bluuebunny/crossref_metadata_2025 huggingface dataset:
After the Introduction into the National Newborn Screening Program: Who Is Receiving Genetic Counseling for Hemoglobinopathies in The Netherlands?
Authors: Kaufmann J.O. , Krapels I.P.C. , Van Brussel B.T.J. , Zekveld-Vroon R.C. , Oosterwijk J.C. , van Erp F. , van Echtelt J. , Zwijnenburg P.J.G. , Petrij F. , Bakker E. , Giordano P.C.
Published: November 2013

Objective: Universal newborn screening for hemoglobinopathies started in The Netherlands in 2007. Herewith severe conditions, such as sickle cell disease, β-thalassemia major and hemoglobin H disease are putatively identified. Additionally, at least 1,800 carriers of hemoglobin variants associated with severe conditions in homozygote or compound heterozygote forms are identified yearly. Thus far, approximately 60 patients and 800 healthy sickle cell (HbS) carriers are reported each year among 180,000 newborns. Results are sent to the general practitioner with the recommendation to inform and diagnose both parents of the healthy carriers to exclude genetic risk, while patients and their parents are referred directly to a pediatrician. This study was performed to determine how often parents of identified carriers and affected newborns are seen in genetic centers for counseling. Methods: In this retrospective study, we collected anonymized data from 7 of the 8 Dutch clinical genetic centers from January 1, 2007, until December 31, 2010. Results: After an initial general increase in total counseling intakes, a decline was noticed in the third year, while the requests for prenatal diagnoses remained relatively stable. In 2007 and 2013, genetic counselors were asked for self-reported knowledge. They found hemoglobinopathy counseling complex, but by 2013, they indicated they had acquired sufficient knowledge on most hemoglobinopathy aspects. Conclusion: We could not observe a significant increase in genetic counseling for hemoglobinopathy after its introduction into newborn screening. Although 120 HbS carriers and 60 patients are expected to be born from couples at risk annually, only 33 at risk couples out of 540 families of diagnosed newborns received optimal care and information at a genetics center in 4 years.
High Glucose Concentration Does Not Modulate the Formation of Arterial Medial Calcification in Experimental Uremic Rats
Authors: Yoshida Tadashi , Yamashita Maho , Horimai Chihiro , Hayashi Matsuhiko
Published: November 2013

High phosphate-induced phenotypic switching of smooth muscle cells (SMCs) into osteogenic cells is critical for the formation of arterial medial calcification in chronic kidney disease. Because vascular calcification is also prevalent in type 2 diabetes, we examined whether glucose concentration affects high phosphate-induced SMC phenotypic switching and calcification. First, the formation of arterial medial calcification was compared among 4 groups: adenine-fed uremic rats, streptozotocin-injected hyperglycemic rats, adenine-fed and streptozotocin-injected uremic/hyperglycemic rats, and control rats. Calcification was obvious in uremic and uremic/hyperglycemic rats, whereas it was undetectable in the others. Aortic calcium contents were significantly elevated in uremic and uremic/hyperglycemic rats, but they were not different between the two groups. Moreover, hyperglycemia had no effects on the reduced expression of SMC differentiation markers including smooth muscle α-actin and SM22α and on the increased expression of osteogenic markers, such as Runx2, in uremic rats. Second, cultured SMCs were incubated in the medium with various concentrations of phosphate (0.9-4.5 mmol/l) and glucose (5-50 mmol/l), and calcium deposition was measured. Although high phosphate dose-dependently increased calcium contents, they were unaffected by glucose concentration. Results suggest that glucose concentration does not directly modulate high phosphate-induced SMC phenotypic switching and arterial medial calcification.
Supernumerary Isochromosome 1, idic(1)(p12), Leading to Tetrasomy 1q in Burkitt Lymphoma
Authors: Roug A.S. , Wendtland P. , Bendix K. , Kjeldsen E.
Published: November 2013

Burkitt lymphoma (BL) is an aggressive mature B-cell neoplasm. The cytogenetic hallmark are MYC-involving translocations, most frequently as t(8;14)(q24;q32). Additional cytogenetic abnormalities are seen in the majority of cases. The most frequent additional aberration involves the long arm of chromosome 1, either as partial or complete trisomy 1q. A very rare additional aberration is a supernumerary isochromosome 1q, i(1)(q10), resulting in tetrasomy 1q. The biological significance of this aberration is unclear. We present a highly aggressive case of BL in a child with immature B-cell immunophenotype (IP) and supernumerary i(1)(q10). Diagnostic karyotyping showed 47,XY,+i(1)(q10),t(8;14)(q24;q32)[2]/47,idem,del(15)(q24)[21]/46,XY[2]. aCGH analysis detected a gain of 1p12qter and a loss of 15q22q25. FISH analysis confirmed the isodicentric chromosome 1, which has not previously been reported in BL. In the literature, supernumerary i(1)(q10) was found in 11 cases of which >80% presented with immature B-cell IP and >60% relapsed or died. Tetrasomy 1q resulting from supernumerary idic(1)(p12) or i(1)(q10) is a rare genetic event in BL and probably associated with immature B-cell IP. We propose that high amplification of genes on chromosome 1p12qter may contribute to the BL IP and disease progression.
Construction of Chromosome Markers from the Lake Victoria Cichlid Paralabidochromis chilotes and Their Application to Comparative Mapping
Authors: Kuroiwa A. , Terai Y. , Kobayashi N. , Yoshida K. , Suzuki M. , Nakanishi A. , Matsuda Y. , Watanabe M. , Okada N.
Published: November 2013

