bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract PR6: Widespread potential for growth factor-driven resistance to anti-cancer kinase inhibitors
Authors: Wilson Timothy R. , Fridlyand Jane , Ribas Antoni , Li Jiang , Koeppen Hartmut , Merchant Mark , Neve Richard , Settleman Jeff , Yan Yibing , Penuel Elicia , Burton Luciana , Chan Emily , Peng Jing , Lin Eva , Wang Yulei , Sosman Jeff
Published: March 2013

Mutationally activated kinases, including EGFR, HER2, ALK, ABL, PDGFR, c-KIT, and BRAF, define a clinically validated class of targets for cancer drug therapy. However, the efficacy of kinase inhibitors in patients whose tumors harbor such alleles is invariably limited by innate or acquired drug resistance. As molecular mechanisms of resistance have begun to be elucidated, a recurrent theme is the engagement of survival signals redundant to those transduced by the targeted oncogenic kinase. Cancer cells typically express multiple receptor tyrosine kinases (RTKs), and many of these can potentially mediate signals that converge on common and critical downstream cell survival effectors - most notably, PI-3 kinase (PI3K) and MAP kinase (MAPK). Consequently, an increase in RTK ligand levels, via autocrine tumor cell production, paracrine contribution by tumor stroma, or systemic production, could confer resistance to inhibitors of an oncogenic kinase with a similar downstream signaling output. Indeed, using a large panel of kinase-“addicted” cancer cell lines, we found that the vast majority of such cells can be “rescued” from drug sensitivity by simply exposing them to one or more RTK ligands that engage redundant survival effectors. Among the findings with immediate clinical implications was the observation that hepatocyte growth factor (HGF) confers resistance to the HER2 kinase inhibitor lapatinib in HER2 amplified breast cancer cells, and to the BRAF inhibitor PLX4032 (vemurafenib) in BRAF mutant melanoma cells. Analysis of systemic HGF levels from PLX4032-treated BRAF mutant metastatic melanoma patients who were enrolled on the BRIM2 study indicated that increased HGF levels were significantly associated with a worse clinical outcome. These observations highlight the extensive redundancy of RTK-transduced signaling in cancer cells and the potentially broad role of widely expressed RTK ligands in both innate and acquired resistance to drugs targeting oncogenic kinases.

This proffered talk is also presented as Poster B38.
Abstract PR7: Paracrine receptor activation by microenvironment triggers bypass survival signals and ALK inhibitor-resistance in EML4-ALK lung cancer cells
Authors: Yano Seiji , Takeuchi Shinji , Nakagawa Takayuki , Yamada Tadaaki
Published: March 2013

Cancer cell microenvironments, including host cells, can critically affect cancer cell behaviors, including drug sensitivity. We recently reported that hepatocyte growth factor (HGF), the ligand of a tyrosine kinase receptor Met, can be produced not only by cancer cells but also host fibroblasts, activates Met and the downstream PI3K/Akt pathway and triggers resistance to EGFR inhibitors in EGFR mutant lung cancer cells (Yano S et al, Cancer Res, 2008). Crizotinib, a dual inhibitor of ALK and Met, shows dramatic effects against EML4-ALK lung cancer cells, but these cells can acquire resistance by several mechanisms, including ALK amplification and gatekeeper mutation. Although elective ALK inhibitors can overcome crizotinib resistance due to these mechanisms, these cells may become resistant to these inhibitors. Here, we determined whether microenvironmental factors trigger ALK inhibitor resistance in EML4-ALK lung cancer cells.

We tested the effects of ligands produced by endothelial cells and fibroblasts, and the cells themselves, on the susceptibility of EML4-ALK lung cancer cell lines to crizotinib and TAE684, a selective ALK inhibitor active against cells with ALK amplification and gatekeeper mutations, both in vitro and in vivo. EML4-ALK lung cancer cells were highly sensitive to ALK inhibitors. EGFR ligands, such as EGF, TGF-α, and HB-EGF, activated EGFR and triggered resistance to crizotinib and TAE684 by transducing bypass survival signaling through Erk1/2 and Akt. HGF activated Met/Gab1 and triggered resistance to TAE684, but not crizotinib, which inhibits Met. Endothelial cells and fibroblasts, which produce the EGFR ligands and HGF, respectively, decreased the sensitivity of EML4-ALK lung cancer cells to crizotinib and TAE684, respectively. EGFR-TKIs re-sensitized these cells to crizotinib and Met-TKI to TAE684 even in the presence of EGFR ligands and HGF, respectively.

Our findings suggest that paracrine receptor activation by ligands from the microenvironment may trigger resistance to ALK inhibitors in EML4-ALK lung cancer cells, and provide a rationale for targeting receptor ligands in the microenvironment for more successful treatment with ALK inhibitors. These observation further raise clinical questions which classes ALK inhibitors are more beneficial for EML4-ALK lung cancer patients.

