bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent Trends in Income, Racial, and Ethnic School Readiness Gaps at Kindergarten Entry
Authors: Reardon Sean F. , Portilla Ximena A.
Published: August 2016

Academic achievement gaps between high- and low-income students born in the 1990s were much larger than between cohorts born two decades earlier. Racial/ethnic achievement gaps declined during the same period. To determine whether these two trends have continued in more recent cohorts, we examine trends in several dimensions of school readiness, including academic achievement, self-control, externalizing behavior, and a measure of students’ approaches to learning, for cohorts born from the early 1990s to the 2000–2010 midperiod. We use data from nationally representative samples of kindergarteners (ages 5–6) in 1998 (  n = 20,220), 2006 (  n = 6,600), and 2010 (  n = 16,980) to estimate trends in racial/ethnic and income school readiness gaps. We find that readiness gaps narrowed modestly from 1998 to 2010, particularly between high- and low-income students and between White and Hispanic students.
A Community Health Coach–Delivered Mental Wellness Intervention: Using Mind–Body Bridging to Reduce Health Disparities in Diverse Communities
Authors: Gren Lisa H. , Jaggi Rachel , Landward Richard , Benson L. Scott , Frost Caren J.
Published: August 2016

Research has shown that members of racial and ethnic minority groups experience greater cumulative stress burden. Because a high cumulative stress burden increases the likelihood of mental health disorders, community health coaches trained in techniques to help community members manage stress more effectively could be an important step toward improving mental health in minority populations. As a pilot project, we invited individuals from organizations representing five minority populations to receive training in Mind–Body Bridging (MBB), a mindfulness approach that teaches skills to calm the mind and relax the body. Participants included community health coaches, organizational leaders, and community members. Surveys of quality of life and self-efficacy were conducted at the beginning and completion of training, and at 9 months following completion. A focus group was also held at training completion to solicit perceptions of the usefulness of MBB among the participants’ respective communities. Eleven participants completed the training. Overall, participants reported regular use of MBB techniques to manage their own stress and showed some moderate improvements in both quality of life and self-efficacy. MBB was generally perceived to be a useful tool for community health coaches, with perceived strengths including the ease of teaching it to others and increased ability to empower community members to handle their own problems more efficiently. Next steps include longitudinal tracking of the coaches’ use of MBB as a coaching tool and monitoring outcomes among the community members receiving the coaching.
Yield of angiographic examinations in isolated intraventricular hemorrhage: A case series and systematic review of the literature
Authors: Hilkens Nina A , van Asch Charlotte JJ , Rinkel Gabriel JE , Klijn Catharina JM
Published: August 2016

Background

It is unknown which patients with non-traumatic isolated intraventricular hemorrhage should undergo angiographic imaging to detect an underlying macrovascular cause and which modality has the highest yield. We studied yield of angiographic examinations in patients with isolated intraventricular hemorrhage.

Methods

We reviewed medical records of patients with intraventricular hemorrhage admitted to the University Medical Center Utrecht between 2002 and 2012. We searched PubMed and Embase for studies on angiographic examinations in intraventricular hemorrhage until January 2014. We calculated yield of angiographic imaging and investigated influence of age, hypertension and anticoagulant use with meta-regression analysis.

Results

We identified 39 patients of whom 30 underwent an angiographic study. CTA suggested a macrovascular abnormality in nine patients, which was confirmed by DSA in seven. In the literature, we found 16 studies describing 209 patients. Pooled analysis showed a yield of 58% for DSA (95% CI 48–68%; 147 patients). One small study described the yield of CTA or MRA (0%; 4 patients). Yield of angiographic imaging decreased with increasing age (−2.6%; −5.0 to −0.2 per year increase) but was not affected by history of hypertension (−8.3%; −80.8 to 64.2) or anticoagulant use (−47.1%; −110.3 to 16.1).

Conclusion

The reported yield of DSA in isolated intraventricular hemorrhage is around 50% but varies considerably, probably due to differences in clinical judgment on the need for angiography performance. The yield is higher in younger patients but based on the available data, it is not possible to set age or other criteria for patients in whom DSA can be safely omitted.
Impact of pre-stroke sulphonylurea and metformin use on mortality of intracerebral haemorrhage
Authors: Wu Teddy Y , Campbell Bruce CV , Strbian Daniel , Yassi Nawaf , Putaala Jukka , Tatlisumak Turgut , Davis Stephen M , Meretoja Atte ,   on behalf of the VISTA-ICH Collaboration
Published: August 2016

Introduction

Few proven therapies for intracerebral haemorrhage exist. Preliminary observational evidence suggests that sulphonylurea and metformin may be protective in ischaemic stroke. We assessed the association of pre-intracerebral haemorrhage sulphonylurea and metformin use on outcome in diabetic patients.

Methods

We merged datasets from the consecutive single-centre Helsinki ICH Study, the intracerebral haemorrhage arm of the Virtual International Stroke Trials Archive (VISTA-ICH) and the Royal Melbourne Hospital ICH Study. Logistic regression adjusting for known predictors of intracerebral haemorrhage outcome (age, sex, baseline Glasgow Coma Scale, National Institutes of Health Stroke Scale, intracerebral haemorrhage volume, infratentorial location, intraventricular extension, and pre-intracerebral haemorrhage warfarin use) estimated the association of metformin and sulphonylurea with all-cause 90-day mortality.