Cichlid fishes in the African Great Lakes are known as a spectacular example of adaptive radiation in vertebrates. Four linkage maps have been constructed to identify the genes responsible for adaptation and speciation, and the genetic linkages of those genes are assumed to play an important role during adaptive evolution. However, it is difficult to analyze such linkages because the linkage groups of one species do not match well with those of the other species. Chromosome markers are a powerful tool for the direct identification of linkage homology between different species. We used information about the linkage map of the Lake Malawi cichlid (Labeotropheus fuelleborni/Metriaclima zebra) to isolate bacterial artificial chromosome (BAC) clones from the BAC library of Paralabidochromis chilotes, Lake Victoria. We identified 18 of 22 P. chilotes chromosomes by single- and multi-color BAC fluorescence in situ hybridization using 19 BAC clones. Comparative mapping with the chromosome markers of P. chilotes in Astatotilapia burtoni (2n = 40) from Lake Tanganyika revealed the chromosome rearrangements that have occurred in this lineage. These chromosome markers will be useful for delineating the process of genome and chromosome evolution in African species.
Floating Vitreous Cyst: Two Clinical Cases
Authors: Lavric Alenka , Urbancic Mojca
Published: November 2013

Purpose: To report two cases of solitary unilateral vitreous cyst. Methods: A complete ocular examination, fundus photography, B-scan ultrasound and spectral-domain optical coherence tomography were performed in both patients. Results: The first patient (a 39-year-old man) presented with transient blurred vision in the right eye. The second patient (a 78-year-old man) reported transient blurred vision in the right eye when changing head position. He was referred to the Eye Hospital because of vitreomacular traction in the other eye. After examination, a diagnosis of vitreous cyst was made in both cases. Conclusions: Vitreous cysts are rare clinical findings. They can occur in normal eyes or in eyes with certain ocular pathologies. When a cyst floats into the visual axis area, it can disturb visual function; therefore, patients usually report transient blurring of vision. A prompt clinical examination is necessary for differentiating this rare condition.
Acceleration of Biliary Cholesterol Secretion Restores Glycemic Control and Alleviates Hypertriglyceridemia in Obese
db
/
db
Mice
Authors: Su Kai , Sabeva Nadezhda S. , Wang Yuhuan , Liu Xiaoxi , Lester Joshua D. , Liu Jingjing , Liang Shuang , Graf Gregory A.
Published: November 2013

Objective—

Recent studies support a role for cholesterol in the development of obesity and nonalcoholic fatty liver disease. Mice lacking the ABCG5 ABCG8 (G5G8) sterol transporter have reduced biliary cholesterol secretion and are more susceptible to steatosis, hepatic insulin resistance, and loss of glycemic control when challenged with a high-fat diet. We hypothesized that accelerating G5G8-mediated biliary cholesterol secretion would correct these phenotypes in obese mice.

Approach and Results—

Obese (
db
/
db
) male and their lean littermates were administered a cocktail of control adenovirus or adenoviral vectors encoding ABCG5 and ABCG8 (AdG5G8). Three days after viral administration, measures of lipid and glucose homeostasis were determined, and tissues were collected for biochemical analyses. AdG5G8 increased biliary cholesterol and fecal sterol elimination. Fasting glucose and triglycerides declined, and glucose tolerance improved in obese mice expressing G5G8 compared with mice receiving control adenovirus. These changes were associated with a reduction in phosphorylated eukaryotic initiation factor 2α and c-Jun N-terminal kinase in liver, suggesting alleviation of endoplasmic reticulum stress. Phosphorylated insulin receptor and protein kinase B were increased, indicating restored hepatic insulin signaling. However, there was no reduction in hepatic triglycerides after the 3-day treatment period.

Conclusions—

Accelerating biliary cholesterol secretion restores glycemic control and reduces plasma triglycerides in obese
db
/
db
mice.
The Novel Desmin Mutant p.A120D Impairs Filament Formation, Prevents Intercalated Disk Localization, and Causes Sudden Cardiac Death
Authors: Brodehl Andreas , Dieding Mareike , Klauke Bärbel , Dec Eric , Madaan Shrestha , Huang Taosheng , Gargus John , Fatima Azra , Šaric Tomo , Cakar Hamdin , Walhorn Volker , Tönsing Katja , Skrzipczyk Tim , Cebulla Ramona , Gerdes Désirée , Schulz Uwe , Gummert Jan , Svendsen Jesper Hastrup , Olesen Morten Salling , Anselmetti Dario , Christensen Alex Hørby , Kimonis Virginia , Milting Hendrik
Published: November 2013

Background—

The intermediate filament protein desmin is encoded by the gene
DES
and contributes to the mechanical stabilization of the striated muscle sarcomere and cell contacts within the cardiac intercalated disk.
DES
mutations cause severe skeletal and cardiac muscle diseases with heterogeneous phenotypes. Recently,
DES
mutations were also found in patients with arrhythmogenic right ventricular cardiomyopathy. Currently, the cellular and molecular pathomechanisms of the
DES
mutations leading to this disease are not exactly known.

Methods and Results—

We identified the 2 novel variants
DES
-p.A120D (c.359C>A) and
DES
-p.H326R (c.977A>G), which were characterized by cell culture experiments and atomic force microscopy. Family analysis indicated a broad spectrum of cardiomyopathies with a striking frequency of arrhythmias and sudden cardiac deaths. The in vitro experiments of desmin-p.A120D reveal a severe intrinsic filament formation defect causing cytoplasmic aggregates in cell lines and of the isolated recombinant protein. Model variants of codon 120 indicated that ionic interactions contribute to this filament formation defect. Ex vivo analysis of ventricular tissue slices revealed a loss of desmin staining within the intercalated disk and severe cytoplasmic aggregate formation, whereas z-band localization was not affected. The functional experiments of desmin-p.H326R did not demonstrate any differences from wild type.