This proffered talk is also presented as Poster A30.
Abstract PR8: Insensitivity to RAF inhibition by vemurafenib in BRAF mutant colorectal cancer by EGFR-mediated reactivation of MAPK signaling
Authors: Corcoran Ryan B. , Hung Kenneth E. , Flaherty Keith T. , Piris Adriano , Wargo Jennifer A. , Settleman Jeffrey , Mino-Kenudson Mari , Engelman Jeffrey A. , Ebi Hiromichi , Turke Alexa B. , Coffee Erin M. , Nishino Michiya , Cogdill Alexandria P. , Brown Ronald D. , Pelle Patricia Della , Dias-Santagata Dora
Published: March 2013

BRAF mutations occur in 10–15% of colorectal cancers (CRCs) and confer adverse outcome in the metastatic setting. While RAF inhibitors such as vemurafenib (PLX4032) have proven effective in BRAF mutant melanoma (∼60–80% response rates), they are surprisingly ineffective in BRAF mutant CRCs (∼5% response rate), and the reason for this disparity remains unclear. Compared to BRAF mutant melanoma cells, BRAF mutant CRC cells were less sensitive to vemurafenib, and P-ERK suppression was not sustained in response to treatment. Although transient inhibition of phospho-ERK by vemurafenib was observed in CRC, rapid ERK re-activation occurred through EGFR-mediated activation of RAS and CRAF. BRAF mutant CRC cell lines and patient tumor specimens expressed significantly higher levels of phospho-EGFR than BRAF mutant melanoma cell lines and primary tumor specimens, suggesting that CRCs are specifically poised for EGFR-mediated resistance. Combined RAF and EGFR inhibition blocked reactivation of MAPK signaling in BRAF mutant CRC cells and markedly improved efficacy in vitro. In vivo, combined RAF and EGFR inhibition led to sustained suppression of MAPK signaling and to robust tumor regressions in BRAF mutant colorectal xenografts. These findings support evaluation of combined RAF and EGFR inhibition in clinical trials in patients with BRAF mutant CRC.

This proffered talk is also presented as Poster B11.
Renal Involvement in AA Amyloidosis: Clinical Outcomes and Survival
Authors: Yilmaz Murvet , Unsal Abdulkadir , Sokmen Mehmet , Kaptanogullari Ozlem Harmankaya , Alkim Canan , Kabukcuoglu Fevziye , Ozagari Aysim , Bor Emire
Published: March 2013

Background: The natural history of AA amyloidosis is typically progressive, leading to multiple organ failure and death. We analyzed the etiology as well as clinical and laboratory features of patients with biopsy-proven AA amyloidosis and evaluated the ultimate outcome. Methods: Seventy-three patients (24 female; mean age 41.85±15.89 years) were analyzed retrospectively. Demographic, clinical and laboratory features were studied and the outcome was assessed. Results: Familial Mediterranean Fever and tuberculosis were the most frequent causes of amyloidosis. Mean serum creatinine and proteinuria at diagnosis were 4.65±4.89 mg/dl and 8.04±6.09 g/day, respectively; and stage I, II, III, IV and V renal disease were present in 19.2%, 13.7%, 16.4%, 11%, and 39.7% of the patients, respectively. ESRD developed in 16 patients during the follow-up period. All of the ESRD patients started a dialysis programme. Thirty patients (41%) died during the follow-up period; median patient survival was 35.9±6.12 months. Old age, tuberculosis etiology, advanced renal disease and low serum albumin levels were associated with a worse prognosis. Serum albumin was a predictor of mortality in logistic regression analysis. Conclusion: The ultimate outcome of the patients with AA amyloidosis is poor, possibly due to the late referral to the nephrology clinics. Early referral may be helpful to improve prognosis.
Troponin I, but not BNP, is Associated with Phosphorus, Calcium and Vitamin D in Stable Coronary Artery Disease
Authors: Nunes José Pedro L.
Published: March 2013

Background: Elevated plasma cardiac troponin, elevated plasma phosphorus and decreased plasma vitamin D have been shown to be associated with negative outcomes. Methods and results: Troponin I, calcium, phosphorus and 25-OH vitamin D were studied in a cohort of 60 patients with stable coronary heart disease and preserved left ventricular function. Using a cut-off value of 0.012 ng/mL for plasma troponin I, patients with higher values (18 patients), when compared to the other patients (n=42), had higher mean values for plasma phosphorus (3.42+0.45 mg/dL vs 3.17+0.45 mg/dL, p= 0.041) and calcium (5.08+0.23 mEq/L vs 4.92+0.18 mEq/L, p= 0.016) and lower values for 25-OH vitamin D (14.2+5.6 ng/mL vs 19.4+8.8 ng/mL, p= 0.032). Binary logistic regression analysis showed that troponin I > 0.012 ng/ml is associated with increased phosphorus, increased calcium and decreased 25-OH vitamin D concentrations. A similar analysis using BNP >100 pg/mL failed to show signifcant associations with phosphorus, calcium and 25-OH vitamin D concentrations. Conclusions: In patients with stable coronary artery disease and preserved left ventricular function, those having cardiac troponin I > 0.012 ng/ml, but not those having BNP >100 pg/mL, had higher plasma phosphorus, higher plasma calcium and lower plasma 25-OH vitamin D concentrations than those having cardiac troponin I ≤ 0.012 ng/ml (or BNP ≤ 100 pg/mL).
Selective Inhibition of the Reverse Mode of Na+/Ca2+ Exchanger Attenuates Contrast-Induced Cell Injury
Authors: Yang Dingping , Yang Dingwei , Jia Ruhan , Ding Guohua
Published: March 2013

