bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversible cerebral vasoconstriction syndrome associated with fingolimod treatment in relapsing–remitting multiple sclerosis three months after childbirth
Authors: Kraemer Markus , Weber Ralph , Herold Michèle , Berlit Peter
Published: August 2015

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by acute thunderclap headache, evidence of vasoconstriction in conventional angiography or magnetic resonance angiography and reversibility of these phenomena within 12 weeks. Some triggering factors, for example drugs such as selective serotonin reuptake inhibitors, sumatriptan, tacrolimus, cyclophosphamide and cocaine, or states such as pregnancy, puerperium or migraine have been described. We describe the case of a 29-year-old woman with RCVS associated with fingolimod three months after childbirth. This case represents the first report of RCVS in fingolimod treatment.
Antiaggregatory Effects of Picotamide in Long-Term Treatment: A 2-Year, Double-Blind Placebo-Controlled Trial
Authors: Cocozza Manlio , Milani Massimo , Picano Tommaso , Oliviero Ugo , Russo Nicola , Coto Vincenzo
Published: August 2015

The ex vivo antiaggregatory activity of picotamide, a dual antithromboxane agent, was assessed to find whether it was maintained in long-term treatment. In a double-blind, placebo-controlled 2-year study, 50 type 2 diabetic patients (35 men and 15 women; mean age 66 ± 5 years) were enrolled and randomly given picotamide, 300 mg t.i.d. or the corresponding placebo. Platelet aggregation studies were performed at baseline and after 1, 3, 6, 12, 18 and 24 months. Compliance to the treatment was assessed by pill count at each visit. Forty-nine patients concluded the study. Starting from month 1, compared with placebo, picotamide-treated patients showed a significant inhibition of agonist-induced (ADP, arachidonic acid and collagen) platelet aggregation (–41%). The antiaggregatory effect was maintained throughout the study. At month 24, in the picotamide group, platelet aggregation was significantly lower compared with placebo (–30%). After 24 months of treatment, 20 out of 23 (86%) picotamide-treated patients showed a significant inhibition of platelet aggregation, whereas the remaining three patients had a normal platelet response. During the study, 12 patients suffered from thrombotic events of death: nine in the placebo group and three in the picotamide group, respectively. It was concluded that picotamide maintains its antiaggregatory effect, in long-term treatment, in more than 85% of patients.
Teaching how to apologize: EFL textbooks and pragmatic input
Authors: Limberg Holger
Published: August 2015

Learners of English as a foreign language (EFL) are exposed to a collection of materials and communicative activities in the classroom through which they learn to use the language competently and appropriately. Textbooks, in particular, are a rich source of input, offering a variety of opportunities to acquire and practice pragmatic competence in specific areas of language use. One such area concerns apologies. As a ubiquitous and routinized pragmatic speech act, apologies are important to master for learners who have violated a socio-cultural norm. This study examines how German textbooks for EFL learners provide input on apologies and what tasks as well as exercises they suggest to practice and perform this act in the classroom. Teaching apologies – like any other speech act – should be based on rich, meaningful and authentic input and tasks in order for learners to appreciate and make use of this competence in real-life communication. The analysis of textbooks for secondary schools in Germany reveals the existence of some apology input, but also a lack of variety in terms of apology expressions. In addition, a noticeable difference between (implicit) input and (explicit) tasks exists, which can have an influence on the development of learners’ apology competence. EFL teachers need to be aware of what textbooks can and cannot offer, and then they need to adapt input and tasks for their teaching.
‘What happened next?’: Developmental changes in mothers’ questions to children
Authors: Kuchirko Yana , Tamis-LeMonda Catherine S , Luo Rufan , Liang Eva
Published: August 2015

Developmental changes in the questions mothers asked during book-sharing interactions with their preschool children and associations between mothers’ questions and children's narrative contributions were examined. Children and mothers from ethnically diverse backgrounds (African American, Dominican and Mexican) were video-recorded sharing the wordless book ‘Frog, Where are You?’ when children were three, four and five years of age. Mothers’ questions were coded as referential (e.g. ‘What's that?’), story-specific (e.g. ‘Where is the boy looking for the frog?’) and open-ended (e.g. ‘What will happen next?’). Mothers decreased their use of referential questions between the child ages of four and five in both frequency and proportion. Story-specific questions increased in frequency and proportion with increasing child age. Open-ended questions decreased in frequency between the child ages of four and five and did not change in proportion over time. Mothers’ question types related to children's narrative contributions concurrently and over time.
Insider Action research as an approach and a method – Exploring institutional encounters from within a birthing context
Authors: Nyman Viola , Berg Marie , Downe Soo , Bondas Terese
Published: August 2015

The aim of this paper was to describe the first person perspective of being a peer midwife and a novice researcher initiating collaborative AR in her own organization to develop knowledge about the first encounters between the labouring woman and her care-givers in a hospital birthing context. It was motivated by the author’s longstanding professional clinical experience of observing and hearing parents’ stories of vulnerability and fear of childbirth, and how staff’s attitudes affected the childbirth experience negatively. Data were collected between 2010 and 2013 and included the researcher’s log with reflections from clinical work, as well as interviews, participant observation, and research group communications. A reflective interpretative lifeworld research approach was used to analyze the data. The experience of being a novice insider action researcher (IARr) consisted of three thematic meanings: “the struggle to initiate a clinical insider action research project,” “standing alone at the messy front line,” and “being a catalytic counterbalance to the prevailing medico technical focus.” The comprehensive understanding was “learning how to clinically reflect on and to voice the tacit components of care.” The strategy used in undertaking this study was influenced by the philosophies of both midwifery care and AR.
Rapid RBE-Weighted Proton Radiation Dosimetry Risk Assessment
Authors: Qutub Mohammad A. Z. , Klein Susan B. , Buchsbaum Jeffrey C.
Published: August 2015

