bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized controlled trial of toremifene 120 mg compared with exemestane 25 mg after prior treatment with a non-steroidal aromatase inhibitor in postmenopausal women with hormone receptor-positive metastatic breast cancer
Authors: Yamamoto Yutaka , Ishikawa Takashi , Hozumi Yasuo , Ikeda Masahiko , Iwata Hiroji , Yamashita Hiroko , Toyama Tatsuya , Chishima Takashi , Saji Shigehira , Yamamoto-Ibusuki Mutsuko , Iwase Hirotaka
Published: May 2013

Background

After the failure of a non-steroidal aromatase inhibitor (nsAI) for postmenopausal patients with metastatic breast cancer (mBC), it is unclear which of various kinds of endocrine therapy is the most appropriate. A randomized controlled trial was performed to compare the efficacy and safety of daily toremifene 120 mg (TOR120), a selective estrogen receptor modulator, and exemestane 25 mg (EXE), a steroidal aromatase inhibitor. The primary end point was the clinical benefit rate (CBR). The secondary end points were objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and toxicity.

Methods

Initially, a total of 91 women was registered in the study and randomly assigned to either TOR120 (n = 46) or EXE (n = 45) from October 2008 to November 2011. Three of the 46 patients in the TOR120 arm were not received treatment, 2 patients having withdrawn from the trial by their preference and one having been dropped due to administration of another SERM.

Results

When analyzed after a median observation period of 16.9 months, the intention-to-treat analysis showed that there were no statistical difference between TOR120 (N = 46) and EXE (n = 45) in terms of CBR (41.3% vs. 26.7%; P = 0.14), ORR (10.8% vs. 2.2%; P = 0.083), and OS (Hazard ratio, 0.60; P = 0.22). The PFS of TOR120 was longer than that of EXE, the difference being statistically significant (Hazard ratio, 0.61, P = 0.045). The results in treatment-received cohort (N = 88) were similar to those in ITT cohort. Both treatments were well-tolerated with no severe adverse events, although the treatment of 3 of 43 women administered TOR120 was stopped after a few days because of nausea, general fatigue, hot flush and night sweating.

Conclusions

TOR120, as a subsequent endocrine therapy for mBC patients who failed non-steroidal AI treatment, could potentially be more beneficial than EXE.

Trial registration number

UMIN000001841
Predictors of exclusive breastfeeding: observations from the Alberta pregnancy outcomes and nutrition (APrON) study
Authors: Jessri Mahsa , Farmer Anna P , Maximova Katerina , Willows Noreen D , Bell Rhonda C ,   APrON Study Team
Published: May 2013

Background

Despite growing evidence that supports the importance of 6-month exclusive breastfeeding, few Canadian mothers adhere to this, and early weaning onto solids is a common practice. This study assessed infant feeding transitions during the first 6 months postpartum and factors that predicted exclusive breastfeeding to 3 and 6 months.

Methods

This prospective cohort study was part of the Alberta Pregnancy Outcomes and Nutrition study (APrON). From an initial sample of 600 pregnant women recruited from Edmonton and Calgary, 402 mothers provided complete details at 3 months postpartum; 300 stayed on to provide information at 6 months postpartum. During pregnancy and at 3 and 6 months postpartum, data on maternal and infant socio-demographic, behavior, and feeding were collected.

Results

Even though there was a high rate of “ever having breastfed” (98.6%), exclusive breastfeeding rates for 3 and 6 months were 54.0% and 15.3%, respectively. After controlling for potential confounders, the study showed that mothers who held post-graduate university degrees were 3.76 times more likely to breastfeed exclusively for 6 months than those without a university degree (95% CI: 1.30-10.92; p = 0.015). In addition, mother of previous children were more likely to breastfeed exclusively for 6 months (OR: 2.21, 95% CI: 1.08-4.52; p = 0.031). Mothers who were in the highest quartile of the Iowa Infant Feeding Attitude Score were 4.29 and 5.40 times more likely to breastfeed exclusively for 3 months (95% CI: 1.31-14.08; p-trend < 0.001) and 6 months (95% CI: 2.75-10.60; P-trend < 0.001), respectively.

Conclusions

The 6-month exclusive breastfeeding rate in Alberta is considerably below national and international breastfeeding recommendations. Professional advice that focuses on prenatal maternal knowledge, attitudes, and misperceptions may promote adherence to World Health Organization breastfeeding guidelines. Knowing that exclusive breastfeeding is less likely to take place among lower-educated, primiparous women may help health practitioners focus their support and education for this group.
Psychometric properties of a French version of a Dutch scale for assessing breast and body image (BBIS) in healthy women
Authors: Resseguier Noémie , Noguès Catherine , Giorgi Roch , Julian-Reynier Claire
Published: May 2013

Background

Genetic testing among women for BRCA1/2 mutation can have various psychological effects, such as those focusing on body image. The aim of this study was to examine the psychometric properties of a generic scale assessing breast and body image (BBIS) in healthy women tested for BRCA1/2 mutations.

Methods

A Dutch body image scale focusing on both general and breast-related body image was translated into French. It was presented to a French cohort of female cancer-free BRCA1/2 mutation carriers and non-carriers (N = 568). The psychometric properties of the scale were studied by assessing its dimensional and factorial structure, internal consistency, construct-related validity, and external validity.