Conclusions—

Because of the functional in vivo and in vitro characterization,
DES
-p.A120D has to be regarded as a pathogenic mutation and
DES
-p.H326R as a rare variant with unknown significance. Presumably, the loss of the desmin-p. A120D filament localization at the intercalated disk explains its clinical arrhythmogenic potential.
Modeling of Arrhythmogenic Right Ventricular Cardiomyopathy With Human Induced Pluripotent Stem Cells
Authors: Caspi Oren , Huber Irit , Gepstein Amira , Arbel Gil , Maizels Leonid , Boulos Monther , Gepstein Lior
Published: November 2013

Background—

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disorder resulting from desmosomal protein mutations. ARVC is characterized pathologically by fibrofatty infiltration and clinically by arrhythmias and sudden cardiac death. We aimed to establish a patient-/disease-specific human induced pluripotent stem cell (hiPSC) model of ARVC.

Methods and Results—

Dermal fibroblasts were obtained from 2 patients with ARVC with plakophilin-2 (
PKP2
) mutations, reprogrammed to generate hiPSCs, coaxed to differentiate into cardiomyocytes (CMs), and then compared with healthy control hiPSC-derived CMs (hiPSC-CMs). Real-time polymerase chain reaction showed a significant decrease in the expression of
PKP2
in the ARVC-hiPSC-CMs. Immunostainings revealed reduced densities of PKP2, the associated desmosomal protein plakoglobin, and the gap-junction protein connexin-43. Electrophysiological assessment demonstrated prolonged field potential rise time in the ARVC-hiPSC-CMs. Transmission electron microscopy identified widened and distorted desmosomes in the ARVC-hiPSC-CMs. Clusters of lipid droplets were identified in the ARVC-CMs that displayed the more severe desmosomal pathology. This finding was associated with upregulation of the proadipogenic transcription factor peroxisome proliferator-activated receptor-γ. Exposure of the cells to apidogenic stimuli augmented desmosomal distortion and lipid accumulation. The latter phenomenon was prevented by application of a specific inhibitor of glycogen synthase kinase 3β (6-bromoindirubin-3'-oxime).

Conclusions—

This study highlights the unique potential of the hiPSC technology for modeling inherited cardiac disorders in general and ARVC specifically. The hiPSC-CMs were demonstrated to recapitulate the ARVC phenotype in the dish, provide mechanistic insights into early disease pathogenesis, and provide a unique platform for drug discovery and testing in this disorder.
Role of Extracellular RNA in Atherosclerotic Plaque Formation in Mice
Authors: Simsekyilmaz Sakine , Cabrera-Fuentes Hector A. , Meiler Svenja , Kostin Sawa , Baumer Yvonne , Liehn Elisa A. , Weber Christian , Boisvert William A. , Preissner Klaus T. , Zernecke Alma
Published: November 2013

Background—

Atherosclerosis and vascular remodeling after injury are driven by inflammation and mononuclear cell infiltration. Extracellular RNA (eRNA) has recently been implicated to become enriched at sites of tissue damage and to act as a proinflammatory mediator. Here, we addressed the role of eRNA in high-fat diet–induced atherosclerosis and neointima formation after injury in atherosclerosis-prone mice.

Methods and Results—

The presence of eRNA was revealed in atherosclerotic lesions from high-fat diet–fed low-density lipoprotein receptor–deficient (
Ldlr
−/−
) mice in a time-progressive fashion. RNase activity in plasma increased within the first 2 weeks (44±9 versus 70±7 mU/mg protein;
P
=0.0012), followed by a decrease to levels below baseline after 4 weeks of high-fat diet (44±9 versus 12±2 mU/mg protein;
P
<0.0001). Exposure of bone marrow–derived macrophages to eRNA resulted in a concentration-dependent upregulation of the proinflammatory mediators tumor necrosis factor-α, arginase-2, interleukin-1β, interleukin-6, and interferon-γ. In a model of accelerated atherosclerosis after arterial injury in apolipoprotein E–deficient (
ApoE

−/−

) mice, treatment with RNase1 diminished the increased plasma level of eRNA evidenced after injury. Likewise, RNase1 administration reduced neointima formation in comparison with vehicle-treated
ApoE

−/−

controls (25.0±6.2 versus 46.9±6.9×10
3
μm
2
,
P
=0.0339) and was associated with a significant decrease in plaque macrophage content. Functionally, RNase1 treatment impaired monocyte arrest on activated smooth muscle cells under flow conditions in vitro and inhibited leukocyte recruitment to injured carotid arteries in vivo.

Conclusions—

Because eRNA is associated with atherosclerotic lesions and contributes to inflammation-dependent plaque progression in atherosclerosis-prone mice, its targeting with RNase1 may serve as a new treatment option against atherosclerosis.
Endothelial Fate Mapping in Mice With Pulmonary Hypertension
Authors: Qiao Lina , Nishimura Toshihiko , Shi Lingfang , Sessions Dane , Thrasher Ama , Trudell James R. , Berry Gerald J. , Pearl Ronald G. , Kao Peter N.
Published: November 2013

Background—

Pulmonary endothelial injury triggers a reparative program, which in susceptible individuals is characterized by neointima formation, vascular narrowing, and the development of pulmonary arterial hypertension. The neointimal cells in human pathological plexiform lesions frequently coexpress smooth muscle α-actin and the endothelial von Willebrand antigen, creating a question about their cellular lineage of origin.