Proton therapy dose is affected by relative biological effectiveness differently than X-ray therapies. The current clinically accepted weighting factor is 1.1 at all positions along the depth–dose profile. However, the relative biological effectiveness correlates with the linear energy transfer, cell or tissue type, and the dose per fraction causing variation of relative biological effectiveness along the depth–dose profile. In this article, we present a simple relative biological effectiveness-weighted treatment planning risk assessment algorithm in 2-dimensions and compare the results with those derived using the standard relative biological effectiveness of 1.1. The isodose distribution profiles for beams were accomplished using matrices that represent coplanar intersecting beams. These matrices were combined and contoured using MATLAB to achieve the distribution of dose. There are some important differences in dose distribution between the dose profiles resulting from the use of relative biological effectiveness = 1.1 and the empirically derived depth-dependent values of relative biological effectiveness. Significant hot spots of up to twice the intended dose are indicated in some beam configurations. This simple and rapid risk analysis could quickly evaluate the safety of various dose delivery schema.
Micromanipulation Techniques in IVF
Authors: Ebner Thomas
Published: August 2015

After the world witnessed groundbreaking early advances in assisted reproduction that utilized conventional in vitro fertilization in the human, more complex invasive techniques of oocyte and embryo manipulation were introduced to treat human subfertility. Amongst these were numerous micromanipulation techniques such as partial zona dissection (PZD; 1988), subzonal insemination (SUZI, 1988) and subsequently ICSI, which became the most powerful tool of assisted fertilization (1992). ICSI requires micromanipulation of both the male and the female gamete. Another important approach is laser-assisted opening of the zona pellucida at different stages of preimplantation development either; to assist hatching (1990) or to remove cells for preimplantation genetic diagnosis (1989), or fragments to restore the integrity of an embryo (1999). Sometimes even blastocysts considered for vitrification need further manipulation in order to artificially shrink the blastocoel which facilitates survival of expanded blastocyst (2002). Other methods for reproductive purposes, however, failed to gain acceptance in population, such as cytoplasm transfer (1997), nuclear transfer (1998) and cloning (1996), to name but a few.
Recovery, Preparation, Storage and Utilization of Spermatozoa for Fertility Preservation in Cancer Patients and Sub-Fertile Men
Authors: Gupta Sajal , Agarwal Ashok , Sharma Reecha , Ahmady Ali
Published: August 2015

Sperm cryopreservation is an important part of an infertility program for patients undergoing infertility treatments, fertility assurance for vasectomy cases, and for fertility preservation due to cancer or other medical conditions. With recent developments in reproductive technology, even men with severely impaired sperm parameters can benefit from cryopreservation as procedures such as intra-cytoplasmic sperm injection (ICSI) require only a few sperm to achieve fertilization and pregnancy. The increasing success of cancer treatment and concerted efforts to ensure quality of life after successful treatment have placed great emphasis on the need to preserve the reproductive capability of young men. It is a highly effective method of protecting male fertility potential, and involves collection, freezing, and long-term storage of sperm. Based on the etiological condition of the patients, sperm can be collected by ejaculation or by surgical retrieval from epididymis or testes. The option to bank sperm should be offered systematically to all patients who may benefit. However, this is not a standard of practice yet; it may be overlooked due to lack of physician awareness regarding the need for fertility preservation and the effectiveness of this option, and/or overestimating the limitations of poor baseline sperm quality leading physician to view cryopreservation as futile. Failure to offer cryopreservation ignores the only possible reproductive option available to certain patients.
Oocyte Lysis following Intracytoplasmic Sperm Injection: Association with Measures of Oocyte Quality and Technician Performance
Authors: McCulloh David H , Goorbarry Jennifer , Shah Shrenik , Ahmad Khaliq
Published: August 2015

The purpose of this investigation was to assess the incidence of oocyte damage (oocyte lysis) following intracytoplasmic sperm injection (ICSI) and its association with oocyte quality and with the personnel performing the procedure. Data concerning damage were accumulated from a laboratory database that tabulated the results of each patient's ICSI results. The incidence of lysis following ICSI was 4.8% of all injected oocytes. The number of oocytes injected and the incidence of intact (not lysed) oocytes that were fertilized by ICSI both were inversely correlated with the incidence of lysis. Individual technicians had distinctively different profiles of lysis, 1PN and 3PN embryos. Technicians in training had slightly elevated incidence of lysis. Whereas evidence is presented that both patient-specific oocyte quality and technician-specific performance are significantly related to the incidence of lysis, the small incremental incidence of lysis associated with each source leads us to believe that the incidence of lysis is largely unpredictable and unsystematic in nature.
Characterization of Mongrel Dog Seminal Plasma Proteins and Their Correlation with Semen Characteristics
Authors: Cheema Ranjna Sandhey , Bhakri Gaurav , Gandotra Vinod Kumar , Dhanju Charanjit Kaur
Published: August 2015