Results

From a dataset of 2404 consecutive intracerebral haemorrhage patients, we included 374 (16%) patients with diabetes. Of these, 113 (30%) died by 90 days. Metformin was used in 148 (40%) patients and sulphonylurea in 115 (31%) patients at intracerebral haemorrhage onset. After adjusting for baseline characteristics, metformin use was associated with lower 90-day mortality (OR 0.51; 95% CI 0.26–0.97; p = 0.041) irrespective of whether the drug was continued or not during the admission, while sulphonylurea use was not associated with mortality (OR 0.96; 95% CI 0.49–1.88; p = 0.906). Haematoma location or evacuation did not modify the association between metformin and mortality; neither did adding insulin use, baseline glucose and serum creatinine into the model (OR 0.50; 95% CI 0.25–0.99; p = 0.047).

Conclusion

Pre-intracerebral haemorrhage metformin use was associated with improved outcome in diabetic intracerebral haemorrhage patients. Our results generate hypotheses which after further validation could be tested in clinical trials.
Early Sonographic Diagnosis of Emphysematous Cholecystitis Successfully Treated With Antibiotics
Authors: Tseng Joseph James , Jeffrey R. Brooke
Published: August 2016

Emphysematous cholecystitis (EC) is an uncommon form of acute cholecystitis, caused by secondary infection of the gallbladder wall with gas-forming organisms. The mortality rate of EC is as high as 25% due to complications such as gangrene, gallbladder perforation, pericholecystic abscess, and bile peritonitis. Traditionally, prompt emergency surgical intervention with open cholecystectomy is recommended for EC treatment. This case study of EC was diagnosed at an early stage with sonography and computed tomography and successfully treated by antibiotic treatment alone without surgery. With characteristic findings on sonography such as echogenic reflectors with posterior shadowing, EC is an important entity for sonographers to be able to identify. In the future as imaging with sonography and CT affords earlier diagnosis of EC, antibiotic therapy might be considered for some patients, but more evidence is needed to obtain the same outcome as this particular case.
Chemotaxis-driven disease-site targeting of therapeutic adult stem cells in dystrophic epidermolysis bullosa
Authors: Alexeev Vitali , Donahue Adele , Uitto Jouni , Igoucheva Olga
Published: August 2016

Background

Dystrophic epidermolysis bullosa (DEB), a rare genodermatosis, is characterized by the formation of intra-epidermal blistering and the development of chronic nonhealing skin wounds. Recently, attempts have been made to develop cell-based therapies for this currently intractable disorder. The molecular mechanisms that govern directional migration of the adult stem cells, allowing their efficient and controlled homing to the skin affected with DEB, are poorly understood. The key mechanism that regulates recruitment of leukocytes and progenitor stem cells to distal anatomical tissues affected with disease is chemotaxis, which depends on the signaling molecules, chemokines, and acts primarily as part of the host defense and repair mechanism.

Methods

Comprehensive proteomic screening of chemokines in the blister fluids of DEB-affected mice was conducted to define the inflammatory and immune activities, thus providing potential to examine local biological mechanisms and define the protein signature within lesional skin as a potential marker of disease activity. Also, the therapeutic relevance of identified chemotactic pathways was investigated in vivo, providing a basis for future clinical investigations.

Results

Assessment of blister fluid-derived chemokines showed a persistent presence of several chemotactic molecules, including CXCL1 + 2 and CXCL5. The majority of blister-originated chemotactic signals were associated with preferential recruitment of CD45+CXCR2+ and CD11b+CXCR2+ leukocytes. Systemic transplantation of an enriched CXCR2 population of mouse adipose-derived stem cells (mADSC) into DEB-affected mice demonstrated effective recruitment of cells to the blistering skin under the influence of blister-derived ligands and deposition of therapeutic type VII collagen.

Conclusions

Collectively, these studies demonstrate that recruitment of mADSC into DEB skin is tightly controlled by disease-site chemotactic activities and suggest a potential mechanism for effective application of therapeutic stem cells for DEB.
Leukocyte-borne α(1,3)-fucose is a negative regulator of β2-integrin-dependent recruitment in lung inflammation
Authors: Buffone Alexander , Nasirikenari Mehrab , Manhardt Charles T , Lugade Amit , Bogner Paul N , Sackstein Robert , Thanavala Yasmin , Neelamegham Sriram , Lau Joseph T Y
Published: August 2016

Leukocyte recruitment in inflammation is a multistep, sequential cascade where the initial step is the selectin-dependent tethering, followed by the formation of firmer integrin-mediated adhesive forces leading to extravasation. The α(1,3)-fucose-containing sialyl-Lewis X (sLeX) is the archetypical ligand on leukocyte surfaces mediating selectin interactions. Canonically, disruption of α(1,3)-fucose formation ablates selectin-mediated adhesion, dramatically reducing trafficking. We report a paradoxical response to α(1,3)-fucose deficiency in which the loss exacerbated rather than attenuated leukocyte recruitment in a murine model of acute airway inflammation. The architecture of the capillary-dominated vasculature in the lung minimized the importance of the selectin dependent step, and we observed that α(1,3)-fucose deficiency augmented CXCR2-mediated Rap1-GTP signaling to enhance the β2-integrin-ICAM-1-binding axis. The data disclose a previously unknown function for α(1,3)-fucose, in which this structure negatively regulates the integrin activation step in leukocyte recruitment.
STAT6 inhibitory peptide given during RSV infection of neonatal mice reduces exacerbated airway responses upon adult reinfection
Authors: Srinivasa Bharat T , Restori Katherine H , Shan Jichuan , Cyr Louis , Xing Li , Lee Soojin , Ward Brian J , Fixman Elizabeth D
Published: August 2016