Methods and Results—

Experimental pulmonary hypertension with neointima formation develops in C57Bl/6 mice subjected to left pneumonectomy followed 1 week later by jugular vein injection of monocrotaline pyrrole (20 μg/μL and 1 μL/g; group P/MCTP). Compared with the group vehicle, by day 35, group P/MCTP developed higher right ventricular systolic pressure (54±5 versus 25±2 mm Hg;
P
<0.01) and right ventricular hypertrophy (0.58±0.16 versus 0.26±0.05;
P
<0.01). Transgenic vascular endothelial-cadherin Cre recombinase or Tie-2 Cre mice were intercrossed with mTomato/mGreen fluorescent protein double-fluorescent Cre reporter mice to achieve endothelial genetic lineage marking with membrane-targeted green fluorescent protein. In control mice, few endothelial lineage–marked cells lining the lumen of small pulmonary arteries demonstrate expression of smooth muscle α-actin. Concurrent with the development of pulmonary hypertension, endothelial lineage–marked cells are prominent in the neointima and exhibit expression of smooth muscle α-actin and smooth muscle myosin heavy chain. Human pulmonary arterial hypertension neointimal lesions contain cells that coexpress endothelial CD31 or von Willebrand antigen and smooth muscle α-actin.

Conclusion—

Neointimal cells in pulmonary hypertension include contributions from the endothelial genetic lineage with induced expression of smooth muscle α-actin and smooth muscle myosin heavy chain.
Syncope in High-Risk Cardiomyopathy Patients With Implantable Defibrillators: Frequency, Risk Factors, Mechanisms, and Association With Mortality
Authors: Ruwald Martin H. , Okumura Ken , Kimura Takeshi , Aonuma Kazutaka , Shoda Morio , Kutyifa Valentina , Ruwald Anne-Christine H. , McNitt Scott , Zareba Wojciech , Moss Arthur J.
Published: November 2013

Background—

There is a relative paucity of studies investigating the mechanisms of syncope among heart failure patients with implantable cardioverter-defibrillators, and it is controversial whether nonarrhythmogenic syncope is associated with increased mortality.

Methods and Results—

The Multicenter Automatic Defibrillator Implantation Trial–Reduce Inappropriate Therapy (MADIT-RIT) randomized 1500 patients to 3 different implantable cardioverter-defibrillator programming arms: (1) Conventional programming with therapy for ventricular tachycardia ≥170 bpm; (2) high-rate cutoff with therapy for ventricular tachycardia ≥200 bpm and a monitoring zone at 170 to 199 bpm, and (3) prolonged 60-second delay with a monitoring zone before therapy. Syncope was a prespecified safety end point that was adjudicated independently. Multivariable Cox models were used to identify risk factors associated with syncope and to analyze subsequent risk of mortality. During follow-up, 64 of 1500 patients (4.3%) had syncope. The incidence of syncope was similar across the 3 treatment arms. Prognostic factors for all-cause syncope included the presence of ischemic cardiomyopathy (hazard ratio [HR], 2.48; 95% confidence interval [CI], 1.42–4.34;
P
=0.002), previous ventricular arrhythmias (HR, 2.99; 95% CI, 1.18–7.59;
P
=0.021), left ventricular ejection fraction ≤25% (HR, 1.65; 95% CI, 0.98–2.77;
P
=0.059), and younger age (by 10 years; HR, 1.25; 95% CI, 1.00–1.52;
P
=0.046). Syncope was associated with increased risk of death regardless of its cause (arrhythmogenic syncope: HR, 4.51; 95% CI, 1.39–14.64,
P
=0.012; nonarrhythmogenic syncope: HR, 2.97; 95% CI, 1.07–8.28,
P
=0.038).

Conclusions—

Innovative programming of implantable cardioverter-defibrillators with therapy for ventricular tachycardia ≥200 bpm or a long delay is not associated with increased risk of arrhythmogenic or all-cause syncope, and syncope caused by slow ventricular tachycardias (<200 bpm) is a rare event. The clinical risk factors associated with syncope are related to increased cardiovascular risk profile, and syncope is associated with increased mortality irrespective of the cause.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00947310.
2013 Thomas Willis Award Lecture
Authors: Lo Eng H.
Published: November 2013

The pathophysiology of stroke is complex. Adaptive and maladaptive signalling occurs between multiple cell types in the brain. There is crosstalk between central and systemic responses. And there are overlapping pathways during initial injury and subsequent repair. These numerous feed-forward and feed-back interactions have made it difficult to translate experimental discoveries into clinical applications. An emerging hypothesis in biomedical research now suggests that contrary to a traditional model, translation may not be efficiently obtained without a rigorous understanding of mechanisms. Hence, to optimize diagnostics and therapeutics for stroke patients, it is necessary to identify and define causal mechanisms. Mirroring the multi-compartment interactions in stroke pathophysiology, bench-to-bedside, and bedside-back-to-bench advances in stroke may be best achieved with inter-disciplinary collaborations between basic research, neuroimaging, and broadly based clinical science. Causation can then be two-fold, ie, dissecting mechanisms and targets, as well as developing future scientists who can blur the boundaries between basic, translational, and clinical research. In systems theory, a critical goal is to distinguish causation from correlation. In stroke research, causation may perhaps be found through a collaborative search for mechanisms.
Remote Ischemic Perconditioning as an Adjunct Therapy to Thrombolysis in Patients With Acute Ischemic Stroke
Authors: Hougaard Kristina Dupont , Hjort Niels , Zeidler Dora , Sørensen Leif , Nørgaard Anne , Hansen Troels Martin , von Weitzel-Mudersbach Paul , Simonsen Claus Z. , Damgaard Dorte , Gottrup Hanne , Svendsen Kristina , Rasmussen Peter Vestergaard , Ribe Lars R. , Mikkelsen Irene K. , Nagenthiraja Kartheban , Cho Tae-Hee , Redington Andrew N. , Bøtker Hans Erik , Østergaard Leif , Mouridsen Kim , Andersen Grethe
Published: November 2013

