bluuebunny/crossref_metadata_2025 huggingface dataset:
Weight Fluctuation and Cancer Risk in Postmenopausal Women: The Women's Health Initiative
Authors: Welti Laura M. , Beavers Daniel P. , Caan Bette J. , Sangi-Haghpeykar Haleh , Vitolins Mara Z. , Beavers Kristen M.
Published: January 2017

Background: Weight cycling, defined by an intentional weight loss and subsequent regain, commonly occurs in overweight and obese women and is associated with some negative health outcomes. We examined the role of various weight-change patterns during early to mid-adulthood and associated risk of highly prevalent, obesity-related cancers (breast, endometrial, and colorectal) in postmenopausal women.

Methods: A total of 80,943 postmenopausal women (age, 63.4 ± 7.4 years) in the Women's Health Initiative Observational Study were categorized by self-reported weight change (weight stable; weight gain; lost weight; weight cycled [1–3, 4–6, 7–10, >10 times]) during early to mid-adulthood (18–50 years). Three site-specific associations were investigated using Cox proportional hazard models [age, race/ethnicity, income, education, smoking, alcohol, physical activity, hormone therapy, diet, and body mass index (BMI)].

Results: A total of 7,464 (breast = 5,564; endometrial = 788; and colorectal = 1,290) incident cancer cases were identified between September 1994 and August 2014. Compared with weight stability, weight gain was significantly associated with risk of breast cancer [hazard ratio (HR), 1.11; 1.03–1.20] after adjustment for BMI. Similarly, weight cycling was significantly associated with risk of endometrial cancer (HR = 1.23; 1.01–1.49). Weight cycling “4 to 6 times” was most consistently associated with cancer risk, showing a 38% increased risk for endometrial cancer [95% confidence interval (CI), 1.08–1.76] compared with weight stable women.

Conclusions: Weight gain and weight cycling were positively associated with risk of breast and endometrial cancer, respectively.

Impact: These data suggest weight cycling and weight gain increase risk of prevalent cancers in postmenopausal women. Adopting ideal body-weight maintenance practices before and after weight loss should be encouraged to reduce risk of incident breast and endometrial cancers. Cancer Epidemiol Biomarkers Prev; 26(5); 779–86. ©2017 AACR.
A Novel Murine GITR Ligand Fusion Protein Induces Antitumor Activity as a Monotherapy That Is Further Enhanced in Combination with an OX40 Agonist
Authors: Leyland Rebecca , Watkins Amanda , Mulgrew Kathy A. , Holoweckyj Nicholas , Bamber Lisa , Tigue Natalie J. , Offer Emily , Andrews John , Yan Li , Mullins Stefanie , Oberst Michael D. , Coates Ulrichsen Jane , Leinster David A. , McGlinchey Kelly , Young Lesley , Morrow Michelle , Hammond Scott A. , Mallinder Philip , Herath Athula , Leow Ching Ching , Wilkinson Robert W. , Stewart Ross
Published: January 2017

Purpose: To generate and characterize a murine GITR ligand fusion protein (mGITRL-FP) designed to maximize valency and the potential to agonize the GITR receptor for cancer immunotherapy.

Experimental Design: The EC50 value of the mGITRL-FP was compared with an anti-GITR antibody in an in vitro agonistic cell–based reporter assay. We assessed the impact of dose, schedule, and Fc isotype on antitumor activity and T-cell modulation in the CT26 tumor model. The activity of the mGITRL-FP was compared with an agonistic murine OX40L-FP targeting OX40, in CT26 and B16F10-Luc2 tumor models. Combination of the mGITRL-FP with antibodies targeting PD-L1, PD-1, or CTLA-4 was analyzed in mice bearing CT26 tumors.

Results: The mGITRL-FP had an almost 50-fold higher EC50 value compared with an anti-murine GITR antibody. Treatment of CT26 tumor-bearing mice with mGITRL-FP–mediated significant antitumor activity that was dependent on isotype, dose, and duration of exposure. The antitumor activity could be correlated with the increased proliferation of peripheral CD8+ and CD4+ T cells and a significant decrease in the frequency of intratumoral Tregs. The combination of mGITRL-FP with mOX40L-FP or checkpoint inhibitor antagonists enhanced antitumor immunity above that of monotherapy treatment.

Conclusions: These results suggest that therapeutically targeting GITR represents a unique approach to cancer immunotherapy and suggests that a multimeric fusion protein may provide increased agonistic potential versus an antibody. In addition, these data provide, for the first time, early proof of concept for the potential combination of GITR targeting agents with OX40 agonists and PD-L1 antagonists. Clin Cancer Res; 23(13); 3416–27. ©2017 AACR.
Synthetic Lethality Exploitation by an Anti–Trop-2-SN-38 Antibody–Drug Conjugate, IMMU-132, Plus PARP Inhibitors in BRCA1/2–wild-type Triple-Negative Breast Cancer
Authors: Cardillo Thomas M. , Sharkey Robert M. , Rossi Diane L. , Arrojo Roberto , Mostafa Ali A. , Goldenberg David M.
Published: January 2017

Purpose: Both PARP inhibitors (PARPi) and sacituzumab govitecan (IMMU-132) are currently under clinical evaluation in triple-negative breast cancer (TNBC). We sought to investigate the combined DNA-damaging effects of the topoisomerase I (Topo I)–inhibitory activity of IMMU-132 with PARPi disruption of DNA repair in TNBC.