Respiratory syncytial virus (RSV)-related hospitalization during infancy is strongly associated with the subsequent development of asthma. Early life RSV infection results in a Th2-biased immune response, which is also typical of asthma. Murine models of neonatal RSV infection have been developed to examine the possible contribution of RSV-driven Th2 responses to the development of airway hyper-responsiveness later in childhood. We have investigated the ability of a cell-penetrating STAT6 inhibitory peptide (STAT6-IP), when delivered selectively during neonatal RSV infection, to modify pathogenesis induced upon secondary RSV reinfection of adults 6 wk later. Neonatal STAT6-IP treatment inhibited the development of airway hyper-responsiveness (AHR) and significantly reduced lung eosinophilia and collagen deposition in adult mice following RSV reinfection. STAT6-IP-treated, RSV-infected neonates had reduced levels of both IL-4 and alternatively activated macrophages (AAMs) in the lungs. Our findings suggest that targeting STAT6 activity at the time of early-life RSV infection may effectively reduce the risk of subsequent asthma development.
CMV induces expansion of highly polyfunctional CD4+ T cell subset coexpressing CD57 and CD154
Authors: Pera Alejandra , Vasudev Anusha , Tan Crystal , Kared Hassen , Solana Rafael , Larbi Anis
Published: August 2016

CD4+ T cells are essential for human CMV infection control. CMV-specific CD4+ T cells possess antiviral functions and participate in anti-CMV humoral/cellular responses. In the elderly, CMV infection impairs immunity to other viruses and has been traditionally associated with T cell senescence; however, recent results suggest that, in younger people, CMV confers immune protection against other pathogens (heterologous immunity). To shed light on this controversy, we analyzed latent CMV infection effects on the quality of young individuals’ immune response, specifically, the presence of polyfunctional T cells through an extensive phenotypic and functional characterization of the CD4+ T cell subset. CD154 expression, degranulation (CD107a), and cytokine production (IFN-γ, TNF-α, and IL-2) as well as T cell phenotype markers (CD57, CD28, and CD27) were analyzed. We demonstrate that CD4+ T cells that coexpress CD57 and CD154, which are exclusively present in CMV-positive individuals, are the most polyfunctional CD4+ subset, whereas CD4+CD27+CD28− T cells associate with lower polyfunctionality. Conversely, the frequency of CD4+CD28+ T cells correlates with higher polyfunctionality of CD4+CD57− T cells from CMV-seronegative individuals and CD4+CD57+CD154+ T cells from CMV-seropositive individuals. Thus, polyfunctionality is a property of central memory CD4+ T cells in CMV-seronegative individuals, whereas after CMV infection, polyfunctional T cells become highly differentiated, which allows efficient eradication of infections. We extend previous observations of the impact of CMV on CD8+ T cell functionality to the CD4+ T cell compartment, revealing CD57 as a polyfunctionality marker of T cells which expands after CMV infection. CD57+ T cells have been associated with inflammatory conditions, but their potential role in the response against infectious disease and vaccination should now be investigated.
Use of Aspirin and P2Y12 Response Assays in Detecting Reversal of Platelet Inhibition With Platelet Transfusion in Patients With Traumatic Brain Injury on Antiplatelet Therapy
Authors: Choi Phillip A. , Parry Phillip V. , Bauer Joshua S. , Zusman Benjamin E. , Panczykowski David M. , Puccio Ava M. , Okonkwo David O.
Published: August 2016

BACKGROUND: At present, guidelines are lacking on platelet transfusion in patients with a traumatic intracranial bleed and history of antiplatelet therapy. The aspirin and P2Y12 response unit (ARU and PRU, respectively) assays detect the effect of aspirin and P2Y12 inhibitors in the cardiac population.

OBJECTIVE: To describe the reversal of platelet inhibition after platelet transfusion using the ARU and PRU assays in patients with traumatic brain injury.

METHODS: Between 2010 and 2015, we conducted a prospective comparative cohort study of patients presenting with a positive head computed tomography and a history of antiplatelet therapy. ARU and PRU assays were performed on admission and 6 hours after transfusion, with a primary end point of detection of disinhibition after platelet transfusion.

RESULTS: One hundred seven patients were available for analysis. Seven percent of patients taking aspirin and 27% of patients taking clopidogrel were not therapeutic on admission per the ARU and PRU, respectively. After platelet transfusion, 51% of patients on any aspirin and 67% of patients on any clopidogrel failed to be reversed. ARU increased by 71 ± 76 per unit of apheresis platelets for patients taking any aspirin, and PRU increased by 48 ± 46 per unit of apheresis platelets for patients taking any clopidogrel.