Background and Purpose—

Remote ischemic preconditioning is neuroprotective in models of acute cerebral ischemia. We tested the effect of prehospital rPerC as an adjunct to treatment with intravenous alteplase in patients with acute ischemic stroke.

Methods—

Open-label blinded outcome proof-of-concept study of prehospital, paramedic-administered rPerC at a 1:1 ratio in consecutive patients with suspected acute stroke. After neurological examination and MRI, patients with verified stroke receiving alteplase treatment were included and received MRI at 24 hours and 1 month and clinical re-examination after 3 months. The primary end point was penumbral salvage, defined as the volume of the perfusion–diffusion mismatch not progressing to infarction after 1 month.

Results—

Four hundred forty-three patients were randomized after provisional consent, 247 received rPerC and 196 received standard treatment. Patients with a nonstroke diagnosis (n=105) were excluded from further examinations. The remaining patients had transient ischemic attack (n=58), acute ischemic stroke (n=240), or hemorrhagic stroke (n=37). Transient ischemic attack was more frequent (
P
=0.006), and National Institutes of Health Stroke Scale score on admission was lower (
P
=0.016) in the intervention group compared with controls. Penumbral salvage, final infarct size at 1 month, infarct growth between baseline and 1 month, and clinical outcome after 3 months did not differ among groups. After adjustment for baseline perfusion and diffusion lesion severity, voxelwise analysis showed that rPerC reduced tissue risk of infarction (
P
=0.0003).

Conclusions—

Although the overall results were neutral, a tissue survival analysis suggests that prehospital rPerC may have immediate neuroprotective effects. Future clinical trials should take such immediate effects, and their duration, into account.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00975962.
Cerebral Vasomotor Reactivity and Risk of Mortality
Authors: Portegies Marileen L.P. , de Bruijn Renée F.A.G. , Hofman Albert , Koudstaal Peter J. , Ikram M. Arfan
Published: November 2013

Background and Purpose—

Accumulating vascular pathology in cerebral arteries leads to impaired cerebral vasomotor reactivity. In turn, impaired cerebral vasomotor reactivity is a risk factor for stroke in clinical populations. It remains unclear whether impaired cerebral vasomotor reactivity also reflects more systemic vascular damage. We investigated whether cerebral vasomotor reactivity is associated with the risk of mortality, focusing particularly on cardiovascular mortality independent from stroke.

Methods—

Between 1997 and 1999, 1695 participants from the Rotterdam Study underwent cerebral vasomotor reactivity measurements using transcranial Doppler. Follow-up was complete until January 1, 2011. We assessed the associations between cerebral vasomotor reactivity and mortality using Cox proportional hazards models, adjusting for age, sex, and blood pressure changes and subsequently for cardiovascular risk factors. We additionally censored for incident stroke.

Results—

During 17 004 person-years, 557 participants died, of whom 181 due to a cardiovascular cause. In the fully adjusted model, the hazard ratio per SD decrease in vasomotor reactivity was 1.10 (95% confidence interval [CI], 1.01–1.19) for all-cause mortality, 1.09 (95% CI, 0.94–1.26) for cardiovascular mortality, and 1.10 (95% CI, 0.99–1.21) for noncardiovascular mortality. These associations remained unchanged after censoring for incident stroke.

Conclusions—

We found that lower cerebral vasomotor reactivity is associated with an increased risk of death. Incident stroke does not affect this association, suggesting that a lower cerebral vasomotor reactivity reflects a generally impaired vascular system.
Incidence of Oral Anticoagulant–Associated Intracerebral Hemorrhage in the Netherlands
Authors: Schols Angel M.R. , Schreuder Floris H.B.M. , van Raak Elisabeth P.M. , Schreuder Tobien H.C.M.L. , Rooyer Fergus A. , van Oostenbrugge Robert J. , Staals Julie
Published: November 2013

Background and Purpose—

The aim of this study was to estimate the annual adult incidence and risk of intracerebral hemorrhage (ICH) and oral anticoagulant–associated ICH (OAC-ICH) in the Netherlands.

Methods—

We retrospectively selected all consecutive adult patients with a nontraumatic ICH seen in 1 of 3 hospitals in the region South-Limburg, the Netherlands, from 2007 to 2009. Crude incidences were age-adjusted to Dutch and European population.

Results—

We identified 652 ICH cases, of which 168 (25.8%) were OAC associated. The adult Dutch age-adjusted annual incidence of ICH and OAC-ICH was 34.8 (95% confidence interval, 32.0–37.8) and 8.7 (95% confidence interval, 7.3–10.3) per 100 000 person-years, respectively. The absolute risk of OAC-ICH was estimated at 0.46% per patient-year of OAC treatment.

