitability of motor cortex, but found no difference in evoked potentials across the levels of attentional load. Our findings indicate that in addition to their role in modifying sensory processing, mechanisms of attention can also be a potent modulator of cortical plasticity

Insulin Resistance and Metabolic Hepatocarcinogenesis with Parent-of-Origin Effects in A×B Mice

Insulin resistance is a defining feature of metabolic syndrome and type 2 diabetes mellitus but also may occur independently of these conditions. Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of these disorders, increases the risk of hepatocellular carcinoma (HCC). However, mechanisms linking hyperinsulinemia to NAFLD and HCC require clarification. We describe a novel model of primary insulin resistance and HCC with strong parent-of-origin effects. Male AB6F1 (A/JCr dam × C57BL/6 sire) but not B6AF1 (B6 dam × A/J sire) mice developed spontaneous insulin resistance, NAFLD, and HCC without obesity or diabetes. A survey of mitochondrial, imprinted, and sex-linked traits revealed modest associations with X-linked genes. However, a diet-induced obesity study, including B6.A chromosome substitution–strain (consomic) mice, showed no segregation by sex chromosome. Thus, parent-of-origin effects were specified within the autosomal genome. Next, we interrogated mechanisms of insulin-associated hepatocarcinogenesis. Steatotic hepatocytes exhibited adipogenic transition characterized by vacuolar metaplasia and up-regulation of vimentin, adipsin, fatty acid translocase (CD36), peroxisome proliferator–activated receptor-γ, and related products. This profile was largely recapitulated in insulin-supplemented primary mouse hepatocyte cultures. Importantly, pyruvate kinase M2, a fetal anabolic enzyme implicated in the Warburg effect, was activated by insulin in vivo and in vitro. Thus, our study reveals parent-of-origin effects in heritable insulin resistance, implicating adipogenic transition with acquired anabolic metabolism in the progression from NAFLD to HCC.National Institutes of Health (U.S.) (NIH grant AA016563)National Institutes of Health (U.S.) (NIH grant CA067529)National Institutes of Health (U.S.) (NIH grant P01CA0267)National Institutes of Health (U.S.) (NIH grant P30ES02109)National Institutes of Health (U.S.) (NIH grant RR007036)National Institutes of Health (U.S.) (NIH grant CA158661)National Institutes of Health (U.S.) (NIH grant CA016086

Brand switching and toxic chemicals in cigarette smoke: A national study

US law requires disclosure of quantities of toxic chemicals (constituents) in cigarette smoke by brand and sub-brand. This information may drive smokers to switch to cigarettes with lower chemical quantities, under the misperception that doing so can reduce health risk. We sought to understand past brand-switching behavior and whether learning about specific chemicals in cigarette smoke increases susceptibility to brand switching

Effectiveness of a structured, framework-based approach to implementation: the Researching Effective Approaches to Cleaning in Hospitals (REACH) Trial

BACKGROUND: Implementing sustainable practice change in hospital cleaning has proven to be an ongoing challenge in reducing healthcare associated infections. The purpose of this study was to develop a reliable framework-based approach to implement and quantitatively evaluate the implementation of evidence-based practice change in hospital cleaning. DESIGN/METHODS: The Researching Effective Approaches to Cleaning in Hospitals (REACH) trial was a pragmatic, stepped-wedge randomised trial of an environmental cleaning bundle implemented in 11 Australian hospitals from 2016 to 2017. Using a structured multi-step approach, we adapted the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to support rigorous and tailored implementation of the cleaning bundle intervention in eleven diverse and complex settings. To evaluate the effectiveness of this strategy we examined post-intervention cleaning bundle alignment calculated as a score (an implementation measure) and cleaning performance audit data collected using ultraviolet (UV) gel markers (an outcome measure). RESULTS: We successfully implemented the bundle and observed improvements in cleaning practice and performance, regardless of hospital size, intervention duration and contextual issues such as staff and organisational readiness at baseline. There was a positive association between bundle alignment scores and cleaning performance at baseline. This diminished over the duration of the intervention, as hospitals with lower baseline scores were able to implement practice change successfully. CONCLUSION: Using a structured framework-based approach allows for pragmatic and successful implementation of clinical trials across diverse settings, and assists with quantitative evaluation of practice change. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry ACTRN12615000325505, registered on 4 September 2015