CONCLUSION: A significant percentage of patients taking aspirin or clopidogrel were not therapeutic and thus would be unlikely to benefit from a platelet transfusion. In patients with measured platelet inhibition, a single platelet transfusion was not sufficient to reverse platelet inhibition in almost half.
Utility of the Aspirin and P2Y12 Response Assays to Determine the Effect of Antiplatelet Agents on Platelet Reactivity in Traumatic Brain Injury
Authors: Parry Phillip V. , Choi Phillip A. , Bauer Joshua S. , Panczykowski David M. , Puccio Ava M. , Okonkwo David O.
Published: August 2016

BACKGROUND: Premorbid antithrombotic medication may worsen intracranial injury and outcome after traumatic brain injury (TBI). Routine laboratory tests are insufficient to evaluate platelet activity.

OBJECTIVE: To profile the spectrum of platelet inhibition, as measured by aspirin and P2Y12 response unit assays, in a TBI population on antiplatelet therapy.

METHODS: This single-center, prospective cohort study included patients presenting to our institution between November 2010 and January 2015 with a clinical history of TBI. Serum platelet reactivity levels were determined immediately on admission and analyzed using the aspirin and P2Y12 response unit assays; test results were reported as aspirin response units and P2Y12 response units. We report congruence between assay results and clinical history as well as differences in assay results between types of antiplatelet therapy.

RESULTS: A sample of 317 patients was available for analysis, of which 87% had experienced mild TBI, 7% moderate, and 6% severe; the mean age was 71.5 years. The mean aspirin response units in patients with a history of any aspirin use was 456 ± 67 (range, 350-659), with 88% demonstrating therapeutic platelet inhibition. For clopidogrel, the mean P2Y12 response unit was 191 ± 70 (range, 51-351); 77% showed therapeutic response.

CONCLUSION: Rapid measurement of antiplatelet function using the aspirin and P2Y12 response assays indicated as many as one fourth of patients on antiplatelet therapy do not have platelet dysfunction. Further research is required to develop guidelines for the use of these assays to guide platelet transfusion in the setting of TBI.
Ten-Year Follow-up on Tumor Growth and Hearing in Patients Observed With an Intracanalicular Vestibular Schwannoma
Authors: Kirchmann Malene , Karnov Kirstine , Hansen Søren , Dethloff Thomas , Stangerup Sven-Eric , Caye-Thomasen Per
Published: August 2016

BACKGROUND: Reports on the natural history of tumor growth and hearing in patients with a vestibular schwannoma (VS) are almost exclusively short-term data. Long-term data are needed for comparison with results of surgery and radiotherapy.

OBJECTIVE: To report the long-term occurrence of tumor growth and hearing loss in 156 patients diagnosed with an intracanalicular VS and managed conservatively.

METHODS: In this longitudinal cohort study, diagnostic and follow-up magnetic resonance imaging and audiometry were compared.

RESULTS: After a follow-up of 9.5 years, tumor growth had occurred in 37% and growth into the cerebellopontine angle had occurred in 23% of patients. Conservative treatment failed in 15%. The pure tone average had increased from 51- to 72-dB hearing level, and the speech discrimination score (SDS) had decreased from 60% to 34%. The number of patients with good hearing (SDS > 70%) was reduced from 52% to 22%, and the number of patients with American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) class A hearing was reduced from 19% to 3%. Hearing was preserved better in patients with 100% SDS at diagnosis than in patients with even a small loss of SDS. Serviceable hearing was preserved in 34% according to AAO-HNS (class A-B) and in 58% according to the word recognition score (class I-II). Rate of hearing loss was higher in patients with growing tumors.

CONCLUSION: Tumor growth occurred in only a minority of patients diagnosed with an intracanalicular VS during 10 years of observation. The risk of hearing loss is small in patients with normal discrimination at diagnosis. Serviceable hearing is preserved spontaneously in 34% according to AAO-HNS and in 58% according to the word recognition score.
Lumbar Cerebrospinal Fluid Biomarkers of Posthemorrhagic Hydrocephalus of Prematurity: Amyloid Precursor Protein, Soluble Amyloid Precursor Protein α, and L1 Cell Adhesion Molecule
Authors: Morales Diego M. , Silver Shawgi A. , Morgan Clinton D. , Mercer Deanna , Inder Terri E. , Holtzman David M. , Wallendorf Michael J. , Rao Rakesh , McAllister James P. , Limbrick David D.
Published: August 2016

BACKGROUND: Intraventricular hemorrhage (IVH) is the most frequent, severe neurological complication of prematurity and is associated with posthemorrhagic hydrocephalus (PHH) in up to half of cases. PHH requires lifelong neurosurgical care and is associated with significant cognitive and psychomotor disability. Cerebrospinal fluid (CSF) biomarkers may provide both diagnostic information for PHH and novel insights into its pathophysiology.

OBJECTIVE: To explore the diagnostic ability of candidate CSF biomarkers for PHH.

METHODS: Concentrations of amyloid precursor protein (APP), soluble APPα (sAPPα), soluble APPβ, neural cell adhesion molecule-1 (NCAM-1), L1 cell adhesion molecule (L1CAM), tau, phosphorylated tau, and total protein (TP) were measured in lumbar CSF from neonates in 6 groups: (1) no known neurological disease (n = 33); (2) IVH grades I to II (n = 13); (3) IVH grades III to IV (n = 12); (4) PHH (n = 12); (5) ventricular enlargement without hydrocephalus (n = 10); and (6) hypoxic ischemic encephalopathy (n = 13). CSF protein levels were compared using analysis of variance, and logistic regression was performed to examine the predictive ability of each marker for PHH.