Conclusions—

The annual incidences of ICH and OAC-ICH are relatively high in the Netherlands when compared with international literature.
Therapeutic Hypothermia After Recanalization in Patients With Acute Ischemic Stroke
Authors: Hong Ji Man , Lee Jin Soo , Song Hee-Jung , Jeong Hye Seon , Choi Huimahn Alex , Lee Kiwon
Published: November 2013

Background and Purpose—

Therapeutic hypothermia improves outcomes in experimental stroke models, especially after ischemia-reperfusion injury. We investigated the clinical and radiological effects of therapeutic hypothermia in acute ischemic stroke patients after recanalization.

Methods—

A prospective cohort study at 2 stroke centers was performed. We enrolled patients with acute ischemic stroke in the anterior circulation with an initial National Institutes of Health Stroke Scale ≥10 who had successful recanalization (≥thrombolysis in cerebral ischemia, 2b). Patients at center A underwent a mild hypothermia (34.5°C) protocol, which included mechanical ventilation, and 48-hour hypothermia and 48-hour rewarming. Patients at center B were treated according to the guidelines without hypothermia. Cerebral edema, hemorrhagic transformation, good outcome (3-month modified Rankin Scale, ≤2), mortality, and safety profiles were compared. Potential variables at baseline and during the therapy were analyzed to evaluate for independent predictors of good outcome.

Results—

The hypothermia group (n=39) had less cerebral edema (
P
=0.001), hemorrhagic transformation (
P
=0.016), and better outcome (
P
=0.017) compared with the normothermia group (n=36). Mortality, hemicraniectomy rate, and medical complications were not statistically different. After adjustment for potential confounders, therapeutic hypothermia (odds ratio, 3.0; 95% confidence interval, 1.0–8.9;
P
=0.047) and distal occlusion (odds ratio, 7.3; 95% confidence interval; 1.3–40.3;
P
=0.022) were the independent predictors for good outcome. Absence of cerebral edema (odds ratio, 5.4; 95% confidence interval, 1.6–18.2;
P
=0.006) and no medical complications (odds ratio, 9.3; 95% confidence interval, 2.2–39.9;
P
=0.003) were also independent predictors for good outcome during the therapy.

Conclusions—

In patients with ischemic stroke, after successful recanalization, therapeutic hypothermia may reduce risk of cerebral edema and hemorrhagic transformation, and lead to improved clinical outcomes.
Effect of Normal Aging Versus Hypertension, Abnormal Body Mass Index, and Diabetes Mellitus on White Matter Hyperintensity Volume
Authors: King Kevin S. , Peshock Ronald M. , Rossetti Heidi C. , McColl Roderick W. , Ayers Colby R. , Hulsey Keith M. , Das Sandeep R.
Published: November 2013

Background and Purpose—

The natural history of white matter hyperintensity (WMH) progression resulting from normal aging versus comorbid vascular insults remains unclear. Therefore we investigated age-related differences in WMH volumes among a group with comorbid hypertension, abnormal body mass index, and diabetes mellitus to a normal aging group drawn from the same population lacking any of these comorbidities.

Methods—

WMH volumes were acquired using 3T MRI for 2011 Dallas Heart Study participants. The slope of the WMH versus age regression was compared between normal and comorbidity groups <50 and ≥50 years of age where a change in slope was demonstrated.

Results—

Aging was linearly associated with greater log WMH volume for both normal (
P
=0.02) and comorbidity (
P
<0.0001) groups. Beyond 50 years of age, more rapid increases in WMH volumes for age were seen in the group with comorbidities (
P
<0.0001) but not in the normal group (
P
=0.173). The between-group difference in slope of expected WMH for age was significantly greater in the comorbidity groups ≥50 years of age (
P
=0.0008) but not <50 years of age (
P
=0.752).

Conclusions—

After 50 years of age, but not before, comorbid hypertension, obesity, and diabetes mellitus were associated with significantly larger WMH volumes for age compared with a normal aging group lacking these conditions. These results support the assertion that age-related differences in WMH volumes are significantly increased in the presence of comorbidities, but the effect is only detectable after 50 years of age.
Neomillspaughia hondurensis (Polygonaceae), a new species from Central America
Authors: ORTIZ-DÍAZ JUAN JAVIER , ARNELAS ITZIAR , TUN JUAN , FLORES JOSÉ SALVADOR
Published: November 2013

A new species Neomillspaughia hondurensis (Polygonaceae) from Honduras is described and illustrated. This species is morphologically and ecollogicaly different from the other two currently known Neomillspaughia species, being more related to N. emarginata than to N. paniculata. A comprehensive comparison and a key for the three species are provided. Se describe e ilustra la nueva especie Neomillspaughia hondurensis (Polygonaceae) de Honduras. Esta especie es morfológicamente y ecológicamente diferente de las dos únicas especies de Neomillspaughia, estando más relacionada con N. emarginata que con N. paniculata. Se proporciona información comparativa de la nueva especie con las especies relacionadas y una clave para la identificación de las mismas.
Barotropic and Baroclinic Annular Variability in the Southern Hemisphere
Authors: Thompson David W. J. , Woodworth Jonathan D.
Published: November 2013

The leading patterns of large-scale climate variability in the Southern Hemisphere are examined in the context of extratropical kinetic energy. It is argued that variability in the Southern Hemisphere extratropical flow can be viewed in the context of two distinct and largely independent structures, both of which exhibit a high degree of annularity: 1) a barotropic structure that dominates the variance in the zonal-mean kinetic energy and 2) a baroclinic structure that dominates the variance in the eddy kinetic energy. The former structure corresponds to the southern annular mode (SAM) and has been extensively examined in the literature. The latter structure emerges as the leading principal component time series of eddy kinetic energy and has received seemingly little attention in previous work.