Experimental Design: In vitro, human TNBC cell lines were incubated with IMMU-132 and various PARPi (olaparib, rucaparib, or talazoparib) to determine the effect on growth, double-stranded DNA (dsDNA) breaks, and cell-cycle arrest. Mice bearing BRCA1/2-mutated or –wild-type human TNBC tumor xenografts were treated with the combination of IMMU-132 and PARPi (olaparib or talazoparib). Study survival endpoint was tumor progression to >1.0 cm3 and tolerability assessed by hematologic changes.

Results: Combining IMMU-132 in TNBC with all three different PARPi results in synergistic growth inhibition, increased dsDNA breaks, and accumulation of cells in the S-phase of the cell cycle, regardless of BRCA1/2 status. A combination of IMMU-132 plus olaparib or talazoparib produces significantly improved antitumor effects and delay in time-to-tumor progression compared with monotherapy in mice bearing BRCA1/2-mutated HCC1806 TNBC tumors. Furthermore, in mice bearing BRCA1/2–wild-type tumors (MDA-MB-468 or MDA-MB-231), the combination of IMMU-132 plus olaparib imparts a significant antitumor effect and survival benefit above that achieved with monotherapy. Most importantly, this combination was well tolerated, with no substantial changes in hematologic parameters.

Conclusions: These data demonstrate the added benefit of combining Topo I inhibition mediated by IMMU-132 with synthetic lethality provided by PARPi in TNBC, regardless of BRCA1/2 status, thus supporting the rationale for such a combination clinically. Clin Cancer Res; 23(13); 3405–15. ©2017 AACR.
Bone-Seeking Matrix Metalloproteinase-2 Inhibitors Prevent Bone Metastatic Breast Cancer Growth
Authors: Tauro Marilena , Shay Gemma , Sansil Samer S. , Laghezza Antonio , Tortorella Paolo , Neuger Anthony M. , Soliman Hatem , Lynch Conor C.
Published: January 2017

Bone metastasis is common during breast cancer progression. Matrix metalloproteinase-2 (MMP-2) is significantly associated with aggressive breast cancer and poorer overall survival. In bone, tumor- or host-derived MMP-2 contributes to breast cancer growth and does so by processing substrates, including type I collagen and TGFβ latency proteins. These data provide strong rationale for the application of MMP-2 inhibitors to treat the disease. However, in vivo, MMP-2 is systemically expressed. Therefore, to overcome potential toxicities noted with previous broad-spectrum MMP inhibitors (MMPIs), we used highly selective bisphosphonic-based MMP-2 inhibitors (BMMPIs) that allowed for specific bone targeting. In vitro, BMMPIs affected the viability of breast cancer cell lines and osteoclast precursors, but not osteoblasts. In vivo, we demonstrated using two bone metastatic models (PyMT-R221A and 4T1) that BMMPI treatment significantly reduced tumor growth and tumor-associated bone destruction. In addition, BMMPIs are superior in promoting tumor apoptosis compared with the standard-of-care bisphosphonate, zoledronate. We demonstrated MMP-2–selective inhibition in the bone microenvironment using specific and broad-spectrum MMP probes. Furthermore, compared with zoledronate, BMMPI-treated mice had significantly lower levels of TGFβ signaling and MMP-generated type I collagen carboxy-terminal fragments. Taken together, our data show the feasibility of selective inhibition of MMPs in the bone metastatic breast cancer microenvironment. We posit that BMMPIs could be easily translated to the clinical setting for the treatment of bone metastases given the well-tolerated nature of bisphosphonates. Mol Cancer Ther; 16(3); 494–505. ©2017 AACR.
Targeting Plk1 to Enhance Efficacy of Olaparib in Castration-Resistant Prostate Cancer
Authors: Li Jie , Wang Ruixin , Kong Yifan , Broman Meaghan M. , Carlock Colin , Chen Long , Li Zhiguo , Farah Elia , Ratliff Timothy L. , Liu Xiaoqi
Published: January 2017

Olaparib is an FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data have also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell-cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors. Herein, by combination with Plk1 inhibitor BI2536, we show a robust sensitization of olaparib in 22RV1, a BRCA1-deficient CRPC cell line, as well as in CRPC xenograft tumors. Mechanistically, monotherapy with olaparib results in an override of the G1–S checkpoint, leading to high expression of Plk1, which attenuates olaparib's overall efficacy. In BRCA1 wild-type C4-2 cells, Plk1 inhibition also significantly increases the efficacy of olaparib in the presence of p53 inhibitor. Collectively, our findings not only implicate the critical role of Plk1 in PARPi resistance in BRCA-mutant CRPC cells, but also shed new light on the treatment of non-BRCA–mutant patient subgroups who might also respond favorably to PARPi. Mol Cancer Ther; 16(3); 469–79. ©2017 AACR.
The CREBBP Acetyltransferase Is a Haploinsufficient Tumor Suppressor in B-cell Lymphoma
Authors: Zhang Jiyuan , Vlasevska Sofija , Wells Victoria A. , Nataraj Sarah , Holmes Antony B. , Duval Romain , Meyer Stefanie N. , Mo Tongwei , Basso Katia , Brindle Paul K. , Hussein Shafinaz , Dalla-Favera Riccardo , Pasqualucci Laura
Published: January 2017