Results

The scale was found to be a satisfactory psychometric tool for assessing both body image and breast image. The three main dimensions which emerged were classified under the headings “values attached to body image”, “satisfaction with body image and perceived attractiveness”, and “satisfaction with breasts”. The BBIS scores were not significantly associated with the participants’ socio-demographic characteristics or their BRCA1/2 mutation carrier status, but significant associations were observed between these scores and the women’s medical and behavioural characteristics.

Conclusions

The BBIS is a generic tool which can be used to assess body image in either affected or unaffected women. The scale will have to be administered to other populations in order to confirm its validity.
Lactobacillus fermentation enhances the inhibitory effect of Hwangryun-haedok-tang in an ovariectomy-induced bone loss
Authors: Shim Ki-Shuk , Kim Taesoo , Ha Hyunil , Lee Kwang Jin , Cho Chang-Won , Kim Han Sung , Seo Dong-Hyun , Ma Jin Yeul
Published: May 2013

Background

Hwangryun-haedok-tang (HRT) is traditional herbal medicine used to treat inflammatory-related diseases in Asia. However, its effect on osteoclastogenesis and bone loss is still unknown. In this study, we evaluated the effect of HRT and its fermented product (fHRT) on the receptor activator for the nuclear factor-κB ligand-induced osteoclastogenesis using murine bone marrow-derived macrophages and postmenopausal bone loss using an ovariectomy (OVX) rat model.

Methods

Tartrate resistant acid phosphatase (TRAP) staining was employed to evaluate osteoclast formation. mRNA level of transcription factor and protein levels of signaling molecules were determined by real-time quantitative polymerase chain reaction and Western blot analysis, respectively. Effect of HRT or fHRT on OVX-induced bone loss was evaluated using OVX rats orally administered HRT, or fHRT with 300 mg/kg for 12 weeks. Micro-CT analysis of femora was performed to analyze bone parameter.

Results

HRT or fHRT treatment significantly decreased TRAP activity and the number of TRAP positive multinuclear cells on osteoclastogenesis. Interestingly, these inhibitory effects of HRT were enhanced by fermentation. Furthermore, fHRT significantly inhibited mRNA and protein expression of nuclear factor of activated T cells cytoplasmic 1, which leads to down-regulation of NFATc1-regulated mRNA expressions such as TRAP, the d2 isoform of vacuolar ATPase V(0) domain, and cathepsin K. Administration of fHRT significantly inhibited the decrease of bone mineral density, and improved bone parameter of femora more than that of HRT and vehicle in OVX rats.

Conclusions

This study demonstrated that lactic bacterial fermentation fortifies the inhibitory effect of HRT on osteoclastogenesis and bone loss. These results suggest that fermented HRT might have the beneficial potential on osteoporosis by inhibiting osteoclastogenesis.
Anti-inflammatory, antioxidant, and antimicrobial activities of Cocos nucifera var. typica
Authors: Silva Rafaela Ribeiro , e Silva Davi Oliveira , Fontes Humberto Rollemberg , Alviano Celuta Sales , Fernandes Patricia Dias , Alviano Daniela Sales
Published: May 2013

Background

Teas from the husk fiber of Cocos nucifera are used in the folk medicine to treat arthritis and other inflammatory processes. Some works show that some varieties have biological activities. However, one of the main variety of the species, C. nucifera var. typica, known in Brazil as “gigante”, was not studied yet. Thus, this study evaluates if this variety has the anti-inflammatory and antimicrobial activities already reported in other varieties.

Methods

C. nucifera aqueous crude extract (10, 50, and 100 mg/kg) and the reference drugs morphine (1 mg/kg) and acetylsalicylic acid (100 mg/kg) were evaluated in models of inflammation (formalin-induced licking and subcutaneous air pouch). The antioxidant activity was evaluated by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) photometric assay and compared with those of the standards (quercetin, rutin, and ascorbic acid). The extract was also screened against Candida albicans, Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus (MRSA), in the agar diffusion method. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by the broth micro-dilution assay. Activities of combinations of the extract and antibiotics (methicillin or vancomycin) against MRSA were evaluated using checkerboard assays.

Results

The extract significantly inhibited the time that the animals spent licking the formalin-injected paws (second phase). The extract also inhibited the inflammatory process induced by subcutaneous carrageenan injection by reducing cell migration, protein extravasation, and TNF-α production. Additionally, the extract showed an antioxidant potential in vitro as good as standards in their antioxidant activity. The extract was active only against S. aureus and MRSA. MIC and the bactericidal concentrations were identical (1,024 μg/ml). The extract and methicillin acted synergistically against the clinical MRSA isolate, whereas an indifferent effect was detected when the extract was combined with vancomycin.