Gpr37 Modulates Progenitor Cell Dynamics in a Mouse Model of Ischemic Stroke

The generation of neural stem and progenitor cells following injury is critical for the function of the central nervous system, but the molecular mechanisms modulating this response remain largely unknown. We have previously identified the G protein-coupled receptor 37 (GPR37) as a modulator of ischemic damage in a mouse model of stroke. Here we demonstrate that GPR37 functions as a critical negative regulator of progenitor cell dynamics and gliosis following ischemic injury. In the central nervous system, GPR37 is enriched in mature oligodendrocytes, but following injury we have found that its expression is dramatically increased within a population of Sox2-positive progenitor cells. Moreover, the genetic deletion of GPR37 did not alter the number of mature oligodendrocytes following injury but did markedly increase the number of both progenitor cells and injury-induced Olig2-expressing glia. Alterations in the glial environment were further evidenced by the decreased activation of oligodendrocyte precursor cells. These data reveal that GPR37 regulates the response of progenitor cells to ischemic injury and provides new perspectives into the potential for manipulating endogenous progenitor cells following stroke

Gpr37l1 Modulates Seizure Susceptibility: Evidence from Mouse Studies and Analyses of a Human Gpr37l1 Variant

Progressive myoclonus epilepsies (PMEs) are disorders characterized by myoclonic and generalized seizures with progressive neurological deterioration. While several genetic causes for PMEs have been identified, the underlying causes remain unknown for a substantial portion of cases. Here we describe several affected individuals from a large, consanguineous family presenting with a novel PME in which symptoms begin in adolescence and result in death by early adulthood. Whole exome analyses revealed that affected individuals have a homozygous variant in GPR37L1 (c.1047G \u3e T [Lys349Asn]), an orphan G protein-coupled receptor (GPCR) expressed predominantly in the brain. In vitro studies demonstrated that the K349N substitution in Gpr37L1 did not grossly alter receptor expression, surface trafficking or constitutive signaling in transfected cells. However, in vivo studies revealed that a complete loss of Gpr37L1 function in mice results in increased seizure susceptibility. Mice lacking the related receptor Gpr37 also exhibited an increase in seizure susceptibility, while genetic deletion of both receptors resulted in an even more dramatic increase in vulnerability to seizures. These findings provide evidence linking GPR37L1 and GPR37 to seizure etiology and demonstrate an association between a GPR37L1 variant and a novel progressive myoclonus epilepsy

Risk of cerebrovascular disease among 13,457 five‐year survivors of childhood cancer: a population based cohort study

Survivors of childhood cancer treated with cranial irradiation are at risk of cerebrovascular disease (CVD), but the risks beyond age 50 are unknown. In all, 13457 survivors of childhood cancer included in the population‐based British Childhood Cancer Survivor Study cohort were linked to Hospital Episode Statistics data for England. Risk of CVD related hospitalisation was quantified by standardised hospitalisation ratios (SHRs), absolute excess risks and cumulative incidence. Overall, 315 (2.3%) survivors had been hospitalised at least once for CVD with a 4‐fold risk compared to that expected (95% confidence interval [CI]: 3.7‐4.3). Survivors of a central nervous system (CNS) tumour and leukaemia treated with cranial irradiation were at greatest risk of CVD (SHR = 15.6, 95% CI: 14.0‐17.4; SHR = 5.4; 95% CI: 4.5‐6.5, respectively). Beyond age 60, on average, 3.1% of CNS tumour survivors treated with cranial irradiation were hospitalised annually for CVD (0.4% general population). Cumulative incidence of CVD increased from 16.0% at age 50 to 26.0% at age 65 (general population: 1.4‐4.2%). In conclusion, among CNS tumour survivors treated with cranial irradiation, the risk of CVD continues to increase substantially beyond age 50 up to at least age 65. Such survivors should be: counselled regarding this risk; regularly monitored for hypertension, dyslipidaemia and diabetes; advised on life‐style risk behaviours. Future research should include the recall for counselling and brain MRI to identify subgroups that could benefit from pharmacological or surgical intervention and establishment of a case‐control study to comprehensively determine risk‐factors for CVD

When Will Adolescents Tell Someone About Dating Violence Victimization?

This study examined factors that influence help-seeking among a diverse sample of adolescents who experienced dating violence. A sample of 57 high school students in an urban community reported on the prevalence and characteristics of dating violence in their relationships. Someone observing a dating violence incident and a survivor’s attaching an emotional meaning to the event significantly influenced adolescents to talk to someone. When dating violence occurred in isolation, survivors were more likely to receive no support from others in the aftermath of the incident. Differences between boys’ and girls’ help-seeking and implications for dating violence intervention and prevention programming are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90887/1/Black-Tolman-Callahan-Saunders- Weisz- 2008-When will adolescents tell someone about dating violence VAW.pd