bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher Risk of Infections with PI3K–AKT–mTOR Pathway Inhibitors in Patients with Advanced Solid Tumors on Phase I Clinical Trials
Authors: Rafii Saeed , Roda Desamparados , Geuna Elena , Jimenez Begona , Rihawi Karim , Capelan Marta , Yap Timothy A. , Molife L. Rhoda , Kaye Stanley B. , de Bono Johann S. , Banerji Udai
Published: February 2015

Purpose: Novel antitumor therapies against the PI3K–AKT–mTOR pathway are increasingly used to treat cancer, either as single agents or in combination with chemotherapy or other targeted therapies. Although these agents are not known to be myelosuppressive, an increased risk of infection has been reported with rapamycin analogues. However, the risk of infection with new inhibitors of this pathway such as PI3K, AKT, mTORC 1/2, or multikinase inhibitors is unknown.

Experimental Design: In this retrospective case–control study, we determined the incidence of infection in a group of 432 patients who were treated on 15 phase I clinical trials involving PI3K–AKT–mTOR pathway inhibitors (cases) versus a group of 100 patients on 10 phase I clinical trials of single agent non-PI3K–AKT–mTOR pathway inhibitors (controls) which did not involve conventional cytotoxic agents. We also collected data from 42 patients who were treated with phase I trials of combinations of PI3K–AKT–mTOR inhibitors and MEK inhibitors and 24 patients with combinations of PI3K–AKT–mTOR inhibitors and cytotoxic chemotherapies.

Results: The incidence of all grade infection was significantly higher with all single-agent PI3K–AKT–mTOR inhibitors compared with the control group [27% vs. 8%, respectively, OR, 4.26; 95% confidence intervals (CI), 1.9–9.1, P = 0.0001]. The incidence of grade 3 and 4 infection was also significantly higher with PI3K–AKT–mTOR inhibitors compared with the control group (10.3% vs. 3%, OR, 3.74; 95% CI, 1.1–12.4; P = 0.02). Also, the combination of PI3K–AKT–mTOR inhibitors and chemotherapy was associated with a significantly higher incidence of all grade (OR, 4.79; 95% CI, 2.0–11.2; P = 0.0001) and high-grade (OR, 2.87; 95% CI, 1.0–7.6; P = 0.03) infection when compared with single-agent PI3K–AKT–mTOR inhibitors.

Conclusions: Inhibitors of the PI3K–AKT–mTOR pathway can be associated with a higher risk of infection. Combinations of PI3K–AKT–mTOR inhibitors and cytotoxic chemotherapy significantly increase the risk of infection. This should be taken into consideration during the design and conduct of trials involving PI3K–AKT–mTOR pathway inhibitors, particularly when combined with chemotherapy or myelosuppressive agents. Clin Cancer Res; 21(8); 1869–76. ©2015 AACR.
Isolated Testicular Metastasis of Prostate Cancer after Radical Prostatectomy: Case Report and Literature Review
Authors: Gibas Artur , Sieczkowski Marcin , Biernat Wojciech , Matuszewski Marcin
Published: February 2015

Clinical recurrence of prostate cancer manifested as a testicular mass is an extremely rare condition. We report a case of a 58-year-old patient with a testicular tumor who underwent orchiectomy 7 years after radical prostatectomy. The pathology analysis confirmed metastasis from prostate carcinoma. After one year, the patient had no signs of biochemical and clinical recurrence. This argues for considering metastasectomy in such patients.
Effects of Tumor Necrosis Factor-α on Podocyte Expression of Monocyte Chemoattractant Protein-1 and in Diabetic Nephropathy
Authors: Chung Choon Hee , Fan Jingyi , Lee Eun Young , Kang Jeong Suk , Lee Seung Joo , Pyagay Petr E. , Khoury Charbel C. , Yeo Tet-Kin , Khayat Mark F. , Wang Amy , Chen Sheldon
Published: February 2015

Background/Aims: Tumor necrosis factor (TNF)-α is believed to play a role in diabetic kidney disease. This study explores the specific effects of TNF-α with regard to nephropathy-relevant parameters in the podocyte. Methods: Cultured mouse podocytes were treated with recombinant TNF-α and assayed for production of monocyte chemoattractant protein-1 (MCP-1) by enzyme-linked immunosorbent assay (ELISA). TNF-α signaling of MCP-1 was elucidated by antibodies against TNF receptor (TNFR) 1 or TNFR2 or inhibitors of nuclear factor-kappaB (NF-κB), phosphatidylinositol 3-kinase (PI3K) or Akt. In vivo studies were done on male db/m and type 2 diabetic db/db mice. Levels of TNF-α and MCP-1 were measured by RT-qPCR and ELISA in the urine, kidney and plasma of the two cohorts and correlated with albuminuria. Results: Podocytes treated with TNF-α showed a robust increase (∼900%) in the secretion of MCP-1, induced in a dose- and time-dependent manner. Signaling of MCP-1 expression occurred through TNFR2, which was inducible by TNF-α ligand, but did not depend on TNFR1. TNF-α then proceeded via the NF-κB and the PI3K/Akt systems, based on the effectiveness of the inhibitors of those pathways. For in vivo relevance to diabetic kidney disease, TNF-α and MCP-1 levels were found to be elevated in the urine of db/db mice but not in the plasma. Conclusion: TNF-α potently stimulates podocytes to produce MCP-1, utilizing the TNFR2 receptor and the NF-κB and PI3K/Akt pathways. Both TNF-α and MCP-1 levels were increased in the urine of diabetic db/db mice, correlating with the severity of diabetic albuminuria.
Gout in Pregnancy: A Case Report and Review of the Literature
Authors: van Veen Teelkien R. , Haeri Sina
Published: February 2015