Conclusions

The extract exhibits anti-inflammatory activity through the inhibition of the cell migration. The mixture of extract constituents and methicillin could lead to the development of a new combination antibiotic against MRSA infections.
Catabolic flexibility of mammalian-associated lactobacilli
Authors: O’Donnell Michelle M , O’Toole Paul W , Ross Reynolds Paul
Published: May 2013

Metabolic flexibility may be generally defined as “the capacity for the organism to adapt fuel oxidation to fuel availability”. The metabolic diversification strategies used by individual bacteria vary greatly from the use of novel or acquired enzymes to the use of plasmid-localised genes and transporters. In this review, we describe the ability of lactobacilli to utilise a variety of carbon sources from their current or new environments in order to grow and survive. The genusLactobacillusnow includes more than 150 species, many with adaptive capabilities, broad metabolic capacity and species/strain variance. They are therefore, an informative example of a cell factory capable of adapting to new niches with differing nutritional landscapes. Indeed, lactobacilli naturally colonise and grow in a wide variety of environmental niches which include the roots and foliage of plants, silage, various fermented foods and beverages, the human vagina and the mammalian gastrointestinal tract (GIT; including the mouth, stomach, small intestine and large intestine). Here we primarily describe the metabolic flexibility of some lactobacilli isolated from the mammalian gastrointestinal tract, and we also describe some of the food-associated species with a proven ability to adapt to the GIT. As examples this review concentrates on the following species -Lb. plantarum,Lb. acidophilus,Lb. ruminis,Lb. salivarius,Lb. reuteriandLb. sakei, to highlight the diversity and inter-relationships between the catabolic nature of species within the genus.
Performance assessment in brain-computer interface-based augmentative and alternative communication
Authors: Thompson David E , Blain-Moraes Stefanie , Huggins Jane E
Published: May 2013

A large number of incommensurable metrics are currently used to report the performance of brain-computer interfaces (BCI) used for augmentative and alterative communication (AAC). The lack of standard metrics precludes the comparison of different BCI-based AAC systems, hindering rapid growth and development of this technology. This paper presents a review of the metrics that have been used to report performance of BCIs used for AAC from January 2005 to January 2012. We distinguish between Level 1 metrics used to report performance at the output of the BCI Control Module, which translates brain signals into logical control output, and Level 2 metrics at the Selection Enhancement Module, which translates logical control to semantic control. We recommend that: (1) the commensurate metrics Mutual Information or Information Transfer Rate (ITR) be used to report Level 1 BCI performance, as these metrics represent information throughput, which is of interest in BCIs for AAC; 2) the BCI-Utility metric be used to report Level 2 BCI performance, as it is capable of handling all current methods of improving BCI performance; (3) these metrics should be supplemented by information specific to each unique BCI configuration; and (4) studies involving Selection Enhancement Modules should report performance at both Level 1 and Level 2 in the BCI system. Following these recommendations will enable efficient comparison between both BCI Control and Selection Enhancement Modules, accelerating research and development of BCI-based AAC systems.
A variable step-size gradient adaptive lattice algorithm for multiple sinusoidal interference cancelation
Authors: Kim Seong-woo , Park Young-cheol , Youn Dae Hee
Published: May 2013

In passive sonar, adaptive algorithms can be used to cancel strong sinusoidal self-interferences. In order to correctly recover low-power target signals during the early stages of processing, these adaptive algorithms must provide fast convergence and, at the same time, narrow notches at the frequencies of the sinusoids. In this respect, the gradient adaptive lattice (GAL) algorithm is a very attractive choice. However, the GAL algorithm with a constant step-size parameter has to compromise between the convergence rate and notch bandwidths. Therefore, in this article, we propose a variable step-size scheme for the GAL algorithm that can achieve both a fast convergence rate and narrow notches. Simulation results demonstrate the efficiency of the proposed algorithm compared to both the conventional GAL algorithm and transversal adaptive filter combined with the variable step-size scheme.
The utility of surgical lung biopsy in cancer patients with acute respiratory distress syndrome
Authors: Chang Chih-Hao , Kao Kuo-Chin , Hu Han-Chung , Hung Chen-Yiu , Li Li-Fu , Wu Ching-Yang , Wang Chih-Wei , Fu Jui-Ying , Huang Chung-Chi , Chen Ning-Hung , Yang Cheng-Ta , Tsai Ying-Huang
Published: May 2013

Background

This retrospective study evaluated the utility and safety of surgical lung biopsy (SLB) in cancer patients with acute respiratory distress syndrome (ARDS).

Methods

All cases of critically ill patients with cancer and diagnosed with ARDS who underwent SLB in a tertiary care hospital from January 2002 to July 2009 were reviewed. Clinical data including patient baseline characteristics, surgical complications, pathological findings, treatment alterations, and survival outcomes were retrospectively collected and analyzed.

Results

A total of 16 critically ill patients with cancer diagnosed with ARDS who underwent SLB were enrolled. The meantime from ARDS onset to SLB was 3.0 ± 1.5 days. All SLB specimens offered a pathological diagnosis, and specific diagnoses were made in 9 of 16 patients. Biopsy findings resulted in a change in therapy in 11 of 16 patients. Overall, the SLB surgical complication rate was 19% (3/16). SLB did not directly cause the observed operative mortality. The ICU mortality rate was 38% (6/16). Patients who switched therapies after SLB had a trend toward decreased mortality than patients without a change in therapy (27% versus 60%; P = 0.299).

Conclusions

In selected critically ill cancer patients with ARDS, SLB had a high diagnostic yield rate and an acceptable surgical complication rate.
Dandy-Walker malformation and Wisconsin syndrome: novel cases add further insight into the genotype-phenotype correlations of 3q23q25 deletions
Authors: Ferraris Alessandro , Bernardini Laura , Sabolic Avramovska Vesna , Zanni Ginevra , Loddo Sara , Sukarova-Angelovska Elena , Parisi Valentina , Capalbo Anna , Tumini Stefano , Travaglini Lorena , Mancini Francesca , Duma Filip , Barresi Sabina , Novelli Antonio , Mercuri Eugenio , Tarani Luigi ,   Italian CBCD Study Group, Bertini Enrico , Dallapiccola Bruno , Valente Enza Maria
Published: May 2013

Background

The Dandy-Walker malformation (DWM) is one of the commonest congenital cerebellar defects, and can be associated with multiple congenital anomalies and chromosomal syndromes. The occurrence of overlapping 3q deletions including theZIC1andZIC4genes in few patients, along with data from mouse models, have implicated both genes in the pathogenesis of DWM.

