bluuebunny/crossref_metadata_2025 huggingface dataset:
Theranostic Agents for Photodynamic Therapy of Prostate Cancer by Targeting Prostate-Specific Membrane Antigen
Authors: Wang Xinning , Tsui Brian , Ramamurthy Gopolakrishnan , Zhang Ping , Meyers Joseph , Kenney Malcolm E. , Kiechle Jonathan , Ponsky Lee , Basilion James P.
Published: June 2016

Prostatectomy has been the mainstay treatment for men with localized prostate cancer. Surgery, however, often can result in major side effects, which are caused from damage and removal of nerves and muscles surrounding the prostate. A technology that can help surgeons more precisely identify and remove prostate cancer resulting in a more complete prostatectomy is needed. Prostate-specific membrane antigen (PSMA), a type II membrane antigen highly expressed in prostate cancer, has been an attractive target for imaging and therapy. The objective of this study is to develop low molecular weight PSMA-targeted photodynamic therapy (PDT) agents, which would provide image guidance for prostate tumor resection and allow for subsequent PDT to eliminate unresectable or remaining cancer cells. On the basis of our highly negatively charged, urea-based PSMA ligand PSMA-1, we synthesized two PSMA-targeting PDT conjugates named PSMA-1-Pc413 and PSMA-1-IR700. In in vitro cellular uptake experiments and in vivo animal imaging experiments, the two conjugates demonstrated selective and specific uptake in PSMA-positive PC3pip cells/tumors, but not in PSMA-negative PC3flu cells/tumors. Further in vivo photodynamic treatment proved that the two PSMA-1–PDT conjugates can effectively inhibit PC3pip tumor progression. The two PSMA-1–PDT conjugates reported here may have the potential to aid in the detection and resection of prostate cancers. It may also allow for the identification of unresectable cancer tissue and PDT ablation of such tissue after surgical resection with potentially less damage to surrounding tissues. Mol Cancer Ther; 15(8); 1834–44. ©2016 AACR.
Acridine Derivatives as Inhibitors of the IRE1α–XBP1 Pathway Are Cytotoxic to Human Multiple Myeloma
Authors: Jiang Dadi , Tam Arvin B. , Alagappan Muthuraman , Hay Michael P. , Gupta Aparna , Kozak Margaret M. , Solow-Cordero David E. , Lum Pek Y. , Denko Nicholas C. , Giaccia Amato J. , Le Quynh-Thu , Niwa Maho , Koong Albert C.
Published: June 2016

Using a luciferase reporter–based high-throughput chemical library screen and topological data analysis, we identified N-acridine-9-yl-N',N'-dimethylpropane-1,3-diamine (DAPA) as an inhibitor of the inositol requiring kinase 1α (IRE1α)–X-box binding protein-1 (XBP1) pathway of the unfolded protein response. We designed a collection of analogues based on the structure of DAPA to explore structure–activity relationships and identified N9-(3-(dimethylamino)propyl)-N3,N3,N6,N6-tetramethylacridine-3,6,9-triamine (3,6-DMAD), with 3,6-dimethylamino substitution on the chromophore, as a potent inhibitor. 3,6-DMAD inhibited both IRE1α oligomerization and in vitro endoribonuclease (RNase) activity, whereas the other analogues only blocked IRE1α oligomerization. Consistent with the inhibition of IRE1α-mediated XBP1 splicing, which is critical for multiple myeloma cell survival, these analogues were cytotoxic to multiple myeloma cell lines. Furthermore, 3,6-DMAD inhibited XBP1 splicing in vivo and the growth of multiple myeloma tumor xenografts. Our study not only confirmed the utilization of topological data analysis in drug discovery but also identified a class of compounds with a unique mechanism of action as potent IRE1α–XBP1 inhibitors in the treatment of multiple myeloma. Mol Cancer Ther; 15(9); 2055–65. ©2016 AACR.
A New Anti-CXCR4 Antibody That Blocks the CXCR4/SDF-1 Axis and Mobilizes Effector Cells
Authors: Broussas Matthieu , Boute Nicolas , Akla Barbara , Berger Sven , Beau-Larvor Charlotte , Champion Thierry , Robert Alain , Beck Alain , Haeuw Jean-François , Goetsch Liliane , Bailly Christian , Dumontet Charles , Matthes Thomas , Corvaia Nathalie , Klinguer-Hamour Christine
Published: June 2016

The type IV C-X-C-motif chemokine receptor (CXCR4) is expressed in a large variety of human cancers, including hematologic malignancies, and this receptor and its ligand, stromal cell–derived factor-1 (SDF-1), play a crucial role in cancer progression. We generated a humanized immunoglobulin G1 mAb, hz515H7, which binds human CXCR4, efficiently competes for SDF-1 binding, and induces a conformational change in CXCR4 homodimers. Furthermore, it inhibits both CXCR4 receptor–mediated G-protein activation and β-arrestin-2 recruitment following CXCR4 activation. The binding of the hz515H7 antibody to CXCR4 inhibits the SDF-1–induced signaling pathway, resulting in reduced phosphorylation of downstream effectors, such as Akt, Erk1/2, p38, and GSK3β. Hz515H7 also strongly inhibits cell migration and proliferation and, while preserving normal blood cells, induces both antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against neoplastic cells. In mouse xenograft models, hz515H7 displays antitumor activities with multiple hematologic tumor cell lines, with its Fc-mediated effector functions proving essential in this context. Furthermore, hz515H7 binds to primary tumor cells from acute myeloid leukemia and multiple myeloma patients. Collectively, our results demonstrate two major mechanisms of action, making hz515H7 unique in this regard. Its potential as a best-in-class molecule is currently under investigation in a phase I clinical trial. Mol Cancer Ther; 15(8); 1890–9. ©2016 AACR.
Laparoscopic and Endoscopic Cooperative Surgery for Plexiform Angiomyxoid Myofibroblastic Tumor
Authors: Nagahisa Yoshio , Itou Tadashi , Okita Chika , Yamakawa Tatsuya , Chen Kai , Kouda Yusuke , Hashida Kazuki
Published: June 2016

