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ObjectiveBroca's aphasia is a syndrome of impaired fluency with retained comprehension. The authors used an unbiased algorithm to examine which neuroanatomical areas are most likely to result in Broca's aphasia following surgical lesions.MethodsPatients were prospectively evaluated with standardized language batteries before and after surgery. Broca's area was defined anatomically as the pars opercularis and triangularis of the inferior frontal gyrus. Broca's aphasia was defined by the Western Aphasia Battery language assessment. Resections were outlined from MRI scans to construct 3D volumes of interest. These were aligned using a nonlinear transformation to Montreal Neurological Institute brain space. A voxel-based lesion-symptom mapping (VLSM) algorithm was used to test for areas statistically associated with Broca's aphasia when incorporated into a resection, as well as areas associated with deficits in fluency independent of Western Aphasia Battery classification. Postoperative MRI scans were reviewed in blinded fashion to estimate the percentage resection of Broca's area compared to areas identified using the VLSM algorithm.ResultsA total of 289 patients had early language evaluations, of whom 19 had postoperative Broca's aphasia. VLSM analysis revealed an area that was highly correlated (p < 0.001) with Broca's aphasia, spanning ventral sensorimotor cortex and supramarginal gyri, as well as extending into subcortical white matter tracts. Reduced fluency scores were significantly associated with an overlapping region of interest. The fluency score was negatively correlated with fraction of resected precentral, postcentral, and supramarginal components of the VLSM area.ConclusionsBroca's aphasia does not typically arise from neurosurgical resections in Broca's area. When Broca's aphasia does occur after surgery, it is typically in the early postoperative period, improves by 1 month, and is associated with resections of ventral sensorimotor cortex and suprama

Dental disease restricts activities in school, work, and home, and often significantly diminishes the quality of life for many children and adults, especially those who are low income or uninsured. Noting that dental caries (tooth decay) is the most common preventable chronic childhood disease, this Kids Count issue brief considers the extent to which children in Rhode Island have access to dental care. The brief describes the effects of inadequate dental care and notes that the groups of children at greatest risk for unmet dental needs are those from low-income families, from minority and immigrant families, with special health care needs, from families with access barriers, or who are young. The report also describes the availability of dental services for children in Rhode Island receiving medical assistance and uses diagrams to illustrate the current resource allocation for dental services for children and adults receiving medical assistance. Dental services for Rhode Island children are described, and including services through community health centers, private dentists, hospital-based dental services, school-based dental services, and school-based dental screenings. The report highlights strategies to improve access to dental services for low-income children in Rhode Island, including: (1) increasing reimbursement rates to dental providers caring for children receiving medical assistance; (2) exploring the potential for a dental benefits manager as a strategy to reduce barriers to care and to increase accountability; (3) maintaining and strengthening the dental services infrastructure at community health centers; (4) and identifying resources and strategies to increase access to interpreters and translation services for clients whose primary language is not English. Four levels of dental treatment are identified and performance measures delineated. The report also delineates recommendations for a dental insurance program for children. (Contains 14 references.) (KB)

This lesson focuses on the U.S. Civil War Battle of Gettysburg (Pennsylvania) at the beginning of July 1863. The lesson is based on the National Register of Historic Places registration file, "Gettysburg Battlefield Historic District," as well as several primary and secondary sources. It could be used with units on the U.S. Civil War or in geography or ethics courses. The lesson considers the actions of the Union and Confederate armies in the Battle of Gettysburg and the personal choices made by some of the participants. Student objectives and a list of materials are given in the lesson's first section, "About This Lesson." The lesson is divided into the following sections: (1) "Setting the Stage: Historical Context"; (2) "Locating the Site: Maps" (subdivided into "Civil War Battles in Maryland and Virginia" and "Both Armies during the Battle"); (3) "Determining the Facts: Readings" (subdivided into "Three Days of Carnage at Gettysburg"; "Perspectives of the Participants"; and "The Gettysburg Address, November 19, 1863"); (4) "Visual Evidence: Images"; (5) "Putting It All Together: Activities" (subdivided into "Putting Yourself in the Shoes of a Civil War Soldier"; "Comparing Perspectives"; and "Persuasive Writing and Speaking"); and "Supplementary Resources." (BT)

BackgroundEpilepsy-associated psychoses are poorly understood, and management is focused on treating epilepsy. Chronic, interictal psychosis that persists despite seizure control is typically treated with antipsychotics. Whether resection of a mesial temporal lobe lesion may improve interictal psychotic symptoms that persist despite seizure control remains unknown.ObservationsIn a 52-year-old man with well-controlled epilepsy and persistent comorbid psychosis, brain magnetic resonance imaging (MRI) revealed an infiltrative, intraaxial, T2 fluid-attenuated inversion recovery intense mass of the left amygdala. The patient received an amygdalectomy for oncological diagnosis and surgical treatment of a presumed low-grade glioma. Pathology was ganglioglioma, World Health Organization grade I. Postoperatively, the patient reported immediate resolution of auditory hallucinations. Patient has remained seizure-free on 2 antiepileptic drugs and no antipsychotic pharmacotherapy and reported lasting improvement in his psychotic symptoms.LessonsThis report discusses improvement of psychosis symptoms after resection of an amygdalar glioma, independent of seizure outcome. This case supports a role of the amygdala in psychopathology and suggests that low-grade gliomas of the limbic system may represent, at minimum, partially reversible etiology of psychotic symptoms.