The objective of this study was to characterize mongrel dog seminal plasma proteins with SDS-PAGE and to determine the correlation between different proteins and semen characteristics. Ejaculate volume, sperm motility, total sperm count, live sperm percent, percentage abnormalities and membrane integrity (hypo osmotic swelling test) were assessed in 5 ejaculates of seven dogs. For each dog, seminal plasma was also pooled from five ejaculates and proteins were separated by SDS-PAGE using polyacrylamide concentration of 13% and 15% in separating gels. There was considerable variation in the semen characteristics among the ejaculates of different dogs. Total protein content of seminal plasma varied from 12.06 to 21.3 mg/ml in different dogs. The number of protein bands ranged from 10–12 in different dogs. The proteins with mol wt of 42, 33, 29, 24 and 14.0 kDa were major proteins in seminal plasma of mongrel dog and ranged from 61.3% to 74.3% in different dogs. There were differences in live sperm percent (CD 5% =21.7) and HOS positive spermatozoa (CD 5% =21.01) among different dogs. There was strong correlation between volume of semen and total sperm concentration (r=+0.87), whereas the correlation between motility vs HOST (r=+0.58) and motility vs live percent (r=+0.60) was moderate. A positive correlation was observed between concentrations of 82, 70, 24, 14 kDa proteins vs percent motility, live sperm percent and percent HOS positive spermatozoa. Our study confirmed the previous conclusion that HOS-test could also be included in routine evaluation of semen. The positive correlation of 14, 24, 70 and 82 kDa proteins with semen characteristics also inferred the role of these proteins in the fertility of mongrel dog semen, which needs to be worked out further for their role in the process of fertilization.
Efficiency and Safety of Human Reproductive Cell/Tissue Vitrification
Authors: Parmegiani L. , Maggiulli R. , Menegazzo M. , Ebner T.
Published: August 2015

Vitrification is a cryopreservation technique increasingly applied in clinical practice for cells and tissue. This review article focuses mainly on the efficiency of vitrification of human reproductive cells and tissue, by analysing the clinical results reported in the literature. The second aspect discussed is safety of vitrification procedure. Different procedures and different types of carriers can be used, and in some cases vitrification requires a direct contact between cell/tissue/carrier and liquid nitrogen; this causes concern regarding the safety of this cryopreservation technique. Although the risk of contamination during cryopreservation remains negligible, this article explains how to overcome the hypothetical risk of contamination when using different types of vitrification carriers, in order to satisfy all existing directives.
Safeguarding the Global Research Cold Chain. In-Country and Transborder Transport of Cryopreserved Biological Specimens
Authors: Bishop Mark
Published: August 2015

The transport of cryopreserved biological products at a consistent temperature of −196°C can present significant challenge to researchers and laboratory personnel that may have little experience in this area. This communication will explore the basic principles for successfully managing the transport of cryogenic shipments both domestically and internationally, examining the need for proper packaging, knowledge of the regulatory environment in the country of destination, and a sound risk management strategy. It will also examine the special circumstances and considerations associated with sending cryopreserved biological samples to emerging nations and how best to safeguard shipments in the face of frail infrastructure, cumbersome regulatory environments, dramatic temperature fluctuations, etc. Finally, it will provide researchers with guidelines on identifying reliable and experienced transport/logistics providers and ensuring that their service capabilities conform to individual shipping needs.
Molecular-Targeted Therapy For Malignant Mesothelioma
Authors: Tada Yuji , Suzuki Toshio , Shimada Hideaki , Hiroshima Kenzo , Tatsumi Koichiro , Tagawa Masatoshi
Published: August 2015

Malignant pleural mesothelioma (MPM) is an intractable disease associated with asbestos exposure, and the number of affected patients will increase in the coming decades. The clinical outcome associated with current treatments is unsatisfactory, and the chemotherapy regimen for mesothelioma has remained unchanged for the past 10 years. Emerging molecular-targeted therapies are a novel way to treat other types of tumors and have been shown to drastically improve clinical response and patient prognosis. Some of these targeted agents had promising effects on MPM at the preclinical level and in various clinical trials that have been conducted over the last decade. Contrary to our expectations, results from the majority of these studies were disappointing and many were terminated at an early stage. No useful predictive or prognostic biomarkers were identified for mesothelioma treatment. Nevertheless, some novel strategies involving focal adhesion kinase inhibitors and immune checkpoint targeting agents showed some antitumor effects. In this article, we review the outcomes of previous clinical trials using molecular-targeted agents and discuss several hurdles that need to be overcome, which hopefully will contribute to a better understanding of this rare malignancy.
Effect of joint configuration on resistance spot weldability of galvanised DP780 steel sheets
Authors: Wei S. T. , Liu R. D. , Lv D. , Lin L. , Lu X. F. , Ding S. W.
Published: August 2015

A 780 MPa galvanised dual phase (DP) steel was two-, three- and four-layer resistance spot welded under different welding parameters and joint configurations. The splash situation, nugget sizes and tensile shear properties of the spot welds were evaluated systematically. The results showed that the splash occurring current increased in the order of two-, three- and four-layer spot welds owing to the increasing metal volume for melting. The joint configuration had a great influence on the tensile shear properties of the spot welds. The three- and four-layer spot welds with proper joint configurations had better weld quality than the two-layer spot weld. Therefore, well designed multilayer spot welds could be used to replace the commonly used two-layer spot welds in actual production.
Foot loading is different in people with and without pincer nails: a case control study
Authors: Sano Hitomi , Shionoya Kaori , Ogawa Rei
Published: August 2015

Background

Recent studies suggest that pincer nails are caused by lack of upward mechanical forces on the toe pad. However, clinically significant pincer nails are also often observed among healthy walkers. It was hypothesized that in these cases, the affected toes do not receive adequate physical stimulation from walking and loading. To test this, the gait characteristics of pincer nail cases were assessed by measuring plantar pressure during walking.