Plexiform angiomyxoid myofibroblastic tumor (PAMT) is a recently described distinctive gastric mesenchymal entity with a peculiar plexiform pattern, bland spindle cells and a myxoid stroma rich in arborizing blood vessels. In this study, we report a new case of this rare gastric tumor resected by laparoscopic and endoscopic cooperative surgery (LECS). A 39-year-old Japanese man was admitted with a gastric mass. Gastroscopy showed an elevated mass in the anterior wall of the gastric antrum. Endoscopic ultrasound examination revealed a focal hypoechoic lesion protruding into the lumen. A partial gastrectomy by LECS was performed, and the patient made an uneventful recovery and remains well 9 months later. The tumor in this case depicted all the typical histopathologic and immunochemical features of gastric PAMT (c-kit negative and smooth muscle actin-positive). Especially, it was characterized by multiple nodules protruding outward within the serosa. Therefore, it is important that the resection line is determined on the serosa to ensure the complete resection of these nodules together.
Factors Associated With Noncompletion During the Run-In Period Before Randomization and Influence on the Estimated Benefit of LCZ696 in the PARADIGM-HF Trial
Authors: Desai Akshay S. , Solomon Scott , Claggett Brian , McMurray John J.V. , Rouleau Jean , Swedberg Karl , Zile Michael , Lefkowitz Martin , Shi Victor , Packer Milton
Published: June 2016

Background—

The 8442 patients randomized in the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial, in which sacubitril/valsartan (LCZ696) reduced both death and HF hospitalization more than enalapril, were a subset of 10 521 patients entering sequential, single-blind run-in periods (enalapril 10 mg twice daily for 2 weeks followed by LCZ696 200 mg twice daily for 4 to 6 weeks) to ensure short-term tolerability of the 2 study medications. We identified the predictors of run-in noncompletion and estimated the implications of noncompletion for the overall study result.

Methods and Results—

Patient factors associated with run-in noncompletion were defined in multivariable logistic regression models. The effectiveness of LCZ696 in a broader cohort approximating the full run-in population was estimated by weighting randomized patients according to the inverse probability of run-in completion; 2079 (19.8%) subjects discontinued the study during the run-in period, including 1102 (10.5%) during the enalapril phase and 977 (9.3%) during the LCZ696 phase. In multivariable models, lower systolic blood pressure, lower estimated glomerular filtration rate, higher N-terminal pro–B-type natriuretic peptide, and ischemic cause of heart failure were associated with higher risk for run-in noncompletion. Repeat analysis of the effect of randomized treatment giving greater weight to randomized patients resembling those who did not complete the run-in did not alter the hazard ratio favoring LCZ696 over enalapril for the primary end point of cardiovascular death or heart failure hospitalization, or the additional key end points of cardiovascular death and all-cause mortality.

Conclusions—

Patients with lower blood pressure, lower glomerular filtration rate, and more severe heart failure were at higher risk for noncompletion during the run-in period of PARADIGM-HF. Weighted analysis of key study outcomes accounting for the effect of run-in noncompletion did not alter the benefit of LCZ696 over enalapril.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01035255.
Early Recovery of Left Ventricular Systolic Function After CoreValve Transcatheter Aortic Valve Replacement
Authors: Dauerman Harold L. , Reardon Michael J. , Popma Jeffrey J. , Little Stephen H. , Cavalcante João L. , Adams David H. , Kleiman Neil S. , Oh Jae K.
Published: June 2016

Background—

Approximately one third of patients with symptomatic aortic stenosis have reduced left ventricular ejection fraction (LVEF) before transcatheter aortic valve replacement. The incidence, predictors, and significance of early LVEF recovery after CoreValve transcatheter aortic valve replacement have not been described.

Methods and Results—

We studied 156 patients from the CoreValve Extreme and High-Risk trials with LVEF ≤40% at baseline who had 30-day LVEF data. All patients underwent core laboratory echocardiographic assessment of LVEF at baseline, post procedure, discharge, 30 days, 6 months, and 1 year. Early LVEF recovery was defined as an absolute increase of ≥10% in EF at 30 days. One-year outcomes were compared between patients with and without early recovery. Multivariable analysis was performed to determine independent predictors of early recovery. Early LVEF recovery occurred in 62% of patients, generally before discharge. By 30 days LVEF increased >17% compared with baseline in the early recovery group with minimal increase in the no–early recovery group (48.9±8.8% versus 31.5±6.9%;
P
<0.001). One-year all-cause mortality was numerically (but not statistically) higher in the no–early recovery group (24% versus 12%;
P
=0.07). Absence of previous myocardial infarction (odds ratio, 0.44; 95% confidence interval, 0.19–1.03) and baseline mean gradient ≥40 mm Hg (odds ratio, 4.59; 95% confidence interval, 1.76–11.96) were identified as predictors of early LVEF recovery.