Inactivating mutations of the CREBBP acetyltransferase are highly frequent in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), the two most common germinal center (GC)–derived cancers. However, the role of CREBBP inactivation in lymphomagenesis remains unclear. Here, we show that CREBBP regulates enhancer/super-enhancer networks with central roles in GC/post-GC cell fate decisions, including genes involved in signal transduction by the B-cell receptor and CD40 receptor, transcriptional control of GC and plasma cell development, and antigen presentation. Consistently, Crebbp-deficient B cells exhibit enhanced response to mitogenic stimuli and perturbed plasma cell differentiation. Although GC-specific loss of Crebbp was insufficient to initiate malignant transformation, compound Crebbp-haploinsufficient/BCL2-transgenic mice, mimicking the genetics of FL and DLBCL, develop clonal lymphomas recapitulating the features of the human diseases. These findings establish CREBBP as a haploinsufficient tumor-suppressor gene in GC B cells and provide insights into the mechanisms by which its loss contributes to lymphomagenesis.

Significance: Loss-of-function mutations of CREBBP are common and early lesions in FL and DLBCL, suggesting a prominent role in lymphoma initiation. Our studies identify the cellular program by which reduced CREBBP dosage facilitates malignant transformation, and have direct implications for targeted lymphoma therapy based on drugs affecting CREBBP-mediated chromatin acetylation. Cancer Discov; 7(3); 322–37. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 235
Comparative Proteomics Uncovers Correlated Signaling Network and Potential Biomarkers for Progression of Prostate Cancer
Authors: Ai Jianzhong , Lu Yi , Wei Qiang , Li Hong
Published: January 2017

Background/Aims: Prostate cancer is one of the most common cancers for males worldwide, and it is prone to show the metastatic foci in lymph node and bone with high mortality. To date, the potential mechanism and the corresponding biomarkers for metastatic prostate cancer are still lacking. Hence, our study aims to clarify the mechanism of prostate cancer progression and identify the useful biomarkers for metastatic prostate cancer. Methods: The proteins and network tightly associated with tumor metastasis were identified using quantitative proteomics. Furthermore, the mRNA level of differential expressed proteins were confirmed using qRT-PCR, and the functional cluster analysis was performed using String and Cytoscape. Results: Totally, our study identified 203 differential proteins closely associated with tumor cell migration, and the mRNA expression of those proteins were verified by qPCR. Moreover, the migration associated molecular network was established using bioinformatics analysis. Conclusion: These data raveled the critical proteins for the cell migration of prostate cancer, and identified the potential markers for diagnosing the metastasis of prostate cancer.
Associations of Body Mass Index With Laboratory and Biomarkers in Patients With Acute Heart Failure
Authors: Streng Koen W. , ter Maaten Jozine M. , Cleland John G. , O’Connor Christopher M. , Davison Beth A. , Metra Marco , Givertz Michael M. , Teerlink John R. , Ponikowski Piotr , Bloomfield Daniel M. , Dittrich Howard C. , Hillege Hans L. , van Veldhuisen Dirk J. , Voors Adriaan A. , van der Meer Peter
Published: January 2017

Background—

Plasma concentrations of natriuretic peptides decline with obesity in patients with heart failure. Whether this is true for other biomarkers is unknown. We investigated a wide range of biomarker profiles in acute heart failure across the body mass index (BMI) spectrum.

Methods and Results—

A total of 48 biomarkers, assessing multiple pathophysiological pathways, were measured in 2033 patients included in PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function), a trial comparing the effects of rolofylline to placebo in patients with acute heart failure. Patients were classified into 4 groups according to BMI (<25, 25–30, 30–35, and >35 kg/m
2
). Of 2003 patients with known weight and height, mean age was 70±12 years and 67% were men. Patients with a higher BMI (>35 kg/m
2
) had higher blood pressures, were younger, and were more often women. Median levels of brain natriuretic peptide were 550 pg/mL in patients with a BMI <25 kg/m
2
and 319 pg/mL in patients with a BMI >35 kg/m
2
(
P
<0.001). Multivariable regression revealed that brain natriuretic peptide (β=−0.250;
P
<0.001) and receptor for advanced glycation endproducts (β=−0.095;
P
<0.007) were inversely correlated to BMI, whereas higher levels of uric acid (β=0.164;
P
<0.001), proadrenomedullin (β=0.171;
P
<0.001), creatinine (β=0.118;
P
=0.003), sodium (β=0.101;
P
=0.006), and bicarbonate (β=0.094;
P
=0.009) were associated with higher BMI. No significant interaction was seen between these 7 biomarkers and BMI on 180-day mortality.

Conclusions—

The plasma concentrations of several biomarkers are either positively or negatively influenced by BMI. These findings suggest that these markers should be interpreted with caution in patients with obesity. Although concentrations differ, their prognostic value for mortality up to 180 days did not differ.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00354458.
Left Ventricular Hypertrophy Is Associated With Increased Infarct Size and Decreased Myocardial Salvage in Patients With ST‐Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
Authors: Nepper‐Christensen Lars , Lønborg Jacob , Ahtarovski Kiril Aleksov , Høfsten Dan Eik , Kyhl Kasper , Ghotbi Adam Ali , Schoos Mikkel Malby , Göransson Christoffer , Bertelsen Litten , Køber Lars , Helqvist Steffen , Pedersen Frants , Saünamaki Kari , Jørgensen Erik , Kelbæk Henning , Holmvang Lene , Vejlstrup Niels , Engstrøm Thomas
Published: January 2017

Background

Approximately one third of patients with ST‐segment elevation myocardial infarction (STEMI) have left ventricular hypertrophy (LVH), which is associated with impaired outcome. However, the causal association between LVH and outcome in STEMI is unknown. We evaluated the association between LVH and: myocardial infarct size, area at risk, myocardial salvage, microvascular obstruction, left ventricular (LV) function (all determined by cardiac magnetic resonance [CMR]), and all‐cause mortality and readmission for heart failure in STEMI patients treated with primary percutaneous coronary intervention.