Background: The precise mechanisms underlying radiocontrast nephropathy (RCN) are not well understood. Intracellular Ca2+ overload is considered to be a key factor in RCN. The Na+/Ca2+ exchanger (NCX) system is one of the main pathways of intracellular Ca2+ overload. We investigated whether intracellular Ca2+ overload via the NCX system was involved in contrast-induced renal tubular cytotoxicity. Methods: NRK-52E cells were exposed to ioversol (100 mg iodine/ml) for 4 h. KB-R7943 (inhibitor of reverse mode of NCX, 4 × 10-5, 4 × 10-6M) was added 1 h before incubation with ioversol. Cell viability and permeability were determined by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase assay. Apoptosis was determined by flow cytometry. Intracellular Ca2+ concentration ([Ca2+]i) and reactive oxygen species (ROS) were detected by confocal microscopy. The expression of NCX1 mRNA and caspase-3 protein was evaluated by reverse transcription-polymerase chain reaction and Western blot, respectively. Results: Ioversol exposure induced significantly increased lactate dehydrogenase release and decreased 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion in NRK-52E cells. Significantly increased apoptosis and caspase-3 protein expression were observed in the NRK-52E cells exposed to ioversol for 4 h. Ioversol treatment induced a significant increase in [Ca2+]i and intracellular ROS. KB-R7943 dose-dependently and significantly suppressed the increase in [Ca2+]i, intracellular ROS and caspase-3 overexpression induced by ioversol and attenuated the contrast-induced NRK-52E cell apoptosis. No significant changes in NCX1 mRNA expression were observed following contrast exposure. Conclusion: Intracellular Ca2+ overload via the reverse mode of NCX, followed by ROS overproduction and caspase-3 overexpression played an important role in the contrast-induced renal tubular cytotoxicity. The reverse mode of the NCX inhibitor KB-R7943 attenuated contrast-induced renal tubular cytotoxicity.
Renal Biopsy in Chronic Kidney Disease: Lessons from a Large Italian Registry
Authors: Zaza Gianluigi , Bernich Patrizia , Lupo Antonio ,   on behalf of the ‘Triveneto’ Register of Renal Biopsies (TVRRB)
Published: March 2013

Background: Renal biopsy procedure in patients with chronic renal failure (CRF) may represent a valid tool to help clinicians in clinical practice. However, the use of this invasive method in CRF is variable and it reflects the hospital biopsy policy. Methods: To better define the CRF-related histological patterns and to assess the clinical utility of this procedure in this extensive group, we analyzed biopsy records of 1,185 CRF patients living in a large area of north-east Italy from 1998 to 2010. Results: Data analysis showed that, although the biopsy incidence rate and the histological features were unchanged, the mean age of our CRF patients increased during the study period (R2 = 0.42, p < 0.01). Primary and secondary glomerulonephritis (SGNs) were the main histological presentations (53.9 and 23%, respectively). SGNs were over-diagnosed in females. Leading histological types were immunoglobulin A nephropathy (22%), focal segmental glomerulosclerosis (12.4%), membranous glomerulonephritis (MGN, 7.5%) and nephroangiosclerosis (7.3%). These forms were also highly frequent in CRF patients with elevated proteinuria and moderate/severe renal damage. Elderly patients were primarily affected by MGN. After biopsy, 49.5% of CRF patients with and 34.1% without nephrotic syndrome received immunosuppression therapy. Conclusions: This study demonstrated that renal biopsy in CRF patients, regardless of age and glomerular filtration rates, is safe and essential to achieve a correct diagnosis and to commence the correct therapy. Additionally, it revealed that, even in patients with severe renal damage, it is possible to perform an accurate histological diagnosis and, interestingly, end-stage kidney disease seems not to be the primary form.
Is Diabetes Mellitus a Heart Disease Equivalent in Women?
Authors: Daniels Lori B. , Grady Deborah , Mosca Lori , Collins Peter , Mitlak Bruce H. , Amewou-Atisso Messan G. , Wenger Nanette K. , Barrett-Connor Elizabeth ,   for the Raloxifene Use for the Heart (RUTH) Trial Investigators
Published: March 2013

Background—

Several studies have concluded that diabetes mellitus and heart disease carry similar risk for future cardiovascular disease (CVD). Most of these studies were too small to quantify independent risks specific to women. The purpose of this study was to determine whether diabetes mellitus is a coronary heart disease (CHD) risk equivalent for prediction of future CHD and CVD events in women.

Methods and Results—

The Raloxifene Use for the Heart (RUTH) trial was an international, multicenter, double-blind, randomized, placebo-controlled trial of raloxifene and CVD outcomes in 10 101 postmenopausal women selected for high CHD risk. Of these, 3672 had a history of diabetes mellitus without known CHD, and 3265 had a history of CHD without known diabetes mellitus. Cox proportional hazard models were used to compare cardiovascular outcomes in these 2 groups. Mean age at baseline was 67.5 years; median follow-up was 5.6 years. There were 725 deaths, including 450 cardiovascular deaths. In age-adjusted analyses, diabetic women had an increased risk of all-cause mortality compared with women with CHD. Although the overall risk of CHD and CVD was lower in diabetic women compared with women with CHD, the risk of fatal CHD, fatal CVD, and all-cause mortality was similar (hazard ratio [95% confidence interval]: 0.85 [0.65–1.12], 0.99 [0.78–1.25], and 1.18 [0.98–1.42], respectively, after adjusting for age, lifestyle factors, CHD risk factors, statin use, and treatment assignment).