BackgroundMild traumatic brain injury (MTBI) causes morbidity and disability worldwide. Pediatric patients are uniquely vulnerable due to developmental and psychosocial factors. Reduced healthcare access in rural/underserved communities impair management and outcome. A knowledge update relevant to current gaps in care is critically needed to develop targeted solutions.MethodsThe National Library of Medicine PubMed database was queried using comprehensive search terms (("mild traumatic brain injury" or "concussion") and ("rural" or "low-income" or "underserved") and ("pediatric" or "child/children")) in the title, abstract, and Medical Subject Headings through December 2022. Fifteen articles on rural/underserved pediatric MTBI/concussion not covered in prior reviews were examined and organized into four topical categories: epidemiology, care practices, socioeconomic factors, and telehealth.ResultsIncidences are higher for Individuals in rural regions, minorities, and those aged 0-4 years compared to their counterparts, and are increasing over time. Rural healthcare utilization rates generally exceed urban rates, and favor emergency departments (vs. primary care) for initial injury assessment. Management guidelines require customization to resource-constrained settings for implementation and adoption. Decreased community recognition of the seriousness of injury is a consensus challenge to care provision by clinicians. Low parental education and income were correlated with decreased MTBI knowledge and worse outcome. Telehealth protocols for triage/consultation and rehabilitation were feasible in improving care delivery to rural and remote settings.ConclusionsPediatric MTBI/concussion patients in rural/underserved regions experience increased risks of injury, geographic and financial healthcare barriers, and poorer outcomes. Globally, under-reporting of injury has hindered epidemiological understanding. Ongoing MTBI education should be implemented for rural caregivers

BackgroundMeningiomas of the atrium of the lateral ventricle present a unique operative challenge. Parietal transcortical approaches have been described with an oblique approach, but a strictly paramedian approach may offer advantages in a dominant hemisphere atrial meningioma.ObservationsThe patient presented with several weeks of intermittent headaches. Magnetic resonance imaging (MRI) showed an enhancing intraventricular mass in the atrium of the left lateral ventricle. Three-dimensional reconstructions were created from a preoperative MRI, with 1-mm slices for neuronavigation. Diffusion tensor imaging (DTI) was obtained, and tracts were reconstructed in the patient's three-dimensional brainspace. DTI tractography delineated a paramedian transparietal corridor devoid of functional white matter tracks. The patient was positioned supine, in a semislouch position. A left parietal craniotomy was performed. Neuronavigation identified a gyrus posterior to the sensory cortex, anterior to the optic radiations and medial to superior longitudinal and arcuate fasciculus fiber tracts. The tumor was debulked to allow mobilization to coagulate capsular blood supply. Gross total resection was achieved. The patient was discharged postoperatively on day 3 without neurological deficits.LessonsA paramedian transparietal approach to a dominant hemisphere meningioma of the lateral ventricle can be a safe and effective way to resect tumors in this anatomically unique operative corridor.

ObjectiveA fundamental question in epilepsy surgery is how to delineate the margins of cortex that must be resected to result in seizure freedom. Whether and which areas showing seizure activity early in ictus must be removed to avoid postoperative recurrence of seizures is an area of ongoing research. Seizure spread dynamics in the initial seconds of ictus are often correlated with postoperative outcome; there is neither a consensus definition of early spread nor a concise summary of the existing literature linking seizure spread to postsurgical seizure outcomes. The present study is intended to summarize the literature that links seizure spread to postoperative seizure outcome and to provide a framework for quantitative assessment of early seizure spread.MethodsA systematic review was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A Medline search identified clinical studies reporting data on seizure spread measured by intracranial electrodes, having at least 10 subjects and reporting at least 1-year postoperative outcome in the English literature from 1990 to 2019. Studies were evaluated regarding support for a primary hypothesis: Areas of early seizure spread represent cortex with seizure-generating potential.ResultsThe search yielded 4562 studies: 15 studies met inclusion criteria and 7 studies supported the primary hypothesis. The methods and metrics used to describe seizure spread were heterogenous. The timeframe of seizure spread associated with seizure outcome ranged from 1-14 seconds, with large, well-designed, retrospective studies pointing to 3-10 seconds as most likely to provide meaningful correlates of postoperative seizure freedom.SignificanceThe complex correlation between electrophysiologic seizure spread and the potential for seizure generation needs further elucidation. Prospective cohort studies or trials are needed to evaluate epilepsy surgery targeting cortex involved

Based on sediment cores and geophysical data collected from Petermann Fjord and northern Nares Strait, NW Greenland, an Arctic ice shelf sediment facies is presented that distinguishes sub and pro ice shelf environments. Sediment cores were collected from sites beneath the present day Petermann Ice Tongue (PIT) and in deglacial sediments of northern Nares Strait with a focus on understanding the glacial and oceanographic history over the last 11,000 cal yr BP. The modern sub ice shelf sediment facies in Petermann Fjord is laminated and devoid of coarse clasts (IRD) due to strong basal melting that releases debris (debris filtering) from the basal ice at the grounding zone driven by buoyant subglacial meltwater and entrained Atlantic Water. Laminated sediments in the deep basin proximal to the gounding zone comprise layers of fine mud formed by suspension settling from turbid meltwater plumes (plumites) interrupted by normally graded very fine sand to medium silt layers with sharp basal contacts and rip-up clasts of mud, interpreted as turbidites. An inner fjord sill limits distribution of sediment gravity flows from the grounding zone to the deep inner fjord basin, such that sites on the inner sill and beyond the ice tongue largely only comprise plumites. Bioturbation and foraminiferal abundances increase with distance from the grounding zone. The benthic foraminiferal species, Elphidium clavatum is absent beneath the ice tongue, but dominant in the turbid meltwater influenced environment beyond the ice tongue. The very sparse IRD in sediments beneath the PIT and in the fjord beyond the PIT derives mainly from englacial debris in the ice tongue, side valley glaciers, rock falls from the steep fjord walls and sea ice.