Methods and results

Using a SNP-array approach, we recently identified three novel patients carrying heterozygous 3q deletions encompassingZIC1andZIC4. Magnetic resonance imaging showed that only two had a typical DWM, while the third did not present any defect of the DWM spectrum. SNP-array analysis in further eleven children diagnosed with DWM failed to identify deletions ofZIC1-ZIC4. The clinical phenotype of the three 3q deleted patients included multiple congenital anomalies and peculiar facial appearance, related to the localization and extension of each deletion. In particular, phenotypes resulted from the variable combination of three recognizable patterns: DWM (with incomplete penetrance); blepharophimosis, ptosis, and epicanthus inversus syndrome; and Wisconsin syndrome (WS), recently mapped to 3q.

Conclusions

Our data indicate that the 3q deletion is a rare defect associated with DWM, and suggest that the hemizygosity ofZIC1-ZIC4genes is neither necessary nor sufficientper seto cause this condition. Furthermore, based on a detailed comparison of clinical features and molecular data from 3q deleted patients, we propose clinical diagnostic criteria and refine the critical region for WS.
The internet user profile of Italian families of patients with rare diseases: a web survey
Authors: Tozzi Alberto E , Mingarelli Rita , Agricola Eleonora , Gonfiantini Michaela , Pandolfi Elisabetta , Carloni Emanuela , Gesualdo Francesco , Dallapiccola Bruno
Published: May 2013

Background

The use of the Internet for searching and sharing health information and for health care interactions may have a great potential for families of children affected with rare diseases. We conducted an online survey among Italian families of patients with rare diseases with the objective to describe their Internet user profile, and to explore how Internet use affects their health decisions.

Methods

All members of UNIAMIO FIMR, a federation of associations of patients with rare diseases, were invited via mail to participate in an online questionnaire including questions on socio-demographic and clinical information, Internet use with a specific focus on health, and impact of web information on health behaviors. Logistic regression models were used to explore the effect of socio-demographic variables and Internet user profile on dependent variables representing the impact of web information on health behaviors. Multiple imputation by chained equations was applied.

Results

A total of 516 parents of patients with rare diseases completed the online questionnaire. Mean age was 43 years. 87% of respondents accessed the Internet daily, 40% through their smartphones. 99% had an email account, 71% had a Facebook account. 66% participate in an online forum on health. 99% searched for information on disease characteristics, 93% on therapy, 89% on diagnosis, 63% on alternative therapies, 62% on nutrition and 54% on future pregnancies. 82% stated that web information increased comprehension of the disease, 65% that it improved management of the disease. For 52% web information increased his or her anxiety. 62% recognized diagnosis, 69% discussed online information with their physician. People participating in forums more frequently stated that Internet information was useful for recognizing their child’s disease (OR 1.68; 95%CI 1.08-2.63) and for improving its management (OR 1.77; 95%CI 1.11-2.81).

Conclusion

Italian parents of patients with rare diseases are active Internet users, engaged in information search and in online communities.

Physicians, health care facilities and health agencies have a great opportunity to engage in online interactions for empowering families of patients of children affected with rare diseases.
TSH receptor antibodies have predictive value for breast cancer – retrospective analysis
Authors: Szychta Paweł , Szychta Wojciech , Gesing Adam , Lewiński Andrzej , Karbownik-Lewińska Małgorzata
Published: May 2013

Background

Associations between breast cancer and thyroid disorders are reported in numerous studies. Relationships between thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb) and breast cancer have been previously demonstrated. However, no analysis has been performed concerning an association between thyrotropin (TSH) receptor antibodies (TSHRAb) and breast cancer. The aim of the study was to evaluate the prevalence of breast cancer or benign breast tumors in patients with Graves’ disease and to analyze a possible relationship between Graves’ disease and these two groups of breast diseases with emphasis to epidemiology and laboratory findings.

Patients and methods

Clinical and laboratory details of 2003 women hospitalized for endocrine disorders were retrospectively analyzed, using an unpaired Student’s t-test, logistic regression analysis, χ
2 test of independence or the two-sided ratio comparison test.

Results

The coexistence of Graves’ disease and breast cancer was statistically significant. We observed TSHRAb and TgAb more frequently in patients with breast cancer. We found that TSHRAb is the only variable possessing predictive value for breast cancer.