Conclusions—

In the RUTH trial, diabetes mellitus was a CHD risk equivalent in women for fatal, but not nonfatal, CHD and CVD.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov/show/NCT00190593
. Unique identifier: NCT00190593.
The Effect of Graduated Compression Stockings on Long-term Outcomes After Stroke
Authors:   The CLOTS Trials Collaboration, Dennis Martin , Sandercock Peter , Reid John , Graham Catriona , Murray Gordon , Venables Graham , Rudd Anthony , Bowler Gill
Published: March 2013

Background and Purpose—

Most randomized controlled trials of venous thromboembolism prophylaxis have focused on reduction of deep vein thrombosis, predominantly asymptomatic deep vein thrombosis, detected on imaging. We aimed to estimate the effects of graduated compression stockings on venous thromboembolism events, survival, and functional status at 6 months after stroke.

Methods—

The CLOTS Trials adopted an international multicentre, parallel group design, with central randomization and a 1:1 treatment allocation. In CLOTS Trial 1, 2518 immobile stroke patients were allocated thigh-length graduated compression stockings or not, and in CLOTS trial 2, 3014 to thigh-length or below-knee graduated compression stockings. We measured vital status, Oxford Handicap Scale, and quality of life (EQ5D-3 L) at 6 months.

Results—

We compared survival in patients enrolled in Trials 1 and 2 with a Cox proportional hazards model, including variables included in our minimization algorithm. In both trials, allocation to thigh-length graduated compression stockings was associated with a very slight, but nonsignificant, increased hazard of death in the first 6 months (Trial 1: hazard ratio, 1.087; 95% confidence interval, 0.913–1.295; and Trial 2: hazard ratio, 1.037; 95% confidence interval, 0.892–1.205). There were no statistically significant differences in venous thromboembolism events, Oxford Handicap Scale, or EQ5D-3 L between the treatment groups in CLOTS Trials 1 or 2.

Conclusions—

Although underpowered to detect clinically important effects on long-term outcomes, our results effectively exclude a >10% relative reduction in the hazard of death within 6 months associated with the use of thigh-length stockings. No other long-term benefits were apparent.
Risk of Stroke or Systemic Embolism in Atrial Fibrillation Patients Treated With Warfarin
Authors: Albertsen Ida Ehlers , Rasmussen Lars Hvilsted , Overvad Thure Filskov , Graungaard Tina , Larsen Torben Bjerregaard , Lip Gregory Y.H.
Published: March 2013

Background and Purpose—

Although oral anticoagulants (OACs) are highly effective in reducing stroke risk in atrial fibrillation, some patients still sustain stroke despite being on an OAC. Our aim was to identify the risk factors that contribute to stroke risk in atrial fibrillation, although patients were taking OACs in a clinical trial setting.

Methods—

We identified contemporary clinical trials that investigated OACs in patients with atrial fibrillation. Event rates per year from each study and pooled event rates and relative risks, all with a 95% confidence interval, were calculated. Statistical heterogeneity was assessed using the
I
2
test.

Results—

Six trials were included in the meta-analysis, with a total of 58 883 patients randomized. Characteristics associated with a higher relative risk of stroke while on an OAC included age ≥75 years (relative risk, 1.46 [95% confidence interval, 1.25–1.69]), female sex (1.30 [1.15–1.49]), previous stroke/transient ischemic attack (1.85 [1.32–2.60]), vitamin K-antagonist naive status (for vitamin K antagonist experienced, 0.85 [0.74–0.97]), moderate and severe renal impairment (1.54 [1.30–1.81] and 2.22 [1.85–2.66], respectively, compared with normal renal function), previous aspirin use (1.19 [1.04–1.37]), Asian race (1.70 [1.42–2.03]), and a CHADS
2
score of ≥3 (1.64 [1.18–2.27]).

Conclusions—

Stroke rates are higher on OACs with some patient clinical characteristics, that is, older age, female sex, previous stroke/transient ischemic attack, vitamin K-antagonist naive status, renal impairment, previous aspirin use, and higher CHADS
2
score. The identified risk factors for stroke while on an OAC could potentially be used to consider a risk assessment tool to flag up high-risk patients while on an OAC (in this case, warfarin). Whether these risk factors apply to novel OACs is uncertain.
Adelaide Stroke Incidence Study
Authors: Leyden James M. , Kleinig Timothy J. , Newbury Jonathan , Castle Sally , Cranefield Jennifer , Anderson Craig S. , Crotty Maria , Whitford Deirdre , Jannes Jim , Lee Andrew , Greenhill Jennene
Published: March 2013

Background and Purpose—

Stroke incidence rates are in flux worldwide because of evolving risk factor prevalence, risk factor control, and population aging. Adelaide Stroke Incidence Study was performed to determine the incidence of strokes and stroke subtypes in a relatively elderly population of 148 000 people in the Western suburbs of Adelaide.

Methods—

All suspected strokes were identified and assessed in a 12-month period from 2009 to 2010. Standard definitions for stroke and stroke fatality were used. Ischemic stroke pathogenesis was classified by the Trial of ORG 10172 in Acute Stroke Treatment criteria.

Results—

There were 318 stroke events recorded in 301 individuals; 238 (75%) were first-in-lifetime events. Crude incidence rates for first-ever strokes were 161 per 100 000 per year overall (95% confidence interval [CI], 141–183), 176 for men (95% CI, 147–201), and 146 for women (95% CI, 120–176). Adjusted to the world population rates were 76 overall (95% CI, 59–94), 91 for men (95% CI, 73–112), and 61 for women (95% CI, 47–78). The 28-day case fatality rate for first-ever stroke was 19% (95% CI, 14–24); the majority were ischemic (84% [95% CI, 78–88]). Intracerebral hemorrhage comprised 11% (8–16), subarachnoid hemorrhage 3% (1–6), and 3% (1–6) were undetermined. Of the 258 ischemic strokes, 42% (95% CI, 36–49) were of cardioembolic pathogenesis. Atrial fibrillation accounted for 36% of all ischemic strokes, of which 85% were inadequately anticoagulated.