While gout is a common inflammatory joint disease, its occurrence in women in their reproductive years is very rare. This is thought to be the result of the uricosuric effect of estrogen. The higher estrogen levels during pregnancy are believed to protect the mother against an acute gout flare. We report a case of a patient with gout who experienced a flare in the third trimester of her pregnancy and a review of the English literature on gout in pregnancy. In addition to this case, we identified 19 pregnancies in 8 women with a diagnosis of gout. Of those, 6 experienced an antepartum flare and 7 a postpartum flare. Our patient developed a gout flare in the third trimester of the pregnancy, which was otherwise complicated by gestational diabetes. Her flare was well controlled with pharmacotherapy (hydrocodone and allopurinol). We hypothesize that her pregnancy induced insulin resistance, which decreased the renal excretion of urate provoked this flare. Little is known about the treatment of acute gout and long-term management during pregnancy. The initiation of preventive treatment with allopurinol should be based on individualized risks and benefits, but we suggest that gestational diabetes justifies its use in the second half of pregnancy.
Differences in Rat and Human Erythrocytes Following Blood Component Manufacturing: The Effect of Additive Solutions
Authors: da SilveiraCavalcante Luciana , Acker Jason P. , Holovati Jelena L.
Published: February 2015

Background: Small animal models have been previously used in transfusion medicine studies to evaluate the safety of blood transfusion products. Although there are multiple studies on the effects of blood banking practices on human red blood cells (RBCs), little is known about the effect of blood component manufacturing on the quality of rat RBCs. Methods: Blood from Sprague-Dawley rats and human volunteers (n = 6) was collected in CPD anticoagulant, resuspended in SAGM or AS3, and leukoreduced. In vitro quality was analyzed, including deformability, aggregation, microvesiculation, phosphatidylserine (PS) expression, percent hemolysis, ATP, 2,3-DPG, osmotic fragility, and potassium concentrations. Results: Compared to human RBCs, rat RBCs had decreased deformability, membrane rigidity, aggregability, and microvesiculation after component manufacturing process. Rat RBCs in SAGM showed higher hemolysis compared to human RBCs in SAGM (rat 4.70 ± 0.83% vs. human 0.34 ± 0.07%; p = 0.002). Rat RBCs in AS3 had greater deformability and rigidity than in SAGM. The number of microparticles/µl and the percentage PS expression were lower in rat RBCs in AS3 than in rat RBCs in SAGM. Hemolysis was also significantly lower in AS3 compared to SAGM (2.21 ± 0.68% vs. 0.87 ± 0.39%; p = 0.028). Conclusion: Rat RBCs significantly differ from human RBCs in metabolic and membrane-related aspects. SAGM, which is commonly used for human RBC banking, causes high hemolysis and is not compatible with rat RBCs.
Management of a Pregnant Woman with Anti-Holley Alloantibody
Authors: Braschler Thomas , Vökt Cora Alexandra , Hustinx Hein , Peyrard Thierry , Infanti Laura , Buser Andreas , Holbro Andreas
Published: February 2015

Background: Holley (Hy) is a high-incidence antigen of the Dombrock blood group system (ISBT 014), present in almost 100% of most populations and more than 99% of Blacks. Since anti-Hy is an extremely rare antibody, data on its clinical relevance and in particular on a possible hemolytic disease of the fetus and newborn (HDFN) are scarce. Case Report: The pregnant patient underwent two autologous whole blood collections at weeks 17 and 19 of gestation with cryopreservation. In our case autologous whole blood collection was well tolerated. There were no signs of HDFN in the healthy newborn. Conclusion: Our case improves our understanding of anti-Hy alloantibodies during pregnancy. Additionally, autologous whole blood collection of RBC units with cryopreservation is a safe and feasible way to manage pregnancies in women with rare alloantibodies, when no compatible donor can be found.
Determining the Effect of Preparation and Storage: An Effort to Streamline Platelet Components as a Source of Growth Factors for Clinical Application
Authors: Sonker Atul , Dubey Anju
Published: February 2015

Background: In the present study, different methods for preparation of platelet-rich plasma (PRP) are investigated in order to standardize the component in terms of growth factor content. The effects of concentration technique and storage duration are also analyzed. Methods: PRP was collected from 40 donors by plateletpheresis as well as by the buffy coat and tube method. Concentration of growth factors was performed using double freeze thaw- and CaCl2-induced degranulation techniques. Growth factor estimation was performed using ELISA. Results: The levels of growth factors were highest in PRP from buffy coat, moderately lower in plasma gained by plateletpheresis and lowest in that obtained by the tube method. Mean levels of platelet-derived growth factors (PDGF) AB and BB are significantly higher when CaCl2 was used for concentrating the growth factors. The mean levels of transforming growth factor β1 and insulin-like growth factor I were higher when applying the double freeze thaw technique. There was a substantial decline in the levels of growth factors during storage. Conclusion: The buffy coat method is suitable as preparation method for PRP in most settings. The double freeze thaw technique is better suited as concentration technique as it causes lysis of both platelets and white blood cells for releasing growth factors and is easier to perform. Growth factors are not stable in plasma, thus PRP should be frozen immediately after preparation.
Fetal Growth Pattern and Prediction of Low Birth Weight in Gastroschisis
Authors: Centofanti Sandra F. , Brizot Maria de Lourdes , Liao Adolfo W. , Francisco Rossana P.V. , Zugaib Marcelo
Published: February 2015