Methods

In total, 12 bilateral pincer nail cases (24 affected feet) and 12 age‐ and sex‐controlled healthy control subjects (24 ft) were enrolled in this prospective case–control study. Plantar pressure during free ambulation in both the barefoot and shod state was assessed using a digital pressure‐plate system named S‐Plate platform (Medicapteurs Co. France). First toe pressure and the frequencies of peak pressure in the first toe, metatarsal head, or other foot areas were calculated.

Results

In both the barefoot and shod state, the pincer nail group had significantly lower pressure on the first toe than the control group. In both the barefoot and shod state, the peak pressure area was mostly the metatarsal head area in the pincer nail group, whereas it was mostly the first toe area in the control group. Binomial logistic regression analysis revealed that peak pressure area was a significant risk factor for pincer nail development.

Conclusion

Walking behavior appears to contribute to pincer nail development. Pincer nails of walkers could be treated by correcting the walking behaviour so that more pressure is placed on the toe pad.
Loop diuretics in acute heart failure: beyond the decongestive relief for the kidney
Authors: Palazzuoli Alberto , Ruocco Gaetano , Ronco Claudio , McCullough Peter A.
Published: August 2015

Current goals in the acute treatment of heart failure are focused on pulmonary and systemic decongestion with loop diuretics as the cornerstone of therapy. Despite rapid relief of symptoms in patients with acute decompensated heart failure, after intravenous use of loop diuretics, the use of these agents has been consistently associated with adverse events, including hypokalemia, azotemia, hypotension, and increased mortality. Two recent randomized trials have shown that continuous infusions of loop diuretics did not offer benefit but were associated with adverse events, including hyponatremia, prolonged hospital stay, and increased rate of readmissions. This is probably due to the limitations of congestion evaluation as well as to the deleterious effects linked to drug administration, particularly at higher dosage. The impaired renal function often associated with this treatment is not extensively explored and could deserve more specific studies. Several questions remain to be answered about the best diuretic modality administration, global clinical impact during acute and post-discharge period, and the role of renal function deterioration during treatment. Thus, if loop diuretics are a necessary part of the treatment for acute heart failure, then there must be an approach that allows personalization of therapy for optimal benefit and avoidance of adverse events.
Clinical study replicability and the pursuit of excellence
Authors: Lanspa Michael J. , Hirshberg Eliotte L. , Miller Russell R. , Morris Alan H.
Published: August 2015

Comparisons of processes of care are common in critical care research. Often, these processes are neither explicit nor replicable and this can result in seemingly irreconcilable results. Here, we briefly review the article by Taniguchi and colleagues, who studied liberation from mechanical ventilation by using either a computerized weaning protocol or one driven by respiratory therapists. We discuss the implications of explicit protocols increasing replicability in clinical research.
Semilinear evolution equations with distributed measures
Authors: Petruşel Adrian , Satco Bianca
Published: August 2015

The aim of the paper is to provide, by an approach based on the Mönch fixed point theorem, existence results for the semilinear evolution problem with distributed measures $$ \textstyle\begin{cases} dx=(-Ax+f(t,x))\,dt+dg, \quad t\in[0,1],\\ x(0)=x_{0}, \end{cases} $$
{

d
x
=
(
−
A
x
+
f
(
t
,
x
)
)

d
t
+
d
g
,

t
∈
[
0
,
1
]
,

x
(
0
)
=

x
0

,

where −A is the infinitesimal generator of a (uniformly or strongly) continuous semigroup $\{T(t),t\geq0\}$
{
T
(
t
)
,
t
≥
0
}
of bounded linear operators, f is not necessarily continuous and $g:[0,1]\to X$
g
:
[
0
,
1
]
→
X
is a regulated function.

Working with Kurzweil-Stieltjes integrals and using a measure of non-compactness allows us to relax the assumptions on the semigroup, on f and g comparing to some already known results.
$C^{*}$-Valued contractive type mappings
Authors: Batul Samina , Kamran Tayyab
Published: August 2015

In this paper we generalize the notion of $C^{*}$

C
∗

-valued contraction mappings, recently introduced by Ma et al., by weakening the contractive condition introduced by them. Using the new notion of $C^{*}$

C
∗

-valued contractive type mappings, we establish a fixed point theorem for such mappings. Our result generalizes the result by Ma et al. and those contained therein except for the uniqueness.
Fixed point of multivalued integral type of contraction mappings
Authors: Stojaković Mila , Gajić Ljiljana , Došenović Tatjana , Carić Biljana
Published: August 2015