The two structures play very different roles in cycling energy through the extratropical troposphere. The SAM is associated primarily with variability in the meridional propagation of wave activity, has a surprisingly weak signature in the eddy fluxes of heat, and can be modeled as Gaussian red noise with an e-folding time scale of approximately 10 days. The baroclinic annular structure is associated primarily with variations in the amplitude of vertically propagating waves, has a very weak signature in the wave fluxes of momentum, and exhibits marked quasi periodicity on time scales of approximately 25–30 days. Implications for large-scale climate variability are discussed.
Pseudo-Orbit Data Assimilation. Part I: The Perfect Model Scenario
Authors: Du Hailiang , Smith Leonard A.
Published: November 2013

State estimation lies at the heart of many meteorological tasks. Pseudo-orbit-based data assimilation provides an attractive alternative approach to data assimilation in nonlinear systems such as weather forecasting models. In the perfect model scenario, noisy observations prevent a precise estimate of the current state. In this setting, ensemble Kalman filter approaches are hampered by their foundational assumptions of dynamical linearity, while variational approaches may fail in practice owing to local minima in their cost function. The pseudo-orbit data assimilation approach improves state estimation by enhancing the balance between the information derived from the dynamic equations and that derived from the observations. The potential use of this approach for numerical weather prediction is explored in the perfect model scenario within two deterministic chaotic systems: the two-dimensional Ikeda map and 18-dimensional Lorenz96 flow. Empirical results demonstrate improved performance over that of the two most common traditional approaches of data assimilation (ensemble Kalman filter and four-dimensional variational assimilation).
The Climatology and Interannual Variability of the East Asian Winter Monsoon in CMIP5 Models
Authors: Gong Hainan , Wang Lin , Chen Wen , Wu Renguang , Wei Ke , Cui Xuefeng
Published: November 2013

In this paper the model outputs from the Coupled Model Intercomparison Project (CMIP) phase 5 (CMIP5) are used to examine the climatology and interannual variability of the East Asian winter monsoon (EAWM). The multimodel ensemble (MME) is able to reproduce reasonably well the circulation features of the EAWM. The simulated surface air temperature still suffers from a cold bias over East Asia, but this bias is reduced compared with CMIP phase 3 models. The intermodel spread is relatively small for the large-scale circulations, but is large for the lower-tropospheric meridional wind and precipitation along the East Asian coast. The interannual variability of the EAWM-related circulations can be captured by most of the models. A general bias is that the simulated variability is slightly weaker than in the observations. Based on a selected dynamic EAWM index, the patterns of the EAWM-related anomalies are well reproduced in MME although the simulated anomalies are slightly weaker than the observations. One general bias is that the northeasterly anomalies over East Asia cannot be captured to the south of 30°N. This bias may arise both from the inadequacies of the EAWM index and from the ability of models to capture the EAWM-related tropical–extratropical interactions. The ENSO–EAWM relationship is then evaluated and about half of the models can successfully capture the observed ENSO–EAWM relationship, including the significant negative correlation between Niño-3.4 and EAWM indices and the anomalous anticyclone (or cyclone) over the northwestern Pacific. The success of these models is attributed to the reasonable simulation of both ENSO’s spatial structure and its strength of interannual variability.
Drag Parameter Estimation Using Gradients and Hessian from a Polynomial Chaos Model Surrogate
Authors: Sraj Ihab , Iskandarani Mohamed , Thacker W. Carlisle , Srinivasan Ashwanth , Knio Omar M.
Published: November 2013

A variational inverse problem is solved using polynomial chaos expansions to infer several critical variables in the Hybrid Coordinate Ocean Model’s (HYCOM’s) wind drag parameterization. This alternative to the Bayesian inference approach in Sraj et al. avoids the complications of constructing the full posterior with Markov chain Monte Carlo sampling. It focuses instead on identifying the center and spread of the posterior distribution. The present approach leverages the polynomial chaos series to estimate, at very little extra cost, the gradients and Hessian of the cost function during minimization. The Hessian’s inverse yields an estimate of the uncertainty in the solution when the latter’s probability density is approximately Gaussian. The main computational burden is an ensemble of realizations to build the polynomial chaos expansion; no adjoint code or additional forward model runs are needed once the series is available. The ensuing optimal parameters are compared to those obtained in Sraj et al. where the full posterior distribution was constructed. The similarities and differences between the new methodology and a traditional adjoint-based calculation are discussed.
Predicting the Onset of the North Australian Wet Season with the POAMA Dynamical Prediction System
Authors: Drosdowsky Wasyl , Wheeler Matthew C.
Published: November 2013