Objectives: To examine growth patterns and predictions of low birth weight in gastroschisis fetuses. Methods: This is a retrospective study of isolated fetal gastroschisis before week 24. Ultrasound fetal biometric parameters - head circumference (HC), abdominal circumference (AC), femur length, HC/AC ratio and estimated fetal weight (EFW) - were plotted against normal growth charts. The percentage difference in mean values between normal and gastroschisis fetuses was determined. The growth deficit for each ultrasound parameter was calculated for the fetuses with 1 examination in each designated period (period I: weeks 20-25+6; period II: weeks 26-31+6; period III: from week 32 until term). For low birth weight prediction, measurements below the 10th percentile in periods I and II were tested. Results: Seventy pregnancies were examined. For all fetal parameters, the mean measurements were lower in fetuses with gastroschisis (p < 0.005). The EFW revealed an increased growth deficit between the periods (p = 0.030). HC was predictive of low birth weight in period II (OR = 6.07; sensitivity = 70.8%; specificity = 71.4%). Conclusions: Fetuses with gastroschisis present a reduced growth pattern, and it appears that no growth recovery occurs after the growth restriction has been established. Between week 26 and week 31+6, an HC measurement below the 10th percentile is associated with an increased risk of low birth weight.
Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review
Authors: Quan Taihao , Fisher Gary J.
Published: February 2015

Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This mini-review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment, which contributes to decline of human skin function.
Autologous Dermal Fibroblast Injections Slow Atrioventricular Conduction and Ventricular Rate in Atrial Fibrillation in Swine
Authors: Tondato Fernando , Zeng Hong , Goodchild Traci , Ng Fu Siong , Chronos Nicolas , Peters Nicholas S.
Published: February 2015

Background—

Nonpharmacological ventricular rate control in atrial fibrillation (AF) without producing atrioventricular (AV) block remains a clinical challenge. We investigated the hypothesis that autologous dermal fibroblast (ADF) injection into the AV nodal area would reduce ventricular response during AF without causing AV block.

Methods and Results—

Fourteen pigs underwent electrophysiology study before, immediately, and 28 days after ≈200 million cultured ADFs (n=8) or saline (n=6) were injected under electroanatomical guidance in the AV nodal area, with continuous 28-day ECG recording. In the ADF group at 28 days postinjection, there were prolongations of PR interval (after versus before: 130±13 versus 113±14 ms,
P
=0.04), of AH interval during both sinus rhythm (92±13 versus 76.8±8 ms,
P
<0.01) and atrial pacing at 400 ms (102±13 versus 91±9 ms,
P
<0.01), and of AV node Wenckebach cycle length (230±19 versus 213±24 ms,
P
<0.01), with no changes in the control group. The RR interval during induced AF 28 days after injections was 24% longer in ADF-treated group compared with controls (488±120 versus 386±116 ms,
P
<0.001). Histological analysis revealed presence of ADF-labeled cells in the AV nodal area at 28 days. Transient accelerated junctional rhythm during injections, and transient nocturnal Mobitz I AV conduction occurred early postinjection in both groups.

Conclusions—

Cells survived for 4 weeks and significantly slowed AV conduction and ventricular rate in acutely induced AF. Critically, despite a large number of injections in the AV nodal area and marked effects on AV conduction, AV block did not occur. Further studies are necessary to determine the clinical feasibility and safety of this strategy for ventricular rate control in AF.
Baseline Distribution of Participants With Depression and Impaired Quality of Life in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial
Authors: Hamo Carine E. , Heitner John F. , Pfeffer Marc A. , Kim Hae-Young , Kenwood Christopher T. , Assmann Susan F. , Solomon Scott D. , Boineau Robin , Fleg Jerome L. , Spertus John A. , Lewis Eldrin F.
Published: February 2015

Background—

Previous studies have demonstrated the psychosocial effect of heart failure in patients with reduced ejection fraction. However, the effects on patients with preserved ejection fraction have not yet been elucidated. This study aimed to determine the baseline characteristics of participants with heart failure with preserved ejection fraction as it relates to impaired quality of life (QOL) and depression, identify predictors of poor QOL and depression, and determine the correlation between QOL and depression.

Methods and Results—

Among patients enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial (TOPCAT), 3400 patients completed the Kansas City Cardiomyopathy Questionnaire, 3395 patients completed European QOL 5D Visual Analog Scale, and 1431 patients in United States and Canada completed the Patient Health Questionnaire-9. The mean summary score on the Kansas City Cardiomyopathy Questionnaire was 54.8, and on European QOL 5D Visual Analog Scale, it was 60.3; 27% of patients had moderate to severe depression. Factors associated with better Kansas City Cardiomyopathy Questionnaire and European QOL 5D Visual Analog Scale via multiple logistic regression analysis were American region, older age, no history of angina pectoris or asthma, no use of hypoglycemic agent, more activity level, and lower New York Heart Association class. Factors associated with depression via multiple logistic regression analysis included younger age, female sex, comorbid angina, chronic obstructive pulmonary disease, use of a hypoglycemic agent, lower activity level, higher New York Heart Association class, and selective serotonin reuptake inhibitor use. There were significant correlations between each of the QOL scores and depression.