Computer Science and programming courses are generally considered to be difficult, particularly for students in the first year of a third-level course. As such, it is an important role to support these students as they begin their education in order to better cement their learning, and to reduce drop-out rates and other early issues. In Ireland, many third-level institutions offer additional dedicated supports to their Computer Science and programming students to augment the traditional lectures, tutorials, and laboratory sessions. This paper provides a review of the current state of Computer Science Support in Ireland. It features case studies from a sample of six third-level institutions, with authors from each institution detailing the support services they offer to their students. A survey was also sent to all third-level institutions in Ireland, asking for feedback about their support services (or lack thereof). Fifteen responses were received from institutions who provide additional supports (no responses were received from institutions without). From the results of this survey, and the authors' personal perspectives and experience, recommendations will be made for those looking to develop their own support services, or to improve upon existing ones. Some of the key findings from this survey are that most supports in Ireland come in the form of dedicated tutors or support centres, more support is offered on average earlier in undergraduate degrees and that most respondents agree that we need to support novice programmers. Some of the recommendations include all institutions offering some form of support service, offering it as a free service and ensuring all ability levels are catered for. Advertising the service appropriately is also important. It is the correct time to undertake such a review due to the continued growth of Computer Science as a subject, not only at third level, but now also at second level with the introduction of Computer Science to the Lea

BackgroundSpinal granulomas form from infectious or noninfectious inflammatory processes and are rarely present intradurally. Intradural granulomas secondary to hematoma are unreported in the literature and present diagnostic and management challenges.ObservationsA 70-year-old man receiving aspirin presented with encephalopathy, subacute malaise, and right lower extremity weakness and was diagnosed with polysubstance withdrawal and refractory hypertension requiring extended treatment. Seven days after admission, he reported increased bilateral lower extremity (BLE) weakness. Magnetic resonance imaging showed T2-3 and T7-8 masses abutting the pia, with spinal cord compression at T2-3. He was transferred to the authors' institution, and work-up showed no vascular shunting or malignancy. He underwent T2-3 laminectomies for biopsy/resection. A firm, xanthochromic mass was resected en bloc. Pathology showed organizing hematoma without infection, vascular malformation, or malignancy. Subsequent coagulopathy work-up was unremarkable. His BLE strength significantly improved, and he declined resection of the inferior mass. He completed physical therapy and was cleared for placement in a skilled nursing facility.LessonsSpinal granulomas can mimic vascular lesions and malignancy. The authors present the first report of paraparesis caused by intradural granuloma secondary to organizing hematoma, preceded by severe refractory hypertension. Tissue diagnosis is critical, and resection is curative. These findings can inform the vigilant clinician for expeditious treatment.

BackgroundDomoic acid (DA) is a naturally occurring neurotoxin harmful to marine animals and humans. California sea lions exposed to DA in prey during algal blooms along the Pacific coast exhibit significant neurological symptoms, including epilepsy with hippocampal atrophy.ObservationsHere the authors describe a xenotransplantation procedure to deliver interneuron progenitor cells into the damaged hippocampus of an epileptic sea lion with suspected DA toxicosis. The sea lion has had no evidence of seizures after the procedure, and clinical measures of well-being, including weight and feeding habits, have stabilized.LessonsThese preliminary results suggest xenotransplantation has improved the quality of life for this animal and holds tremendous therapeutic promise.

In discrete event simulation (DES) models, stochastic behaviour is modelled by sampling random variates from probability distributions to determine event outcomes. However, the distribution of outcomes for an event from a real system is often dynamic and dependent on the current system state. This paper proposes the use of artificial neural networks (ANN) in DES models to determine the current distribution of each event outcome, conditional on the current model state or input data, from which random variates can then be sampled. This enables more realistic and accurate modelling of stochastic behaviour. An application is in digital twin models that aim to closely mimic a real system by learning from its past behaviour and utilising current data to predict its future. The benefits of the approach introduced in this paper are demonstrated through a realistic DES model of load-haul-dump vehicle operations in a production area of a sublevel caving mine., A digital twin to support sustainable and available production as a service, Produktion2030, Sweden, Production Centred Maintenance (PCM) for real time predictive maintenance decision support to maximise production efficiency, The Knowledge Foundation, Sweden

In discrete event simulation (DES) models, stochastic behaviour is modelled by sampling random variates from probability distributions to determine event outcomes. However, the distribution of outcomes for an event from a real system is often dynamic and dependent on the current system state. This paper proposes the use of artificial neural networks (ANN) in DES models to determine the current distribution of each event outcome, conditional on the current model state or input data, from which random variates can then be sampled. This enables more realistic and accurate modelling of stochastic behaviour. An application is in digital twin models that aim to closely mimic a real system by learning from its past behaviour and utilising current data to predict its future. The benefits of the approach introduced in this paper are demonstrated through a realistic DES model of load-haul-dump vehicle operations in a production area of a sublevel caving mine., A digital twin to support sustainable and available production as a service, Produktion2030, Sweden, Production Centred Maintenance (PCM) for real time predictive maintenance decision support to maximise production efficiency, The Knowledge Foundation, Sweden