Methods and Results

In this substudy of the DANAMI‐3 trial, 764 patients underwent CMR. LVH was defined by CMR and considered present if LV mass exceeded 77 (men) and 67 g/m
2
(women). One hundred seventy‐eight patients (24%) had LVH. LVH was associated with a larger final infarct size (15% [interquartile range {IQR}, 10–21] vs 9% [IQR, 3–17];
P
<0.001) and smaller final myocardial salvage index (0.6 [IQR, 0.5–0.7] vs 0.7 [IQR, 0.5–0.9];
P
<0.001). The LVH group had a higher incidence of microvascular obstruction (66% vs 45%;
P
<0.001) and lower final LV ejection fraction (LVEF; 53% [IQR, 47–60] vs 61% [IQR, 55–65];
P
<0.001). In a Cox regression analysis, LVH was associated with a higher risk of all‐cause mortality and readmission for heart failure (hazard ratio 2.59 [95% CI, 1.38–4.90],
P
=0.003). The results remained statistically significant in multivariable models.

Conclusions

LVH is independently associated with larger infarct size, less myocardial salvage, higher incidence of microvascular obstruction, lower LVEF, and a higher risk of all‐cause mortality and incidence of heart failure in STEMI patients treated with primary percutaneous coronary intervention.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01435408.
Neuroimaging Biomarkers Predict Brain Structural Connectivity Change in a Mouse Model of Vascular Cognitive Impairment
Authors: Boehm-Sturm Philipp , Füchtemeier Martina , Foddis Marco , Mueller Susanne , Trueman Rebecca C. , Zille Marietta , Rinnenthal Jan Leo , Kypraios Theodore , Shaw Laurence , Dirnagl Ulrich , Farr Tracy D.
Published: January 2017

Background and Purpose—

Chronic hypoperfusion in the mouse brain has been suggested to mimic aspects of vascular cognitive impairment, such as white matter damage. Although this model has attracted attention, our group has struggled to generate a reliable cognitive and pathological phenotype. This study aimed to identify neuroimaging biomarkers of brain pathology in aged, more severely hypoperfused mice.

Methods—

We used magnetic resonance imaging to characterize brain degeneration in mice hypoperfused by refining the surgical procedure to use the smallest reported diameter microcoils (160 μm).

Results—

Acute cerebral blood flow decreases were observed in the hypoperfused group that recovered over 1 month and coincided with arterial remodeling. Increasing hypoperfusion resulted in a reduction in spatial learning abilities in the water maze that has not been previously reported. We were unable to observe severe white matter damage with histology, but a novel approach to analyze diffusion tensor imaging data, graph theory, revealed substantial reorganization of the hypoperfused brain network. A logistic regression model from the data revealed that 3 network parameters were particularly efficient at predicting group membership (global and local efficiency and degrees), and clustering coefficient was correlated with performance in the water maze.

Conclusions—

Overall, these findings suggest that, despite the autoregulatory abilities of the mouse brain to compensate for a sudden decrease in blood flow, there is evidence of change in the brain networks that can be used as neuroimaging biomarkers to predict outcome.
Ditylenchus laurae sp. n. (Tylenchida: Anguinidae) from Poland – a new species of the D. dipsaci complex associated with a water plant, Potamogeton perfoliatus L.
Authors: Skwiercz Andrzej Tomasz , Kornobis Franciszek Wojciech , Winiszewska Grażyna , Przybylska Arnika , Obrępalska-Stęplowska Aleksandra , Gawlak Magdalena , Subbotin Sergei A.
Published: January 2017

The genus Ditylenchus consists of more than 60 species, some of which are plant parasites. In this paper we report on Ditylenchus laurae sp. n. from Poland, a new species associated with the aquatic plant, Potamogeton perfoliatus L. Ditylenchus laurae sp. n. is characterised by a long and slender body with L = 1881 (1523-2095) μm and 1875 (1690-2089) μm, a = 88.8 (72.5-102.5) and 89.7 (71.9-97.9), stylet length = 10.8 (9.6-12.1) μm and 8.3 (7.7-9.0) μm, tail length = 117.2 (103.5-126.7) μm and 102.4 (98.3-113.6) μm in females and males, respectively; four incisures, rounded stylet knobs, long basal bulb (about ten times as long as wide), post-vulval uterine sac from 4.3-5.6 vulval body diam. long, and mucronate tail. Characterisation using the ITS rRNA, COI and hsp90 gene sequences was conducted and a phylogenetic analyses revealed that D. laurae sp. n. belongs to the D. dipsaci complex.
Systematics and biogeography of Cuban porcelain crabs (Decapoda: Anomura: Porcellanidae)
Authors: DIEZ YANDER L. , LIRA CARLOS
Published: January 2017