Conclusions—

Patients with heart failure with preserved ejection fraction, who were younger had higher New York Heart Association class or comorbid angina pectoris, had lower activity levels, lived in Eastern Europe or were taking hypoglycemic agents, were more likely to have impaired QOL and depression.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00094302.
Quantifying the Utility of Taking Pills for Cardiovascular Prevention
Authors: Hutchins Robert , Viera Anthony J. , Sheridan Stacey L. , Pignone Michael P.
Published: February 2015

Background—

The decrease in utility attributed to taking pills for cardiovascular prevention can have major effects on the cost-effectiveness of interventions but has not been well studied. We sought to measure the utility of daily pill-taking for cardiovascular prevention.

Methods and Results—

We conducted a cross-sectional Internet-based survey of 1000 US residents aged ≥30 in March 2014. We calculated utility values, using time trade-off as our primary method and standard gamble and willingness-to-pay techniques as secondary analyses. Mean age of respondents was 50 years. Most were female (59%) and white (63%); 28% had less than a college degree; and 79% took ≥1 pills daily. Mean utility using the time trade-off method was 0.990 (95% confidence interval, 0.988–0.992), including ≈70% not willing to trade any amount of time to avoid taking a preventive pill daily. Using the standard gamble method, mean utility was 0.991 (0.989–0.993), with 62% not willing to risk any chance of death. Respondents were willing to pay an average of $1445 to avoid taking a pill daily, which translated to a mean utility of 0.994 (0.940–0.997), including 41% unwilling to pay any amount. Time trade-off–based utility varied by age (decreasing utility as age increased), sex, race, numeracy, difficulty with obtaining pills, and number of pills taken per day but did not vary by education level, literacy, or income.

Conclusions—

Mean utility for taking a pill daily for cardiovascular prevention is ≈0.990 to 0.994.
Local Association Between Endothelial Dysfunction and Intimal Hyperplasia: Relevance in Peripheral Artery Disease
Authors: Heinen Yvonne , Stegemann Emilia , Sansone Roberto , Benedens Kolja , Wagstaff Rabea , Balzer Jan , Rassaf Tienush , Lauer Thomas , Kelm Malte , Heiss Christian
Published: February 2015

Background

Endothelial dysfunction is a key factor in the development of atherosclerosis. Commonly, endothelial function is determined in the brachial artery, whereas patients with peripheral artery disease (
PAD
) present with lower limb atherosclerosis. We hypothesized that in
PAD,
a segmental or local association exists between endothelial dysfunction and atherosclerotic structural changes.

Methods and Results

We used ultrasound to study endothelial function as flow‐mediated vasodilation, intima media thickness, and local stiffness of the superficial femoral artery (
SFA
) and brachial artery (
BA
).
PAD
patients with symptomatic
SFA
or below‐the‐knee disease were compared with age‐matched patients without
PAD
and young healthy controls.
PAD
patients with
SFA
or below‐the‐knee disease exhibited endothelial dysfunction of the proximal
SFA
(flow‐mediated vasodilation: 3.9±0.6%, 3.7±0.6%) compared with healthy controls (7.4±1.0%) and patients without
PAD
(5.4±0.6%). Brachial artery flow‐mediated vasodilation values were not different in
PAD
patients with
SFA
or below‐the‐knee disease compared with patients without
PAD
, but they were significantly lower than those of healthy controls. Endothelial dysfunction correlated with increased intima media thickness or plaque thickness at the site of flow‐mediated vasodilation measurement across vascular sites. In
PAD
patients with
SFA
disease,
SFA
flow‐mediated vasodilation was further impaired within and distal to stenosis (prestenosis 3.9±0.6%, intrastenosis 2.3±0.7%, poststenosis 2.5±0.6%) and recovered within 24 hours after
SFA
balloon angioplasty to prestenotic values but not to the brachial artery or
SFA
values in patients without
PAD
or controls.

Conclusion

A close association exists between local endothelial function and atherosclerotic structural remodeling, suggesting that in
PAD
, local and segmental factors—in addition to systemic factors—influence local endothelial function. Our data point toward a pathophysiological role for lower extremity endothelial dysfunction in
PAD
.
Impact of Perioperative Infarcts After Cardiac Surgery
Authors: Patel Nikil , Horsfield Mark A. , Banahan Caroline , Janus Justyna , Masters Katie , Morlese John , Egan Vincent , Chung Emma M.L.
Published: February 2015

Background and Purpose—

Brain injury after cardiac surgery is a serious concern for patients and their families. The purpose of this study was to use 3-T fluid attenuated inversion recovery MRI to characterize new and preexisting cerebral ischemic lesions in patients undergoing cardiac surgery and to test whether the accumulation of new ischemic lesions adversely affects cognition.

Methods—

Digital comparison of before and after fluid attenuated inversion recovery MRI images was performed for 77 cardiac surgery patients. The burden of preexisting versus new ischemic lesions was quantified and compared with the results of baseline and postoperative neuropsychological testing.

Results—

After surgery, new lesions were identified in 31% of patients, averaging 0.5 lesions per patient (67 mm
3
[0.004%] of brain tissue). Patients with preexisting lesions were 10× more likely to receive new lesions after surgery than patients without preexisting lesions. Preexisting ischemic lesions were observed in 64% of patients, averaging 19.4 lesions (1542 mm
3
[0.1%] of brain tissue). New lesions in the left hemisphere were significantly smaller and more numerous (29 lesions; median volume, 44 mm
3
; volume range, 5–404 mm
3
) than those on the right (10 lesions; median volume, 128 mm
3
; volume range, 13–1383 mm
3
), which is consistent with a cardioembolic source of particulate emboli. Overall, the incidence of postoperative cognitive decline was 46% and was independent of whether new lesions were present.