In this paper the fixed point of multivalued mapping is considered. A generalization of the well-known Nadler contraction principle, the Khan contraction theorem and the fixed point theorem in complete metric space with a convex structure is proved. The main result of the paper is formulated by three theorems where the mappings, defined over the complete metric space, are assumed to satisfy some integral type of contraction.
The complete genome sequence of the rumen methanogen Methanosarcina barkeri CM1
Authors: Lambie Suzanne C. , Kelly William J. , Leahy Sinead C. , Li Dong , Reilly Kerri , McAllister Tim A. , Valle Edith R. , Attwood Graeme T. , Altermann Eric
Published: August 2015

Methanosarcina species are the most metabolically versatile of the methanogenic Archaea and can obtain energy for growth by producing methane via the hydrogenotrophic, acetoclastic or methylotrophic pathways. Methanosarcina barkeri CM1 was isolated from the rumen of a New Zealand Friesian cow grazing a ryegrass/clover pasture, and its genome has been sequenced to provide information on the phylogenetic diversity of rumen methanogens with a view to developing technologies for methane mitigation. The 4.5 Mb chromosome has an average G + C content of 39 %, and encodes 3523 protein-coding genes, but has no plasmid or prophage sequences. The gene content is very similar to that of M. barkeri Fusaro which was isolated from freshwater sediment. CM1 has a full complement of genes for all three methanogenesis pathways, but its genome shows many differences from those of other sequenced rumen methanogens. Consequently strategies to mitigate ruminant methane need to include information on the different methanogens that occur in the rumen.
Microseismic and seismic denoising via ensemble empirical mode decomposition and adaptive thresholding
Authors: Han Jiajun , van der Baan Mirko
Published: August 2015

Random and coherent noise exists in microseismic and seismic data, and suppressing noise is a crucial step in seismic processing. We have developed a novel seismic denoising method, based on ensemble empirical mode decomposition (EEMD) combined with adaptive thresholding. A signal was decomposed into individual components called intrinsic mode functions (IMFs). Each decomposed signal was then compared with those IMFs resulting from a white-noise realization to determine if the original signal contained structural features or white noise only. A thresholding scheme then removed all nonstructured portions. Our scheme is very flexible, and it is applicable in a variety of domains or in a diverse set of data. For instance, it can serve as an alternative for random noise removal by band-pass filtering in the time domain or spatial prediction filtering in the frequency-offset domain to enhance the lateral coherence of seismic sections. We have determined its potential for microseismic and reflection seismic denoising by comparing its performance on synthetic and field data using a variety of methods including band-pass filtering, basis pursuit denoising, frequency-offset deconvolution, and frequency-offset empirical mode decomposition.
Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors
Authors: Rock Cheryl L. , Flatt Shirley W. , Byers Tim E. , Colditz Graham A. , Demark-Wahnefried Wendy , Ganz Patricia A. , Wolin Kathleen Y. , Elias Anthony , Krontiras Helen , Liu Jingxia , Naughton Michael , Pakiz Bilgé , Parker Barbara A. , Sedjo Rebecca L. , Wyatt Holly
Published: August 2015

Purpose

Obesity increases risk for all-cause and breast cancer mortality and comorbidities in women who have been diagnosed and treated for breast cancer. The Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) study is the largest weight loss intervention trial among survivors of breast cancer to date.

Methods

In this multicenter trial, 692 overweight/obese women who were, on average, 2 years since primary treatment for early-stage breast cancer were randomly assigned to either a group-based behavioral intervention, supplemented with telephone counseling and tailored newsletters, to support weight loss or a less intensive control intervention and observed for 2 years. Weight and blood pressure were measured at 6, 12, 18, and 24 months. Longitudinal mixed models were used to analyze change over time.

Results

At 12 months, mean weight loss was 6.0% of initial weight in the intervention group and 1.5% in the control group (P < .001). At 24 months, mean weight loss in the intervention and control groups was 3.7% and 1.3%, respectively (P < .001). Favorable effects of the intervention on physical activity and blood pressure were observed. The weight loss intervention was more effective among women older than 55 years than among younger women.

Conclusion

A behavioral weight loss intervention can lead to clinically meaningful weight loss in overweight/obese survivors of breast cancer. These findings support the need to conduct additional studies to test methods that support sustained weight loss and to examine the potential benefit of intentional weight loss on breast cancer recurrence and survival.
High Doses of Antimetabolites Followed by High-Dose Sequential Chemoimmunotherapy and Autologous Stem-Cell Transplantation in Patients With Systemic B-Cell Lymphoma and Secondary CNS Involvement: Final Results of a Multicenter Phase II Trial
Authors: Ferreri Andrés J.M. , Donadoni Giovanni , Cabras Maria Giuseppina , Patti Caterina , Mian Michael , Zambello Renato , Tarella Corrado , Di Nicola Massimo , D'Arco Alfonso M. , Doa Gianluca , Bruno-Ventre Marta , Assanelli Andrea , Foppoli Marco , Citterio Giovanni , Fanni Alessandro , Mulè Antonino , Caligaris-Cappio Federico , Ciceri Fabio
Published: August 2015

Purpose

Treatment of secondary CNS dissemination in patients with aggressive lymphomas remains an important, unmet clinical need. Herein, we report the final results of a multicenter phase II trial addressing a new treatment for secondary CNS lymphoma based on encouraging experiences with high doses of antimetabolites in primary CNS lymphoma and with rituximab plus high-dose sequential chemoimmunotherapy (R-HDS) in relapsed aggressive lymphoma.