Conclusions—

Stroke incidence in Adelaide has not increased compared with previous Australian studies, despite the aging population. Cardioembolic strokes are becoming a higher proportion of all ischemic strokes.
Marx on the Dialectics of Elliptical Motion
Authors: Weston Thomas
Published: March 2013

Abstract

It is a widespread view that Marx did not apply dialectics to nature, and that Engels’s writings on this subject are a distortion of his outlook. This paper examines Marx’s discussion of elliptical motion and some other physical phenomena, and shows that he did indeed find contradictions and oppositions in nature, and thus recognised a dialectics of nature. In addition to analysing relevant passages in Marx’s texts, his study of the physics and mathematics of elliptical motion is reviewed and compared with Hegel’s position.

Marx’s conception of how dialectical contradictions are resolved is reviewed in order to interpret his claim that the contradiction in elliptical motion is ‘solved’ but not ‘overcome’ by that motion. Textual evidence is presented that Marx regarded ‘real contradictions’ as resolved only by ‘development’, a process in which the conflict between the opposing sides of the contradiction becomes more intense. The consequences of this interpretation for Marx’s analysis of elliptical motion are explored, and some alternative interpretations are discussed.
Judicial Activism, Punitivism and Supranationalisation: Illiberal and Antidemocratic Tendencies of the Inter-American Court of Human Rights
Authors: Malarino Ezequiel
Published: March 2013

This article takes a critical look at the following three key characteristics in recent judgements of the Inter-American Court: judicial activism, punitivism and supranationalisation. First, it seeks to illustrate that the Inter-American Court has modified in some significant regards the legal framework agreed upon by State parties (judicial activism); second, that this activism has undermined some of the liberal guarantees limiting the State’s power in criminal matters and has led to the creation of a law of exception (punitivism, or illiberal and contra conventionem judicial activism); third, that the Court, on the basis of the Convention’s provision on reparations, has required States to adopt measures that negatively affect their sovereignty, and has thus become dangerously close to acting as legislator, judge and supreme administrative authority of the American States (supranationalisation).
‘Special Protection Measures’: States Parties’ reporting on article 38 of the Convention of the Rights of the Child
Authors: Poulatova Chaditsa
Published: March 2013

In 1989 when the Convention on the Rights of the Child (CRC) came into existence children officially became right holders. This article reviews States Parties’ reporting on Article 38 of the CRC to test how far the reporting guidelines have been fully met by the States Parties’ reports to the Committee on the Rights of the Child. The first section analyses the adequacy and the depth of the reports submitted by the States Parties’ up to the 44thsession of the Committee (January 2007). The second examines and evaluates the Committee’s use of List of Issues and its Concluding Observations. The third examines the relationship between the reporting performance and the geographical region, income level and regime type of the States Parties to the CRC. The fourth focuses on States Parties that have experienced war/conflict over the past years and have a well established record of use of child soldiers either in government or non-governmental militia groups. The fifth concludes that States Parties have provided the Committee with poor, inadequate or no reporting on article 38, despite its significance.
Social rights and the United Nations – Child Rights Convention (UN-CRC): Is the CRC a help or hindrance for developing universal and egalitarian social policies for children’s wellbeing in the ‘developing world’?
Authors: Khadka Suman
Published: March 2013

Children’s social policies, which are crucial for attaining social rights and welfare/wellbeing, are influenced by the Child Rights Convention (CRC). However, despite the CRC becoming the unilateral framework for interpreting child wellbeing, its inherent complexities and the persistent deprivations experienced by children in ‘developing’ countries calls for alternate approaches while formulating children’s social policies. Key limitations of the CRC include inappropriate prioritisation of rights when resources are limited or when rights conflict, the apolitical nature of the Convention itself and its failure to integrate into wellbeing analysis the existence of two different welfare states/or lack of it in the world. Despite the usefulness of ‘welfare state frameworks’ in combating absolute child poverty in the West, it is rarely applied in the South. This article analyses CRC from the political economy perspective focusing on social rights and the ‘developing’ world which offers a useful critique to the mainstream child rights discourse.
India and the Responsibility to Protect: A Tale of Ambiguity
Authors: Virk Kudrat
Published: March 2013

Military intervention to halt atrocities is one of the most contentious aspects of R2P and with which India has often expressed disagreement in the past. Since the 2005 World Summit, however, there has been an apparent softening in that opposition. This article takes a close-up look at the empirical record, revealing ambiguity in Indian attitudes from the outset that militates against categorizing them as either ‘for’ or ‘against’ humanitarian intervention. The portrait that emerges is of a reactive actor driven incrementally away from a default preference for sovereignty as autonomy, whilst harbouring deep concerns about armed intervention. This article suggests that cautious and reluctant accommodation offers the best description of India’s still unresolved stance on humanitarian intervention. That fits in with a broad preference for pragmatism in foreign policy, which has struggled to balance traditional concerns with a ‘new’ ambition to acquire and sustain greater power-political influence in a changing world.
Tilting at Windmills? The Indian Debate over the Responsibility to Protect after UNSC Resolution 1973
Authors: Hall Ian
Published: March 2013