Conclusions—

New lesions after cardiac surgery added a small (≈4%) contribution to the burden of preexisting cerebrovascular disease and did not seem to affect cognitive function.

Clinical Trial Registration—

URL:
http://public.ukcrn.org.uk
. Unique identifier: UKCRN ID: 11702.
Association Between Socioeconomic Deprivation and Functional Impairment After Stroke
Authors: Chen Ruoling , Crichton Siobhan , McKevitt Christopher , Rudd Anthony G. , Sheldenkar Anita , Wolfe Charles D.A.
Published: February 2015

Background and Purpose—

Previous findings of the association between socioeconomic deprivation and functional impairment after stroke are inconsistent. There is a lack of data on long-term association. We assessed the association and differences by age, sex, prestroke comorbidities, and stroke phenotypes.

Methods—

We examined data from the South London Stroke Register cohort of 1995 to 2011, recording all first-ever strokes in patients of all ages in South London. A total of 2104 patients were alive at 3 months after stroke. Socioeconomic deprivation was measured using the index of multiple deprivation based on patient postcodes, and functional impairment after stroke was defined as a Barthel index of <15.

Results—

At 3 months after stroke, 643 patients had functional impairment (30.6%; 95% confidence interval, 28.6%–32.5%). Compared with the first quartile of index of multiple deprivation (the least deprived), multivariate-adjusted odds ratios for functional impairment in patients with the second, third, and fourth quartiles were 1.29 (95% confidence interval, 0.94–1.76), 1.33 (0.97–1.82), and 1.78 (1.31–2.43), overall
P
=0.004. The association was significant in patients aged ≥65 years (corresponding odds ratios were 1.49 [1.02–2.17], 1.21 [0.83–1.75], and 1.94 [1.34–2.81];
P
=0.003); in women,
P
=0.008, in patients who do not have prestroke comorbidities,
P
=0.009, and in patients with ischemic stroke,
P
<0.001, but not significant in their counterpart patients. There were similar patterns of the associations of socioeconomic deprivation with impairment at 3 years after stroke.

Conclusions—

There are significant inequalities in short- and long-term functional recovery after stroke. General socioeconomic improvement, targeting groups at high risk of functional impairment is likely to reduce inequality in functional recovery after stroke.
How Sustained Is 24-Hour Diffusion-Weighted Imaging Lesion Reversal?
Authors: Soize Sebastien , Tisserand Marie , Charron Sylvain , Turc Guillaume , Ben Hassen Wagih , Labeyrie Marc-Antoine , Legrand Laurence , Mas Jean-Louis , Pierot Laurent , Meder Jean-François , Baron Jean-Claude , Oppenheim Catherine
Published: February 2015

Background and Purpose—

Here, we assessed how sustained is reversal of the acute diffusion lesion (RAD) observed 24 hours after intravenous thrombolysis, and the relationships between RAD fate and early neurological improvement.

Methods—

We analyzed 155 consecutive patients thrombolyzed intravenously 152 minutes (median) after stroke onset and who underwent 3 MR sessions: 1 before and 2 after treatment (median times from onset, 25.6 and 54.3 hours, respectively). Using voxel-based analysis of diffusion-weighted imaging (DWI)
1
, DWI
2
, and DWI
3
lesions on coregistered image data sets, we assessed the outcome of RAD voxels (hyperintense on DWI
1
but not on DWI
2
) as transient or sustained on DWI
3
, and their relationships with early neurological improvement, defined as ΔNational Institutes of Health Stroke Scale ≥8 or National Institutes of Health Stroke Scale ≤1 at 24 hours.
T
max
and apparent diffusion coefficient values were compared between sustained and transient RAD voxels.

Results—

The median (interquartile range) baseline National Institutes of Health Stroke Scale and DWI
1
lesion volume were 11 (7–18) mL and 15.6 (6.0–50.9) mL, respectively. The median (interquartile range) RAD volume on DWI
2
was 2.8 (1.1–6.6) mL, of which 70% was sustained on DWI
3
. Sixteen (10.3%) patients had sustained RAD ≥10 mL. As compared with transient RAD voxels, sustained RAD voxels had nonsignificantly higher baseline apparent diffusion coefficient values (median [interquartile range], 793 [717–887] versus 777 [705–869]×10
−6
mm
2
·s
−1
, respectively;
P
=0.08) and significantly better perfusion (
T
max
, mean±SD, 6.3±3.2 versus 7.8±4.0 s;
P
<0.001). At variance with transient RAD, the volume of sustained RAD was associated with early neurological improvement in multivariate analysis (odds ratio, 1.08; 95% confidence interval, [1.01–1.17], per 1-mL increase;
P
=0.03).

Conclusions—

After thrombolysis, over two-thirds of the DWI lesion reversal captured on 24-hour follow-up MR is sustained. Sustained DWI lesion reversal volume is a strong imaging correlate of early neurological improvement.
Ethnic Cleansing as Genocide – Assessing the Croatian Genocide Case before the icj
Authors: Vajda Maja Munivrana
Published: February 2015

This article considers whether and if so, under what conditions, the practice of forced population transfer can be regarded a form of genocide, notwithstanding its formal exclusion from the Genocide Convention. This is particularly relevant in the context of the pending genocide case before the International Court of Justice between Croatia and Serbia since both states essentially base their claims on acts of ethnic cleansing. International case law on this matter is far from clear, yet it points to the conclusion that ethnic cleansing may rise to genocide when carried out with genocidal intent. In contrast, Croatian courts seem to have simply equated the intent to ethnically clean a given area with the intent to destroy. Following a brief overview of Croatian case law, this article considers the viability of the pending genocide allegations and whether the Croatian claim and Serbian counter-claim have any prospects of success.
Iranian Women and Legal Pluralism: The Impact on Women’s Rights
Authors: Van Engeland Anicée
Published: February 2015