Patients and Methods

HIV-negative patients with aggressive B-cell lymphoma and secondary CNS involvement at diagnosis or relapse, age 18 to 70 years, and Eastern Cooperative Oncology Group performance status ≤ 3 were enrolled and treated with high-doses of methotrexate and cytarabine, followed by R-HDS (cyclophosphamide, cytarabine, and etoposide) supported by autologous stem-cell transplantation (ASCT). Treatment included eight doses of rituximab and four doses of intrathecal liposomal cytarabine. The primary end point was 2-year event-free survival; the planned accrual was 38 patients.

Results

Thirty-eight patients were enrolled; CNS disease was detected at presentation in 16 patients. Toxicity was usually hematologic and manageable, with grade 4 febrile neutropenia in 3% of delivered courses and grade 4 nonhematologic toxicity in 2% of delivered courses. Four patients died because of toxicity. Autologous stem cells were successfully collected in 24 (89%) of 27 patients (median, 10 × 106/kg); 20 patients underwent ASCT. Complete response was achieved in 24 patients (complete response rate, 63%; 95% CI, 48% to 78%). At a median follow-up of 48 months, 17 patients remained relapse free, with a 2-year event-free survival rate of 50% ± 8%. At 5 years, 16 patients were alive, with a 5-year overall survival rate of 41% ± 8% for the whole series and 68% ± 11% for patients who received transplantation. Systemic (extra-CNS) and/or meningeal disease did not affect outcome.

Conclusion

The combination of high doses of antimetabolites, R-HDS, and ASCT is feasible and effective in patients age 18 to 70 years old with secondary CNS lymphoma, and we propose it as a new standard therapeutic option.
Diacetylspermine Is a Novel Prediagnostic Serum Biomarker for Non–Small-Cell Lung Cancer and Has Additive Performance With Pro-Surfactant Protein B
Authors: Wikoff William R. , Hanash Samir , DeFelice Brian , Miyamoto Suzanne , Barnett Matt , Zhao Yang , Goodman Gary , Feng Ziding , Gandara David , Fiehn Oliver , Taguchi Ayumu
Published: August 2015

Purpose

We have investigated the potential of metabolomics to discover blood-based biomarkers relevant to lung cancer screening and early detection. An untargeted metabolomics approach was applied to identify biomarker candidates using prediagnostic sera from the Beta-Carotene and Retinol Efficacy Trial (CARET) study.

Patients and Methods

A liquid chromatography/mass spectrometry hydrophilic interaction method designed to profile a wide range of metabolites was applied to prediagnostic serum samples from CARET participants (current or former heavy smokers), consisting of 100 patients who subsequently developed non–small-cell lung cancer (NSCLC) and 199 matched controls. A separate aliquot was used to quantify levels of pro-surfactant protein B (pro-SFTPB), a previously established protein biomarker for NSCLC. On the basis of the results from the discovery set, blinded validation of a metabolite, identified as N1,N12-diacetylspermine (DAS), and pro-SFTPB was performed using an independent set of CARET prediagnostic sera from 108 patients with NSCLC and 216 matched controls.

Results

Serum DAS was elevated by 1.9-fold, demonstrating significant specificity and sensitivity in the discovery set for samples collected up to 6 months before diagnosis of NSCLC. In addition, DAS significantly complemented performance of pro-SFTPB in both the discovery and validations sets, with a combined area under the curve in the validation set of 0.808 (P < .001 v pro-SFTPB).

Conclusion

DAS is a novel serum metabolite with significant performance in prediagnostic NSCLC and has additive performance with pro-SFTPB.
Type 2 Iodothyronine Deiodinase Activity Is Required for Rapid Stimulation of PI3K by Thyroxine in Human Umbilical Vein Endothelial Cells
Authors: Aoki Tomoyuki , Tsunekawa Katsuhiko , Araki Osamu , Ogiwara Takayuki , Nara Makoto , Sumino Hiroyuki , Kimura Takao , Murakami Masami
Published: August 2015

Thyroid hormones (THs) exert a number of physiological effects on the cardiovascular system. Some of the nongenomic actions of T3 are achieved by cross coupling the TH receptor (TR) with the phosphatidylinositol 3-kinase (PI3K)/protein kinase Akt (Akt) pathway. We observed that both T3 and T4 rapidly stimulated Akt phosphorylation and Ras-related C3 botulinum toxin substrate 1 (Rac1) activation, which resulted in cell migration, in a PI3K-dependent manner in human umbilical vein endothelial cells (HUVECs). We identified the expression of type 2 iodothyronine deiodinase (D2), which converts T4 to T3, and TRα1 in HUVECs. D2 activity was significantly stimulated by (Bu)2cAMP in HUVECs. The blockade of D2 activity through transfection of small interfering RNA (siRNA) specific to D2 as well as by addition of iopanoic acid, a potent D2 inhibitor, abolished Akt phosphorylation, Rac activation, and cell migration induced by T4 but not by T3. The inhibition of TRα1 expression by the transfection of siRNA for TRα1 canceled Akt phosphorylation, Rac activation, and cell migration induced by T3 and T4. These findings suggest that conversion of T4 to T3 by D2 is required for TRα1/PI3K-mediated nongenomic actions of T4 in HUVECs, including stimulation of Akt phosphorylation and Rac activation, which result in cell migration.
Desaturase Activity Is Associated With Weight Status and Metabolic Risk Markers in Young Children
Authors: Wolters Maike , Schlenz Heike , Börnhorst Claudia , Risé Patrizia , Galli Claudio , Moreno Luis A. , Pala Valeria , Siani Alfonso , Veidebaum Toomas , Tornaritis Michael , Fraterman Arno , de Henauw Stefaan , Marild Staffan , Molnar Denes , Ahrens Wolfgang ,   on behalf of the IDEFICS consortium
Published: August 2015

Context:

Activity of delta-9, delta-6, and delta-5 desaturases (D9D, D6D, D5D) are associated with obesity, insulin resistance, and dyslipidemia.