Conclusions

The strong relationship between Graves’ disease and breast cancer is proposed. We suggest that TSHRAb could be described as a positive determinant of breast cancer. The present data call attention to the usefulness of screening for breast cancer in long-term follow-up of patients with autoimmune thyroid disorders, especially of those with Graves’ disease. Similarly, screening for autoimmune thyroid disorders should be performed in patients with nodular breast disease. Additionally, the article draws ideas for further research in order to develop targeted treatment for more successful outcome in patients with breast cancer.
Implication of Insulin Receptor A Isoform and IRA/IGF-IR Hybrid Receptors in the Aortic Vascular Smooth Muscle Cell Proliferation: Role of TNF-α and IGF-II
Authors: Gómez-Hernández Almudena , Escribano Óscar , Perdomo Liliana , Otero Yolanda F. , García-Gómez Gema , Fernández Silvia , Beneit Nuria , Benito Manuel
Published: May 2013

To assess the role of insulin receptor (IR) isoforms (IRA and IRB) in the proliferation of vascular smooth muscle cells (VSMCs) involved in the atherosclerotic process, we generated new VSMC lines bearing IR (wild-type VSMCs; IRLoxP+/+ VSMCs), lacking IR (IR−/− VSMCs) or expressing IRA (IRA VSMCs) or IRB (IRB VSMCs). Insulin and different proatherogenic stimuli induced a significant increase of IRA expression in IRLoxP+/+ VSMCs. Moreover, insulin, through ERK signaling, and the proatherogenic stimuli, through ERK and p38 signaling, induced a higher proliferation in IRA than IRB VSMCs. The latter effect might be due to IRA cells showing a higher expression of angiotensin II, endothelin 1, and thromboxane 2 receptors and basal association between IRA and these receptors. Furthermore, TNF-α induced in a ligand-dependent manner a higher association between IRA and TNF-α receptor 1 (TNF-R1). On the other hand, IRA overexpression might favor the atherogenic actions of IGF-II. Thereby, IGF-II or TNF-α induced IRA and IGF-I receptor (IGF-IR) overexpression as well as an increase of IRA/IGF-IR hybrid receptors in VSMCs. More importantly, we observed a significant increase of IRA, TNF-R1, and IGF-IR expression as well as higher association of IRA with TNF-R1 or IGF-IR in the aorta from ApoE−/− and BATIRKO mice, 2 models showing vascular damage. In addition, anti–TNF-α treatment prevented those effects in BATIRKO mice. Finally, our data suggest that the IRA isoform and its association with TNF-R1 or IGF-IR confers proliferative advantage to VSMCs, mainly in response to TNF-α or IGF-II, which might be of significance in the early atherosclerotic process.
ERα-Targeted Therapy in Ovarian Cancer Cells by a Novel Estradiol-Platinum(II) Hybrid
Authors: Brasseur K. , Leblanc V. , Fabi F. , Parent S. , Descôteaux C. , Bérubé G. , Asselin E.
Published: May 2013

As we previously showed, we have synthesized a new family of 17β-estradiol-platinum(II) hybrids. Earlier studies revealed the VP-128 hybrid to show high efficiency compared with cisplatin toward hormone-dependent breast cancer cells. In the present research, we have studied the antitumor activity of VP-128 in vitro and in vivo against ovarian cancer. In nude mice with ovarian xenografts, VP-128 displayed selective activity toward hormone-dependent tumors and showed higher efficiency than cisplatin to inhibit tumor growth. Similarly, in vitro, transient transfection of estrogen receptor (ER)-α in ERα-negative A2780 cells increased their sensitivity to VP-128-induced apoptosis, confirming the selectivity of VP-128 toward hormone-dependent tumor cells. In agreement, Western blot analysis revealed that VP-128 induced higher caspase-9, caspase-3, and poly (ADP-ribose) polymerase cleavage compared with cisplatin. The activation of caspase-independent apoptosis was also observed in ERα-negative A2780 cells, in which VP-128 rapidly induced the translocation of apoptosis-inducing factor to the nucleus. Conversely, subcellular localization of apoptosis-inducing factor was not modified in ERα-positive Ovcar-3 cells. We also discovered that VP-128 induces autophagy in ovarian cancer cells because of the formation of acidic vesicular organelles (AVOs) and increase of Light Chain 3B-II protein responsible for the formation of autophagosomes; pathways related to autophagy (AKT and mammalian target of rapamycin) were also down-regulated, supporting this mechanism. Finally, the inhibition of autophagy using chloroquine increased VP-128 efficiency, indicating a possible combination therapy. Altogether these results highlight the beneficial value of VP-128 for the treatment of hormone-dependent ovarian cancers and provide preliminary proof of concept for the efficient targeting of ERα- by 17β-estradiol-Pt(II)-linked chemotherapeutic hybrids in these tumors.
Grieved and Disordered: Gender and Emotion in Early Modern Patient Narratives
Authors: Weisser Olivia
Published: May 2013

By focusing on firsthand accounts of illness by patients rather than the writing of medical authors, this article shows that the emotions assume a much greater role in early modern explanations of the onset of illness than historians have supposed. In addition to spiritual, physical, and environmental causes of ill health, patients commonly attributed everyday disorders to their emotional responses to social stimuli, such as money problems, ruined relationships, or distressing news. The article argues that men and women perceived this physical process in gendered ways, according to patterns linked to prevailing expectations of gendered behavior, written conventions for expressing emotions such as grief and sorrow, as well as medical beliefs about men’s and women’s bodies. The resulting analysis offers rich insights into the words and views of patients and into gendered experiences and self-constructions in early modern England.
Magical Politics from Poitou to Armenia: Mélusine, Jean de Berry, and the Eastern Mediterranean
Authors: Burns E. Jane
Published: May 2013