BackgroundProsopagnosia is a rare neurological condition characterized by the impairment of face perception with preserved visual processing and cognitive functioning and is associated with injury to the fusiform gyrus and inferior longitudinal fasciculus (ILF). Reports of this clinical impairment following resection of right temporal lobe diffuse gliomas in the absence of contralateral injury are exceedingly scarce and not expected as a complication of surgery.ObservationsThe authors describe the case of a young female patient found to have an incidental diffuse glioma in the right inferior temporal lobe despite evidence of preoperative ILF disruption by the tumor. Following resection of the lesion, despite the preoperative disruption to the ILF by the tumor, the patient developed prosopagnosia. There was no evidence of contralateral, left-sided ILF injury.LessonsGiven the significant functional impairment associated with prosopagnosia, neurosurgeons should be aware of the exceedingly rare possibility of a visual-processing deficit following unilateral and, in this case, right-sided inferior temporal lobe glioma resections. More investigation is needed to determine whether preoperative testing can determine dominance of facial-processing networks for patients with lesions in the right inferior posterior temporooccipital lobe and whether intraoperative mapping could help prevent this complication.

The Lucy Mission accomplishes its science during a series of five flyby encounters with seven Trojan asteroid targets. This mission architecture drives a concept of operations design that maximizes science return, provides redundancy in observations where possible, features autonomous fault protection and utilizes onboard target tracking near closest approach. These design considerations reduce risk during the relatively short time-critical periods when science data is collected. The payload suite consists of a color camera and infrared imaging spectrometer, a high-resolution panchromatic imager, and a thermal infrared spectrometer. The mission design allows for concurrent observations of all instruments. Additionally, two spacecraft subsystems will also contribute to the science investigations: the Terminal Tracking Cameras will obtain wide field-of-view imaging near closest approach to determine the shape of each of the Trojan targets and the telecommunication subsystem will carry out Doppler tracking of the spacecraft to determine the mass of each of the Trojan targets.

Digital twins (DT) form part of the Industry 4.0 revolution within manufacturing and related industries. A DT is a digital model (DM) of a real system that features continuous and automated synchronisation and feedback of optimisations between the real and digital domains. A core technology for predictive capabilities from DT is discrete event simulation (DES). The modelling cycle for developing and analysing DES models is significantly different compared to DM. A DT specific DES modelling cycle is introduced that is evolved from that of DM. The availability of specialised software tools for DT tailored to these differences would benefit industry., Funding Agencies:Project Production Centred Maintenance for real-time predictive maintenance decision support to maximise production efficiency - Swedish Knowledge Foundation Produktion2030, the Strategic innovation programme for sustainable production in Sweden

In under a century of existence, the Republic of Iraq has adopted seven national flags. The circumstances of these modifications occurred under times of tremendous political transformation following wars and military coups. The evolution of Iraqi vexillology often corresponded to sub-national violence and direct challenges to state authority. This thesis considers Iraqi identity through the lens of its national flags and iconography from 1921 to 2017. It argues that Iraqi flags and iconography constitute an archive revealing a national identity organized around an emphasis on ethnicity and transhistorical relationships.

Non-communicable diseases (NCDs) are medical conditions that, by definition, are non-infectious and non-transmissible among people. Much of current NCDs are generally due to genetic, behavioral, and metabolic risk factors that often include excessive alcohol consumption, smoking, obesity, and untreated elevated blood pressure, and share many common signal transduction pathways. Alterations in cell and physiological signaling and transcriptional control pathways have been well studied in several human NCDs, but these same pathways also regulate expression and function of the protein synthetic machinery and mRNA translation which have been less well investigated. Alterations in expression of specific translation factors, and disruption of canonical mRNA translational regulation, both contribute to the pathology of many NCDs. The two most common pathological alterations that contribute to NCDs discussed in this review will be the regulation of eukaryotic initiation factor 2 (eIF2) by the integrated stress response (ISR) and the mammalian target of rapamycin complex 1 (mTORC1) pathways. Both pathways integrally connect mRNA translation activity to external and internal physiological stimuli. Here, we review the role of ISR control of eIF2 activity and mTORC1 control of cap-mediated mRNA translation in some common NCDs, including Alzheimer's disease, Parkinson's disease, stroke, diabetes mellitus, liver cirrhosis, chronic obstructive pulmonary disease (COPD), and cardiac diseases. Our goal is to provide insights that further the understanding as to the important role of translational regulation in the pathogenesis of these diseases.

Calving events of Petermann Glacier, northwest Greenland, in 2010 and 2012 reduced the length of its ice tongue by c. 25 km, allowing exploration of newly uncovered seafloor during the Petermann 2015 Expedition. This article presents the results of foraminiferal analysis and environmental data from thirteen surface sediment samples in northern Nares Strait and Petermann Fjord, including beneath the modern ice tongue. This is the first study of living foraminifera beneath an arctic ice tongue and the first modern foraminiferal data from this area. Modern assemblages were studied to constrain species environmental preferences and to improve paleoenvironmental interpretations of foraminiferal assemblages. Sub-ice tongue assemblages differed greatly from those at all other sites, with very low faunal abundances and being dominated by agglutinated fauna, likely reflecting low food supply under the ice tongue. Fjord fauna were comprised of 80 percent or more calcareous species. Notably,Elphidium clavatumis absent beneath the ice tongue although it is dominant in the fjord. Increasing primary productivity associated with the transition to mobile sea ice, diminishing influence of the Petermann Glacier meltwater with distance from the grounding line, and increased influence of south-flowing currents in Nares Strait are the important controls on the faunal assemblages.