India voted for United Nations Security Council Resolution 1970, but abstained from Resolution 1973 authorizing a no-fly zone over Libya, subsequently criticizing the NATO campaign. This stance provoked much comment within India and among foreign commentators on Indian foreign policy. Some praised it as morally superior to approving military action, which was portrayed by some as Western ‘neo-colonialism’. Others, however, were critical of India’s unwillingness to back intervention in Libya and the principle of the Responsibility to Protect. For the critics, India’s objections to UNSC 1973 merely demonstrated the continued weakness of the foreign policy establishment and its inability to balance power politics and ethical values. This article evaluates these various positions, but argues that while the Libyan episode stimulated an unprecedented amount of comment in India about R2P, it is unlikely that the Indian government or leading Indian commentators will soon shift their positions.
Two new species of Mallomonas (Chrysophyceae: Synurales): Mallomonas temonis and Mallomonas divida
Authors: NĚMCOVÁ YVONNE , KREIDLOVÁ JANA
Published: March 2013

This paper describes two new species of Mallomonas. Mallomonas temonis was identified in the Table Mountain Plateau, South Africa; Mallomonas divida was identified in Aquitaine, France. The descriptions are based on silica-scale morphology studied by means of transmission and scanning electron microscopy. Mallomonas temonis belongs to the section Heterospinae. A scale is surrounded by a submarginal rib connected at lateral parts by a strong, more or less transversal rib. Mallomonas divida belongs to the section Torquatae. The shield of scales is covered by regularly arranged, delicate papillae and marked by one or several rows of more distinctive papillae.
Australian marsh beetles (Coleoptera: Scirtidae). 2. Pachycyphon, a new genus of presumably terrestrial Australian Scirtidae
Authors: ZWICK PETER
Published: March 2013

The genus Pachycyphon is erected for marsh beetles (Coleoptera: Scirtidae) from tropical rainforests in Queensland, Australia. The following species are included: P. corpulentus sp. n., P. crassus sp. n., P. elegans sp. n., P. funicularis sp. n., P. gravis sp. n., P. monteithi sp. n., P. obesus sp. n., P. pinguis sp. n., P. serratus sp. n., P. turgidus sp. n. (the type species). Females are wingless and have fossorial ovipositors, a terrestrial larval life is therefore hypothesized. Pachycyphon is compared with other genera, especially probable relatives from temperate rainforests in southeasternAustralia.
A new Trimerocephalus species (Trilobita, Phacopidae) from the Late Devonian (Early Famennian) of Poland
Authors: KIN ADRIAN , BŁAŻEJOWSKI BŁAŻEJ
Published: March 2013

This study presents a detailed morphological analysis of a new species belonging to the blind trilobite Trimerocephalus McCoy, 1849, T. chopini n. sp., based on exceptionally well preserved articulated specimens from the Late Devonian (Early Famennian) of the Holy Cross Mountains in central Poland. The occurrence of this taxon in Kowala Quarry near Kielce has been reported previously, with specimens often found in single-file queues representing migratory behaviour that was followed by a mass mortality event that preserved these assemblages. The new taxon is compared with other species of Trimerocephalus and is interpreted as being most closely related to a clade consisting of T. caecus, T. lelievrei, T. mimbi, T. shotoriensis and T. tardispinosus.
Field of Dreams or Dream Team? Assessing Two Models for Drought Impact Reporting in the Semiarid Southwest
Authors: Meadow Alison M. , Crimmins Michael A. , Ferguson Daniel B.
Published: March 2013

To make decisions about drought declarations, status, and relief funds, decision makers need high-quality local-level drought impact data. In response to this need in Arizona the Arizona DroughtWatch program was created, which includes an online drought impacts reporting system. Despite extensive and intensive collaboration and consultation with the intended public participants, Arizona DroughtWatch has had few consistent users and has failed to live up to its goal of providing decision makers or the public with high-quality drought impacts data. Based on an evaluation of the DroughtWatch program, the authors found several weaknesses in the public-participation reporting-system model including that participation was reduced because of participants' over-commitment and time constraints, consultation fatigue, and confusion about the value of qualitative impact reports. Based on these findings, the authors recommend that professional resource agency personnel provide the backbone of drought impacts monitoring to ensure that decision makers receive the high-quality, consistent information they require. Public participation in impacts monitoring efforts can also be improved using this model. Professional observers can help attract volunteers who consider access to high-quality data an incentive to visit the Arizona DroughtWatch site and who may be more likely to participate in impacts monitoring if they see examples of how the information is being used by decision makers.
Influences of Sea Surface Temperature Gradients and Surface Roughness Changes on the Motion of Surface Oil: A Simple Idealized Study
Authors: Zheng Yangxing , Bourassa Mark A. , Hughes Paul
Published: March 2013

The authors' modeling shows that changes in sea surface temperature (SST) gradients and surface roughness between oil-free water and oil slicks influence the motion of the slick. Physically significant changes occur in surface wind speed, surface wind divergence, wind stress curl, and Ekman transport mostly because of SST gradients and changes in surface roughness between the water and the slick. These remarkable changes might affect the speed and direction of surface oil. For example, the strongest surface wind divergence (convergence) occurring in the transition zones owing to the presence of an oil slick will induce an atmospheric secondary circulation over the oil region, which in turn might affect the surface oil movement. SST-related changes to wind stress curl and Ekman transport in the transition zones appear to increase approximately linearly with the magnitude of SST gradients. Both surface roughness difference and SST gradients give rise to a net convergence of Ekman transport for oil cover. The SST gradient could play a more important role than surface roughness in changes of Ekman transport when SST gradients are large enough (e.g., several degrees per 10 km). The resulting changes in Ekman transport also induce the changes of surface oil movement. Sensitivity experiments show that appropriate selections of modeled parameters and geostrophic winds do not change the conclusions. The results from this idealized study indicate that the feedbacks from the surface oil presence to the oil motion itself are not trivial and should be further investigated for consideration in future oil-tracking modeling systems.
Parameterization of Wind Farms in Climate Models
Authors: Fitch Anna C. , Olson Joseph B. , Lundquist Julie K.
Published: March 2013