Conclusions—

Nearly two thirds of patients with reduced LVEF will have a marked early improvement after transcatheter aortic valve replacement. Early LVEF recovery is associated with improved clinical outcomes and is most likely among patients with higher baseline aortic valve gradients and no previous myocardial infarction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01240902.
Loss of Notch3 Signaling in Vascular Smooth Muscle Cells Promotes Severe Heart Failure Upon Hypertension
Authors: Ragot Hélène , Monfort Astrid , Baudet Mathilde , Azibani Fériel , Fazal Loubina , Merval Régine , Polidano Evelyne , Cohen-Solal Alain , Delcayre Claude , Vodovar Nicolas , Chatziantoniou Christos , Samuel Jane-Lise
Published: June 2016

Hypertension, which is a risk factor of heart failure, provokes adaptive changes at the vasculature and cardiac levels. Notch3 signaling plays an important role in resistance arteries by controlling the maturation of vascular smooth muscle cells.
Notch3
deletion is protective in pulmonary hypertension while deleterious in arterial hypertension. Although this latter phenotype was attributed to renal and cardiac alterations, the underlying mechanisms remained unknown. To investigate the role of Notch3 signaling in the cardiac adaptation to hypertension, we used mice with either constitutive
Notch3
or smooth muscle cell–specific conditional
RBPJκ
knockout. At baseline, both genotypes exhibited a cardiac arteriolar rarefaction associated with oxidative stress. In response to angiotensin II–induced hypertension, the heart of
Notch3
knockout and SM-
RBPJκ
knockout mice did not adapt to pressure overload and developed heart failure, which could lead to an early and fatal acute decompensation of heart failure. This cardiac maladaptation was characterized by an absence of media hypertrophy of the media arteries, the transition of smooth muscle cells toward a synthetic phenotype, and an alteration of angiogenic pathways. A subset of mice exhibited an early fatal acute decompensated heart failure, in which the same alterations were observed, although in a more rapid timeframe. Altogether, these observations indicate that Notch3 plays a major role in coronary adaptation to pressure overload. These data also show that the hypertrophy of coronary arterial media on pressure overload is mandatory to initially maintain a normal cardiac function and is regulated by the Notch3/RBPJκ pathway.
Leisure Time Physical Activity and Cardio‐Metabolic Health: Results From the Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil)
Authors: Lin Xiaochen , Alvim Sheila M. , Simoes Eduardo J. , Bensenor Isabela M. , Barreto Sandhi M. , Schmidt Maria I. , Ribeiro Antonio L. , Pitanga Francisco , Almeida Maria Conceição C. , Liu Simin , Lotufo Paulo A.
Published: June 2016

Background

Although increasing effort has been devoted to the promotion of a healthy lifestyle such as leisure time physical activity for cardio‐metabolic health, specific evidence supporting health policy remains sparse, particularly in those ethnically diverse populations where cardio‐metabolic diseases are reaching epidemic proportion and yet are grossly understudied.

Methods and Results

We conducted a cross‐sectional analysis of the baseline data from 10 585 participants aged 35 to 74 free of cardiovascular diseases in the Brazilian Longitudinal Study of Adult Health. Leisure time physical activity status was defined by the American Heart Association and the World Health Organization recommendations (≥150 min/week moderate activities or 75 min/week vigorous activities). In total, 1183 (21%) women and 1387 (29%) men were active. After accounting for covariates, the favorable effects of leisure time physical activity on cardio‐metabolic parameters were evident. Specifically, the average blood pressure, heart rate, and Framingham Risk Score for cardiovascular diseases of the active were significantly lower within each sex. The
OR
s comparing the active versus the inactive women were 0.78 (95%
CI
: 0.66–0.92) for hypertension and 0.78 (95%
CI
: 0.65–0.93) for cardiovascular diseases in 10 years. Among men, the
OR
s were 0.75 (95%
CI
: 0.65–0.87) for hypertension and 0.73 (95%
CI
: 0.61–0.87) for diabetes. The 10‐year risk of cardiovascular diseases was significantly lower among the active men with a 33% reduction (
OR
=0.67, 95%
CI
: 0.57–0.78).