Background and importanceApraxia of speech is a disorder of articulatory coordination and planning in speech sound production. Its diagnosis is based on deficits in articulation, prosody, and fluency. It is often described concurrent with aphasia or dysarthria, while pure apraxia of speech is a rare entity.Clinical presentationA right-handed man underwent focal surgical resection of a recurrent grade III astrocytoma in the left hemisphere dorsal premotor cortex located in the posterior middle frontal gyrus. After the procedure, he experienced significant long-term speech production difficulties. A battery of standard and custom language and articulatory assessments were administered, revealing intact comprehension and naming abilities, and preserved strength in orofacial articulators, but considerable deficits in articulatory coordination, fluency, and prosody-consistent with diagnosis of pure apraxia of speech. Tractography and resection volumes compared with publicly available imaging data from the Human Connectome Project suggest possible overlap with area 55b, an under-recognized language area in the dorsal premotor cortex and has white matter connectivity with the superior longitudinal fasciculus.ConclusionThe case reported here details a rare clinical entity, pure apraxia of speech resulting from resection of posterior middle frontal gyrus. While not a classical language area, emerging literature supports the role of this area in the production of fluent speech, and has implications for surgical planning and the general neurobiology of language.

An efficient algorithm is presented for computing exact system and survival signatures of K-terminal reliability in undirected networks with unreliable edges. K-terminal reliability is defined as the probability that a subset K of the network nodes can communicate with each other. Signatures have several advantages over direct reliability calculation such as enabling certain stochastic comparisons of reliability between competing network topology designs, extremely fast repeat computation of network reliability for different edge reliabilities and computation of network reliability when failures of edges are exchangeable but not independent. Existing methods for computation of signatures for K-terminal network reliability require derivation of cut-sets or path-sets which is only feasible for small networks due to the computational expense. The new algorithm utilises binary decision diagrams, boundary set partition sets and simple array operations to efficiently compute signatures through a factorisation of the network edges. The performance and advantages of the algorithm are demonstrated through application to a set of benchmark networks and a sensor network from an underground mine.

Background: The objective of this study was to evaluate early changes in magnetic resonance imaging (MRI) and clinical disease activity measures as predictors of later structural progression in early rheumatoid arthritis (RA). Methods: This was a post hoc analysis of data pooled across treatments from a three-arm (tofacitinib monotherapy, tofacitinib with methotrexate [MTX], or MTX monotherapy) trial of MTX-naïve patients with early, active RA. Synovitis, osteitis and erosions were assessed with the Outcome Measures in Rheumatology (OMERACT) RA MRI scoring system (RAMRIS) and RAMRIQ (automated quantitative RA MRI assessment system; automated RAMRIS) at months 0, 1, 3, 6 and 12. Radiographs were assessed at months 0, 6 and 12, and clinical endpoints were assessed at all timepoints. Univariate and multivariate analyses explored the predictive value of early changes in RAMRIS/RAMRIQ parameters and disease activity measures, with respect to subsequent radiographic progression. Results: Data from 109 patients with a mean RA duration of 0.7 years were included. In univariate analyses, changes in RAMRIS erosions at months 1 and 3 significantly predicted radiographic progression at month 12 (both p < 0.01); changes in RAMRIQ synovitis and osteitis at months 1 and 3 were significant predictors of RAMRIS erosions and radiographic progression at month 12 (all p < 0.01). In subsequent multivariate analyses, RAMRIS erosion change at month 1 (p < 0.05) and RAMRIQ osteitis changes at months 1 and 3 (both p < 0.01) were significant independent predictors of radiographic progression at month 12. Univariate analyses demonstrated that changes in Clinical Disease Activity Index (CDAI) and Disease Activity Score in 28 joints, erythrocyte sedimentation rate (DAS28-4[ESR]) at months 1 and 3 were not predictive of month 12 radiographic progression. Conclusions: MRI changes seen as early as 1 month after RA treatment initiation have the potential to better predict long-term r

Core HU2008029-12PC from the Disko trough mouth fan on the central West Greenland continental slope is used to test whether an ice shelf covered Baffin Bay during the Last Glacial Maximum (LGM) and at the onset of the deglaciation. We use benthic and planktic foraminiferal assemblages, stable isotope analysis of planktic forams, algal biomarkers, ice-rafted detritus (IRD), lithofacies characteristics defined from CT scans, and quantitative mineralogy to reconstruct paleoceanographic conditions, sediment processes and sediment provenance. The chronology is based on radiocarbon dates on planktic foraminifers using a Delta R of 140 +/- 30 C-14 years, supplemented by the varying reservoir estimates of Stern and Lisiecki (2013) that provide an envelope of potential ages. HU2008029-12PC is bioturbated throughout. Sediments between the core base at 11.3 m and 4.6 m (LGM through HS1) comprise thin turbidites, plumites and hemipelagic sediments with Greenlandic provenance consistent with processes active at the Greenland Ice Sheet margin grounded at or near the shelf edge. Abundance spikes of planktic forams coincide with elevated abundance of benthic forams in assemblages indicative of chilled Atlantic Water, meltwater and intermittent marine productivity. IRD and IP25 are rare in this interval, but brassicasterol, an indicator of marine productivity reaches and sustains low levels during the LGM. These biological characteristics are consistent with a sea-ice covered ocean experiencing periods of more open water such as leads or polynyas in the sea ice cover, with chilled Atlantic Water at depth, rather than full iceshelf cover. They do not support the existence of a full Baffin Bay ice shelf cover extending from grounded ice on the Davis Strait. Initial ice retreat from the West Greenland margin is manifested by a pronounced lithofacies shift to bioturbated, diatomaceous mud with rare IRD of Greenlandic origin at 467 cm (16.2 cal ka BP; Delta R = 140 yrs) within HS1. A spi