For assessing the impacts of wind farms on regional climate, wind farms may be represented in climate models by an increase in aerodynamic roughness length. Studies employing this method have found near-surface temperature changes of 1–2 K over wind farm areas. By contrast, mesoscale and large-eddy simulations (LES), which represent wind farms as elevated sinks of momentum, generally showed temperature changes of less than 0.5 K. This study directly compares the two methods of representing wind farms in simulations of a strong diurnal cycle. Nearly the opposite wake structure is seen between the two methods, both during the day and at night. The sensible heat fluxes are generally exaggerated in the enhanced roughness approach, leading to much greater changes in temperature. Frequently, the two methods display the opposite sign in temperature change. Coarse resolution moderates the sensible heat fluxes but does not significantly improve the near-surface temperatures or low-level wind speed deficit. Since wind farm impacts modeled by the elevated momentum sink approach are similar to those seen in observations and from LES, the authors conclude that the increased surface roughness approach is not an appropriate option to represent wind farms or explore their impacts.
Transient Isolated Scrotal Hair Development in Infancy
Authors: Janus Dominika , Wojcik Malgorzata , Tyrawa Katarzyna , Starzyk Jerzy
Published: March 2013

Isolated scrotal hair development in infancy is a rare disorder that has not been well characterized in the literature. We present a retrospective analysis of 5 male patients referred to the Endocrine Department at the age of 3 to 6 months for the assessment of isolated scrotal hair development. There were no other signs of androgenization and testes were of normal infant size. Three mothers were receiving dydrogesterone during pregnancy and one of them was also receiving desogestrel during breast-feeding. All infants were developing well. In all boys, complete regression of scrotal hair was noted after 4 to 7 months of observation. It seems that the condition is benign and probably occurs in boys with increased response of cells within hair follicles to raised androgen levels during “mini puberty” of early infancy. Nevertheless, all infants with signs of androgenization need urgent full investigation and probably further follow-up until puberty.
Influence of steel fibers and fiber-reinforced polymers on the impact resistance of one-way concrete slabs
Authors: Yoo Doo-Yeol , Yoon Young-Soo
Published: March 2013

In this study, to estimate the impact resistance of steel fiber-reinforced concrete slabs strengthened with fiber-reinforced polymer sheets, a series of 50 × 100 × 350 mm3 sized slabs with 0.5%–1.5% (by volume) of steel fibers and two types of fiber-reinforced polymer sheets were impact-tested using drop-weight impact test machine. From the test results, the maximum impact load, dissipated energy and the number of drops before failure were all increased, whereas the maximum deflection and support rotation were reduced by strengthening the steel fiber-reinforced concrete slabs with externally bonded fiber-reinforced polymer sheets in the tensile zone. It was noticed that the impact resistance of the steel fiber-reinforced concrete slabs was substantially improved by externally strengthening the fiber-reinforced polymer sheets. In addition, the dynamic response of the steel fiber-reinforced concrete slabs strengthened with fiber-reinforced polymer sheets under a low-velocity impact load was analyzed using explicit code LS-DYNA with strain rate-dependent material models and debonding failure analysis. These numerical analyses were verified by comparing with the experimental results.
Measuring Centrality and Power Recursively in the World City Network: A Reply to Neal
Authors: Boyd John P. , Mahutga Matthew C. , Smith David A.
Published: March 2013

In a recent article, Zachary Neal (2011) distinguishes between centrality and power in world city networks and proposes two measures of recursive power and centrality. His effort to clarify oversimplistic interpretations of relational measures of power and position in world city networks is appreciated. However, Neal’s effort to innovate methodologically is based on theoretical reasoning that is dubious when applied to world city networks. And his attempt to develop new measures is flawed since he conflates ‘eigenvector centrality’ with ‘beta centrality’ and then argues that ‘eigenvector-based approaches’ to recursive power and centrality are ill-suited to world city networks. The main problem is that his measures of ‘recursive’ centrality and power are not recursive at all and thus are of very limited utility. It is concluded that established eigenvector centrality measures used in past research (which Neal critiques) provide more useful gauges of power and centrality in world city networks than his new indexes.
A Refinement of Collaborative Circles Theory
Authors: Corte Ugo
Published: March 2013

Farrell’s (2001) theory of collaborative circles provides a useful frame for analyzing the interpersonal dynamics that enable creative collaboration in small groups, but it leaves contextual factors of collaboration undertheorized. Using ethnographic data on freestyle BMXers in Greenville, North Carolina, this article demonstrates how resource mobilization theory’s conception of resources can specify the enabling and constraining aspects of a circle’s environment in a theoretically satisfying way. Specifically, I find that the enabling interpersonal dynamics found by Farrell rely on distinct arrangements of material, moral, and what I term locational resources. During the formation stage, a welcoming skatepark and moral support from the local community afforded the group the space and time it needed to unite, articulate a common vision, and produce dramatic innovations in their sport. During the separation stage, increased resources from the commercialization of freestyle BMX influenced both the separation of the circle and the production of the scene that followed.
Comparison of Plaintiff and Defendant Expert Witness Qualification in Malpractice Litigation in Otolaryngology
Authors: Eloy Jean Anderson , Svider Peter F. , Patel Dharti , Setzen Michael , Baredes Soly
Published: March 2013

Objective

Malpractice litigation contributes to rising health care costs in the United States. The role of expert witness testimony has been controversial in the past, with medical professional societies issuing statements regarding ethical obligations of physicians. Our objectives were to examine the relative qualifications of expert witnesses testifying on behalf of plaintiffs vs defendants.