Objective:

To investigate the association of estimated desaturase activities with weight status, insulin resistance, and dyslipidemia in children, cross-sectionally and longitudinally.

Design:

The IDEFICS (Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants) cohort study was used, with examinations at baseline (T0) and after 2 years (T1).

Setting and Participants:

Children aged 2 to less than 10 years from eight European countries were recruited in kindergartens/primary schools. Children with available data on fatty acids, outcome, and covariate information were included in the analyses.

Methods:

Whole blood fatty acids were analyzed in 2600 children at baseline. D9D (16:1n-7/16:0), D6D (20:3n-6/18:2n-6), and D5D (20:4n-6/20:3n-6) activities were estimated from product-precursor fatty acids ratios. Body mass index (BMI), Homeostatic Model Assessment index, and high-density lipoprotein cholesterol (HDL), and triglycerides (TG) served as outcomes for weight status, insulin resistance, and dyslipidemia, respectively. Linear and logistic regression and repeated measures models were used to assess the cross-sectional and longitudinal associations between desaturase activity and outcomes.

Results:

In the cross-sectional analysis, D9D and D6D were positively associated with BMI and TG z-scores and inversely with HDL z-scores. D5D was inversely associated with BMI and TG z-scores (ie, a D5D increase of 1 unit is associated with a BMI z-score decrease of 0.07 and a 28% lower odds ratio for TG ≥75th percentile). Longitudinally, similar associations were found for T0 desaturase activities with BMI and for T0 D6D with HDL at follow-up (T1). Baseline D6D and D5D were positively associated with the change of HDL z-score from T0 to T1, and D6D with the change of Homeostatic Model Assessment index z-score.

Conclusion:

Desaturase activities are associated with metabolic risk markers already in young children and appear to predict the metabolic risk.
Caresser's Dominion: Race, Nation, and Calypso in Postwar Canada
Authors: Eldridge Michael
Published: August 2015

Just after World War II, the Canadian Broadcasting Corporation hired the Trinidadian calypsonian Lord Caresser to host a weekly program airing on its nationwide network and its fledgling International Service. His engagement, this essay argues, had less to do with “carry[ing] calypso to the world” (as a CBC press release put it) than with projecting to the world a particular image of Canada—as a modern, diverse, racially tolerant nation. That project was compromised, however, by Canada's fraught history with the West Indies. Reading Caresser's CBC career in the context of proposals for Canadian–West Indies “union” and the infamous West Indian Domestic Scheme of the 1950s, Eldridge uncovers some of the more obscure origins of Canada's imperfect multiculturalism.
José E. Muñoz's Critical Caribbean Crossroads
Authors: Horn Maja
Published: August 2015

This essay is a personal reflection on how Horn's scholarship on gender, sexuality, and performance in the hispanophone Caribbean has been shaped by the oeuvre of the late critical theorist José E. Muñoz. In particular, Horn compares and contrasts the uses of “hybridity” and “performance” in Muñoz's work to the work of Antonio Benítez-Rojo, another Cuban/Cuban American scholar who has foregrounded the role of performance in the Caribbean. The author furthermore suggests how Muñoz's later critical work on subjectivity, sexuality, and evidence speaks to queer Dominican cultures, experiences, and epistemologies.
“What Comes after Loss?”: Ana Mendieta after José
Authors: Alvarado Leticia
Published: August 2015

This essay is a brief reflection on Ana Mendieta's Silueta Series, the Cuban diaspora, Latinidad, and ultimately brownness, after the loss of José E. Muñoz.
Primordial germ cells: the first cell lineage or the last cells standing?
Authors: Johnson Andrew D. , Alberio Ramiro
Published: August 2015

Embryos of many animal models express germ line determinants that suppress transcription and mediate early germ line commitment, which occurs before the somatic cell lineages are established. However, not all animals segregate their germ line in this manner. The ‘last cell standing’ model describes primordial germ cell (PGC) development in axolotls, in which PGCs are maintained by an extracellular signalling niche, and germ line commitment occurs after gastrulation. Here, we propose that this ‘stochastic’ mode of PGC specification is conserved in vertebrates, including non-rodent mammals. We postulate that early germ line segregation liberates genetic regulatory networks for somatic development to evolve, and that it therefore emerged repeatedly in the animal kingdom in response to natural selection.
The embryo reunited with its membranes in Göttingen
Authors: Stern Claudio
Published: August 2015