A Maintenance Procedure is conducted in order to prevent the failure of a system or to restore the functionality of a failed system. Such a procedure consists of a series of tasks, each of which has a distribution of times to complete and a probability of being performed incorrectly. The inclusion of tests can be used to identify any maintenance errors which have occurred. When an error is identified it can be addressed through a corresponding correction sequence which will have associated costs and add to the maintenance process completion time. A modified FMEA approach has been used to identify the possible tests. By incorporating any selection of tests into the maintenance process it can then analysed using a discrete-event simulation to predict the expected completion time distribution. The choice of tests to perform and when to do them is then made to successfully complete the maintenance objective in the shortest possible time using a genetic algorithm. The methodology is demonstrated by applying it to the repair process for a car braking system. The developed method is suitable for application in abroad range of industries., Funding agency:Faste Laboratory, Centre for Functional Product Innovation at Luleå University of Technology

The provenance of sand-sized ice-rafted debris (IRD) sourced from Greenland is currently difficult to determine. Such knowledge, if it could be ascertained with a high degree of certainty, could be applied to the Greenland-proximal marine records to improve both our understanding of modern-day spatial patterns of iceberg rafting and the past history of the Greenland Ice Sheet (GIS). Recent studies have highlighted the utility of the Pb-isotope composition of individual sand-sized feldspars and the Ar-40/Ar-39 ages of individual sand-sized hornblendes in this regard. However, before any such provenance toolkit can be applied to the palaeo-record, it is necessary first to determine whether this approach can be used to track the sources of known recent Greenland-proximal IRD deposition. To this end we present new records of the Pb-isotope composition and the Ar-40/Ar-39 ages of individual sand-sized grains of feldspars and homblendes, respectively, from modern Greenland glacifluvial and ford sands and Holocene to modern Greenland-proximal marine sediments. These new data demonstrate that sand-sized feldspars and hornblendes glacially eroded by the GIS exhibit distinct intra- and inter-tectonic terrane differences in their Pb-isotope compositions and ages and that these differences are clearly expressed in the geochemistry and geochronology of sand-sized IRD deposited in marine sediments around Greenland. Although overlap exists between some Greenland-proximal IRD 'source fields' defined by these data, our approach has the potential to both better understand spatial patterns of Greenland-derived IRD in the modern day as well as during past episodes of iceberg calving.

The climate of the Holocene, the current interglacial covering the past 11,700 years, has been relatively stable compared to previous periods. Nevertheless, repeating occurrence of rapid natural climate changes that challenged human society are seen in proxy reconstructions. Ocean sediment cores for example display prominent peaks of enhanced ice rafted debris (IRD) during the Holocene with a multidecadal to millennial scale periodicity. Different mechanisms were proposed that caused these enhanced IRD events, for example variations in the incoming total solar irradiance (TSI), volcanic eruptions and the combination of internal climate variability and external forcings. We investigate the probable mechanisms causing the occurrence of IRD-events over the past 6000 years using a fully coupled climate- ice sheet - iceberg model (iLOVECLIM). We performed 19 experiments that differ in the applied forcings (TSI, volcanic) and the initial atmospheric conditions. To explore internal ice sheet variability one further experiment was done with fixed climate conditions. All the model runs displayed prominent peaks of enhanced iceberg melt flux (IMF), independent of the chosen experimental set-up. The spectral analysis of the experiments with the ice-sheet- climate model coupled displays significant peaks at 2000, 1000 years in all the experiments and at 500 years in most runs. The experiment with fixed climate conditions displays one significant peak of about 1500 years related to internal ice sheet variability. This frequency is modulated to 2000 and 1000 years in all the experiments with a coupled climate- ice sheet due to interactions between the climate components. We further investigate the impact of minimum TSI events on the timing and occurrence of enhanced IMF. In the experimental set-up that was forced with idealized sinusoidal TSI variations (+/- 4 Wm(-2)), we find a significant occurrence of an increased iceberg melt flux about 60 years after the minimum TSI value. Y

The deglacial history and oceanography of Uummannaq Trough, central West Greenland continental shelf, was investigated using foraminiferal, sedimentological, and bathymetric records together with a radiocarbon chronology, providing a timeline for the retreat of glacial ice after the Last Glacial Maximum (LGM). To map ice stream retreat, data were collected from cores from the outer (JR175-VC45 and JR175-VC43) and inner (JR175-VC42) Uummannaq Trough. A large ice stream, fed by confluent glaciers draining the interior of the Greenland Ice Sheet, extended across the outer shelf during the LGM and was in retreat by 15.0 cal kyr BP. Foraminiferal data indicate that the ‘warm’ West Greenland Current (WGC) was established prior to 14.0 cal kyr BP, which is the hitherto earliest record of Atlantic Water found on the West Greenland shelf. For each of the cores, foraminifera indicate that ice sheet retreat was followed quickly by incursion of the WGC, suggesting that the warm water may have enhanced ice retreat. Prior to the Younger Dryas cold event, the radiocarbon chronology indicates that the ice sheet retreated to the mid-shelf, where it subsequently stabilised and formed a large grounding-zone wedge (GZW). After the Younger Dryas, around 11.5 cal kyr BP, the ice retreated rapidly from the GZW and into the fjords.