RESULTS: Lumbar CSF levels of APP, sAPPα, L1CAM, and TP were selectively increased in PHH compared with all other conditions (all P < .001). The sensitivity, specificity, and odds ratios of candidate CSF biomarkers for PHH were determined for APP, sAPPα, and L1CAM; cut points of 699, 514, and 113 ng/mL yielded odds ratios for PHH of 80.0, 200.0, and 68.75, respectively.

CONCLUSION: Lumbar CSF APP, sAPPα, L1CAM, and TP were selectively increased in PHH. These proteins, and sAPPα, in particular, hold promise as biomarkers of PHH and provide novel insight into PHH-associated neural injury and repair.
Vertically- and horizontally-transmitted memories – the fading boundaries between regeneration and inheritance in planaria
Authors: Neuhof Moran , Levin Michael , Rechavi Oded
Published: August 2016

The Weismann barrier postulates that genetic information passes only from the germline to the soma and not in reverse, thus providing an obstacle to the inheritance of acquired traits. Certain organisms such as planaria – flatworms that can reproduce through asymmetric fission – avoid the limitations of this barrier, thus blurring the distinction between the processes of inheritance and development. In this paper, we re-evaluate canonical ideas about the interaction between developmental, genetic and evolutionary processes through the lens of planaria. Biased distribution of epigenetic effects in asymmetrically produced parts of a regenerating organism could increase variation and therefore affect the species' evolution. The maintenance and fixing of somatic experiences, encoded via stable biochemical or physiological states, may contribute to evolutionary processes in the absence of classically defined generations. We discuss different mechanisms that could induce asymmetry between the two organisms that eventually develop from the regenerating parts, including one particularly fascinating source – the potential capacity of the brain to produce long-lasting epigenetic changes.
Prolyl endopeptidase is involved in the degradation of neural cell adhesion molecules in vitro
Authors: Jaako Külli , Waniek Alexander , Parik Keiti , Klimaviciusa Linda , Aonurm-Helm Anu , Noortoots Aveli , Anier Kaili , Van Elzen Roos , Gérard Melanie , Lambeir Anne-Marie , Roßner Steffen , Morawski Markus , Zharkovsky Alexander
Published: August 2016

Membrane-associated glycoprotein neural cell adhesion molecule (NCAM) and its polysialylated form (PSA-NCAM) play an important role in brain plasticity by regulating cell–cell interactions. Here, we demonstrate that the cytosolic serine protease prolyl endopeptidase (PREP) is able to regulate NCAM and PSA-NCAM. Using a SH-SY5Y neuroblastoma cell line with stable overexpression of PREP, we found a remarkable loss of PSA-NCAM, reduced levels of NCAM180 and NCAM140 protein species, and a significant increase in the NCAM immunoreactive band migrating at an apparent molecular weight of 120 kDa in PREP-overexpressing cells. Moreover, increased levels of NCAM fragments were found in the concentrated medium derived from PREP-overexpressing cells. PREP overexpression selectively induced an activation of matrix metalloproteinase-9 (MMP-9), which could be involved in the observed degradation of NCAM, as MMP-9 neutralization reduced the levels of NCAM fragments in cell culture medium. We propose that increased PREP levels promote epidermal growth factor receptor (EGFR) signaling, which in turn activates MMP-9. In conclusion, our findings provide evidence for newly-discovered roles for PREP in mechanisms regulating cellular plasticity through NCAM and PSA-NCAM.
Cdc48 and Ubx1 participate in a pathway associated with the inner nuclear membrane that governs Asi1 degradation
Authors: Pantazopoulou Marina , Boban Mirta , Foisner Roland , Ljungdahl Per O.
Published: August 2016

The nuclear envelope is a barrier comprising outer and inner membranes that separate the cytoplasm from the nucleoplasm. The two membranes have different physical characteristics and protein compositions. The processes governing the stability of inner nuclear membrane (INM) proteins are not well characterized. In Saccharomyces cerevisiae, the INM Asi1–Asi3 complex, principally composed of integral membrane proteins Asi1 and Asi3, is an E3 ubiquitin ligase. In addition to its well-documented function in endoplasmic reticulum (ER)-associated degradation, the Doa10 E3 ubiquitin ligase complex partially localizes to the INM. The Asi1–Asi3 and Doa10 complexes define independent INM-associated degradation (INMAD) pathways that target discrete sets of nuclear substrates for proteasomal degradation. Here, we report that Asi1 is rapidly turned over (t1/2≤30 min). Its turnover depends on ubiquitin-mediated degradation by nucleus-localized proteasomes, exhibiting a clear requirement for the E2 ubiquitin-conjugating enzyme Ubc7, Cue1 and the AAA ATPase Cdc48 and co-factor Ubx1. Asi1 turnover occurs largely independently of the Asi1–Asi3 or Doa10 complexes, indicating that it is subject to quality control at the INM in a manner distinct from that of the characterized INMAD pathways.
Desmin and αB-crystallin interplay in the maintenance of mitochondrial homeostasis and cardiomyocyte survival
Authors: Diokmetzidou Antigoni , Soumaka Elisavet , Kloukina Ismini , Tsikitis Mary , Makridakis Manousos , Varela Aimilia , Davos Constantinos H. , Georgopoulos Spiros , Anesti Vasiliki , Vlahou Antonia , Capetanaki Yassemi
Published: August 2016