The fourteenth-century Roman de Mélusine by Jean d’Arras is a story of dynastic expansion and political legitimization that extends far beyond the territorial battles fought by the French royal family during the Hundred Years War. In fact, Jean d’Arras’s narrative of Lusignan history pointedly pulls away from the Valois line of its patron, the Duke of Berry, replacing paternal lineage with a primary bond between mother and sons. In this instance, Jean de Berry’s claim to Lusignan territory is secured not by documents proving local inheritance but by a flying woman/snake mother who provides political legitimization in large part because of her unparalleled trans-Mediterranean reach.
Recasting England: The Varieties of Antiquarian Responses to the Proposed Union of Crowns, 1603–1607
Authors: Parker Brett F.
Published: May 2013

In 1604, the Elizabethan Society of Antiquaries examined three components of King James’s proposed Anglo-Scottish union: the unity of name, law, and Parliament. As members of the Society reconstructed English history in their papers, a variety of historical and constitutional positions emerged concerning English institutions and national identity. This article argues that these various renderings of English ancient constitutionalism reveal a protean and heightened sense of England’s juridical past. It contextualizes these divergent narratives in the identity crisis engendered by the proposed Anglo-Scottish union and gives special attention to those antiquaries who saw the law and Parliament as a more recent and complicated development. In doing so, these antiquaries portrayed a constitution that was neither ancient nor immutable, but rather one that was constructed from a mishmash of foreign customs. By analyzing the antiquaries’ arguments, this article seeks to broaden the historiographical understanding of ancient constitutionalism and to show that the antiquaries made a significant contribution to early Stuart political thought.
Oligosaccharide Analysis in Urine by MALDI-TOF Mass Spectrometry for the Diagnosis of Lysosomal Storage Diseases
Authors: Xia Baoyun , Asif Ghazia , Arthur Leonard , Pervaiz Muhammad A , Li Xueli , Liu Renpeng , Cummings Richard D , He Miao
Published: May 2013

BACKGROUND

There are 45 known genetic diseases that impair the lysosomal degradation of macromolecules. The loss of a single lysosomal hydrolase leads to the accumulation of its undegraded substrates in tissues and increases of related glycoconjugates in urine, some of which can be detected by screening of free oligosaccharides (FOS) in urine. Traditional 1-dimensional TLC for urine oligosaccharide analysis has limited analytical specificity and sensitivity. We developed fast and robust urinary FOS and glycoaminoacid analyses by MALDI–time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry for the diagnosis of oligosaccharidoses and other lysosomal storage diseases.

METHODS

The FOS in urine equivalent to 0.09 mg creatinine were purified through sequential passage over a Sep-Pak C18 column and a carbograph column and were then permethylated. MALDI-TOF/TOF was used to analyze the permethylated FOS. We studied urine samples from individuals in 7 different age groups ranging from 0–1 months to ≥17 years as well as urine from known patients with different lysosomal storage diseases.

RESULTS

We identified diagnostic urinary FOS patterns for α-mannosidosis, galactosialidosis, mucolipidosis type II/III, sialidosis, α-fucosidosis, aspartylglucosaminuria (AGU), Pompe disease, Gaucher disease, and GM1 and GM2 gangliosidosis. Interestingly, the increase in urinary FOS characteristic of lysosomal storage diseases relative to normal FOS appeared to correlate with the disease severity.

CONCLUSIONS

The analysis of urinary FOS by MALDI-TOF/TOF is a powerful tool for first-tier screening of oligosaccharidoses and lysosomal storage diseases.
Evidence for increased tissue androgen sensitivity in neurturin knockout mice
Authors: Simanainen Ulla , Gao Yan Ru (Ellen) , Desai Reena , Jimenez Mark , Spaliviero Jennifer , Keast Janet R , Handelsman David J
Published: May 2013

Neurturin (NTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family and signals through GDNF family receptor alpha 2 (GFRα2). We hypothesised that epithelial atrophy reported in the reproductive organs ofNtn(Nrtn)- andGfrα2(Gfra2)-deficient mice could be due to NTN affecting the hormonal environment. To investigate this, we compared the reproductive organs ofNtn- andGfrα2-deficient male mice in parallel with an analysis of their circulating reproductive hormone levels. There were no significant structural changes within the organs of the knockout mice; however, serum and intratesticular testosterone and serum LH levels were very low. To reconcile these observations, we tested androgen sensitivity by creating a dihydrotestosterone (DHT) clamp (castration plus DHT implant) to create fixed circulating levels of androgens, allowing the evaluation of androgen-sensitive endpoints. At the same serum DHT levels, serum LH levels were lower and prostate and seminal vesicle weights were higher in theNtnknockout (NTNKO) mice than in the wild-type mice, suggesting an increased response to androgens in the accessory glands and hypothalamus and pituitary of the NTNKO mice. Testicular and pituitary responsiveness was unaffected in the NTNKO males, as determined by the response to the human chorionic gonadotrophin or GNRH analogue, leuprolide, respectively. In conclusion, our results suggest that NTN inactivation enhances androgen sensitivity in reproductive and neuroendocrine tissues, revealing a novel mechanism to influence reproductive function and the activity of other androgen-dependent tissues.
Core Structures of Dislocations within CdTe Grains
Authors: Li Chen , Pennycook Timothy J. , Leonard Donovan N. , Jones Kim , Wang Zhiwei , Al-Jassim Mowafak , Paudel Naba , Yan Yanfa , Pennycook Stephen J.
Published: May 2013