Changes in the Holocene interaction of the (i) cold/fresh East Greenland Current (EGC) and (ii) warm/saline Irminger Current (IC) in northern Denmark Strait have been reconstructed from benthic and planktic foraminifera assemblages, ice-rafted debris, grain-size analyses and quantitative X-ray diffraction. During the time from c. 10 600 to 8000 cal a BP, palaeoceanographic reconstructions reveal waning deglacial influence from the receding Greenland Ice Sheet and presence of a strong EGC caused low surface water productivity. From c. 8000 cal a BP, a predominant influence of Atlantic-sourced IC waters on subsurface water conditions became established in northern Denmark Strait, which accompanied low surface water productivity. Relatively warm surface and subsurface water conditions, i.e. reduced EGC and strong IC influence, are found from c. 6500 to 4500 cal a BP, representing Holocene optimum-like conditions. A mid- to late Holocene EGC strengthening caused increased stratification and formation of a distinct halocline. However, we recognize millennial-scale periods of reduced stratification by an enhanced influence of Atlantic-sourced IC Water on surface water conditions: (i) at c. 2500–1400 cal a BP the time of the Roman Warm Period and (ii) at c. 300 cal a BP the later part of the Little Ice Age. These periods of oceanic warming probably relate to changes in the Subpolar Gyre dynamics that led to enhanced entrainment of Atlantic-sourced IC Water into northern Denmark Strait.

Recent developments in ultra-dense optical components coupled with micro-scale electro-mechanical systems have led to the ability to create a new type of optical device: the free-space self-aligning optical transmitter/receiver. With automatic search and alignment, high-speed data or power transfer, and low-power operation, this new tool is poised to become an important tool in many systems. Utilizing MEMS technology and high speed electronic control and sensing, one half of this device allows for independent beam control, automatic beam scanning and steering, as well as incoming beam detection and positioning. Pairing this host module up with a client module outfitted with a new high-speed optical modulator (also developed at UCSD) and a classic corner cube reflector, yields a unique blend of technologies that allows for secure high-speed point-to-point communications or even remote sensing and power transfer systems

The Laurentide Ice Sheet (LIS) was a large, dynamic ice sheet in the early Holocene. The glacial events through Hudson Strait leading to its eventual demise are recorded in the well-dated Labrador shelf core, MD99-2236 from the Cartwright Saddle. We develop a detailed history of the timing of ice-sheet discharge events from the Hudson Strait outlet of the LIS during the Holocene using high-resolution detrital carbonate, ice rafted detritus (IRD), Ύ18O, and sediment color data. Eight detrital carbonate peaks (DCPs) associated with IRD peaks and light oxygen isotope events punctuate the MD99-2236 record between 11.5 and 8.0 ka. We use the stratigraphy of the DCPs developed from MD99-2236 to select the appropriate ΔR to calibrate the ages of recorded glacial events in Hudson Bay and Hudson Strait such that they match the DCPs in MD99-2236. We associate the eight DCPs with H0, Gold Cove advance, Noble Inlet advance, initial retreat of the Hudson Strait ice stream (HSIS) from Hudson Strait, opening of the Tyrrell Sea, and drainage of glacial lakes Agassiz and Ojibway. The opening of Foxe Channel and retreat of glacial ice from Foxe Basin are represented by a shoulder in the carbonate data. ΔR of 350 years applied to the radiocarbon ages constraining glacial events H0 through the opening of the Tyrell Sea provided the best match with the MD99-2236 DCPs; ΔR values and ages from the literature are used for the younger events. A very close age match was achieved between the 8.2 ka cold event in the Greenland ice cores, DCP7 (8.15 ka BP), and the drainage of glacial lakes Agassiz and Ojibway. Our stratigraphic comparison between the DCPs in MD99-2236 and the calibrated ages of Hudson Strait/Bay deglacial events shows that the retreat of the HSIS, the opening of the Tyrell Sea, and the catastrophic drainage of glacial lakes Agassiz and Ojibway at 8.2 ka are separate events that have been combined in previous estimates of the timing of the 8.2 ka event from marine records.

We use quantitative X-ray diffraction to determine the mineralogy of late Quaternary marine sediments from the West and East Greenland shelves offshore from early Tertiary basalt outcrops. Despite the similar basalt outcrop area (60 000–70 000 km2), there are significant differences between East and West Greenland sediments in the fraction of minerals (e.g. pyroxene) sourced from the basalt outcrops. We demonstrate the differences in the mineralogy between East and West Greenland marine sediments on three scales: (1) modern day, (2) late Quaternary inputs and (3) detailed down-core variations in 10 cores from the two margins. On the East Greenland Shelf (EGS), late Quaternary samples have an average quartz weight per cent of 6.22.3 versus 12.83.9 from the West Greenland Shelf (WGS), and 12.024.8 versus 1.9 2.3wt% for pyroxene. K-means clustering indicated only 9% of the samples did not fit a simple EGS vs. WGS dichotomy. Sediments from the EGS and WGS are also isotopically distinct, with the EGS having higher eNd (18 to 4) than those from the WGS (eNd¼25 to 35). We attribute the striking dichotomy in sediment composition to fundamentally different long-term Quaternary styles of glaciation on the two basalt outcrops.