Conclusions

We observed beneficial effects of leisure time physical activity on cardio‐metabolic health in this large Brazilian population that are consistent with studies in North America and Europe.
Property beyond princely authority: the intellectual and legal roots of Ulrik Huber’s fundamental law
Authors: van Nifterik Gustaaf
Published: June 2016

In this paper I argue for a rule-of-law-reading of Ulrik Huber’s fundamental law on freedom of property. My aim is to show that there is enough contemporary intellectual and legal context for such a reading. I do so by arguing along three lines: the medieval tradition that rooted the origin of private property in natural law, protection of property in the constitution of Holland in the seventeenth century, and property rights protected by fundamental law in English common law.
When Is the Right to Justice Undermined? Identifying and Applying International and Islamic Human Rights Law Standards for Domestic Judicial Processes: The Case of the Seven Bahá’í Leaders and Iran’s Revolutionary Courts
Authors: Ghahraman Golriz
Published: June 2016

Section one of this article is divided in two parts, defining a ‘competent tribunal established by law’, and secondly independence and impartiality, including both structural and substantive standards for assessment. The second section provides an assessment of the legitimacy of the process in terms of minimum standards of due process. This part consists of three sub-sections, addressing three aspects of the right to due process that most gravely risk political manipulation of trials. These are: the principle of legality; procedural transparency; and the right to be represented by competent defence counsel. Both these sections also apply the components identified to the general operation of Iran’s Revolutionary Courts. Finally, section three will analyse the conduct of Iran’s Revolutionary Courts in the particular trials of the seven Bahá’í leaders (known as the ‘Yaran’ or ‘friends’) in Iran in 2010.
Bosnian Days of Reckoning: Review of the Sequence of Protests in Bosnia and Herzegovina 2013–14, and Future Prospects of Resistance
Authors: Mujkić Asim
Published: June 2016

The purpose of this text is to explore the possibilities of civic resistance and struggle in the context of ethnonational, deeply divided societies such as Bosnia and Herzegovina, in the light of its June 2013 ‘jmbg’ (citizen’s identity number) and ‘February 2014’ protests. The 2013 and 2014 protests occurred not only in Sarajevo, but also elsewhere in the country, and, to some extent, crossed the entity and its ethnic boundaries. If viewed in the context of regional uprisings from Maribor (Slovenia) via Athens to Taksim (Turkey), the Bosnian sequence of protests shared with them some common ground, or a similar cause – that is, the protests were against social injustice and the system that produces laws and political structures that maintain their hegemonic privileges and hierarchy. The analysis of protests in Bosnia provided in this text will also offer insights into some alternatives in articulating the new democratic counter-power that go beyond ethnonationalistic confines.
Molecular phylogenetic identification of two new brown-rot corticioid fungi in Dacryobolus from southwestern China
Authors: YUAN HAI-SHENG , KAN YU-HE , WAN XIAN-ZHEN
Published: June 2016

Two new brown-rot corticioid fungi, Dacryobolus gracilis and D. montanus, are described from Chongqing Municipality and Guangxi Autonomous Region, southwestern China. Dacryobolus gracilis is characterized by fragile, ceraceous basidiocarps, odontioid hymenophore with slender aculei, presence of long aculeal cystidia in the central part of the aculei and narrowly allantoid basidiospores; D. montanus is characterized by resupinate, ceraceous basidiocarps, odontioid hymenophore with thicker aculei, absence of cystidia or cystidioles, and narrowly allantoid basidiospores. Molecular phylogeny inferred from internal transcribed spacer (ITS) and ribosomal large subunit (nLSU) sequences data indicated that these two new species were clustered with the other species of Dacryobolus with a strong support. These two new species are described and illustrated in this paper. A key to known species of Dacryobolus is provided.
Zingiber skornickovae, a new species of Zingiberaceae from Central Vietnam
Authors: LÝ NGỌC-SÂM
Published: June 2016

Zingiber skornickovae, a new species from central Vietnam, is described and illustrated. A comparison with the two most closely related species of Zingiber sect. Cryptanthium, Z. thorelii and Z. recurvatum, and a key to all procumbent flowering species in Vietnam are provided.
Cladocolea molotensis (Loranthaceae), a new species for the cloud forest of Guerrero, Mexico
Authors: MARTÍNEZ-AMBRIZ EMMANUEL , LOZADA-PÉREZ LUCIO
Published: June 2016

A new species of Cladocolea, belonging to the cloud forest from the region of the Costa Grande of Guerrero, Mexico, is described and illustrated. Cladocolea molotensis is morphologically similar to C. loniceroides, but it differs by the leaf base being rounded to obtuse, the presence of conspicuous calcium oxalate crystals in the leaf surface and the peduncle, the pistillate flowers being tetramerous or pentamerous, the petals glabrous and staminodes usually inconspicuous or absent in the pistillate flowers.
Mussaenda campanulata (Rubiaceae), a new monomorphic species from China
Authors: DUAN TINGTING , LI SHIJIN , ZHANG DIANXIANG
Published: June 2016

A new monomorphic species of Mussaenda from China is illustrated and described. The new species, Mussaenda campanulata, is similar to M. shikokiana, but differing by its smaller drying papery leaves, faint yellow, campanulate-funnelform corolla, and lack of calycophylls. Moreover, the pollen morphology of M. campanulata is also reported.
FAMILY DIADOCIDIIDAE
Authors: FALASCHI RAFAELA LOPES
Published: June 2016

Diadocidiidae are a small family belonging to the suborder Bibionomorpha. Three species were described for the Neotropical region, two from Costa Rica and one from Brazil, and one additional undescribed species from Colombia is reported here for the first time.
FAMILY STRATIOMYIDAE
Authors: FACHIN DIEGO AGUILAR , DE ASSIS-PUJOL CRISTIANE VIEIRA
Published: June 2016