Study Design and Setting

Analysis of expert witness and physician demographic data available on several databases.

Methods

The Westlaw legal database (Thomson Reuters, New York, New York) was searched for otolaryngologist expert witness testimony. Length of experience, practice setting, and subspecialty training information were obtained from hospital, practice, departmental, and state licensing board sites. Scholarly impact was assessed using calculation of the h‐index from the Scopus database.

Results

Plaintiff expert witnesses had significantly less experience than those testifying for defendants (31.8 vs 35.4 years, P =. 047) and lower scholarly impact (h = 6.3 vs 10, P =. 045). A significantly higher proportion of defendant witnesses were in academic practice (49.3% vs 31.7%, P =. 042). No differences were detected in postresidency fellowship training patterns.

Conclusion

Upon comparison of otolaryngologist expert witnesses, practitioners testifying on behalf of plaintiffs had statistically fewer years of experience, had a lower scholarly impact, and were less likely to work in an academic setting. Otolaryngologists who repeatedly served as expert witnesses were more likely to be testifying on behalf of plaintiffs than defendants. Professional societies need to frequently update guidelines on expert witness testimony and address the ethical obligations of practitioners.
Causal inversion of non-minimum-phase systems for hardware-in-the-loop transmission testing
Authors: Sahinkaya Mehmet N , Wang Pengfei , Akehurst Sam
Published: March 2013

Hardware-in-the-loop transmission testing requires precise speed and torque tracking of the actuators that emulate the engine and vehicle dynamics. System-inversion-based feedforward controllers offer a solution, but they do not work for non-minimum-phase systems. Preview filters can provide stable approximate inversion of non-minimum-phase systems, but they require future values, which are not available in hardware-in-the-loop tests. This article develops a simple but effective controller to enable preview filters to provide causal inversion within the frequency range of interest. Causality is achieved by adding manual delays to the measured response signal either in a closed-loop or open-loop configuration, followed by system identification in the frequency domain. The proposed controller was initially validated experimentally for precise speed and torque tracking of uncoupled actuators. Then additional compensators were designed to deal with two dynamometers, which are coupled through a transmission system. The effectiveness of the proposed coupled controllers is demonstrated experimentally by using the dual actuator hardware-in-the-loop transmission test facility and commercially supplied models for the engine, driver and vehicle.
Perceived Barriers to and Ideas for Weight Control Interventions in Malay Homemakers
Authors: Ng Li Whye Cindy , Malhotra Rahul , Lai Danny , Tai E. Shyong , Østbye Truls
Published: March 2013

Objective. To develop a better understanding of perceived barriers to and ideas for weight loss and maintenance among Malay homemakers in Singapore. Methods. Interventions for weight management were reviewed, and 5 focus groups were conducted among overweight and obese Malay homemakers (n = 24) to explore barriers to and concepts and ideas pertaining to weight loss and maintenance. Results. Barriers identified included the lack of time, finances, and motivation. Ideas that were most appealing included free health screening, workshops on how best to manage children and family, regular fun group activities, monetary incentives for participation in activities for healthy living, and flexible part-time jobs. Conclusion. The focus groups provided useful insights pointing toward possible interventions that could appeal to Malay homemakers in Singapore. The most appealing approaches were those that were time flexible and had the least financial burden or had a financial benefit.
Anticoagulant and Antithrombotic Actions of AVE5026, an Enriched Anti-Xa Hemisynthetic Ultra-Low-Molecular-Weight Heparin
Authors: Hoppensteadt Debra A. , Gray Angel , Jeske Walter P. , Walenga Jeanine M. , Fareed Jawed
Published: March 2013

Introduction:

AVE5026 represents a new generation of ultra-low-molecular-weight heparin (LMWH) with high anti-Xa and low anti-IIa activities (anti Xa–IIa ratio >30). In addition, AVE5026 exhibits a relatively higher proportion of AT components.

Materials and Methods:

The anticoagulant, antiplatelet, antithrombotic, and bleeding effects of AVE5026 in comparison to other heparins were investigated in this study.

Results:

AVE5026 demonstrated weak effects in the global clotting assays; however, in the amidolytic anti-Xa assay, AVE5026 produced strong inhibitory effects. AVE5026 showed no cross-reactivity with the heparin-induced thrombocytopenia antibodies in the platelet aggregation system. AVE5026 produced a dose-dependent antithrombotic response after intravenous (IV) and subcutaneous (SC) administration in thrombosis models. The relative bleeding effects of AVE5026 in a rat tail bleeding and rabbit blood loss model were negligible after both IV and SC administration.

Conclusions:

This superior safety efficacy index in animal models in comparison with other LMWH may translate into improved antithrombotic efficacy with decreased bleeding risk.