The association of desmin with the α-crystallin Β-chain (αΒ-crystallin; encoded by CRYAB), and the fact that mutations in either one of them leads to heart failure in humans and mice, suggests a potential compensatory interplay between the two in cardioprotection. To address this hypothesis, we investigated the consequences of αΒ-crystallin overexpression in the desmin-deficient (Des−/−) mouse model, which possesses a combination of the pathologies found in most cardiomyopathies, with mitochondrial defects as a hallmark. We demonstrated that cardiac-specific αΒ-crystallin overexpression ameliorates all these defects and improves cardiac function to almost wild-type levels. Protection by αΒ-crystallin overexpression is linked to maintenance of proper mitochondrial protein levels, inhibition of abnormal mitochondrial permeability transition pore activation and maintenance of mitochondrial membrane potential (Δψm). Furthermore, we found that both desmin and αΒ-crystallin are localized at sarcoplasmic reticulum (SR)–mitochondria-associated membranes (MAMs), where they interact with VDAC, Mic60 – the core component of mitochondrial contact site and cristae organizing system (MICOS) complex – and ATP synthase, suggesting that these associations could be crucial in mitoprotection at different levels.
Destined for disadvantage
Authors: Allingham Sue
Published: August 2016

There is rarely a dull week in the world of the early years, let along a quiet month! With an all-new ministerial team in place facing a major shake-up of early years funding, there is much to digest.
Review of mandatory health checks could lead to greater disadvantage
Authors: Reitemeier Bob , Bayram Liz , Leitch Neil
Published: August 2016

MA Education Ltd, St Jude's Church, Dulwich Road, London, SE24 0PB neil.henty@markallengroup.com
Early years PISA testing
Authors: Moss Peter
Published: August 2016

The use of test scores to drive education policy is both controversial and very much on the government's agenda, so we should be concerned at the impending prospect of cross-national early years assessments.
We are all partners when a child communicates
Authors: Tassoni Penny
Published: August 2016

Children can make significant gains in their language development if they regularly experience supportive, but naturalistic, language opportunities that other ‘luckier’ children have had access to.
Teachers have the chance to make a lasting impact
Authors: Johnson Jennie
Published: August 2016

Much has been written about Early Years Teacher Status and the long-term benefits to staff, settings, and children. This article profiles managers who can see just how beneficial the status has become.
Recognising problems with spelling and reading
Authors: Burmeister Janina
Published: August 2016

In the past, it was thought that a child could not be identified as having dyslexia before the age of six or seven-years-old, when the parents or teachers expressed concern, but this view has changed.
Supporting young children in multi-lingual settings
Authors: Barley Ruth
Published: August 2016

Following on from last month's article, Ruth Barley explores children's views on culture and identity, and how home or first language plays a significant role when it comes to defining friendship groups.
We need more males in the early years workforce
Authors: Cowley Gemma
Published: August 2016

Despite, former Tory leadership contender, Andrea Leadsom's claims, there is a real need to attract more men into the early years workforce, given that many will make excellent role-models for boys.
How residential mobility affects children in settings
Authors: Thomas Elizabeth
Published: August 2016

There are many factors we look out for when observing children's changing behaviours, but how often do we take into account the effect of moving house on a child. How does this impact on learning?
Mapping young children's development: Are we on the right path?
Authors: Chilvers Di
Published: August 2016

Di Chilvers returns to the fundamentals of assessment for learning, keeping the child visible in the process and getting back to making informed decisions about children's progress.
How to hide from prying eyes
Authors: Leitch Neil
Published: August 2016

In an ideal world, government policy-making would be open and transparent. Those making decisions would engage with those affected and we would all have a clear understanding how policies are developed.
Focusing on quality outcomes
Authors: Dubiel Jan
Published: August 2016

The sudden ‘rediscovery’ of the importance of early years provision as key to supporting social mobility is welcome, though no real surprise to our sector, which has been telling government this for some time.
The perfect challenging conditions
Authors: Scott Kym
Published: August 2016

Are we putting up ceilings to children's learning? If so, how do we provide the right conditions that will support children in becoming self-regulating learners who will always seek to challenge themselves.
Training requirements will put children's health first
Authors: Gibbin Fay
Published: August 2016

New paediatric first aid certificate requirements, launched in September this year, will benefit the early years sector by ensuring all Level 2 and 3 practitioners have potentially life-saving skills and knowledge.
A natural place to learn
Authors: Jefferies Tina
Published: August 2016

Nourishing health, wellbeing and learning is a vital element of early years provision, but how you achieve this will depend on many factors. Having an outdoor space with a garden is a great start.
Nothing new under the sun? Ideas and innovation
Authors: Brown Paula
Published: August 2016

How can we encourage young children to be inventors and innovators? How do we show them that setbacks are not only natural, but an inevitable part of the process of learning and discovery.
Such simple pleasures
Authors: Clarke Jenni
Published: August 2016

Jenni Clarke explores the health benefits and cognitive development to be gained through playing with mud, in a series of three articles. Each one focusing on a particular aspect of effective learning.
World space week is go!
Authors: Hammond Paula
Published: August 2016

To celebrate all things cosmic, we take the ‘spheres’ of the universe as inspiration in our quest to get children active, with a series of challenges designed to be fun, informative and, most of all, healthy.
Developing a policy to empower informal carers to administer subcutaneous medication in community palliative care; a feasibility project
Authors: Lee Louise , Howard Kay , Wilkinson Lyn , Kern Cheryl , Hall Sarah
Published: August 2016

Background:

This article describes the development and implementation of a policy to support community professionals to train informal carers to give, ‘as required ‘, subcutaneous medications to their relative. In a rural county, Lincolnshire, despite out of hours responsive services, patients could wait up to one hour for subcutaneous medications. Additionally there were increasing requests from carers to participate in this role.