Marine crustaceans are a well-known invertebrates group in Cuban waters, but some taxa are not well catalogued and the literature about them is scattered. In this work, we present the checklist of porcelain crabs of Cuban Archipelago, including the literature registers and unpublished author’s data. A key to the identification of 8 genera and 23 species of the Cuban porcelain crabs is provided. Information about the local distribution of species is presented. In addition, we analyzed the porcelain crab faunal affinities between the ecoregions of the Cuban platform, Greater Antilles islands and the Tropical Northwestern Atlantic (TNA) province. For the first time, we record the presence of the monotypic genus Parapetrolisthes Haig in Cuba. On the Cuban platform, the highest similarities are between the Southcentral and Northwestern ecoregions (50%) and between Northcentral and Northeastern (40%). In the Greater Antilles, Cuba and Puerto Rico are the most similar (54%), but in general, the porcelain crab composition shows a high variation (e. g. 19% between Hispaniola and Puerto Rico). In the Tropical Northwestern Atlantic, five homogeneous groups of porcelain crab species are distinguished. Cuban fauna is most similar to that of Floridian, Western Caribbean and Southern Gulf of Mexico ecoregions. The decrease in species richness is evident from south to north in the TNA Province.
Subcritical Destabilization of African Easterly Waves by Saharan Mineral Dust
Authors: Nathan Terrence R. , Grogan Dustin F. P. , Chen Shu-Hua
Published: January 2017

A theoretical framework is presented that exposes the radiative–dynamical relationships that govern the subcritical destabilization of African easterly waves (AEWs) by Saharan mineral dust (SMD) aerosols. The framework is built on coupled equations for quasigeostrophic potential vorticity (PV), temperature, and SMD mixing ratio. A perturbation analysis yields, for a subcritical, but otherwise arbitrary, zonal-mean background state, analytical expressions for the growth rate and frequency of the AEWs. The expressions are functions of the domain-averaged wave activity, which is generated by the direct radiative effects of the SMD. The wave activity is primarily modulated by the Doppler-shifted phase speed and the background gradients in PV and SMD.

Using an idealized version of the Weather Research and Forecasting (WRF) Model coupled to an interactive dust model, a linear analysis shows that, for a subcritical African easterly jet (AEJ) and a background SMD distribution that are consistent with observations, the SMD destabilizes the AEWs and slows their westward propagation, in agreement with the theoretical prediction. The SMD-induced growth rates are commensurate with, and can sometimes exceed, those obtained in previous dust-free studies in which the AEWs grow on AEJs that are supercritical with respect to the threshold for barotropic–baroclinic instability. The clarity of the theoretical framework can serve as a tool for understanding and predicting the effects of SMD aerosols on the linear instability of AEWs in subcritical, zonal-mean AEJs.
Analysis of the Southward Wind Shift of ENSO in CMIP5 Models
Authors: Abellán Esteban , McGregor Shayne , England Matthew H.
Published: January 2017

During the mature phase of El Niño–Southern Oscillation (ENSO) events there is a southward shift of anomalous zonal winds (SWS), which has been suggested to play a role in the seasonal phase locking of ENSO. Motivated by the fact that coupled climate models tend to underestimate this feature, this study examines the representation of the SWS in phase 5 of the Coupled Model Intercomparison Project (CMIP5). It is found that most models successfully reproduce the observed SWS, although the magnitude of the zonal wind stress anomaly is underestimated. Several significant differences between the models with and without the SWS are identified including biases in the magnitude and spatial distribution of precipitation and sea surface temperature (SST) anomalies during ENSO. Multiple-linear regression analysis suggests that the climatological meridional SST gradient as well as anomalous ENSO-driven convective activity over the northwest Pacific both might play a role in controlling the SWS. While the models that capture the SWS also simulate many more strong El Niño and La Niña events peaking at the correct time of year, the overall seasonal synchronization is still underestimated in these models. This is attributed to underestimated changes in warm water volume (WWV) during moderate El Niño events so that these events display relatively poor seasonal synchronization. Thus, while the SWS is an important metric, it is ultimately the magnitude and zonal extent of the wind changes that accompany this SWS that drive the changes in WWV and prime the system for termination.
The South Atlantic Subtropical High: Climatology and Interannual Variability
Authors: Sun Xiaoming , Cook Kerry H. , Vizy Edward K.
Published: January 2017

ERA-Interim and JRA-55 reanalysis products are analyzed to document the annual cycle of the South Atlantic subtropical high (SASH) and examine how its interannual variability relates to regional and large-scale climate variability. The annual cycle of the SASH is found to have two peaks in both intensity and size. The SASH is strongest and largest during the solstitial months when its center is either closest to the equator and on the western side of the South Atlantic basin during austral winter or farthest poleward and in the center of the basin in late austral summer. Although interannual variations in the SASH’s position are larger in the zonal direction, the intensity of the high decreases when it is positioned to the north. This relationship is statistically significant in every month. Seasonal composites and EOF analysis indicate that meridional changes in the position of the SASH dominate interannual variations in austral summer. In particular, the anticyclone tends to be displaced poleward in La Niña years when the southern annular mode (SAM) is in its positive phase and vice versa. Wave activity flux vectors suggest that ENSO-related convective anomalies located in the central-eastern tropical Pacific act as a remote forcing for the meridional variability of the summertime SASH. In southern winter, multiple processes operate in concert to induce interannual variability, and none of them appears to dominate like ENSO does during the summer.
Visual Hull Method for Realistic 3D Particle Shape Reconstruction Based on High-Resolution Photographs of Snowflakes in Free Fall from Multiple Views
Authors: Kleinkort C. , Huang G.-J. , Bringi V. N. , Notaroš B. M.
Published: January 2017