The family Stratiomyidae has more than 2,800 described species, of which 1001 species belongs to the Neotropics. This catalog for Colombia presents 87 species distributed in 32 genera, and ten subfamilies. Merosargus gracilis and the genus Microchrysa, with a single species M. bicolor are recorded for the first time to Colombia. The fauna is very expressive but still poorly known, representing nearly one tenth of the Neotropical diversity of the family in numbers of species, and one fifth of generic diversity.
FAMILY XYLOMYIDAE
Authors: FACHIN DIEGO AGUILAR , DE ASSIS-PUJOL CRISTIANE VIERA
Published: June 2016

This family is poor known in Colombia with only two known species of two genera, Solva tuberculata and Arthropeina colombiana.
FAMILY THEREVIDAE
Authors: RODRIGUES PAULA FERNANDA MOTTA , CALHAU JULIA
Published: June 2016

This catalogue presents the Colombian fauna of stiletto flies (Diptera: Therevidae). According to available literature, only four species, distributed in three genera, are registered to this country, Ataenogera brevicornis (Bromley, 1934), Brachylinga punctifrons (Kröber, 1914), B. xanthoperna Irwin and Webb, 1991 and Chromolepida pruinosa (Coquillett, 1904).
FAMILY SYRINGOGASTRIDAE
Authors: RUNG ALESSANDRA
Published: June 2016

This catalog features the three species of Syringogastridae that have been reported for Colombia. It is entirely based on literature data and contains no new records.
FAMILY CONOPIDAE
Authors: ROCHA LEONARDO SILVESTRE GOMES , MELLO-PATIU CÁTIA ANTUNES DE
Published: June 2016

A catalogue of the Conopidae known from Colombia, with 16 species distributed in four genera, is presented. The richest group is Stylogaster Macquart. Geographic distributions are given for each species.
FAMILY PERISCELIDIDAE
Authors: RUNG ALESSANDRA
Published: June 2016

This catalog summarizes information on the three species of Periscelididae known to occur in Colombia. One species belongs to the subfamily Periscelidinae, and two to the Stenomicrinae. This catalog includes no new record for Colombia.
FAMILY CURTONOTIDAE
Authors: MELLO RAMON LUCIANO
Published: June 2016

The family Curtonotidae is represented in the New World only by the genus Curtonotum Macquart. This catalogue presents the three species of Curtonotum recorded from Colombia: C. bivittatum Klymko & Marshall, C. trypetipenne Hendel and C. tumidum (Enderlein).
FAMILY STREBLIDAE
Authors: DICK CARL W. , GRACIOLLI GUSTAVO , GUERRERO RICARDO
Published: June 2016

This catalog presents 73 species distributed among 19 genera and three subfamilies of streblid bat flies recorded in Colombia. For each genus we present synonymies and type species, and for each species account we present synonymies, type host, disposition of type material, and specific localities and departments for records known from Colombia.
FAMILY RHINOPHORIDAE
Authors: NIHEI SILVIO S.
Published: June 2016

Only one species of Rhinophoridae has been recorded to Colombia so far, Bezzimyia busckii Townsend, 1919. However, three other species of the genus Bezzimyia are listed in the present catalogue, for they occur on nearby areas and are likely to occur in the country as well.
FAMILY SARCOPHAGIDAE
Authors: DE MELLO-PATIU CÁTIA ANTUNES
Published: June 2016

A catalogue of Sarcophagidae recorded from Colombia is presented, including 102 species in 26 genera, and two subfamilies. The geographical distribution by department is also given.
Impact of Satellite Data Assimilation in Atmospheric Reanalysis on the Marine Wind and Wave Climate
Authors: Sasaki Wataru
Published: June 2016

This study investigated the impact of assimilating satellite data into atmospheric reanalyses on trends in ocean surface winds and waves. Two experiments were performed using a numerical wave model forced by near-surface winds: one derived from the Japanese 55-year Reanalysis (JRA-55; experiment A) and the other derived from JRA-55 using assimilated conventional observations only (JRA-55C; experiment B). The results showed that the satellite data assimilation reduced upward trends of the annual mean of wave energy flux (WEF) in the midlatitude North Pacific and southern ocean (30°–60°S), south of Australia, from 1959 to 2012. It was also found that the assimilation of scatterometer winds reduced the near-surface wind speed in the midlatitude North Pacific after the mid-1990s, which resulted in the reduced trend in WEF from 1959 to 2012. By contrast, assimilation of the satellite radiances for 1973–94 increased near-surface wind speed in the southern ocean, south of Australia, whereas the assimilation of the scatterometer winds after the mid-1990s reduced wind speed. The latter led to the reduced trend in WEF south of Australia from 1959 to 2012.
A Simple Model for Sheddies: Ocean Eddies Formed from Shed Vorticity
Authors: Southwick O. R. , Johnson E. R. , McDonald N. R.
Published: June 2016