Aim:

To provide a safe and effective framework via a robust policy to support informal carers to give, as required, subcutaneous medications in today's health-care environment.

Methods:

A group of professionals working in adult community palliative care formed a working party to scope the literature and existing policies, and to consider risks, legalities and local infrastructure. The policy was developed and based on available literature. A consultation process on the policy was commenced before a series of educational workshops supported its roll out.

Results:

The small number of informal carers (n=5) who undertook this role reported positive experiences and felt empowered. Professionals found the policy was able to be implemented quickly and was adhered to.

Conclusion:

From the small numbers audited it could be suggested that if the process is well managed and the informal carers feel supported they can safely and effectively administer subcutaneous injections in community palliative care. More importantly, if a policy is available, staff can respond to requests from carers in a timely manner.
Exploring the spiritual needs of families with seriously ill children
Authors: Ferrell Betty , Wittenberg Elaine , Battista Vanessa , Walker Gay
Published: August 2016

Although we know that families of seriously ill children experience spiritual distress, especially at the end of the child's life, there is little information on the specific spiritual needs of families. In order to develop further training for nurses in paediatrics and help nurses develop skills for communicating about spirituality, this research examined the spiritual needs of families based on nurses' experiences with families of seriously ill children. Nurses' experiences revealed that families' anger with God, blame/regret, forgiveness, and ritual and cultural traditions are salient spiritual needs requiring effective nurse communication skills to support families of ill children.
Nurse-led palliative care services facilitate an interdisciplinary network of care
Authors: Imhof Lorenz , Kipfer Stephanie , Waldboth Veronika
Published: August 2016

Background:

Caring for palliative patients at home is complex and challenging. Specialist palliative care exists to provide high quality of care in complex situations. This study aimed to describe the characteristics of a specialist nurse-led palliative care service in an urban Swiss region.

Methods:

A qualitative study design adopting a grounded theory approach was used. Semi-structured interviews were conducted with 41 participants including family caregivers, home care nurses, referring services, treating physicians, specialist nurses and external politicians. In addition, statistical information was included.

Findings:

Specialist nurses played an important role in building and maintaining an interdisciplinary network of care, necessary for the management of complex palliative situations. They performed tasks such as to “include” members and to “negotiate” the network of care with the family and providers. They “tailored” the support to patients and families' needs and as a result “empowered” the network of care.

Conclusion:

A nurse-led palliative care service facilitated interdisciplinary palliative home care to the benefit of all agents involved.
Research Roundup
Authors: Costello John
Published: August 2016

Synopses of a selection of recently published research articles of relevance to palliative care.
Politics and palliative care: Chad
Authors: Smyth Dion
Published: August 2016

Dion Smyth's review of the internet for palliative nursing
Low-dose dexamethasone during arthroplasty
Authors: Wegener Jessica T. , Kraal Tim , Stevens Markus F. , Hollmann Markus W. , Kerkhoffs Gino M.M.J. , Haverkamp Daniël
Published: August 2016

Dexamethasone is commonly applied during arthroplasty to control post-operative nausea and vomiting (PONV). However, conflicting views of orthopaedic surgeons and anaesthesiologists regarding the use of dexamethasone raise questions about risks of impaired wound healing and surgical site infections (SSI). The aim of this systematic review is to determine the level of evidence for the safety of a peri-operative single low dose of dexamethasone in hip and knee arthroplasty. We systematically reviewed literature in PubMed, EMBASE and Cochrane databases and cited references in articles found in the initial search from 1980 to 2013 based on predefined inclusion criteria. The review was completed with a ‘pro’ and ‘con’ discussion. After identifying 11 studies out of 104, only eight studies met the inclusion criteria. In total, 1335 patients were studied without any incidence of SSI. Causes of SSI are multifactorial. Therefore, 27 205 patients would be required (power = 90%, alpha = 0.05) to provide substantiated conclusions on safety of a single low dose of dexamethasone. Positively, many studies demonstrated showed convincing effects of low-dose dexamethasone on prevention of PONV and dose-dependent effects on post-operative pain and quality of recovery. Dexamethasone induces hyperglycaemia, but none of the studies demonstrated a concomitant SSI. Conversely, animal studies showed that high dose dexamethasone inhibits wound healing. A team approach of anaesthesiologists and orthopaedic surgeons is mandatory in order to balance the risk–benefit ratio of peri-operatively applied steroids for individual arthroplasty patients. We did not find evidence that a single low dose of dexamethasone contributes to SSI or wound healing impairment from the current studies.