This article analyzes how Iranian women have become legal actors and unofficial source of law in the Islamic republic of Iran, compelling the government to align on universal women’s rights standards. Iranian women have initiated and supported amendments, bills and reforms to enhance their rights and to work towards the implementation of universal women’s rights standards. The path they have opted for to reform Iranian law is original from many viewpoints: firstly, the reform of Iranian law takes place from the bottom to the top of the society as it is carried out by civil society; then women activists and groups support the reform of methods of interpretation of Islamic legal sources in order to see the emergence of more human rights-orientated interpretations of Islamic law: Eventually to reach their aim of conciliation between Iranian law, Islamic law and universal women’s rights, Iranian women have drawn their inspirations for a reformed Iranian law from many legal sources, giving a practical meaning to the notion of legal pluralism.
Check on Foreign Debt Agreements in the Jordanian Legal System
Authors: Shabeeb Lina Abdallah Khalil , Aljaghoub Mahasen
Published: February 2015

The system of checks and balances, adopted by the Jordanian Constitution is highly
weakened by the High Tribunal’s interpretation of Article 33 (addressing international
relations) in Decision number 1/1962; especially regarding foreign debt agreements,
where such agreements, entered into by the Executive Power, are, almost always,
excluded from the approval of the National Assembly.

Unfortunately, the 2011 Constitutional Reform missed a golden opportunity to
amend this Article; therefore, the alternative would be for the Constitutional Court,
the successor of the High Tribunal, to present a different approach, especially since
the authorities supporting the Tribunal’s decision can be revised to present a different
interpretation that allows a better check over foreign debt, which has been rising
recently to alarming levels.

The best candidate to initiate this change is the National Assembly, especially the
Chamber of Deputies, either by submitting a request to the Court to this effect, or by
carrying a legislative reform amending the Public Debt Management Law from the one
side and, from the other side, drafting a law for the check over the Executive Power’s role
in conducting external agreements in general, and foreign debt agreements, in particular;
a law that balances the relations between the two Powers, regarding their financial
functions, and enhances the democratization of the Jordanian System.
Molecular phylogenetic and morphological analyses of the traditional tribe Coriandreae (Umbelliferae-Apioideae)
Authors: Terenteva Elena I , VALIEJO-ROMAN CARMEN M. , SAMIGULLIN TAHIR H. , PIMENOV MICHAEL G. , TILNEY PATRICIA M.
Published: February 2015

All eight genera (Coriandrum, Bifora, Fuernrohria, Schrenkia, Schtschurowskia, Kosopoljanskia, Lipskya and Sclerotiaria) of the tribe Coriandreae (Umbelliferae), delimited on the basis of morphological characters, were studied using molecular systematic methods to check the monophyly of the tribe. Plastid psbA-trnH data contained very little information and were incongruent with nrDNA data. The nrDNA analyses clearly showed that the tribe Coriandreae consists of three separate groups, differing in their sequences of ITS and ETS of nuclear ribosomal DNA. Only Bifora appears to be closely related to Coriandrum, whereas Fuernrohria falls into tribe Careae, and the five remaining taxa, endemic or subendemic to Middle Asia, form a separate clade, informally named the “Schrenkia clade”. The species of Kosopoljanskia do not form a monophyletic clade, being scattered in molecular trees among the Schrenkia species. Kosopoljanskia and Schrenkia are regarded as congeneric. One new species is described and two new nomenclatural combinations are proposed.
A new species and new section of Viola (Violaceae) from Guangdong, China
Authors: Fan Qiang , Chen Sufang , Wang Longyuan , Chen Zaixiong , Liao Wenbo
Published: February 2015

Viola hybanthoides W. B. Liao et Q. Fan (Violaceae), a new species from Mount Danxia of Guangdong province in China, is described and illustrated. The most distinctive characters of Viola hybanthoides are the subshrub habit, the anterior petal with a long stalk-like claw (up to 3.5 mm, ca. 1/3 of the petal’s length), and the very short upper petals (only 2.5–3 mm long, less than 1/2 of the lateral petals’ length), all of which are characters shared with some Hybanthus species. These characters of this species are distinguishable from all other Viola species, which are usually herbs, and have the anterior petal without a long stalk-like claw and much longer upper petals (usually more than 8 mm long). Based on the new species, a new Viola section Danxiaviola W. B. Liao et Q. Fan is described. To distinguish Viola sections in China, an identification key is provided.
Three new species of the diatom genus Halamphora (Bacillariophyta) from the prairie pothole lakes region of North Dakota, USA
Authors: STEPANEK JOSHUA G , KOCIOLEK J PATRICK
Published: February 2015

The prairie pothole region of North America is characterized by a large number of lakes and wetlands created during the last glacial retreat. These waterbodies are characterized by their generally small sizes (70% of waterbodies are less than 0.4 ha), high densities (as many as 40 waterbodies km −2) and elevated but variable conductivities, ranging between 230–70,000 µS cm−1. Although this region boasts a great number and diversity of habitats, few studies have investigated the diatom diversity present. Presented here are descriptions and illustrations of three new species from the genus Halamphora based on light microscope and scanning electron microscope observations. Halamphora pratensis was collected from Long Lake, Burleigh County, with a conductivity of 2187 µS cm−1, and appears to be most closely allied with the common freshwater H. veneta group within the genus. Halamphora pertusa and H. attenuata were collected from Salt Alkaline Lake, Kidder County, with an elevated conductivity of 9811 µS cm−1. Both of these taxa, although unique, exhibit some morphological similarity to several marine and estuarine species.
A revision of Boreantrops Kits & Marshall (Diptera: Sphaeroceridae: Archiborborinae)
Authors: KITS JOEL H. , MARSHALL STEPHEN A.
Published: February 2015