A visual hull method for reconstruction of realistic 3D shapes of snowflakes and other hydrometeors based on high-resolution photographs of particles in free fall from multiple views captured by a multiangle snowflake camera (MASC), or another similar instrument, is proposed and presented. The visual hull of an object is the maximal domain that gives the same silhouettes as the object from a certain set of viewpoints. From the measured fall speed and the particle shape reconstruction, the particle density and dielectric constant are estimated. This is the first time 3D shape reconstructions based on multiple high-resolution photographs of real (measured) snowflakes are performed. The results are clearly much better than any similar data in the literature. They demonstrate—in experiments involved in real snowstorm observations and those with simulated and fake 3D-printed snowflakes—sufficient silhouette information from the five cameras of the expanded MASC system and excellent performance of the implemented mechanical calibration and software self-calibration of the system. In addition to enabling realistic “particle by particle” computations of polarimetric radar measurables for winter precipitation, the visual hull 3D shape reconstructions of hydrometeors can be used for microphysical characteristics analyses, hydrometeor classification, and improvement of radar-based estimations of liquid-equivalent snow rates.
Convectively Induced Stabilizations and Subsequent Recovery with Supercell Thunderstorms during the Mesoscale Predictability Experiment (MPEX)
Authors: Trapp Robert J. , Woznicki Joseph M.
Published: January 2017

The adiabatic and diabatic processes inherent to midlatitude deep convective storms are well known to modify the atmospheric temperature, moisture, and winds especially within horizontal scales equivalent to a Rossby radius of deformation. Such modifications, or “feedbacks,” induced by supercell thunderstorms were a particular focus of the Mesoscale Predictability Experiment (MPEX), owing to the unique supercell dynamics and associated supercell intensity and longevity. During the MPEX field phase, which was conducted 15 May–15 June 2013 within the Great Plains region of the United States, radiosonde observations collected in immediate supercell wakes exhibited temperature lapse rates that were qualitatively and quantitatively similar to preconvective lapse rates above the boundary layer.

Complementary idealized model simulations were used to confirm that there was little residual effect of the supercell in the wake of the moving storm except within the area occupied by the surface cold pool, and where stabilizations were induced adiabatically by transient gravity wave disturbances. The persistency of the (i) cold pool, and its inhibition to surface-based convection, depended on the evolving cold pool strength and environmental winds; and (ii) gravity wave effects depended on the Doppler-shifted phase speed relative to the moving storm. Otherwise, recovery of the wake environment to its preconvective state occurred approximately over a time scale defined by the updraft length scale and horizontal advective velocity scale.
Distribution of Single-Banded Snowfall in Central U.S. Cyclones
Authors: Baxter Martin A. , Schumacher Philip N.
Published: January 2017

A climatology of single-banded snowfall in the central United States and the variability of processes at work in its formation are presented. Ninety-eight snowbands are identified in association with 66 cyclones over 5 yr spanning the winters from 2006/07 through 2010/11. An additional 38 cyclones featured nonbanded snowfall exceeding 4 in. (10.2 cm). Nearly twice as many bands were observed to the northeast of the surface low than to the northwest. Over each snowband’s life cycle, the median (mean) snowband lasted 4.0 (5.2) h, was 42 (45) km wide, 388 (428) km long, and had an aspect ratio of 10.2 (10.8). A common appearance exists for snowbands in different large-scale flow regimes and locations relative to the surface cyclone. The median snowband elongates during the first half of its life span, with its width remaining constant. During the second half of the median snowband’s life span, the length and width contract. Composite analysis of the synoptic and broad mesoscale environments that snowbands form in illustrates that the juxtaposition of the ingredients necessary for snowbands are similar no matter which quadrant of the surface low the band is located in, indicating that the synoptic-scale flow determines where these ingredients are organized with respect to the cyclone. The frequency of banded snowfall within each northern quadrant of the surface low, the typical snowband characteristics and their evolution, and the patterns that give rise to snowbands documented by this work can all prove useful to forecasters tasked with maintaining situational awareness in the presence of many solutions provided by ensemble numerical weather prediction.
Is In-Stent Restenosis After a Successful Coronary Stent Implantation Due to Stable Angina Associated With TG/HDL-C Ratio?
Authors: Kundi Harun , Korkmaz Ahmet , Balun Ahmet , Cicekcioglu Hulya , Kiziltunc Emrullah , Gursel Koray , Cetin Mustafa , Ornek Ender , Ileri Mehmet
Published: January 2017