Recent studies show that vertical eddy diffusivity is sufficient on its own to introduce intense horizontal shear layers at sloping ocean margins (Molemaker et al.; Gula et al.; Dewar et al.). These layers influence mesoscale energy and potential vorticity budgets but cannot be fully represented in models without sloping boundaries, no-slip boundary conditions, and sufficiently high resolution. This paper investigates the detachment of these shear layers and their subsequent rolling up into concentrated eddies. These shed eddies, or “sheddies,” may have significant oceanographic impacts. Their growth is considered using a simple point vortex model that adapts the Brown–Michael model of vortex shedding to quasigeostrophic flow and allows detailed consideration of the vorticity fluxes. The model shows good qualitative agreement with observations and experimental and numerical results. It is applied to a number of examples of well-known cases of sheddy formation, including the Agulhas cyclones, California Undercurrent, and Canary Eddy Corridor, and also is used to investigate the effects of shed vorticity in the growth of the Cook Strait eddy and the interaction of the North Brazil Current rings with the islands of the Lesser Antilles.
Intercomparison of Unmanned Aircraftborne and Mobile Mesonet Atmospheric Sensors
Authors: Houston Adam L. , Laurence Roger J. , Nichols Tevis W. , Waugh Sean , Argrow Brian , Ziegler Conrad L.
Published: June 2016

Results are presented from an intercomparison of temperature, humidity, and wind velocity sensors of the Tempest unmanned aircraft system (UAS) and the National Severe Storms Laboratory (NSSL) mobile mesonet (NSSL-MM). Contemporaneous evaluation of sensor performance was facilitated by mounting the Tempest wing with attached sensors to the NSSL-MM instrument rack such that the Tempest and NSSL-MM sensors could collect observations within a nearly identical airstream. This intercomparison was complemented by wind tunnel simulations designed to evaluate the impact of the mobile mesonet vehicle on the observed wind velocity.

The intercomparison revealed strong correspondence between the temperature and relative humidity (RH) data collected by the Tempest and the NSSL-MM with differences generally within sensor accuracies. Larger RH differences were noted in the presence of heavy precipitation; however, despite the exposure of the Tempest temperature and humidity sensor to the airstream, there was no evidence of wet bulbing within precipitation. Wind tunnel simulations revealed that the simulated winds at the location of the NSSL-MM wind monitor were ~4% larger than the expected winds due to the acceleration of the flow over the vehicle. Simulated vertical velocity exceeded 1 m s−1 for tunnel inlet speeds typical of a vehicle moving at highway speeds. However, the theoretical noncosine reduction in winds that should result from the impact of vertical velocity on the laterally mounted wind monitor was found to be negligible across the simulations. Comparison of the simulated and observed results indicates a close correspondence, provided the crosswind component of the flow is small.
A Case Study on the Far-Field Properties of Propagating Tropospheric Gravity Waves
Authors: Stephan Claudia C. , Alexander M. Joan , Hedlin Michael , de Groot-Hedlin Catherine D. , Hoffmann Lars
Published: June 2016

Mesoscale gravity waves were observed by barometers deployed as part of the USArray Transportable Array on 29 June 2011 near two mesoscale convective systems in the Great Plains region of the United States. Simultaneously, AIRS satellite data indicated stratospheric gravity waves propagating away from the location of active convection. Peak perturbation pressure values associated with waves propagating outside of regions where there was precipitation reached amplitudes close to 400 Pa at the surface. Here the origins of the waves and their relationship to observed precipitation are investigated with a specialized model study. Simulations with a 4-km resolution dry numerical model reproduce the propagation characteristics and amplitudes of the observed waves with a high degree of quantitative similarity despite the absence of any boundary layer processes, surface topography, or moist physics in the model. The model is forced with a three-dimensional, time-dependent latent heating/cooling field that mimics the latent heating inside the precipitation systems. The heating is derived from the network of weather radar precipitation observations. This shows that deep, intense latent heat release within the precipitation systems is the key forcing mechanism for the waves observed at ground level by the USArray. Furthermore, the model simulations allow for a more detailed investigation of the vertical structure and propagation characteristics of the waves. It is found that the stratospheric and tropospheric waves are triggered by the same sources, but have different spectral properties. Results also suggest that the propagating tropospheric waves may potentially remotely interact with and enhance active precipitation.
Observing Boundary-Layer Winds from Hot-Air Balloon Flights
Authors: de Bruijn Evert I. F. , de Haan Siebren , Bosveld Fred C. , Schreur Ben Wichers , Holtslag Albert A. M.
Published: June 2016

High-resolution upper-air wind observations are sparse, and additional observations are a welcome source of meteorological information. In this paper the potential of applying balloon flights for upper-air wind measurements is explored, and the meteorological content of this information is investigated. The displacement of a hot-air balloon is a measure for the wind speed and direction and thus a potential source for wind observations in the lower part of the troposphere. The response time of the balloon on the changing wind is fast in the beginning and levels off for smaller relative wind speeds. Four case studies are presented, and the balloon-derived winds are compared with other wind observations and with results from the HIRLAM–ALADIN Research on Mesoscale Operational NWP in Europe (HARMONIE) model. It turns out that hot-air balloon tracks can indeed produce useful wind observations just above and in the atmospheric boundary layer (ABL).
Some Notes on the Semantics of οἱ δοκοῦντες in Galatians 2
Authors: Malik Peter
Published: June 2016

This article investigates Paul’s use of the term οἱ δοκοῦντες in the letter to the Galatians. Firstly, the term is considered from the standpoint of lexical semantics. Secondly, select relevant parallels from Ancient Greek literature are adduced and studied comparatively. Based on these considerations, it is argued that Paul uses οἱ δοκοῦντες as a rhetorical device, whereby he distances himself from the Jerusalem leaders and, in so doing, turns his opponents’ argument against them.
The Effect of Continuous Enteral Nutrition on Gastric Acidity in Humans
Authors: Kearns Patrick J.
Published: June 2016