Boreantrops Kits & Marshall is a recently described genus of flies in the family Sphaeroceridae. Species occur from Brazil and Bolivia north to northern Mexico, mostly in humid montane environments. Two species were included in the genus when originally described, B. calceatus (Duda) and B. mexicanus (Steyskal). Here we revise the genus to include 32 species, including the following 30 new species:  B. albipes, B. alytothrix, B. apterus, B. auranticeps, B. avignis, B. boliviensis, B. challabamba, B. costaricensis, B. cryptopygium, B. durango, B. emarginatus, B. friburguensis, B. guatemalensis, B. hispidus, B. hondurensis, B. inbio, B. longiphallus, B. masneri, B. machinator, B. oaxacensis, B. peruvianus, B. pollex, B. punctipennis, B. subemarginatus, B. subfoveolatus, B. suchixtepecensis, B. talamanca, B. wayqecha, B. zacapa, B. zamora. A key is provided for all known species.
Description of two new species of the leafhopper genus Karachiota (Hemiptera: Cicadellidae: Typhlocybinae: Dikraneurini ) from China
Authors: JIAO MENG
Published: February 2015

Two new species of the dikraneurine leafhopper genus Karachiota Ahmed are reported from China: Karachiota recurva sp. nov. and Karachiota aristata sp. nov.. A key of all species of the genus is provided.
Mustilia (Smerkata) zolotuhini, a new species (Lepidoptera: Endromidae) from China
Authors: Saldaitis Aidas , Ivinskis Povilas , Rimsaite Jolanta
Published: February 2015

The genus Mustilia Walker subgenus Smerkata Zolotuhin 2007 was revised by Zolotuhin (2007) to include seven species from the South–Palearctic to Oriental regions: (Mustilia (Smerkata) phaeopera Hampson (type species), Mustilia (Smerkata) fusca Kishida, Mustilia (Smerkata) craptalis Zolotuhin, Mustilia (Smerkata) soosi Zolotuhin, Mustilia (Smerkata) brechlini Zolotuhin, Mustilia (Smerkata) tzarica Zolotuhin, and Mustilia (Smerkata) ulliae Zolotuhin. An unanticipated discovery of a new species from Sichuan Province, China adds an eighth species to this subgenus.
Idealized Large-Eddy Simulations of a Tropical Cyclone–like Boundary Layer
Authors: Green Benjamin W. , Zhang Fuqing
Published: February 2015

The tropical cyclone (TC) boundary layer (TCBL)—featuring extreme winds over a rough ocean—is difficult to study observationally. With increasing computational power, high-resolution large-eddy simulation (LES) has become an attractive tool to advance understanding of the TCBL. Here, an idealized Cartesian-based LES is employed to investigate boundary layers driven by extreme TC-like winds. The LES includes the effects of centripetal acceleration through an “effective” Coriolis parameter f* = f + 2Vg/R, with the Earth Coriolis parameter f, gradient wind Vg, and (fixed) radius R. Multiple LES experiments are conducted to elucidate how the boundary layer develops and persists in the strongly rotating TC environment. In all simulations, an overshooting jet develops, the height of which increases with Vg, R, and surface drag. Normalized jet strength also increases with R and drag but decreases with Vg. Turbulent diffusivity Km—which must be parameterized in mesoscale and global models but can be diagnosed by LES—varies considerably both within and among simulations. Also evident is a pseudo-inertial oscillation with a period close to the theoretical 2π/f* and an amplitude that decreases exponentially with time. The LES simulations agree with the linear theory for partial-slip Ekman spirals, except when the effects of Km overwhelmingly counter the effects of Vg.
Monsoon-Induced Biases of Climate Models over the Tropical Indian Ocean
Authors: Li Gen , Xie Shang-Ping , Du Yan
Published: February 2015

Long-standing biases of climate models limit the skills of climate prediction and projection. Overlooked are tropical Indian Ocean (IO) errors. Based on the phase 5 of the Coupled Model Intercomparison Project (CMIP5) multimodel ensemble, the present study identifies a common error pattern in climate models that resembles the IO dipole (IOD) mode of interannual variability in nature, with a strong equatorial easterly wind bias during boreal autumn accompanied by physically consistent biases in precipitation, sea surface temperature (SST), and subsurface ocean temperature. The analyses show that such IOD-like biases can be traced back to errors in the South Asian summer monsoon. A southwest summer monsoon that is too weak over the Arabian Sea generates a warm SST bias over the western equatorial IO. In boreal autumn, Bjerknes feedback helps amplify the error into an IOD-like bias pattern in wind, precipitation, SST, and subsurface ocean temperature. Such mean state biases result in an interannual IOD variability that is too strong. Most models project an IOD-like future change for the boreal autumn mean state in the global warming scenario, which would result in more frequent occurrences of extreme positive IOD events in the future with important consequences to Indonesia and East Africa. The Intergovernmental Panel on Climate Change (IPCC) Fifth Assessment Report (AR5) characterizes this future IOD-like projection in the mean state as robust based on consistency among models, but the authors’ results cast doubts on this conclusion since models with larger IOD amplitude biases tend to produce stronger IOD-like projected changes in the future.
Incidence of eating disorders in Danish psychiatric secondary healthcare 1970–2008
Authors: Gammelmark Carina , Jensen Signe OW , Plessen Kerstin J , Skadhede Søren , Larsen Janne Tidselbak , Munk-Jørgensen Povl
Published: February 2015

Objective:

Is an increased focus on eating disorders during the past few decades reflected by increasing occurrence in the psychiatric health service system.