Cite this article: Wegener JT, Kraal T, Stevens MF, Hollman MW, Kerkhoffs GMMJ, Haverkamp D. Low-dose dexamethasone during arthroplasty: what do we know about the risks? EFORT Open Rev 2016;1:303-309. DOI: 10.1302/2058-5241.1.000039.
An Automated Method for Identifying Individuals with a Lung Nodule Can Be Feasibly
Implemented Across Health Systems
Authors: Farjah Farhood , Halgrim Scott , Buist Diana S.M. , Gould Michael K. , Zeliadt Steven B. , Loggers Elizabeth T. , Carrell David S.
Published: August 2016

Introduction: The incidence of incidentally detected lung nodules is rapidly
rising, but little is known about their management or associated patient outcomes. One
barrier to studying lung nodule care is the inability to efficiently and reliably
identify the cohort of interest (i.e. cases). Investigators at Kaiser Permanente
Southern California (KPSC) recently developed an automated method to identify
individuals with an incidentally discovered lung nodule, but the feasibility of
implementing this method across other health systems is unknown.Methods: A random sample
of Group Health (GH) members who had a computed tomography in 2012 underwent chart
review to determine if a lung nodule was documented in the radiology report. A
previously developed natural language processing (NLP) algorithm was implemented at our
site using only knowledge of the key words, qualifiers, excluding terms, and the logic
linking these parameters.Results: Among 499 subjects, 156 (31%, 95% confidence interval
[CI] 27-36%) had an incidentally detected lung nodule. NLP identified 189 (38%, 95% CI
33-42%) individuals with a nodule. The accuracy of NLP at GH was similar to its accuracy
at KPSC: sensitivity 90% (95% CI 85-95%) and specificity 86% (95% CI 82-89%) versus
sensitivity 96% (95% CI 88-100%) and specificity 86% (95% CI
75-94%).Conclusion: Automated methods designed to identify individuals with an
incidentally detected lung nodule can feasibly and independently be implemented across
health systems. Use of these methods will likely facilitate the efficient conduct of
multi-site studies evaluating practice patterns and associated outcomes.
What Alert Thresholds Should Be Used to Identify Critical Risk Results: A Systematic Review of the Evidence
Authors: Campbell Craig A , Georgiou Andrew , Westbrook Johanna I , Horvath Andrea R
Published: August 2016

BACKGROUND

Pathology laboratories are required to immediately report results which indicate a patient is at critical risk, but there is little consensus about what values are deemed critical. The aim of this review was to systematically review the literature on alert thresholds for common chemistry and hematology tests in adults and to provide an explicit and ranked source of this evidence.

METHODS

The literature search covered the period of 1995–2014. Evidence sources were critically appraised and ranked using the 1999 Stockholm hierarchy for analytical performance specifications in laboratory medicine modified for establishing decision limits.

RESULTS

The 30 most frequently reported laboratory tests with alert thresholds are presented with evidence rankings. Similar thresholds were reported in North America, Europe and Asia. Seventy percent of papers reported thresholds set by individual institutions, while 18% contained thresholds from surveys of laboratories or clinicians. Forty-six percent of the papers referred to 1 or both of the 2 American laboratory surveys from the early 1990s. “Starter sets” of alert thresholds were recommended by 6 professional bodies, 3 of which were collaborations between pathologists and clinicians. None of the 9 outcome studies identified dealt with confounding factors.

CONCLUSIONS

Recommendations by professional bodies based on outdated surveys of the former state of the art or consensus are currently the best sources of evidence for laboratories to build their alert list. Well-designed outcome studies and greater collaboration between clinicians and the laboratory are needed to identify the most appropriate alert thresholds that signify actionable, critical or significant risk to patient well-being.
Folk music in a digital age: The importance of face-toface community values in filk music
Authors: Childs-Helton Sally
Published: August 2016

Filk is broadly defined as the traditional folk-based music and related community created by and for a sub-community of science fiction and fantasy fans. Born in the 1950s, filk today includes international participants of various experience levels and musical styles. Social context and music are equally important in this tradition; prominent values include self-expression, play and building a face-to-face co-creative, collaborative group experience. This article, founded on Textual Poachers (1992), assumes that filk remains a folk music in many ways, and that filkers still prefer face-to-face musical and personal interaction in spite of a lively, diverse online filk community. I gathered ethnographic data through participant-observation and a questionnaire to examine the following questions. How does the filk community value face-to-face and online interaction, how do filkers negotiate moving between these two domains and how do the domains interact? With four generations of filkers now active, are there generational differences? I postulate that the face-to-face group creativity and co-creation in filk is based on a fluid and permeable performer/audience boundary, allowing individual and group expression to happen simultaneously. This in-person, real-time, deeply immersive co-created experience reinforces a strong sense of community, making face-to-face interaction highly valued.
Fandom’s new frontier: Star Trek in the concert hall
Authors: Mccorkle Brooke
Published: August 2016

Star Trek’s fan group stands out as one of the oldest and most prominent within ‘nerd culture’, in both popular media and fan studies scholarship. The franchise has a long history of fan participation via fanzines, fan fiction, cosplay and conventions. Fan participation and consumption of Trek-related music has an equally extensive history. This article examines new ways in which music and Star Trek fandom intersect by focusing on the concert movies Star Trek: The Ultimate Voyage and Star Trek Movie Live. In these events, live musicians, typically an orchestra, performed a score in synchronization with projected visuals from a pre-existing movie or television show. The comparison of the events’ different approaches to format and marketing inform different means of fan musical engagement with Star Trek. Star Trek: The Ultimate Voyage attracted older ‘hard core’ fans by harnessing nostalgia in service of the production. Alternatively, Star Trek Movie Live opened up the doors of fandom to include not only Trekkers, but also other fandom subcultures and the general public. Ultimately, both events represent opportunities for the expansion of the classical music repertoire and the broadening of audiences.