A forecast product focusing on the onset of the north Australian wet season using a dynamical ocean–atmosphere model is developed and verified. Onset is defined to occur when a threshold rainfall accumulation of 50 mm is reached from 1 September. This amount has been shown to be useful for agricultural applications, as it is about what is required to generate new plant growth after the usually dry period of June–August. The normal (median) onset date occurs first around Darwin in the north and Cairns in the east in late October, and is progressively later for locations farther inland away from these locations. However, there is significant interannual variability in the onset, and skillful predictions of this can be valuable. The potential of the Predictive Ocean–Atmosphere Model for Australia (POAMA), version 2, for making probabilistic predictions of onset, derived from its multimember ensemble, is shown. Using 50 yr of hindcasts, POAMA is found to skillfully predict the variability of onset, despite a generally dry bias, with the “percent correct” exceeding 70% over about a third of the Northern Territory. In comparison to a previously developed statistical method based solely on El Niño–Southern Oscillation, the POAMA system shows improved skill scores, suggesting that it gains from additional sources of predictability. However, the POAMA hindcasts do not reproduce the observed long-term trend in onset dates over inland regions to an earlier date despite being initialized with the observed warming ocean temperatures. Understanding and modeling this trend should lead to further enhancements in skill.
The monetary cost of offender trajectories: Findings from Queensland (Australia)
Authors: Allard Troy , Stewart Anna , Smith Christine , Dennison Susan , Chrzanowski April , Thompson Carleen
Published: November 2013

This study assessed the longitudinal costs of offender trajectories in Queensland (Australia) to provide policymakers with evidence that could be used to promote the use of crime prevention programs. Few studies have assessed these costs and minimal research has been conducted outside the United States. The study addressed three research questions: (1) What are the monetary costs of crime? (2) What is the optimal number of offender trajectories in an Australian offender cohort? and (3) What are the monetary costs of officially recorded offending for individuals on different offender trajectories? The Semi-Parametric Group-based Method (SPGM) was used to determine the number of offender trajectories in the Queensland Longitudinal Database. This database included 41,377 individuals who were born in 1983 and 1984 and guilty of offences in Queensland that were committed when aged 10–25 years old. The costs of crime were assessed using two approaches. First, criminal justice system costs were estimated based on the number and type of contacts that individuals had with the criminal justice system as well as the length of any supervision served. Second, wider social and economic costs were assessed based on offence type. Results indicated that there were five offender trajectories, including two chronic, one moderate and two low trajectories. When costs were applied to the offender trajectories, offenders in the two chronic groups were 4.8% of the cohort but accounted for 41.1% of the total costs. On average, each chronic offender cost between $186,366 and $262,799 by the time they turned 26 years old, with 60% of the costs accounted for by the criminal justice system. On average, each chronic offender cost over 20 times more than offenders in the two low offending groups. These findings provide further evidence for the potential benefits of implementing interventions that target chronic offenders.
For Grades or Money? Charter School Failure in North Carolina
Authors: Paino Maria , Renzulli Linda A. , Boylan Rebecca L. , Bradley Christen L.
Published: November 2013

Purpose: Charter schools are unique public schools in part because this type of school can close if it fails to meet objectives set forth by the chartering body that approved it. Thus far, however, little research has been conducted into the causes of charter school closures. In this article, we examine charter school accountability. Research Design: We consider four types of accountability to guide our event history analysis of environmental influences that affect charter school closures in North Carolina. In addition, we present two case studies of schools that closed in North Carolina to better illustrate the differing micro-level processes that can lead to the closure of a school. Findings: We find evidence that market, bureaucratic, and financial accountability processes influence the likelihood that a school will close. The initiation of closure procedures, however, is more complex than our quantitative model alone suggests and our two case studies illustrate the key role that financial accountability plays in charter school closures in North Carolina.
When Health Is an Attitudinal Matter
Authors: Cipolletta Sabrina , Consolaro Federica , Horvath Peter
Published: November 2013

Health and illness are complex constructs for which a biomedical approach alone is insufficient. The purpose of the present study was to explore how personal attitudes toward health and illness affect health experience. By adopting a constructivist perspective, we carried out individual semistructured interviews with 15 persons enrolled in a yoga class in northern Italy. We analyzed the interview data using interpretative phenomenological analysis and found that participants’ attitudes toward health and wellness were linked to their experiences and perceptions of health and illness, their somatic awareness, and their constructions of themselves and of their relations. The findings point toward the importance of people taking responsibility for their health. In addition, they suggest that health care should be personalized: approaching people as a complex unity and health and illness as inextricable parts of their lives.
The high cost to health and social care of managing falls in older adults living in the community in Scotland
Authors: Craig J , Murray A , Mitchell S , Clark S , Saunders L , Burleigh L
Published: November 2013

Background and aims

Estimate costs for health and social care services in managing older people in the community who fall.

Method and results

Analyses of predominantly national databases using cost of illness methodologies. In Scotland, 294,000 (34%) of people over 65 years and living in the community fall at least once a year. Of these 20%, almost 60,000 people contacted a medical service for assistance. There were almost 30,000 attendances at GP practices, over 36,100 calls to the Scottish Ambulance Service and 46,816 people presenting at A&E, with 16,549 admitted, 30% with a hip fracture. Mortality was high, 7% during the hospital stay, rising to over 12% at 1 year. Over 20% of patients were unable to return to their homes. Associated costs were over £470 million, with 60% incurred by social services, mainly providing long-term care. Cost per person falling was over £1720, rising to over £8600 for those seeking medical assistance. A hip fracture admission cost £39,490, compared with £21,960 for other falls-related admissions.

Conclusions

Transparent, robust cost information demonstrates the substantial burden of falls for health and social care services and should be a driver for implementing evidence-based interventions to reduce falls.
Post-operative cyclizine misuse
Authors: Woodfield J , St George EJ
Published: November 2013

Cyclizine is commonly prescribed as an anti-emetic post-operatively. We report a case of a 51-year-old woman who developed addiction to intravenous cyclizine following regular administration at recommended doses. This is the first report of cyclizine misuse post-operatively. We compare this case to cyclizine abuse reported amongst other populations. Prescribers should be aware of the potential of cyclizine as a drug of abuse.