Abstract: This study examines 24‐hour gastric pH response under four nutritional conditions in 11 normal subjects. The conditions include: fasting, normal meals, and infusion of an equicaloric nutritional solution either parenterally or intraduodenally (i.d.). The volunteers underwent four 24‐hour intragastric pH measurement studies. Serum glucose, calcium, immunoreactive insulin, and gastrin levels were determined at various intervals. Median 24‐hour gastric pH values were significantly lower during i.d. infusion than during parenteral feeding but were not significantly different from fasting or normal diet values. Median 24‐hour serum glucose levels during i.d. infusion were higher than during fasting and lower than during parenteral nutrition. Median 24‐hour serum insulin levels during i.d. infusion were higher than during fasting but similar to levels during parenteral nutrition. Neither median 24‐hour gastrin levels nor calcium levels were altered by the various regimens. The authors conclude that continuous i.d. nutrient infusion produces gastric pH values similar to fasting or normal meal levels, whereas parenteral nutrition increases gastric pH. This suggests that under physiologic conditions, gastric acidity is under feedback control
Enhancing Self-Help Career Planning Using Theory-Based Tools
Authors: Reardon Robert C.
Published: June 2016

From the earliest days of the vocational guidance movement, controversy existed regarding the place of self-report in assessment. Contemporary career theories, cognitive information processing theory (CIP), and Holland’s typological theory (Realistic, Investigative, Artistic, Social, Enterprising, Conventional [RIASEC]) provide ideas and tools for informing this issue. CIP theory includes self-help among three levels of career service delivery. Readiness screening including in both theories is the mechanism for determining which individuals can benefit from differentiated services, for example, self-help, brief staff assisted, and individual case managed. This article shows how these theories can be used in career assessment and describes tools and procedures for service delivery. A narrative flowchart illustrates how a practitioner would work with individuals in this enhanced self-help approach.
Regulation of lipid deposition in farm animals: Parallels between agriculture and human physiology
Authors: Bergen Werner G , Brandebourg Terry D
Published: June 2016

For many years, clinically oriented scientists and animal scientists have focused on lipid metabolism and fat deposition in various fat depots. While dealing with a common biology across species, the goals of biomedical and food animals lipid metabolism research differ in emphasis. In humans, mechanisms and regulation of fat synthesis, accumulation of fat in regional fat depots, lipid metabolism and dysmetabolism in adipose, liver and cardiac tissues have been investigated. Further, energy balance and weight control have also been extensively explored in humans. Finally, obesity and associated maladies including high cholesterol and atherosclerosis, cardiovascular disease, insulin resistance, hypertension, metabolic syndrome and health outcomes have been widely studied. In food animals, the emphasis has been on regulation of fatty acid synthesis and lipid deposition in fat depots and deposition of intramuscular fat. For humans, understanding the regulation of energy balance and body weight and of prevention or treatment of obesity and associated maladies have been important clinical outcomes. In production of food animals lowering fat content in muscle foods while enhancing intramuscular fat (marbling) have been major targets. In this review, we summarize how our laboratories have addressed the goal of providing lean but yet tasty and juicy muscle food products to consumers. In addition, we here describe efforts in the development of a new porcine model to study regulation of fat metabolism and obesity. Commonalities and differences in regulation of lipid metabolism between humans, rodents and food animals are emphasized throughout this review.
A review of entitlement
Authors: Jordan Peter J. , Ramsay Sheryl , Westerlaken Kristie M.
Published: June 2016

Interest in employee entitlement perceptions is increasing in academia and in organizations. Entitlement has a long history of being conceptualized as a personality trait in psychology closely aligned with narcissism. Research on workplace entitlement has generally revealed links with negative workplace behaviors, indicating costly outcomes for individuals, teams, and organizations. Our aim in this article is to review the literature on workplace entitlement perceptions, identifying how the construct has changed definition over time, and indicating related constructs that impact on research within industrial and organizational psychology. This review progresses research in this field by examining the nomological network around entitlement and resolving current inconsistencies in the construct definition of entitlement in the workplace, and establishing a set of firm future research directions for entitlement research.
EZH2 phosphorylation by JAK3 mediates a switch to noncanonical function in natural killer/T-cell lymphoma
Authors: Yan Junli , Li Boheng , Lin Baohong , Lee Pei Tsung , Chung Tae-Hoon , Tan Joy , Bi Chonglei , Lee Xue Ting , Selvarajan Viknesvaran , Ng Siok-Bian , Yang Henry , Yu Qiang , Chng Wee-Joo
Published: June 2016

Key Points

JAK3-mediated phosphorylation of EZH2 resulted in EZH2 oncogenic function independent of its enzymatic activity. Targeted inhibition of JAK3 may be a promising treatment in NK/TL through suppressing noncanonical EZH2 activity.
FcγRIIB on liver sinusoidal endothelial cells is essential for antibody-induced GPVI ectodomain shedding in mice
Authors: Stegner David , Popp Michael , Lorenz Viola , Wax Jacqueline K. , Gessner J. Engelbert , Nieswandt Bernhard
Published: June 2016

Key Points

Antibody-induced shedding of platelet GPVI in vivo and the associated transient thrombocytopenia depend on liver sinusoidal endothelial cell-expressed FcγRIIB.
Recent global trends in the prevalence and incidence of dementia, and survival with dementia
Authors: Prince Martin , Ali Gemma-Claire , Guerchet Maëlenn , Prina A. Matthew , Albanese Emiliano , Wu Yu-Tzu
Published: June 2016

Background

Current projections of the scale of the coming dementia epidemic assume that the age- and sex-specific prevalence of dementia will not vary over time, and that population ageing alone (increasing the number of older people at risk) drives the projected increases. The basis for this assumption is doubtful, and secular trends (that is, gradual decreases or increases in prevalence over long-term periods) are perfectly plausible.