We examined the impact of the preprocedural triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio on risk of in-stent restenosis (ISR). Patients with typical anginal symptoms and/or positive treadmill or myocardial perfusion scintigraphy test results who underwent successful coronary stent implantation due to stable angina were examined; 1341 patients were enrolled. The hospital files of the patients were used to gather data. Cox regression analysis showed that the TG/HDL-C ratio was independently associated with the presence of ISR ( P < .001). Moreover, diabetes mellitus ( P = .007), smaller stent diameter ( P = .046), and smoking status ( P = .001) were also independently associated with the presence of ISR. Using a cutoff of 3.8, the TG/HDL-C ratio predicted the presence of ISR with a sensitivity of 71% and a specificity of 68%. Also, the highest quartile of TG/HDL-C ratio had the highest rate of ISR ( P < .001). Measuring preprocedural TG/HDL-C ratio, in fasting or nonfasting samples, could be beneficial for the risk assessment of ISR. However, further large-scale prospective studies are required to establish the exact role of this simple, easily calculated, and reproducible parameter in the pathogenesis of ISR.
Photoangiolytic Laser Treatment of Early Glottic Cancer: A New Management Strategy
Authors: Zeitels Steven M. , Burns James A. , Lopez-Guerra Gerardo , Anderson R. Rox , Hillman Robert E.
Published: January 2017

The 532 nm pulsed KTP (potassium titanyl phosphate) laser and the 585 nm pulsed dye laser (PDL) are photoangiolytic lasers that have been demonstrated to be effective for managing vocal fold dysplasia. The putative mechanism of action is selective photoangiolysis of the sublesional microcirculation. On the basis of this experience, early glottic cancers were treated by selectively targeting the intralesional and sublesional microvasculature. This approach was derived from Folkman's concepts of neoplastic growth resulting from tumor angiogenesis. Staged microlaryngeal treatment was adopted, because it facilitated optimal functional results, and was considered safe, because early glottic cancer rarely metastasizes. Furthermore, intercurrent disease during conventional incremental radiotherapy is typical in treating early glottic cancer. A pilot group of 22 patients with early glottic cancer (13 T1, 9 T2) were treated with a fiber-based angiolytic laser. Eleven of the 22 had unilateral disease and were entirely treated by laser photoangiolysis as a sole modality. Eleven of the 22 had bilateral disease; 5 of the 11 were treated entirely (bilaterally) by laser photoangiolysis, and 6 of the 11 only underwent laser treatment of the less involved vocal fold, with conventional resection being done on the dominant side of the cancer. The initial 8 of the 22 were treated with the PDL, and the latter 14 of the 22 were treated with the pulsed KTP laser. No patient has cancer presently, and none have undergone posttreatment radiotherapy or open surgery. The mean follow-up is 27 months, 13 of the 22 patients have at least 2 years of follow-up, and the first patient was treated just over 5 years ago. Objective measures of vocal function revealed that photoangiolytic treatment of early glottic cancer resulted in significant postoperative improvements despite the fact that half of the patients had bilateral disease. Angiolytic lasers effectively involuted early glottic cancer, with microsurgically directed nonionizing radiation of the dense neoplastic blood supply resulting in complete tumor regression. This approach is conceptually attractive, because it is repeatable, it preserves all conventional cancer treatment options, and it results in excellent vocal function by improving phonatory mucosal wave vibration. Observations from this investigation suggest that this new and novel cancer treatment strategy is effective; however, larger patient cohorts, longer follow-up, and multi-institutional confirmation will be necessary to establish incontrovertible oncological efficacy.
Impact of light exposure on thyroid-stimulating hormone results using the Siemens Advia Centaur TSH-3Ultra assay
Authors: Armer Jane , Giles Diane , Lancaster Ian , Brownbill Kathryn
Published: January 2017

Background

Thyroid-stimulating hormone (TSH) is used as the first-line test of thyroid function. Siemens Healthcare Diagnostics recommend that Siemens Centaur reagents must be protected from light in the assay information and on reagent packaging. We have compared the effect of light exposure on results using Siemens TSH-3Ultra and follicle-stimulating hormone reagents. The thyroid-stimulating hormone reagent includes fluoroscein thiocyanate whereas the follicle-stimulating hormone reagent does not.

Methods

Three levels of quality controls were analysed using SiemensTSH-3Ultra and follicle-stimulating hormone reagent packs that had been kept protected from light or exposed to light at 6-h intervals for 48 h and then at 96 h.

Results

Thyroid-stimulating hormone results were significantly lower after exposure of TSH-3Ultra reagent packs to light. Results were >15% lower at all three levels of quality control following 18 h of light exposure and continued to decrease until 96 h. There was no significant difference in follicle-stimulating hormone results whether reagents had been exposed to or protected from light.

Conclusions

Thyroid-stimulating hormone results but not follicle-stimulating hormone results are lowered after exposure of reagent packs to light. Laboratories must ensure that TSH-3Ultra reagents are not exposed to light and analyse quality control samples on every reagent pack to check that there has not been light exposure prior to delivery. The labelling on TSH-3Ultra reagent packs should reflect the significant effect of light exposure compared with the follicle-stimulating hormone reagent. We propose that the effect of light exposure on binding of fluoroscein thiocyanate to the solid phase antibody causes the falsely low results.
A double-blind, randomized, placebo-controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression
Authors: Romijn Amy R , Rucklidge Julia J , Kuijer Roeline G , Frampton Chris
Published: January 2017

Objectives:

This trial investigated whether probiotics improved mood, stress and anxiety in a sample selected for low mood. We also tested whether the presence or severity of irritable bowel syndrome symptoms, and levels of proinflammatory cytokines, brain-derived neurotrophic factor and other blood markers, would predict or impact treatment response.