An EMBO workshop entitled ‘Embryonic-Extraembryonic Interfaces’ took place in Göttingen, Germany, in May 2015. It showcased the enormous breadth of this area not only by touching on the molecular and cellular mechanisms of development, but also because of its coverage of particularly interesting evolutionary questions and of several medically related aspects. This Meeting Review discusses some highlights from the workshop and the emerging themes in the field.
Phylogeny and speciation in Saxifraga sect. Ciliatae (Saxifragaceae): Evidence from psbA‐trnH, trnL‐F and ITS sequences
Authors: Gao Qing-Bo , Li Yin-Hu , Gornall Richard J. , Zhang Zhuo-Xin , Zhang Fa-Qi , Xing Rui , Fu Peng-Cheng , Wang Jiu-Li , Liu Hai-Rui , Tian Zun-Zhe , Chen Shi-Long
Published: August 2015

Nearly half of the species in the large genus Saxifraga belong to Saxifraga sect. Ciliatae, a largely Sino‐Himalayan taxon. We report here that evidence from chloroplast DNA sequences (psbA‐trnH, trnL‐F) and from nuclear sequences (ITS) indicates that this section is monophyletic and composed of at least three main lineages, corresponding to (1) a clade made up of species from S. subsect. Gemmiparae, subsect. Cinerascentes, subsect. Flagellares and subsect. Hemisphaericae, in which the last three subsections are nested in the first; (2) a clade of species belonging to S. subsect. Rosulares (including S. subsect. Serpyllifoliae); and (3) a clade of species belonging to S. subsect. Hirculoideae. Species relationships in S. subsect. Rosulares and subsect. Hirculoideae are not well resolved. A molecular clock analysis indicates that the diversification of S. sect. Ciliatae into its three lineages dates from ca. 9.48 Ma, coinciding with orogenic events associated with one of the most important phases of uplift of the Qinghai‐Tibet Plateau. Extensive diversifications within S. subsect. Rosulares and subsect. Hirculoideae have been more recent (ca. 4.51 Ma and 2.12 Ma, respectively), again correlated with Qinghai‐Tibet Plateau uplift events and, in the case of S. subsect. Hirculoideae, have occurred at a rate comparable to that seen in the radiation of Hawaiian fruit flies.
Phylogeny, diversification and biogeographic implications of the eastern Mediterranean endemic genus Ricotia (Brassicaceae)
Authors: Özüdoğru Barış , Akaydın Galip , Erik Sadık , Al-Shehbaz Ihsan A. , Mummenhoff Klaus
Published: August 2015

Ricotia (Brassicaceae) is a genus of nine species endemic to the eastern Mediterranean region. Its phylogenetic relationships, monophyly, and tribal placement have not yet been adequately addressed. To achieve this, sequence data from the nuclear‐encoded ribosomal internal transcribed spacer (ITS) and chloroplast DNA (trnL‐F region) were analysed by parsimony, maximum likelihood, and Bayesian methods for 45 Ricotia accessions, representing all species and covering their entire distribution ranges, along with outgroups of selected members of main Brassicaceae lineages and tribes. The results clearly indicate, with high posterior probability/bootstrap support, that Ricotia is monophyletic and together with Lunaria should be assigned, with Biscutella and Megadenia, to tribe Biscutelleae. Divergence time estimations, using both a secondary calibration approach and published ITS substitution rates, indicate that the origin of Ricotia (crown group age, 9.2–11.3 Ma) predates the onset of the Mediterranean climate after the Messinian Salinity Crisis (5.9–5.3 Ma). We tentatively conclude that diversification within Ricotia was affected by climate changes during that geological epoch which had a great impact on the speciation history of the Mediterranean flora and fauna. Ancestral area reconstruction analyses revealed that Mediterranean Ricotia species arose in southwest Anatolia (likely Antalya region), whereas the origin of the genus remained unclear. Finally, a perennial life cycle appears to be ancestral in Ricotia, as revealed by an ancestral character state reconstruction analysis.
Patterns of behaviour
Authors: White Hilary
Published: August 2015

Pattern pervades all areas of a child's life, from tangible objects in the environment to ways in which routines are established. Hilary White provides a guide to children's grasp of this key concept.
That special someone
Authors: Chambers Sue
Published: August 2015

Child expert Sue Chambers begins a new four-part series exploring the role of the key person. She starts by defining the role, placing it in the context of the setting and looks at the particular skills that are required.
Off the beaten track
Authors: Cruikshank Sarah
Published: August 2015

September will see the 78th anniversary of Tolkien's The Hobbit. The Hobbit's adventures can be used as a platform for a number of literacy activities. Here, Sarah Cruickshank shares some of her ideas.
Tap into everyday maths
Authors: Doyle Phoebe
Published: August 2015

Phoebe Doyle offers some ideas for encouraging Maths learning by making the most of real life opportunities, to help children feel both confident and competent in their learning.
Shiver me timbers!
Authors: Williams Brenda
Published: August 2015

International Talk Like a Pirate Day falls on the 19th of September each year. It provides a great opportunity to break the ice at the beginning of term and to get the whole school involved.
Revitalizing cinematic potential under authoritarian rule: Reporting from the second edition of the Human Rights Human Dignity International Film Festival (HRHDIFF), Yangon, Myanmar, 15–19 June 2014
Authors: Grøn Nis
Published: August 2015

The following is a report from the second edition of the Human Rights Film Festival in Yangon, Myanmar. Here we take a closer look at the realization of the newly established international film festival in Myanmar, and at how, despite the difficult socio-political conditions under which the organizers and local film-makers work, this festival is the result of courage and conviction as well as a belief in the power of cinema as a tool for social dialogue and change.