CdTe is well known as an excellent photovoltaic material for high efficiency solar cell applications because it has a direct band-gap, low fabrication cost and high optical absorption coefficient. However, the nonradiative recombination and low average minority carrier lifetime caused by the defects in CdTe solar cells limit its efficiency. So far, grain boundaries (GB) have been considered to be the major origin of the nonradiative recombination. However, we show that CdTe grains contain many dislocations that could limit device efficiency. Scanning transmission electron microscopy (STEM) was used to determine the atomic structure of intrinsic and extrinsic stacking faults and their terminating partial dislocation cores. Z-contrast images are sensitive to atomic number and are able to distinguish Cd and Te atomic columns. Unpaired Cd and Te atomic columns were found to form the partial dislocation cores, suggesting the presence of dangling bonds. These defects are likely to be electrically active, and may be the origin of the low minority carrier lifetime.
Improvement of Minority Carrier Lifetime in Thick 4H-SiC Epi-layers by Multiple Thermal Oxidations and Anneals
Authors: Cheng Lin , O’Loughlin Michael J. , Suvorov Alexander V. , Van Brunt Edward R. , Burk Albert A. , Agarwal Anant K. , Palmour John W.
Published: May 2013

This paper details the development of a technique to improve the minority carrier lifetime of 4H-SiC thick (≥ 100 μm) n-type epitaxial layers through multiple thermal oxidations. A steady improvement in lifetime is seen with each oxidation step, improving from a starting ambipolar carrier lifetime of 1.09 µs to 11.2 µs after 4 oxidation steps and a high-temperature anneal. This multiple-oxidation lifetime enhancement technique is compared to a single high-temperature oxidation step, and a carbon implantation followed by a high-temperature anneal, which are traditional ways to achieve high ambipolar lifetime in 4H-SiC n-type epilayers. The multiple oxidation treatment resulted in a high minimum carrier lifetime of 6 µs, compared to < 2 µs for other treatments. The implications of lifetime enhancement to high-voltage/high-current 4H-SiC power devices are also discussed.
Strain States in YSZ / RE2O3 (RE = Er, Y) Multilayers as a Function of Layer Thickness and Their Effect on Interface Conductivity and Diffusion
Authors: Keppner J. , Korte C. , Schubert J. , Zander W. , Ziegner M. , Stolten D.
Published: May 2013

In this study the strain states in alternating multilayers of an extrinsic O2− ion conductor yttria stabilized zirconia (YSZ) and an insulator RE2O3 (RE = Er, Y) are investigated as a function of the layer thickness. Multilayers with narrow columnar crystallites and coherent phase boundaries were grown by pulsed laser deposition (PLD). A detailed strain analysis is performed by X-Ray Diffraction XRD, measuring distinct reflections in and perpendicular to the interface planes. Because of small columnar crystallites in the layers, the interfacial strain decays by shear with increasing distance from the interface. The extent of the strained interface regions in the YSZ layers is estimated from XRD data. By using a quantitative analytical model based on the pressure dependence of the free migration enthalpy for vacancies the results are compared to former published experimental data on O2− ion conductivity and diffusion.
Advantages of Hydrogen Peroxide as an Oxidant for Atomic Layer Deposition and Related Novel Delivery System
Authors: Spiegelman Jeff , Alvarez Dan , Holmes Russell J. , Heinlein Ed , Shamsi Zohreh
Published: May 2013

Proposed is the use of Hydrogen Peroxide (H2O2) as the ideal oxidant for atomic layer deposition of metal oxide films. H2O2 has similar oxidation properties to Ozone while simultaneously having slightly stronger proton transfer properties than water. Vital to the success of any vapor phase chemistry is delivery of stable compositions, temperature and pressure. This study demonstrates the viability of a new membrane technology for the precise delivery of H2O2/ H2O mixtures starting from a liquid range of 30-70%. An in-situ gas phase cleaning process to remove carbon contamination from Ge(100) surfaces using gas phase H2O2 has been characterized.
Design and construction of bridges in Fiji
Authors: Amir-Ansari Siavash
Published: May 2013

Fiji is one of the smaller developing countries that has managed the development and maintenance of its highway structures with minimal reliance on other countries. Fiji is a collection of approximately 330 islands located 2000 km northeast of New Zealand in the Pacific Ocean. The total land area of the islands is 18 270 sq. km, 110 islands of which are inhabited. The terrain of the country is mountainous and of volcanic origin. It is located in a seismic zone and is subject to extreme hurricanes, floods and tsunamis. The public works department of the Fijian government maintains over 500 road bridges throughout the islands. The geology of the land means that bridge foundations tend to be an expensive component of bridge design and construction. This paper provides an overview of the Public Works Department of Fiji Government since its establishment in the nineteenth century during British colonial rule. It has effectively managed in-house and locally sourced labour for the design, construction and maintenance of a large number of bridges on widely scattered islands. Exceptions have included the reconstruction of three longer bridges, which in recent years were damaged during hurricane floods. These bridges were tendered internationally because of financial aid regulations and were constructed by overseas companies.
Estimating extinction from species–area relationships: why the numbers do not add up
Authors: He Fangliang , Hubbell Stephen
Published: May 2013