Method:

Seventy-nine participants (10 dropouts) not currently taking psychotropic medications with at least moderate scores on self-report mood measures were randomly allocated to receive either a probiotic preparation (containing Lactobacillus helveticus and Bifidobacterium longum) or a matched placebo, in a double-blind trial for 8 weeks. Data were analysed as intent-to-treat.

Results:

No significant difference was found between the probiotic and placebo groups on any psychological outcome measure (Cohen’s d range = 0.07–0.16) or any blood-based biomarker. At end-point, 9 (23%) of those in the probiotic group showed a ⩾60% change on the Montgomery–Åsberg Depression Rating Scale (responders), compared to 10 (26%) of those in the placebo group ([Formula: see text], p = ns). Baseline vitamin D level was found to moderate treatment effect on several outcome measures. Dry mouth and sleep disruption were reported more frequently in the placebo group.

Conclusions:

This study found no evidence that the probiotic formulation is effective in treating low mood, or in moderating the levels of inflammatory and other biomarkers. The lack of observed effect on mood symptoms may be due to the severity, chronicity or treatment resistance of the sample; recruiting an antidepressant-naive sample experiencing mild, acute symptoms of low mood, may well yield a different result. Future studies taking a preventative approach or using probiotics as an adjuvant treatment may also be more effective. Vitamin D levels should be monitored in future studies in the area. The results of this trial are preliminary; future studies in the area should not be discouraged.
The Impact of Computers on Students' Writing: A Comparative Study of the Effects of Pens and Word Processors on Writing Context, Process and Product
Authors: Snyder Ilana
Published: January 2017

This study investigated the impact of word processors on students' writing by examining three critical elements of the writing situation: writing context, process and product. Using a pretest-posttest control group design, the study compared two intact Year 8 classes, one using pens for composing and the other using computers, within the context of an all-girls school. A major emphasis of the research was the computer's impact on the quality of texts, representing three genres, which the students produced over a school year. The findings suggested that the computer classroom was more student-centred, less teacher-dominated and more work-focused, and the atmosphere was more co-operative and collaborative. Students' composing behaviours varied according to the genre of the task rather than according to the influence of the writing tool.
Restructuring Minority Schooling
Authors: Corson David
Published: January 2017

This article looks at organisational and curricular responses to cultural diversity which are presently operating alongside one another in New Zealand schooling. It begins with a critique of the minimal curricular response now recommended for government schools: the incorporation of programs in taha Maori (things Maori) within the mainstream curriculum of schools. It then looks at two recent responses which are structural and curricular: the modification of existing schools to take account of Maori student presence within them; and the development of Nga Kura Kaupapa Maori (Maori culture and language immersion primary schools) which are founded upon organisational and pedagogical features which are consistent with Maori cultural values. Conclusions are drawn relevant to the education of ‘involuntary minority’ cultures in Australia whose structural values and mores are very different from the dominant culture. A comparison of the values of Koori and Maori lends support to the view that Australian education could borrow with profit from the New Zealand example.
Equality or Quality? Selection to Prevocational Courses in South Australia 1981 to 1984
Authors: Bradley Denise
Published: January 2017

This paper outlines and analyses the debate in South Australia between 1981 and 1984 about entry to trade training and highlights the contradictions between government policies on equal opportunity for women in technical and further education and reform of trade training through the implementation of prevocational training courses. The debate about selection to prevocational courses was dominated till 1984 by those who argued that the persons chosen should be quality entrants, already exhibiting skills well beyond any minimum level of acceptability. Ways of aiding women to enter and succeed in these courses were not pursued and advocates for women, excluded from the tripartite decision-making processes, were unable to have arguments about equality for women considered in the debate until late in the process of reform of trade training.
The Soviet Union and Nordic Security
Authors: Holst Johan Jörgen
Published: January 2017

The author distinguishes between Soviet objectives of system preservation and system extension. Soviet policies vis-à-vis the Nordic area have been conceived primarily in the context of system preservation. Thus the Soviet Union has pursued a policy of no experiments and accepts the status quo as tolerable. The preferred Soviet model is that of a neutralist and fragmented Nordic system.

The Soviet naval expansion has resulted in the forward deployment of the Northern and Baltic fleets to the Greenland — Iceland — Faeroe Islands gap. There are several structural instabilities associated with a Soviet naval strategy of forward deployment. It also affects the efficacy and credibility of US reinforcements to Norway.

The North European security zone is likely to remain of considerable significance to the management of the Central Balance while oil drilling on the Norwegian continental shelf introduces a new element of uncertainty. In their negotiations with the EC the Nordic states appear to be preserving the regional equilibrium and the Soviet Union has made no serious objections.
System Transformation in Nigeria
Authors: Stokke Olav
Published: January 2017

In this paper the processes of integration and disintegration within the Nigerian Federation up to the secession of Biafra are analysed. The ‘modern’ and the ‘traditional’ political systems and sub-systems are identified and the cultural setting is outlined. The focus is concentrated on the distribution of the enforcement powers, the utilitarian powers and the identive powers between the centres of the federal system and the regional sub-systems, as manifested by subsequent constitutions and by the social bases of the political parties. In such a context the integrative and disintegrative effects of the political parties at the cultural, the federal and the regional levels are discussed. The major political crises of the early 1960s are outlined as are the developments after the military coup d'etats of 1966 leading to the secession. On this basis some preconditions for a successful secession are suggested, and the extent to which these were fulfilled or not in the case under consideration is discussed.