Methods

We carried out a systematic review of studies of trends in prevalence, incidence and mortality for people with dementia, conducted since 1980.

Results

We identified nine studies that had tracked dementia prevalence, eight that had tracked dementia incidence, and four that had tracked mortality among people with dementia. There was some moderately consistent evidence to suggest that the incidence of dementia may be declining in high-income countries. Evidence on trends in the prevalence of dementia were inconsistent across studies and did not suggest any clear overall effect. Declining incidence may be balanced by longer survival with dementia, although mortality trends have been little studied. There is some evidence to suggest increasing prevalence in East Asia, consistent with worsening cardiovascular risk factor profiles, although secular changes in diagnostic criteria may also have contributed.

Conclusions

We found no evidence to suggest that the current assumption of constant age-specific prevalence of dementia over time is ill-founded. However, there remains some uncertainty as to the future scale of the dementia epidemic. Population ageing seems destined to play the greatest role, and prudent policymakers should plan future service provision based upon current prevalence projections. Additional priorities should include investing in brain health promotion and dementia prevention programs, and monitoring the future course of the epidemic to chart the effectiveness of these measures.
Vestibular function following unilateral cochlear implantation for profound sensorineural hearing loss
Authors: le Nobel Gavin J. , Hwang Euna , Wu Adrian , Cushing Sharon , Lin Vincent Y.
Published: June 2016

Background

Many Canadians are affected by sensorineural hearing loss (SNHL) and those with severe or profound hearing loss may have poor hearing function despite optimized hearing aids. Cochlear implants (CI) offer effective hearing rehabilitation for these patients, however, concern continues to exist regarding possible effects of CI on the vestibular system and balance. The objective of this study was to conduct a pilot study assessing the effects of unilateral cochlear implantation (CI) on balance and the vestibular system in post-lingually deafened adults.

Methods

Twelve patients were included in this pilot study and were assessed pre-operatively and at immediate, 1 week, and 1 month post-operative intervals. Assessments consisted of the dizziness handicap inventory (DHI), subjective visual vertical (SVV), and timed up-and-go testing (TUG). When applicable, testing was repeated with the CI on and off.

Results

Many patients were found to have deviated SVV at pre-operative and post-operative assessments. However, statistically significant changes were not seen when comparing pre-operative and post-operative SVV or when comparing SVV with the CI on and with the CI off. DHI was found to improve in five patients and worsen in two patients, however, no statistically significant change was found in DHI scores or with TUG testing.

Conclusions

This current pilot study does not indicate that CI surgery or implant activity influence vestibular or balance function, however, this pilot study is underpowered and greater numbers of patients would need be assessed to confirm these findings.
Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer
Authors: Sternberg Cora , Armstrong Andrew , Pili Roberto , Ng Siobhan , Huddart Robert , Agarwal Neeraj , Khvorostenko Denis , Lyulko Olexiy , Brize Arija , Vogelzang Nicholas , Delva Rémy , Harza Mihai , Thanos Anastasios , James Nicholas , Werbrouck Patrick , Bögemann Martin , Hutson Thomas , Milecki Piotr , Chowdhury Simon , Gallardo Enrique , Schwartsmann Gilberto , Pouget Jean-Christophe , Baton Frédérique , Nederman Thore , Tuvesson Helen , Carducci Michael
Published: June 2016

Purpose

Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit.

Patients and Methods

Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point.

Results

In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain.

Conclusion

In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.
Management of Brain Metastases in ALK-Positive Non–Small-Cell Lung Cancer
Authors: Rusthoven Chad G. , Doebele Robert C.
Published: June 2016

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

A 54-year-old man with a former 15-pack-year smoking history presents with cough and dyspnea. Initial work-up with imaging demonstrates a right suprahilar mass measuring 4.7 cm as well as several enlarged hilar and ipsilateral mediastinal lymph nodes. Bronchoscopy with biopsy reveals adenocarcinoma consistent with a lung primary. Staging with positron emission tomography/computed tomography (PET/CT) reidentifies the primary mass and lymph nodes and shows several PET-avid bone metastases. Brain magnetic resonance imaging (MRI) demonstrates a 1.6-cm right parietal mass with mild vasogenic edema and four additional brain metastases measuring 4 to 9 mm in size. Molecular testing is positive for an anaplastic lymphoma kinase (ALK) gene rearrangement using fluorescence in situ hybridization and negative for EGFR, ROS1, RET, BRAF, KRAS, and other oncogenes. The patient denies any neurologic symptoms and has no significant findings on neurologic exam. He is referred to you for management options for newly diagnosed stage IV (T2aN2M1b) lung adenocarcinoma.