Researchers commonly use species–area relationships (SAR) to estimate extinction rates caused by habitat loss by reversing the SAR, extrapolating backward from area to calculate expected species loss. We have previously shown that the backward SAR method considerably overestimates extinction rates due to a previously unrecognized sampling artifact. Jacob Bock Axelsen, Uri Roll, Lewi Stone, and Andrew Solow recently argued that the backward SAR method is correct and the method does not overestimate extinction rates. In this paper, we further elaborate and clarify our previous results. We show that the backward SAR method gives the correct extinction rate only under a strict complementary‐area sampling design, which is not used in practice because it requires knowing which species are endemic to the area of destroyed habitat, or the number of species in the complementary area. Because of this problem, researchers substitute a power‐law model for the SAR in the backward SAR equation. However, this substitution violates the backward SAR method's requirement for complementary sampling. With this model substitution, the backward SAR equation is no longer correct, except in the special case of randomly distributed species. For the complementary sampling or random distribution of species, the first individual of a species to be encountered and the last individual to be encountered to lose the species are exchangeable (or the same individual). But this is not the case for other sampling designs or if species are not randomly distributed and explains why the backward SAR method fails to correctly estimate extinction rates. Our proofs and results are general and explain the widely recognized overestimation of extinction by the backward SAR method. We suggest future directions for developing general theory for estimating species extinction from species–area relationships. Until then, however, the backward SAR method should not be used to estimate species extinction in practice.
Three large fire years threaten resilience of closed crown black spruce forests in eastern Canada
Authors: Boiffin J. , Munson A. D.
Published: May 2013

An emerging paradigm regarding vegetation response to climate warming is that the interaction of weather extremes and disturbance will trigger abrupt changes in ecosystem types by overcoming resilience of dominant species. Black spruce (Picea mariana (Mill.)) ecosystems are widespread across the North American boreal forest, because of ecophysiological adaptations that allowed these communities to thrive in fire‐prone areas. We investigated resilience of spruce‐moss forests to weather‐disturbance interaction after a 3‐year period (2005 to 2007) of major fire activity caused by extreme fire weather in eastern Canada. Pre‐ and post‐fire conifer densities and environmental parameters related to seed rain, post‐fire seedbeds, microclimate, and post‐fire weather were measured in 133 burned stands throughout the closed‐crown forest of Quebec. Critically low black spruce (BS) regeneration was observed in almost all of the stands, leading to a decrease in stand density and a shift of species dominance from BS to jack pine (Pinus banksiana (Lamb.), JP). The studied sites were characterized by thick residual organic matter, resulting in a predominance of charred duff, a seedbed associated with low water retention and high variation in temperature. While high levels of JP seedling establishment were reported on this seedbed, it was unfavorable to BS germination and survival in the context of warm and dry weather that prevailed in post‐fire summers. In these ecosystems, early vegetation establishment patterns are generally reliable predictors of future stand composition and the exclusion of BS will presumably be maintained through succession. During large fire years, high proportions of the landscape are subjected to the interaction of fire regime and weather that creates unsuitable conditions for BS regeneration. Hence, vegetation change is susceptible to happen at a broad scale. Therefore, the frequency of major fire years could have a decisive influence on the rate of vegetation response to climate change in this biome.
Toward a Universal Maintenance Intervention: Integrating Cognitive-Behavioral Treatment With Motivational Interviewing for Maintenance of Behavior Change
Authors: Naar-King Sylvie , Earnshaw Paul , Breckon Jeff
Published: May 2013

Improvements in behavior following active interventions diminish over time across a broad spectrum of behaviors. Motivational interviewing (MI) has been found to increase intrinsic motivation forinitialbehavior change, but there has been little discussion on how to integrate MI and the cognitive-behavioral treatments (CBTs) commonly used tomaintainchange. A prominent CBT approach to relapse prevention that has been tested in multiple behavioral domains includes the following maintenance strategies: managing the goal violation effect, flexible goal setting, identifying triggers and developing coping skills, and increasing self-efficacy and social support. Using a model of integration where MI is the foundation for CBT delivery, the integration of specific relational and technical components of MI and CBT strategies for maintenance of change are described. A universal maintenance intervention that uses MI as an integrative framework to deliver CBT may address maintenance of behavior change across multiple behavioral domains. Further research is necessary to confirm whether delivering MI with fidelity adds to the effectiveness of CBT maintenance interventions.
Cognitive-Behavioral Group Therapy for Heterogeneous Anxiety and Mood Disorders in a Psychiatric Hospital Outpatient Clinic
Authors: Dwyer Lynndall , Olsen Sara , Oei Tian Po S.
Published: May 2013

Recent literature has shown that group cognitive-behavioral therapy (CBT) is effective for individuals with heterogeneous anxiety disorders. However, these studies have used a narrow range of outcome measures, and have not included global measures such as quality of life. In addition, heterogeneous mood disorders have not been well researched. The aim of this study was to replicate and extend on previous studies by assessing the effectiveness of group CBT treatment programs designed for use with heterogeneous anxiety or depressive disorders. Global outcome measures of quality of life and social functioning were assessed in addition to outcome measures of anxiety and mood symptoms. There were 173 patients who completed either group CBT for anxiety disorders or for depressive disorders. Symptom measures and quality of life measures were used to determine treatment effectiveness. Results demonstrated that the treatments were effective in reducing overall symptom severity and improving quality of life. Treatment gains were maintained to 12 month follow-up. However, the degree of change was considerably lower than that found in comparable trials with diagnostically homogenous samples. Overall, group CBT for heterogeneous diagnostic populations was effective but requires further investigation and refinement.