We examine variations in the ice-rafted sources for sediments in the Iceland/East Greenland offshore marine archives by utilizing a sediment unmixing model and link the results to a coupled iceberg-ocean model. Surface samples from around Iceland and along the E/NE Greenland shelf are used to define potential sediment sources, and these are examined within the context of the down-core variations in mineralogy in the <2 mm sediment fraction from a transect of cores across Denmark Strait. A sediment unmixing model is used to estimate the fraction of sediment <2 mm off NW and N Iceland exported across Denmark Strait; this averaged between 10 and 20%. Both the sediment unmixing model and the coupled iceberg-ocean model are consistent in finding that the fraction of "far-travelled" sediments in the Denmark Strait environs is overwhelmingly of local, mid-East Greenland, provenance, and therefore with a significant cross-channel component to their travel. The Holocene record of ice-rafted sediments denotes a three-part division of the Holocene in terms of iceberg sediment transport with a notable increase in the process starting ca 4000 cal yr BP. This latter increase may represent the re-advance during the Neoglacial period of land-terminating glaciers on the Geikie Plateau to become marine-terminating. The contrast in spectral signals between these cores and the 1500-yr cycle at VM28-14, just south of the Denmark Strait, combined with the coupled iceberg-model results, leads us to speculate that the signal at VM28-14 reflects pulses in overflow waters, rather than an ice-rafted signal.

This paper re-evaluates how well quantitative x-ray diffraction (qXRD) can be used as an exploratory method of the weight percentage (wt%) of volcaniclastic sediment, and to identify tephra events in marine cores. In the widely used RockJock v6 software programme, qXRD tephra and glass standards include the rhyodacite White River tephra (Alaska), a rhyolitic tephra (Hekla-4) and the basaltic Saksunarvatn tephra. Experiments of adding known wt% of tephra to felsic bedrock samples indicated that additions >= 10 wt% are accurately detected, but reliable estimates of lesser amounts are masked by amorphous material produced by milling. Volcaniclastic inputs range between 20 and 50 wt%. Primary tephra events are identified as peaks in residual qXRD glass wt% from fourth-order polynomial fits. In cores where tephras have been identified by shard counts in the >150 mu m fraction, there is a positive correlation (validation) with peaks in the wt% glass estimated by qXRD. Geochemistry of tephra shards confirms the presence of several Hekla-sourced tephras in cores B997-317PC1 and -319PC2 on the northern Iceland shelf. In core B997-338 (north-west Iceland), there are two rhyolitic tephras separated by ca. 100 cm with uncorrected radiocarbon dates on articulated shells of around 13 000 yr B. P. These tephras may be correlatives of the Borrobol and Penifiler tephras found in Scotland. The number of Holocene tephra events per 1000 yr was estimated from qXRD on 16 cores and showed a bimodal distribution with an increased number of events in both the late and early Holocene.

Based on quantitative X-ray diffraction mineralogical analysis of cores HU2008029-0006/0008 (857-m water depth) located south of the Davis Strait sill, we seek answers to two questions: (i) the temporal correlation of NW Labrador Shelf Sea Heinrich (H-) and Baffin Bay detrital carbonate (BBDC) events, and (ii) the provenance of the sediments? A sediment-unmixing model (SedUnMix) is used to determine provenance variations. Although 12 radiocarbon dates were obtained there were many age reversals and we favour a depth/age model for HU2008029-0008PC based on correlations to well-dated neighbouring cores north and south of Davis Strait. We find no correlation between H- and BBDC events except for H-0, which appears to be a broadly synchronous event along the NE Canadian margin and is correlative with an episode of major moraine building along this flank of the Laurentide Ice Sheet. Unmixing of the sediment composition based on six potential glacial source regions indicates that the bulk of the sediment in 0008PC is derived from glacial erosion of West Greenland, but is punctuated by intervals when dolomite-rich sediments, derived from outcrops north of Baffin Bay, dominate the composition. Estimated dates on these BBDC events are -13, 25 and 30–38 cal ka BP.

BackgroundNXN-188 is a combined neuronal nitric oxide synthase (nNOS) inhibitor and 5-hydroxytryptamine 1B/1D (5-HT(1B/1D)) receptor agonist. Using preclinical models, we evaluated whether these two unique therapeutic principles have a synergistic effect in attenuating stimulated calcitonin gene-related peptide (CGRP) release, a marker of trigeminal activation.MethodsWe examined the effect of NXN-188 on: (1) KCl-, capsaicin- and resiniferatoxin (RTX)-induced immunoreactive CGRP (iCGRP) release from isolated preparation of rat dura mater, trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC); and (2) capsaicin- and electrical stimulation (ES)-induced middle meningeal artery (MMA) dilation in a rat closed-cranial window.ResultsNXN-188 inhibited: (1) KCl-stimulated iCGRP release from dura mater (% decrease mean ± SEM, lowest effective concentration) (35 ± 6%, 30 µM), TG (24 ± 11 %, 10 µM) and TNC (40 ± 8%, 10 µM); (2) capsaicin- and RTX-induced iCGRP release from dura mater; and (3) capsaicin- and ES-induced increase in dural artery diameter (32 ± 5%, 3 mg kg(-1) intravenous (i.v.) and 36 ± 1%, 10 mg kg(-1) i.v.).ConclusionsNXN-188 inhibits CGRP release from migraine-relevant cephalic tissues. Its effect is most likely mediated via a combination of nNOS-inhibition and 5-HT(1B/1D) receptor agonism in dura mater while the mechanisms of action for inhibition of CGRP release from TG and TNC have to be investigated further.