Method:

All first-time diagnoses of eating disorders identified in the Danish Central Psychiatric Research Register 1970–2008 constitute the present research database. Age-standardized rates per 100,000 inhabitants were calculated and autoregressive models were fitted for males and females separately as well as for in- and outpatients.

Results:

The incidence of eating disorders diagnosed in Danish psychiatric secondary healthcare has increased considerably during a nearly 40-year period of observation both within the general category of eating disorders and also specifically for anorexia nervosa. The steepest increase is seen within females aged 15–19 years, where the highest incidences are also found. Anorexia nervosa constitutes the vast majority of all eating disorders. Throughout the time interval investigated, the number of males, however, is negligible compared to females. Most patients are seen in outpatient services, increasing towards recent years. However, the number of patients being treated as inpatients has increased linearly through the entire four decenniums investigated.

Conclusions:

Changes in registration principles, public awareness and higher acceptance of mental disorders in the public is the most obvious explanation for the incidence increase of anorexia nervosa and other eating disorders. This study does not answer whether there has been an increase in true incidence in the population.
You Want Me to Learn How?
Authors: Dill Dennis
Published: February 2015

Today’s teachers have many personalized learning options available to them, and several are free. The author discusses how to use social media for professional learning and the advantages of attending an edcamp.
Role Model or Authentic Professional?
Authors: Merz Sandy
Published: February 2015

Do teachers need to be good role models? The author presents examples of teacher behavior and discusses the difference between being a role model and an authentic professional.
Life 101: Time Management
Authors: McCune Michael
Published: February 2015

Colleges offer many activities for students, and some students have trouble managing their time to fit everything in. The author, a recent college graduate, offers two time management strategies: study in between classes and be present in the moment.
Maurice Casey on the Resurrection and Bereavement Experiences
Authors: Siniscalchi Glenn B.
Published: February 2015

Casey seeks to undercut the apologetic case for Jesus’ resurrection. By appealing to data about ‘bereavement experiences,’ he launches a series of interconnected arguments against the credibility of the resurrection. But there are many reasons for rejecting Casey’s hypothesis on the origins of believing in the resurrection of Jesus: his understanding of bereavement experiences is unreliable and therefore cannot account for the original meaning assigned to the Easter appearances. He himself admits that bereavement apparitions cannot explain all of the appearances. Lastly Paul’s testimony indicates that the appearances were bodily in nature. Given that the appearances should be understood as ‘resurrection appearances,’ it follows that Jesus’ tomb was empty. This overall depiction of Easter faith is consistent with the background of Second Temple Judaism and the relevant New Testament data. Thus the apologists’ concern to argue for Jesus’ resurrection may continue to be endorsed.
Is a Catholic University a Good ‘Idea’? Reflections on Catholic Higher Education from a Newmanian Perspective
Authors: Merrigan Terrence
Published: February 2015

This article reflects on John Henry Newman’s discussion of the ‘idea’ of a Catholic university and situates his thought in this regard against the background of his understanding of the development of ‘ideas’ in general. For Newman, an idea, to be ‘real,’ must find expression in history and culture which, in turn, shape the particular expressions of the idea. What unites these expressions is their claim to represent the original ‘idea’; what distinguishes them is the degree of their approximation to that same ‘idea.’ The application of these insights throws light on Newman’s approach to the Catholic university as a place where all knowledge, including religious knowledge, is pursued for its own sake, and his conviction that a Catholic university ‘distinguishes’ itself by the depth of its commitment to this principle.
Primary tumour growth in an orthotopic osteosarcoma mouse model is not influenced by analgesic treatment with buprenorphine and meloxicam
Authors: Husmann K , Arlt M J E , Jirkof P , Arras M , Born W , Fuchs B
Published: February 2015

Little is known about the treatment of bone pain in animal models of bone cancer. In the present study, the orthotopic 143-B human osteosarcoma xenotransplantation model was used to address the following questions: (1) Can repetitive analgesic treatment extend the experimental period by prolonging the time to reach humane endpoints and (2) Does repetitive analgesic treatment affect bone tumour development and metastasis? The analgesics, buprenorphine and meloxicam, were either applied individually or in combination at 12 h intervals as soon as the animals began to avoid using the tumour cell injected leg. While control mice treated with NaCl showed continuous body weight loss, the major criterion previously for terminating the experiments, animals treated with analgesic substances did not. The control mice had to be sacrificed 26 days after tumour cell injection, whereas the groups of animals with the different pain treatments were euthanized after an additional eight days. Importantly, primary intratibial tumour growth was not affected in any of the experimental groups by any of the pain treatment procedures. Between days 26 and 34 after tumour cell injection an increase of about 100% of the number of lung metastases was found for the groups treated with buprenorphine alone or together with meloxicam, but not for the group treated with meloxicam alone. In summary, the results indicated that both buprenorphine and meloxicam are suitable analgesics for prolonging the experimental periods in an experimental intratibial osteosarcoma mouse model.